Download A. Keck, University of Illinois

Human Bioavailability Trials
with High Selenium Foods
Anna S. Keck1 and John W. Finley2
1 Dep.
of Food Sciences & Human Nutrition, University of Illinois, Urbana IL
2USDA/ARS, Grand Forks Human Nutrition Research Center, Grand Forks ND
Grand Forks,ND
November 4, 2004
Sources and Amounts of Selenium
 How much selenium is optimal?
 50-100 g Se/d sufficient to prevent deficiencies
(based on intake observations in areas where there
are no signs of deficiency)
 Selenium may provide cancer protective effects at
higher levels; ~150 -400 g Se/d
 Dietary sources of selenium:
 Meat, grains (wheat) & Brazil nuts
700
700
600
600
500
500
400
400
150
150
100
100
50
0
Keck et al., In Press
50
0
Selenium Toxicity
 High dosages of selenium can be toxic:
 a total intake of 1,000 g Se/d on a regular basis may lead to
toxicity (as reported in 1 Chinese village)
 Typical signs of selenium toxicity
 hair and nail loss
 brittle nails or hooves
 and GI-tract disturbances
 In the northern Great Plains of the US has the highest
selenium levels of the country:
 cattle and horses can develop "blind staggers," a debilitating
hoof disease caused by eating high-Se grains and Seaccumulator plants such as locoweed (Astragalus)
Selenium Accumulator Plants
 Crucifers that accumulate selenium include canola,
Brussels sprouts, Indian mustard & broccoli
 Other selenium-accumulator plants: garlic & onion
 Much of the selenium in accumulator plants is in the
form of selenium analogs of sulfur amino acids &
methylated seleno amino acids
Irion (1999), Med Hypotheses 53, 232-5
Kotrebai et al (2000) Analyst 125, 71-8
Does the Chemical Form
of Selenium Matter?
 Inorganic Salts
 Sodium selenite was used in the Keshan disease intervention study, given
as a 500 or 1,000 g tablet /wk
 Used in most lab animal studies
 Selenomethionine (SeMet) -Commonly found Se in food
 The amino acid methionine with Se substituted for the S
 Dominant form of selenium in high-Se yeast -used in the cancer
intervention studies
 Organic forms of selenium are less toxic than inorganic
forms
 Different selenium forms have different degrees of
bioavailability
Accumulation of Selenium in Tissues
-Plateauing (plasma & Testis)
1.5
A
Plasma
 Selenate
 Broccoli
 Beef
 Wheat
1.0
0.5
0.0
0
0.5
1
1.5
2
Dietary Selenium (ug/g)
Accumulation:
Se from beef >>Se from broccoli & wheat ~selenate
Keck et al., In Progress
Accumulation of Selenium in Tissues
-Non-Plateauing (liver, prostate, muscle, kidney, spleen)
1.5
C
Muscle
 Selenate
 Broccoli
 Beef
 Wheat
1.0
0.5
0.0
0
0.5
1
1.5
2
Dietary Selenium (ug/g)
Accumulation:
Se from beef >> Se from wheat & broccoli >> Selenate
Keck et al., In Progress
Accumulation of Selenium in Tissues
-Linear
Accumulation in Brain:
Se from beef >> Se from wheat & broccoli >> Selenate
0.6
Brain Se (ug/g)
0.5
0.4
0.3
0.2
0.1
0
0
0.5
1
1.5
2
 Selenate
 Broccoli
 Beef
 Wheat
Dietary Se (ug/g)
Keck et al., In Progress
Thioredoxin Reductase Activity
 Selenate
 Broccoli
 Beef
 Wheat
60
B
Colon
50
40
30
20
10
0
0
0.5
1
1.5
2
Dietary Selenium (ug/g)
Activation of Selenoprotein activity:
Se from broccoli & wheat >> Se from beef & Selenate
Keck et al., In Progress
Selenium in Foods
MEAT
WHEAT
NH3
COOH
NH3
Transulfuration
pathway
CH-CH2-CH2-Se-CH3
Selenomethionine
COOH
General proteins
MEAT
CH-CH2-SeH
Selenocysteine
Lyase
tRNA-C-C-COH
SELENATE SELENITE
SeO3
SeO4
GS-Se-SG
GSH
GSH
SeH2
O tRNA-serine
Lyase
NH3
H-Se-CH3
CH-CH2-Se-CH3
COOH
Se-methyl-selenocysteine
BROCCOLI
GARLIC
Lyase
CH3-Se-CH3
O
tRNA-selenocystein
BREATH
Lyase
CH3-Se-CH3
CH3
tRNA-C-C-C-SeH
URINE
Selenoprotein incorporation
GSH-Px (5)
deIodinase (3)
Selenoprotein p
Selenoprotein W
TR
Selenophosphate synthase 2
15kDa selenoprotein
18kDa selenoprotein
Human Selenium-Foods Trials
 1. Consumption of Se from Whole Wheat
Cereal by Se-Adequate Men, Grand Forks
Human Nutrition Center, USDA-ARS
 2. Consumption of Se from Broccoli by SeAdequate Men, Grand Forks Human Nutrition
Center, USDA-ARS
 3. Consumption of Se from High-Se Foods by
Se-Deficient Men, Xichang county, Sichuan
province, China
Criteria for Participating in the Human
Selenium-Food Trials at the GFHNRC





Male 18-45 years old
Healthy
Non-smoking
No prescription drug or supplement use
Willing to eat only food and drinks provided by
GFHNRC for ~16 weeks (Wheat study only)
Se-Wheat Trial:Consumption of Selenium Enriched
Whole Wheat Cereal by Selenium-Adequate Men
Dietary Treatments:
1.High Se-Wheat Cereal (Se-W)
Grown in South Dakota
2.Low Se-Wheat Cereal (W)
Both wheat cereals made by a food company
Design:
4 wk
100 g cereal/day
refined wheat
~56 g Se/d
12wk
100 g cereal/day
whole wheat
~56 or 306 g Se/d
Plasma Se (ng/ml)
Plasma Selenium
200
*
150
Selenium from
wheat increased
plasma selenium
by 42%
100
50
0
baseline
Se-Wheat
post
Wheat
GSH-Px (mUnits/min)
Glutathione Peroxidase Activity
in Red Blood Cells
60
50
40
30
Selenium
had no effect
20
10
0
baseline
Se-Wheat
post
Wheat
Non-Significant Data Collected





C-reactive protein
VLDL
Triglycerides
Catalase
SOD
Ongoing Analysis
DNA damage in WBC
Exercise –oxidative stress
Se-Broccoli Trial: Consumption of Selenium
Enriched Broccoli by Selenium-Adequate Men
Dietary Treatments:
– High Se Broccoli (Se-B, 27 or 270 g/Se)
– Low Se broccoli + sodium selenate (B+Se, 27 or 270 g/Se)
– Low Se Broccoli (B, 0.27 or 2.7 g/Se)
Design:
9 g for 6weeks
-Self selected diet
2 wk
washout
90 g for 6weeks
Plasma Selenium
160
Plasma Se(ng/mL)
*
120
Selenium from broccoli
increased plasma
selenium by 12 %
80
9
Amount (g)
Se-B
B+Se
90
B
Non-Significant Data Collected






C-reactive protein
VLDL
Triglycerides
ECSOD
T3, free T3
T4, free T4
Ongoing Analysis
DNA damage in WBC
Plasma Selenoprotein distribution
China study: Consumption of SeleniumFoods by Selenium Deficient Men
Dietary Treatments:
1.Low Se foods, 4.2 g Se/d (beef, wheat & broccoli)
2.High-Se broccoli,100 g Se/d (low beef & wheat)
3.High-Se wheat,100 g Se/d (low beef & broccoli)
4.High-Se beef,100 g Se/d (low broccoli & wheat)
Location: Xichang county
(Se-deficient region),
Sichuan province, China
60 healthy men (19-45 old,15/ grp)
Consumed 1 food package (~25g dry) daily for 3 months
Blood Selenium of Chinese Men Consuming 100
g Se/d as Broccoli, Wheat or Beef for 3 Months
160
*
120
*
Se (ng/mL)
*
*
80
All foods were equally
effective in increasing
blood selenium
concentrations
*
*
40
0
Conc
Change
Broccoli
Conc
Change
Conc
Wheat
Change
Beef
Conc
Change
Control
Treatments
*Significantly different
from control (p = 0.001)
Mean +/- Std error
Total Daily Urine Excretion of Selenium
b
60
b
Urine Se (g/day)
50
a
40
30
a
20
10
More selenium
from broccoli
and beef excreted
into urine
than from wheat
0
Pre
Post
Broccoli
Pre
Post
Wheat
Different letters indicate
significant differences (p<0.05)
Pre
Post
Beef
Pre
Post
Control
Mean +/- Std error
China study
 Data collection is finished
 Analysis ongoing
 Endpoints:
 Retention of stable isotope intrinsically incorporated
into food
 EEGs, (resting/evoked)
 cognitive testing
 Selenium status
 WBC COMET
Summary
 Selenium from wheat and beef accumulate more in
animal tissues than sodium selenate salt or selenium
from broccoli
 Selenium from wheat accumulates more in plasma
than selenium from broccoli in selenium-adequate
men (42% vs. 12%)
 In selenium-deficient humans, selenium from wheat,
beef and broccoli were equally effective in
accumulating in blood (2.1-2.5-fold) but more
selenium from broccoli and beef was excreted in the
urine than from selenium wheat
Acknowledgement
Grand Forks Human
Nutrition Research Center:
John W. Finley, PhD
Brian Gregoire
Taylor Jepson
Korry Hinze, PhD
Pete Leary
Kevin Miller, PhD
Karl Wald, PhD
Cindy Davis, PhD (at NCI)
Bonnie Hoverson and Kitchen staff
Sandy Gallager & Clinical/nurse staff
LuAnn Johnson
Emily Neilson
Fundings:
IFAFS-USDA, General Mills
National Institute of Nutrition
& Food Safety, Chinese Center
For Disease Control & Prevention
Junquan Gao, PhD
X. Li
Oregon State University:
Phil Whanger, PhD
University of Illinois:
Elizabeth H. Jeffery, PhD