Download Whole grain - an important part of a healthy Nordic diet

Doctoral Thesis for the degree of Doctor of Philosophy, Faculty of Food Science and
Nutrition
Whole grain - an important part of a
healthy Nordic diet
Alkylresorcinols as biomarkers for whole grain wheat and rye intake
Óla Kallý Magnúsdóttir
University of Iceland
Faculty of Food Science and Nutrition
School of Health Science
Reykjavík 2014
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Academic Dissertation
University of Iceland, Faculty of Food Science and Nutrition, School of Health Sciences and
Landspitali-National University Hospital, Unit for Nutrition Research
Supervised by
Professor Inga Thorsdottir, University of Iceland
Professor Ingibjorg Gunnarsdottir, University of Iceland
PhD Committee
Professor Inga Thorsdottir, University of Iceland
Professor Ingibjorg Gunnarsdottir, University of Iceland
Professor Matti Uusitupa, University of Eastern Finland
Opponents
Professor Ann-Sofie Sandberg, Chalmers University of Technology, Gothenburg, Sweden
Professor Ingibjorg Hardardottir, University of Iceland, Reykjavik, Iceland
Dissertation for the Degree of Ph.D. in Nutrition
© Óla Kallý Magnúsdóttir 2014
Design: Prentlausnir
Printed in Iceland by Prentlausnir, Reykjavík 2014
ISBN 978-9935-9130-7-4
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It is health that is real wealth and not pieces of gold and silver
- Mahatma Gandhi4
Dissertation for the Degree of Ph.D. in Nutrition
Presented at the University of Iceland in 2014
Abstract
Background: Evidence for the health benefits of whole grain consumption are mainly derived
from epidemiological studies as findings in intervention studies have been inconsistent. The
reason for inconclusive results from intervention studies may relate to lack of accurate and
objective measures of whole grain intake. Alkylresorcinols (AR) appear to be highly
promising biomarkers of whole grain wheat and rye intake although there are still many
factors that are poorly understood. The main aim of this dissertation was to increase
knowledge on the use of plasma AR as dietary biomarkers by assessing whether plasma AR
could be used as biomarkers of whole grain intake in the healthy Nordic diet (ND) and to
evaluate the association between plasma AR and glucose metabolism and blood lipid
concentrations in a population with metabolic syndrome. Most intervention studies evaluating
the health effects of whole grain, especially whole grain rye, have been conducted in
populations accustomed to high intakes. Therefore, the feasibility of conducting an
intervention with high consumption of whole grain rye in a population of Icelandic men, with
habitually low whole grain intake, was also evaluated using plasma AR to measure dietary
compliance.
Methods: This PhD project was based on data from two extensive research projects, an
intervention study that was a part of SYSDIET - Systems biology in controlled dietary
interventions and cohort studies and the feasibility study ARI, conducted as a follow up of
HELGA: Nordic Health – Whole grain Food.
In the SYSDIET study participants (30–65 years, body mass index 27–40 kg/m2 with
two more features of metabolic syndrome, but without diabetes) were recruited through six
centers in the Nordic countries and randomly assigned to a ND (N=104) or a control diet
(N=96) for 18 or 24 weeks depending on the study center. Plasma AR concentrations were
analyzed (N=158) and nutrient intake was calculated from 4-day food records at weeks 0, 12
and 18/24. Determinants of AR concentration at 18/24 weeks were assessed using linear
regression. Reproducibility of AR measurements between weeks 12 and 18/24 was evaluated
using intra-class correlation (ICC). Associations between total plasma AR concentration and
AR C17:0/C21:0 homolog ratio, as an indication of the relative whole-grain rye intake, and
glucose metabolism and blood lipid measures were investigated in pooled (ND + control
group) regression analyses at 18/24 weeks.
In the ARI feasibility study participants (males, 42-80 years with type 2 diabetes) were
randomized into either a rye group (N=14) or a control group (N=9) for 26 weeks.
Participants in the rye group were provided with, and asked to consume, 100 g/day of whole
grain rye. Acceptability and compliance to the whole grain rye intake was assessed with
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questionnaires, 4-day weighed food record and plasma AR concentrations and AR
C17:0/C21:0 homolog ratio.
Results: Median (IQR) fasting plasma total AR concentration increased from 73 (88) to 106
(108) nmol/L, or 45%, between week 0 and 18/24 (P <0.001). The AR concentration was
significantly higher in the ND group than in the control group at 18/24 weeks (P <0.001) and
study group was a significant determinant for total plasma AR at week 18/24 (P <0.001). The
ICCs for total plasma AR between weeks 12 and 18/24 were 0.44 – 0.72. There was a
significant difference in baseline total plasma AR concentration between study centers with
median concentration of 108 (96) nmol/L and 108 (72) nmol/L in Oulu and Kuopio,
respectively, and 43 (37) nmol/L in Reykjavik.
In a pooled analyses at 18/24 weeks, the AR C17:0/C21:0 ratio was inversely
associated with fasting serum insulin concentrations (B (95% CI): -0.43 (-0.77 to -0.08)) and
positively associated with the insulin sensitivity indices Matsuda ISI (0.23 (0.07 to 0.40)) and
disposition index (0.77 (0.11 to 1.43)). Additionally, the AR ratio C17:0/C21:0 was inversely
associated with LDL cholesterol concentrations (-0.41 (-0.80 to -0.02)), LDL/HDL
cholesterol ratio (-0.20 (-0.37 to -0.03)), log non-HDL cholesterol (-0.20 (-0.37 to -0.03)),
apolipoprotein B (-0.12 (-0.24 to 0.00)) and triglyceride concentrations (-0.35 (-0.59 to -0.12))
and positively associated with HDL cholesterol concentration (0.11 (0.00 to 0.21)). Total
plasma AR concentration at week 18/24 was neither associated with glucose metabolism
outcomes nor blood lipid measurements.
Twelve participants in the rye group finished the ARI feasibility study and 8 in the
control group. Whole grain rye intake and total plasma AR increased significantly in the rye
group (P=0.003 and P=0.004, respectively). The mean (SD) whole grain rye consumption of
the rye group during the intervention was 93 (44) g/day and 10 (8) g/day in the control group,
which did not change during the intervention. Seven out of 12 participants in the rye group
had a mean intake of ≥100 g/day of whole grain rye during the intervention. Four participants
in the rye group experienced discomfort in the digestive system in weeks 0-13 weeks and two
in weeks 13-26.
Conclusion: The results suggest that the total AR concentration may be valid biomarkers for
a healthy Nordic diet, in which whole grain wheat and rye are important components, and that
the AR ratio C17:0/C21:0 may be used as a marker of relative whole grain rye intake.
Additionally, the results indicate that increased proportion of whole grain rye, reflected by the
AR C17:0/C21:0 ratio, is associated with lower fasting insulin, increased insulin sensitivity
and favorable blood lipid outcomes. Icelanders have a habitually low intake of whole grain
rye. However, the ARI feasibility study was well received by the population studied, as seen
in the low dropout, acceptability and good compliance to the dietary intervention.
Keywords: alkylresocinols, Nordic diet, whole grain, rye consumption, dietary biomarker
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Ritgerð fyrir doktorsvörn í næringarfræði við Háskóla Íslands 2014
Ágrip
Inngangur: Faraldsfræðirannsóknir hafa margsinnis sýnt fram á tengsl milli heilkornaneyslu
og minni áhættu krónískra sjúkdóma en niðurstöður úr íhlutandi rannsóknum hafa verið
misvísandi. Möguleg skýring á mótsagnakenndum niðurstöðum úr íhlutunum er sú að ekki
hefur verið til nákvæmur og hlutlaus mælikvarði fyrir heilkornaneyslu. Notkun
alkýlresorsínóla (AR) sem lífvísa fyrir neyslu á heilkornahveiti og -rúg lofar góðu þrátt fyrir
að enn sé margt óþekkt um notkun þeirra. Meginmarkmið ritgerðarinnar var að auka þekkingu
á notkun AR sem lífvísa með því að skoða hvort hægt væri að nota AR í blóðvökva sem
lífvísi fyrir heilkornaneyslu í heilsusamlegu norrænu mataræði og með því að meta tengsl
milli AR í blóðvökva við sykurefnaskipti og styrk blóðfitu hjá einstaklingum með
efnaskiptavillu. Fyrri íhlutanir sem hafa metið heilsufarsleg áhrif heilkornaneyslu, sérstaklega
heilkorna rúgs, hafa verið gerðar þar sem neysla á heilu korni er mikil fyrir. Það var því
æskilegt að meta fýsileika slíkrar rannsóknar meðal íslenskra karlmanna, sem neyta að jafnaði
lítils magns af heilu korni, og nota AR í blóðvökva sem mælikvarða á fylgni.
Aðferðir: Doktorsverkefnið er byggt á gögnum frá tveimur öndvegisverkefnum Nordforsk,
íhlutunarrannsókn sem er hluti af SYSDIET – Systems biology in controlled dietary
interventions and cohort studies og á fýsileikarannsókninni ARI, sem er áframhald af
verkefninu HELGA: Nordic Health – Whole Grain Food.
SYSDIET íhlutunin var framkvæmd á 6 rannsóknarstofum í Finnlandi, Svíþjóð,
Danmörku og Ísland. Þátttakendur voru á aldrinum 30-65 ára, með líkamsþyngdarstuðul 2740 kg/m2 og tvö önnur einkenni efnaskiptavillu, en án sykursýki 2. Þeim var slembiraðað í tvo
hópa, hóp sem fylgdi heilsusamlegu norrænu mataræði (ND, N=104) eða hóp sem fylgdi
viðmiðunarmataræði (N=96), í 18 eða 24 vikur (misjafnt eftir rannsóknarsofum). Í
rannsóknarvikum 0, 12 og 18/24 var AR í blóðvökva mælt (N=158) og næringarefnainntaka
metin með fjögurra daga fæðuskráningu á viku 0, 12 og 18/24.
Ákvarðandi þættir fyrir styrk AR í blóðvökva á viku 18/24 voru metnir með línulegri
aðhvarfsgreiningu og áreiðanleiki AR mælinga í íhlutuninni var metinn með innanflokks
fylgni (ICC). Gögn frá báðum hópunum voru tekin saman og tengsl heildarstyrks AR í
blóðvöka og hlutfalls AR raðkvæmana C17:0/C21:0 (sem vísbending um hlutfallslega neyslu
heilkorna rúgs af heildar heilkorna rúgi og -hveiti) við sykurefnaskipti og blóðfitu í lokaviku
íhlutunarrannsóknarinnar voru metin.
Í fýsileikarannsókninni ARI voru þátttakendur karlar á aldrinum 42-80 ára með
sykursýki af gerð 2. Þeim var slembiraðað í tvo hópa, rúghóp (N=14) eða viðmiðunarhóp
(N=9) í 26 vikur. Þátttakendur í rúghópi voru beðnir um að borða 100 g af heilkornarúgi
daglega. Ásættanleiki og fylgni við heilkornaneysluna voru metin með spurningalistum,
fjögurra daga fæðuskráningu og AR styrk í blóðvökva.
Niðurstöður: Heildarstyrkur AR í blóðvökva jókst úr 73 (88) í 106 (108) nmol/L, eða um
45%, frá viku 0 til loka rannsóknarinnar (P >0.001). Heildarstyrkur AR var þá marktækt hærri
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í ND hópi en viðmiðunarhópi (P <0.001) og rannsóknarhópur var ákvarðandi þáttur fyrir
heildarstyrk AR í lok rannsóknar (P <0.001). ICC fyrir heildarstyrk AR frá viku 12 til 18/24
var á bilinu 0.44 – 0.72. Marktækur munur var milli rannsóknarstofa á heildarstyrk AR við
upphaf rannsóknar þar sem miðgildi var 108 (96) nmol/L hjá þátttakendum frá Oulu og 108
(72) nmol/L hjá þátttakendum frá Kuopio, á meðan miðgildið var 43 (37) nmol/L hjá
þátttakendum frá Reykjavík.
Þegar gögn frá bæði ND hópi og viðmiðunarhópi voru sameinuð var AR hlutfallið
C17:0/C21:0 neikvætt tengt styrki á fastandi insúlíni (B (95% CI): -0.43 (-0.77 til -0.08)) og
jákvætt tengt vísum um insúlínnæmi, Matsuda (0.23 (0.07 til 0.40)) og DI (0.77 (0.11 til
1.43)). Auk þess var AR hlutfallið C17:0/C21:0 neikvætt tengt styrki á LDL kólesteróli (-0.41
(-0.80 til -0.002)), hlutfalli LDL og HDL kólesteróls (-0.20 (-0.37 til -0.03)), ekki-HDL
kólesteróli (-0.20 (-0.37 til -0.03)), apólípópróteini B (-0.12 (-0.24 til 0.00)) og þríglýseríðum
(-0.35 (-0.59 til -0.12)) og jákvætt tengt HDL-kólesteróli (0.11 (0.00 to 0.21)). Ekki var
marktækt samband milli þessarra breyta og heildarstyrks AR í blóðvökva við lok rannsóknar.
Tólf þátttakendur í rúghópi kláruðu fýsileikarannsóknina ARA og 8 í viðmiðunarhópi.
Neysla á heilkornarúgi og heildarstyrkur AR í blóðvökva jókst marktækt í rúghópi (P=0.003
og 0.004) og meðalneyslan á heilkornarúgi í íhlutuninni var 93 (44) g/dag. Meðalneysla 7
þátttakanda í rúghópi var yfir 100 g/dag. Engin breyting varð á rúgneyslu í viðmiðunarhópi og
var meðalneyslan 10 (8) g/dag. Fjórir þátttakendur fundu fyrir óþægindum í meltingarvegi á
fyrstu 13 vikunum og tveir á vikum 13-26.
Ályktun: Niðurstöðurnar benda til þess að styrkur AR í blóðvökva geti verið gildur lífvísir í
heilsusamlegu norrænu mataræði og að hægt sé að nota AR hlutfallið C17:0/C21:0 sem
mælikvarða á hlutfallslega rúgneyslu. Auk þess benda niðurstöðurnar til þess að aukinn hluti
heilkornarúgs, mælt með AR hlutfallinu C17:0/C21:0, sé tengt lægra fastandi insúlíni, auknu
insúlínnæmi og hagstæðari blóðfitugildum. Þó Íslendingar borði jafnan lítið magn heilkorns
bentu lítið brottfall og góð fylgni við mataríhlutunina í fýsileikarannsókninni til þess að
íhlutun af slíku tagi sé möguleg.
Lykilorð: alkýlresorsínólar, norrænt mataræði, heilkorn, rúgneysla, lífvísir
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Table of Contents
Abstract ...................................................................................................................................... 5
Ágrip........................................................................................................................................... 7
List of figures ........................................................................................................................... 11
List of tables ............................................................................................................................. 11
Abbreviations ........................................................................................................................... 13
List of original papers .............................................................................................................. 14
1. Introduction .......................................................................................................................... 15
2. Background .......................................................................................................................... 16
2.1. What is the healthy Nordic diet? ................................................................................... 16
2.2. Whole grain ................................................................................................................... 19
2.2.1. Whole grain cereals in the Nordic diet ................................................................... 20
2.2.2. Whole grain intake estimation methods and their limitations ................................ 22
2.3. Dietary biomarkers in nutritional science ...................................................................... 22
2.3.1. Dietary biomarkers of whole grain intake .............................................................. 23
2.3.2. Alkylresorcinols as biomarker of whole grain wheat and rye intake ..................... 23
2.3.3. Alkylresorcinols C17:0/C21:0 homologue ratio as marker of relative rye intake . 26
2.3.4. Bioactivity of alkylresorcinols ................................................................................ 26
2.4. Whole grain intake and human health ........................................................................... 26
2.4.1. Whole grain effects on glucose and insulin ............................................................ 27
2.4.2. Whole grain effects on blood lipids ........................................................................ 28
3. Aims ..................................................................................................................................... 30
4. Methods ................................................................................................................................ 31
4.1. The SYSDIET intervention ........................................................................................... 31
4.1.1. Study design ............................................................................................................ 31
4.1.2. Study population ..................................................................................................... 32
4.1.3. Dietary intervention ................................................................................................ 33
4.1.4. Dietary assessment.................................................................................................. 35
4.1.5. Anthropometric measurements ............................................................................... 35
4.1.6. Oral glucose tolerance tests .................................................................................... 36
4.1.7. Biochemical measurements ..................................................................................... 36
4.1.8. Dietary biomarkers ................................................................................................. 37
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4.2. ARI feasibility study ...................................................................................................... 37
4.2.1. Participants and study design ................................................................................. 37
4.2.2. Study diet ................................................................................................................. 38
4.2.3. Physical activity ...................................................................................................... 39
4.2.4. Compliance and acceptability ................................................................................. 39
4.2.5. Anthropometric and biochemical measurements .................................................... 40
4.3. Statistical analysis.......................................................................................................... 40
4.4. Approvals....................................................................................................................... 42
5. Results and discussion .......................................................................................................... 43
5.1. The SYSDIET intervention ........................................................................................... 43
5.1.1. Baseline characteristics of the participants ............................................................ 43
5.1.2. Changes observed during the intervention ............................................................. 44
5.2. Plasma alkylresorcinols as dietary biomarkers in healthy Nordic diet (Paper I) ........... 46
5.2.1. Changes in plasma alkylresorcinols concentrations during the intervention ........ 46
5.2.2. Determinants of plasma alkylresorcinols concentration ........................................ 48
5.2.3. Six to twelve week reproducibility of plasma alkylresorcinols ............................... 49
5.2.4. Correlations between alkylresorcinols and nutrient intake .................................... 51
5.3. Plasma alkylresorcinols and cardiovascular risk factors (Papers II-III) ........................ 51
5.3.1. Glucose and insulin parameters ............................................................................. 51
5.3.2. Blood lipids ............................................................................................................. 53
5.4. ARI feasibility study (Paper IV) .................................................................................... 55
5.4.1. Baseline ................................................................................................................... 55
5.4.2. Rye and dietary fiber consumption ......................................................................... 56
5.4.3. Compliance ............................................................................................................. 57
5.4.4. Acceptability ........................................................................................................... 58
6. Strengths and limitations ...................................................................................................... 60
7. Conclusion ............................................................................................................................ 61
8. Future perspectives ............................................................................................................... 62
9. Acknowledgements .............................................................................................................. 63
10. References .......................................................................................................................... 64
Papers I – IV
Appendix
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List of figures
Figure 1. Yearly supply of barley, rye and oats for human consumption in the Nordic
countries, kg per capita 1961-2011 .......................................................................................... 20
Figure 2. Study design of the SYSDIET intervention ............................................................. 32
Figure 3. Outline of the study design and main outcome measurements at each visit ............ 38
Figure 4. Flow chart of the SYSDIET study ........................................................................... 43
Figure 5. Total plasma alkylresorcinols concentrations for participants in healthy Nordic diet
(ND) and control groups at week 0, 12 and 18/24. Values are medians and bars represent the
interquartile range (IQR) .......................................................................................................... 47
Figure 6. Rye consumption and total dietary fiber intake for rye group (RG) and control
group (CG) at week 0, 13 and 26 of the intervention. .............................................................. 57
Figure 7. Total plasma alkylresorcinols (AR) concentration and AR C17:0/C21:0 ratio for rye
group (RG) and control group (CG) at week 0, 13 and 26 of the intervention ........................ 58
Figure 8. The rye group´s acceptability of the rye products (n = 12) assessed by three
questions at week 13 (13 w) and week 26 (26 w): a) I have experienced digestive discomfort
after I started eating rye products b) I like food products that contain rye and c) I would prefer
products that contain rye more than other products ................................................................. 59
List of tables
Table 1. Different definitions of a Healthy Nordic Diet .......................................................... 18
Table 2. Dietary fiber content and composition of whole grain wheat, whole grain rye,
dehulled oats, and naked barley ............................................................................................... 21
Table 3. Alkylresorcinols (AR) content range and AR ratio C17:0/C21:0 reported in
commonly consumed cereal grains .......................................................................................... 24
Table 4. Advised nutrient composition and suggested food items of for the study diets ........ 34
Table 5. Whole grain rye, energy, fiber, added sugar and salt content for the rye products
provided for the rye group in the study .................................................................................... 38
Table 6. Baseline characteristics of the participants in the healthy Nordic diet (ND) group and
the control group who completed the SYSDIET study and had valid blood samples for
alkylresorcinols analyses at week 0 and 18/24 ......................................................................... 44
Table 7. Total dietary fiber intake in healthy Nordic diet (ND) and control groups during the
intervention............................................................................................................................... 45
Table 8. Total plasma alkylresorcinols (AR) concentration and AR C17:0/C21:0 ratio for the
healthy Nordic diet group (ND) and control group at baseline and after the 18/24 week
intervention............................................................................................................................... 46
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Table 9. Regression coefficients for factors affecting plasma total alkylresorcinols (AR) at
week 18/24 (log transformed) .................................................................................................. 48
Table 10. Baseline dietary intake of fiber, plasma total alkylresorcinols (AR) and AR
C17:0/C21:0 ratio at different study centers ............................................................................ 49
Table 11. Estimated intra-class correlation coefficients (ICC, based on log-transformed
values) between week 12 and 18/24 for all participants combined, healthy Nordic diet (ND)
group and control groups .......................................................................................................... 50
Table 12. Correlations for plasma total alkylresorcinols and intakes of various nutrients
abundant in whole grain for both healthy Nordic diet (ND) and control group ....................... 51
Table 13. Regression models for fasting insulin and insulin sensitivity indices at 18/24 weeks
(log transformed values)........................................................................................................... 52
Table 14. Regression models for concentrations of serum LDL, HDL, non-HDL cholesterol,
triglycerides and apolipoprotein B and the cholesterol LDL-C/HDL-C ratio at 18/24 weeks. 54
Table 15. Baseline characteristics of the participants in the ARI feasibility study ................. 56
Table 16. Energy and macronutrient intake for both groups at week 0, 13 and 26 ................. 57
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Abbreviations
AACC
AOAC
ARI
Apo A1
Apo B
AR
BMI
CV
CVD
DI
EFSA
ENL
EPIC
FFQ
GC-MS
GluAUC0-30
HDL
(HMG)-CoA
ICC
IDF
IGI
IGI 120
IL-Ra 1
InsAUC0-30
IQR
ISI
LDL
ND
OGTT
SD
SYSDIET
American Association of Cereal Chemists
Association of Analytical Chemists
A rye intervention
Apolipoprotein A1
Apolipoprotein B
Alkylresorcinols
Body mass index
Coefficient of variation
Cardiovascular diseases
Disposition index
European Food Safety Authority
Enterolactone
European Prospective Investigation into Cancer and Nutrition
Food frequency questionnaires
Gas chromatography–mass spectrometry
30 minutes area under the curve for glucose
High density lipoprotein
Hepatic hydroxymethylglutarate
Intra-class correlation
International Diabetes Federation
Insulinogenic index
Insulinogenic index at 120 minutes
Interleukin-1 Ra
30 minutes area under the curve for insulin
Interquartile range
Insulin sensitivity index
Low density lipoprotein
healthy Nordic diet
Oral glucose tolerance test
Standard deviation
Systems biology in controlled dietary interventions and cohort studies
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List of original papers
This dissertation is based on the following papers, which will be referred to in the text by their
respective Roman numerals:
I
Title: Plasma alkylresorcinols reflect important whole-grain components of a healthy
Nordic diet
Authors: OK Magnusdottir,R Landberg, I Gunnarsdottir, L Cloetens, B Åkesson, G
Önning, SE Jonsdottir, F Rosqvist, U Schwab, KH Herzig, MJ Savolainen, L Brader,
K Hermansen, M Kolehmainen, K Poutanen, M Uusitupa, I Thorsdottir, U Risérus
Status: Journal of Nutrition 2013; 143: 1383-1390.
II
Title: Plasma alkylresorcinols C17:0/C21:0 ratio, a biomarker of relative whole grain
rye intake, is associated to insulin sensitivity - a randomized study
Authors: OK Magnusdottir,R Landberg, I Gunnarsdottir, L Cloetens, B Åkesson, M
Landin-Olsson, F Rosqvist, D Iggman, U Schwab, KH Herzig, MJ Savolainen, L
Brader, K Hermansen, M Kolehmainen, K Poutanen, M Uusitupa, I Thorsdottir, U
Risérus
Status: European Journal of Clinical Nutrition 2014; 68: 453-458.
III
Title: Whole grain rye intake, reflected by a biomarker, is associated with favorable
blood lipid outcomes in subjects with the metabolic syndrome – a randomized study
Authors: OK Magnusdottir,R Landberg, I Gunnarsdottir, L Cloetens, B Åkesson, F
Rosqvist, U Schwab, KH Herzig, J Hukkanen, MJ Savolainen, L Brader, K
Hermansen, M Kolehmainen, K Poutanen, M Uusitupa, U Risérus, I Thorsdottir
Status: PLOS ONE, in press
IV
Title: Increasing rye consumption among men with type 2 diabetes: a feasibility study
Authors: : OK Magnusdottir, R Landberg, I Gunnarsdottir, KT Magnusson, G
Hallmans, RD Hansen, C Kyrø, A Olsen, A Tjønneland, I Thorsdottir, L
Steingrimsdottir
Status: manuscript
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1. Introduction
The principal aim of this dissertation was to increase knowledge on the use of plasma
alkylresorcinols (AR) concentrations as dietary biomarkers for whole grain wheat and rye
intake. This PhD project was in close collaboration with two extensive research projects,
SYSDIET - Systems biology in controlled dietary interventions and cohort studies and
HELGA: Nordic Health — Whole Grain Food, both of which were funded as Nordic Centres
of Excellence in Food, Nutrition and Health by NordForsk.
It is well accepted that Western population would benefit from higher consumption of
whole grains as whole grain and cereal fiber consumption has almost consistently been
inversely associated with the risk of developing chronic diseases in epidemiological studies
[1-3]. Findings in intervention studies have, however, been inconsistent [4, 5].
Nutritional science relies on accurate dietary information to assess compliance to
dietary interventions and to investigate diet-disease associations. However, dietary assessment
instruments rely most often on self-reporting, which is prone to measurement errors [6-10].
Collecting data on whole grain intake can be especially challenging because of the broad
selection of foods contributing to these intakes and the difficulty that consumers and
researchers have in assessing the whole grain content of foods consumed [11-13]. Hence, the
reason why results from intervention studies are often inconclusive may relate to absence of
accurate and objective measures of whole grain intake. The use of dietary biomarkers could
be one way to improve the validity of dietary assessment in combination with, or as an
alternative for, self-reports or as a tool for secondary analysis, where non-compliant
individuals can be excluded on the basis of biomarker measurements [14-17].
AR have been proposed as biomarkers for whole grain and bran intake of wheat and
rye [12, 18-20] and for cereal fiber intake in populations with a high intake of whole grain
wheat and rye [21]. Controlled whole grain and bran intervention studies show that plasma
AR concentration increases proportionally with AR and whole grain intake [18, 22-26] and
can be used as a biomarker of compliance to a whole grain diet [20, 27]. Additionally, the
ratio of the AR homologues C17:0 and C21:0 differs between cereals species [28] and the
ratio in plasma samples have been suggested to reflect proportion of whole grains consumed
[25]. Currently, AR appear to be highly promising biomarkers of whole grain wheat and rye
intake [12, 29] although there are still many factors that are poorly understood. Analysis of
plasma AR as a biomarker in the healthy Nordic diet, which is rich in whole grain wheat and
rye, adds valuable knowledge of plasma AR as biomarkers and their use in future studies of
the healthy Nordic diet. Additionally, the analyses of the association between plasma AR and
clinical biomarkers of health and the usage of plasma AR as a measure of compliance in
intervention studies adds knowledge and weight to further usage of plasma AR as biomarkers
of whole grain wheat and rye intake in nutritional science.
15
2. Background
2.1. What is the healthy Nordic diet?
It is scientifically substantiated that dietary quality has an important impact on the risk of
chronic diseases [30]. In nutritional science, traditional analysis has focused on evaluating the
effect of a single food or nutrient on the risk of developing disease. This approach has been
successful in the past and has helped to eliminate a number of deficiency diseases in many
parts of the world. However, it appears to be less effective in addressing the most important
present-day nutrition-related health problems. Globally, there have been rapid changes in the
food environment where traditional, regionally available foods have been and are still being
replaced by modern industrial and processed foods [31, 32]. This dietary pattern, often
referred to as Westernized dietary pattern, is typically dense in energy and characterized by
high intakes of fat and saturated fatty acids, processed and red meats, refined cereals and food
products with added refined sugars, fat and salt [31-33]. These swift changes in food and
eating patterns, together with over-consumption, has been suggested to be one of the main
determinants for many of the chronic diseases seen today [31-34]. Therefore, in recent years,
the focus of nutritional research has moved toward evaluating the overall impact of diets and
patterns of food consumption on health outcomes, instead of single nutrients or food items.
Such an approach has resulted in a significant amount of new and original research [33, 35].
The focus of current nutritional recommendations has also changed with more emphasis on
food-based dietary guidelines where advice on dietary intake is conveyed at the food level
[33].
The best known example of a prudent whole diet is the Mediterranean diet,
representing the diet traditionally consumed in Southern Europe. The Mediterranean diet has
been extensively studied and it has been associated with improved health and prevention of
chronic diseases in many studies [36-40]. The acceptance of the diet has, however, not been
easy in other parts of the Western world [41]. Instead of imposing one universal diet it would
be more sensible to tailor practical recommendations for healthy eating to regional
circumstances. Most countries or regions do have their own traditional and regionally
appropriate foods that could be as health enhancing as the ingredients of the Mediterranean
diet. Such regional tailoring of recommendations are important for the environment and also
for health, as it would be easier to adhere to such diets due to the availability of food items,
taste preferences, cultural differences and familiarity of the foods [31, 41-43].
The dietary habits in the Nordic countries have several common features and trends in
food consumption tend to be similar [44-46]. Although the modern Nordic diet resembles the
conventional Western diet, and is therefore not considered to be positively related to health
outcomes [45], it also includes a range of foods with expected health-promoting effects. Plant
foods such as berries, apples, pears, cabbages, root vegetables and potatoes thrive well in the
Nordic climate, as well as oats, rye and barley. Also, the long coastlines of the Nordic
countries provide rich sources of fish [31, 46, 47]. Several prospective epidemiological
studies have studied Nordic dietary patterns, including traditional Nordic food with expected
16
health-promoting effects, and concluded that it is associated with important health benefits,
lower total mortality [48] and incidence of colorectal cancer [47].
The health effects of the healthy Nordic diet have been studied in a number of
interventions studies and results suggest beneficial effects on cardiovascular risk factors and
mortality [48-52]. Although definitions of the healthy Nordic diet are not completely
congruent it is generally defined by healthy foods that can be produced in the Nordic
countries and are traditionally consumed (Table 1). Common features include berries,
vegetables (mainly cruciferous vegetables), whole grain products (mainly oats, barley and
rye), fish and game and free-range or pasture fed animals [31, 51, 53, 54]. When compared to
a conventional Western diet the healthy Nordic diet has generally more dietary fibers, lower
salt content and higher quality of dietary fat [51, 53, 55, 56].
17
Table 1. Different definitions of a Healthy Nordic Diet
Food choice based on:
Bere and Brug (2009) [31]
Ability to be produced locally
over large areas in the Nordic
countries without usage of
external energy, e.g. greenhouses,
New Nordic diet – OPUS project [54]
SYSDIET study [51]
Nutritional value
Health
Traditional Nordic food items
Agricultural traditions
Gastronomic potential, palatability
Seasonal variations
Nordic identity and cultural heritage
Diet and nutrition profile based on
2004 Nordic Nutrition
Recommendation[57]
Habitual use of food items, foods
commonly available in local super
markets
Sustainability, locally grown foods and
organic food production
Tradition as a food source
Possessing better potential for
health-enhancing effects than
similar foods within the same
food group
Ability to be eaten as foods, not
only in small amounts as dietary
supplements (e.g. spices)
Key food items
NORDIET study [49, 53]
Native berries
Cabbage
Oat/barley/rye
Rapeseed oil
Native fish and other seafood
Wild and pasture-fed land-based
animals
Diet and nutrition profile based on
2004 Nordic nutrition
recommendation[57] and 80% of
the diet should be ”Nordic”
Fruits, berries, vegetables and root
vegetables
Potatoes
Whole grains in general and
specific whole grain cereals based
on oat, barley and rye
Rapeseed oil, vegetable fat spread
Nuts, mainly almonds
Fish, especially fatty fish Poultry,
lamb, game, small portions of red
meat and sausages
Low fat dairy
Fundamental guidelines:
- More calories from plant foods and
fewer from meat
- More foods from the sea and lakes
- More foods from the wild
countryside
Fruits and vegetables, including
berries, cabbages, root vegetables and
legumes
Potatoes
Fresh herbs
Plants and mushrooms from the wild
countryside
Whole grains
Nuts
Fish and shellfish
Seaweed
Free-range livestock, including pigs
and poultry and game
Fruits and vegetables, including
berries
Whole grain, of which at least 50%
rye, barley and oat
Rapeseed and/or sunflower and/or
soybean oil
Fish, fatty and lean
White meat, poultry, game
Low fat dairy
18
2.2. Whole grain
Since the beginning of agriculture, cereals have been a part of the human diet. Cereals were
traditionally consumed as whole grain and it is only within the last hundred years that people
have consumed refined grain products [58].
The American Association of Cereal Chemists (AACC) define whole grain as follows:
“Whole grains shall consist of the intact, ground, cracked or flaked caryopsis, whose
principal anatomical components – the starchy endosperm, germ and bran – are present in
the same relative proportions as they exist in the intact caryopsis” [59]. This definition has
also been adopted by the U.S. Food and Drug Administration [60]. The European
HEALTHGRAIN Forum suggested that small losses of components, i.e. less than 2% of the
grain and/or 10% of the bran, that occur through processing methods consistent with safety
and quality, should be allowed [61]. The main cereals consumed as whole grain are wheat,
corn, rice, oats, barley and rye. Millets, sorghum, teff, triticale, canary seed, Job’s tears, fonio,
wild rice are also included in the definition of whole grain, and some definitions also include
the pseudocereals amaranth, quinoa and buckwheat [60, 61].
Although a working definition exists for whole grains and relevant whole grain
ingredients, no universal agreement on the exact definition of whole grain products exists,
with questions remain regarding the processing of the grains, range of cereals to be included
and proportion of whole grain in the food. Typically whole grain food contains a certain
proportion of intact, flaked or broken kernels, coarsely ground kernels or flour of whole grain
but different proportions have been used across studies. Many of the studies on whole grain
and disease have used the definition of whole grain products by Jacobs et al [62], which
proposes that ≥ 25% of product weight must be whole grain, but other definitions have been
used as well [60, 63-65]. In 2013, the AACC International Board of Directors approved the
Whole Grain Working Group’s characterization of a whole grain product: “A whole grain
food must contain 8 grams or more of whole grain per 30 grams of product” [66] and this
definition was also proposed at a whole grain expert roundtable discussion in 2014 [13].
The Keyhole Symbol is a public symbol on packages for food products used in the
Nordic countries, which meet certain criteria on nutritional value. Thus, food products with
the keyhole symbol are healthier than other products in the same food category that do not
meet the criteria. To be allowed to use the Keyhole Symbol soft bread should contain ≥25%
whole grain, and crisp bread, pasta, breakfast cereals, and porridge should contain at least
≥50% whole grain to fulfill the requirements. For flours, flakes, and kernels the content of
whole grain should be 100% [67, 68].
In addition to different definitions of whole grain and whole grain products in previous
studies, changes in dietary fiber characteristics during processing and preparation of whole
grain products, such as molecular weight distribution and extractability, are considerable. This
may impact the physiological effects of whole grain consumption, the chemical and
nutritional composition as well as physical structures and functional properties in various
ways [69-71].
19
2.2.1. Whole grain cereals in the Nordic diet
Food supply quantity
kg/capita/year
The most commonly consumed cereals in the Scandinavian countries are wheat, rye and oats,
while barley has been used to a lesser extent [31, 72]. Oats, barley and rye do, however, grow
better in colder climates than e.g. wheat and are produced in many areas in the Nordic
countries [31]. Still, the proportion of wheat as a total of cereal consumption has increased in
the last decades and today, around 80% of all grains consumed in the Nordic countries are
wheat [31, 72]. Wheat is usually consumed as white flour, while oats, barley and rye are most
often consumed as whole grains which make them an important constituent of the healthy
Nordic diet.
Among the Nordic countries, Sweden is the only country that has data on whole grain
intake in their most recent national dietary survey among adults. The data showed an average
intake of 42 g/day of whole grain for adults age 18-80 years old [73]. In Denmark, data from
the 2011-2013 Danish National Survey of Dietary habits and Physical activity were used to
estimate the whole grain intake and the results showed an average intake of 55 g/day [74].
Rye is the second most commonly consumed grain, behind wheat, in the Nordic
countries [72, 75]. In Iceland, rye and oatmeal were the main types of whole grain in the diet
during the first half of the 20th century and in 1930 the average rye consumption was 152
g/day [76]. However, according to food supply data, rye consumption has decreased
dramatically in the last 50 years in Iceland, as well as in other countries (Figure 1) [72, 77]. In
2011, the average rye consumption in Iceland was 8 g/day, the lowest among the Nordic
countries while the average was 47 g/day in Denmark, 45 g/day in Finland, 32 g/day in
Sweden and 18 g/day in Norway [72]. The change in oat consumption has not been as
dramatic. In Iceland the average oat consumption was 13 g/day in 2011 compared to 25 g/day
in 1961. In 2011 the average oat consumption was 28 g/day in Denmark, 18 g/day in Finland,
13 g/day in Norway and negligible in Sweden [72].
20
18
16
14
12
10
8
6
4
2
0
Barley and products
Rye and products
Oats
1961 1970 1980 1990 2000 2011
Figure 1. Yearly supply of barley, rye and oats for human consumption in the Nordic
countries, kg per capita 1961-2011 [72]
20
In line with these results a subgroup analysis of the participants in the HELGA study,
including data from Denmark, Sweden and Norway, showed a clear national difference in the
sources of whole grain intake [75]. In the populations studied whole grain rye constituted
more than 70% of the total whole grain intake in Denmark, more than 50% in Sweden but
only 20% in Norway. Whole grain oats made up 6 to 19% of the total whole grain intake in
the three countries [75].
Bread is by far the most common rye product, followed by rye flakes, which are
frequently used for baking, porridge and breakfast cereals. Oats are not as suitable for making
bread due to the lack of gluten and are therefore often prepared as a porridge, flakes or
breakfast cereals made from crushed or rolled oats. Oats are however utilized in a variety of
baked items as oat flour or oatmeal, and breads can be made from a mixture of oatmeal and
wheat flour [78]. Barley has primarily been used in animal feed as well as for production of
malt and only to a limited extent for human consumption [31, 72].
Rye, oats and barley are rich sources of vitamins, minerals and bioactive compounds
[79-81]. Rye is particularly high in dietary fiber with 20% of dry matter consisting of fiber,
compared to 10% in oats and 15% in barley (Table 2) [69, 82]. The main dietary fiber
components of rye are arabinoxylan, fructan, β-glucan and cellulose [71, 83] while β-glucans
are more abundant in oats and barley (Table 2) [71]. Thus, the physiological effects of dietary
fiber differ depending on which cereal has been consumed and thereby the nutritional and
potential health effects are also influenced.
Table 2. Dietary fiber content and composition of whole grain wheat, whole grain rye,
dehulled oats, and naked barley [71]
Component
Wheat
Total dietary fiber, %
13.5
Arabinoxylan, %
5.6
Cellulose, %
2.5
β-Glucan, %
0.8
Fructan, %
1.3
Klason lignin, %
0.8
Data are presented as percentage of dry matter
Rye
Oats
Barley
19.9
8.9
2.9
1.5
4.1
1.1
10.2
2.0
1.3
5.0
0.2
1.4
15.2
5.2
1.9
4.6
1.6
0.7
21
2.2.2. Whole grain intake estimation methods and their limitations
Nutritional science relies on accurate dietary information to assess compliance to dietary
interventions and to investigate diet-disease associations. Dietary assessment methods include
food frequency questionnaires (FFQs), diet histories, 24-hour recalls and weighed or
estimated food records [84]. However, most dietary assessment instruments rely on selfreporting which is prone to both systematic and random errors. These errors are due to e.g. the
use of food tables, variations in frequency of food consumption or portion size, misreporting
or failure to report usual diet, as well as changes in typical habits whilst taking part in a study
[6-10]. In addition, dietary assessment methods are often not designed to assess whole grain
intake, with e.g. limited number of questions in FFQs which can be used to rank subjects
according to their whole grain intake and that may result in an underestimation and inaccurate
measures of intake [11].
The increase in the availability of whole grain products during the past decade has
made accurate assessment of whole grain intake increasingly challenging. The existing whole
grain food composition data is limited and up-to-date nutrient databases are needed to better
assess whole grain intake and capture the changing whole grain food supply [13]. The lack of
a uniform definition of whole grain products, the increasing breadth of different foods and
processing methods this food category covers, and the difficulty that consumers and
researchers have in accurately knowing the whole grain content of foods consumed adds to
the challenge [11-13].
One way to avoid some of the obstacles associated with traditional dietary assessment
instruments is to use dietary biomarkers as an alternative, or as a complement, to self-reports.
Biomarkers have the potential to bypass the inherent errors associated with traditional diet
assessment tools, be less subject to intra-individual variation, and can allow blind assessment
of compliance in dietary intervention trials where a true placebo is not feasible. It also allows
for a specific association of certain parts of a complex diet with health variables [14-17].
However, factors such as genetic variability, lifestyle/physiologic factors (e.g. smoking),
dietary factors, biological sample and analytical methodology [29, 85] can skew the
biomarker measures. As a result, it is imperative to assess the validity, reproducibility of the
biomarkers, as well as the ability to detect changes over time and robustness across diverse
populations. The use of dietary biomarkers, especially for whole grain intake, will be
discussed in the following sections.
2.3. Dietary biomarkers in nutritional science
Dietary biomarkers, or nutritional biomarkers, are compounds related to a certain food or
nutrient that are measurable in biological tissues and fluids (e.g. plasma, urine and/or adipose
tissue), and thus can objectively reflect intake of specific dietary components [84]. There are a
number of compounds that have been suggested and used as dietary biomarkers of food
and/or nutrients and their purpose may be different depending on the types of study. Firstly,
dietary biomarkers can be used for validation of traditional dietary assessment instruments
22
[27, 86-89]. Dietary biomarkers can also be used in combination with, or as an alternative for,
self-reports to estimate intake in studies of association between diet and disease risk, or as
independent tools to confirm such associations derived using traditional dietary instruments
[90-95]. Additionally, in randomized controlled trials, dietary biomarkers can be used to
measure compliance or as a tool for secondary analysis, where non-compliant individuals can
be excluded on the basis of the biomarker measurements [95-99]. Hence, dietary biomarkers
can provide an important link between dietary exposure and disease, especially in situations
where traditional dietary assessment methods for different reasons provide poor intake
estimates.
2.3.1. Dietary biomarkers of whole grain intake
There is currently no generally accepted biomarker of overall whole grain intake. The
mammalian lignin enterolactone (ENL) has been evaluated as one such biomarker as whole
grain, especially rye, is rich in precursors of ENL and the concentration of ENL in plasma,
serum and urine increases with whole grain intake [100-102]. However, there are several
other sources of ENL precursors in the diet and the formation of ENL is dependent on the gut
flora as well as other non-dietary determinants [25, 102-104]. The ENL concentration may
therefore not be a suitable biomarker for whole grain intake.
About 10-15 years ago, AR were initially suggested to be a potential biomarker of
whole grain wheat and rye intake [20, 105, 106]. A method for the analysis of AR in plasma
was developed and initial biomarker evaluation studies were conducted [25, 107-111]. Plasma
AR as a biomarker for whole grain wheat and rye intake will be discussed in sections 2.3.2.
and 2.3.3.
To date, no other biomarker for whole grains, or specific whole grain type, has been
specifically identified and validated. Studies on metabolites have discovered potential markers
of certain whole grain food intakes using metabolomics, such as metabolites from
benzoxazinoids, as a marker for rye intake [112] but further studies need to be developed.
2.3.2. Alkylresorcinols as biomarker of whole grain wheat and rye intake
AR belong to a large group of phenolic lipids. Structurally they consist of a 1,3dihydroxybenzene ring (resorcinol), which is alkylated at position 5 by a saturated, oddnumbered hydrocarbon side-chain consisting of 17 to 25 carbon atoms (C13:0 - C27:0) [105].
AR are abundant in the outer layers of rye and wheat, found in low amounts in barley, maize
and peas, in trace amounts in refined white flour and absent in most other foods consumed in
the human diet [105]. The ratio of different homologues differs between different cereals and
can be used to differentiate between AR containing cereals. Barley, for example, has a larger
portion of C25:0 compared to other cereals, though overall it has much lower total AR
concentrations (Table 3) [105, 113].
23
Table 3. Alkylresorcinols (AR) content range and AR ratio C17:0/C21:0 reported in
commonly consumed cereal grains
Cereal
Rye
(Secale cereal)
Common wheat
(Triticum aestivum)
Durum wheat
(Triticum durum)
Einkorn wheat
(Triticum monococcum)
Emmer wheat
(Triticum dicoccon)
Spelt wheat
(Triticum spelta)
Barley
(Hordeum vulgare)
AR range,
µg/g dry matter
568-1231
AR C17:0/C21:0 ratio
References
0.80-1.30
[28, 79, 114-116]
300-943
0.09-0.24
194-687
0.01-0.02
[28, 115, 117,
118]
[105, 117]
545-654
0.04
[105, 117]
531-784
0.05
[105, 117]
490-741
0.09-0.14
[105, 117]
8-210
0.05-0.46
[28, 81, 113]
The average daily intake of AR has been estimated, using food supply data or consumption
data, and was found to differ within populations and between countries [119]. Food supply
data was obtained by converting amounts of milled rye/wheat to per capita amounts and then
multiplying this value by the average AR content of that cereal. According to this method, the
intake of AR ranged from 12 mg/day in the United Kingdom (UK), where white bread is
mostly consumed and 18 mg/day in Sweden, to nearly 40 mg/day in Finland. In the alternative
method utilizing food consumption data, individual food records (in Sweden) or household
shopping data (in the UK) were used to estimate AR concentrations based on a typical recipe
for the food in question. According to this data, the mean intake of AR in Sweden was 23
mg/day and in the UK 12 mg/day. The Swedish data was further analyzed and the intake of
AR was found to be higher in males than females and higher in the older age groups [119].
Intakes at the low end of the range may, however, be an underestimate as the small amounts
present in white wheat flour were not accounted for.
AR are stable during food processing and absorption is around 60% in the human
digestive tract [106, 120], though data from pigs and humans suggest that at higher doses the
percent absorbed is lower [23, 121]. After absorption, AR are suggested to be transported in
lipoproteins (mostly HDL) [25] and may be distributed and stored in some tissues, especially
adipose tissue [122]. The absorption half-life of AR is about 6-8 hours [107] and the half-life
of AR in plasma is around 5 hours [107]. Thus, strictly defined, plasma AR should be
regarded as a short-term biomarker but under stable and frequent intake conditions, it also
reflects long-term exposure fairly well [123].
24
Plasma levels of AR vary widely even at steady state, with mean overnight fasting
levels being 38 - 388 nmol/L with a moderate to high rye intake [108-110] and 943 nmol/L
with an extremely high (483 g/day) rye intake [24]. Plasma AR hardly ever reach zero, even
after avoiding whole grain products for a certain time in trials. This is at least partly due to the
storage of dietary AR in adipose tissue and liberation during low or no intake [122]. The total
plasma AR concentration and concentrations of five AR homologues (C17:0, C19:0, C21:0,
C23:0 and C25:0) was recently evaluated in ten Western European countries using data from
the European Prospective Investigation into Cancer and Nutrition (EPIC). A considerable
variation was observed across countries, both in plasma concentrations of total AR and
concentrations of AR homologues. High concentrations of plasma total AR were found in
participants from Scandinavia and Central Europe and lower concentrations in those from the
Mediterranean countries. The geometric mean plasma total AR concentrations were between
35 and 41 nmol/L in samples drawn from fasting participants in the Central European and
Scandinavian countries and below 23 nmol/L in participants from the Mediterranean countries
[124].
Correlations between plasma AR and various measures of their intake (AR intake,
whole grain intake, cereal fiber intake) range between 0.25 and 0.58, with better correlations
with more detailed dietary intake instruments [18, 19, 26, 109, 125]. Intervention studies
focusing on whole grain and bran intake have shown that plasma AR concentration
proportionally increases with AR and whole grain intake [18, 22-26]. As a biomarker for
whole grain wheat and rye intakes, AR can be used to categorize subjects as low and high
consumers of whole grain foods [19, 126] and also as a marker for compliance to a whole
grain diet in intervention studies [20, 27]. The reproducibility of plasma AR measurements,
evaluating whether a single measurement of a biomarker can reflect average levels over a
longer time period, have been reported to be good under intervention conditions (intraclass
correlation coefficient ICC = 0.88-0.9), and moderate under free-living conditions (ICC =
0.42-0.48) [19, 22, 127]. These studies further support the proposed use of fasting plasma AR
as a biomarker of whole grain intake, especially in populations where whole grain wheat and
rye intake is high and relatively consistent. However, further studies are needed to establish
cut-off points for determining when a person is complying with a diet or has not been eating a
certain amount of whole grain per day.
As an alternative to relying on plasma AR, quantification of AR in adipose tissue is
possible through adipose tissue biopsy samples [122]. The importance of the pool and factors
governing its turnover are, however, still unknown. In addition, the AR metabolites DHPPA
and DHBA in plasma and urine have also been suggested to serve as biomarkers for whole
grain rye and wheat intake [21, 128-130] although they have been less extensively studied
than the intact AR.
25
2.3.3. Alkylresorcinols C17:0/C21:0 homologue ratio as marker of relative rye intake
The ratio of C17:0/C21:0 is approximately 0.1 in wheat and 1 in rye, and this ratio has been
suggested to be a method for determining if a cereal product contains wheat, rye or a mixture
[28]. The C17:0/C21:0 ratio is to some extent reflected in fasting plasma samples and may be
used to differentiate sources of cereals consumed [25]. In plasma, the ratio after a rye diet is
somewhat lower than 1, usually around 0.6-0.8 after regular whole grain/bran rye
consumption [23, 25] and a ratio above 0.15 is usually indicative of some rye intake [12]. In a
cross sectional study from Sweden, where rye consumption is appreciable, the C17:0/C21:0
ratio was 0.5 in samples drawn eight hours since last meal [123] and in the EPIC study the
ratio was 0.1 in the UK and 0.17 in Italy where the main source was wheat while it was 0.43
in Sweden [124]. The reason for a lower ratio in plasma compared to what is observed in
whole grain/bran rye foods is likely due to faster metabolism of the AR homologue C17:0
[107, 131]. However, further insight into absorption and metabolism of the different
homologues is needed to clarify to what extent factors other than whole grain rye and wheat
affect the C17:0/C21:0 ratio [12].
2.3.4. Bioactivity of alkylresorcinols
A wide variety of bioactivities have been ascribed to AR from in vitro tests. AR have been
found to have slight antimutagenic effects and some antioxidant capacity although this is
weak compared to known antioxidants such as α-tocopherol [132, 133]. The effective
concentrations are high, ranging from 2.5 to 100 mol/L, while the maximum concentration
after a single meal containing 190 mg of AR from rye (120 g of rye bran) is 3-4 mol/L [107].
Such high intakes are not likely to be observed at “normal” intakes. Only limited in vivo work
has been carried out on possible biological function of AR and oral dosing with pure AR has
not been tested in humans [12].
2.4. Whole grain intake and human health
Today, there is a general long-standing view among major governmental, scientific and nonprofit organizations that the Western population would benefit from higher consumption of
whole grains as a way to reduce the risk of developing chronic diseases. As a result, whole
grain intake, as a part of a healthy diet, has been directly or indirectly promoted in the dietary
guidelines in a number of countries as well as by the World Health Organization [33, 134,
135].
Evidence of the health benefits of whole grains have mainly been derived from
epidemiological studies which have shown protective associations but not the causal links
between whole grain intake and health. Furthermore, most of the prospective cohort studies
reported in the literature are from large American cohorts, where the dominant whole grain
cereal consumed is wheat.
26
A consistent inverse association between intake of whole grain foods and
cardiovascular diseases (CVD) has been reported in these epidemiological studies [1-3]. In a
meta-analysis of prospective cohort studies Mellen et al [1] suggested that an average of 2.5
servings/day, compared to 0.2 servings/day, was associated with a 21% lower risk of CVD
events in adult populations. This finding was similar to an earlier meta-analysis by Anderson
et al [3].
Whole grain and cereal fiber consumption has repeatedly been inversely associated
with the risk of type 2 diabetes and insulin sensitivity in observational studies [2, 136-139]. In
a systematic review Priebe et al [140] found that 10 out of 11 prospective cohort studies
showed that high intakes of whole grains and cereal fiber was associated with a 27-30% and
28-37% decreased risk of developing type 2 diabetes, respectively. Similar results were
obtained in the Nurses’ Health Studies I and II that included more than 160 000 women [137].
In a systematic review of 15 observational studies on whole grain consumption and
measures of body weight and adiposity, consumption of three servings of whole grain foods
per day was associated with 0.63 kg/m2 reduction in body mass index (BMI) and 2.7 cm
decrease in waist circumference [141]. Whole grain foods have also been associated with a
reduced risk of some cancers and evidence from prospective studies show the associations are
strongest for cancer of the gastrointestinal tract [142, 143].
The underlying mechanisms for the protective effect of whole grain foods on
development of chronic diseases are thought to be diverse but are not fully understood [144,
145]. Results from epidemiological studies still remain to be confirmed by randomized
controlled trials as only few intervention studies on whole grain and disease have been
published. Most of these studies have been short-term with a small numbers of subjects as
they are difficult to perform. Studies have to rely on compliance over long periods of time if
the primary endpoints are the development of chronic diseases, such as CVD and type 2
diabetes. Reports on the effects of various sources of whole grain food on risk markers or
intermediate endpoints of CVD and diabetes and results have also been inconsistent [4, 5].
2.4.1. Whole grain effects on glucose and insulin
Potential mechanisms for the beneficial effects of whole grains on the risk of type 2 diabetes
are diverse since whole grains are rich in nutrients and phytochemicals. Given that insulin
resistance increases the risk of type 2 diabetes [146-148], insulin sensitivity may be one
important mechanism through which whole grain consumption confers protection.
A whole grain, high fiber diet has been suggested to enhance insulin receptor
sensitivity through chronic lowering of the overall dietary glycemic index and related insulin
secretion [149-155]. However, findings from intervention studies exploring the effect of
whole grain consumption on glucose and insulin concentrations or insulin resistance and
sensitivity have been inconsistent [5, 156-160]. Tighe et al [156] found no effects of three
whole grain food portions a day on glucose and insulin concentrations or markers of insulin
resistance and sensitivity after 12 weeks and Brownlee et al [5] reported the same conclusion
in the WHOLEheart Study. Pereira et al [149] did, however, find that whole grain
consumption had an effect on fasting plasma insulin concentration and insulin sensitivity and
27
Landberg et al [159] showed positive effects of higher rye consumption for 6 weeks on
fasting plasma insulin, using total plasma AR as a measure of compliance. Several
intervention studies have also shown diminished levels of postprandial insulin following a rye
bread meal [161-163]. The lower postprandial insulin response after rye bread consumption,
as compared to wheat bread, may be due to the difference in structure rather than fiber
content, as consumption of low fiber rye bread have been shown to have similar effects as
high fiber rye bread consumption [164, 165]. Moreover, an improved early insulin response
has been shown after rye bread interventions [164, 165]. The inconsistent results in
intervention studies might be due to differences in the type, amount, structure, processing and
preparation of whole grain products and carbohydrates consumed [71, 166]. Lack of
compliance and/or objective measurement of whole grain intake might also be an issue but
good adherence has, however, been indicated in most studies using weighed food records.
Other suspected mechanisms that might explain the effect of whole grain on insulin
sensitivity include slower gastric emptying [167], metabolic effects of certain micronutrients,
such as magnesium, selenium and vitamin E [154, 168-172], as well as through short-chain
fatty acid production by intestinal bacteria leading to enhanced hepatic glucose oxidation and
insulin clearance [173-176].
2.4.2. Whole grain effects on blood lipids
A number of intervention studies have found that whole grains lower serum total and LDLcholesterol [158, 177-179]. In respect to hypocholesterolemic effects oats are probably the
most studied cereal [180-183] and it is now well established that minimally processed βglucans in oats and barley reduce blood cholesterol concentration in both
normocholesterolemic and hypercholesterolemic subjects [184, 185]. The European Food
Safety Authority (EFSA) has approved two health claims on the subject: β-glucans contribute
to the maintenance of normal blood cholesterol levels [186] and oat β-glucan has been shown
to lower/reduce blood cholesterol. Blood cholesterol lowering may reduce the risk of
(coronary) heart disease [187]. Wheat fiber, however, does not appear to affect blood
cholesterol [188] and therefore it is often used as a control in experimental studies. The
mechanisms that have been proposed to cause the reduction in cholesterol levels revolve
around the fiber and phytochemical content of whole grains, particularly water-soluble
viscose fiber [144, 189]. Studies have shown that the cholesterol lowering effect of β-glucans
is dependent on the molecular weight and subsequent viscosity [70].
Few intervention studies have studied the effects of rye on blood lipids in humans.
Rye is especially high in dietary fiber, ranging between 18-22%, and rye contains substantial
amounts of extractable beta-glucans (1.5% of dry matter vs. 5.0% and 4.6% in oats and
barley, respectively, see Table 2) and arabinoxylans, which could contribute to cholesterol
reduction through similar mechanism as β-glucans from oats and barley [82, 83]. Animal
studies have shown cholesterol lowering effects of rye consumption [190-192] and that rye
could affect blood lipids by increasing the hepatic hydroxymethylglutarate (HMG)-CoA
reductase activity, which regulates cholesterol synthesis in the liver [190] or by increasing the
total concentration of bile acids in the bile [191, 193]. Bile acid excretion stimulates bile acid
28
synthesis from serum cholesterol, so reducing cholesterol levels in the blood. Studies in
humans have, however, been conflicting. One study reported that rye bread consumption
decreased total and LDL cholesterol in men with moderately elevated serum cholesterol [177]
and another showed lower plasma free-cholesterol, total cholesterol, triglycerides and
phospholipids after a high fiber rye diet compared to a low fiber wheat diet [178]. However,
Moazzami et al showed an unfavorable shift in serum cholesterol levels after rye bread intake
in postmenopausal women [194].
29
3. Aims
The aim of this dissertation was to increase knowledge on the use of plasma AR
concentrations as dietary biomarkers for whole grain wheat and rye intake.
The specific aims were to evaluate:
1. Whether plasma AR could be used as biomarkers for whole grain intake in the healthy
Nordic diet.
2. The association between plasma AR and glucose metabolism in a population with
metabolic syndrome.
3. The association between plasma AR and blood lipid concentrations in a population
with metabolic syndrome.
4. The feasibility of conducting an intervention with high consumption of whole grain
rye in a population of men with habitually low whole grain and fiber intake.
30
4. Methods
The thesis is based on two extensive research projects, SYSDIET - Systems biology in
controlled dietary interventions and cohort studies and HELGA: Nordic Health — Whole
Grain Food, both of which were funded as Nordic Centers of Excellence in Food, Nutrition
and Health by NordForsk.
Papers I-III are part of the SYSDIET study, a randomized controlled multicenter
intervention study performed in six intervention centers (Kuopio and Oulu, Finland, Lund and
Uppsala, Sweden, Aarhus, Denmark, and Reykjavik, Iceland). The main aim of the SYSDIET
intervention was to clarify whether a Nordic alternative for healthy food pattern in a weightstable condition would have beneficial effects on insulin resistance, glucose tolerance, serum
lipids and lipoproteins, and inflammatory markers in people with metabolic syndrome. The
main results from the SYSDIET intervention, i.e. the adherence to the diet and the effects on
insulin resistance, glucose tolerance, serum lipids and lipoproteins and inflammatory markers,
have been published previously [51]. Additionally 7 papers, including 3 which are a part of
this thesis, have been published to date from the study [50, 55, 95, 195-197].
Paper IV of the thesis is a part of ARI (A rye intervention), a feasibility study that was
conducted as a follow up of HELGA: Nordic Health – Whole grain Food, examining the
acceptability and adherence to increased rye consumption in a group of Icelandic men with
type 2 diabetes.
4.1. The SYSDIET intervention
4.1.1. Study design
The participants were screened for inclusion and exclusion criteria followed by a one month
run-in period during which all participants followed their habitual diet. After the run-in
period, participants fulfilling the inclusion criteria were randomized into a healthy Nordic diet
(ND) group or a control diet group for the next 18 to 24 weeks. In the original protocol, the
study length was 24 weeks but after a consultation with the NordForsk Panel and Scientific
committee members the study period was shortened to 18 weeks in four centers (Aarhus,
Uppsala, Reykjavik and Oulu). The rationale a for shorter intervention period was that an 18
week intervention was considered to give the same information on the main results as that
obtained from a 24 week trial, total costs were lowered, and recruitment of study subjects
would be easier for a shorter trial. In Lund and Kuopio, where the intervention was started
earlier, the original study design, i.e. 24 week intervention, was followed. In Kuopio and
Lund the intervention was carried out from October 2009 to June 2010, in Aarhus from
January 2010 to September 2010, in Oulu from December 2009 to October 2010, in
Reykjavik from March 2010 to October 2010 and in Uppsala from June 2010 to November
2010.
31
The study participants were scheduled to visit the study clinic at 2-4 week intervals
with the major visits at week 0, 12 and either 18 or 24 weeks (Figure 2). The staff in all study
centers was trained to perform the measurements in a similar way and a common quality
management protocol was made familiar to all staff members at each study site. The study
participants were advised to keep their weight and physical activity constant during the
intervention and not to change their smoking and drinking habits or drug treatment during the
study.
Figure 2. Study design of the SYSDIET intervention
4.1.2. Study population
Participants were recruited through advertising in newspapers, at workplaces and from
previous clinical or epidemiological trials. Altogether 309 individuals were contacted and
completed the screening visits. From these individuals, 200 started the intervention, 104 in the
ND group and 96 in the control group. There were 8 dropouts in the ND group and 26 in the
control group during the study period. Thus, 96 individuals in the ND group and 70 in the
control group, in total 166 individuals, completed the trial.
The inclusion criteria were age 30 - 65 years, BMI 27 - 38 kg/m2 and two other criteria
for metabolic syndrome as defined by the International Diabetes Foundation (IDF) [198],
except a diagnosis of type 2 diabetes, i.e. fasting plasma glucose <7.0 mmol/l (and a 2-h
glucose value <11.1 mmol/l at baseline detected by an oral glucose tolerance test). Antihypertensive and lipid lowering medication was allowed but without changes during the trial.
The main exclusion criteria included any chronic disease or condition which could
hamper the adherence to the dietary intervention protocol, poor compliance, chronic liver,
thyroid and kidney diseases, alcohol abuse (>40 g/d), diabetes, fasting triglycerides >3.0
mmol/l, total cholesterol >6.5 mmol/l and blood pressure >160/100 mmHg. A few study
participants with triglycerides between 3 and 4 mmol/l and with BMI between 38 and 40
32
kg/m2 were, however, included due to the fact that they were committed to the trial. Other
exclusion criteria were a recent myocardial infarction (<6 months), corticosteroid therapy,
psychiatric disorders needing drug treatment, cancer under treatment, celiac disease, allergies
to cereals or fish and other serious and extensive food allergies. Exceptional diets were also
an exclusion criterion as well as binge eating [199]. Inhaled corticosteroids were permitted.
Participants taking fish and vegetable oil supplements or using stanol or sterol esters
were asked to discontinue using these supplements at least 4 weeks before the beginning of
the intervention. None of the study participants were excluded due to non-compliance with
regard to the study protocol. The allowed weight change during the study was aimed to be less
than 4 kg.
Following the 4 week run-in period randomization (1:1) was performed by matching
participants according to gender and medians of age, BMI and fasting plasma glucose at
screening resulting in equal amounts of certain strata classes among the groups.
4.1.3. Dietary intervention
The study diets were introduced to the participants at week 0 by a clinical nutritionist or
dietician. The fourth edition of the Nordic nutrition recommendations formed the basis of the
diet in the ND group [57] and the mean nutrient intake in the Nordic countries formed the
basis for the control diet. The target nutrient composition and food items recommended in the
study diets are summarized in Table 4. The main nutrient differences between the diets were
the amount of dietary fiber and salt, and the quality of dietary fat. Both the ND and the control
diets were isocaloric based on the evaluation of the habitual diet (calculated from a 4 day food
record) during the run in period.
Key food products were provided to the study participants in both groups. The
individuals in the ND group received whole grain products such as oats and barley, crisp
breads, whole grain wheat and rye breads, berry products such as frozen berries and dried
berry powder as well as rapeseed oil and vegetable oil based spreads. Furthermore, fish (fatty
and lean) was either directly provided or the cost for purchase was reimbursed to the study
participants of the ND group. The individuals in the control diet group received low fiber
cereal products, e.g. breads with fiber content less than 6 g/100 g and ordinary pasta and dairy
fat based spread. The study participants kept dietary records regarding the intake of cereal
products, berry products, vegetables and fish with a check-list. These records were checked at
each visit to the study center, including the visits when the groceries were delivered to the
participants, i.e. at 1-2 week intervals.
Any intake of supplements was to be discontinued at least four weeks prior to entering
the study. An exception was made for vitamin D supplements in Iceland which the
participants could continue to use providing they kept it unchanged. The vitamin D
supplementation was not included in the nutrient calculations.
33
Table 4. Advised nutrient composition and suggested food items of for the study diets
Nutrients
Carbohydrate, E%
Sucrose, E%
Fiber, g
Protein, E%
Fat, E%
Saturated, E%
Monounsaturated +
Polyunsaturated, E%
Salt, g
Healthy Nordic diet
45-52
≤10, max. 50 g/day
≥35 g/day or 4 g/MJ
18-20
30-35
<10
minimum 2/3 of total fat intake
6 g for women, 7 g for men
Control diet
45-47
no restrictions
15-20
18-20
35
15
15
5
≤10
Advised food items
Cereal products
≥25% of total energy as whole grain, of which
≥50% as rye, barley and oat.
Whole grain pasta and unpolished rice
(≥6 g fiber/100 g) ≥2 meals/week
Low salt content (≤1.0%) in breads
Cereals with no added sugar or honey
Bread (≥6 g fiber/100 g) ≥6 slices/day
Vegetables, berries
and fruits
(potatoes not
included)
Fruits, vegetables and berries ≥500 g, of which
berries ≥150 g/day, fruits ≥175 g/day and
vegetables ≥175 g/day
≥25% of energy as refined
grain, of which ≥90% as
wheat
Fruits and vegetables 200250 g/day
No bilberries
Dietary fats
Rapeseed oil
Rapeseed and/or sunflower oil and/or soybean oil
based margarines with no trans fatty acids and
>2/3 of unsaturated fats
Unsalted nuts and seeds can be included in the
diet
Butter or other milk fat
based spread (≥50% of
total fat as saturated)
Dairy products
Low fat liquid dairy ≤1% fat
Cheese ≤17% fat
≥2 portions/day
Sweetened yoghurt and other fruit milk products
avoided
No limitations
Fish
≥3 meals/week, two fatty fish (≥4% of fat) meals
and one low fat fish meal
≤1 meal/week
Meat
Preferably white meat, poultry
Low fat choices
Game
No limitations
Avoidance of sugar-sweetened beverages
Fruit and berry juices ≤1 glass/day
No limitations
Beverages
34
4.1.4. Dietary assessment
The dietary intake was assessed using a consecutive 4 day (Wednesday to Saturday or Sunday
to Wednesday) food record, with either weighed or estimated portion sizes. The baseline food
diaries were recorded in the 4 week run-in period of the intervention. Dietary intake during
the intervention was recorded at week 2 (data not included in this thesis) 12 and 18/24.
Participants received both oral and written instructions on how to fill in the dietary records
and were provided with electronic household scales or valid standardized household measure
information on how to give information about the amount of food consumed.
At each center the nutrient intake from food diaries was calculated, using national
nutrient databases (Aivo Finland Ltd, Turku, based on the database of the National Institute of
Health and Welfare, Finland, Dietist XP Software Package, version 3.1 [2009] linked to
Swedish Food Database 2009, Sweden, Master Dieatist System version 1.235 [2007] based on
Danish National Food administration database, Denmark, and The Icelandic Food
Composition Database [ISGEM], Iceland). All the databases use EuroFIR definitions for
chemicals and total dietary fiber determined by the AOAC methods [200-203].
4.1.5. Anthropometric measurements
Height was measured at week 0 with a calibrated stadiometer with a precision of 0.5 cm.
During the measurements participants were in a fully erect position with the shoulder blades,
buttocks and heels touching the wall. Participants were asked to stand straight, with heels and
knees almost together, shoulders relaxed and arms hanging at sides.
Body weight was measured at every visit to the clinic, i.e at screening, week 0, 2, 4, 8,
12, 16 and 18/24. Weight was measured in light clothes on a digital calibrated scale. It was
measured to the nearest 0.1 kg with the subject standing motionless on the scale, weight
equally distributed on each leg and arms hanging freely. BMI was calculated from the
recorded height and weight using the standard formula, dividing the participants´ weight (kg)
by the square of the height (m2).
The waist circumference was measured at the screening visit, week 0, 12 and 18/24.
For the measurement of waist circumference participants stood erect with arms relaxed at the
sides and the feet slightly apart from each other with weight equally distributed on each leg.
The lowest rib margin and the iliac crest were located and the midway between those two
levels was marked. A flexible tape was then placed firmly on the measuring line and ensured
that its position was horizontal all around the waist. Participants were asked to breathe
normally and a measurement was made at the end of a gentle exhaling. All measures were
performed twice using a flexible tape measure and recorded with the accuracy of 0.1 cm.
Body composition was determined at week 0, 12 and 18/24 by bioelectrical impedance
analysis (Kuopio: STA/ BIA Body Composition Analyzer and Bodygram Software, Akern
Bioresearch Srl, Florence, Italy, Reykjavik: STA/BIA Body Composition Analyzer, Akern
Bioresearch Srl, Florence, Italy, Lund: Xitron Hydra 4200 instrument, Xitron Technologies,
San Diego, USA, Uppsala: Tanita BC-558Segmental Body Composition Monitor, Tokyo,
35
Japan, Aarhus: multi-frequency bioimpedance spectroscopy analyzer, UniQuest-Seac, SFB3,
Brisbane, Australia. Body composition was not measured in Oulu).
4.1.6. Oral glucose tolerance tests
Oral glucose tolerance tests (OGTT) were performed at week 0, 12 and 18/24. Participants
were instructed to have an overnight fast before the OGTT and on arrival to the study clinics,
fasting venous blood samples for plasma glucose and plasma or serum insulin measurements
were collected. The participants were then asked to drink a glucose solution and finish it in
less than 3 minutes. The glucose solution contained 75 g of D(+)-Glucose anhydrous Ph.Eur
dissolved in 300 ml of water. In some cases 1.6 g of citric acid was also added to the solution.
Participants were asked to remain in the testing area during the test and were not allowed to
smoke or eat during the examination. Venous blood samples for plasma glucose and plasma
or serum insulin measurements were collected 30 and 120 minutes after the glucose load. The
samples were kept in ice until centrifugation in the local laboratory.
4.1.7. Biochemical measurements
Blood samples were taken at the screening visit and at week 0, 12 and 18/24. Glucose and
lipid analyses (triglycerides, total cholesterol and HDL cholesterol) were performed locally
and apolipoproteins A1 (Apo A1) and B (Apo B) centrally in the University of Eastern
Finland and Kuopio University Hospital according to the standard operational procedures
agreed by all centers using automated clinical chemistry analyzers and routine clinical
chemistry methods. For these automated analyses, the equipment and system reagents were
from Siemens Healthcare Diagnostics (Tarrytown, NY, USA), Thermo Fisher Scientific
(Vantaa, Finland), Roche Diagnostics GmbH (Mannheim, Germany) (in two laboratories),
Toshiba (Japan), Abbott Laboratories (Irving, TX, USA), Ortho-Clinical Diagnostics and
Johnson & Johnson (New Brunswick, NJ, USA). The sample material was either plasma or
serum as required by the analytical method in each laboratory. The within-run variations
(CV%) for the biochemical measurements were 0.4–4.6%. The between-run CV% was 0.5–
6%. Plasma insulin was measured centrally in Aarhus University Hospital, Denmark using the
ELISA method from Dako Denmark A/S, Glostrup, Denmark, with a within-run and betweenrun CV% <8% and <10%, respectively. LDL-C concentrations were calculated using
Friedewald’s formula.
From data of the oral glucose tolerance test insulinogenic index (IGI), the ratio of the
30 minutes areas under the curve for insulin and glucose (InsAUC0-30/GluAUC0-30) and
Stumvoll was calculated for evaluation of early phase insulin secretion (IGI = (Insulin 30
min–Insulin 0 min) / (Glucose 30 min–Glucose 0 min) and Stumvoll = 1283 + 1.829 × insulin
30 min (pmol/l) − 138.7 × glucose 30 min (mmol/L) + 3.772 × insulin 0 min (pmol/l)).
Insulinogenic index at 120 minutes (IGI 120) was calculated for late phase insulin secretion
(IGI 120 = (insulin 120 min–insulin 0 min) / (glucose 120 min–glucose 0 min)). Matsuda
insulin sensitivity index (ISI) and disposition index (DI) were calculated for evaluation of
36
insulin sensitivity (Matsuda ISI=(10000/√([glucose 0 min x insulin 0 min] x [arithmetic mean
of glucose 0, 30 and 120 min x arithmetic mean of insulin 0, 30 and 120 min]) [204] and
DI=Matsuda ISI x insulinogenic index).
4.1.8. Dietary biomarkers
Blood samples used for analysis of plasma AR were collected at week 0, 12 and 18/24 (N =
158). AR in plasma samples were analyzed at the Department of Food Science, BioCenter at
the Swedish University of Agricultural Sciences. AR homologues C17:0-C25:0 were
measured in 0.2 ml plasma samples according to a previously published gas chromatography–
mass spectrometry (GC-MS) method [205]. Quality control samples (N = 4) were included in
each batch to ensure appropriate within- and between batch precision (CV <15%). Samples
from the same individual were analyzed within the same batch and samples from different
centers were allocated randomly between batches. The ratio between the AR homologues
C17:0 and C21:0, a marker of relative intake of whole grain rye of overall whole grain rye
and wheat intake, was calculated.
4.2. ARI feasibility study
4.2.1. Participants and study design
Participants were referred to the study by general practitioners in three health care clinics in
the capital area of Iceland. Participants were 23 males, aged 42 to 80 diagnosed with type 2
diabetes or prediabetes by their family doctor. The exclusion criteria included any chronic
disease and/or condition, which could hamper the adherence to the dietary intervention
protocol.
Participants followed their habitual diet for a week before randomization into a rye
group (N=14) or a control group (N=9) for 26 weeks. All participants had three major visits,
at week 0, 13 and 26 (Figure 3). Additionally, there was a group meeting with a clinical
nutritionist in week 2 where participants received general recommendations on a healthy diet
as well as a meeting with a physical therapist and a personal trainer during the first weeks.
The participants in the rye group came every 2-3 weeks, to pick up the rye products that were
provided and both groups were offered to pick up vegetable packages free of charge every 4
weeks. The intervention was carried out in April to November 2013.
37
Figure 3. Outline of the study design and main outcome measurements at each visit
4.2.2. Study diet
Participants in the rye group were instructed to consume 100 g of whole grain rye each day
for 26 weeks and rye products equivalent to this intake were provided free of charge. The
products provided to the rye group and their rye content are listed in Table 5. The participants
in the control group were asked to remain their usual diet, but avoid rye products. Weight loss
during the study period was allowed.
Table 5. Whole grain rye, energy, fiber, added sugar and salt content for the rye products
provided for the rye group in the study
Whole grain rye, Energy,
g
kcal
Rye flakes (used for porridge)
100
335
Rye bread 1
50
193
Rye bread 2
38
235
Rye bread 3
59
179
Rye bread 4
59
162
Rye crisp bread
94
360
Data are presented as g or kcal per 100 g of product
Fiber, Sugar, Salt,
g
g
g
11.7
0
<0.01
8.3
1.5
1.2
7.5
0.8
1.2
8.0
N/A
1.5
10.6
2.9
1.2
19
0.9 <0.01
Participants in the rye group received both oral and written information on the amount of rye
in the products provided and other common whole grain rye products, and how to reach 100 g
of rye a day in their diet. To simplify, the participants in the rye group were asked to obtain
ten points every day, where one point was earned for every 10 g of whole grain rye consumed.
A color-printed booklet with names and pictures of the rye products provided in the study, as
well as other common whole grain rye products, was handed to the participants. The booklet
included information on nutritional value, amount of whole grain rye per 100 g of product and
38
per serving (e.g. slice of bread) and amount of points earned per serving. Altogether the
booklet contained information on 32 rye products.
Dietary intake was assessed using a consecutive 4-day (Wednesday to Saturday)
weighed food record before week 0, at week 13 and 26. Participants received both written and
oral instructions on how to fill in the diet records and were provided with electronic
household scales. At the 0 week visit a nutritionist reviewed the first food diary with each
participant and suggested exchanges for rye products. Rye porridge (from rye flakes) was
recommended daily, to facilitate the rye consumption without adding increased energy to the
diet. In addition, daily consumption of 1 - 4 slices of rye bread (dependent on the type of
bread) was recommended.
The nutrient intake from food diaries was calculated using The Icelandic Food
Composition Database [ISGEM], Iceland). The database use EuroFIR definitions for
chemicals and total dietary fiber determined by the AOAC methods [200].
4.2.3. Physical activity
After randomization, all participants (rye and control groups) were asked to exercise
vigorously for at least 45 minutes three days/week, and walk at least 10 000 steps on other
days, for 26 weeks. A gym membership and a pedometer were provided to all participants free
of charge. In the beginning of the study each participant met with a physical therapist who
evaluated the physical condition of the participants. Following that meeting the participants
met with a personal trainer who gave them an individualized exercise program and showed
them the exercises and the workout equipment. The participants were free to contact the
personal trainer during the intervention period to get different (less/more advanced) programs.
Thus, every participant got an exercise program designed for their needs, e.g. interests, age,
strengths and weaknesses.
4.2.4. Compliance and acceptability
AR in plasma were used to assess compliance to the whole grain rye intake with measures of
total plasma AR and the AR C17:0/C21:0 ratio [12, 20, 196, 197], in addition to a weighed
food diary. The plasma samples were analyzed at the Department of Food Science, BioCenter
at the Swedish University of Agricultural Sciences as described in section 4.1.8.
To measure the acceptability of the products at week 13 and 26, participants in the rye
group were given three statements and asked to check whether they strongly agreed, agreed,
neither nor, disagreed or strongly disagreed. The statements were: 1) I have experienced
digestive discomfort after I started eating rye products 2) I like food products that contain rye
and 3) I would prefer products that contain rye more than other products.
39
4.2.5. Anthropometric and biochemical measurements
Height was measured at week 0 with a calibrated stadiometer with a precision of 0.5 cm.
Body weight, waist circumference and body composition was measured at weeks 0, 13 and 26
according to the protocol described in section 4.4.2.
OGTTs were performed at week 0 and week 26 according to protocol described in
section 4.1.6. except for venous blood samples for plasma glucose and plasma or serum
insulin measurements were collected 60 and 120 minutes after the glucose load.
Measurements on glucose and blood lipids (triglycerides, total cholesterol and HDL
cholesterol) were performed in the local laboratory according to standard operational
procedures. Automated clinical chemistry analyzers and routine clinical chemistry methods
were used to measure glucose, insulin, triglycerides, total cholesterol and HDL cholesterol.
LDL-C concentrations were calculated using Friedewald’s formula.
4.3. Statistical analysis
Data entering
All intervention centers in the SYSDIET study entered their data into Microsoft Office Excel
2007 (Windows) data form prior to pooling the data in a joint database maintained at VTT
Technical Research Centre of Finland. Data was exported from the database and imported to
SPSS (Statistical Package for the Social Sciences) for Windows, version 20.0 (SPSS Inc.,
Chicago, Illinois, USA) in which most statistical analysis was done for the SYSDIET study,
as well as the ARI feasibility study.
Descriptive analyses
All analyses for the SYSDIET intervention illustrated in the thesis were performed with N =
158, i.e. the participants who completed the intervention and had valid plasma samples for AR
analysis at both week 0 and 18/24, unless otherwise indicated. Power analyses were done
during the study design phase in the SYSDIET study. Based on scientific experience and the
power calculations, 80-90 participants were expected to provide sufficient statistical power
(alpha <0.05, beta >0.8) to detect 10% difference in serum cholesterol levels between groups.
For the ARI feasibility study all participants that completed the intervention were included in
the analyses (N = 20).
Normality of variables was checked by visual inspection. Normal variables were
described as means and standard deviations (SD) while skewed variables were described
using medians and interquartile range (IQR). Independent sample t-tests or Mann-Whitney U
test were used to compare medians between groups and genders. Paired sample t-tests or
Wilcoxon´s signed rank tests were used to compare values between baseline and midpoint
(week 12 in SYSDIET and week 13 in ARI) or the end of the interventions (week 18/24 in
SYSDIET and week 26 in ARI). The answers to the acceptability questions in the ARI
feasibility study were combined before statistical analysis combining strongly agree and agree
to agree and strongly disagree and disagree to disagree.
40
Determinants of plasma AR
To explore the determinants for total plasma AR concentration at 18/24 weeks in the
SYSDIET study a linear regression for total plasma AR at 18/24 weeks was performed with
group, baseline concentration for total plasma AR, gender, age, BMI, study center and
triglycerides at 18/24 weeks as factors in the model. As the distribution of total plasma AR
was right skewed, log transformation was performed before this analysis to better
approximate normal distribution. One-way ANOVA was used to compare means between
study centers and Spearman rank correlation coefficient (rs) was used to calculate correlation
between total plasma AR concentration and various nutrients abundant in whole grains.
Reproducibility
Reproducibility, a measure of intra-person stability in dietary intake or biomarker
concentration during the intervention, was assessed by estimating the intra-class correlation
coefficient (ICC). ICC is defined as the intra-person variance divided by the total variance
(i.e. the sum of intra- and inter-person variance), and it assumes a common mean between
replicate measurements. ICC was calculated using freely available SAS macro [206] that was
imported to SAS 9.2 (SAS Institute). All ICC estimates were based on log-transformed
values.
Examining associations between plasma AR and cardiovascular risk factors
For the SYSDIET study, secondary analyses were performed with data from the ND and
control groups combined. Associations between total plasma AR and AR C17:0/C21:0 ratio at
18/24 weeks and various glucose, insulin and blood lipid outcomes were analyzed using linear
regression. Where distributions were skewed log-transformation was performed on the
dependent variables for linear regression. For evaluating the association to glucose and insulin
outcomes, linear regression for fasting plasma glucose, insulin, Matsuda, DI and IGI was
performed with AR C17:0/C21:0 ratio, baseline values for the dependent variable, age,
gender, BMI and smoking as factors (model 1). For evaluating the association to blood lipid
outcomes linear regression for total, LDL, HDL, non-HDL cholesterol, Apo A1 and B and
LDL/HDL cholesterol ratio was performed with AR C17:0/C21:0 ratio, baseline values for
the dependent variable, BMI and statin use as factors (model 1). The linear regressions were
also performed with total plasma AR concentration instead of C17:0/C21:0 in model 1. As rye
often contains more AR compared to wheat, total plasma AR concentration was added as a
variable (model 2) in addition to the variables in model 1, to prevent confounding of high AR
content. Furthermore, we individually adjusted for saturated fat intake calculated from food
records and serum phospholipid fatty acids myrisitc acid, palmitic acid, omega-3 fatty acids
and C15:0 for the blood lipid analyses, to prevent confounding of dietary fat intake. In all
analyses, model residuals were checked normality visually, with help of QQ-plots.
41
4.4. Approvals
Local ethical committees in Denmark, Finland, Iceland and Sweden reviewed and approved
the SYSDIET study protocol which followed the Helsinki declaration guidelines. The ARI
feasibility study was approved by the National Bioethical Committee in Iceland, Local Ethical
Committee at the Landspitali-University Hospital in Iceland, Local Ethical Committee at the
Primary Health Care of the Capital Area and by the Icelandic Data Protection Commission.
Informed written consent was obtained from all participants in both studies prior to
participation.
42
5. Results and discussion
The main findings from the four papers are hereby discussed. More detailed descriptions of
the results are found in papers I-IV.
5.1. The SYSDIET intervention
5.1.1. Baseline characteristics of the participants
In total, 200 participants started the intervention, 104 in the ND group and 96 in the control
group. Participants completing the trial were 96 in the ND group (92%) and 70 in the control
group (72%). Blood samples for AR analysis at week 0 and week 18/24 were obtained from
158 participants (Figure 4).
Figure 4. Flow chart of the SYSDIET study
43
Baseline characteristics of the participants that finished the study and had valid blood sample
for AR analyses at week 0 and 18/24 are shown in Table 6. Approximately two-thirds of the
participants were classified as obese (BMI ≥30 kg/m2) and one-third as overweight (BMI 25–
29.99 kg/m2). Eighty participants had fasting plasma glucose ≥5.6 mmol/L at week 0.
Baseline characteristics between the two groups were not significantly different.
Table 6. Baseline characteristics of the participants in the healthy Nordic diet (ND) group and
the control group who completed the SYSDIET study and had valid blood samples for
alkylresorcinols analyses at week 0 and 18/24
ND group
(N = 93)
Age, years
54.8 (8.1)
Weight, kg
89.7 (13.5)
2
BMI, kg/m
31.6 (3.4)
Waist circumference, cm
103 (10)
†
Fat , %
39 (8)
Blood pressure systolic, mm Hg
130 (15)
diastolic, mm Hg
82 (11)
‡
Smoking , n (%)
6 (6)
‡
Statin use , n (%)
19 (20)
‡
Metabolic syndrome , n (%)
85 (91)
Data are presented as mean (SD) unless otherwise indicated
Abbreviations: BMI, body mass index
†
n = 122, n = 72 in ND group and n = 50 in control group
‡
Data are presented as number (%)
Control group
(N = 65)
54.2 (8.3)
93.2 (13.8)
31.8 (2.9)
106 (3)
39 (7)
130 (17)
80 (11)
7 (9)
18 (28)
56 (86)
5.1.2. Changes observed during the intervention
The main results from the SYSDIET intervention, dietary intake and health effects have been
published previously [51] and will only shortly be discussed here. Consistent with the
isocaloric study design there was no change in total energy intake during the study and energy
intake was not different between the groups. Hence, body weight remained constant during
the intervention in both groups. In general, dietary compliance was satisfactory as evidenced
from the dietary records [51].
One of the most prominent changes in nutrient composition during the intervention
was increased fiber intake in the ND group [51]. The median fiber intake at week 0 was 21 (8)
g/day and 2.5 (1.0) g/MJ and during the intervention, the median intake of dietary fiber
increased by 71% (P <0.001) in the ND group and decreased by 20% in the control group
44
(P<0.001) (Table 7). By week 12, both groups had reached the predetermined goals for fiber
intake of at least 35 g/day (or 4 g/MJ) and 15-20 g/day, in the ND and control groups
respectively, and the intake was steady throughout the intervention.
Table 7. Total dietary fiber intake in healthy Nordic diet (ND) and control groups during the
intervention
ND group
(N = 80)
Week 0
Week 18/24
Control group
(N = 60)
Week 0
Week 18/24
Dietary fiber intake, g/day
21.1 (8.8)
36.0 (15.1)#
20.0 (7.1)
Data are presented as medians (IQR)
* Significantly different from ND group at that time point, P <0.05
#
Significantly different from baseline in that group, P <0.05
16.0 (6.2)*#
The main results from the SYSDIET intervention were that the healthy Nordic diet did not
modify insulin sensitivity and glucose tolerance but resulted in significant between-group
changes in non-HDL cholesterol, LDL to HDL cholesterol ratio and Apo A1 to Apo B ratio
favoring protection from atherosclerosis. Additionally, there was a significant increase in
interleukin-1 Ra (IL-1 Ra) levels [51].
Exploration of the participants that had valid plasma samples for AR analyses (N =
158) showed similar results with no significant differences between groups in indices of
insulin sensitivity or -secretion. At week 0, median fasting plasma glucose was 5.7 (0.9)
mmol/L in both groups and did not change significantly during the intervention period [197].
There were small, but significant, decreases in concentrations of total cholesterol (P = 0.018),
LDL (P = 0.006) and non-HDL cholesterol (P = 0.006) and LDL/HDL cholesterol ratio (P =
0.003) within the ND group from week 0 to 18/24 but not within the control group [207].
45
5.2. Plasma alkylresorcinols as dietary biomarkers in healthy Nordic diet (Paper I)
5.2.1. Changes in plasma alkylresorcinols concentrations during the intervention
The change in dietary fiber intake in the present study was reflected in increased plasma AR
concentration in the ND group, suggesting that cereal fiber from wheat and rye substantially
contributed to the increased fiber intake. There was a 68% increase in total plasma AR
concentration in the ND group during the intervention, with median concentrations increasing
from 73 (88) nmol/L at week 0 to 106 (108) nmol/L (P = 0.001) at week 18/24, while a slight
decrease was seen in the control group (P = 0.021) (Table 8). Even at baseline, the total
plasma AR was relatively high compared to the participants in the EPIC study where the
geometric mean plasma total AR concentrations were between 35 and 41 nmol/L in
participants from the Central European and Scandinavian countries and below 23 nmol/L in
participants from the Mediterranean countries [124]. Plasma levels have, however, been found
to vary widely, with previous studies reporting mean levels between 38 - 388 nmol/L with a
moderate to high rye intake [108-110].
Table 8. Total plasma alkylresorcinols (AR) concentration and AR C17:0/C21:0 ratio for the
healthy Nordic diet group (ND) and control group at baseline and after the 18/24 week
intervention
ND group
Week 0
Week 18/24
71 (70)
61 (40)*#
C17:0/C21:0 ratio
0.3 (0.2)
0.3 (0.2)
0.3 (0.2)
Data are presented as medians (IQR)
* Significantly different from ND group at that time point, P <0.05
#
Significantly different from baseline, P <0.05
0.2 (0.2)*#
Total plasma AR, nmol/L
73 (88)
106 (108)#
Control group
Week 0
Week 18/24
There was no difference between the groups at baseline in total plasma AR concentration but
the difference was significant both at week 12 and 18/24 (P <0.001) (Figure 5). Previous data
suggest that total plasma AR meets most of the criteria of a good biomarker for intake of
whole grain cereal fiber and whole grain wheat and rye, particularly with frequent
consumption and a wide range of intake [12, 18, 19, 21, 23]. Total plasma AR concentration
increases proportionally with AR and whole grain intake [18, 22-26] and can be used to
categorize subjects as low and high consumers of whole grain foods [19, 126]. Furthermore, it
can be used as a marker for compliance to a whole grain diet in intervention studies [20, 27].
46
Plasma total alkylresorcinols, nmol/L
160
*
140
*
120
ND
100
80
60
Control
40
20
0
Week 0
Week 12
Week 18/24
Figure 5. Total plasma alkylresorcinols concentrations for participants in healthy Nordic diet
(ND) and control groups at week 0, 12 and 18/24. Values are medians and bars represent the
interquartile range (IQR)
*
Different from control group at that time, P <0.05
The C17:0/C21 ratio for the ND group and control group at week 0 and week 18/24 are shown
in Table 8. The median AR C17:0/C21:0 did not change in the ND group during the
intervention and at 18/24 weeks it was 0.3 (0.2). However, the C17:0/C21:0 ratio decreased
significantly in the control group and was 0.2 (0.2) at week 18/24. Although the ratio of
C17:0/C21:0 is approximately 1.0 in rye the ratio is expected to be somewhat lower in plasma
samples and has typically been around 0.6-0.8 in fasting samples after a whole grain rye
intervention for 1-8 weeks [23, 25]. It is important to note that the AR C17:0/C21:0 ratio is a
marker of relative rye intake, not absolute intake, and the lower ratio in the present study than
in previous studies may be indicative of higher whole grain wheat intake as other whole grain
products than provided were not allowed in these studies. A ratio above 0.15 is usually
indicative of some rye intake [12]. The reason for the lower ratio in plasma compared to what
is found in whole grain/bran rye foods is likely due to faster metabolism of the AR
homologue C17:0 [107, 131] but further insight into absorption and metabolism of the
different homologues is necessary [12].
47
5.2.2. Determinants of plasma alkylresorcinols concentration
Diet group allocation (ND group vs. control group; P < 0.001) and total plasma AR
concentration at baseline (P < 0.001) were predictors of total plasma AR concentration at
week 18/24 with adjusted R2 = 0.38 (Table 9).
Table 9. Regression coefficients for factors affecting plasma total alkylresorcinols (AR) at
week 18/24 (log transformed)
B† (95% CI)
P-value
Model 1 log AR 18/24WK
Adjusted R Squared = 0.38
Study group‡
0.234 (0.157, 0.311)
<0.001
AR week 0
0.354 (0.212, 0.496)
<0.001
Gender
0.026 (-0.055, 0.106)
0.53
Age
0.003 (-0.001, 0.008)
0.17
BMI
0.002 (-0.009, 0.014)
0.70
Triglycerides 18/24 weeks
0.110 (0.042, 0.177)
0.002
Study center
-0.019 (-0.041, 0.003)
0.09
Abbreviations: BMI, body mass index
†
B reflects the change in the log-transformed outcome variable for each 1-unit changes in the
independent variable.
‡
Healthy Nordic diet group (ND) compared with control group
Serum triglycerides concentration at week 18/24 was also a significant determinant for total
plasma AR at 18/24 weeks (P = 0.002). Blood lipids were expected to correlate with total
plasma AR concentration as studies have suggested that AR is transported in lipoproteins [19,
25]. The finding that serum triglycerides were a significant predictor of total plasma AR
concentration suggests that factors that cause transient increases in plasma triglycerides may
also be important for the repeatability of plasma AR measurements [125].
Study center was of borderline significance (P = 0.09) as a determinant for total
plasma AR at week 18/24. Significant differences were in baseline values for total plasma AR
concentration, as well as the AR C17:0/C21: ratio, among study centers (Table 10). At the
two Finnish centers, Oulu and Kuopio, the participants had the highest median (IQR)
concentrations, 108 (96) nmol/L and 108 (72) nmol/L, respectively, whereas in Reykjavik the
lowest median concentration was observed, 43 (37) nmol/L. The differences in total plasma
AR among centers are likely to reflect differences in whole grain wheat and rye intake in the
source populations, which also resulted in differences in total dietary fiber intake. Hence, the
increase in total plasma AR concentration in Finnish participants during the intervention was
48
not as high as in participants from other centers. Instead, Finnish participants in the control
group had a greater decrease in AR concentration. Similarly, for the other centers, total
plasma AR concentration increased substantially in the ND group and decreased in the control
group, but not as sharply as in the Finnish control group.
Table 10. Baseline dietary intake of fiber, plasma total alkylresorcinols (AR) and AR
C17:0/C21:0 ratio at different study centers†
Dietary intake‡
Plasma concentration
Fiber,
Fiber,
Total AR,
AR C17:0/C21:0
Study center
g/day
g/MJ
nmol/L
ratio
b
ab
a
Oulu (N = 35)
21 (7)
2.7 (0.9)
108 (96)
0.3 (0.2)a
Kuopio (N = 32)
25 (11)a
3.1 (1.5)a
108 (72)a
0.4 (0.2)a
Reykjavik (N = 15)
18 (8)b
1.8 (0.7)c
43 (37)c
0.2 (0.2)b
Lund (N = 37)
19 (8)b
2.2 (0.7)c
59 (36)b
0.2 (0.1)b
Uppsala (N = 9)
22 (8)ab
2.5 (0.7)bc
56 (46)bc
0.2 (0.3)b
0.3 (0.2)b
Aarhus (N = 30)
22 (12)ab
2.4 (1.1)bc
67 (77)b
Data are presented as median (IQR)
†
Labeled medians in a column without a common letter differ, P <0.05.
‡
N = 151, Oulu N = 35, Kuopio N = 31, Reykjavik N = 13, Lund N = 36, Uppsala N = 8,
Aarhus N = 28
Total plasma AR concentration was not significantly different between genders, and gender
was not a significant factor in the model (Table 9). Several studies have found higher plasma
AR concentration in men compared to women which has been attributed to higher intake of
foods containing AR by men and more rapid elimination of AR in women [12, 19, 22, 28].
AR is present in adipose tissue [122, 208] and as women generally have greater fat stores than
men, it may result in lower plasma AR. In the present study, the women had a higher body fat
percentage than men, suggesting that factors other than variations in body fat may have
caused the lack of gender difference.
5.2.3. Six to twelve week reproducibility of plasma alkylresorcinols
The reliability of AR plasma measurements at week 12 and 18/24 was moderate to good, with
intra-class correlation (ICC) 0.44 – 0.72 (Table 11). The ICC was higher among men than
women and higher in ND group than control group. This is similar or higher than seen in
previous studies [12, 22, 24, 127]. The ICC has been reported to be 0.42-0.48 over a 2- to 4month period under free living condition [12, 19, 22, 127] and a ICC of 0.88 - 0.90 was
reported in a 6 week intervention setting with extremely high daily intake of rye bran/wholegrain rye products [24]. Similarly, higher reliability was observed in the ND group in the
49
present study than in the control group as ND group had higher and more frequent intake of
AR. The variation in free-living subjects makes it difficult to classify an individual’s whole
grain wheat and rye intake with precision, from a single sample. Nevertheless AR are
considered a valid measure for comparing different populations, as mean plasma AR are well
correlated with mean AR intake when results from relevant studies are combined [12].
Table 11. Estimated intra-class correlation coefficients (ICC, based on log-transformed
values) between week 12 and 18/24 for all participants combined, healthy Nordic diet (ND)
group and control groups
All
Dietary fiber intake
Both genders
0.86 (0.82-0.90)
Men
0.89 (0.84-0.94)
Women
0.84 (0.77-0.89)
Total plasma alkylresorcinols
Both genders
0.68 (0.59 - 0.76)
Men
0.72 (0.58-0.83)
Women
0.72 (0.64-0.79)
Data are presented as ICC (95% CIs)
ND group
Control group
0.74 (0.63-0.82) 0.42 (0.24-0.62)
0.80 (0.64-0.90) 0.49 (0.24-0.75)
0.69 (0.54-0.80) 0.36 (0.15-0.65)
0.66 (0.54-0.77) 0.49 (0.32-0.67)
0.69 (0.49-0.84) 0.55 (0.30-0.78)
0.64 (0.49-0.77) 0.44 (0.22-0.69)
The half-life of AR is relatively short, about 5 hours, and the absorption half-life is about 6-8
hours [107]. Strictly defined, AR should be regarded as a short-term biomarker but under
stable and frequent intake conditions absorption and elimination counteract each other and it
may reflect exposure fairly well [123]. In the present study, cereals and bread were consumed
on a daily basis thus, plasma AR concentrations should be stable and appropriately reflect
intake during the intervention period. It is, however, important to note that the use of plasma
AR as a biomarker of whole grain intake is not practical in populations who primarily
consume other types of whole grains which do not contain AR, such as oats or brown rice, or
when whole grains are not regularly consumed.
50
5.2.4. Correlations between alkylresorcinols and nutrient intake
Positive correlations were observed between plasma total AR concentration and total fiber
intake at week 0, 13 and 26, as well for vitamin E, folate and magnesium (Table 12), nutrients
abundant in whole grains [33]. Under dietary intervention settings, total plasma AR have
previously been found to correlate with insoluble fiber [109] as well as dietary fiber [18].
Table 12. Correlations for plasma total alkylresorcinols and intakes of various nutrients
abundant in whole grain for both healthy Nordic diet (ND) and control group
Baseline
Week 12
ND Control
All
All
group group
Total fiber intake
0.26*
0.47* 0.19
0.18
Vitamin E
0.26*
0.44* 0.33*
0.18
Folate
0.32*
0.24* -0.01
-0.01
Magnesium
0.35*
0.36* 0.23* -0.01
Values are presented as Spearman´s correlation coefficients (rs).
* Significant correlation, P < 0.05
Week 18/24
ND Control
All
group group
0.57* 0.37* 0.34*
0.49* 0.27*
0.20
0.40* 0.21*
0.08
0.44* 0.39*
0.02
5.3. Plasma alkylresorcinols and cardiovascular risk factors (Papers II-III)
The range of total plasma AR at week 18/24 was 14 to 499 nmol/L when the ND and control
groups were combined for secondary analyses to investigate the associations between plasma
AR at 18/24 weeks and 1) glucose metabolism and 2) blood lipid concentrations.
5.3.1. Glucose and insulin parameters
Total plasma AR concentration at week 18/24 was not significantly correlated with
concentrations of fasting plasma glucose (P = 0.51), insulin (P = 0.57) or other measures of
insulin sensitivity or –secretion, when adjusted for baseline value of the dependent variable,
age, gender, BMI and smoking. Combining the data from both weeks 12 and 18/24 did not
change the results.
Interestingly, the AR ratio C17:0/C21:0, reflecting the relative intake of whole grain
rye of whole grain rye and wheat intake, was inversely associated with fasting insulin
concentrations when adjusted for the same covariates (model 1, P = 0.016) and also when
total plasma AR was added to the regression model to prevent confounding of high AR
content (model 2, P = 0.011) (Table 13). Total plasma AR and the AR C17:0/C21:0 ratio were
weakly correlated (Spearman´s rho = 0.20, P = 0.012).
51
The AR C17:0/C21:0 ratio was also positively associated with the insulin sensitivity
indices Matsuda ISI (P = 0.005 and P=0.004 for model 1 and 2, respectively) and DI (P =
0.022 and P=0.023 for model 1 and 2, respectively) (Table 13). The AR C17:0/C21:0 ratio
was, however, not associated with fasting plasma glucose or the indices for early and late
insulin secretion [197]. Thus, relative whole grain rye intake, reflected by the AR ratio
C17:0/C21:0, seems to be associated with lower fasting plasma insulin and increased insulin
sensitivity.
Table 13. Regression models for fasting insulin and insulin sensitivity indices at 18/24 weeks
(log transformed values)
Dependent variable Independent variable
B† (95% CI)
at 18/24 weeks
at 18/24 weeks
Fasting insulin
Model 1
AR C17:0/C21:0
-0.43 (-0.77 to -0.08)
Model 2
AR C17:0/C21:0
-0.45 (-0.79 to -0.10)
Matsuda
Model 1
AR C17:0/C21:0
0.23 (0.07 to 0.40)
Model 2
AR C17:0/C21:0
0.24 (0.08 to 0.40)
DI
Model 1
AR C17:0/C21:0
0.77 (0.11 to 1.43)
Model 2
AR C17:0/C21:0
0.77 (0.11 to 1.43)
†
B reflects the change in the log-transformed outcome variable for each 1-unit changes in the
independent variable.
Model 1: adjusted for baseline value for the dependent variable, age, gender, BMI and
smoking
Model 2: adjusted for baseline value for the dependent variable, total plasma AR, age, gender,
BMI and smoking
Abbreviations: AR, alkylresorcinols; DI, disposition index; BMI, body mass index
There are conflicting findings from previous intervention studies evaluating the effects of
whole grain intake on glucose metabolism [159, 160, 209, 210], presumably due to
differences in the type, amount, structure and preparation of whole grain products consumed
[166] and different methodologies used for glucose and insulin analyses [157]. Poor
compliance may also contribute to these varied findings, although good adherence has been
indicated in most studies using weighed food records. In a whole grain intervention study by
Kristensen et al [211] the effects on body composition were clearer after excluding
noncompliant participants based on total plasma AR concentration. Marklund et al [95] also
got greater cardiometabolic effects of a healthy Nordic diet among compliant participants
using a combination of dietary biomarkers to assess compliance. In both studies food records
indicated good compliance. Hence, without an objective measurement of compliance, such as
52
dietary biomarkers, it is difficult to rule out the possibility of low adherence to the
intervention diet. Nevertheless, whole grain intake has repeatedly been associated with
decreased risk of type 2 diabetes in epidemiological studies [2, 136-140], presumably due to
enhanced insulin receptor sensitivity through chronic lowering of the overall dietary glycemic
index and related insulin secretion [149-155].
The inverse associations between C17:0/C21:0 and fasting insulin and insulin
sensitivity indices observed in the present study are in line with previous findings showing
positive effects of higher rye consumption on fasting plasma insulin and to a lesser extent on
fasting plasma glucose [159]; further supporting the use of the ratio of the homologues C17:0
and C21:0 as an indicator of whole grain/bran rye intake. Although the AR C17:0/C21:0 ratio
reflects only the relative wholegrain/bran rye consumption of total whole grain wheat and rye
intake, not total rye intake, the advised whole grain rye intake was high in the present study in
relation to other sources of AR and therefore the ratio should reflect the total rye intake
reasonably well. Rye was mostly consumed in the form of bread.
Several intervention studies have shown diminished levels of postprandial insulin
following a rye bread meal [161, 162, 164], possibly explained by structural differences
between rye and whole-wheat breads [164, 212]. The lower postprandial insulin response
after rye bread consumption as compared to wheat bread may be due to the difference in
structure rather than fiber content of whole grain, as low fiber rye bread showed the same
results as high fiber rye bread consumption [163, 165]. Moreover, an improved early insulin
response has been exhibited after rye bread interventions [163, 165]. In the present study there
was, however, no significant association between the AR C17:0/C21:0 ratio and early or late
insulin secretion phase as measured by insulin secretion indices.
5.3.2. Blood lipids
Total plasma AR concentration was not significantly associated with concentrations of fasting
serum total cholesterol (P = 0.95), LDL cholesterol (P = 0.23), HDL cholesterol (P = 0.25),
LDL-C/HDL-C ratio (P = 0.13), triglycerides (P = 0.14), Apo A1 (P = 0.09) or Apo B (P =
0.86) after adjusting for confounders. Several animal and human studies have shown
cholesterol lowering effects of whole grain rye [177, 178, 190-192] but the lack of
associations in these studies may be due to considerable amount of AR intake originating
from whole grain wheat. Whole grain wheat intake does not typically affect blood cholesterol
and is thus often used as a control in experimental studies [188].
Supporting that hypothesis, the AR C17:0/C21:0 ratio was inversely associated with
LDL cholesterol concentration when adjusted for baseline LDL cholesterol concentration,
BMI, age and statin use (model 1, P = 0.040) and also when total plasma AR was added to the
regression model (model 2, P = 0.046) (Table 14). Similarly, AR C17:0/C21:0 ratio was
inversely associated with LDL/HDL cholesterol ratio (P = 0.020 and P = 0.024 for model 1
and model 2, respectively), non-HDL cholesterol (P <0.001 for both model 1 and model 2),
triglycerides (P = 0.004 and P=0.002 for model 1 and model 2, respectively) and
apolipoprotein B concentrations (P = 0.047 for both model 1 and model 2) and positively
associated with HDL cholesterol concentration (P = 0.044 and P = 0.049 for model 1 and
53
model 2, respectively) (Table 14). Including saturated fatty acids calculated from food records
to the models did not change the results nor did including the serum phospholipid fatty acids
myristic acid, palmitic acid, omega-3 fatty acids and C15:0, except for HDL cholesterol in
which the association with C17:0/C21:0 became borderline significant (P = 0.067). Thus,
increased relative whole grain rye intake, reflected by the AR ratio C17:0/C21:0, seems to be
associated with favorable blood lipid outcomes.
Table 14. Regression models for concentrations of serum LDL, HDL, non-HDL cholesterol,
triglycerides and apolipoprotein B and the cholesterol LDL-C/HDL-C ratio at 18/24 weeks
Dependent variable at
Independent variable at
B† (95% CI)
18/24 weeks
18/24 weeks
LDL cholesterol
Model 1
AR C17:0/C21:0
-0.41 (-0.80 to -0.02)
Model 2
AR C17:0/C21:0
-0.40 (-0.79 to -0.01)
Log HDL cholesterol
Model 1
AR C17:0/C21:0
0.11 (0.00 to 0.21)
Model 2
AR C17:0/C21:0
0.11 (0.00 to 0.21)
Log LDL/HDL cholesterol
Model 1
AR C17:0/C21:0
-0.20 (-0.37 to -0.03)
Model 2
AR C17:0/C21:0
-0.20 (-0.37 to -0.03)
Log non HDL cholesterol
Model 1
AR C17:0/C21:0
-0.84 (-1.22 to -0.45)
Model 2
AR C17:0/C21:0
-0.81 (-1.19 to -0.44)
Log triglycerides
Model 1
AR C17:0/C21:0
-0.35 (-0.59 to -0.12)
Model 2
AR C17:0/C21:0
-0.37 (-0.60 to -0.13)
Log apoliprotein B
Model 1
AR C17:0/C21:0
-0.12 (-0.24 to 0.00)
Model 2
AR C17:0/C21:0
-0.12 (-0.24 to 0.00)
†
B reflects the change in the log-transformed outcome variable for each 1-unit changes in the
independent variable.
Model 1: adjusted for baseline value of the dependent variable, BMI, age and statin use
Model 2: adjusted for baseline value of the dependent variable, total plasma AR, BMI, age
and statin use
Abbreviations: AR, alkylresorcinols; HDL, high-density lipoprotein; LDL, low-density
lipoprotein; BMI, body mass index
54
Health effects of rye are far less studied than oats and barley and studies on the effects of rye
consumption on blood cholesterol are scarce. The mechanisms that have been proposed to
cause the reduction in blood cholesterol levels focus on the fiber and phytochemical content
of whole grains, particularly water-soluble viscose fiber [144, 189] and it has been established
that the cholesterol lowering effect of β-glucans is dependent on the molecular weight and
subsequent viscosity [70]. Rye is particularly high in dietary fiber, ranging between 18-22%,
and it contains substantial amounts of extractable β-glucans and arabinoxylans, which may
contribute to cholesterol reduction through a similar mechanism as β-glucans from oats and
barley [70, 82]. Animal studies have shown that rye can affect blood lipid concentrations by
increasing the total concentration of bile acids in the bile [190, 191].
Previous studies have shown that rye bread consumption decreases total and LDL
cholesterol concentrations in men with moderately elevated serum cholesterol [177], and
lower concentrations of plasma free-cholesterol, total cholesterol, triglycerides and
phospholipids have been demonstrated after a high fiber rye diet than a low fiber wheat diet
[178]. Additionally, animal studies have shown cholesterol lowering effects of rye
consumption [190-192]. However, Moazzami et al showed an unfavorable shift in serum
cholesterol levels after rye bread intake in postmenopausal women [194]. Processing of rye
and other whole grains, such as fermentation, have been reported to influence the molecular
weight of cereal dietary fiber, hence it is possible that the lower viscosity of the fibers could
explain the lack of beneficial effects reported in some studies [82]. Nevertheless, these results
suggest that higher relative whole grain rye consumption is associated with favorable
outcomes in blood lipids and this association needs to be further studied.
5.4. ARI feasibility study (Paper IV)
As Icelanders had the lowest intake of dietary fiber and whole grain rye in the SYSDIET
intervention [196], the acceptance and compliance to a high whole grain rye intake was
explored in a feasibility study (ARI).
Altogether, 23 men started the intervention, 14 in the rye group and 9 in the control
group. The drop-out rate was low with only three men dropping out of the study, two in the
rye group and one in the control group. Two men dropped out during the first weeks for
personal reasons not related to the intervention and one had a medical condition and was not
able to finish the intervention. Thus, 20 men (87%) completed the study, 12 in the rye group
and 8 in the control group.
5.4.1. Baseline
The mean age of the participants was 59 (11) years. Baseline characteristics are presented in
Table 15. The BMI for the participants at baseline was 24 – 38 kg/m2. There was no
significant difference between the groups in baseline characteristics except that participants in
the control group took more steps/day than participants in the rye group.
55
Table 15. Baseline characteristics of the participants in the ARI feasibility study
Age, years
Height, cm
Weight, kg
Body mass index, kg/m2
Waist circumference, cm
Fat, %
Data are presented as mean (SD)
Rye group
(n = 14)
57 (11)
178 (6)
99.4 (11.8)
31.5 (4.4)
114 (10)
32.9 (5.0)
Control group
(n = 9)
62 (11)
178 (8)
93.5 (13.8)
29.4 (3.0)
109 (8)
34.4 (3.5)
5.4.2. Rye and dietary fiber consumption
At week 0 the rye consumption was 11 (19) g/day and as expected, there was a highly
significant increase in rye consumption in the rye group from week 0 to week 26, with
reported rye intake increasing to 103 (38) g/day at week 13 and 86 (41) g/day at week 26 (P =
0.003). The rye consumption in the control group was unchanged (Figure 6).The mean rye
consumption for the rye group in the intervention was 93 (44) g/day, equivalent to an 8-fold
increase in daily rye consumption. The mean rye consumption in the control group was 10 (8)
g/day. The rye consumption was right skewed with 7 out of 12 participants consuming ≥100
g/day of rye during the intervention, three consuming 60 to 99 g/day and two consuming
below 60 g/day. The fiber intake at week 0 was also low, 19 g/day, comparable to the average
consumption of Icelandic men, 17.7 g/day, according to recent National Dietary Survey [213].
Reflecting the changes in rye intake, there was a borderline significant increase in fiber intake
in the rye group, with mean intake 19 (10) g/day at week 0, 33 (10) g/day at week 13 and 28
(7) g/day at week 26 (P = 0.06).
On average, 72% of daily rye consumption in the rye group came from the rye flakes
which emphasizes the importance of including rye porridge in future studies. Whole grain rye
porridge has also been shown to improve satiety compared to wheat bread breakfast,
subsequent decreased hunger and desire to eat up to 8 hours after consumption [214, 215].
Possibly the habitually low bread consumption of Icelandic adults may favor the acceptability
of the porridge, as introduction of a bread meal may cause greater changes in the daily diet
than changes in breakfast choice.
56
40
RG
100
80
60
40
CG
20
0
Fiber consumption, g/day
Rye consumption, g/day
120
35
RG
30
25
20
CG
15
10
5
0
Week 0
Week 13
Week 26
Week 0
Week 13
Week 26
Figure 6. Rye consumption and total dietary fiber intake for rye group (RG) and control
group (CG) at week 0, 13 and 26 of the intervention.
There was no significant difference between groups in energy or macronutrient intake during
the intervention (Table 16) indicating that the rye products were not added to the baseline diet
but exchanged for other carbohydrate rich food. The carbohydrate intake seemed to increase
in the rye group between weeks 13 and 26 and decrease in the control group but the change
was not statistically significant nor was the difference between the groups.
Table 16. Energy and macronutrient intake for both groups at week 0, 13 and 26
Rye group
Control group
Week 0
Week 13
Week 26
Week 0
Week 13
Week 26
Energy, kcal
2000 (534) 2175 (629) 1995 (631) 2410 (325) 2249 (655) 2230 (578)
Carbohydrates, E%
39 (5)
39 (4)
43 (5)
43 (8)
43 (9)
38 (6)
Protein, E%
21 (5)
21 (5)
20 (4)
19 (3)
18 (2)
17 (3)
Fat, E%
34 (7)
36 (5)
37 (6)
35 (8)
38 (7)
39 (6)
Added sugar, E%
6 (2)
6 (2)
5 (3)
8 (7)
7 (7)
5 (4)
Data are presented as means (SD)
5.4.3. Compliance
In addition to dietary records, compliance to the study diet was assessed with plasma AR as
dietary biomarker. Similar to rye and dietary fiber intake, the total plasma AR concentration
and the AR C17:0/C21:0 ratio increased in the rye group but not in the control group
indicating good compliance to the whole grain rye intake (Figure 7). As discussed previously
plasma AR has been established as a biomarker for whole grain wheat and rye intake in
numerous studies [18, 19, 196] and the AR C17:0/C21:0 ratio has been suggested as an
indicator of relative rye intake [25, 28, 197]. For the rye group in the present study, the mean
57
AR C17:0/C21:0 ratio went from 0.22 (0.14) at week 0 to 0.34 (0.15) at week 13 and then
decreased slightly, to 0.29 (0.10), at week 26. Comparing the results to ND group in the
SYSDIET study, the AR C17:0/C21:0 ratio at week 0 was 0.3 (0.2) but did, however, not
change during the intervention, probably due to already high ratio in the Finnish participants
at baseline [197]. This might be one reason for the lack of health effects in the SYSDIET
study. Good compliance has also been reported in similar intervention studies, conducted in
Sweden and Finland where overall rye consumption is higher. In all studies rye products were
provided to the participants free of charge, as was done in the present study [159, 163, 165,
178].
RG
80,0
60,0
40,0
CG
20,0
0,0
Week 0
Week 13
Week 26
AR C17:0/C21:0 ratio
Total plasma AR, nmol/L
100,0
0,4
0,35
0,3
0,25
0,2
0,15
0,1
0,05
0
RG
CG
Week 0
Week 13
Week 26
Figure 7. Total plasma alkylresorcinols (AR) concentration and AR C17:0/C21:0 ratio for rye
group (RG) and control group (CG) at week 0, 13 and 26 of the intervention
5.4.4. Acceptability
The men in the rye group were generally pleased with the rye products and few reported
digestive discomfort. Four of the twelve participants in the rye group had experienced
digestive discomfort in the first 13 weeks of rye consumption and two participants in the latter
13 weeks (Figure 8). The rye intake tended to be higher for those who claimed they had felt
discomfort. The mean rye consumption at 13 weeks for the four men that had experienced
discomfort in the first weeks was 130 (13) g/day while it was 94 (42) g/day for those had not
experienced any discomfort. Similarly, at week 26, the mean consumption for the two
participants that had experienced digestive discomfort in the latter 13 weeks was 123 (9)
g/day while it was 91 (31) g/day for those that did not experience any discomfort. The
difference in rye consumption between those that did experience discomfort and those that did
not was, however, not statistically significant. These results indicate, however, that it might be
difficult to increase rye consumption over 100 g/day in this population. However, the
participants seemed to adapt to the products, i.e. fewer felt discomfort at week 26 than 13,
more participants liked the products and more answered that they would prefer rye products.
58
The results of the acceptability in the present study are similar to the study by Pereira
et al [149] where 9 of 11 participants preferred a whole grain diet after a crossover controlled
feeding trial with two 6-week feeding periods, whole grain (dietary fiber 28 g/day) vs. refined
grain (dietary fiber 17.8 g/day) with no difference between groups in recorded indigestion.
Landberg et al [24], also using a crossover design with two 6-week feeding periods but with
much higher amounts of whole grain rye (dietary fiber 67 g/day) reported greater dropout,
with 7 of 24 participants did not finishing the study because of constipation and 17
participants reporting mild constipation. This indicates that some men may not tolerate such
high intakes of dietary fiber, at least not without a longer adaption period.
Six participants answered positively at week 13 when asked if they liked the rye
products and eight at week 26. At week 26 no participant disliked the products. Similarly, at
week 26 eight participants stated that they would prefer products that contain rye more than
other products and no participants disagreed (Figure 8).
a) 10
b) 10
13 w
26 w
6
4
13 w
26 w
26 w
2
agree
6
13 w
4
13 w 26 w
13 w
2
13 w
0
26 w
8
Participants, n
Participants, n
8
26 w
0
neither nor
disagree
agree
neither nor
disagree
Participants, n
c) 10
26 w
8
6
13 w
13 w
4
26 w
2
13 w
26 w
0
agree
neither nor
disagree
Figure 8. The rye group´s acceptability of the rye products (n = 12) assessed by three
questions at week 13 (13 w) and week 26 (26 w): a) I have experienced digestive discomfort
after I started eating rye products b) I like food products that contain rye and c) I would prefer
products that contain rye more than other products
59
6. Strengths and limitations
The strengths of the SYSDIET study include reliable and comparable methods that were used
in six different centers in four Nordic countries. The same study protocol was used in all
centers and analyses of plasma AR were done centrally in Uppsala, Sweden. The SYSDIET
study was, however, designed to reveal mechanisms by which Nordic foods and diets could
be modified to promote health and prevent chronic diseases. Thus, it was not designed
specifically to assess the effects of whole grain intake on health outcomes but of the overall
Nordic diet. This is a limitation to the present analyses of the SYSDIET study as confounding
effects from other food sources cannot be completely excluded and analyses were partly
cross-sectional. Information on the intake of food was not available from the study centers but
detailed information on whole grain and/or whole grain products, and other food products,
would have strengthened the conclusions in the present analyses. Nevertheless, the results
suggest that participants were compliant with the whole grain intake recommended (at least
whole grain rye and wheat).
The strengths of the ARI feasibility study are that the population studied had habitual
low intake of whole grain and fiber and the results are of high importance for the design of
future studies. Additionally, a rye intervention with patients with type 2 diabetes has not been
done before. The number of participants was, however, low and resulted in power issues for
analyses of health effects that would have been an interesting addition to the study.
In both studies plasma AR were used as biomarkers for whole grain wheat and rye
intake instead of (SYSDIET), and in conjunction with (ARI feasibility study), self-reported
estimates. The suitability of AR as a biomarker for whole grain wheat and rye intake has been
shown in many studies, and at present it appears to be the best option. The use of dietary
biomarkers instead of, or preferably in conjunction with, self-reported intake to measure
compliance or diet-disease relationships is an approach that should be further studied and
utilized in future research. It is, however, important to note that the half-life of plasma AR is
short and therefore it may not be suitable at irregular and small intakes and although the
reproducibility has been reported to be good in intervention settings it is somewhat lower in
free-living subjects. Nevertheless, plasma AR can be used to distinguish between high and
very low consumers of whole grain rye and wheat in epidemiological studies and as a
compliance marker in dietary interventions, including whole grain wheat and rye intake.
AR is a dietary biomarker for whole grain wheat and rye intake, not other whole
grains, such as oats, and barley contains only a small amount compared to wheat and rye.
Additionally, the AR ratio C17:0/C21:0 only reflects relative intake of whole grain rye, not
absolute intake, but where intake is high and stable it reflects absolute intake relatively well.
Other markers are therefore warranted to monitor whole grain intake from other cereal
sources. To date, no such markers have, however, been identified or validated.
60
7. Conclusion
The results of the present study suggest that fasting total plasma AR concentration may be
used as a biomarker in a population consuming the healthy Nordic diet, in which whole grain
wheat and rye are important contributors. Hence, the results further support the proposed use
of fasting plasma AR as a biomarker of whole grain wheat and rye intake, especially in
populations where whole grain wheat and rye intake is high and relatively consistent. The
results of the present study also support the use of the ratio of the AR homologues C17:0 and
C21:0 as an indicator of relative rye intake in intervention studies where a diet rich in whole
grain rye is being investigated. Although the ratio reflects only the relative whole grain/bran
rye consumption of total whole grain wheat and rye intake the ratio may reflect total rye
intake reasonably well where rye intake is high in relation to other sources of AR.
In cross-sectional settings the AR C17:0/C21:0 ratio was inversely associated fasting
insulin concentration and positively associated with insulin sensitivity indicating that
increased proportion of whole grain rye in the diet may be associated with lower fasting
insulin concentration and increased insulin sensitivity. Increased proportion of whole grain
rye, reflected by AR C17:0/C21:0, was also associated with favorable outcomes in blood lipid
concentrations.
The baseline dietary fiber intake and total plasma AR differed substantially between
study centers with the highest fiber and plasma AR concentration in Finland and the lowest in
Iceland. The feasibility study, carried out in Iceland, produced valuable information that can
be used to design a randomized controlled trial aimed to assess the health effects of high rye
consumption in a population not accustomed to high intakes. The dropout-rate in the
feasibility study was low and the good compliance and in general good acceptability of the
rye products showed that the intervention was well received by the population studied.
61
8. Future perspectives
The present study provides useful knowledge regarding the use of plasma AR as a biomarker
for whole grain wheat and rye intake as a part of the healthy Nordic diet and the utilization of
plasma AR as a biomarker in nutritional science. Plasma AR is a highly promising biomarker
for whole grain wheat and rye intake but still there are many factors that are poorly
understood.






The validity of plasma AR as a biomarker for various amounts of whole grain intake
needs to be determined, especially at low intakes and in non-European populations in
order to assess their applicability across different range/types of whole grain intake.
The validity of plasma AR against other assessment methods in free-living subjects
needs to be evaluated.
The potential use of plasma AR measurements in combination with traditional dietary
assessment methods for intake estimation should be evaluated.
For measure of compliance there is still uncertainty around cut-off points for
determining when a person has consumed a certain quantity of whole grain per day, or
if they are naturally low absorbers/metabolizers of AR.
Deeper understanding of the absorption and metabolism of AR is needed with more
strict, high-quality interventions on the effects of rye and rye products on changes in
plasma AR and on human physiology.
Deeper understanding of the absorption and metabolism of the different homologues is
needed for more accurate use of C17:0/C21:0 ratio for determining the source of AR
consumed.
It is important to keep in mind that AR is only a marker of whole grain wheat and rye intake
and an objective marker of overall whole grain intake and/or for other types of cereals is
desirable. Studies on metabolites have discovered potential markers of certain whole grain
food intakes using metabolomics, an interesting field of research.
Although rye is the second most consumed cereal in the Nordic countries after wheat,
studies on the health effects of whole grain rye are scarce. The results from the ARI feasibility
study showed that increased whole grain rye intake was well accepted by Icelandic men but
further studies on how to increase compliance in interventions, and in clinical work, is
needed. The knowledge gained from the study should be utilized for future research on the
effects of whole grain rye consumption, using plasma AR and AR C17:0/C21:0 ratio as a
measure of compliance, on insulin sensitivity and, in particular, blood lipids, which is an area
of research that is very limited.
62
9. Acknowledgements
The present work was carried out at the Unit for nutrition research, Faculty of Food Science
and Nutrition, School of Health Science, University of Iceland and Landspítali – The National
University Hospital of Iceland. Funding was provided by Nordforsk NcoE in Food, Nutrition
and Health: Project 070014 SYSDIET (Systems biology in controlled dietary interventions
and cohort studies) and project HELGA: Nordic Health – Whole Grain Food, the Consortium
Agreement for Consortium on Health and Ageing Network of Cohorts in Europe and the
United States (CHANCES) (EG Grant agreement No: 242244) and the Icelandic Research
Fund for Graduate Students (1206880061).
I would never have been able to complete this huge task on my own so in the
following paragraphs I would like to express gratitude to all the people who played a part.
First of all I would like to thank my hard working supervisors, Inga Þórsdóttir and Ingibjörg
Gunnarsdóttir, for giving me this opportunity and for the guidance and support through this
process. Furthermore I would like to thank Laufey Steingrímsdóttir, who initiated and
coordinated the ARI feasibility study and Þórhallur Ingi Halldórsson for his advice, statistics
lessons and reading over my thesis. I want to thank all my co-workers at the Unit for Nutrition
Research and the team of dietitians at Landspitali National-University Hospital, you made the
work so much more fun. It is a pleasure to have worked with such professional, practical and
experienced individuals.
I want to thank those that took part in the data collection. Svandís Erna Jónsdóttir who
together with me collected the data in the SYSDIET study and I also thank Laufey
Hrólfsdóttir and Auður Benediktsdóttir who worked with me to collect data in the ARI
feasibility study. My endless gratitude goes also to the participants of the studies as it goes
without saying that without their contribution the research could not have been conducted.
I would furthermore like to thank my co-authors of the papers, who are all outstanding
scientists, for providing their useful contributions and comments. I especially want to thank
Rikard Landberg, who has been my “alkylresorcinols mentor“. He has been extremely helpful
and willing to share his knowledge and experience and he has served me incredibly well
throughout this work.
I would like to thank my dear friends and fellow PhD students, Ása Vala, Cindy, Ólöf
Helga, Svandís and Tinna. It is hard to describe it in words how much fun I´ve had with you
these years and your friendship alone made all the work worth it. Cindy gets special thanks
for the support during the last year, reading over the thesis and answering endless English
grammar questions and Svandís for mental support over these stressful last couple of months.
Finally I want to thank my family. I thank my parents and my parents in law for all their love,
support and the faith they have in me and everything I do, kinder and more generous people
are hard to find. I am forever grateful to my wonderful husband, Guðmundur, for his endless
patience and encouragement throughout this journey and always believing in me. Last, but
certainly not least, I would like to thank my two daughters, Þórunn and Hrafnhildur, for
making me smile and reminding me every day what truly matters in life.
Reykjavik, September 2014
Óla Kallý Magnúsdóttir
63
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80
Paper I
Supplemental Material can be found at:
http://jn.nutrition.org/content/suppl/2013/08/11/jn.113.17558
8.DCSupplemental.html
The Journal of Nutrition
Nutrition and Disease
Plasma Alkylresorcinols Reflect Important
Whole-Grain Components of a Healthy
Nordic Diet1-4
Ola Kally Magnusdottir,5* Rikard Landberg,6 Ingibjorg Gunnarsdottir,5 Lieselotte Cloetens,7
Björn Åkesson,7,8 Gunilla Önning,7 Svandis Erna Jonsdottir,5 Fredrik Rosqvist,9 Ursula Schwab,10,11
Karl-Heinz Herzig,12 Markku J. Savolainen,13 Lea Brader,14 Kjeld Hermansen,14
Marjukka Kolehmainen,10,15 Kaisa Poutanen,10,15 Matti Uusitupa,10,16 Inga Thorsdottir,5 and Ulf Risérus9
Downloaded from jn.nutrition.org at LANDSPITALI UNIVERSITY HOSPITAL LIBRARY on August 21, 2013
5
Unit for Nutrition Research, Landspitali, The National University of Iceland, Faculty of Food Science and Nutrition and School of
Health Sciences, University of Iceland, Reykjavı́k, Iceland; 6Department of Food Science, BioCenter, Swedish University of Agricultural
Sciences, Uppsala, Sweden; 7Biomedical Nutrition, Pure and Applied Biochemistry, Lund University, Lund, Sweden; 8Department of
Clinical Nutrition, Skåne University Hospital, Lund, Sweden; 9Department of Public Health and Caring Sciences, Clinical Nutrition and
Metabolism, Uppsala University, Uppsala, Sweden; 10Institute of Public Health and Clinical Nutrition, University of Eastern Finland,
Kuopio, Finland; 11Institute of Clinical Medicine, Internal Medicine, Kuopio University Hospital, Kuopio, Finland; 12Institute of
Biomedicine, Department of Physiology and Biocenter of Oulu, Oulu University, Oulu, Finland, and Department of Psychiatry, Kuopio
University Hospital, Kuopio, Finland; 13University of Oulu, Institute of Clinical Medicine, Department of Internal Medicine and
Biocenter Oulu, Oulu, Finland, and Oulu University Hospital, Clinical Research Center, Oulu, Finland; 14Department of Medicine and
Endocrinology MEA, Aarhus University Hospital, Aarhus, Denmark; 15Valtion Teknillien Tutkimuskeshus, Technical Research Center of
Finland, Espoo and Kuopio, Finland; and 16Research Unit, Kuopio University Hospital, Kuopio, Finland
Abstract
Biomarkers of dietary intake can be important tools in nutrition research. Our aim was to assess whether plasma alkylresorcinol
(AR) and b-carotene concentrations could be used as dietary biomarkers for whole-grain, fruits and vegetables in a healthy
Nordic diet (ND). Participants (n = 166), 30–65 y with a body mass index of 27–40 kg/m2 and two more features of metabolic
syndrome (International Diabetes Federation definition, slightly modified), were recruited through six centers in the Nordic
countries and randomly assigned to an ND or control diet for 18 or 24 wk, depending on study center. Plasma AR and
b-carotene were analyzed and nutrient intake calculated from 4-d food records. Median fiber intake increased in the ND
group from 2.5 g/MJ at baseline to 4.1 g/MJ (P < 0.001) at end point (week 18 or 24), and median (IQR) fasting plasma total
AR concentration increased from 73 (88) to 106 (108) nmol/L, or 45%, from baseline to end point (P < 0.001). The AR
concentration was significantly higher in the ND group (P < 0.001) than in the control group at end point. b-Carotene intake
tended to increase in the ND group (P = 0.07), but the plasma b-carotene concentration did not change significantly
throughout the study and did not differ between the groups at follow-up. In conclusion, an ND resulted in higher dietary
fiber intake and increased plasma total AR concentration compared with the control diet, showing that the total AR
concentration might be a valid biomarker for an ND in which whole-grain wheat and rye are important components. No
significant difference in plasma b-carotene concentrations was observed between the ND and control groups, suggesting
that b-carotene may not be a sensitive enough biomarker of the ND.
Introduction
Several studies have shown a strong inverse relationship between
fruit and vegetable consumption and prevalence of chronic
diseases such as hypertension, coronary heart disease, and stroke
1
The study was supported by NordForsk NCoE in Food Nutrition and Health:
Project 070014 SYSDIET (Systems Biology in Controlled Dietary Interventions
and Cohort Studies). This study was also funded by the Academy of Finland,
Finnish Diabetes Research Foundation, Finnish Foundation for Cardiovascular
Research, the Sigrid Juselius Foundation, and EVO funding from Kuopio
University Hospital (Finland); the Druvan Foundation, ESPEN, Skåne County
Council Research and Development Foundation, Swedish Council for Working
Life and Social Research, the Heart-Lung Foundation, Diabetesfonden and
Foundation Cerealia (Sweden); the Danish Obesity Research Centre (DanORC,
www.danorc.dk), the Danish Council for Strategic Research (DairyHealth,
J. Nutr. 143: 1383–1390, 2013.
(1–4). Moreover, the intake of whole-grain cereals has been inversely associated with type 2 diabetes, coronary heart disease,
and other cardiovascular risk factors (5–8). Despite this evidence, no consistent findings have been demonstrated in intervention
BioFunCarb) (Denmark), the Agricultural Productivity Fund (Iceland), and the
Icelandic Research Fund for graduate students (1206880061). The following
companies provided food products for the study participants: Kesko Food and
Raisio Group (Finland); Belico Food AB, Bunge Finland, Fazer Bageri Sverige,
Lantmännen, Oatly AB, Olle Svensson AB, Procordia Food AB, Pågen AB,
Unilever, and Wasabröd AB (Sweden); Lantmännen Food R&D, Jan Import A/S,
Ardo A/S, Scandic Food A/S, WASA, Glyngøre Limfjord A/S, Royal Greenland
A/S, and Arla Foods (Denmark); the Mother Earth Farm at Vallanes (Iceland); and
Unilever Nordic (Sweden, Denmark, Iceland).
ã 2013 American Society for Nutrition.
Manuscript received February 11, 2013. Initial review completed March 27, 2013. Revision accepted June 03, 2013.
First published online July 10, 2013; doi:10.3945/jn.113.175588.
1383
Methods
The current analysis is part of the SYSDIET study, a randomized controlled multicenter study performed in six intervention centers (Kuopio
2
Author disclosures: O. K. Magnusdottir, R. Landberg, I. Gunnarsdottir, L.
Cloetens, B. Åkesson, G. Önning, S. E. Jonsdottir, F. Rosqvist, U. Schwab, K.-H.
Herzig, M. J. Savolainen, L. Brader, K. Hermansen, M. Kolehmainen, K.
Poutanen, M. Uusitupa, I. Thorsdottir, and U. Risérus, no conflicts of interest.
3
The study was registered at clinicalTrials.gov as NCT00992641.
4
Supplemental Tables 1-5 are available from the ‘‘Online Supporting Material’’
link in the online posting of the article and from the same link in the online table of
contents at http://jn.nutrition.org.
17
Abbreviations used: AR, alkylresorcinols; ICC, intraclass correlation coefficient; ND, Nordic diet; SYSDIET, Systems Biology in Controlled Dietary
Interventions and Cohort Studies.
*To whom correspondence should be addressed: E-mail: [email protected].
1384
Magnusdottir et al.
and Oulu, Finland; Lund and Uppsala, Sweden; Aarhus, Denmark; and
Reykjavik, Iceland). This study examined the health effects of a healthy
ND, compared with a habitual diet in the Nordic countries, in a study
group with features of metabolic syndrome. Local ethical committees
approved the SYSDIET study protocol, which followed the Helsinki
declaration guidelines. Informed written consent was obtained from all
participants. The study design was reported in detail previously (12).
Study participants Study participants were mainly recruited through
newspaper advertisements or previously took part in clinical or epidemiological trials in the study centers. The inclusion criteria were 30–65 y
of age, BMI of 27–40 kg/m2, and two other criteria for metabolic
syndrome as defined by the International Diabetes Foundation (39),
although individuals with type 2 diabetes were excluded. Antihypertensive and lipid-lowering medications were allowed but without changes
during the trial. The comprehensive inclusion and exclusion criteria have
been described previously (12).
In total, 201 individuals started the intervention: 104 in the ND
group and 97 in the control group. At trial completion, 96 participants
were in the ND group (92%) and 70 in the control group (72%). Complete dietary records from both baseline (week 0) and end point (week 18
or 24) were available for 158 participants.
Study design The study design and the main clinical and biochemical
measurements were described previously (12). Before randomization
into the ND or control group, for 1 mo participants followed their habitual diet except oil supplements and food enriched with plant stanol or
sterol were discontinued. Participants then followed either the ND or
control diet for 18 or 24 wk. For financial and logistic reasons the study
period was 18 wk for four centers (Aarhus, Uppsala, Reykjavik, and Oulu)
and 24 wk for two centers (Lund and Kuopio) where the intervention
was started earlier (12).
Staff in all study centers were trained to perform measurements in a
similar way, and the quality management protocol was made available to
all of them. The study participants were advised to keep physical activity
constant and not to change their smoking and drinking habits or drug
treatment during the study.
Study diets Nordic nutrition recommendations formed the basis of
the ND (40), and the mean nutrient intake in the Nordic countries
formed the basis for the control diet. Participants in the ND group were,
among other things, advised to consume $25% of total energy as whole
grain, of which $50% should be rye, barley, and oats, and $6 slices/day
of bread with $6 g fiber/100 g (one slice equals 30–40 g of bread). They
were asked to consume $500 g of fruit/d ($175 g/d), vegetables
($175 g/d), and berries ($150 g/d). Participants in the control group
were asked to consume $25% of energy as refined grain: $90% wheat.
They were also asked to keep fruit and vegetable consumption between
200 and 250 g/d. The food items recommended are summarized
(Supplemental Table 1).
Key products were provided to the participants in both groups. The
ND group received whole-grain products such as oats and barley, crisp
bread, whole-grain wheat and rye breads, berry products (frozen berries
and dried powder), and rapeseed oil– and vegetable oil–based spreads.
Furthermore, fish (fatty and lean) was either directly provided or the cost
for purchase was reimbursed to ND group participants. Control group
participants received low-fiber cereal products, for example, breads with
fiber content <6 g/100 g and ordinary pasta and dairy fat–based spread.
Participants were instructed by a clinical nutritionist or dietitian during all visits. Participants kept dietary records on their intake of cereal
products, berry products, vegetables, and fish. These records were checked
at each visit to the study center, including visits when groceries were
delivered to participants, which was at 1- to 2-wk intervals. Any intake of
supplements was to be discontinued at least 4 wk before entering the
study. An exception was made for vitamin D supplements in Iceland, which
the participants could continue to use providing they kept dosage unchanged.
Vitamin D supplementation was not included in the nutrient calculations.
The target nutrient composition of the diets is summarized in Table 1.
Dietary assessment Dietary intake was assessed using a consecutive
4-d (Wednesday to Saturday or Sunday to Wednesday) food record, with
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studies. Recent Danish and Swedish studies suggest that a ‘‘healthy
Nordic diet" composed of typical Nordic food items may induce
similar health effects as the Mediterranean diet (9–11). In the
controlled intervention study Systems Biology in Controlled
Dietary Interventions and Cohort Studies (SYSDIET),17 a healthy
Nordic, isocaloric diet caused moderate improvements in lipid
profile and resulted in lower levels of the inflammation marker
IL 1 receptor antagonist compared with a control diet (12).
Most dietary assessment instruments rely to some extent on
self-reporting, which is prone to systematic and random measurement errors as a result of, for example, under or overreporting and imprecision (13,14). Collecting valid data on dietary
fiber and whole-grain intake can be especially challenging because of the broad selection of foods contributing to these
intakes (15). One way to avoid some of the obstacles associated
with traditional dietary assessment instruments is to use dietary
biomarkers as a complement to self-reports (16–20).
Alkylresorcinols (ARs) have been proposed as biomarkers for
whole-grain and bran intake of wheat and rye (15,21,22) and for
cereal fiber intake (23). ARs are 3,5-dihydroxy-alkylbenzenes
(phenolic lipids) abundant in the outer layers of rye and wheat,
found in low amounts in barley, and absent in highly refined white
flour and in most other foods consumed by humans. Controlled
whole-grain and bran intervention studies have shown that plasma
AR concentrations increase proportionally with AR and wholegrain intake (22,24–28). Thus, AR can be a useful biomarker to
categorize participants as low or high consumers of whole-grain
foods (15,29) and to monitor their compliance with a wholegrain diet in intervention studies (21,30).
Carotenoids have been proposed as biomarkers of fruit and
vegetable intake (31,32). They are generally found in plant foods,
mainly yellow and orange fruits, orange root vegetables, and
green leafy vegetables. Population studies have indicated that
b-carotene may be a reliable biomarker for the intake of fruits
and vegetables (33), although not all studies agree (32,34). In
addition to being a possible biomarker of dietary intake, plasma
b-carotene is linked as a risk factor for diseases as previously
reviewed (35). Low plasma b-carotene is a risk factor for insulin
resistance, type 2 diabetes, and metabolic syndrome (36, 37),
and a relationship between dietary b-carotene and metabolic
syndrome has also been observed (38).
The aim of the present study was to assess whether AR and
b-carotene plasma concentrations could be used as dietary biomarkers of a healthy Nordic diet (ND), rich in whole-grain
wheat and rye as well as fruits and vegetables, and a control diet
in the SYSDIET study and to determine their relationships with
reported dietary fiber intake in individuals with markers of metabolic syndrome (12).
either weighed or estimated portion sizes. The baseline food diaries were
recorded during the 1-mo period before the intervention and then at
week 2 (data not included in this paper), week 12, and the end point. The
nutrient intake during the intervention has been published elsewhere
(12). The main focus of our study was on the intake of dietary fiber,
b-carotene, and other nutrients abundant in fruits, vegetables, and whole
grains.
At each center information from the food diaries was used to calculate nutrient intake, using national nutrient databases. All the databases used EuroFIR definitions for chemicals and total dietary fiber
determined by AOAC methods (41–44).
TABLE 1 Advised nutrient composition of a healthy Nordic diet
and control diet during the intervention1
Nutrient
Carbohydrate, E%
Sucrose, E%
Fiber, g/d
Protein, E%
Fat, E%
Saturated, E%
Monounsaturated fat +
polyunsaturated fat, E%
Salt, g
Women
Men
1
E%, percent of daily energy intake.
Maximum: 50 g/d.
3
Or 4 g/MJ.
2
Nordic diet
Control diet
45–52
#102
$353
18–20
30–35
,10
At least 2/3 of
total fat intake
45–47
No restrictions
15–20
18–20
35
15
15 + 5
6
7
#10
#10
Results
Data at baseline
Baseline characteristics of the participants are shown in Supplemental Table 2. No difference in basic baseline characteristics
existed between dropouts and those who completed the study
(data not shown).
No significant difference in AR or b-carotene concentration
in plasma was observed between the ND and control groups at
randomization (Table 2).When all participants were analyzed
together at baseline, median (IQR) intake of dietary fiber was
21 (8) g/d and 2.5 (1.0) g/MJ, intake of b-carotene was 2.0 (3.1)
mg/d, the plasma AR concentration was 72 (73) nmol/L, and the
plasma b-carotene concentration was 0.35 (0.32) mmol/L.
Changes observed during the intervention
Dietary fiber intake. Consistent with the isocaloric study design, no change in total energy intake occurred during the study.
During the intervention, the median (IQR) intake of dietary fiber
increased by 71%, to 36 (15) g/d, in the ND group (P < 0.001) at
end point and decreased by 20%, to 16 (6) g/d, in the control
group (P < 0.001). The goal of dietary fiber intake of at least
35 g/d or 4 g/MJ in the ND group was reached at week 12 and
was steady throughout the intervention.
Plasma AR concentrations. No difference in plasma total AR
concentrations was observed between sexes within the groups at
any time. However, at end point, median (IQR) plasma total AR
concentrations increased to 106 (108) nmol/L in the ND group
(P = 0.001) but decreased slightly in the control group, to 61 (40)
nmol/L (P = 0.021) (Table 2). The difference in plasma total AR
concentrations between the two groups was significant at week
12 and at end point (P < 0.001) (Fig. 1A).
Dietary biomarkers of a healthy Nordic diet
1385
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Biochemical measurements and body composition Analyses of
concentrations of plasma glucose, cholesterol, HDL cholesterol, and
TGs were performed in local laboratories as described elsewhere (12).
Fasting LDL cholesterol concentrations were calculated by the Friedewald equation. Blood pressure was measured using automatic blood
pressure devices. Waist circumference was measured midway between
the lowest rib and iliac crest. Body composition was determined by
bioelectrical impedance analysis (Kuopio: STA/BIA Body Composition
Analyzer and Bodygram Software; Akern Bioresearch. Reykjavik: STA/
BIA Body Composition Analyzer, Akern Bioresearch. Lund: Xitron
Hydra 4200, Xitron Technologies. Uppsala: Tanita BC-558 Segmental
Body Composition Monitor. Aarhus: UniQuest-SEAC SFB-3; UniQuest
Oulu: body composition not measured). Staff at each center were trained
to perform the measurements according to the standard operational
procedures agreed on by all centers.
Blood samples used for analysis of plasma AR and b-carotene were
collected at baseline, week 12, and end point. Plasma AR samples were
analyzed at the Department of Food Science, Uppsala BioCenter, Swedish
University of Agricultural Sciences. AR homologs C17:0–C25:0 were
measured in 0.2-mL plasma samples according to a previously published
GC-MS method (45). Quality control samples (n = 4) were included in
each batch to ensure appropriate within- and between-batch precision
(CV < 10–15%). Samples from the same individual were analyzed within
the same batch, and samples from different centers were allocated randomly between batches.
Plasma b-carotene samples were analyzed at Biomedical Nutrition,
Lund University, using a commercial HPLC kit (catalog no. 32000,
Chromsystems). Samples from the same individual were included in the
same batch. The kit consisted of mobile phase, calibrator, control samples, column, internal standard, precipitation reagent, and extraction
buffer. All samples were prepared in a room protected from direct sunlight. The manufacturerÕs manual was followed, and quality controls
were included in each batch (CV = 10%). HPLC analysis was performed
using a Shimadzu liquid chromatograph system equipped with a vacuum
degasser, a solvent delivery module, an autoinjector, a column oven, and
a diode-array detector.
Data pooling and statistical analysis Data from all intervention centers were entered into Microsoft Office Excel 2007 before they were
pooled in a joint centralized database maintained at VTT Technical
Research Centre, Helsinki, Finland. Data were imported to SPSS for
Windows, version 20.0 (SPSS) for statistical analysis. Level of significance in all analyses was set at P < 0.05.
Normality of variables was checked by inspection of histograms and
by using the Kolmogorov-Smirnov one-sample test. Values are reported
as means 6 SDs if normally distributed or as medians and IQRs if not
normally distributed.
Independent sample t test or Mann-Whitney U test was used to compare data between sexes and groups. Paired samples t test or WilcoxonÕs
signed rank test was used to compare values between baseline and week
12 or the end point. One-way ANOVA was used to compare baseline
plasma AR and plasma b-carotene between centers. Spearman rank
correlation coefficient (rs) was used to calculate the correlation between
both plasma AR and b-carotene concentrations and various nutrients
abundant in whole-grain food and vegetables.
As the distributions of plasma AR and b-carotene concentrations
were right skewed, log transformation was performed before further
statistical analysis to better approximate normal distribution. Linear
regression for plasma total AR and plasma b-carotene was used with
group, baseline concentration, sex, age, BMI, and TGs as factors in the
model. Additionally, study center was included in the model for plasma
AR. The residuals from the model were examined for normality.
Reproducibility, a measure of the intraperson stability in dietary intake or biomarker concentration during the intervention, was assessed
by estimating the intraclass correlation coefficient (ICC). ICC is defined
as the intraperson variance divided by the total variance (i.e., the sum of
intra- and interperson variance), and it assumes a common mean between replicate measurements. We calculated ICC using a freely available SAS macro (46) that was imported to SAS 9.2 (SAS Institute). All
ICC estimates are based on log-transformed values.
TABLE 2 Dietary intakes of energy, fiber, and b-carotene and plasma biomarker concentrations
in a healthy Nordic diet group and control group at baseline (week 0), week 12, and end point
(week 18 or 24)1
Week 0
Week 12
Week 18 or 24
Change2
%
8.22 (2.72)
8.31 (2.98)
8.53 (2.05)
8.80 (2.56)
8.19 (2.66)
8.35 (2.60)
0
0
21 (9)
20 (7)
35 (13)3
15 (7)4
36 (15)3,4
16 (6)4
71
220
2.5 (1.2)
2.5 (1.1)
4.1 (1.2)3,4
1.8 (0.7)4
4.1 (1.1)3,4
1.8 (0.8)4
38
227
2.4 (3.0)
1.7 (3.3)
3.1 (4.3)3,4
1.7 (1.6)4
2.9 (3.5)3
1.4 (2.1)4
22
221
73 (87)
70 (70)
91 (88)3
57 (43)4
106 (105)3,4
61 (40)4
45
214
0.36 (0.34)
0.29 (0.34)
0.39 (0.37)4
0.36 (0.27)
0.36 (0.32)
0.33 (0.34)
0
14
1
Values are presented as median (IQR). AR, alkylresorcinols.
Proportional changes between week 0 and week 18 or 24.
3
Different from control at that time (P , 0.05).
4
Different from baseline in that group (P = 0.05).
2
Determinants of plasma AR concentrations. Diet group
allocation (ND group vs. control group; P < 0.001) and plasma
AR concentration at baseline (P < 0.001) were predictors of AR
concentration at end point (with adjusted R2 = 0.38). Serum TG
concentration at end point was also an important factor in the
model, and study center was of borderline significance (P 5 0.09)
(Table 3). Considerable differences were found in the plasma
AR concentrations among all study centers at baseline, and at
the two Finnish centers, Kuopio and Oulu, the participants had
the highest median (IQR) concentrations [108 (72) and 108 (96)
nmol/L, respectively], whereas in Iceland the lowest concentration was observed [43 (37) nmol/L]. The differences among all
centers were explained by differences in whole-grain and/or bran
intake from wheat and rye, which resulted in differences in total
dietary fiber intake (Supplemental Table 3).
Plasma AR concentrations showed moderate to good stability over a period of 6–12 wk, from week 12 to end point [(ICC =
0.44–0.72) Supplemental Table 4]. Positive correlations were
noted between plasma total AR and total fiber intake at all time
points as well as between plasma total AR and intake of vitamin E,
folate, and magnesium (rs = 0.24–0.57) (Supplemental Table 5).
Dietary b-carotene and plasma b-carotene concentration.
b-Carotene intake increased during the intervention and was
higher in the ND than the control group (Table 2). In the ND
group median (IQR) intake of b-carotene was 2.4 (3.0) mg/d
at baseline, increasing to 3.1 (4.3) mg/d (P = 0.008) at week 12
and borderline significantly to 2.9 (3.5) mg/d (P = 0.07) at end
point. In the control group b-carotene intake decreased from 1.7
(3.3) at baseline to 1.7 (1.6) mg/d at week 12 (P = 0.007) and 1.4
(2.1) mg/d at end point (P = 0.019).
1386
Magnusdottir et al.
The median (IQR) plasma b-carotene concentration did not
change significantly throughout the study either in the ND group
or in the control group [0.36 (0.32) mmol/L and 0.33 (0.34)
mmol/L, respectively, at endpoint] (Fig. 1B). Dividing b-carotene
values by LDL cholesterol, TGs, total cholesterol and TGs, or
body fat mass did not change the results.
Determinants of plasma b-carotene concentrations. The
ND group was not a significant predictor of plasma b-carotene
concentration at end point, but baseline b-carotene concentration and BMI were significant predictors (with adjusted R2 = 0.63).
The length of the intervention (18 or 24 wk) was of borderline
significance (P = 0.054) in the model (Table 3). Plasma b-carotene
concentrations showed good stability over the period of 12 wk
(ICC = 0.83–0.88) (Supplemental Table 4).
A positive correlation was found between plasma b-carotene
and fiber intake at baseline (P = 0.005), but it was borderline
significant at week 12 (P = 0.054) and end point (P = 0.110)
(Supplemental Table 5). Positive correlations were found between
plasma b-carotene and b-carotene as calculated from food records at all time-points, with correlation coefficients in the range
rs = 0.28–0.39. Additionally, there were significant correlations
of plasma b-carotene to vitamin C intake at baseline (P = 0.011)
and to the intake of vitamin C and folate at end point (P = 0.005
and P = 0.039, respectively).
Discussion
One of the most prominent changes in nutrient composition
during the SYSDIET intervention was increased fiber intake in
the ND group, whereas slightly decreased fiber intake was seen
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Dietary intake (n = 154)
Energy, MJ/d
Nordic diet
Control diet
Fiber intake, g/d
Nordic diet
Control diet
Fiber intake, g/MJ
Nordic diet
Control diet
b-Carotene, mg/d
Nordic diet
Control diet
Plasma biomarker concentrations (n = 149)
Total AR, nmol/L
Nordic diet
Control diet
b-Carotene, mmol/L
Nordic diet
Control diet
in the control group. Both groups reached the predetermined
goals (35 g/d or 4.0 g/MJ in the ND group and 15–20 g/d in the
control group) by week 12. The change in fiber intake was
reflected in increased plasma AR concentrations in the ND group,
showing that cereal fiber from wheat and rye substantially contributed to the increased fiber intake. Our findings suggest that
plasma total AR concentration is a good biomarker for wholegrain wheat and rye, the main contributing foods in the ND. In
addition, previous data suggested that AR meets most of the
criteria of a good biomarker for intake of whole-grain wheat and
rye foods and cereals, particularly at frequent consumption and
wide range of intake (15,22,23). Plasma AR is responsive to
whole-grain wheat and rye intake, and the long-term reproducibility is moderate (24–26,47). In the present study there was a
great difference in AR concentration between the two groups,
with an increase in the ND group and a decrease in the control
group. Blood lipids were expected to correlate with AR concentration because plasma AR is transported in lipoproteins (15,27).
The finding that serum TGs were a significant predictor for AR
concentration suggests that factors that result in transient increases in plasma TG concentration may also be important for
the repeatability of plasma AR measurements (48).
Unlike in previous findings, we found that the plasma AR
concentration was not significantly different between sexes at
any time, and sex was not a significant covariate in the
regression model. In several studies men had higher plasma
AR concentration than women (15,24,47,49), which has been
attributed to higher intake of foods containing AR by men
compared with women and a more rapid elimination of AR in
TABLE 3 Regression coefficients for factors affecting plasma
total alkylresorcinols and plasma b-carotene at end point (week 18
or 24)1
B (95% CI)
P
2
Model 1 log, ARs (n = 154)
ND vs. control group
Baseline plasma log
Sex (F/M)
Age (y)
BMI (kg/m2)
TGs (mmol/L)
Study center
Model 2 log, b-carotene (n = 166)3
ND vs. control group
Baseline plasma log
Sex (F/M)
Age (y)
BMI (kg/m2)
TGs (mmol/L)
0.234 (0.157, 0.311)
0.354 (0.212, 0.496)
0.026 (20.055, 0.106)
0.003 (20.001, 0.008)
0.002 (20.009, 0.014)
0.110 (0.042, 0.177)
20.019 (20.041, 0.003)
,0.001
,0.001
0.53
0.17
0.70
0.002
0.09
20.002 (20.057, 0.053)
0.746 (0.645, 0.847)
0.048 (20.012, 0.109)
0.001 (20.002, 0.005)
20.010 (20.019, 20.002)
20.024 (20.071, 0.023)
0.95
,0.001
0.12
0.39
0.017
0.32
1
Log-transformed values. B reflects the change in the log-transformed outcome
variable for each 1-unit changes in the independent variable. AR, alkylresorcinols; ND,
Nordic diet.
2
Adjusted r2 = 0.38.
3
Adjusted r2 = 0.63.
Dietary biomarkers of a healthy Nordic diet
1387
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FIGURE 1 Plasma concentrations for participants in healthy Nordic
diet (ND) and control (C) groups at baseline, 12 wk, and 18 or 24 wk
(end point). Values are medians, and bars represent the IQR (A)
Plasma total alkylresorcinols concentration (ND group, n = 94; control
group, n = 65). *Different from C at that time, P , 0.05. (B) Plasma
b-carotene concentration (ND group, n = 96; control group, n = 70).
women. In general, women have a larger distribution volume
because of their higher body fat content, which may result in
lower plasma AR concentration. In the present study, women
had a higher body fat percentage as well, suggesting that
factors other than variations in body fat may have caused the
lack of a sex difference in AR concentration.
A marked difference existed in baseline values for plasma AR
concentration among study centers. Rye consumption is widespread in Finland and more common than in other Nordic countries (50). Hence, the increase in plasma AR concentration in
Finnish participants during the intervention was not as sharp as
in participants from other centers. Instead, Finnish participants
in the control group had a greater decrease in AR concentration.
Similarly, for the other centers, AR concentration greatly increased in the ND group and decreased in the control group but
not as sharply as in the Finnish participants.
The reliability of plasma measurements of AR at week 12 and
end point was moderate to good, with the ICC being similar or
higher than in previous studies (24,26,51). Higher reliability was
observed in the ND group than the control group. Strictly defined, AR should be regarded as a short-term biomarker, but
under stable and frequent intake conditions, it also reflects longterm exposure fairly well (52). The half-life of AR is relatively
short (5 h), and the absorption half-life is about 6–8 h (53).
Absorption and elimination counteract each other when whole
grains are consumed regularly, with resulting stable plasma concentrations. Because cereals and bread were consumed on a daily
basis in the present study, plasma AR concentrations would be
stable and appropriately reflect intake during the intervention
period. Note, however, that the use of plasma AR as a biomarker
of whole-grain intake is not practical in populations who primarily consume other types of whole grains such as oats or brown
rice, because these cereals do not contain AR.
No significant difference in plasma b-carotene concentration
was found between the ND and the control group. The baseline
concentration of plasma b-carotene corroborates with data obtained in nonvegetarians in similar groups (54). The reproducibility
1388
Magnusdottir et al.
are important contributors to fiber intake and concomitantly
AR intake. Despite a significant correlation between plasma
b-carotene and b-carotene intake at baseline, the ND did not
cause a significant change, suggesting plasma b-carotene may not
be a sensitive enough biomarker of the foods in the ND under the
given time frame. Taken together, these findings show that parallel
assessment of dietary biomarkers and dietary intakes is useful
and may facilitate accurate interpretation of dietary intervention
studies.
Acknowledgments
We thank Ms. M. Debiec for help with the analysis of b-carotene
in plasma and Cindy Mari Imai for proofreading the manuscript. M.U., K.P., M.J.S., I.T., B.Å., U.R., and K.H. designed
the research. U.S., M.K., L.C., G.Ö., L.B., I.G., O.K.M., S.E.J.,
and F.R. conducted the research. R.L., B.Å., and L.C. provided
essential materials. O.K.M. and R.L. performed statistical analysis, and O.K.M. wrote the paper. All authors have read and
approved the final manuscript.
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shown that the bioavailability of b-carotene from highly processed food is higher than that from raw material (58,59). Total
fat and protein intake was similar in the two groups, but dietary
fiber intake was much higher in the ND group than in the control
group. Controlled intervention studies have shown that the presence of dietary fiber in vegetables and fruits (i.e., dietary pectin)
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Paper II
European Journal of Clinical Nutrition (2014), 1–6
& 2014 Macmillan Publishers Limited All rights reserved 0954-3007/14
www.nature.com/ejcn
ORIGINAL ARTICLE
Plasma alkylresorcinols C17:0/C21:0 ratio, a biomarker
of relative whole-grain rye intake, is associated to insulin
sensitivity: a randomized study
OK Magnusdottir1,2, R Landberg3,4, I Gunnarsdottir1,2, L Cloetens5, B Åkesson5,6, M Landin-Olsson7, F Rosqvist8, D Iggman8,9,
U Schwab10,11, K-H Herzig12,13, MJ Savolainen14,15, L Brader16, K Hermansen16, M Kolehmainen10,17, K Poutanen10,17,
M Uusitupa10,18, I Thorsdottir1,2 and U Risérus8
BACKGROUND/OBJECTIVES: Few studies have used biomarkers of whole-grain intake to study its relation to glucose metabolism.
We aimed to investigate the association between plasma alkylresorcinols (AR), a biomarker of whole-grain rye and wheat intake,
and glucose metabolism in individuals with metabolic syndrome (MetS).
SUBJECTS/METHODS: Participants were 30–65 years of age, with body mass index 27–40 kg/m2 and had MetS without diabetes.
Individuals were recruited through six centers in the Nordic countries and randomized to a healthy Nordic diet (ND, n ¼ 96), rich in
whole-grain rye and wheat, or a control diet (n ¼ 70), for 18–24 weeks. In addition, associations between total plasma AR
concentration and C17:0/C21:0 homolog ratio as an indication of the relative whole-grain rye intake, and glucose metabolism
measures from oral glucose tolerance tests were investigated in pooled (ND þ control) regression analyses at 18/24 weeks.
RESULTS: ND did not improve glucose metabolism compared with control diet, but the AR C17:0/C21:0 ratio was inversely
associated with fasting insulin concentrations (P ¼ 0.002) and positively associated with the insulin sensitivity indices Matsuda ISI
(P ¼ 0.026) and disposition index (P ¼ 0.022) in pooled analyses at 18/24 weeks, even after adjustment for confounders. The AR
C17:0/C21:0 ratio was not significantly associated with insulin secretion indices. Total plasma AR concentration was not related to
fasting plasma glucose or fasting insulin at 18/24 weeks.
CONCLUSIONS: The AR C17:0/C21:0 ratio, an indicator of relative whole-grain rye intake, is associated with increased insulin
sensitivity in a population with MetS.
European Journal of Clinical Nutrition advance online publication, 19 February 2014; doi:10.1038/ejcn.2014.12
Keywords: alkylresorcinols; insulin sensitivity; whole grain; rye
INTRODUCTION
Whole-grain and cereal fiber consumption has been inversely
associated with the risk of type 2 diabetes and insulin sensitivity in
observational studies,1–5 but findings have been inconsistent in
intervention studies.6–11 A possible reason for the inconclusive
results seen in intervention studies may be inadequate dietary
compliance. Nutritional science relies on accurate dietary
information to assess compliance to dietary interventions and to
investigate diet–disease associations. However, most dietary
assessment instruments rely to some extent on self-reporting,
which is prone to measurement errors.12,13 The use of dietary
biomarkers could be one way to improve the validity of dietary
assessment in combination with, or as an alternative for, selfreports or as a tool for secondary analysis, where noncompliant
individuals can be excluded on the basis of the biomarker
measurements.
Alkylresorcinols (AR) have been proposed as biomarkers for
whole-grain and bran intake of wheat and rye14–16 and for cereal
fiber intake in populations with a high intake of whole-grain
wheat and rye.17 AR are almost exclusively present in the outer
parts of wheat and rye grains and not in refined white flour.18,19
Controlled whole-grain and bran intervention studies show
that plasma AR concentration increases proportionally with AR
and whole-grain intake16,20–24 and can be used as a biomarker
of compliance to a whole-grain diet.15,25 Previously, we have
demonstrated that AR are useful biomarkers for whole-grain
wheat and rye intake as part of a healthy Nordic diet (ND).26 Total
plasma AR have been associated with lower body mass index
1
Unit for Nutrition Research, Landspitali-The National University Hospital of Iceland, Reykjavı́k, Iceland; 2Faculty of Food Science and Nutrition and School of Health Sciences,
University of Iceland, Reykjavı́k, Iceland; 3Department of Food Science, BioCenter, Swedish University of Agricultural Sciences, Uppsala, Sweden; 4Division of Nutritional
Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden; 5Biomedical Nutrition, Pure and Applied Biochemistry, Lund University, Lund,
Sweden; 6Department of Clinical Nutrition, Skåne University Hospital, Lund, Sweden; 7Department of Endocrinology, Skåne University Hospital, Lund, Sweden; 8Department of
Public Health and Caring Sciences, Clinical Nutrition and Metabolism, Uppsala University, Uppsala, Sweden; 9Center for Clinical Research Dalarna, Falun, Sweden; 10Institute of
Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland; 11Institute of Clinical Medicine, Internal Medicine, Kuopio University Hospital, Kuopio, Finland;
12
Department of Physiology and Biocenter of Oulu, Institute of Biomedicine, Oulu University, Oulu, Finland; 13Department of Psychiatry, Kuopio University Hospital, Kuopio,
Finland; 14Department of Internal Medicine and Biocenter Oulu, Institute of Clinical Medicine, University of Oulu, Oulu, Finland; 15Clinical Research Center, Oulu University
Hospital, Oulu, Finland; 16Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark; 17VTT, Technical Research Centre of Finland, Espoo
and Kuopio, Kuopio, Finland and 18Research Unit, Kuopio University Hospital, Kuopio, Finland. Correspondence: OK Magnusdottir, Unit for Nutrition Research, Landspitali-The
National University Hospital of Iceland, Reykjavik IS-101, Iceland.
E-mail: [email protected]
Received 4 October 2013; revised 6 December 2013; accepted 4 January 2014
Alkylresorcinols ratio and insulin sensitivity
OK Magnusdottir et al
2
(BMI) in older adults, but no associations between AR and glucose
metabolism were found.27
The ratio of the AR homologs C17:0 and C21:0 differs between
cereal species and can be used to differentiate between the
whole-grain sources in food products.19 The ratio of C17:0/C21:0 is
typically 0.1 in common wheat and 1.0 in rye, and the relative
intake of whole-grain rye and wheat is to some extent reflected by
this ratio in plasma samples.23
In the present study the aim was to investigate the association
between plasma AR, as a biomarker for whole-grain wheat and rye
intake, and glucose metabolism in a population with features
of metabolic syndrome participating in a randomized dietary
intervention.28 Furthermore, the associations between the AR
C17:0/C21:0 ratio, as a marker of relative whole-grain bran/rye
intake, and glucose and insulin parameters were analyzed.
the participants, that is at 1–2 weeks intervals, and the subjects also
returned 4-day food records at baseline, week 12 and 18/24 weeks.
Biochemical measurements
Automated clinical chemistry analyzers and routine clinical chemistry
methods were used to measure cholesterol, triglycerides and high-density
lipoprotein cholesterol. The equipment and system reagents were from
Siemens Healthcare Diagnostics (Tarrytown, NY, USA), Thermo Fisher
Scientific (Vantaa, Finland), Roche Diagnostics GmbH (Mannheim,
Germany) (in two laboratories), Toshiba (Tochigi, Japan), Abbott Laboratories
(Irving, TX, USA), Ortho-Clinical Diagnostics and Johnson & Johnson (New
Brunswick, NJ, USA).28 Low-density lipoprotein cholesterol concentrations
were calculated using Friedewald’s formula (low-density lipoprotein ¼ total
cholesterol high-density lipoprotein cholesterol (triglycerides/5)).
Two-hour oral glucose tolerance test
MATERIALS AND METHODS
The current study is part of the SYSDIET study, a randomized controlled
multicenter parallel group study with balanced randomization (1:1)
performed in six intervention centers (Kuopio and Oulu, Finland; Lund
and Uppsala, Sweden; Aarhus, Denmark and Reykjavik, Iceland) examining
the health effects of a ND in a population with metabolic syndrome. All
local ethical committees approved the SYSDIET study protocol which
followed the Helsinki declaration guidelines. Informed written consent
was obtained from all participants. The study design, inclusion and
exclusion criteria, study diets, the main measurements and analyses
performed at each time point and main results have been previously
reported in detail.28
A 2-h oral glucose tolerance test was performed at baseline, week 12 and
at 18/24 weeks. The subjects were instructed to fast for 12 h before the oral
glucose tolerance test. Fasting samples for plasma glucose, plasma insulin
and triglycerides were collected at time point 0, before the glucose
solution was ingested. The subjects were asked to drink 75 g of D( þ )
-glucose anhydrous Ph.Eur and 1.6 g of citric acid dissolved in 300 ml water
in o3 min. Blood samples for glucose and insulin analyses were collected
30 and 120 min after the glucose load. Analyses of plasma glucose were
performed in local laboratories using standard operational procedures.
Plasma insulin was analyzed at Aarhus University Hospital using the ELISA
method from Dako Denmark A/S, Glostrup, Denmark, with a within-run
and between-run CVo8% and o10%, respectively.
Analysis of AR
Study participants
Participants in the study were primarily recruited through advertisement in
newspapers, but also from previous clinical or epidemiological trials. In
brief, the inclusion criteria were age 30–65 years, BMI 27–40 kg/m2 and two
diagnostic criteria for metabolic syndrome outlined by the International
Diabetes Federation,29 except type 2 diabetes.
Study design
Before randomization into the ND group and the control group,
participants had a 1-month run-in period, during which all the participants
followed their habitual diet. Owing to financial and logistic reasons, the
study period was 18 weeks at four centers (Aarhus, Uppsala, Reykjavik and
Oulu) and 24 weeks at two centers (Lund and Kuopio), where the
intervention was initiated earlier.28 The major visits to the study clinics
were on week 0 (baseline), week 12 and 18/24 weeks.
The randomization was done by staff in each study center as described
elsewhere.28 The staff in all study centers was trained to perform
measurements in a similar way and the quality management protocol
was available for all of the staff members. The allowed weight change
during the study was aimed to be o±4 kg.
Study diets
The study diets were isocaloric. Nordic nutrition recommendations formed
the basis of the diet in the ND group and the mean nutrient intake in the
Nordic countries formed the basis for the control diet. Participants in the
ND group were, among other things, advised to consume X25% of total
energy as whole grain, of which X50% was comprised of rye, barley and
oat that included X6 slices/day of bread with X6 g fiber/100 g (one
slice ¼ 30–40 g of bread). Participants in the control group were asked to
consume X25% of energy as refined grain, of which X90% was made
from wheat.
Key products were provided to the study participants in both groups.
The individuals in the ND group received whole-grain products such as
oats and barley, crisp breads, whole-grain wheat and rye breads. The
individuals in the control group received low-fiber cereal products, for
example breads with fiber content o6 g/100 g and ordinary pasta.
The participants met a clinical nutritionist or a dietitian at all
study visits. The study participants kept dietary records regarding the
intake of cereal products. These records were checked at each visit to
the study center, including the visits when the groceries were delivered to
European Journal of Clinical Nutrition (2014) 1 – 6
Blood samples analyzed for AR were collected at baseline, week 12 and
18/24. Determination of AR in plasma samples were made in collaboration
with the HELGA-Centre at Department of Food Science, BioCenter at
Swedish University of Agricultural Sciences. A gas chromatography mass
spectrometry method was used to quantify AR homologs C17:0–C25:0 in
0.2 ml plasma samples, as described previously.30 Quality control samples
(n ¼ 4) were included in each batch to ensure appropriate within- and
between-batch precision (CVo15%). Samples from each subject were
analyzed within the same batch, and samples from different centers were
allocated randomly between batches.
Data pooling and statistical analysis
All intervention centers entered their data into the Microsoft Office Excel
2007 (Windows) data form before pooling the data in a joint database
maintained at VTT Technical Research Centre of Finland. Data was
exported from the database and imported to SPSS (Statistical Package
for the Social Sciences) for Windows, version 20.0 (SPSS Inc., Chicago, IL,
USA) for statistical analysis. Level of significance in all analyses was set at
Po0.05.
Normality of variables was checked by inspection and by using the
Kolmogorov–Smirnov test. Values are described as means and s.d. if
normally distributed or as medians and interquartile range if not normally
distributed. Independent sample t-tests or Mann–Whitney’s U-test were
used to compare data between groups. When comparing values at
baseline to week 18/24 values, paired samples t-test or the Wilcoxon
signed-rank test was used.
From data of the oral glucose tolerance test insulinogenic index (IGI), the
ratio of the 30-min areas under the curve for insulin and glucose (InsAUC030/GluAUC0-30) and Stumvoll was calculated for evaluation of early-phase
insulin secretion (IGI ¼ (insulin 30 min insulin 0 min)/(glucose 30 min
glucose 0 min) and Stumvoll ¼ 1283 þ 1.829 insulin 30 min (pmol/l)
138.7 glucose 30 min (mmol/l) þ 3.772 insulin 0 min (pmol/l)). IGI at
120 min (IGI 120) was calculated for late-phase insulin secretion (IGI
120 ¼ (insulin 120 min insulin 0 min)/(glucose 120 min glucose 0 min)).
Matsuda insulin sensitivity index (ISI) and disposition index (DI) were
calculated for evaluation of insulin sensitivity (Matsuda ISI ¼ (10 000/
O((glucose 0 min insulin 0 min) (arithmetic mean of glucose at 0, 30
and 120 min arithmetic mean of insulin at 0, 30 and 120 min)))31 and
DI ¼ Matsuda ISI IGI).
Secondary analyses were performed with data from the ND and control
groups combined and associations between total AR and the AR
C17:0/C21:0 ratio at 18/24 weeks, and various glucose and insulin
& 2014 Macmillan Publishers Limited
Alkylresorcinols ratio and insulin sensitivity
OK Magnusdottir et al
3
outcomes were analyzed. As the distributions were skewed, logtransformation was performed on dependent variables for linear regression to better approximate normal distribution. Linear regressions for
fasting plasma glucose, insulin, Matsuda, DI and IGI was calculated, with AR
C17:0/C21:0 ratio, baseline value for the dependent variable, age, gender,
BMI and smoking as factors in model 1. As rye often contains more AR
compared with wheat, total plasma AR was added as a variable to model 2,
in addition to the variables in model 1, to prevent confounding of high AR
content. Spearman’s r was calculated to estimate the correlation between
AR C17:0/C21:0 ratio and total plasma AR.
RESULTS
In total, 201 individuals started the intervention; 104 in the ND
group and 97 in the control group. Individuals completing the trial
were 96 in the ND group (92%) and 70 in the control group (72%).
There was no difference in basic baseline characteristics between
dropouts and those who completed the study (data not shown).
Blood samples for AR analysis at week 0 and week 18/24 were
obtained from 158 participants.
Consistent with the isocaloric study design there was no change
in total energy intake during the study and energy intake was not
different between the groups. Hence, body weight remained
constant during the intervention in both groups. The mean age of
the participants was 54.5±8.2 years, body weight 91.2±13.5 kg,
BMI 31.7±3.2 kg/m2 and waist circumference 104.3±9.7 cm.
Sixty-three percent of the participants were classified as obese
(BMIX30 kg/m2) and 37% as overweight (BMI 25–29.99 kg/m2) at
baseline. Ninety-eight individuals (59%) had fasting plasma
glucose X5.6 mmol/l at baseline and 161 (97%) had metabolic
syndrome. There were no differences in baseline characteristics
between the ND and control groups.28
Both total plasma AR concentration and the ratio of C17:0/C21:0
were significantly higher in the ND group compared with the
control group at 18/24 weeks (Table 1). Fasting plasma glucose
was 5.7±0.9 mmol/l in both groups at baseline and did not
change significantly during the intervention period. There were no
significant differences between the ND group and control group
in concentrations of fasting glucose, 2 h glucose (results described
elsewhere28), fasting insulin, 2 h insulin, other calculated glucose
metabolism parameters or the changes in these values during the
intervention (Table 1).
All participants (both ND and control groups) were combined
for secondary analyses on the associations between AR and
glucose metabolism. Total plasma AR concentration at 18/24
weeks was not significantly correlated with concentrations of
fasting plasma glucose (P ¼ 0.51) or insulin (P ¼ 0.57) when
adjusted for baseline value of the dependent variable, age,
gender, BMI and smoking. Combining the data from both weeks
12 and 18/24 did not change the results. Interestingly, the AR ratio
C17:0/C21:0, reflecting the proportion of whole-grain rye to wholegrain rye þ whole-grain wheat, was inversely associated with
fasting insulin concentrations when adjusted for baseline value of
insulin, age, gender, BMI and smoking (model 1, P ¼ 0.016) and
also when total plasma AR was added to the regression model
(model 2, P ¼ 0.011) (Table 2). Total plasma AR and the AR
C17:0/C21:0 ratio was weakly correlated (r ¼ 0.20, P ¼ 0.012). The
AR C17:0/C21:0 ratio was also positively associated with the insulin
sensitivity indices Matsuda ISI (P ¼ 0.005 and P ¼ 0.004 for model 1
and 2, respectively) and DI (P ¼ 0.022 and P ¼ 0.023 for model 1
and 2, respectively) (Table 2). The AR C17:0/C21:0 ratio was,
however, not associated with fasting plasma glucose (P ¼ 0.12 and
P ¼ 0.11 for model 1 and 2, respectively), or the indices for early
and late insulin secretion, that is, IGI (P ¼ 0.54 and P ¼ 0.59 for
model 1 and 2, respectively), InsAUC0-30/GluAUC0-30 (P ¼ 0.65
and P ¼ 0.54 for model 1 and 2, respectively), Stumvoll or IGI 120
(P ¼ 0.93 and P ¼ 0.99 for model 1 and 2, respectively) and IGI 120
(P ¼ 0.11 and P ¼ 0.12 for model 1 and 2, respectively).
DISCUSSION
In the present study, consuming a ND rich in whole-grain
cereals for either 18 or 24 weeks did not improve glucose
metabolism compared with a control diet. When values from both
groups were pooled, no association between total plasma
AR concentration and glucose metabolism parameters were
observed.
There are conflicting findings from previous intervention
studies evaluating the effects of whole-grain intake on glucose
and insulin concentrations and calculated parameters of insulin
sensitivity8,11,27,32 presumably owing to differences in the type,
amount, structure and preparation of whole-grain products
consumed33 and different methodologies used for glucose and
insulin analyses.7 Poor compliance could also contribute to these
diverse findings, although good adherence has been indicated in
most studies using weighed food records. In a whole-grain
intervention study by Kristensen et al.9 the effects on body
composition were clearer after excluding noncompliant subjects
based on AR concentration, although food records indicated good
compliance. Hence, without an objective measurement of
Table 1. Total plasma alkylresorcinol (AR) concentration, AR C17:0/C21:0 ratio and insulin variables for the healthy Nordic diet group (ND) and
control group at baseline and after the 18/24-week intervention
Healthy ND
Week 0
a,b
Total plasma AR , nmol/l
C17:0/C21:0 ratioa,b
Fasting insulin, pmol/l
Insulin 2 h, pmol/l
Matsuda ISI
DI
IGI
InsAUC0-30/GluAUC0-30
Stumvoll
IGI 120
73
0.3
51
210
5.8
392
68
21.6
733
116
(88)
(0.2)
(33)
(180)
(4.0)
(432)
(58)
(13.3)
(441)
(394)
Control
Week 18/24
106
0.3
52
251
5.7
411
69
24.0
818
100
c
(108)
(0.2)
(42)
(225)
(4.9)
(427)
(64)
(15.2)
(398)
(255)
Week 0
Week 18/24
71 (70)
0.3 (0.2)
58 (38)
218±255
4.9 (3.8)
400 (461)
87 (85)
24.0 (18.9)
828 (526)
104 (311)
61 (40)c,d
0.2 (0.2)d
61 (43)
236±237
4.7 (3.6)
377 (501)
83 (89)
26.0 (15.1)
850 (567)
120 (276)
Abbreviations: AR, alkylresorcinols; DI, disposition index; IGI, insulinogenic index; InsAUC0-30/GluAUC0-30, the ratio of the 30-min areas under the curve for
insulin and glucose; IGI 120, insulinogenic index at 120 min. Data are presented as medians (interquartile range), n ¼ 166, ND group n ¼ 96 and control group
n ¼ 70. aData on total plasma AR has been published previously.31 bn ¼ 158, ND group n ¼ 93 and control group n ¼ 65. cSignificantly different from week 0 in
that group, Po0.05. dSignificantly different from the ND group at that time point, Po0.05.
& 2014 Macmillan Publishers Limited
European Journal of Clinical Nutrition (2014) 1 – 6
Alkylresorcinols ratio and insulin sensitivity
OK Magnusdottir et al
4
Table 2.
Regression models for fasting plasma glucose, insulin, insulin
sensitivity indices and indices of insulin secretion (log-transformed
values)
Dependent
variable at
18/24 weeks
Fasting glucose
Model 1
Model 2
Ba (95% CI)
Independent
variable at 18/24
weeks
AR C17:0/C21:0
AR C17:0/C21:0
Total AR
0.049 ( 0.111 to 0.014)
0.051 ( 0.113 to 0.012)
0.000 (0.000 to 0.000)
AR C17:0/C21:0
AR C17:0/C21:0
Total AR
0.425 ( 0.769 to 0.082)
0.445 ( 0.788 to 0.102)
0.0001 (0.000 to 0.001)
AR C17:0/C21:0
AR C17:0/C21:0
Total AR
0.234 (0.071 to 0.396)
0.240 (0.077 to 0.404)
0.000 ( 0.001 to 0.000)
AR C17:0/C21:0
AR C17:0/C21:0
Total AR
0.768 (0.111 to 1.426)
0.773 (0.107 to 1.433)
0.000 ( 0.002 to 0.001)
AR C17:0/C21:0
AR C17:0/C21:0
Total AR
0.072 ( 0.161 to 0.305)
0.065 ( 0.170 to 0.299)
0.000 (0.000 to 0.001)
InsAUC-30/GluAUC-30
Model 1
AR C17:0/C21:0
Model 2
AR C17:0/C21:0
Total AR
0.030 ( 0.162 to 0.101)
0.041 ( 0.172 to 0.090)
0.000 (0.000 to 0.001)
Fasting insulin
Model 1
Model 2
Matsuda
Model 1
Model 2
DI
Model 1
Model 2
IGI 0 min
Model 1
Model 2
Stumvoll
Model 1
Model 2
Log IGI 120 min
Model 1
Model 2
AR C17:0/C21:0
AR C17:0/C21:0
Total AR
0.007 ( 0.147 to 0.161)
0.001 ( 0.155 to 0.154)
0.000 (0.000 to 0.001)
AR C17:0/C21:0
AR C17:0/C21:0
Total AR
0.309 ( 0.683 to 0.066)
0.301 ( 0.680 to 0.079)
0.000 ( 0.001 to 0.001)
Abbreviations: AR, alkylresorcinols; CI, confidence interval; DI, disposition
index; IGI, insulinogenic index; InsAUC0-30/GluAUC0-30, the ratio of the
30 min areas under the curve for insulin and glucose; IGI 120, insulinogenic
index at 120 min. Model 1: adjusted for baseline value of the dependent
variable, age, gender, BMI and smoking. Model 2: adjusted for baseline
value of the dependent variable, age, gender, BMI and smoking. aB reflects
the change in the log-transformed outcome variable for each 1-unit
change in the independent variable.
compliance, such as biomarkers, it is difficult to rule out the
possibility of low adherence to the intervention diet.
The most interesting results of the present study are the inverse
associations between the AR C17:0/C21:0 ratio and fasting plasma
insulin concentration and insulin sensitivity indices, Matsuda ISI
and DI, that is, the higher the ratio the better was the insulin
sensitivity. Matsuda ISI is the most commonly used index to
illustrate peripheral insulin sensitivity, of mostly peripheral muscle
tissue insulin sensitivity.34 We also found an association between
DI and AR C17:0/C21:0, which suggests that AR may also have a
role with improvement of beta-cell function when the respective
insulin sensitivity has been taken into account, as DI reflects
insulin secretion but takes into account the insulin sensitivity
effect.34
European Journal of Clinical Nutrition (2014) 1 – 6
Although the ratio of C17:0/C21:0 is B1.0 in rye, the ratio is
somewhat lower in plasma samples, typically around 0.6–0.8 in
fasting samples after a whole-grain rye intervention for 1–8
weeks.21,23 In populations where rye is not commonly consumed
the ratios are generally lower and a ratio above 0.15 is usually
indicative of some rye intake.35 The ratio in free-living Swedish
population, where rye consumption is appreciable, is 0.5.36 The
reason for lower ratio in plasma compared with what is observed
in whole-grain bran/rye foods is likely due to faster metabolism of
the AR homolog C17:0,37,38 but further insight into absorption and
metabolism of the different homologs is needed to explain to
what extent factors other than whole-grain rye and wheat affect
the C17:0/C21:0 ratio.35
The inverse association between C17:0/C21:0 and fasting insulin
and insulin sensitivity indices observed in the present study is in
line with previous findings showing positive effects of higher rye
consumption on fasting plasma insulin and to a less extent on
fasting plasma glucose8 supporting the use of the ratio of the
homologs C17:0 and C21:0 as an indicator of whole-grain/bran rye
intake. It is, however, important to note that the AR C17:0/C21:0
ratio reflects only the relative whole-grain/bran rye consumption
of total whole-grain wheat and rye intake, not total rye intake. In
the present study the advised whole-grain rye intake was high in
relation to other sources of AR and therefore the ratio should
reflect the total rye intake reasonably well. Rye was mostly
consumed in the form of bread.
Several intervention studies have shown diminished levels of
postprandial insulin following a rye bread meal,39–41 possibly
explained by structural differences between rye and whole-wheat
breads.41,42 The lower postprandial insulin response after rye
bread consumption as compared with wheat bread may be due to
the difference in structure rather than fiber content in the whole
grain, as low-fiber rye bread showed the same results as high-fiber
rye bread consumption.43,44 Moreover, an improved early insulin
response has been shown after rye bread interventions.43,44 In the
present study, there was, however, no significant association
between the AR C17:0/C21:0 ratio and early or later insulin
secretion phase as measured by insulin secretion indices.
One of the strengths of the present study is that AR is used as a
dietary biomarker for whole-grain rye and wheat intake instead of
self-reported estimates. Previously, we have demonstrated that AR
is a good biomarker for the ND under intervention conditions with
moderate-to-good reliability.26 Also, reliable and comparable
methods were used in six centers in four Nordic countries and
the same study protocol was followed in all centers. However, it is
important to note that AR is only a biomarker for whole-grain rye
and wheat consumption, and therefore other markers are
warranted in order to monitor whole-grain intake from other
cereal sources.
CONCLUSION
The results support the use of the ratio of the homologs C17:0 and
C21:0 as an indicator of rye intake in intervention studies where a
diet rich in whole-grain rye is being investigated and also suggests
that increased proportion of whole-grain rye in the diet may be
associated with lower fasting insulin concentrations and increased
insulin sensitivity.
CONFLICT OF INTEREST
The authors declare no conflict of interest.
ACKNOWLEDGEMENTS
We express sincere gratitude to the participants taking part in the study. We also
thank Vanessa de Mello Laaksonen and Maria Lankinen for help with calculations and
all staff involved in the intervention. The study was supported by NordForsk NCoE in
& 2014 Macmillan Publishers Limited
Alkylresorcinols ratio and insulin sensitivity
OK Magnusdottir et al
5
Food Nutrition and Health: Project 070014 SYSDIET (Systems biology in controlled
dietary interventions and cohort studies). This study was also funded by the Academy
of Finland, Finnish Diabetes Research Foundation, Finnish Foundation for Cardiovascular Research, The Sigrid Juselius Foundation and EVO funding from Kuopio
University Hospital (Finland); the Druvan Foundation, ESPEN, Skåne County Council
Research and Development Foundation, Swedish Research Council for Health,
EXODIAB (Excellence of Diabetes Research in Sweden), The Heart-Lung Foundation,
Diabetesfonden and Foundation Cerealia (Sweden); The Danish Obesity Research
Centre (DanORC, www.danorc.dk), The Danish Council for Strategic Research
(DairyHealth, BioFunCarb) (Denmark), The Agricultural Productivity Fund (Iceland)
and the Icelandic Research Fund for graduate students (1206880061).
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28 Uusitupa M, Hermansen K, Savolainen MJ, Schwab U, Kolehmainen M, Brader L et al.
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37 Landberg R, Linko AM, Kamal-Eldin A, Vessby B, Adlercreutz H, Aman P. Human
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& 2014 Macmillan Publishers Limited
Paper III
Title: Whole grain rye intake, reflected by a biomarker, is associated with favorable blood lipid
outcomes in subjects with the metabolic syndrome – a randomized study
Authors: Ola Kally Magnusdottir1, Rikard Landberg2,3, Ingibjorg Gunnarsdottir1, Lieselotte
Cloetens4, Björn Åkesson4,5, Fredrik Rosqvist6, Ursula Schwab7,8, Karl-Heinz Herzig9, Janne
Hukkanen10, Markku J Savolainen10, Lea Brader11, Kjeld Hermansen11, Marjukka
Kolehmainen7,12, Kaisa Poutanen7,12, Matti Uusitupa7,13, Ulf Risérus6, Inga Thorsdottir1
1
Unit for Nutrition Research, Landspitali -The National University Hospital of Iceland and
Faculty of Food Science and Nutrition, School of Health Sciences, University of Iceland,
Reykjavík, Iceland
2
Department of Food Science, BioCenter, Swedish University of Agricultural Sciences, Uppsala,
Sweden
3
Division of Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska
Institutet, Stockholm, Sweden
4
Biomedical Nutrition, Pure and Applied Biochemistry, Lund University, Lund, Sweden
5
Department of Clinical Nutrition, Skåne University Hospital, Lund, Sweden
6
Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism, Uppsala
University, Uppsala, Sweden
7
Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland
8
Institute of Clinical Medicine, Internal Medicine, Kuopio University Hospital, Kuopio, Finland
9
Institute of Biomedicine, Department of Physiology and Biocenter, Oulu University, Oulu,
Finland and Department of Psychiatry, Kuopio University Hospital, Kuopio, Finland
10
Department of Internal Medicine and Biocenter, Institute of Clinical Medicine, University of
Oulu, Oulu, Finland and Clinical Research Center, Oulu University Hospital, Oulu, Finland.
11
Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus,
Denmark
12
VTT Technical Research Centre of Finland, Espoo and Kuopio, Finland
13
Research Unit, Kuopio University Hospital, Kuopio, Finland
Corresponding author:
Ola Kally Magnusdottir
E-mail: [email protected]
Address: Eiriksgata 29, IS-101 Reykjavik, Iceland
Telephone: +354 543 8421
Fax: +354 543 4824
Abstract
Background and aim
Few studies have explored the possible plasma cholesterol lowering effects of rye consumption.
The aim of this secondary analysis in the SYSDIET study was to investigate the association
between plasma alkylresorcinols (AR), a biomarker for whole grain wheat and rye intake, and
blood lipid concentrations in a population with metabolic syndrome. Furthermore, we analyzed
the associations between the AR C17:0/C21:0 ratio, a suggested marker of the relative intake of
whole grain/bran rye, and blood lipid concentrations.
Methods
Participants were 30-65 years of age, with body mass index (BMI) 27-40 kg/m2 and had
metabolic syndrome. Individuals were recruited through six centers in the Nordic countries and
randomized either to a healthy Nordic diet (ND, n=93), rich in whole grain rye and wheat, as
well as berries,
fruits and vegetables, rapeseed oil, three fish meals per week and low-fat dairy products, or a
control diet (n=65) for 18/24 weeks. Associations between total plasma AR concentration and
C17:0/C21:0 homologue ratio and blood lipids were investigated in pooled (ND + control group)
regression analyses at 18/24 weeks adjusted for baseline value for the dependent variable, age,
BMI and statin use.
Results
When adjusted for confounders, total plasma AR at 18/24 weeks was not significantly associated
with blood lipids but the AR ratio C17:0/C21:0 was inversely associated with LDL cholesterol
concentrations (B (95% CI): -0.41 (-0.80 to -0.02)), log LDL/HDL cholesterol ratio (-0.20 (-0.37
to -0.03)), log non-HDL cholesterol (-0.20 (-0.37 to -0.03)), log apolipoprotein B (-0.12 (-0.24 to
0.00)) and log triglyceride concentrations (-0.35 (-0.59 to -0.12)).
Discussion
Increased proportion of whole grain rye, reflected by a biomarker, in the diet is associated with
favorable blood lipid outcomes, a relationship that should be further investigated.
ClinicalTrials.gov identifier: NCT00992641
(http://clinicaltrials.gov/ct2/show/NCT00992641?term=NCT00992641&rank=1)
1
Introduction
2
Epidemiological studies have shown an inverse relationship between diets rich in whole grain
3
and the risk of many diet-related diseases, including cardiovascular diseases [1,2], metabolic
4
syndrome [3] and type 2 diabetes [4]. A number of intervention studies have shown that
5
intake of whole grains lowers serum total and LDL cholesterol concentrations [5-8], blood
6
pressure [9,10] and improves insulin sensitivity [11-13]. Animal studies have shown
7
cholesterol lowering effects of rye consumption [14-16] but few intervention studies have
8
studied the effects of rye on blood lipids in humans, despite the fact that whole grain rye
9
products contain substantial amounts of extractable arabinoxylans and β-glucans [17] that
10
may contribute to cholesterol reduction. One study has shown that rye bread consumption
11
decreased total and LDL cholesterol concentrations in men with moderately elevated serum
12
cholesterol [5] but another study showed an unfavorable shift in serum cholesterol
13
concentrations after rye bread intake in postmenopausal women [18].
14
In nutritional science it is essential to have accurate dietary information to assess
15
compliance to dietary interventions and to investigate diet-disease associations. Collecting
16
valid data on whole grain intake can, however, be challenging due to the broad selection of
17
foods contributing to these intakes [19]. The use of alkylresorcinols (AR) as dietary
18
biomarkers for whole grain wheat and rye intake could improve the validity of dietary
19
assessment of whole grain in combination with, or as an alternative for, self-reports [19-22]. It
20
may also be used as a tool for secondary analysis, where non-compliant individuals can be
21
excluded on the basis of the biomarker measurements. AR are 3,5-dihydroxy-phenolic lipids
22
with an odd-numbered alkyl chain generally ranging from C17 to C25. Among commonly
23
consumed foods, AR are almost exclusively present in the outer parts of wheat and rye grains,
24
and just at trace amounts in refined white flour [23,24]. The ratio of the AR homologues
25
C17:0 and C21:0 differs between cereals but is consistent within cereal species
26
(approximately 0.1 in wheat and 1 in rye ) [24] and may be used to differentiate sources of
27
cereals consumed via plasma measurements [25]. We have previously demonstrated that AR
28
are useful biomarkers for whole grain wheat and rye intake as part of a healthy Nordic diet
29
[26]. Furthermore, significant between-group changes in non-HDL cholesterol concentrations
30
and LDL to HDL cholesterol ratio was found in the randomized dietary intervention with a
31
healthy Nordic diet (SYSDIET) [27].
32
The present study is based on a secondary analysis of the SYSDIET intervention trial
33
and the aim was to investigate the association between plasma AR, a biomarker for whole
34
grain wheat and rye intake, and blood lipid concentrations in a population with metabolic
35
syndrome (MetS) participating in a randomized dietary intervention. Furthermore, the
36
associations between the AR C17:0/C21:0 ratio, a suggested marker of the relative whole
37
grain/bran rye intake, and blood lipids were analyzed.
38
39
Methods
40
The current study was a part of the SYSDIET study, a randomized controlled multicenter
41
parallel group study with balanced randomization (1:1) performed in six intervention centers
42
(Kuopio and Oulu, Finland; Lund and Uppsala, Sweden; Aarhus, Denmark and Reykjavik,
43
Iceland) examining the health effects of a healthy Nordic diet (ND) in a population with
44
MetS. The protocol for this trial and supporting CONSORT checklist are available as
45
supporting information; see Checklist S1 and Protocol S1.
46
All local ethical committees (Research Ethics Committee of the Hospital District of
47
Northern Savo and Northern Ostrobothnia Hospital District,Oulu, Finland, Regional Ethical
48
Review Board, Lund and The Regional Ethical Review Board in Uppsala, Sweden, Ethical
49
Committee of Aarhus County, Denmark and The Icelandic Bioethics Committee, Iceland)
50
approved the SYSDIET study protocol which followed the Helsinki declaration guidelines
51
and informed written consent was obtained from all participants. The trial was registered at
52
ClinicalTrials.gov (ClinicalTrials identifier: NCT00992641,
53
http://clinicaltrials.gov/ct2/show/NCT00992641?term=NCT00992641&rank=1) in October
54
2009, once all local ethical committees had given their approval. The authors confirm that all
55
ongoing and related trials for this intervention are registered.
56
The study design, inclusion and exclusion criteria, study diets, the main measurements
57
and analyses performed at each time point and main results have previously been reported in
58
detail [27]. The present study is a secondary analysis where the association between AR and
59
blood lipids at the end of the intervention was examined.
60
61
Study participants
62
Participants in the study were primarily recruited through advertisements in newspapers, but
63
also from previous clinical or epidemiological trials. In brief, the inclusion criteria were age
64
30-65 years, body mass index (BMI) 27 - 40 kg/m2, and two diagnostic criteria for metabolic
65
syndrome as outlined by the International Diabetes Federation [28], except type 2 diabetes.
66
67
Study design
68
Participants were randomly assigned to either a healthy Nordic diet or an average Nordic
69
(control) diet for 18 or 24 weeks. Due to financial and logistic reasons the study period was
70
18 weeks at 4 centers (Aarhus, Uppsala, Reykjavik and Oulu) and 24 weeks at 2 centers
71
(Lund and Kuopio) where the intervention was initiated earlier [27]. The major visits to the
72
study clinics were on week 0 (baseline), week 12 and week 18/24. In Kuopio and Lund, the
73
intervention was carried out from October 2009 to June 2010, in Aarhus, from January 2010
74
to September 2010, in Oulu, from December 2009 to October 2010, in Reykjavik, from
75
March 2010 to October 2010 and in Uppsala, from June 2010 to November 2010.
76
The randomization was done by staff in each study center as described elsewhere [26].
77
The staff in all study centers was trained to perform measurements in a similar way and the
78
quality management protocol was available for all staff members. The allowed weight change
79
during the study was aimed to be less than ±4 kg due to the isocaloric design applied.
80
81
Study diets
82
The study diets were planned to be isocaloric. Nordic nutrition recommendations formed the
83
basis of the diet in the ND group [29] and the mean nutrient intake in the Nordic countries
84
formed the basis for the control diet. Participants in the ND group were advised to consume
85
≥25% of total energy as whole grain, of which ≥50% was comprised of rye, barley and oat
86
which included ≥6 slices/day of bread with ≥6 g fiber/100 g (one slice equals 30-40 g of
87
bread). Participants in the control group were asked to consume ≥25% of energy as refined
88
grain, of which ≥90% made from wheat. Furthermore, the participants in the ND group were
89
encouraged to consume ≥500 g of fruits, vegetables and berries daily, use rapeseed and/or
90
sunflower and/or soybean oil based margarines, choose low fat milk and dairy products,
91
consume three fish meals a week, choose low fat meat, and to avoid sugar-sweetened
92
beverages while the control group was advised to keep their habitual diet. Key food products
93
were provided to the study participants in both groups. The individuals in the ND group
94
received whole grain products such as oatmeal and barley, crisp breads, whole grain wheat
95
and rye breads. The individuals in the control group received low fiber cereal products, e.g.
96
breads with fiber content less than 6 g/100 g and ordinary pasta. The study diets have
97
previously been described in detail [27].
98
The participants were instructed by a clinical nutritionist or a dietitian at all study
99
visits. The study participants kept dietary records regarding the intake of cereal products.
100
These records were checked at each visit to the study center, including the visits when the
101
groceries were delivered to the participants, i.e. at 1-2 week intervals and the subjects also
102
returned 4-day weighed food records at baseline, week 2, 12 and 18/24 [27].
103
104
Biochemical measurements
105
Blood samples were collected at week 0, 12 and 18/24. Automated clinical chemistry
106
analyzers and routine clinical chemistry methods were used to measure concentrations of total
107
and HDL cholesterol, triglycerides and apoplipoproteins A1 and B. The equipment and
108
system reagents and CV%´s have been described previously [27]. LDL cholesterol
109
concentrations were calculated using Friedewald's formula.
110
Determination of AR in plasma samples were made in collaboration with the HELGA-
111
Centre at Department of Food Science, BioCenter at Swedish University of Agricultural
112
Sciences. A gas chromatography mass spectrometry (GC-MS) method was used to quantify
113
AR homologues C17:0-C25:0 in 0.2 ml plasma samples as described previously [30]. Quality
114
control samples (n=4) was included in each batch to ensure appropriate within- and between
115
batch precision (CV <15%). Samples from each subject were analyzed within the same batch
116
and samples from different centers were allocated randomly between batches.
117
118
Data pooling and statistical analysis
119
All intervention centers entered their data into Microsoft Office Excel 2007 (Windows) data
120
form prior to pooling the data in a joint database maintained at VTT Technical Research
121
Centre of Finland. Data was exported from the database and imported to SPSS (Statistical
122
Package for the Social Sciences) for Windows, version 20.0 (SPSS Inc., Chicago, Illinois,
123
USA) for statistical analysis. Level of significance in all analyses was set at P<0.05.
124
Normality of variables was checked by inspection and by using the Kolmogorov–
125
Smirnov test. Values are described as means and standard deviations (SD) if normally
126
distributed or as medians and interquartile range (IQR) if not normally distributed.
127
The analyses were performed with data from the ND and control groups combined and
128
associations between total AR and the AR C17:0/C21:0 ratio at 18/24 weeks and various
129
blood lipid outcomes were analyzed. Where distributions were skewed (every variable except
130
total and LDL cholesterol concentrations), log-transformation was performed on dependent
131
variables for linear regression to better approximate normal distribution. The distribution of
132
AR C17:0/C21:0 ratio across total plasma AR was checked by inspection.
133
Linear regressions for fasting concentrations of total, LDL, HDL, non-HDL
134
cholesterol, apolipoproteins A1 and B, triglycerides and LDL/HDL cholesterol ratio with total
135
plasma AR or AR C17:0/C21:0 ratio (model 1), baseline value for the dependent variable,
136
age, BMI and statin use, as factors were performed. As rye often contains more AR than
137
wheat, total plasma AR was added as a variable, in addition to the variables in model 1 when
138
the associations between AR C17:0/C21:0 ratio was examined, to prevent confounding of
139
high AR content (model 2). To account for multiple testing, we used the Bonferroni
140
correction approach, using a significance level of alpha divided by the number of independent
141
outcomes, that is 0.05/8 = 0.006. Furthermore, we individually adjusted for saturated fat
142
intake calculated from food records and serum phospholipid fatty acids myristic acid, palmitic
143
acid, omega-3 fatty acids and C15:0, to prevent confounding of dietary fat intake.
144
145
Results
146
Altogether 166 participants finished the study and of those 158 subjects had blood samples for
147
AR and blood lipid analyses from all time points and that group was used for analyses in the
148
present study (Figure 1). There was no difference between dropouts and those who completed
149
the study in baseline BMI (P = 0.797), waist circumference (P=0.228), age (P = 0.959) or
150
triglyceride (P = 0.055), total cholesterol (P=0.743), HDL cholesterol (P = 0.216) or LDL
151
cholesterol (P =0.686) concentrations.
152
There was no change in total energy intake during the study and energy intake was not
153
different between the groups, hence, body weight remained constant during the intervention in
154
both groups. The mean age of the participants was 54.5 (8.2) years, body weight 91.2 (13.5)
155
kg, BMI 31.7 (3.2) kg/m2 and waist circumference 104.3 (9.7) cm as described previously
156
[31]. Baseline lipid concentrations and the number of statin users in by intervention group, are
157
shown in Table 1. The prevalence of MetS was 90%. No differences were observed between
158
the groups at baseline in clinical characteristics.
159
There were small, but significant, decrease in concentrations of total cholesterol (5.1
160
(1.2) mmol/L at 18/24 weeks, P=0.018), LDL (3.2 (1.1) mmol/L at 18/24 weeks, P=0.006)
161
and non-HDL cholesterol (3.8 (1.3) mmol/L at 18/24 weeks, P=0.006) and LDL/HDL
162
cholesterol ratio (2.3 (1.3) at 18/24 weeks, P=0.003) within the ND group from week 0 to
163
18/24 but not within the control group. Results on the effects of the SYSDIET intervention,
164
with ND, on blood lipid concentrations and other health outcomes have been reported
165
previously [27]. Both total plasma AR concentration and the ratio of C17:0/C21:0 were
166
significantly higher in the ND group than in the control group at 18/24 week (Table 2) and the
167
range of total plasma AR was 14 to 499 nmol/L. There was no skew towards higher AR
168
C17:0/C21:0 ratios for higher total plasma AR concentrations.
169
All participants (both ND and control groups) were combined for secondary analyses
170
on the associations between AR and blood lipids concentrations at 18/24 weeks. Total plasma
171
AR concentration at 18/24 weeks was not significantly correlated with concentrations of
172
fasting serum total cholesterol (P=0.95), LDL cholesterol (P=0.23), HDL cholesterol
173
(P=0.25), LDL-C/HDL-C ratio (P=0.13), triglycerides (P=0.14), apolipoprotein A1 (P=0.09)
174
or apolipoprotein B (P=0.86) after adjusting for confounders. However, the AR C17:0/C21:0
175
ratio, which reflects the proportion of whole grain rye of whole grain rye and whole grain
176
wheat combined, was inversely associated with LDL cholesterol concentration when adjusted
177
for baseline LDL cholesterol concentration, BMI, age and statin use (model 1, P=0.040) and
178
also when total plasma AR was added to the regression model (model 2, P=0.046) (Table 3).
179
Similarly, AR C17:0/C21:0 ratio was inversely associated with LDL/HDL cholesterol
180
ratio (P=0.020 and P=0.024 for model 1 and model 2, respectively), non-HDL cholesterol
181
(P<0.001 for both model 1 and model 2), triglyceride (P=0.004 and P=0.002 for model 1 and
182
model 2, respectively) and apolipoprotein B concentrations (P=0.047 for both model 1 and
183
model 2) and positively associated with HDL cholesterol concentration (P=0.044 and
184
P=0.049 for model 1 and model 2, respectively). Including saturated fatty acids calculated
185
from food records to the models did not change the results nor did including the serum
186
phospholipid fatty acids myristic acid, palmitic acid, omega-3 fatty acids and C15:0, except
187
for HDL cholesterol in which the association with C17:0/C21:0 became borderline significant
188
(P=0.067). However, using the Bonferroni correction approach to account for multiple testing
189
the associations for LDL cholesterol, HDL cholesterol, LDL/HDL cholesterol ratio and
190
apolipoprotein B concentrations would not be considered significant while associations for
191
non-HDL cholesterol and triglyceride concentration are robust for this correction (P<0.006).
192
193
Discussion
194
Favorable changes in serum LDL cholesterol concentration and LDL to HDL cholesterol ratio
195
were observed in participants consuming a healthy Nordic diet, established with a healthy
196
dietary pattern approach, and thus also rich in whole grain cereals, for either 18 or 24 weeks
197
[27]. In the intervention the participants in the ND group were advised to consume ≥25% of
198
total energy as whole grain, of which ≥50% was comprised of rye, barley and oat, and to
199
make favorable changes in dietary fat intake, and therefore a change in serum cholesterol
200
concentration in the ND group was expected. Some studies have found that whole grain diets
201
lower serum total and LDL cholesterol concentrations [5-8]. The cholesterol lowering effects
202
of β-glucans in oats and barley have been extensively studied [32,33] and the European Food
203
Safety Authority (EFSA) has approved two health claims on the subject: β-glucans contribute
204
to the maintenance of normal blood cholesterol levels [34] and oat β-glucan has been shown
205
to lower/reduce blood cholesterol. Blood cholesterol lowering by increased oats intake may
206
reduce the risk of (coronary) heart disease [35].
207
In the present study, both ND and control groups were pooled for secondary analysis
208
on the association between plasma AR and blood lipids at 18/24 weeks. Plasma AR has been
209
established as a biomarker for whole grain wheat and rye intake [19,21,26] and has previously
210
been studied regarding associations with BMI and metabolic risk factors [36,37]. We
211
observed no association between total plasma AR concentration and serum lipid
212
concentrations, possibly due to a considerable amount of AR intake originating from whole
213
grain wheat. Whole grain wheat intake does typically not affect blood cholesterol and is thus
214
often used as a control in experimental studies [38]. Interestingly, the AR C17:0/C21:0 ratio,
215
an indicator of relative rye intake, was associated with favorable changes in concentrations of
216
LDL-, HDL-, and non HDL cholesterol, LDL/HDL cholesterol ratio and triglycerides, even
217
after adjustment for fatty acids composition of serum phospholipids, with the exception of
218
HDL cholesterol where the association became borderline significant. The ratio of the AR
219
homologues C17:0 and C21:0 differs between cereal species and can be used to differentiate
220
between the whole grain sources in food products [24]. The ratio of AR C17:0/C21:0 is
221
approximately 0.1 in wheat and 1 in rye and the ratio is to some extent reflected in fasting
222
plasma samples, although it is generally lower, typically around 0.6-0.8 in fasting samples
223
after a whole grain rye intervention for 1-8 weeks, and can be used to differentiate which AR
224
containing cereals have been consumed [25,39,40].
225
Health effects of rye are far less studied than oats and barley and studies on the effects
226
of rye consumption on cholesterol are scarce. The mechanisms that have been proposed to
227
cause the reduction in plasma cholesterol levels focus on the fiber and phytochemical content
228
of whole grains, particularly water-soluble viscose fiber [41,42], and it has been established
229
that the cholesterol lowering effect of β-glucans is dependent on the molecular weight and
230
subsequent viscosity [43]. Rye is particularly high in dietary fiber, ranging between 18-22%,
231
and it contains substantial amounts of extractable β-glucans and arabinoxylans, which could
232
contribute to cholesterol reduction through a similar mechanism as β-glucans from oats and
233
barley [17,44]. Animal studies have shown that rye could affect blood lipid concentrations by
234
increasing the total concentration of bile acids in the bile [14-15].
235
Previous studies have shown that rye bread consumption decreases total and LDL
236
cholesterol concentrations in men with moderately elevated serum cholesterol [5], and lower
237
concentrations of plasma free-cholesterol, total cholesterol, triglycerides and phospholipids
238
have been demonstrated after a high fiber rye diet than a low fiber wheat diet [6].
239
Additionally, animal studies have shown cholesterol lowering effects of rye consumption [14-
240
16]. However, Moazzami et al showed an unfavorable shift in serum cholesterol levels after
241
rye bread intake in postmenopausal women [18]. Processing of rye and other whole grains,
242
such as fermentation, have been reported to influence the molecular weight of cereal dietary
243
fiber, hence it is possible that lower viscosity of the fibers could explain the lack of beneficial
244
effects reported in some studies [17]. Nevertheless, the results of the present study suggest
245
that whole grain rye consumption is associated with favorable outcomes in blood lipids and
246
this association should be further studied.
247
One of the strengths of the present study is that we used AR as a dietary biomarker for
248
whole grain rye and wheat intake instead of self-reported estimates. As collecting valid data
249
on whole grain intake can be challenging, the use of biomarkers to assess intake and/or
250
compliance to dietary interventions is a way to avoid some of the obstacles associated with
251
self-reporting [19]. Previously, we have demonstrated that AR is a good biomarker for the ND
252
under intervention conditions with moderate to good reliability [26] and our data supports the
253
use of the AR C17:0/C21:0 ratio as an indicator for whole grain rye intake in intervention
254
studies where a diet rich in whole grain rye is being investigated [31]. Although the AR
255
C17:0/C21:0 ratio reflects only the relative whole grain/bran rye consumption of total whole
256
grain wheat and rye intake, and not the total rye intake, the advised whole grain rye intake in
257
the present study was high in relation to other sources of AR and therefore the ratio should
258
reflect the total rye intake reasonably well. However, the present study does not offer any
259
mechanistic explanations behind the possible cholesterol-lowering by whole grain rye, and
260
more needs to be done to explain the association. Nevertheless, the results do motivate further
261
research on this topic. Some confounding effects from oats intake are possible, as participants
262
consuming more rye might also consume more oats, and confounding effects from other food
263
sources cannot be excluded. However, this is probably not explaining the main results.
264
Previous studies suggest that plasma AR may be transported in VLDL and HDL [45], which
265
could affect the results of the present study, as well as numerous dietary and non-dietary
266
factors potentially influencing biomarker concentrations [19]. Nevertheless, since the AR
267
C17:0/C21:0 ratio, but not total plasma AR, was associated with cholesterol concentrations,
268
and the associations did not change when adjusted for total plasma AR, we believe our
269
findings indicate that the associations we found are related to whole grain rye intake and not
270
by the fact that AR may be transported in certain lipoproteins.
271
272
Conclusion
273
Our findings suggest that a greater proportion of whole grain rye in a Nordic diet is associated
274
with favorable outcomes in blood lipid concentrations, an association that warrants further
275
investigation.
276
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Funding
The study was supported by NordForsk NCoE in Food Nutrition and Health: Project 070014
SYSDIET (Systems biology in controlled dietary interventions and cohort studies
(http://www.nordforsk.org/en?set_language=en). This study was also funded by the Academy
of Finland, Finnish Diabetes Research Foundation, Finnish Foundation for Cardiovascular
Research, The Sigrid Juselius Foundation, and EVO funding from Kuopio University
Hospital (Finland: US, KHH, JH, MJS, MK, KP, MU); the Druvan Foundation, ESPEN,
Skåne County Council Research and Development Foundation, Swedish Research Council for
Health, Working Life and Welfare, EXODIAB (Excellence of Diabetes Research in Sweden),
The Heart-Lung Foundation, Diabetesfonden and Foundation Cerealia (Sweden: RL, LC, BÅ,
FR, UR); The Danish Obesity Research Centre (DanORC, www.danorc.dk), The Danish
Council for Strategic Research (DairyHealth, BioFunCarb) (Denmark: LB, KH), The
Agricultural Productivity Fund (Iceland: IG, OKM, IT) and the Icelandic Research Fund for
graduate students (1206880061)http://rannis.is/ (OKM).
The following companies provided food products for the study participants: Kesko
Food Ltd, Raisio Group, Bunge Finland Ltd (Finland); Belico Food AB, Fazer Bageri
Sverige, Lantmännen, Oatly AB, Olle Svensson AB, Procordia Food AB, Pågen AB,
Unilever, Wasabröd AB (Sweden); Lantmännen Food R&D, Jan Import A/S, Ardo A/S,
Scandic Food A/S, WASA, Glyngøre Limfjord A/S, Royal Greenland A/S, Arla Foods
(Denmark); The Mother Earth Farm at Vallanes (Iceland); and Unilever Nordic (Sweden,
Denmark, Iceland).
Acknowledgement
Authors express sincere gratitude to the participants taking part in the study. We also thank all
staff involved in the intervention.
Figure 1. Flow chart of the study
Table 1. Baseline blood lipid concentrations and statin use of the participants. Values are
presented as medians (IQR).
ND group
Control group
(n=93)
(n=65)
Total cholesterol, mmol/L
5.3 (1.2)
5.1 (1.5)
HDL cholesterol, mmol/L
1.4 (0.5)
1.3 (0.6)
LDL cholesterol, mmol/L
3.2 (1.1)
3.1 (1.5)
Non-HDL cholesterol, mmol/L
3.9 (1.3)
3.7 (1.6)
LDL-C/HDL-C
2.5 (1.4)
2.4 (1.8)
Triglycerides 0 min, mmol/L
1.3 (0.8)
1.4 (0.8)
Apolipoprotein A1, g/L
1.4 (0.3)
1.4 (0.3)
Apolipoprotein B, g/L
1.0 (0.4)
1.0 (0.4)
19
18
Statin use, n
Abbreviations: HDL, high-density lipoprotein; LDL, low-density lipoprotein
Table 2. Dietary fiber intake, total plasma alkylresorcinols (AR) concentration and AR
C17:0/C21:0 ratio for the healthy Nordic diet group (ND) and control group at baseline and
after the 18/24 week intervention. Values are medians (IQR).
ND group (n = 93)
Dietary fiber intake1,2, g/day
Control group (n = 65)
Week 0
Week 18/24
Week 0
Week 18/24
21.1 (8.8)
36.0 (15.1)#
20.0 (7.1)
16.0 (6.2)*#
73 (88)
106 (108)#
71 (70)
61 (40)*#
0.3 ± 0.2
0.3 ± 0.2
0.3 ± 0.2
0.2 ± 0.2*#
Total plasma AR1, nmol/L
C17:0/C21:0 ratio1
*significantly different from ND group at that time point
#
significantly different from baseline
1
Data published previously [31]
2
n = 140, ND group n = 80 and control group n = 40
Abbreviations: ND, healthy Nordic diet; AR, alkylresorcinols
Table 3. Regression models for concentrations of serum total, HDL, LDL, non HDL
cholesterol and triglycerides and the cholesterol LDL-C/HDL-C ratio
Dependent variable at
Independent variable at
18/24 weeks
18/24 weeks
B1 (95% CI)
Total cholesterol
Model 1
AR C17:0/C21:0
-0.33 (-0.78 to 0.12)
Model 2
AR C17:0/C21:0
-0.33 (-0.78 to 0.12)
Model 1
AR C17:0/C21:0
-0.41 (-0.80 to -0.02)
Model 2
AR C17:0/C21:0
-0.40 (-0.79 to -0.01)
Model 1
AR C17:0/C21:0
0.11 (0.00 to 0.21)
Model 2
AR C17:0/C21:0
0.11 (0.00 to 0.21)
LDL cholesterol
Log HDL cholesterol
Log LDL-C/HDL-C cholesterol
Model 1
AR C17:0/C21:0
-0.20 (-0.37 to -0.03)
Model 2
AR C17:0/C21:0
-0.20 (-0.37 to -0.03)
Model 1
AR C17:0/C21:0
-0.84 (-1.22 to -0.45)
Model 2
AR C17:0/C21:0
-0.81 (-1.19 to -0.44)
Log non HDL cholesterol
Log triglycerides
Model 1
AR C17:0/C21:0
-0.35 (-0.59 to -0.12)
Model 2
AR C17:0/C21:0
-0.37 (-0.60 to -0.13)
Model 1
AR C17:0/C21:0
0.05 (-0.03 to 0.13)
Model 2
AR C17:0/C21:0
0.05 (-0.03 to 0.13)
Model 1
AR C17:0/C21:0
-0.12 (-0.24 to 0.00)
Model 2
AR C17:0/C21:0
-0.12 (-0.24 to 0.00)
Log apolipoprotein A1
Log apoliprotein B
1
B reflects the change in the log-transformed outcome variable for each 1-unit changes in the
independent variable.
Model 1: adjusted for baseline value of the dependent variable, BMI, age and statin use
Model 2: adjusted for baseline value of the dependent variable, total AR, BMI, age and statin
use
Abbreviations: ND, healthy Nordic diet; AR, alkylresorcinols; HDL, high-density lipoprotein;
LDL, low-density lipoprotein; BMI, body mass index
Paper IV
Title: Increasing rye consumption among men with type 2 diabetes: a feasibility study
Keywords: alkylresorcinols, rye consumption, feasibility, acceptability, whole grain,
compliance
Authors: Ola Kally Magnusdottir1,Rikard Landberg2,3, Ingibjorg Gunnarsdottir1, Kristjan
Thor Magnusson4, Göran Hallmans5, Rikke Dalgaard Hansen6, Cecilie Kyrø6, Anja Olsen6,
Anne Tjønneland6, Inga Thorsdottir1, Laufey Steingrimsdottir1
1
Unit for Nutrition Research, Landspitali -The National University Hospital of Iceland,
Faculty of Food Science and Nutrition and School of Health Sciences, University of Iceland,
Reykjavík, Iceland,
2
Department of Food Science, BioCenter, Swedish University of Agricultural Sciences,
Uppsala, Sweden
3
Division of Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska
Institutet, Stockholm, Sweden
4
Center for Sport and Health Sciences, School of Education, University of Iceland, Reykjavík,
Iceland
5
Department of Public Health and Clinical Medicine, Nutritional Research, Umeå University,
Umeå, Sweden
6
Danish Cancer Society Research Center, Strandboulevarden 49, DK-2100 Copenhagen,
Denmark
Corresponding author:
Ola Kally Magnusdottir
E-mail: [email protected]
Address: Eiriksgata 29, IS-101 Reykjavik, Iceland
Telephone: +354 543 8422
Fax: +354 543 4824
Conflict of interests
The authors declare no conflict of interest.
Funding
The study was funded by Nordic Center of Excellence, HELGA: Nordic Health – Whole grain
Food, the Consortium Agreement for Consortium on Health and Ageing Network of Cohorts
in Europe and the United Std States (CHANCES) - EG Grant agreement No: 242244 – WP4
and The Icelandic Research Fund for graduate students (1206880061).
Abstract
Background and aim: Intervention studies have indicated beneficial effects of whole grain
rye consumption but studies on acceptability and compliance to such interventions in
populations not accustomed to high intake is needed. The aim was to determine the feasibility
of conducting an intervention with high consumption of whole grain rye and vigorous
physical activity (PA) for 6 months in a population of men with type 2 diabetes (DM2) and
habitually low whole grain intake.
Methods: Participants (males, 42-80 years with DM2) were randomized into either a rye
group (n=14) or a control group (n=9) for 26 weeks. Participants in the rye group were
provided with, and asked to consume, 100 g/day of whole grain rye. Acceptability and
compliance was assessed with questionnaires, 4-day food record and plasma alkylresorcinols
(AR). Participants in both groups were instructed to exercise vigorously three days/week and
walk ≥10000 steps on other days.
Results: In total, 87% of the participants finished the study. Rye intake and total plasma AR
increased significantly in the rye group (P=0.003 and P=0.004, respectively) and the mean rye
consumption during the intervention was 93±44 g/day. In the control group, the mean rye
intake was 10±8 g/day during the intervention. Four participants in the rye group experienced
digestive discomfort in weeks 0-13 weeks and two in weeks 13-26. PA levels did not change
significantly during the intervention for the rye group or the control group and no participant
reached 10 000 steps/day.
Discussion: The dietary intervention was well received by the intervention group as seen in
low dropout, good compliance and acceptability. Poor compliance to prescribed PA in the
intervention emphasizes the need for improved methods to encourage PA in diabetic
populations.
1
Introduction
2
The most important grains consumed in the Western world are wheat, corn, rice, oats, barley and
3
rye. Rye is a cereal of specific interest as it is particularly high in dietary fiber [1], and
4
traditionally consumed as whole grain. Rye is mostly consumed in the Northern and Eastern
5
European countries [2]. In Iceland, rye and oatmeal were the main types of whole grain in the
6
diet during the first half of the 20th century and in 1930 the average rye consumption was 152
7
g/day according to import figures, but cereals have not been grown in Iceland for human
8
consumption to any extent [3]. Rye consumption has, however, decreased dramatically during
9
the last 50 years in Iceland, as well as in many other countries [2,4]. According to food supply
10
data the average rye consumption in Iceland was 31 g/day in 1961 but 8 g/day in 2011. The
11
average rye consumption in 2011 was higher in the other Nordic countries, 47 g/day in Denmark,
12
45 g/day in Finland, 32 g/day in Sweden and 18 g/day in Norway [2]. Furthermore, Iceland also
13
has the lowest consumption of total dietary fiber among all the Nordic countries [5-8].
14
Several intervention studies have indicated beneficial effects of rye consumption on
15
metabolic processes [9-13]. Studies have shown positive effects of high rye consumption on
16
fasting plasma insulin and, to a less extent, on fasting plasma glucose [9,10] and an improved
17
early insulin response has been shown after rye bread interventions [11,13]. These studies have,
18
however, been conducted in countries accustomed to a relatively high rye intake (i.e. Finland and
19
Sweden) and the effects of rye consumption were investigated over a short period of time,
20
generally 6-12 weeks. To date, no intervention study on the health effects of whole grain rye
21
intake has been conducted on patients with type 2 diabetes. Before implementing an intervention
22
with high consumption of whole grain rye in a population unaccustomed to high intakes, it is
23
important to explore to what extent it is possible to increase the consumption and the
24
acceptability of whole grain rye products.
25
Physical activity (PA) also plays a crucial role in the management of type 2 diabetes with
26
extensive research reporting improvement in glucose control with increased PA [14-17].
27
Nevertheless, the majority of people with type 2 diabetes are inactive [15,18,19] and it is
28
therefore of great importance to encourage increased PA in this population.
29
The aim of the present study was to determine the feasibility of conducting an
30
intervention with high consumption of whole grain rye and vigorous PA for 6 months in a
31
population of men with habitually low whole grain and fiber intake. The present feasibility study
32
investigated the dropout, acceptability and adherence to the intervention in a population
33
comprised of 23 men diagnosed with type 2 diabetes.
34
35
Methods
36
The present study is a feasibility study conducted as a follow up of Nordforsk Nordic Center of
37
Excellence Program, HELGA: Nordic Health – Whole grain Food. Informed consent was
38
obtained from all participants and the study received approval from the Icelandic National
39
Bioethics Committee and the Data Protection Commission.
40
41
Participants and study design
42
Participants were referred to the study by general practitioners in three health care clinics in the
43
capital area of Iceland. Participants were 23 males, aged 42 – 80 years and diagnosed with type 2
44
diabetes or pre-diabetes by their family doctor. The exclusion criteria included any chronic
45
disease and/or condition, which could hamper the adherence to the dietary intervention protocol.
46
The duration of the intervention was 26 weeks and participants followed their habitual
47
diet for a week before randomization into either the rye group (n = 14) or the control group (n =
48
9). All participants had three major visits, at week 0, weeks 13 and 26 (Figure 1). Additionally
49
there was a group meeting for all participants with a clinical nutritionist in week 2 where
50
participants received general recommendations on a healthy diet, as well as a meeting with a
51
physical therapist and a personal trainer during the first weeks. The participants in the rye group
52
came to the clinic every 2-3 weeks, to pick up the rye products that were provided and both
53
groups were offered to pick up vegetable packages free of charge every 4 weeks. The
54
intervention was carried out from April to November 2013.
55
56
Study diet
57
Participants in the rye group were instructed to consume 100 g of whole grain rye each day for
58
26 weeks and rye products equivalent to this intake were provided free of charge. The products
59
provided to the rye group were rye flakes to use for rye porridge, rye crisp bread and rye bread.
60
The rye content of the products provided is listed in Table 1. The participants in the control
61
group were asked to maintain their usual diet, but avoid rye products, and were offered whole
62
wheat breads free of charge
63
Participants in the rye group received both oral and written information on the amount of
64
rye in the products provided, as well as other common whole grain rye products, and how to
65
reach 100 g rye a day. To simplify, the participants were asked to obtain ten points every day,
66
where one point was earned for every 10 g of whole grain rye consumed. A color-printed booklet
67
with names and pictures of the rye products provided in the study, as well as other common
68
whole grain rye products available in local supermarkets, was also given to the participants in the
69
rye group. The booklet included information on the total nutritional value, the amount of whole
70
grain rye per 100 g of product and per serving (e.g. slice of bread) and number of points earned
71
per serving. Altogether the booklet contained information on 32 rye products.
72
Dietary intake was assessed using a consecutive 4-day (Wednesday to Saturday) weighed
73
food record collected prior to week 0, at week 13 and 26. Participants received both written and
74
oral instructions on how to fill in the diet records and were provided with electronic household
75
scales. At the week 0 visit, a nutritionist reviewed the first food diary with each participant and
76
suggested exchanges for rye products. Rye porridge (from rye flakes) was recommended daily,
77
to facilitate the rye consumption without adding increased energy to the diet. In addition, daily
78
consumption of 1 - 4 slices of rye bread (dependent on the type of bread) was recommended.
79
The nutrient intake from food diaries was calculated using The Icelandic Food
80
Composition Database [ISGEM], Iceland). The database uses EuroFIR definitions for chemicals
81
and total dietary fiber determined by the AOAC methods [20]. Whole grain rye intake was
82
calculated manually.
83
84
Physical activity
85
After randomization, all participants in both groups were asked to exercise vigorously for at least
86
45 minutes three days/week, and walk at least 10 000 steps on other days, for 26 weeks. A gym
87
membership and a pedometer were provided to all participants free of charge. At the beginning
88
of the study, each participant met with a physical therapist who evaluated the physical condition
89
of the participants. Following that meeting the participants met with a personal trainer who gave
90
them individualized exercise programs and showed them the exercises and the workout
91
equipment. The participants were free to contact the personal trainer during the intervention
92
period to get a different (less/more advanced) program if necessary. Thus, every participant
93
received an exercise program designed for their needs, e.g. interests, age, strengths and
94
weaknesses.
95
Accelerometers were used (Actigraph™ GT1M monitors) to assess both volume and
96
intensity of PA during waking hours for four consecutive days (Wednesday to Saturday) at three
97
time-points during the intervention, before week 0, week 13 and week 26.
98
99
Compliance and acceptability
100
Alkylresorcinols (AR) in plasma were used to assess compliance to the whole grain rye diet with
101
measures of total plasma AR and the AR C17:0/C21:0 ratio [10,21-23], in addition to the
102
weighed food diary. The plasma samples were analyzed at the Department of Food Science,
103
BioCenter at the Swedish University of Agricultural Sciences. AR homologues C17:0-C25:0
104
were measured in 0.2 ml plasma samples according to a previously published GC-MS method
105
[24]. Quality control samples (n = 4) were included in each batch to ensure appropriate within-
106
and between batch precision (CV <10-15%). Samples from the same individual were analyzed
107
within the same batch.
108
To measure the acceptability of the products participants in the rye group were, at week
109
13 and 26, given three statements and asked to check whether they strongly agreed, agreed,
110
neither agreed nor disagreed, disagreed or strongly disagreed. The statements were: 1) I have
111
experienced digestive discomfort after I started eating rye products 2) I like food products that
112
contain rye and 3) I would prefer products that contain rye more than other products.
113
114
115
Anthropometric measurements
116
Height was measured at week 0 with a calibrated stadiometer with a precision of 0.5 cm. Body
117
weight was measured at weeks 0, 13 and 26. Weight was measured in light clothing on a digital
118
calibrated scale to the nearest 0.1 kg. Body mass index (BMI) was calculated from the recorded
119
height and weight using the standard formula, dividing the participants´ weight (kg) by the
120
square height (m2). The waist circumference was measured at week 0, week 13 and 26, midway
121
between the lowest rib margin and the iliac crest. All measures were performed twice using a
122
flexible tape measure and recorded with the accuracy of 0.1 cm. Body composition was
123
determined at weeks 0, 13 and 26 by bioelectrical impedance analysis (STA/BIA Body
124
Composition Analyzer, Akern Bioresearch Srl, Florence, Italy).
125
126
Biochemical measurements
127
Measurements of fasting glucose, insulin and blood lipids (triglycerides, total cholesterol and
128
HDL cholesterol) were performed in Landspitali – University Hospital according to standard
129
operational procedures. Automated clinical chemistry analyzers and routine clinical chemistry
130
methods were used to measure glucose, insulin, triglycerides, total cholesterol and HDL
131
cholesterol. LDL-C concentrations were calculated using Friedewald’s formula.
132
133
Statistical analysis
134
All data analyses were done in SPSS (Statistical Package for the Social Sciences) for Windows,
135
version 20.0 (SPSS Inc., Chicago, Illinois, USA) for statistical analysis. Level of significance in
136
all analyses was set at P<0.05.
137
Normality of variables was checked by inspection and by using the Kolmogorov–
138
Smirnov test. Values are described as means and standard deviations (SD) if normally distributed
139
or as medians and interquartile range (IQR) if not normally distributed. Independent sample t-
140
tests or Mann-Whitney’s U test were used to compare data between groups. When comparing
141
values at week 0 to week 26, paired samples t-test or Wilcoxon signed ranks test was used.
142
The answers to the acceptability questions were combined before statistical analysis
143
combining strongly agree and agree to agree and strongly disagree and disagree to disagree.
144
145
Results
146
Altogether, 23 men started the intervention, 14 in the rye group and 9 in the control group. Three
147
dropped out of the study, two in the rye group and one in the control group. Two dropped out
148
during the first weeks for personal reasons not related to the intervention and one had a medical
149
condition and was not able to finish the intervention. Thus, 20 men completed the study, 12 in
150
the rye group and 8 in the control group. The participants were 42 to 80 years old, with a mean ±
151
SD age of 59 ± 11 years. Baseline characteristics are presented in Table 2. The BMI for the
152
participants at baseline was 24 – 38 kg/m2. There was no significant difference between the
153
groups in baseline characteristics except for participants in the control group had more steps/day
154
than participants in the rye group.
155
156
Dietary intake
157
There was a significant increase in rye consumption in the rye group from week 0 to week 26,
158
with reported rye intake increasing from 11 ± 19 g/day at week 0, to 103 ± 38 g/day at week 13
159
and 86 ± 41 g/day at week 26 (P = 0.003). Rye consumption in the control group did not change.
160
The mean rye consumption during the intervention was 93 ± 44 g/day in the rye group and 10 ±
161
8 g/day for the control group. The rye consumption was right skewed with 7 out of 12
162
participants consuming ≥100 g/day of rye during the intervention, three consuming between 60
163
and 99 g/day and two consuming less than 60 g/day. On average, 72% of the daily rye
164
consumption in the rye group came from the rye porridge.
165
Reflecting the changes in rye intake, there was a borderline significant increase in fiber
166
intake in the rye group, with mean intake 19 ± 10 g/day at week 0, 33 ± 10 g/day at week 13 and
167
28 ± 7 g/day at week 26 (P = 0.06). The fiber intake in the control group was unchanged.
168
Similarly, the total plasma AR concentration and the AR C17:0/C21:0 ratio increased in the rye
169
group, although borderline significant for AR C17:0/C21:0 (P = 0.004 and 0.060, respectively),
170
and not in the control group (Figure 2). There was no significant difference between groups in
171
energy or macronutrient intake during the intervention (Table 3).
172
Four of the twelve participants in the rye group experienced digestive discomfort in the
173
first 13 weeks of rye consumption and two participants in the latter 13 weeks (Figure 3 a)). The
174
mean rye consumption at 13 weeks for the four men that experienced discomfort in the first
175
weeks was 130 ± 13 g/day while it was 94 ± 42 g/day for those who did not experienced any
176
discomfort. Similarly, at week 26, the mean consumption for the two participants that
177
experienced digestive discomfort in the latter 13 weeks was 123 ± 9 g/day while it was 91 ± 31
178
g/day for those that did not experience any discomfort. The difference in rye consumption
179
between those that did experience discomfort and those that did not was, however, not
180
statistically significant.
181
182
Six participants answered positively when asked if they liked the rye products at week 13
and eight at week 26. At week 26 no participants disliked the products Figure 3 b). Similarly, at
183
week 26 eight participants stated that they would prefer products that contain rye more than other
184
products and no participants disagreed (Figure 3 c)).
185
186
Physical activity
187
PA did not change significantly during the intervention neither for the rye group nor the control
188
group (Table 4). For the rye group, the mean steps/day were 3195 ± 988 at week 0, 3581 ± 1298
189
at week 13 and 3817 ± 1401 at week 26. The mean steps/day for the control group were 4347 ±
190
2514 at week 0, 4477 ± 2138 at week 13 and 3970 ± 1076 at week 26. Participants in the control
191
group had significantly more steps/day at baseline than participants in the rye group but there
192
was no significant difference between the groups during the intervention. No participants
193
reached 10 000 steps a day.
194
195
Discussion
196
Findings from this feasibility study suggest that an intervention consisting of up to 100 g whole
197
grain rye a day is well accepted in free living men with habitual low rye and fiber consumption,
198
as measured by drop-out, compliance and acceptability of the products. At week 0 the rye
199
consumption was low, or 11 g/day. In line with the aims of the study, there was a highly
200
significant increase in rye consumption in the rye group from week 0 to week 26, while the rye
201
consumption in the control group was unchanged, indicating a good compliance to the dietary
202
intervention. A total of 20 participants finished the study, or 87% of those who started the
203
intervention, with the rye group increasing their rye intake eight fold on average. Good
204
compliance has also been reported in previous intervention studies, conducted in Sweden and
205
Finland where general rye consumption is greater. In all studies, including the present study, rye
206
products were provided to the participants free of charge [9,11-13]. Most of the rye the
207
participants consumed in the present study came from the rye flakes during breakfast
208
emphasizing the importance of including rye porridge in future studies. Compared to a wheat
209
bread breakfast, whole grain rye porridge has also been shown to improve satiety and decrease
210
subsequent hunger and desire to eat up to 8 hours after consumption [25,26]. Possibly the
211
habitually low bread consumption of Icelandic adults may favor the acceptability of the porridge,
212
as introduction of a bread meal may cause greater changes in the daily diet than changes in
213
breakfast choice.
214
There was no difference between the groups in energy or macronutrient intake during the
215
intervention indicating that the rye products were not added to the baseline diet but were
216
exchanged for other carbohydrate rich food. At week 0 the fiber intake was 19 g/day, comparable
217
to the 17.7 g/day reported for Icelandic men in a recent Icelandic National Dietary Survey [27].
218
Similar to the increase in whole grain rye consumption, there was an increase in total fiber intake
219
as well as total plasma AR concentration and the AR C17:0/C21:0 ratio. Plasma AR has been
220
established as a biomarker for whole grain wheat and rye intake in numerous studies [23,28,29]
221
and the AR C17:0/C21:0 ratio has been suggested to be an indicator of relative rye intake
222
[10,30,31]. In the present study, the mean AR C17:0/C21:0 ratio went from 0.22 at week 0 to
223
0.34 at week 13 in the rye group and then decreased slightly, to 0.29, at week 26. Although the
224
AR C17:0/C21:0 ratio is approximately 1.0 in whole grain rye and 0.1 in whole grain wheat, in
225
fasting plasma samples the ratio is somewhat lower, around 0.6-0.8 in fasting samples after a
226
whole grain rye intervention for 1-8 weeks [31,32]. It is important to note that the AR
227
C17:0/C21:0 ratio is a marker of relative rye intake, not absolute intake, and the lower ratio in
228
the present study than in previous studies may be indicative of higher whole grain wheat intake
229
as other whole grain products than provided were not allowed in these studies. The ratio in a
230
Swedish population, where rye consumption is appreciable, was 0.5 in samples drawn 8 hours
231
since last meal [33]. The reason for lower ratio in plasma compared to what is observed in whole
232
grain rye foods is likely due to faster metabolism of the AR homologue C17:0 [34,35] and as the
233
absorption half-life of AR is about 6-8 hours and the half-life of AR in plasma is around 5 hours
234
[34], the time since last meal may influence the ratio. In a multicenter intervention with a healthy
235
Nordic diet, rich in whole grain oats, rye and barley, the ratio was comparable to the results of
236
the present study [10]. Ratio above 0.15 is usually indicating some rye intake [21].
237
The men in the rye group were generally pleased with the rye products and few felt
238
digestive discomfort. The rye intake tended to be higher for those who expressed discomfort
239
indicating that it might be difficult to increase rye consumption beyond 100 g/day in this
240
population. However, the participants seemed to adapt to the products, i.e. fewer felt discomfort
241
at week 26 than 13, more participants liked the products and more answered that they would
242
prefer rye products. The results of the acceptability in the present study is similar to the study by
243
Pereira et al [36] where 9 of 11 participants preferred whole grain diet after a crossover
244
controlled feeding trial with two 6-week feeding periods, whole grain (dietary fiber 28 g/day) vs.
245
refined grain (dietary fiber 17.8 g/day), with no difference between groups in recorded
246
indigestion. Landberg et al [9], also using crossover design with two 6 weeks feeding periods
247
but much higher amounts of whole grain rye (dietary fiber 67 g/day) reported greater drop-out,
248
with 7 of 24 participants not finishing the study because of constipation and 17 participants
249
reporting mild constipation. This indicates that some men may not tolerate such high intake of
250
dietary fiber, at least not without a longer adaption period.
251
While compliance to the dietary intervention was good, the participants did not increase
252
their PA during the intervention and no participant reached the recommended 10 000 steps/day.
253
Other measures for PA showed similar results. The main emphasis in the present study was on
254
the rye consumption and the lack of compliance to the PA advice may be due to the complexity
255
of achieving and maintaining simultaneous changes in both diet and PA. Previous studies have
256
reported that managing changes in multiple behaviors at the same time can be problematic
257
[15,16,18,37,38]. Studies have shown that the most effective PA interventions in diabetic
258
populations are those associated with a greater frequency of contact between the participants and
259
the counselor [39,40]. Thus, better support and monitoring may have been needed to improve the
260
PA in the present study. Pedometers are increasingly being used for self-monitoring and have
261
been shown to increase the number of daily steps taken by people with type 2 diabetes during a
262
16 week intervention although additional strategies are needed for long-term change. [41].
263
The majority of early studies investigating the effects of PA on type 2 diabetes have
264
incorporated structured exercise programs [42,43] but in recent years interventions aimed at
265
increasing PA using behavior change techniques have been increasingly implemented and
266
recommended [44,45]. The question of the best way to promote PA in this population is,
267
however, still unanswered. Even though the benefits of PA for type 2 diabetes are clear, the
268
majority of people with type 2 diabetes report they are inactive [15,18,19] and attempts to
269
become more active are often met with failure [46-48]. Diabetic patients have been found to be
270
even less ready to engage in PA and other self-care behaviors than patients with other chronic
271
conditions [49] and people with type 2 diabetes perceive the lowest belief in the effectiveness of
272
PA in diabetes management [46]. Thus, increasing PA in this population is challenging and this
273
issue needs to be addressed in the design of future studies.
274
The lack of compliance to the PA advice is a clear limitation to the present study, but at
275
the same time points to the urgent need to find effective means to encourage PA in diabetic
276
populations. Nevertheless, PA was not significantly different between groups during the
277
intervention which makes them comparable for evaluating the health effects of whole grain rye
278
consumption. The strengths of the present study are that the population studied had habitually
279
low intake of whole grain and fiber and the results are important for the design of future studies.
280
Additionally, a rye intervention in patients with type 2 diabetes has not been done before. Self-
281
reported dietary intake was used in conjunction with a dietary biomarker that gives an objective
282
measurement of compliance to rye intake. Previous studies have shown that total plasma AR can
283
be used as a dietary biomarker for whole grain wheat and rye intake [22,23,28,29] and the AR
284
C17:0/C21:0 ratio as an indicator of rye intake [10]. The use of dietary biomarker instead of, or
285
preferably in conjunction with, self-reported intake to measure compliance or investigate a diet-
286
disease relationship is an approach that should be further studied and utilized in future research.
287
288
Conclusion
289
The present feasibility study, carried out in an Icelandic population with habitual low whole
290
grain rye intake, produced valuable results that can be used to design a randomized trial aimed to
291
assess the health effects of high rye consumption. The low dropout-rate, good compliance and in
292
general good acceptability of the rye products showed that the intervention was well received by
293
the intervention group. However, poor compliance to prescribed PA in the intervention
294
emphasizes the need for improved methods to encourage PA in diabetic populations.
295
296
Acknowledgements
297
Authors express sincere gratitude to the participants taking part in the study. We thank Laufey
298
Hrólfsdóttir, Auður Benediktsdóttir and Tinna Eysteinsdóttir for help in planning and conducting
299
the intervention. The following companies provided food products for the study participants:
300
Heilsa Ltd, Myllan, Bernhöftsbakarí, Eggert Kristjánsson Ltd., Sölufélag garðyrkjumanna,
301
Íslenskt ameríska (Ísam), K. Karlsson and Sporthúsið.
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13. Juntunen KS, Laaksonen DE, Poutanen KS, Niskanen LK, Mykkanen HM (2003) High-fiber
rye bread and insulin secretion and sensitivity in healthy postmenopausal women. Am J
Clin Nutr 77: 385-391.
14. Boule NG, Haddad E, Kenny GP, Wells GA, Sigal RJ (2001) Effects of exercise on glycemic
control and body mass in type 2 diabetes mellitus: a meta-analysis of controlled clinical
trials. Jama 286: 1218-1227.
15. Zanuso S, Jimenez A, Pugliese G, Corigliano G, Balducci S (2010) Exercise for the
management of type 2 diabetes: a review of the evidence. Acta Diabetol 47: 15-22.
16. Thomas DE, Elliott EJ, Naughton GA (2006) Exercise for type 2 diabetes mellitus. Cochrane
Database Syst Rev: Cd002968.
17. Umpierre D, Ribeiro PA, Kramer CK, Leitao CB, Zucatti AT, et al. (2011) Physical activity
advice only or structured exercise training and association with HbA1c levels in type 2
diabetes: a systematic review and meta-analysis. Jama 305: 1790-1799.
18. Taylor R (2008) Pathogenesis of type 2 diabetes: tracing the reverse route from cure to cause.
Diabetologia 51: 1781-1789.
19. Michie S, Prestwich A (2010) Are interventions theory-based? Development of a theory
coding scheme. Health Psychol 29: 1-8.
20. The Icelandic Food Composition Database (ISGEM). Matís ohf.
21. Ross AB (2012) Present status and perspectives on the use of alkylresorcinols as biomarkers
of wholegrain wheat and rye intake. J Nutr Metab 2012: 462967.
22. Ross AB, Kamal-Eldin A, Aman P (2004) Dietary alkylresorcinols: absorption, bioactivities,
and possible use as biomarkers of whole-grain wheat- and rye-rich foods. Nutr Rev 62:
81-95.
23. Magnusdottir OK, Landberg R, Gunnarsdottir I, Cloetens L, Akesson B, et al. (2013) Plasma
alkylresorcinols reflect important whole-grain components of a healthy Nordic diet. J
Nutr 143: 1383-1390.
24. Landberg R, Åman P, Kamal-Eldin A (2009) A rapid gas chromatography-mass
spectrometry method for quantification of alkylresorcinols in human plasma. Anal
Biochem 385: 7-12.
25. Isaksson H, Sundberg B, Aman P, Fredriksson H, Olsson J (2008) Whole grain rye porridge
breakfast improves satiety compared to refined wheat bread breakfast. Food Nutr Res 52.
26. Isaksson H, Tillander I, Andersson R, Olsson J, Fredriksson H, et al. (2012) Whole grain rye
breakfast - sustained satiety during three weeks of regular consumption. Physiol Behav
105: 877-884.
27. Thorgeirsdottir H, Valgeirsdottir H, Gunnarsdottir I, Gisladottir E, Gunnarsdottir B, et al.
(2011) The Icelandic National Nutrition Survey 2011. Reykjavik: Icelandic Directorate of
Health, Icelandic Food and Veterinary Authority and Unit for Nutrition Research.
28. Ross AB, Bourgeois A, Macharia HN, Kochhar S, Jebb SA, et al. (2012) Plasma
alkylresorcinols as a biomarker of whole-grain food consumption in a large population:
results from the WHOLEheart Intervention Study. Am J Clin Nutr 95: 204-211.
29. Landberg R, Kamal-Eldin A, Andersson A, Vessby B, Aman P (2008) Alkylresorcinols as
biomarkers of whole-grain wheat and rye intake: plasma concentration and intake
estimated from dietary records. Am J Clin Nutr 87: 832-838.
30. Chen Y, Ross AB, Aman P, Kamal-Eldin A (2004) Alkylresorcinols as markers of whole
grain wheat and rye in cereal products. J Agric Food Chem 52: 8242-8246.
31. Linko-Parvinen AM, Landberg R, Tikkanen MJ, Adlercreutz H, Penalvo JL (2007)
Alkylresorcinols from whole-grain wheat and rye are transported in human plasma
lipoproteins. J Nutr 137: 1137-1142.
32. Landberg R, Aman P, Friberg LE, Vessby B, Adlercreutz H, et al. (2009) Dose response of
whole-grain biomarkers: alkylresorcinols in human plasma and their metabolites in urine
in relation to intake. Am J Clin Nutr 89: 290-296.
33. Landberg R, Aman P, Hallmans G, Johansson I (2013) Long-term reproducibility of plasma
alkylresorcinols as biomarkers of whole-grain wheat and rye intake within Northern
Sweden Health and Disease Study Cohort. Eur J Clin Nutr.
34. Landberg R, Linko AM, Kamal-Eldin A, Vessby B, Adlercreutz H, et al. (2006) Human
plasma kinetics and relative bioavailability of alkylresorcinols after intake of rye bran. J
Nutr 136: 2760-2765.
35. Marklund M, Stromberg EA, Hooker AC, Hammarlund-Udenaes M, Aman P, et al. (2013)
Chain Length of Dietary Alkylresorcinols Affects Their In Vivo Elimination Kinetics in
Rats. J Nutr.
36. Pereira MA, Jacobs DR, Jr., Pins JJ, Raatz SK, Gross MD, et al. (2002) Effect of whole
grains on insulin sensitivity in overweight hyperinsulinemic adults. Am J Clin Nutr 75:
848-855.
37. Snowling NJ, Hopkins WG (2006) Effects of different modes of exercise training on glucose
control and risk factors for complications in type 2 diabetic patients: a meta-analysis.
Diabetes Care 29: 2518-2527.
38. Kavookjian J, Berger BA, Grimley DM, Villaume WA, Anderson HM, et al. (2005) Patient
decision making: strategies for diabetes diet adherence intervention. Res Social Adm
Pharm 1: 389-407.
39. Greaves CJ, Sheppard KE, Abraham C, Hardeman W, Roden M, et al. (2011) Systematic
review of reviews of intervention components associated with increased effectiveness in
dietary and physical activity interventions. BMC Public Health 11: 119.
40. Keyserling TC, Samuel-Hodge CD, Ammerman AS, Ainsworth BE, Henriquez-Roldan CF,
et al. (2002) A randomized trial of an intervention to improve self-care behaviors of
African-American women with type 2 diabetes: impact on physical activity. Diabetes
Care 25: 1576-1583.
41. Tudor-Locke C, Bell RC, Myers AM, Harris SB, Ecclestone NA, et al. (2004) Controlled
outcome evaluation of the First Step Program: a daily physical activity intervention for
individuals with type II diabetes. Int J Obes Relat Metab Disord 28: 113-119.
42. Sevick MA, Dunn AL, Morrow MS, Marcus BH, Chen GJ, et al. (2000) Cost-effectiveness
of lifestyle and structured exercise interventions in sedentary adults: results of project
ACTIVE. Am J Prev Med 19: 1-8.
43. Hanefeld M, Fischer S, Schmechel H, Rothe G, Schulze J, et al. (1991) Diabetes Intervention
Study. Multi-intervention trial in newly diagnosed NIDDM. Diabetes Care 14: 308-317.
44. Avery L, Flynn D, van Wersch A, Sniehotta FF, Trenell MI (2012) Changing physical
activity behavior in type 2 diabetes: a systematic review and meta-analysis of behavioral
interventions. Diabetes Care 35: 2681-2689.
45. Kirk AF, Barnett J, Mutrie N (2007) Physical activity consultation for people with Type 2
diabetes: evidence and guidelines. Diabet Med 24: 809-816.
46. Wilson W, Ary DV, Biglan A, Glasgow RE, Toobert DJ, et al. (1986) Psychosocial
predictors of self-care behaviors (compliance) and glycemic control in non-insulindependent diabetes mellitus. Diabetes Care 9: 614-622.
47. Hays LM, Clark DO (1999) Correlates of physical activity in a sample of older adults with
type 2 diabetes. Diabetes Care 22: 706-712.
48. Krug LM, Haire-Joshu D, Heady SA (1991) Exercise habits and exercise relapse in persons
with non-insulin-dependent diabetes mellitus. Diabetes Educ 17: 185-188.
49. Boyle RG, O'Connor PJ, Pronk NP, Tan A (1998) Stages of change for physical activity,
diet, and smoking among HMO members with chronic conditions. Am J Health Promot
12: 170-175.
Figures
Figure 1. Outline of the study design and main outcome measurements at each visit
Rye consumption, g/day
RG
100
80
60
40
CG
20
Fiber consumption, g/day
b)
a) 120
0
Week 13
RG
30
25
20
CG
15
10
5
Week 26
Week 0
d)
100,0
RG
80,0
60,0
40,0
CG
20,0
0,0
Week 0
Week 13
AR C17:0/C21:0 ratio
Total plasma AR, nmol/L
35
0
Week 0
c)
40
Week 13
0,4
0,35
0,3
0,25
0,2
0,15
0,1
0,05
0
Week 26
Week 26
RG
CG
Week 0
Week 13
Week 26
Figure 2. Changes in a) rye consumption, b) total dietary fiber intake, c) total plasma
alkylresorcinols (AR) concentration and d) AR C17:0/C21:0 ratio for the rye group (RG) and the
control group (CG) from week 0 to 26 of the intervention.
a) 10
b) 10
13 w
26 w
6
4
13 w
26 w
26 w
2
agree
6
13 w
4
13 w 26 w
13 w
2
13 w
0
26 w
8
Participants, n
Participants, n
8
26 w
0
neither nor
disagree
agree
neither nor
disagree
Participants, n
c) 10
26 w
8
6
13 w
13 w
4
26 w
2
13 w
26 w
0
agree
neither nor
disagree
Figure 3. The rye group´s acceptability of the rye products (n = 12) assessed by three questions
at week 13 (13 w)and week 26 (26 w): a) I have experienced digestive after I started eating rye
products b) I like food products that contain rye and c) I would prefer products that contain rye
more than other products.
Tables
Table 1. Whole grain rye, energy, fiber, added sugar and salt content for the rye products
provided for the rye group in the study
Whole grain rye,
Energy,
g
kcal
g
g
g
Rye flakes (porridge)
100
335
11.7
0
<0.01
Rye bread 1
50
193
8.3
1.5
1.2
Rye bread 2
38
235
7.5
0.8
1.2
Rye bread 3
59
179
8.0
N/A
1.5
Rye bread 4
59
162
10.6
2.9
1.2
Rye crisp bread
94
360
19
0.9
<0.01
Data are presented as g or kcal per 100 g of product
Fiber, Sugar,
Salt,
Table 2. Baseline characteristics of the participants
Rye group
Control group
(n = 14)
(n = 9)
Age, years
57 ± 11
62 ± 11
Height, cm
178 ± 6
178 ± 8
Weight, kg
99.4 ± 11.8
93.5 ± 13.8
2
Body mass index, kg/m
31.5 ± 4.4
29.4 ± 3.0
Waist circumference, cm
114 ± 10
109 ± 8
Fat, %
32.9 ± 5.0
34.4 ± 3.5
Fat free mass, kg
65.7 ± 6.1
61.3 ± 9.3
136
±
12
Systolic blood pressure, mm Hg
136 ± 11
79 ± 8
Diastolic blood pressure, mm Hg
74 ± 5
1.5 ± 0.7
Triglycerides, mmol/L
1.6 ± 0.9
4.4 ± 1.2
Total cholesterol, mmol/L
4.5 ± 0.8
1.2
±
0.3
HDL cholesterol, mmol/L
1.2 ± 0.2
2.5 ± 1.1
LDL cholesterola), mmol/L
2.7 ± 0.7
Glucose 0 min, mmol/L
7.0 ± 1.4
6.8 ± 1.2
Insulin 0 min, mU/L
18.2 ± 14.0
12.2 ± 5.0
HOMA-IR
5.4 ± 3.3
3.8 ± 2.0
Marital statusb)
13 (93)
8 (89)
Married/in a relationship, n (%)
1 (7)
1 (11)
Divorced/widower, n (%)
b)
Education
Elementary school, n (%)
2 (14)
1 (11)
7 (50)
3 (33)
College, n (%)
4 (29)
4 (44)
University, n (%)
1 (7)
1 (11)
Other, n (%)
b)
Smoking status
7 (50)
2 (22)
Never, n (%)
6 (43)
6 (67)
Former, n (%)
1 (7)
1 (11)
Current, n (%)
b)
Medication
9 (64)
6 (67)
Blood pressure, n (%)
8 (57)
6 (67)
Lipid lowering, n (%)
7 (50)
3 (33)
Diabetes, n (%)
c)
Physical activity
Steps/day
3195 ± 988
4477 ± 2138*
Counts per minute (CPM)
347 ± 80
370 ± 138
Data are presented as mean ± standard deviation unless otherwise indicated
*
Significantly different from rye group
a)
n = 22, n = 14 in rye group and n = 8 in control group
b)
Data are presented as number (percentage)
c)
n = 21, n = 13 in rye group and n = 8 in control group
Table 3. Energy and macronutrient intake for rye and control groups at week 0, 13 and 26.
Rye group
Week 0
Energy, kcal
Week 13
Control group
Week 26
Week 0
Week 13
Week 26
2000 ± 534
2175 ± 629
1995 ± 631
2410 ± 325
2249 ± 655
2230 ± 578
Carbohydrates, E%
39 ± 5
39 ± 4
43 ± 5
43 ± 8
43 ± 9
38 ± 6
Dietary fiber, g/day
19 ± 10
33 ± 10
28 ± 7
18 ± 8
21 ± 9
15 ± 7
Added sugar, E%
6±2
6±2
5±3
8±7
7±7
5±4
Protein, E%
21 ± 5
21 ± 5
20 ± 4
19 ± 3
18 ± 2
17 ± 3
Fat, E%
34 ± 7
36 ± 5
37 ± 6
35 ± 8
38 ± 7
39 ± 6
Data are presented as mean ± standard deviation
Table 4. Physical activity for the rye and the control groups at the beginning and the end of the
intervention.
Rye group (n = 12)
Control group (n = 8)
Week 0
Week 26
Week 0
Week 26
3195 ± 988
3817 ± 1401
4347 ± 2514*
3970 ± 1076
347 ± 80
475 ± 137
370 ± 138
194 ± 90
Sedentary, %
71 ± 5
64 ± 4
69 ± 8
60 ± 7
Light activity, %
24 ± 5
29 ± 2
26 ± 5
33 ± 7
Moderate activity, %
4±2
7±3
4±3
6±2
Vigorous activity, %
0
0
0
1±0
Steps, steps/day
Counts per minute
Data are presented as mean ± standard deviation
*
Significantly different from rye group
Appendix
Instructions for the study groups and questionnaires
i
ii
Instructions for the healthy Nordic diet group in the SYSDIET study - ICELANDIC
LEIÐBEININGAR UM MATARÆÐI
Tilraunahópur
Helstu markmið næstu 6 mánaða (24 vikna) eru að:
 Auka neyslu grófra kornvara og heilkorns
 Auka neyslu ávaxta, grænmetis og berja
 Neyta 3 fiskmáltíða á viku: 2 máltíðir af feitum fisk og 1 máltíð af
mögrum fisk
 Auka neyslu jurtaolíu og viðbits með jurtaolíum
iii
GRÓFAR KORNVÖRUR
Brauð
Skiptið út brauðum sem þið eruð vön að borða fyrir eftirtalin gróf brauð
(≥6g trefjar/100g)
Dæmi:

Maltbrauð

Normalbrauð

Fitty brauð

Danskt rúgbrauð (t.d. frá Myllunni)

Flatkökur

Gróf súrdeigsbrauð úr rúgi

Ráðskonubrauð (frá Myllunni)

Seydd rúgbrauð (hámark 2 sneiðar á dag)
 Borðið ≥ 6 sneiðar af grófu brauði daglega (miðað við að hver sneið sé 30-35g).
 Skipta má 2 brauðsneiðum út fyrir 3 dl (~1 diskur) af hafragraut
Vinsamlegast merkjið við daglega neyslu grófra brauða í sérstökum spurningarlista
Pasta og hrísgrjón
Neytið a.m.k. 2-3 í viku grófs pasta og/eða hýðishrísgrjóna (≥6g trefjar/100g).
Vinsamlegast merkjið við vikulega neyslu pasta og hrísgrjóna í sérstökum spurningarlista
Almennt:
 Veljið kornvörur úr rúgi, byggi og höfrum umfram aðrar vörur.
 Veljið vörur sem innihalda lítið salt.
 Veljið ósætt morgunkorn, án viðbætts sykurs eða hunangs.
 Hafragrautur er hollur morgunmatur!
iv
ÁVEXTIR, GRÆNMETI OG BER
Borðið a.m.k. 500 g af ávöxtum, grænmeti og berjum á dag.
Skiptið neyslu milli berja, grænmetis og ávaxta á eftirfarandi hátt:
 Ber: Borðið a.m.k. 150-200g af berjum daglega (t.d. 1,5 dl af
aðalbláberjum + 3 tsk af berjadufti). Borðið aðalbláber helst daglega. Borðið einnig
jarðarber umfram aðrar tegundir.
Dæmi um aðrar tegundir berja (fersk eða frosin) sem hægt er að neyta eru bláber, rifsber,
krækiber, hindber, kirsuber, brómber, garðaber, ylliber og týtuber.
15-20 g (u.þ.b. 4,5 – 6 tsk) af berjadufti jafngilda því að borða 150 – 200 g af ferskum eða frosnum berjum.
Hægt er að nota berjaduftið út á t.d. mjólkurvörur og grauta
 Ávextir: Borðið a.m.k. 175g af ávöxtum daglega (dæmi: 1 epli og 1 mandarína). Endilega
borðið fjölbreytt úrval ávaxta t.d. epli, perur, appelsínur, mandarínur, banana o.s.frv.
 Grænmeti: Borðið a.m.k. 175g af grænmeti daglega (dæmi: 1 tómatur, 5 cm gúrkubiti og 1
dl blómkál). Endilega borðið fjölbreytt úrval grænmetis t.d. tómata, gúrku, salat, gulrætur,
lauk, sellerí, graslauk, blaðlauk, spergilkál, hvítkál, blómkál, rófur, dill, steinselju o.s.frv.
Athugið að kartöflur teljast ekki sem grænmeti!
Vinsamlegast merkjið við daglega neyslu berja, ávaxta og grænmetis í sérstökum spurningarlista
FISKUR
Neytið a.m.k. 3 fiskimáltíða á viku
 Þar af tvisvar feitan fisk (≥ 4-5% fita), t.d. lax, regnbogasilung, eldissilung,
hlýra, rauðmaga, síld, makríl, túnfisksteikur, stórlúðu.
 Þar af einu sinni magran fisk (< 4% fita), t.d. ýsu, þorsk, skötusel, steinbít, rauðsprettu, kola, saltfisk
(útvatnaður), humar, hörpudisk, keilu, kolmunna, rækjur, ufsa, vatnableikju.
v
KJÖT
Veljið magurt kjöt
 Fuglakjöt
 Lambakjöt (veljið magra hluta lambsins með ≤10% fitu)
 Villibráð
 Svínakjöt (veljð magra hluta með ≤10% fita)
 Nautakjöt (veljið magra hluta með ≤10% fita)
MJÓLK OG MJÓLKURVÖRUR
Vinsamlegast notið magrar mjólkurvörur.
Borðið a.m.k. 2 skammta af mjólk/mjólkurvörum daglega (1 skammtur = 2,5 dl af
drykkjarmjólk, 25g af osti, lítil dós af skyri eða jógúrt)
 Mjólk, súrmjólk, jógúrt/jógúrtdrykkir, skyr/skyrdrykkir sem er neytt á að vera með ≤1,4g af fitu
í 100g
Dæmi:
o
Undanrenna
o
Fjörmjólk
o
Skyr
o
Skyrdrykkir
o
Mysa
o
Létt ab mjólk
 Ostur þarf að innihalda ≤17g af fitu í hverjum 100g en einnig má nota jurtaosta.
Dæmi:
o
Gouda (11% eða 17% fita)
o
Fjörostur (9% fita)
o
Létt smurostar (6% fita)
o
Mysingur (8% fita)
o
Kotasæla (4,5% fita)
vi
FITA
 Repjuolía (rapeseed oil) á að vera notuð í allri matreiðslu.
 Nota á eingöngu Becel sem viðbit á brauð.
DRYKKIR
Vatn er besti svaladrykkurinn, neyta má kolsýrðs vatns að vild!
 Ekki á að neyta sykraðra gosdrykkja.
 Takmarkið neyslu gosdrykkja með sætuefnum við að hámarki 1-2 glös daglega.
 Takmarkið neyslu ávaxta og berjasafa við að hámarki 1,5 dl daglega.
HREYFING
Þar sem líkamsþyngd þín á að haldast stöðug út tímabilið ættirðu ekki að breyta neinu varðandi
venjubundna hreyfingu þína.
BÆTIEFNI
Takið inn eina töflu af D-vítamíni daglega.
vii
Instructions for the healthy Nordic diet group in the SYSDIET study - ENGLISH
DIET INSTRUCTIONS
Experimental diet
Main goals during the following six months are:
 to increase the use of whole grain cereal products
 to increase the use fruits, vegetables and berries
 to consume 3 fish meals per week (2 fatty fish and 1 low fat fish)
 to increase the use of vegetable oil and vegetable oil based spreads
WHOLE GRAIN CEREAL PRODUCTS
Breads
Replace all the breads in your habitual diet by test breads.
Test breads will be used _________ slices per day as follows:





Whole grain rye bread
Endosperm rye bread
xx
xx
xx
_______ slices per day
_______ slices per day
_______ slices per day
_______ slices per day
_______ slices per day
If you wish, you may substitute 2 slices of bread for 3,0 dl of whole grain porridge (e.g. made of
oat flakes).
Please mark the use of test breads daily for the separate questionnaire.
Pasta and rice
Consume whole grain pasta and unpolished rice (≥ 6 g fiber/100 g)
in 2-3 meals or more per week.
Please mark the use of pasta and rice weekly for the separate questionnaire.
viii

FRUITS, VEGETABLES AND BERRIES
o
Consume 500 g or more of fruits, berries and vegetables per
day.
o
Construct the amount as follows:

Berries (≥ 150-200 g/day = e.g. 1,5 dl of frozen bilberries + 3 tbsp of berry powder)
o variety of bilberries (e.g. whole berries, puree, extract), strawberries and one of the
following: blueberries, black and red currants, raspberries, cherries, blackberries,
gooseberries, elderberries, cloudberries, cowberries (wild)

Fruits (≥ 175 g/day = e.g. 1 apple + 1 mandarin)
o e.g. apples, pears, oranges, mandarins, bananas, quince

Vegetables (≥ 175 g/day = e.g. 1 tomato + 5 cm of cucumber + 1 dl of cauliflower)
o e.g. tomato, cucumber, lettuce, carrot, leak, onion, rhubarb, sweet beet, turnip, parsnip,
parsley, dill, radish, beetroot, chive, brassica [broccoli, Brussels sprout, cabbage (red and
white), cale, cauliflower, swede], celery root
o Please note that potatoes are not regarded as vegetable.
Please mark the use of fruits, vegetables and berries daily for the separate questionnaire.
FISH
Consume 3 fish meals per week (2 fatty fish meals
+ 1 low fat fish meal).
 Fatty fish: e.g. salmon, rainbow trout, Baltic herring,
vendace, trout, herring, mackerel, bream, mackerel, sardine,
brisling
 Low fat fish: e.g. whitefish, pike, cod, saithe, perch,
pikeperch, haddock, halibut, plaice
MEAT
Prefer low fat choices.
 e.g. poultry, lamb (lean products, ≤ 10 % of fat), game, pig (lean products, ≤ 10 %), beef
(lean products, ≤ 10 %)
ix
FATS
Rapeseed oil (brands) should be used in cooking and rapeseed and/or sunflower oil and/or
soyabean oil based margarines (brands) as spread.
MILK PRODUCTS
Please use low fat milk products minimum 2 portions daily.
(1 portion =2.5 dl of liquid milk products or 2 slices of cheese)
 milk, sour milk, yogurts, skyrs etc. (≤ 1 % of fat)
 cheese (≤ 17 % of fat) or vegetable oil based cheese
DRINKS
 Sugar-containing soft drinks should be avoided.
 Limit the use of fruit and berry juices for max. 1 glass (1.5 dl)/day
OTHER ASPECTS DURING THE STUDY
Please keep your exercise habits as before, since the aim is that your body weight remains stable during
the study.
x
Instructions for the control group in the SYSDIET study - ICELANDIC
LEIÐBEININGAR UM MATARÆÐI
Viðmiðunarhópur
Helstu markmið næstu 6 mánaða (24 vikna) eru að:
 Að nota kornafurðir með lágu trefjainnihaldi
 Að nota viðbit sem inniheldur mjólkurfitu (Smjör eða Smjörva)
 Borða í mesta lagi 200-250g af berjum, ávöxtum og grænmeti daglega
 Neyta 1 fiskmáltíðar á viku
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KORNVÖRUR
Brauð
Skiptið út brauðum sem þið eruð vön að borða fyrir brauð sem innihalda minna en 5-6g af
trefjum í 100g.
Dæmi:

Samlokubrauð, fín (t.d. Bónusbrauð, Heimilisbrauð o.s.frv.)

Franskbrauð

Snittubrauð

Sigtibrauð

Skonsur o.s.frv.
Vinsamlegast merkjið við daglega neyslu brauða í sérstökum spurningarlista
 Borðið brauðsneiðar daglega (miðað við að hver sneið sé 30-35g) og helst brauð úr fínmöluðu hveiti.
 Skipta má 2 brauðsneiðum út fyrir 3 dl (~1 diskur) af graut með lágt trefjainnihald (t.d.
hrísmjölsgraut).
Pasta og hrísgrjón
Notið hveiti pasta (fínt) og hvít hrísgrjón (sem innihalda minna en 5-6 g af trefjum í hverjum 100g).
Almennt:
 Veljið kornvörur úr fínunnu hveiti umfram aðrar vörur.
 Ekki neyta kornvara/brauðs sem innihalda heil korn
 Ekki neyta súrdeigsbrauðs sem er búið til úr rúgi
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ÁVEXTIR, GRÆNMETI OG BER
Dagleg neysla berja, ávaxta og grænmetis ætti ekki að fara yfir 200-250g.
Borðið í mesta lagi 50g (1 dl) af berjum daglega og 150-200g af ávöxtum/grænmeti.
 Vinsamlegast takið eftir að ekki á að neyta aðalbláberja á tímabilinu!
 Athugið að kartöflur teljast ekki sem grænmeti!
FISKUR
Fiskneysla á að takmarkast við í mesta lagi 1 máltíð á viku.
KJÖT
Neyta má alls kjöts og kjötvara að vild á tímabilinu.
MJÓLK OG MJÓLKURVÖRUR
Neyta má mjólkurvara að vild.
FITA
Notið viðbit með mjólkurfitum (t.d. íslenskt Smjör eða Smjörva) við alla matreiðslu og
matarundirbúning.
DRYKKIR
Neyta má allra drykkja að vild, þ.m.t. sykraðra gosdrykkja
HREYFING
Þar sem líkamsþyngd þín á að haldast stöðug út tímabilið ættirðu ekki að breyta neinu varðandi
venjubundna hreyfingu þína.
BÆTIEFNI
Takið inn eina töflu af D-vítamíni daglega.
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Instructions for the control group in the SYSDIET study - ENGLISH
Instructions for the control group in the SYSDIET study - ENGLISH
DIET INSTRUCTIONS
Control diet
Main goals during the following six months are:




to use low fiber cereal products
to use milk fat based spreads, butter is also allowed
to consume moderate amount of fruits, vegetables and berries
to limit the use of fish
CEREAL PRODUCTS
Breads
Replace all the breads in your habitual diet by test breads.
Test breads will be used _________ slices per day as follows:





Refined wheat bread
Wheat oat bread
xx
xx
xx
_______ slices per day
_______ slices per day
_______ slices per day
_______ slices per day
_______ slices per day
If you wish, you may substitute 2 slices of bread for 3,0 dl of porridge that is low in fiber (e.g.
rice or semolina).
Please mark the use of test breads daily for the separate questionnaire.
Pasta and rice
Prefer pasta and rice products that are low in fiber (≤ 5-6 g fiber/100 g)
xiv
FRUITS, VEGETABLES AND BERRIES
Consume maximum 50 g (1dl) of berries per day and maximum 150-200 g of fruits and
vegetables.
Please note that bilberries should NOT be used during the study.
FISH
Consume maximum 1 fish meal per week.
FATS
Use milk fat based spreads (brand) or butter on top of breads and in cooking and baking.
OTHER ASPECTS DURING THE STUDY
Please keep your exercise habits as before, since the aim is that your body weight remains stable during
the study.
xv
Background questionnaire in the SYSDIET study - ICELANDIC
Upplýsingar um bakgrunn þátttakenda
Númer þátttakanda________________
Svara skal upplýsingum um eigin bakgrunn á þetta eyðublað. Allar upplýsingar eru meðhöndlaðar sem
algjört trúnaðarmál.
Vinsamlegast svaraðu eftirfarandi spurningum með því að draga hring utan um það númer sem við á. Ef
þörf er á skaltu útskýra svarið nánar á tilheyrandi línum eða aftan á blaðið.
I) BAKGRUNNUR
1. Kyn
1) Karlkyn
2) Kvenkyn
2. Hver er hjúskaparstaða þín?
1) Gift/ur
2) Í sambúð
3) Einhleyp/ur
4) Fráskilin/n
5) Ekkja/ekkill
3. Hver er menntun þín?
1) Grunnskóli – hef lokið grunnskólaprófi
2) Verkmenntaskóli/iðnskóli – hef lokið verklegu prófi
3) Framhaldsskóli – hef lokið stúdentsprófi
4) Háskóli – hef lokið grunnnámi
5) Háskóli – hef lokið framhaldsnámi
6) Önnur menntun
4. Við hvað starfarðu (þ.e. aðal starfsvettvangur)?
1) Bóndi eða garðyrkjubóndi
2) Byggingavinna eða verksmiðjustarf
3) Skrifstofustarf, þjónustustarf eða önnur kyrrsetustörf
4) Í námi
5) Heimavinnandi
6) Öryrki eða ellilífeyrisþegi
7) Atvinnulaus
xvi
II) HEILSUFAR
5. Ertu almennt heilsuhraust/ur eða hvernig meturðu núverandi heilsu þína?
1) Góð heilsa
2) Í meðallagi
3) Slæm heilsa
6. Hefur læknir greint þig með eftirtalda sjúkdóma?
1. Kransæðastífla (hjartaáfall)
2. Kransæðasjúkdómar
3. Hjartabilun
4. Aðrir hjartakvillar
5. Hjartakveisa
6. Heilablóðfall
7. Helti (sem kemur og fer vegna hjartasjúkdóms)
8. Háþrýstingur
9. Sykursýki
10. Krabbamein
11. Nýrnabilun
12. Lifrarsjúkdómar
13. Tíðar þvagfærasýkingar
14. Gallsteinar
15. Liðagigt
16. Tíðir smitsjúkdóma
17. Astmi
18. Ofvirkur skjaldkirtill
19. Vanvirkur skjaldkirtill
20. Ristilbólgusjúkdómar
21. Glúteinóþol
22. Mjólkursykursóþol
23. Hægðatregða meðhöndluð með lyfjum
24. Annar langvinnur sjúkdómur
1)
1)
1)
1)
1)
1)
1)
1)
1)
1)
1)
1)
1)
1)
1)
1)
1)
1)
1)
1)
1)
1)
1)
1)
Já
Já
Já
Já
Já
Já
Já
Já
Já
Já
Já
Já
Já
Já
Já
Já
Já
Já
Já
Já
Já
Já
Já
Já
2)
2)
2)
2)
2)
2)
2)
2)
2)
2)
2)
2)
2)
2)
2)
2)
2)
2)
2)
2)
2)
2)
2)
2)
Nei
Nei
Nei
Nei
Nei
Nei
Nei
Nei
Nei
Nei
Nei
Nei
Nei
Nei
Nei
Nei
Nei
Nei
Nei
Nei
Nei
Nei
Nei
Nei
7. Tekurðu lyf að staðaldri?
1) Já
2) Nei
Ef já, vinsamlegast tilgreindu öll þau lyf sem þú tekur reglulega, þ.e. heiti lyfsins, tilgang
notkunar og skammtastærð:
_____________________________________________________________________
_____________________________________________________________________
xvii
8. Notar þú reglulega einhver fæðubótarefni, náttúruefni eða náttúrulyf án lyfseðils (s.s. vítamín,
steinefni og/eða lýsi) eða fæðuafurðir sem innihalda stanol eða stanolestera?
1) Já – vinsamlegast tilgreindu (tegund og skammtastærð)
_____________________________________________________________________
_____________________________________________________________________
2) Nei
III) LÍFSSTÍLL
9. Ertu á einhverju sérstöku mataræði (s.s. mjólkursykurfríu fæði, mjólkursykurskertu fæði, glúteinfríu
fæði, megrun, fæðuofnæmi)?
1) Já – vinsamlegast tilgreindu __________________________________________
2) Nei
10. Reykir þú?
1) Já, reglulega
2) Já, stöku sinnum
3) Ég er hætt/ur að reykja – hvenær?______________________________________
4) Ég hef aldrei reykt
11. Ef þú reykir daglega, hversu mikið reykirðu?
____________ sígarettur/dag
____________ píputóbak/dag
____________ vindla/dag
12. Hversu oft drekkurðu bjór, pilsner eða annað dauft áfengi?
0) Daglega
1) 3-5 sinnum í viku
2) 1-2 sinnum í viku
3) Nokkrum sinnum í mánuði
4) Einu sinni í mánuði eða sjaldnar
5) Ég drekk ekki dauft áfengi
13. Hversu mikið drekkurðu í einu af daufu áfengi (skrifaðu inn fjölda)?
__________ 0,33 l flöskur/dósir
__________ 0,5 l flöskur/dósir
xviii
14. Hversu oft drekkurðu rauðvín, hvítvín eða annað vín?
0) Daglega
1) 3-5 sinnum í viku
2) 1-2 sinnum í viku
3) Nokkrum sinnum í mánuði
4) Einu sinni í mánuði eða sjaldnar
5) Ég drekk ekki vín
15. Hversu mikið drekkurðu í einu af víni (skrifaðu inn fjölda)?
__________ glös
__________ flöskur
16. Hversu oft drekkurðu sterkt vín?
0) Daglega
1) 3-5 sinnum í viku
2) 1-2 sinnum í viku
3) Nokkrum sinnum í mánuði
4) Einu sinni í mánuði eða sjaldnar
5) Ég drekk ekki sterkt vín
17. Hversu mikið drekkurðu í einu af sterku víni (skrifaðu inn fjölda)?
__________ skammta/skot (4 cl)
__________ flöskur (0,5 l)
IV) HREYFING
18. Hversu líkamlega erfið er vinnan þín? Ef þú ert atvinnulaus, vinsamlegast merktu við fyrsta
valmöguleikann.
1) Aðallega skrifstofuvinna, ekki mikil ganga
2) Geng talsvert mikið en lyfti hvorki né ber þunga hluti
3) Geng mjög mikið og lyfti þungum hlutum eða geng mikið upp og niður stiga
4) Mjög líkamlega erfið vinna, lyfti eða ber mikið af þungum hlutum, moka o.þ.h.
19. Hvernig ferðastu á milli staða?
1) Með bíl eða strætó
2) Geng ____________ mín/dag
3) Hjóla_____________ mín/dag
xix
20. Stundarðu einhverja hreyfingu í frístundum þínum?
a) Garðyrkja, veiðar, berjatínsla o.þ.h.
1) 4 sinnum í viku eða oftar
2) 2-3 sinnum í viku
3) Einu sinni í viku
4) 2-3 sinnum í mánuði
5) Sjaldnar
b) Líkamleg áreynsla 30 mín í senn þannig að þú verðir móð/ur (ganga, hjóla, skokka, skíða
o.þ.h.):
1) 4 sinnum í viku eða oftar
2) 2-3 sinnum í viku
3) Einu sinni í viku
4) 2-3 sinnum í mánuði
5) Sjaldnar
xx
Background questionnaire in the SYSDIET study - ENGLISH
Backgound information form
CONFIDENTIAL
Number of the participant:________________________
The background information for the study is collected with this form. All information will be handled
with absolute confidentiality.
Kindly answer the following questions by circling the number of the suitable option. If needed, specify
the answer on the line or back of the paper.
I BACKGROUND
1. Gender
1 male
2 female
2. Marital status
1 Married
2 Domestic partnership
3 Unmarried
4 Judicial separation or divorced
5 Widower/Widow
3. What is your education?
1 Elementary or comprehensive school
2 Middle school
3 Vocational school/secondary modern school
4 Upper secondary school or senior high school
5 College-level training
6 Polytechnic or vocational high school
7 University
6 Other education, please specify______________________________________
4. What is your profession – what kind of work you do most of your time?
1 Farming, stock raising, forest work
2 Factory, mine or construction work
3 Office work, service trade, mental work
4 Studying
5 House wife or husband
6 Pensioner or senior citizen
7 Unemployed
xxi
II HEALTH STATUS
5. How do you see your health and well being at the moment?
1. good
2. average
3. poor
6. Has your physician diagnosed some of these diseases ?
1. Coronary thrombosis (myocardial infarction) 1. Yes 2. No
2. Coronary artery disease
1. Yes 2. No
3. Congestive heart failure/cardiac insufficiency 1. Yes 2. No
4. Other cardiac problem
1. Yes 2. No
5. Angina pectoris
1. Yes 2. No
6. Ischaemic attack
1. Yes 2. No
7. Intermittent claudication
1. Yes 2. No
8. Hypertension
1. Yes 2. No
9. Diabetes
1. Yes 2. No
10. Cancer
1. Yes 2. No
11. Renal failure
1. Yes 2. No
12. Hepatic disease
1. Yes 2. No
13. Frequent urinary tract infection/cytitis
1. Yes 2. No
14. Cholelithiasis
1. Yes 2. No
15. Rheumatoid arthritis
1. Yes 2. No
16. Frequent infectious diseases
1. Yes 2. No
17. Asthma bronchiale
1. Yes 2. No
18. Hyperthyroidism
1. Yes 2. No
19. Hypothyroidism
1. Yes 2. No
20. Inflammatory bowel disease
1. Yes 2. No
21. Celiac disease
1. Yes 2. No
22. Lactose intolerance
1. Yes 2. No
23. Constipation with medication
1. Yes 2. No
24. Other chronic disease
1. Yes 2. No
Please specify?_____________________________________
7. Do you have regular medication?
1 Yes
2 No
If so, please write here all the medication you use regularly: name, purpose of use and
dosage : ______________________________________________________________
_____________________________________________________________________
_____________________________________________________________________
_____________________________________________________________________
_____________________________________________________________________
xxii
8. Do you use regularly any nutritional supplements or natural products without description (vitamin
and/or mineral supplements, fish or vegetable oil supplements) or stanol- or sterol-ester-containing
food products ?
1 Yes, please specify (brand name, dosage/day)?
_____________________________________________________________________
_____________________________________________________________________
_____________________________________________________________________
2 No
III LIFESTYLE HABITS
9. Do you have a special diet (such as lactose free, low-lactose, gluten free, weight loosing, food allergy)?
1 Yes, please speficy___________________________________________________
2 No
10. Do you smoke?
1 Yes, regularly
2 Yes, occationally
3 I have ceased smoking, when ?__________________
4 I have never smoked
11. If you smoke daily, how many portions/ day?
____________ cigarettes/day
____________ pipe tobacco/day
____________ cigars/day
12. How often do you drink beer, cider, or other mild alcoholic beverages?
0 Daily
1 3-5 times/week
2 1-2 times/week
3 Twice/couple of times /month
4 Once a month or more seldom
5 I do not drink mild alcoholic beverages
13. How much do you drink mild alcoholic beverages at once ?
__________ 0,33 l bottles/ cans (strike out unnecessary option)
__________ 0,5 l bottles/ cans
14. How often do you drink wine?
0 Daily
1 3-5 times/week
2 1-2 times/week
3 Twice/couple of times /month
4 Once a month or more seldom
5 I do not drink wine
xxiii
15. How much do you drink wine at once?__________ glasses / bottles (strike out unnecessary option)
16. How often do you drink alcoholic spirits?
0 Daily
1 3-5 times/week
2 1-2 times/week
3 Twice/couple of times /month
4 Once a month or more seldom
5 I do not drink alcoholic spirits
17. How much do you drink alcoholic spirits at once?
__________ serving portions (4 cl) / 0,5 l bottles (strike out unnecessary option)
IV PHYSICAL EXERCISE
18. How physically demanding is your work? If you are unemployed, please choose the first option.
1 Mainly office work, not much walking
2 Walking quite a lot, but no raising or carrying of heavy objects
3 Very much walking and raising of objects, or climbing of stairs or uphills
4 Heavy physical work, including a lot of raising or carrying of heavy objects, digging,
shoveling, or deforesting
19. How do you commute?
1 By car or public transportation
2 Walking ____________ min/day
3 Cycling_____________ min/day
20. Do you do leisure time physical exercise?
Gardening, timbering, picking berries, fishing etc.:
1 4 times a week or more
2 2-3 times/week
3 Once a week
4 2-3 times/month
5 More seldom
Fitness training ½ hour at once so that you become breathless (walking, cycling, skiing,
jogging etc.):
1 4 times a week or more
2 2-3 times/week
3 Once a week
4 2-3 times/months
5 More seldom
xxiv
Instructions for rye group in the ARI feasibility study - ICELANDIC
Rúghópur
Helstu markmið næstu 6 mánaða eru:
 Að borða að minnsta kosti 100 g af heilkorna rúgi daglega
 Að öðru leyti borða samkvæmt ráðleggingum um mataræði sykursjúkra
 Að hreyfa þig rösklega þrisvar í viku, í að minnsta kosti 45 mínútur í senn, og að
ganga að minnsta kosti 10.000 skref aðra daga
Matur
Fundur með næringarráðgjafa í sal 9 í Sporthúsinu fimmtudaginn 18.apríl kl.20:00.
Makar eru velkomnir á fundinn!
Þú getur sótt brauð og aðrar rúgvörur þér að kostnaðarlausu, annan hvern miðvikudag frá kl 11 til 13 á
rannsóknarstöð RÍN í Kópavogi (við munum senda ykkur sms daginn áður til að minna á þennan tíma).
Einu sinni í mánuði verður líka grænmeti í boði.
Þú færð matardagbók til að halda utan um rúgneysluna. Við mælum með því að þið aukið rúgneysluna
rólega fyrstu dagana en séuð komnir í fullan skammt (100 g eða 10 punkta) á annarri viku. Mikilvægt er
að drekka vel samhliða aukinni trefjaneyslu.
Hreyfing
Nafn þitt hefur nú verið skráð í Sporthúsinu og þú getur gefið þig fram í afgreiðslu til að opna aðganginn.
Vilji maki þinn kaupa kort á afslætti í Sporthúsinu (4400 kr. á mánuði árskort) skaltu tala við Ríkharð
Óskar Guðnason, hann er með skrifstofu á móti afgreiðslunni í Sporthúsinu.
Þú getur nú farið á fund með sjúkraþjálfara í Sporthúsinu, þú átt tíma ____________________
Þá átt síðan tíma hjá honum Vali einkaþjálfara í Sporthúsinu ____________________
Við mælum með því að byrja rólega og auka svo smátt og smátt hreyfinguna. Sjúkraþjálfari og hann
Valur upp í Sporthúsi munu leiðbeina þér varðandi það hvaða álag hentar þér.
Þátttakendur munu fá skrefamæla til að fylgjast með hreyfingu sinni.
Næstu mælingar
Næstu skráningar í matardagbók og hreyfidagbók fara fram _______________
Mælingar í Kópavogi: ___________________
Ef einhverjar spurningar vakna ekki hika við að hafa samband í tölvupósti ([email protected] eða ) eða í síma 543-8420
eða 695-988.
xxv
Instructions for the control group in the ARI feasibility study - ICELANDIC
Hreyfihópur
Helstu markmið næstu 6 mánaða eru:
 Takmarka neyslu matvara sem innihalda rúg
 Að öðru leyti borða samkvæmt ráðleggingum um mataræði sykursjúkra?
 Að hreyfa þig rösklega þrisvar í viku, í að minnsta kosti 45 mínútur í senn, og að
ganga að minnsta kosti 10.000 skref aðra daga
Matur
Fundur með næringarráðgjafa í sal 9 í Sporthúsinu fimmtudaginn 18.apríl kl.20:00.
Makar eru velkomnir á fundinn!
Þú getur sótt heilhveitibrauð þér að kostnaðarlausu annan hvern miðvikudag frá kl 11 til 13 á
rannsóknarstöð RÍN í Kópavogi (við munum senda ykkur sms daginn áður til að minna á þennan tíma).
Einu sinni í mánuði verður líka grænmeti í boði.
Hreyfing
Nafn þitt hefur nú verið skráð í Sporthúsinu og þú getur gefið þig fram í afgreiðslu til að opna aðganginn.
Vilji maki þinn kaupa kort á afslætti í Sporthúsinu (4400 kr. á mánuði árskort) skaltu tala við Ríkharð
Óskar Guðnason, hann er með skrifstofu á móti afgreiðslunni í Sporthúsinu.
Þú getur nú farið á fund með sjúkraþjálfara í Sporthúsinu, þú átt tíma ____________________
Þá átt síðan tíma hjá honum Vali einkaþjálfara í Sporthúsinu ____________________
Við mælum með því að byrja rólega og auka svo smátt og smátt hreyfinguna. Sjúkraþjálfari og hann
Valur upp í Sporthúsi munu leiðbeina þér varðandi það hvaða álag hentar þér.
Þátttakendur munu fá skrefamæla til að fylgjast með hreyfingu sinni.
Næstu mælingar
Næstu skráningar í matardagbók og hreyfidagbók fara fram _______________
Mælingar í Kópavogi: ___________________
Ef einhverjar spurningar vakna ekki hika við að hafa samband í tölvupósti ([email protected]) eða í síma 543-8420 eða
695-988.
xxvi
Booklet for rye products in the ARI feasibility study - ICELANDIC
Númer þátttakanda: _____________
xxvii
Af hverju að velja helkorna rúg?
Þegar talað er um heilkorn er átt við þegar allir hlutar kornsins eru notaðir, hvort sem
kornið er notað í heilu lagi eða malað, og á það við um bygg, hafra, hveiti, rúgur, hirsi,
hrís og maís. Venjulegt hvítt hveiti er til dæmis ekki heilkornaafurð þar sem búið er að
fjarlægja „skelina/hýðið“ og kímið og þar með töluvert af hollustuefnum kornsins.
Heilkorn eru einstaklega holl þar sem þau innihalda alla hluta kornsins og því öll
hollustuefni þess (trefjar, prótein, vítamín og steinefni).
Skel: trefjaríkasti hlutinn, steinefni,
B-vítamín
Frækjarni: aðallega kolvetni og
sterkja
Kím: mikið af E- og B-vítamínum,
próteinum og öðrum hollefnum
Heilkorn eru mjög mettandi, sem þýðir að við borðum minna og eigum auðveldara með
að stjórna þyngdinni. Einnig eru trefjarnar sérstaklega góðar fyrir meltinguna.
Hollustuefnin í heilkorni geta einnig minnkað hættuna á að fá sykursýki, hjarta- og
æðasjúkdóma og ákveðnar tegundir krabbameins. Þó er ekki fullvitað hvaða efni það
eru í heilkorninu sem hafa þessi áhrif, eða jafnvel hvort það sé samspil milli ákveðinni
efna. Því er mikilvægt að neyta heilkorns, en ekki aðeins ákveðinnna hluta kornsins.
Sænskir samstarfsaðilar okkar hafa sýnt fram á að mataræði sem inniheldur mikinn rúg
og trefjar lækkar insúlínstyrk í blóði og blóðsykur helst stöðugri (hefur jákvæð áhrif á
blóðsykurstjórnun).
xxviii
Hvernig virkar stigakerfið?
Þátttakendur í íhlutunarhópi eru beðnir um að borða a.m.k. 100 g af rúgi á dag. Til að
auðvelda ykkur að fylgjast með og skrá niður rúgneysluna verður farið eftir stigakerfi,
þar sem hver rúgvara gefur ákveðið mörg stig
Stigakerfið er hugsað þannig að um 10g af rúgi gefi 1 stig. Í hverri viku eruð þið beðnir
um að neyta rúgvara sem gefa samtals um 70 stig, eða um 10 stigum að meðaltali á
dag. Hægt er að hliðra neyslunni aðeins til, t.d. borða sem samsvarar færri stigum einn
daginn, en þá verður að reyna bæta það upp með því að fá fleiri stig einhvern annan
dag. En heildarfjöldi stiga ætti ekki að fara undir 70 á viku.
Meðfylgjandi er listi af vörum sem innihalda heilkorna rúg og gefið upp hversu mörg stig
einn skammtur af vörunni gefur. Ef verið er að neyta annarra rúgvara en þeirra sem eru
á listanum, vinsamlegast hafið samband við rannsóknaraðila hægt sé að reikna út
hversu mörg stig hver skammtur gefur ykkur.
Við mælum með því að þið aukið rúgneysluna jafnt og þétt fyrstu tvær vikur
íhlutunarinnar, byrjið rólega en séuð komnir í fullan skammt (a.m.k. 100 g, eða 10
punkta á dag) í annarri viku. Gott er t.d. að byrja á tveim rúgbrauðsneiðum á dag og
bæta svo grautnum inn í vikunni þar á eftir. Þannig ætti meltingarkerfið að ná að aðlagst
breyttri neyslu og auknum trefjum. En alltaf er þó einhver möguleiki á því að þið finnið
fyrir óróa í maga og auknum vindgangi til að byrja með, það er alveg eðlilegt.
Ef spurningar vakna, endilega hafið samband (Óla Kallý Magnúsdóttir, sími 543 8422
([email protected]) eða Laufey Hrólfsdóttir, sími 695 9898 ([email protected]))
xxix
Heill rúgur
Heilan rúg má leggja í bleyti eða sjóða og nota meðal annars í bakstur og sem meðlæti
(svipað og bygg).
Stig
10g af ósoðnum rúgi gefa 1 stig
Rúgflögur
Rúgflögur minna einna helst á grófvalsaða hafra, en eru úr heilum rúgkjörnum, þær eru
þó heldur þéttari í sér. Rúgflögur má borða eins og haframjöl, með mjólk eða súrmjólk,
einnig er gott að bæta við kanil, rúsínum, eplabitum, múslí eða öðru þess háttar. Einnig
má sjóða flögurnar í graut (sjá skjal sem heitir uppskriftir).
Rúgflögurnar eru 100% heill rúgur og við mælum með því að borða rúgflögur
sem flesta daga, en það auðveldar að ná tilskildum stigafjölda yfir daginn. Fyrirtækið
Heilsa ehf. styrkir rannsóknina með því að sjá þátttakendum fyrir rúgflögum allt
rannsóknartímabilið.
Stig
10g ósoðnum rúgflögum gefa 1 stig
60g af ósoðnum rúgflögum (u.þ.b. 1½ dL) gefa 6 stig
100g af ósoðnum rúgflögum (u.þ.b. 2 ½ dL) gefa 10 stig
xxx
Rug Fras (Rúgkoddar)
Rug Fras er tegund af morgunkorni, sem svipar til Havrefras (Hafrakoddar). Í Rugfras
eru um 62% heilkorna rúgur. Rug Fras má t.d. borða sem hluta af morgunmat eða sem
millimál.
Stig
16g af Rugfras gefa 1 stig
50g af Rugfras (u.þ.b. 4 dL) gefa 3 stig
Rúgflakes (unnið morgunkorn)
Svipaðar kornflögum, nema innihalda heilkorna rúg ásamt öðrum korntegundum. Henta
vel sem hluti af morgunmat eða jafnvel sem millimáltíð.
Stig
20g af rugflakes (u.þ.b. 1 dL) gefa 1 stig
40g af rugflakes (u.þ.b. 2 dL) gefa 2 stig
Hrökkbrauð
Finn crisp, þetta klassíska þunna, inniheldur 94% heilkorna rúg.
Finn crisp, kringlótt, inniheldur 72% heilkorna rúg
xxxi
Wasa, hlutfall rúgs í mismunandi tegundum, ~90%
Burger, inniheldur 95% heilmalaðan rúg. Allar tegundir Burger hrökkbrauðs í lagi,
innihalda ~90% heilmalaðan rúg eða meira)
Ryvita dark rye, 95% heilmalaður rúgur
Hver hrökkbrauðssneið gefur 1 stig, nema Finn crisp þunnt – þá eru tvær sneiðar sem
gefa 1 stig.
xxxii
Rúgbrauð – Brauð sem innihalda heilkorna rúg
Brauð sem innihalda rúg ættu að koma við sögu á hverju degi. Munið að vigta
brauðsneiðarnar, alla vega í byrjun til að geta skráð réttan stigafjölda, ekki er verra að
skera brauðið nokkuð þykkt. Búið er að reikna út stig fyrir nokkrar algengar tegundir af
brauði eins og sjá má í listanum hér að neðan.
Myllan styrkir rannsóknina með brauðgjöfum og þátttakendur geta nálgast brauð
frá Myllunni hjá rannsóknaraðilum. Að sjálfsögðu má þó neyta annarra brauða en þeirra
sem verða sköffuð, en endilega hafið þá samband við rannsóknaraðila til að hægt sé að
reikna út hversu marga punkta ein sneið er að gefa ykkur. Mikið er til af góðum
innfluttum rúgbrauðum og auk þess er hægt að fá óseytt rúgbrauð í flestum
handverksbakaríum.
Mikill munur getur verið á rúginnihaldi brauða og þyngd brauðsneiða, því getur
verið mikill munur á því hversu mörg stig fást fyrir eina brauðsneið. Einnig verður að
hafa í huga að þó seytt rúgbrauð, þrumari og jöklabrauð innihaldi 40-45% rúg, þá
innihalda þessi brauð einnig hátt hlutfall af viðbættum sykri, eða kringum 20%
(20g/100g) og eru því ekki hentug sem aðaluppspretta rúgs.
Maltbrauð, inniheldur um 50% heilmalaðan rúg. Ein 40 g sneið gefur 2 stig. Inniheldur
auk þess 1,5g sykur. 8,3-8,8 g trefjar og 472mg natríum í 100g (jafngildir 1,2g af
matarsalt).
Danskt rúgbrauð, inniheldur 38% heilan/heilmalaðan rúg. Ein 40 g sneið gefur 1,5 stig.
Inniheldur auk þess 0,8g sykur, 7,5 g trefjar og 480mg natríum í 100g (jafngildir 1,2g af
matarsalti).
xxxiii
Ráðskonubrauð, inniheldur rúmlega 30% heilmalaðan rúg. Ein 40 g sneið gefur 1 stig.
Inniheldur auk þess 1,5g sykur, 6,2 g trefjar og 498mg natríum í 100g (jafngildir 1,2g af
matarsalti).
Lífskorn, inniheldur 25-27% heilmalaðan rúg. Ein 35 g sneið gefur 1 stig. Inniheldur
auk þess 0g sykur, 7-9g trefjar og 490mg natríum í 100g (jafngildir 1,2g af matarsalti).
Sólkjarnarúgbrauð, inniheldur um 24% heilan/heilmalaðan rúg. Ein 40 g sneið gefur 1
stig. Inniheldur auk þess 1,6g sykur, 6.9 g trefjar og 492mg natríum í 100g (jafngildir
1,2g af matarsalti).
Jöklabrauð, inniheldur um 45% heilmalaðan rúg. Ein 50 g sneið gefur 2,5 stig.
Inniheldur auk þess 21,5g sykur, 7,6 g trefjar og 565mg natríum í 100g (jafngildir 1,4g af
matarsalti).
xxxiv
Þrumari, inniheldur rúmlega 40% heilmalaðan rúg. Ein 50 g sneið gefur 2 stig.
Inniheldur auk þess 19,4g sykur, 7,3 g trefjar og 343mg natríum í 100g (jafngildir 0,9g af
matarsalti).
Seytt rúgbrauð, inniheldur rúmlega 40% heilmalaðan rúg. Ein 40 g sneið gefur 1,5 stig
(forskorið), ein 50 g sneið gefur 2 stig. Inniheldur auk þess 19,4g sykur, 7.3 g trefjar og
343 mg natríum í 100 g (jafngildir 0,9g af matarsalti).
Delba Sunflower seed bread, inniheldur 56% heilmalaðan rúg. Tvær litlar sneiðar
(62.5g) gefa 3,5 stig. Inniheldur auk þess 8,1 g af trefjum og 600 mg natríum í 100 g
(jafngildir 1.5g af matarsalti)
xxxv
Delba RYE BREAD, inniheldur 59% heilmalaðan rúg. Tvær litlar sneiðar (62.5g) gefa
3,5 stig. Inniheldur auk þess 8g af trefjum og 600 mg natríum í 100 g (jafngildir 1.5g af
matarsalti)
Delba 5 Grain Bread, inniheldur 48% heilmalaðan rúg. Tvær litlar sneiðar (62.5g) gefa
3 stig.
Mestemacher Wholemeal Rye Bread, inniheldur 59% heilmalaðan rúg. Ein 71g sneið
gefur 4 stig. Inniheldur auk þess 2.9g sykur, 10.6 g trefjar og 500 mg natríum í 100 g
(jafngildir 1.2g af matarsalti).
Brauð frá Bernhöftsbakarí, inniheldur um 44% heilmalaðan rúg. Tvær sneiðar (80g)
gefa 3,5 stig.
xxxvi
Biona Organic Rye bread, inniheldur 62% heilmalaðan rúg. Ein 71g sneið gefur 4,5
stig. Inniheldur auk þess 10.1 g trefjar og 1.13 g af salti í 100g.
Biona Organic Rye bread. Sunflower seed, inniheldur 57% heilmalaðan rúg. Ein 71
sneið gefur 4 stig. Inniheldur auk þess 9.7 g trefjar og 0.95 g af salti í 100g.
Biona Organic Rye bread. Amaranth / Quinoa. Inniheldur 54% heilmalaðan rúg. Ein
71 sneið gefur 4 stig. Inniheldur auk þess 10.1 g trefjar og 0.98 g salt í 100 g.
Finn Crisp Rye snack. Inniheldur 81% heilmalaðan rúg. 30 g gefa 2,5 stig. Inniheldur
auk þess 18 g trefjar og 700 mg natríum í 100 g (jafngildir 1,7 g af matarsalti)
xxxvii
Dæmi um hvernig skrá má í rúgdagbókina:
Dagur:____Mánudagurinn 4.mars 2013___________________
Vara
Hlutfall rúgs pr
100g af vöru
Stig á einingu
Hversu mikið
borðað
Hversu mörg
stig
Rúgflögur
100%
1 stig á 10g, t.d.
1dL=40g sem
gera 4 stig
1,5dL (í
morgungraut)
6
Heill rúgur
100%
1 stig á 10g af
ósoðnum rúg.
Ef soðinn þá 1
stig á 25g
Rugfras
62%
1 stig á 1 dL
Hrökkbrauð (Finn
Crisp þunnt)
94%
1 sneið 0,5
punktar
2 stk með kvöld
kaffinu
1
Hrökkbrauð (Finn
Crisp kringlótt)
72%
1 stig á sneið
Hrökkbrauð
Wasa/Burger
~90%
1 stig á sneið
50%
2 stig á sneið
2 sneiðar í
hádegismat
4
Hrökkbrauð
annað_________
Brauð:
maltbrauð
Brauð
_____________
Annað
_____________
Annað
_____________
Annað
_____________
Annað
_____________
Annað
_____________
Alls: 11 stig
xxxviii
Rúgdagbók
Dagur:_____________________________
Vara
Hlutfall rúgs pr
100g af vöru
Stig á einingu
Rúgflögur
100%
1 stig á 10g, t.d.
1dL=40g sem
gera 4 stig
Heill rúgur
100%
1 stig á 10g af
ósoðnum rúg.
Ef soðinn þá 1
stig á 25g
Rugfras
62%
1 stig á 1 dL
Hrökkbrauð (Finn
Crisp þunnt)
94%
1 sneið 0,5 stig
Hrökkbrauð (Finn
Crisp kringlótt)
72%
1 stig á sneið
Hrökkbrauð
Wasa/Burger
~90%
1 stig á sneið
Hversu mikið
borðað
Hversu mörg
stig
Hrökkbrauð
annað_________
Brauð
_____________
Brauð
_____________
Annað
_____________
Annað
_____________
Annað
_____________
Annað
_____________
Annað
_____________
xxxix
Food diary and instructions in the ARI feasibility study - ICELANDIC
Númer þátttakanda: _____________
Matardagbók
Rannsóknastofa í næringarfræði
xl
LEIÐBEININGAR FYRIR FÆÐUSKRÁNINGU
ALMENNAR UPPLÝSINGAR





Skráðu allt sem þú borðar og drekkur í 4 daga samfleytt, frá miðvikudegi til laugardags.
Skrifaðu í matardagbókina um leið og þú borðar svo ekkert gleymist.
Það á að vigta allan mat og drykk. Drykki má þó skrá í millilítrum (ml) eða desilítrum (dl)
ef fólk vill það frekar.
Reyndu að borða eins og venjulega og ekki láta fæðuskráninguna hafa áhrif á hvað þú
borðar.
Byrjaðu alltaf að skrá fyrstu máltíð (t.d. morgunmatinn) daginn sem skráningin hefst.
FÆÐUSKRÁNING
 Byrjið á nýrri blaðsíðu fyrir hvern dag og skrifið dagsetninguna efst á hvert blað (sjá dæmi á






næstu bls.)
Skrifið tímasetningu máltíða við hverja máltíð (fyrsti dálkurinn). Gott er að hafa eitt línubil á
milli máltíða hvers dags.
Skrifið bara eina fæðutegund í hverja línu (t.d. “þriggjakornabrauð” í eina línu og “Smyrja” í
næstu línu).
Lýsið mat, drykk og magni eins nákvæmlega og hægt er:
o Gefið upp tegund af matvælum (t.d. hvort þið notið undanrennu eða léttmjólk) og
jafnvel framleiðanda eða vörumerki matvælanna. Gefið upp fisktegund (skrifið t.d.
”soðin ýsa”) og kjöttegund (t.d. ”ungnautahakk 8-12% fita”) í stað þess að skrifa
einungis ”fiskur” eða ”kjöt”.
o Lýsið matreiðsluaðferðum, skrifið t.d. hvort kjötið var steikt, soðið eða grillað, hvort
grænmetið var hrátt, soðið eða niðursoðið og hvort ávextirnir voru borðaðir ferskir
eða niðursoðnir o.s.frv.
o Ef um er að ræða heimatilbúna blandaða rétti (t.d. pottrétti þar sem ekki er hægt að
vigta hvert matvæli beint á diskinn), þá er best ef grófleg uppskrift fylgir með (a.m.k.
hvaða hráefni voru notuð). T.d. ”Pottréttur: 2 msk repjuolía, 300 g nautakjöt (10%
fita), 1 laukur, tómatar í dós (stærð dósar), hvítlaukur og krydd.” Og fylla svo inn
hversu mikið var borðað af umræddum rétti.
Ef maturinn er ekki kláraður af diskinum, vigtið þá afganga og skráið hversu mikið var
afgangs.
Ekki gleyma að skrá alla drykki (einnig vatn), millibita og sælgæti.
Ef lýsi eða önnur bætiefni/fæðubótarefni/náttúruefni eru tekin inn skráið þau þá líka.
xli
DÆMI UM SKRÁNINGU MÁLTÍÐA
Dagssetning: Mánudagur 14.janúar
Kl.
7:30
10:15
Matur / drykkur (heiti, lýsing, vöruteg)
Skammtað
magn (g)
Magn
afgangs (g)
Magn sem
er neytt (g)
Hafragrautur
294
294
Undanrenna
120
Þriggjakornabrauð (muna að skrifa nafn
á bakaríi eða framleiðanda)
Smjör
37
37
5
5
Ostur, Gouda 17%
22
22
Epli
137
Kaffi
220
43
31
77
106
220
O.s.fr
v.
xlii
LEIÐBEININGAR FYRIR VIGTUN MATVÆLA OG DRYKKJA
NÚLLSTILLING: Til að fá þyngdina á hverri matartegund fyrir sig þarf að
núllstilla vogina á milli tegunda með því að ýta á ”reset” eða ”0” (mismunandi
eftir vogum).
Dæmi 1: Vigtun á brauði með viðbiti og osti
Best er að setja disk á vogina og núllstilla, setja síðan brauðsneiðina á diskinn og skrá
þyngdina á brauðinu. Vogin er núllstillt aftur með diskinn og brauðið á voginni, smyrjið
brauðsneiðina og þá sést þyngd viðbitsins á voginni. Núllstillið svo aftur áður en osturinn er
settur á brauðið til að geta skráð þyngd ostsins. Það getur verið erfitt að vigta eitthvað sem er
minna en 3 grömm á þennan hátt en í þeim tilvikum er hægt að skrifa ”< 3 g”.
Dæmi 2: Vigtun á kvöldmat (t.d. fiskur með kartöflum og grænmeti).
Diskurinn er settur á vogina og vogin núllstillt. Vigtið síðan hverja fæðutegund fyrir sig og
munið að núllstilla á milli. Setjið fiskinn á diskinn og skráið þyngd fisksins. Stillið aftur á núll
með diskinn og fiskinn enn á voginni. Kartöflurnar eru næst settar á diskinn og þyngdin skráð.
Stillt aftur á núll eins og áður. Setjið hverja grænmetistegund fyrir sig á vogina, vigtið og
núllstillið á milli. Ef forblandað salat er notað tilgreinið þá helstu hráefni í salatinu t.d. salatblöð,
gúrka, tómatar. Ef dressing er notuð núllstillið þá vogina áður en dressingunni er hellt yfir
salatið.
ATH! Ef ekki er klárað af disknum vigtið þá afganga eftir máltíðina og skráið það sem er
afgangs (t.d. bein í kjöti eða eplakjarni). Alla óæta hluta þarf að vigta eftir máltíðina og skrá
sem afgang.
Þegar fæðuskráningu er lokið skilið þá matardagbókinni og voginni í næstu
heimsókn.
Ef þið hafið einhverjar spurningar vinsamlega hafið samband við:
Auði Benediktsóttur í síma 543 8424 (tölvupóstfang [email protected]) eða
Laufeyju Hrólfsdóttur í síma 543 8420 (tölvupóstfang [email protected]) eða
Ólu Kallý Magnúsdóttur í síma 543 1452 (tölvupóstfang [email protected])
xliii
DAGUR 1 (___________________)
Dagssetning:
Kl.
Matur / drykkur (heiti, lýsing, vöruteg)
Skammtað
magn (g)
Magn afgangs
(g)
Magn sem er
neytt (g)
xliv
Background questionnaire in the ARI feasibility study
Númer þátttakanda: ___________
SPURNINGAR UM LÍFSSTÍL
Tóbaksnotkun
Já
Nei
Hefur þú einhvern tímann reykt sígarettur, vindla, vindlinga eða pípu daglega yfir eitt ár
eða lengur? (Ef nei, farið að spurningum um áfengisneyslu)
□
□
Reykir þú núna?
(Ef nei, farið á spurningu um fyrri reykingar)
□
□
Núverandi reykingar
Hversu margar sígarettur/vindla/vindlinga/pípur reykir þú að jafnaði á dag?
Sígarettur
stk
Vindlar
stk
Vindlingar
stk
Pípur
stk
Fyrri reykingar
ára
Á hvaða aldri byrjaðir þú að reykja?
Í hversu mörg ár reyktir þú/hefur þú reykt?
ár
Hvenær hættir þú að reykja (ef á við)?
ára
Tímabil þar sem ekki var reykt inn á milli?
Ef já, á hvaða aldri reyktir þú ekki?
frá
til
ára
frá
til
ára
frá
til
ára
Hversu margar sígarettur/vindla/vindlinga/pípur reyktir þú jafnaði á dag?
Sígarettur
stk
Vindlar
stk
Vindlingar
stk
Pípur
stk
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Áfengisnotkun
Hversu gamall varst þú þegar þú byrjaðir að neyta áfengra drykkja? (vinsamlegast merkið aðeins við einn
valmöguleika)
Aldrei
drukkið
Undir 14 ára
14-16 ára
17-18 ára
19-20 ára
21-25 ára
Eldri en 25 ára
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Núverandi áfengisneysla
Hversu oft neytirðu áfengra drykkja? (vinsamlegast merkið aðeins við einn valmöguleika)
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Ég drekk ekki áfengi
Minna en einu sinni í mánuði
1-3 sinnum í mánuði
1-2 sinnum í viku
3-4 sinnum í viku
5-6 sinnum í viku
Daglega
Þegar þú neytir áfengis, hversu mikið drekkur þú að jafnaði í hvert skipti? (Einn einfaldur drykkur jafngildir
t.d. einu léttvínsglasi, einum litlum bjór eða einföldum sterkum drykk).
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Einn drykk
2-3 drykki
4-5 drykki
6-7 drykki
8 drykki eða meira
Fyrri áfengisneysla
Hversu oft neyttir þú áfengra drykkja á eftirfarandi aldri? (Merkið við eins og við á, vinsamlegast merkið
aðeins við einn valmöguleika fyrir hvern aldur)
Tvítugur
Þrítugur
Fertugur
Fimmtugur
Sextugur
Drakk ekki áfengi
Minna en einu sinni í mánuði
1-3 sinnum í mánuði
1-2 sinnum í viku
3-4 sinnum í viku
5-6 sinnum í viku
Daglega
xlvi
Þegar þú neyttir áfengis, hversu mikið drakkst þú að jafnaði í hvert skipti?
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Einn drykk (einfaldur drykkur t.d.eitt vínglas, einn lítill bjór, eitt staup)
2-3 drykki
4-5 drykki
6-7 drykki
8 drykki eða meira
Heilsufarsupplýsingar
Ertu almennt heilsuhraustur?
Ef nei, hvaða heilsubrestir?______________________________________
Já
Nei
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Já
Nei
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Já
Nei
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Hvenær varst þú greindur með sykursýki eða
forsykursýki?______________________________________
Hefur einhver í fjölskyldu þinni verið greindur með sykursýki af gerð 2?
Ef já, hver/hverjir?______________________________________
Tekur þú núna einhver lyf(þ.m.t. náttúrulyf)?
Ef já, merkið við það sem við á
Hormónalyf (nafn lyfs____________________________________)
Bólgueyðandi lyf (nafn lyfs________________________________)
Blóðþrýstingslækkandi lyf (nafn lyfs__________________________)
Blóðfitulækkandi lyf (nafn lyfs______________________________)
Blóðþynningarlyf (nafn lyfs________________________________)
Ofnæmislyf (nafn lyfs____________________________________)
Lyf við sykursýki (nafn lyfs________________________________)
Sýklalyf (nafn lyfs_______________________________________)
Verkjalyf (nafn lyfs______________________________________)
Annað: ______________________________________________
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Menntun og staða
Hver er menntun þín?
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Grunnskólamenntun
Framhaldsskólamenntun
Iðnmenntun
Háskólamenntun (Ba, BSc, BEd)
Æðri háskólagráða (MSc, PhD)
Annað: ______________________
Hver er núverandi staða þín?
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Nemi
Launþegi
Sjálfstætt starfandi
Atvinnulaus
Öryrki
Ellilífeyrisþegi
Annað: ______________________
Hver er hjúskaparstaða þín?
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Einhleypur
Í sambandi
Í sambúð/giftur
Fráskilinn
Ekkjumaður
Annað: ______________________
Hverjir búa á heimilinu (auk þín)?
Maki
Börn yngri en 18
Börn eldri en 18
Aðrir: __________________________
Já
Nei
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Rúgneysla
Eftirfarandi spurningar eiga við upplifun þína af rúgneyslu síðastliðna þrjá mánuði
Mjög
sammála
Sammála
Hvorki
sammála né
ósammála
ósammála
Mjög
ósammála
Ég hef fundið fyrir óþægindum í meltingarfærum
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Mér finnst gott að borða vörur sem innihalda rúg
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Ég myndi kjósa vörur sem innihalda rúg fram yfir
vörur sem innihalda ekki rúg
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Hvernig hefur upplifun þín verið af rúgneyslu síðastliðna þrjá mánuði? Hvaða rúgvörur myndir
þú helst kjósa, (þ.e. rúgbrauð, rúggraut, rúghrökkbrauð, morgunkorn með rúgi) og hvaða vörur
eru sístar að þínu mati.
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