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European Journal of Clinical Nutrition (2006) 60, 1145–1159
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REVIEW
Cereal grains and legumes in the prevention of
coronary heart disease and stroke: a review of the
literature
I Flight and P Clifton
CSIRO Human Nutrition, Adelaide, South Australia, Australia
A number of reviewers have examined studies investigating the relationship between coronary heart disease and stroke prior to
2000. Since then, several key studies have been published. Five studies have examined the relationship between wholegrain
consumption, coronary heart disease (CHD) and cardiovascular (CVD) disease and found protection for either or both diseases.
The researchers concluded that a relationship between wholegrain intake and CHD is seen with at least a 20% and perhaps a
40% reduction in risk for those who eat wholegrain food habitually vs those who eat them rarely. Notwithstanding the fact that
fibre is an important component of wholegrains, many studies have not shown an independent effect of fibre alone on CHD
events. Thus in terms of CHD prevention, fibre is best obtained from wholegrain sources. Wholegrain products have strong
antioxidant activity and contain phytoestrogens, but there is insufficient evidence to determine whether this is beneficial in CHD
prevention. Soluble fibre clearly lowers cholesterol to a small but significant degree and one would expect that this would
reduce CHD events. There have been a small number of epidemiological studies showing soy consumption is associated with
lower rates of heart disease. Countering the positive evidence for wholegrain and legume intake has been the Nurses Health
Study in 2000 that showed women who were overweight or obese consuming a high glycaemic load (GL) diet doubled their
relative risk of CHD compared with those consuming a low GL diet. Although the literature relating GL with CHD events is
somewhat mixed, the relationship with risk factors such as HDL cholesterol, triglyceride and C reactive protein is relatively clear.
Thus, carbohydrate-rich foods should be wholegrain and, if they are not, then the lowest glycaemic index (GI) product should
be used. Promotion of carbohydrate foods should be focused on wholegrain cereals because these have proven to be associated
with health benefits. There is insufficient evidence about whether the addition of other components of wholegrains such as
polyphenolics or minerals (such as magnesium or zinc) would improve the health benefits of refined grain foods and this needs
investigation. Whether adding bran to refined carbohydrate foods can improve the situation is also not clear, and it was found
that added bran lowered heart disease risk in men by 30%. This persisted after full adjustment (including GL) suggesting, at least
in men, that fibre may be more important than GI. Thus there are two messages:
(1) The intake of wholegrain foods clearly protects against heart disease and stroke but the exact mechanism is not clear. Fibre,
magnesium, folate and vitamins B6 and vitamin E may be important.
(2) The intake of high GI carbohydrates (from both grain and non-grain sources) in large amounts is associated with an increased risk of
heart disease in overweight and obese women even when fibre intake is high but this requires further confirmation in normalweight women.
Recommendation: Carbohydrate-rich foods should be wholegrain and if they are not, then the lowest GI product available should be
consumed. Glycemic index is largely irrelevant for foods that contain small amounts of carbohydrate per serve (such as most
vegetables).
European Journal of Clinical Nutrition (2006) 60, 1145–1159. doi:10.1038/sj.ejcn.1602435; published online 3 May 2006
Correspondence: Dr P Clifton, CSIRO Human Nutrition, Gate 13 Kintore
Avenue, (PO Box 10041, Adelaide BC), Adelaide, South Australia 5000,
Australia.
E-mail: [email protected]
Guarantor: P Clifton.
Contributors: PC initiated this review. IF searched the literature and wrote the
review, with significant input from PC. IF contributed her expertise in data
synthesis and PC contributed his nutritional and clinical expertise.
Received 9 May 2005; revised 19 December 2005; accepted 28 February
2006; published online 3 May 2006
Introduction
Grains (in particular wheat, maize, rice, barley, sorghum,
oats, rye and millet) and the foods made from them provide
more than 56 per cent of the energy and 50 per cent of the
protein consumed by humans worldwide (reported in
Cereal grains and legumes in the prevention of CHD and stroke: a review
I Flight and P Clifton
1146
Table 1 Selected components in wholegrains and their postulated mechanismsa
Component
Antioxidant
Dietary fibre
Oligosaccharides
Flavonoids
Inositols
Lignin
n-3 fatty acids
Phenolics
Phytates
Phytoestrogens
Protease inhibitors
Saponins
Selenium
Tocopherols
Zinc
O
O
O
O
O
O
O
O
O
Tumour
growth suppressor
Enzyme
modulator
Binding
scavenger
O
O
O
O
O
O
O
O
O
O
O
O
Chemical
inactivator
Lipid-lowering
Gut modifier
Hormonal
effects
O
O
O
O
O
O
O
O
O
a
Source: Slavin et al. (1999).
National Health and Medical Research Council, 2003).
Consumption of cereal grains forms the basis of a healthy
diet, and all current dietary guidelines have cereal foods as
the largest component of the recommended daily intake
(National Health and Medical Research Council, 2003).
Notwithstanding these guidelines, most adults do not
have enough grains in their diet. In Australia, the 1995
National Nutrition Survey found that even among those
adults with the highest intake, on the day of the survey only
34 per cent of men and 21 per cent of women met the
recommended seven servings a day (National Health and
Medical Research Council, 2003). In the US, the average
intake of wholegrains is less than one serving per day, and
less than 10 per cent of Americans consume three servings
per day (reported in Dietary Guidelines 2005 Advisory
Committee, 2004). As a result, Australian dietary guidelines
exhort adults to ‘eat plenty of cereals (including breads, rice,
pasta and noodles), preferably wholegrain (National Health
and Medical Research Council, 2003). Likewise, one of the
key recommendations of the United States 2005 Dietary
Guidelines is ‘Consume 3 or more ounce-equivalents of
wholegrain products per day, with the rest of the recommended grains coming from enriched or wholegrain products. In general, at least half the grains should come from
wholegrains’ (Dietary Guidelines 2005 Advisory Committee,
2004).
International attention is being directed towards efforts to
increase whole grain consumption, as exemplified by the
2005 Whole Grains and Health Global Summit (Marquart
and Jones, 2005) and the recent launch of the European
Union HEALTHGRAIN Integrated Project, aimed at ‘exploiting bioactivity of European cereal grains for improved
nutrition and health benefits’ (www.healthgrain.org).
Cereal grains are an excellent source of carbohydrate,
dietary fibre and protein. They are good sources of B-group
vitamins, vitamin E and a number of minerals, notably iron,
zinc, magnesium and phosphorus. Additionally, wholegrain
European Journal of Clinical Nutrition
foods contain a large number of identified phytochemicals,
such as phytoestrogens, antioxidants and phenolics, which,
together with vitamins and minerals, may be protective
against gastrointestinal cancers and cardiovascular disease
(Table 1). These components may act together in a
synergistic fashion (Slavin et al., 2001).
Milled wholegrains can be nutritionally superior to intact
wholegrains for human consumption because poorly digested compounds are removed during the milling process,
and nutrient bioavailability is enhanced (Slavin et al., 2000).
Food Standards Australia New Zealand has proposed a
definition of the term ‘wholegrain’ as ‘wholegrain means
the intact grain or the dehulled, ground, milled, cracked or
flaked grain where the constituents – endosperm, germ and
bran – are present in such proportions that represent the
typical ratio of those fractions occurring in the whole cereal,
and includes wholemeal’ (FSANZ (Food Standards Australia
New Zealand), 2004). Thus the distinction between intact
and milled grain is removed which is consistent with
epidemiological investigations that do not make this
distinction.
Refined grains, where the bran and germ have been
removed, have reduced nutrient content (Table 2) compared
to wholegrains because the milling process results in the loss,
to varying degrees, of dietary fibre, vitamins, minerals,
lignans, phytoestrogens, phenolic compounds and phytic
acid (Slavin, 2004). The starchy endosperm remaining after
milling is ground to produce refined white flour.
Earlier reviewers of the literature (pre-2000) concluded that
consumption of grains exerted a cardioprotective influence
(Anderson, 1995; Kushi et al., 1999; Slavin et al., 1999). This
report identifies reviews and studies published since 1999. We
carried out a search for studies and reviews of studies in
PubMed (www.ncbi.nlm.nih.gov/entrez/query.fcgi) using key
words relating to coronary heart disease (CHD), cardiovascular disease and stroke, combined with key words describing whole grains, cereal grains, dietary fibre, soy and
Cereal grains and legumes in the prevention of CHD and stroke: a review
I Flight and P Clifton
1147
Table 2
Compositional differences between whole and refined wheata
Component
Whole wheat
Refined wheat
Bran (%)
Germ (%)
Total dietary fibre (%)
Insoluble dietary fibre (%)
Soluble dietary fibre (%)
Protein (%)
Fat (%)
Starch and sugar (%)
Total minerals
14
2.5
13
11.5
1.1
14
2.7
70
1.8
o0.1
o0.1
3
1.9
1.0
14
1.4
83
0.6
Selected minerals
Zinc (mg/g)
Iron (mg/g)
Selenium (mg/g)
29
35
0.06
8
13
0.02
7.5
0.57
1.4
0.11
Selected vitamins
Vitamin B-6 (mg/g)
Folic acid (mg/g)
Phenolic compounds
Ferulic acid (mg/g)
b-tocotrienol (mg/g)
Phytate phosphorus (mg/g)
5
32.8
0.4
5.7
2.9
0.1
a
Source: Slavin et al., 1999.
legumes. A total of 53 reviews or studies for cereal grains and
heart disease risk factors in humans, five studies for stroke
and 12 studies for legumes and heart disease are included.
Wholegrains and CHD
Wholegrain consumption has been shown to be linked to
improvements in body mass index (BMI) (McKeown et al.,
2002; Steffen et al., 2003), insulin sensitivity (McKeown
et al., 2002; Liese et al., 2003; Steffen et al., 2003) and diabetes
(Venn and Mann, 2004), all of which are important risk
factors for heart disease. Consumption of wholegrains has
been shown to improve insulin sensitivity (Pereira et al.,
2002) although Juntunen et al. (2003) could not confirm
this.
Several reviews published since 1999 have concluded that
nutritional approaches to the prevention of CHD should
include the consumption of wholegrains (Anderson et al.,
2000; Richardson, 2000; McBurney, 2001; Slavin et al., 2001;
Anderson, 2002; Liu, 2002; Truswell, 2002; Anderson, 2003;
Hu, 2003; Slavin, 2004). The studies reviewed defined
wholegrain as either intact or milled grain with bran, germ
and endosperm in the same proportion as the unmilled
grain. Wholegrain foods were arbitrarily defined as those
foods with 425% by weight wholegrain or bran.
Anderson et al. (2000) carried out a meta-analysis of results
from three large prospective studies (Fraser et al., 1992; Jacobs
et al., 1998, 1999; Liu et al., 1999) which specifically
examined the relationship of risk of CHD to wholegrain
(Table 3). They concluded that persons in the highest,
compared to those in the lowest, quintile for wholegrain
intake had a 28% reduction in their risk for CHD (RR 0.72,
95% CI 0.49–0.94), a result which provides strong support for
the hypothesis that generous intakes of wholegrains are
cardioprotective. A subsequent update of this data (Anderson,
2003) included a fifth study (Liu et al., 2000a) which scarcely
altered the results (relative ratio (RR) 0.72, 95% CI
0.48–0.94).
The fact that the associations found in these studies
behaved in a dose–response manner and that the studies had
been controlled for other dietary and lifestyle factors,
including BMI, led Pereira and Liu (2003) to also conclude
that ‘y wholegrain foods, through their fibre, antioxidants,
and other components, reduce the risk of CHD in a causal
manner’.
Jensen et al. (2004) followed a cohort of 42 850 male health
professionals aged 40–75 years who were free from cardiovascular disease, cancer and diabetes at baseline in 1986.
Daily wholegrain intakes (grams per day) were derived from a
detailed and validated semiquantitative food frequency
questionnaire (FFQ). The participants were followed with
repeated questionnaires on lifestyle and health every 2 years
and with detailed FFQs every 4 years. During 14 years of
follow-up, 1818 incident cases of CHD occurred. After CHD
risk factors and intakes of bran and germ added to foods were
controlled for, the hazard ratio (HR) of CHD between lowest
and highest quintiles of wholegrain consumption (median
intake 3.5 vs 42.4 g/day) was 0.82 (95% CI 0.70–0.96; P for
trend ¼ 0.01). The authors acknowledge that a greater intake
of wholegrains was related to an overall healthier diet and
lifestyle. They performed stratified analyses to address
potential confounding by healthy participant characteristics
and found no discrepant results with respect to the main
finding of protection from heart disease with wholegrains in
subgroups including never smokers and non-drinkers.
A further review (Jacobs and Gallaher, 2004) has also
reported the results of more recent prospective studies of
wholegrain consumption (Table 3). The reviewers concluded
that a relationship between wholegrain intake and CHD is
seen with at least a 20% and perhaps a 40% reduction in risk
for those who eat wholegrain food habitually vs those who
eat them rarely.
Jacobs and Gallaher consider that, given the wide
variability in study designs, an estimated risk reduction of
20–40% is ‘impressively robust’. Study participants included
men and women; participants from the US (Liu et al., 2000a;
Bazzano et al., 2003; Liu et al., 2003; Mozaffarian et al., 2003;
Steffen et al., 2003) and Norway (Jacobs et al., 2001). The
cardio protective benefit is seen in the bulk of studies
involving middle-aged participants as well as in the single
study of the elderly (Mozaffarian et al., 2003). Findings,
which were consistently positive for wholegrains, occurred
using a variety of different data collection methodologies.
Studies described in Table 3 were conducted in cultural
European Journal of Clinical Nutrition
1148
Author
Participants
(no.)
Population sample
Outcome variable
Follow-up
(years)
Relative risk (95% CI)
Fraser et al. (1992)
31 208
US Seventh Day Adventists
CHD events
8
0.56 (0.35–0.89)
Jacobs et al. (1998)
34 492
CHD death
9
0.70 (0.50–0.98)
Jacobs et al. (1999)
38 740
Iowa sample from driving
licenses
Iowa sample from driving
licenses
CHD death
9
0.82 (0.66–1.01)
Liu et al. (1999)
75 521
US nurses
CHD events
10
0.72 (0.54–0.91)
Liu et al. (2000a)
75 521
US nurses
Ischaemic stroke
12
0.69 (0.50–0.98)
Jacobs et al. (2001)
33 848
CVD death
14
0.77 (0.60–0.98)
Liu et al. (2003)
86 190
Norwegians sampled in
three counties
US physicians
6
0.80 (0.66–0.97)
9
0.76 (0.64–0.90)
11
0.72 (CHD)
(0.53–0.97)
0.75 (stroke)
(0.46–1.22)
0.80 (0.63–1.01)
Mozaffarian et al.
(2003)b
Steffen et al. (2003)
Bazzano et al. (2003)
3588
11 940
9776
CVD death (MI and
stroke)
US residents aged 465 years CVD event
without CVD at baseline
US samples in four cities
CHD event,
ischaemic stroke
US population-based sample CHD event
19
Comments
For usual consumption of whole wheat rather than
white bread, inverse but not significant for CHD
death
For the highest vs lowest quintile of whole grain
intake
For those in the highest vs lowest quintile of whole
grain intake; similar reductions were seen for CHD,
stroke and other CVD deaths, although the finding
was weakest for stroke
For the highest vs lowest quintile of whole grain
intake
For ischaemic stroke in the highest vs lowest
quintile of wholegrain intake
Between high and low wholegrain break intake
scores
For men who ate wholegrain breakfast cereals
(4or ¼ 1 serving/day) compared to those who
rarely or never consumed whole grain cereal, with
reductions in CHD death but not stroke
For dark bread (specific comparison not specified);
breakfast cereals unrelated
For the highest vs lowest quintile of wholegrain
intake, although the findings for stroke did not
reach statistical significance; findings were similar
in black and white subjects
Unspecified risk reduction when data were
analysed by food source of cereal fibre, similar to
CHD risk reduction for cereal fibre (20% reduction
per 4.5 g cereal fibre per 1735 kcal/day)
Abbreviations: CHD, coronary heart disease; CVD, cardiovascular disease; MI, myocardial infarction; CI, confidence interval.
a
Adapted from Anderson (2002) and Jacobs and Gallaher (2004).
b
This is the only paper that studies and finds a protective effect of wholegrains in the elderly. Only dark bread was found to be protective, but the grain content of breakfast cereals was subject to considerable
misclassification.
Cereal grains and legumes in the prevention of CHD and stroke: a review
I Flight and P Clifton
European Journal of Clinical Nutrition
Table 3 Effect of wholegrain intake on CHD risk – prospective epidemiologic studiesa
Cereal grains and legumes in the prevention of CHD and stroke: a review
I Flight and P Clifton
1149
settings in which commercially available wholegrain wheat
and oat products predominated.
Summary
In conclusion, Jacobs and Gallaher and other reviewers find
that there is good evidence that wholegrain foods substantially reduce the risk of CHD. Whether all grains are equal in
this respect cannot be concluded from these studies, nor can
the effectiveness of different parts of the grain. Results from
Jensen et al. (2004) suggest that added bran may confer
additional benefits; clearly this proposition needs more
verification.
Whole grains and stroke
Liu et al. (2000a) examined the relationship of whole grain
intake and risk of ischaemic stroke in a 12-year follow-up of
the Nurses Health Study. The baseline population for
analysis consisted of 75 521 women between 38 and 63
years, without previous diagnosis of diabetes mellitus,
angina, myocardial infarction, stroke or other cardiovascular
diseases. Incident cases of stroke were confirmed by reviewing medical records and classified as ischaemic where the
stroke emanated from thrombotic or embolic occlusion of a
cerebral artery, resulting in infarction. Whole grain intake
was reported through a self-administered FFQ. During
861 900 years of follow-up, an inverse association between
whole grain intake and ischaemic stroke risk was observed;
the relative risk for ischaemic stroke in the highest quintile
(median intake 2.7 servings/day) was 0.69 (95% CI, 0.50–
0.98, P ¼ 0.04 for trend) relative to the lowest quintile
(median intake 0.13 servings/day), adjusted for other stroke
risk factors. No such inverse relationship was observed for
refined grain intake. The authors also examined the
possibility that specific constituents (folate, potassium,
magnesium, vitamin E and fibre) explained the protective
effect of whole grains. Adjustment for those components
attenuated the inverse relation of whole grain intake with
ischaemic stroke (RR, 0.76; 95% CI, 0.51–1.15, when
comparing the highest vs the lowest quintiles, P ¼ 0.38 for
trend). However, the inverse relation remained (even though
not statistically significant) suggesting that other constituents may confer additional protection. The authors acknowledge that their findings may not be generalizable to other
populations (98% of their cohort were white).
Steffen et al. (2003) did include more African American
men and women in their prospective study (10 and 16 per
cent, respectively). They followed 11 940 men and women
from four US cities, aged 45–64 years, over 11 years. Usual
dietary intakes were assessed using a FFQ at baseline and 6
years later. Overall, they found a beneficial effect of whole
grain on risks of total mortality and incident coronary artery
disease but not on the risk of ischaemic stroke, after
adjustment for potential confounders (RR, 0.75, 95% CI,
0.46–1.22 when comparing the highest vs the lowest
quintiles, P ¼ 0.15 for trend). It is noteworthy, however, that
this inverse result is not far removed from that found by Liu
et al. (2000a) as described above, albeit nonsignificant.
Steffen and coworkers highlight an important limitation of
their FFQ, which potentially misclassified whole-grained
consumption as refined-grain consumption, thereby creating the possibility for attenuation of the true HR.
Mozaffarian et al. (2003) followed 3588 men and women
aged 65 þ years at baseline for 8.6 years to determine the
association between fibre consumption from fruit, vegetables
and cereal sources and incident cerebrovascular disease
(CVD), defined as combined incident stroke, fatal and
nonfatal myocardial infarction, and CHD death. In secondary analyses, they found that higher cereal fibre intake was
associated with lower risk of total stroke (HR, 0.78, 95% CI,
0.64–0.95) and ischaemic stroke (HR, 0.76, 95% CI, 0.60–
0.95) when comparing the 80th percentile with the 20th
percentile.
Fung et al. (2004) examined the relationship between
stroke risks in women and overall dietary patterns, specifically a ‘prudent’ diet (characterized by higher intakes of
fruits, vegetables, whole grains, fish and poultry) and a
‘western’ diet (with higher intakes of red and processed
meats, refined grains, full-fat dairy products, desserts and
sweets). They followed 71 768 women aged between 38 and
63 years, without a history of CVD or diabetes at baseline, for
14 years. Dietary intake was ascertained by FFQ, which
assessed food intake during the previous year, from which
dietary pattern scores were calculated. After adjustment for
stroke risk factors, they found women in the highest quintile
of the Western pattern score had a relative risk of 1.58
(95% CI, 1.15–2.15, P ¼ 0.0002 for trend) for total strokes and
1.56 (95% CI, 1.05–2.33; P ¼ 0.02 for trend) for ischaemic
stroke when compared with the lowest quintiles. For the
prudent pattern, after adjustment, the RRs were 0.78
(95% CI, 0.61–1.01; P ¼ 0.13 for trend) for total stroke and
0.74 (95% CI, 0.54–1.02, P ¼ 0.13 for trend) for ischaemic
stroke.
Summary
There are few studies to date that specifically examine the
relationship between whole grain intakes and risk of stroke.
The studies described above have shown mixed results when
adjustment has been made for potential confounders.
However, the trends are strongly suggestive of a protective
effect of whole grain on risk of stroke.
Cereal fibre and CHD
A number of researchers have found that a higher intake of
cereal fibre is associated with a lower risk of CHD, although
results tend not to be statistically significant after adjusting
for multiple confounding factors (Anderson et al., 2000;
European Journal of Clinical Nutrition
Cereal grains and legumes in the prevention of CHD and stroke: a review
I Flight and P Clifton
1150
Truswell, 2002; Bazzano et al., 2003; Mozaffarian et al., 2003).
Pereira and associates (2004) pooled the results of nine
studies, yielding a total of 310 278 men and women who had
a total of 6959 CHD events, of which 1869 were deaths. With
cereal fibre fitted as a continuous variable, each 10 g/day
increment in cereal fibre had a nonsignificant relative risk of
0.90 for total CHD events and a significant relative risk of
0.75 for CHD deaths (Table 4). The associations appeared to
be independent of other dietary factors, sex, age, baseline
BMI, history of hypertension, diabetes and hypercholesterolaemia. The authors suggest that failure to reach significance
for total CHD events may be because of the limitations of
some FFQs to accurately quantify cereal fibre intake or to
small numbers of events in women.
Anderson et al. (2000) also performed a pooled analysis
that explored the relationship between wholegrains and
whole wheat bread, cereal fibre, total dietary fibre, fruits and
vegetables and risk for CHD. After adjustment for confounding factors, they found that the strongest inverse association
was between wholegrain and whole wheat bread intake and
risk of CHD. Cereal fibre by itself had the least influence on
CHD risk (RR 0.90; 95% CI, 0.80–1.01).
A similar finding was made by Mozaffarian et al. (2003).
After adjustment for potential confounders, the overall
reduction in cardiovascular disease risk from consumption
of cereal fibre was 14% (HR 0.86, 95% CI, .075–0.99) when
the 20th percentile of intake (o1.7 g/day) was compared
with the highest quintile (46.3 g/day). However, when post
hoc analyses were conducted to investigate whether the
observed lower cardiovascular disease risk was related to fibre
from any specific food group, it was found that the lower risk
appeared to be predominantly related to fibre intake from
dark breads such as whole wheat, rye or pumpernickel (i.e.
wholegrain intake) (HR 0.76; 95% CI 0.64–0.90). Other cereal
fibres had a nonsignificant influence (high fibre, bran or
granola cereals (HR 0.99; 95% CI 0.84–1.17), other cold
cereals (HR 0.98; 95% CI 0.94–1.02), cooked cereals (HR 1.01,
95% CI 0.92–1.11)). The authors did not state whether these
other cold or cooked cereal fibres were wholegrain or refined
grain products.
In contrast, Jensen et al. (2004) investigated the association between daily intake of wholegrains, additional bran
and germ and CHD risk in men in a cohort of 42 850 health
professionals. As described earlier, they found that men with
the highest intake of wholegrain had an 18% lower risk of
CHD than men in the lowest quintile. To ascertain whether
the effect of added bran and germ conferred even greater
benefits, the wholegrain content of all grain foods eaten was
determined, and bran or germ contained in those foods
measured as an amount that would typically be found in the
type of wholegrain. Wheat bran, corn bran, oat bran, rice
bran and wheat germ added to foods either during processing or by participants while cooking were considered to be
added bran and germ. They found that the HR of CHD in
men with the highest intake of added bran (median intake
11.10 g/day) was 0.70 (95% CI 0.60–0.82) compared with
Table 4 Study-specific and pooled multivariate risks of CHD per 10 g/day increments of cereal fibrea
Study
World Health Organization (1988)
Men
Women
Knekt et al. (1994)
Men
Women
Kushi et al. (1996) (women only)
Pietinen et al. (1996) (men only)
Rimm et al. (1996a) (men only)
Folsom et al. (1997)
Men
Women
Wolk et al. (1999) (women only, 1980 inception)
Wolk et al. (1999) (women only, 1986 inception)
Liu et al. (2002) (women only)
Total number of participants
Pooled (95% confidence intervals)
P-value for relative riskb
P-value for heterogeneityc
a
Baseline cohort
Person-years of follow-up
CHD events (RR)
CHD deaths (RR)
9521
10 555
39 230
43 872
0.83
3.52
0.54
—
2712
2481
24 599
23 643
0.95
0.75
0.82
0.44
30 180
21 141
41 574
294 620
121 813
383 206
—
1.02
0.77
0.49
0.94
0.68
5240
6481
45 861
58 199
0.68
1.95
0.90
—
81 415
61 706
37 272
31 0278
513 915
607 049
190 755
2 346 762
1.69
0.66
0.93
1.34
0.61
0.03
0.90 (0.77–1.07)
0.23
0.02
0.75 (0.63–0.91)
0.003
0.30
Adapted from Pereira et al. (2004). No 95% confidence intervals for relative risks were reported for individual study regression analyses.
Abbreviations: CHD, coronary heart disease; RR, relative risk.
P-value, test for no association.
C
P-value, test for between-studies heterogeneity.
The italicised values are a device to draw attention to the fact that they represent the pooled RRs of the individual study RRs, with 95% confidence intervals. In Pereira
et al’s (2004) paper (from which this table is adapted), this information was shown in bold-face type.
b
European Journal of Clinical Nutrition
Cereal grains and legumes in the prevention of CHD and stroke: a review
I Flight and P Clifton
1151
men with no intake of added bran (P for trend o0.001).
Thus, men with the highest intake of added bran had a 30%
lower risk of CHD than men who do not consume added
bran. Added germ was not associated with CHD risk
(although the intake of added germ was very low in this
population).
Bazzano et al. (2003) examined the relationship between
dietary fibre intake and risk of CHD and CVD in 9776 adults
who participated in the First National Health and Nutrition
Examination Survey (NHANES 1) Epidemiologic Follow-up
Study (NHEFS) conducted in the US. After adjusting for
‘healthy habits’ (regular exercise, not smoking, low dietary
intake of cholesterol and saturated fats), they found that
consumption of at least 4.5 g of cereal fibre per 1735 kcal was
associated with a nonsignificant 20% lower risk of CHD (RR
0.80, 95% CI, 0.63–1.01; P ¼ 0.06 for trend) and a nonsignificant 11% lower risk of death from CHD (RR, 0.89, 95%
CI, 0.76–1.02; P ¼ 0.10 for trend). A limitation of this study is
that dietary fibre was estimated using a single 24-h dietary
recall with no follow-up data collected, which may have
resulted in misclassification of usual dietary fibre intake
(there is no data to show which is the best instrument to
assess fibre intake).
Lairon et al. (2003) in France investigated the relationship
between dietary fibre intake and cardiovascular risk factors
in a subsample of 4080 people (2168 male, 1912 women; 45–
60 years at inclusion) drawn from the Supplementation en
Vitamines et Mineraux Antioxydants (SU.VI.MAX) study
population of 12 735 participants. This study was a randomized double-blind, placebo-controlled primary prevention
trial designed to test the efficacy of daily supplementation
with antioxidant vitamins and minerals at non-pharmacological doses in reducing cancers and cardiovascular diseases.
The study commenced in 1994 and followed subjects for 8
years. Total dietary fibre intake data were ascertained by
obtaining 12 different, validated 24-h dietary records from
each participant during the 4 years after inclusion in the
study. The dietary questionnaire came with instruction
manuals for coding foods, including photographs for selecting seven different portion sizes. A number of clinical and
biochemical indices were determined when participants
joined the study, and preliminary data on the association
of these indices with level and type of dietary fibre intake
was presented.
For men, a number of significant differences were found
between the participants in the highest and lowest quintiles
of total dietary fibre intake (426.3 vs o15.2 g/day). Cereal
fibre was most consistently associated with the studied
variables, and the highest intake was significantly associated
with a lower BMI, systolic blood pressure and plasma glucose
(P ¼ 0.05). For women, the only significant difference
between those participants with the highest vs the lowest
quintile of total dietary fibre intake (421.1 vs. o12.7 g/day)
was observed for a lower BMI in those with the highest
intake. For women, only vegetable fibre displayed an
association (Table 5). To date, detailed clinical data and the
Table 5 Comparison of clinical and biochemical indices for the highest
and lowest quintiles of dietary fibre intake for men and women
participating in the SU.VI.MAX studya
Variable
Gender
Difference (%) highest vs
lowest total dietary fibre
intake quintile
Fibre source
associationb
BMI
Men
Women
4.9
1.3
TDF, CF, FF VF
Systolic pressure
(mm Hg)
Men
3.8
TDF, CF
Women
2.2
Plasma cholesterol Men
Women
3.2
þ 0.1
Plasma
triacylglycerols
(mmol/l)
Plasma glucose
(mmol/l)
Men
16.2
Women
10.0
Men
5.2
Women
2.3
TDF
CF
Abbreviations: BMI, body mass index; CF, cereal fibre; FF, fruit fibre; TDF, total
dietary fibre; VF, vegetable fibre.
a
Source: (Lairon et al., 2003).
b
Comparison between 1st and 5th quintiles for CF, FF, TDF or VF, adjusted for
energy intake. The association of the fibre source indicated was significant
(Po0.05).
incidence of cardiovascular events in relation to fibre intake
from this study have not been published.
Ness et al. (2002) followed up a secondary prevention,
randomized controlled trial in South Wales, UK, conducted
by Burr et al. (1989). Between 1983 and 1987, Burr and coworkers allocated men under 70 years who had survived a
myocardial infarction to receive fibre advice or not (other
groups received fish advice/or not and fat advice/or not).
Participants were encouraged to eat at least six slices of
wholemeal bread per day, or an equivalent amount of cereal
fibre from a mixture of wholemeal bread, high-fibre breakfast
cereals and wheat bran. At 6 months, cereal fibre intake in
the fibre advice group was 19 and 9 g/day in those not given
fibre advice. At 2 years, fibre intake was 17 and 9 g/day,
respectively. After 2 years, the results were unclear, in that
total mortality increased (not statistically significant) in
those who were advised to eat more wholegrain. There were
a number of limitations to this study including compliance,
short follow-up and no objective check of fibre intake
(Truswell, 2002).
When Ness and co-workers followed up (between 1999 and
2000) the surviving participants from this cohort (n ¼ 443
who received fibre advice, n ¼ 436 who did not), they found
no differences in self-reported weight, current smoking,
medication use, aspirin use or dietary supplement use. At
follow-up, those allocated to receive fibre advice had a
significantly higher fibre intake, although the absolute
difference was small (6.2 (s.d. 5.4) vs 5.0 (4.4) g/day,
European Journal of Clinical Nutrition
Cereal grains and legumes in the prevention of CHD and stroke: a review
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1152
Table 6 Mortality from CHD in men who received advice to eat more
cereal fibre compared with those who did not in the Diet and
Reinfarction Trial (DART) 1983-2000a
Follow-up
period (years)
Number of CHD
deaths advice/no advice
0–2
2–5
5–10
10 þ
Overall
109/86
85/73
100/111
83/91
377/361
Adjusted
hazardb (CI)
1.35
1.27
0.96
0.94
1.11
(1.02,
(0.93,
(0.73,
(0.70,
(0.96,
1.80)
1.75)
1.26)
1.27)
1.29)
a
adapted from Ness et al. (2002).
Adjusted for history of myocardial infarction, angina, hypertension at
baseline, X-ray evidence of cardiomegaly, pulmonary congestion or pulmonary oedema at baseline, and treatment (at entry) with b-blockers, other
antihypertensives, digoxin/antiarrythmics, or anticoagulants.
Abbreviations: CHD, coronary heart disease; CI, confidence interval.
b
Po0.01). CHD mortality increased in those given fibre
advice in the first two follow-up time periods, as reported
in Burr et al.’s paper, but reduced in the later time
periods such that there was no long-term effect on survival
(Table 6).
In following up Burr et al.’s cohort, Ness and co-workers
acknowledge that dietary advice stopped after 2 years and
recent data were collected when around half of the original
participants had died. The researchers cannot discount the
possibility that the diets of those who survived are different
from those who did not. Follow-up diet was assessed with a
limited number of questions focused on fibre intake; questionnaire data were not collected on other aspects of current
diet and it is thus possible that important differences in diet
were not detected. The authors concluded that the failure of
longer term data to confirm the initial but nonsignificant
increased risk of CHD deaths in men who were given advice to
eat more cereal fibre suggested that increased fibre intake was
not harmful. The results do, however, suggest that increasing
cereal fibre intake by a small degree does not confer any
immediate survival advantage. It must be borne in mind,
however, that this was a secondary prevention trial of CHD, in
which the influence of environmental factors on the
pathological process is likely to be weaker than in a primary
prevention trial (Truswell, 2002).
Jacobs et al. (2000) argued that the potential health effects
of cereal fibre may depend on its source. They hypothesized
that the nutrients eaten with fibre (antioxidants and
minerals) play a role in protection against chronic disease
and that the results of studies of cereal fibre intake would
depend on the mix of fibre from wholegrain compared to
refined grain. They examined all-cause, CHD and cancer
mortality data from 11 040 participants participating in the
prospective Iowa Women’s Health Study. They compared
two groups of women, matched to consume B6 g/day of
total cereal fibre. One group (n ¼ 3559) consumed on average
77% of their cereal fibre from refined grain sources (o3.6 g/
2000 kcal of wholegrain fibre and X3.6 g/2000 kcal of refined
grain fibre). The second group (n ¼ 7481) consumed on
European Journal of Clinical Nutrition
average 71% of their grain fibre from wholegrain sources
(3.6–6.0 g/2000 kcal wholegrain fibre and o3.6 g/2000 kcal
refined grain fibre). This group was followed from baseline in
1986 to December 1997, during which time 1341 total
deaths occurred (274 from CHD; 247 with complete data
included in multivariate analysis). After adjusting for healthy
lifestyle characteristics, a multivariate regression showed
that women who consumed on average 1.9 g refined grain
fibre/2000 kcal and 4.7 g wholegrain fibre/2000 kcal had a
17% lower all-cause mortality rate (95% CI 0.73–0.94) and a
nonsignificant 11% lower CHD rate (95% CI 0.66–1.20) than
women who consumed predominantly refined grain fibre
(4.5 g/2000 kcal but only 1.3 g wholegrain fibre/2000 kcal).
Despite these findings reflecting statistically nonsignificant reductions for CHD deaths, the authors state that
women who were excluded from the matched design
because they consumed more than 6 g/2000 kcal of wholegrain fibre (generally accompanied by small amounts of
refined grain fibre) had statistically significantly reduced
total, CHD and all-cause mortality rates, compared to
women who ate little wholegrain fibre.
Jacobs and co-workers thereby demonstrated that a similar
amount of total cereal fibre had dissimilar associations with
total mortality, depending on whether the fibre came from
foods that contained primarily wholegrain or refined grain.
They suggested that consumption of the plant constituents
that are botanically linked to fibre may confer health
benefits above and beyond effects of the fibre itself.
These results highlight the emerging ‘wholegrain story’
(Anderson et al., 2000) which argues that health benefits
stem from more than just the fibre; the wholegrain is
nutritionally more important because it delivers a whole
package of nutrients and phytoprotective substances that
may work synergistically to promote health (Anderson et al.,
2000; Richardson, 2000; Jacobs and Steffen, 2003; Jacobs and
Gallaher, 2004; Slavin, 2004).
Summary
Thus although fibre is an important component of wholegrains, many studies have not shown an independent effect
of fibre alone on CHD events and/or deaths. Thus in terms of
CHD prevention, fibre is probably best obtained from
wholegrain sources.
Soluble fibre and CHD
There is little epidemiological data on the association
between soluble fibre and heart disease even though soluble
fibre clearly lowers serum cholesterol concentration and also
lowers glucose in diabetics. A cholesterol-lowering claim is
allowed for oat-derived beta glucan (rolled oats, oat bran,
whole oat flour, the soluble fraction of alpha-amylasehydrolysed oat bran or whole oat flour with a beta-glucan
content up to 10 percent) by the United States Food and
Drug Administration (USFDA, 1997).
Cereal grains and legumes in the prevention of CHD and stroke: a review
I Flight and P Clifton
1153
In a study of female health professionals, fibre was
associated with protection from heart disease (Liu et al.,
2002). The association with insoluble fibre was stronger than
for soluble fibre although neither separately was significant.
The association with total fibre was insignificant after full
adjustment.
In a secondary prevention study in men with angina, Burr
et al. (2003) found no effects of advice to increase fruit and
vegetables and oats on total or cardiovascular mortality
although compliance was not well assessed and, in the small
number of people actually assessed, it was low.
A meta analysis of 11 clinical intervention trials (Anderson
and Major, 2002) involving legumes (other than soy beans)
found overall a 6.2% lowering of LDL cholesterol and 22%
lowering of triglycerides. The hypocholesterolaemic effects
of legumes appear related, in estimated order of importance,
to soluble dietary fibre, vegetable protein, oligosaccharides,
isoflavones, phospholipids and fatty acids, and saponins.
Oat beta glucan may be ineffective at lowering serum
cholesterol concentration when baked into bread and
cookies. Jenkins et al. (2002b) confirmed that 4 servings/
day of beta glucan or psyllium delivering 8 g/day of soluble
fibre lowered total cholesterol by 2.1% which would have a
useful population rather than individual effect on heart
disease risk.
Conclusion
Soluble fibre clearly lowers cholesterol to a small and
significant degree and one would expect that this would
reduce CHD events.
Phenolic compounds, antioxidant activity and
disease
The primary phenols in cereals are flavonoids and phenolic
acids (Adom and Liu, 2002; Adom et al., 2003), which are
found predominantly in the bran (Slavin et al., 2000). Corn
had the highest total phenolic content (15.5570.60 mmol of
gallic acid equiv/g of grain) of the grains tested, followed by
wheat (7.9970.39), oats (6.5370.19) and rice (5.5670.17).
The major portion of phenolics in grains existed in the
bound form (85% in corn, 75% in oats and wheat and 62% in
rice). Ferulic acid was the major phenolic compound, with
free, soluble-conjugated and bound ferulic acids present in
the ratio of 0.1:1:100. Corn had the highest total antioxidant
activity (181.4270.86 mmol of vitamin C equiv/g of grain),
followed by wheat (76.7071.38), oats (74.6771.49) and rice
(55.7771.62).
Bound phytochemicals (mostly phenolics) were the major
contributors to the total antioxidant activity: 90% in wheat,
87% in corn, 71% in rice and 58% in oats. Bound
phytochemicals survived stomach and intestinal digestion
to reach the colon. This may partly explain the mechanism
by which grain consumption contributes to the prevention
of colon cancer and other digestive diseases. Wheat contains
a total flavonoid content of 105–142 mmol gallic acid
equivalents/100 g. Barley contains about 4–12 times as many
polyphenols per 100 g as red wine, which is similar to soy.
However, the amount of polyphenol per serve would be
quite similar.
Kris-Etherton et al. (2002) report that several population
studies have found an inverse association between flavonoid
intake and risk of coronary disease. In the Zutphen Elderly
Study, a high intake of flavonoids (around 30 mg/day from
tea, onions and apples predominantly) was associated with
approximately a 50% reduction in CHD mortality rate
compared with individuals who had a low flavonoid intake
(o19 mg/day) (Hertog et al., 1993). Rimm et al. (1996b) did
not find an association between new diagnosis of nonfatal
myocardial infarction in 496 participants and flavonol and
flavone intake. However, they did report a significant
association (RR ¼ 0.63) between flavonoid intake and subsequent coronary mortality in 4814 men with existing CHD.
For those studies that have reported an association,
putative mechanisms of action include inhibition of LDL
oxidation and inhibition of platelet aggregation and
adhesion. One measure of antioxidant activity is expressed
as Trolox or water-soluble vitamin E equivalents (TE). Miller
et al. (2000) analysed the antioxidant content of cereals,
fruit and vegetables and found that breakfast cereals are
equal or higher than any of the vegetables and the majority
of fruits. A 41 g average serving of ready-to-eat breakfast
cereal provided 1120 TE, while an 86 g average serving of
vegetables or fruits provided 380 and 1020 TE, respectively.
Wholegrain wheat- and oat-based products were on average
higher in antioxidants than products from refined rice
or corn ingredients. Even so, the rice and corn products
had a higher TE than nearly all vegetables and a majority
of fruits.
Using a different analytical method, Halvorsen et al. (2002)
in Norway analysed the antioxidant content of cereals, fruits
and vegetables and found that wholemeal flours of barley,
common millet and oats contained the highest levels of
antioxidants among the cereals. White flour contained
between 23 and 54% of the antioxidant content of the
wholemeal variants of the various cereals. Wholemeal wheat
flour had a greater mean antioxidant concentration
(0.33 mmol/100 g) than apples, bananas, pears, melon and
watermelon, but less than grapes (1.45 mmol/100 g), oranges,
plums, pineapples, lemons and apricots (among other fruits).
Among vegetables, wholemeal wheat flour had a greater
antioxidant concentration than garlic, cabbage and squash
but less than chilli pepper (2.46 mmol/100 g), red cabbage,
spinach, onion and broccoli (among other vegetables).
Conclusion
Wholemeal grain products have strong antioxidant activity.
Whether this is beneficial in CHD prevention is not known.
European Journal of Clinical Nutrition
Cereal grains and legumes in the prevention of CHD and stroke: a review
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Unsaturated fatty acids and wholegrains
Wholegrains as part of a prudent diet
Wholegrain wheat contains about 3% lipids and wholegrain
oats around 7.5%, of which there are approximately equal
amounts of oleic and linoleic acid and 0.1–0.2% linolenic
acid. Oleic acid and linoleic acid are associated with lowering
total cholesterol and LDL-cholesterol (McPherson and
Spiller, 1995) but the amount in cereals would be unlikely
to alter plasma lipids.
An emerging trend in dietary analysis is to consider the
whole dietary pattern, rather than the effect of individual
nutrients or foods, on health (Hu, 2002). This approach is
considered to more closely approximate the ‘real world’,
where people eat meals consisting of a variety of foods,
rather than isolated nutrients. Thus, complicated interactions among nutrients and non-nutrient substances can be
taken into account.
Hu (2003) reported on two cohort studies – the Nurses’
Health Study (Fung et al., 2001b) and the Health Professionals’ Follow-up Study (Hu et al., 2000). Factor analysis was
used to examine associations between major eating patterns
and risk of CHD. Diet was identified as a ‘prudent’ pattern
(higher intakes of fruit, vegetables, legumes, fish, poultry
and wholegrains) or a ‘Western’ pattern (higher intakes of
red and processed meats, sweets and desserts, French fries
and refined grains).
In the Nurses’ Health Study, after coronary risk factors
were adjusted for, the prudent diet score was associated with
an RR of 0.76 (95% CI, 0.60–0.98; P for trend ¼ 0.03)
comparing the highest with the lowest quintile. The same
quintile comparison yielded an RR of 1.46 (95% CI 1.07–
1.99; P for trend ¼ 0.02) for the Western pattern.
Similar associations were found in the Health Professionals’ Follow-up Study. After adjusting for confounders,
the RRs from the lowest to highest quintiles of the prudent
pattern score were 1.0, 0.87, 0.79, 0.75 and 0.70 (95% CI,
0.56–0.86; P for trend o0.0001). In contrast, the RRs across
the same quintiles of the Western pattern score were 1.0,
1.21, 1.36, 1.40, 1.64 (95% CI 1.24–2.17; P for trend
o0.0001).
Fung et al. (2001a) also examined the relation between
major eating patterns and biochemical markers of coronary
artery disease and obesity. They observed inverse correlations
between the prudent pattern score and both fasting insulin
(0.25, Po0.05) and homocysteine (0.20, Po0.01); a
positive correlation was observed with folate (0.28,
Po0.0001).
Phytoestrogens and wholegrains
Phytoestrogens are divided into three classes: isoflavonones,
coumestans and lignans. The isoflavones, genistein and
daidzein, are found predominantly in soybeans. The primary
source of dietary lignans is flaxseed oil, but it is also found in
varying concentrations in soybeans, seaweed, wholegrains
(particularly rye), fruits and vegetables (Kris-Etherton et al.,
2002). Eating wholemeal rye bread at least doubles serum
and urine enterolactone concentrations compared with
white wheat bread (Juntunen et al., 2000).
In a Finnish cross-sectional, 24-h dietary recall survey of
2852 men and women aged 25–64 years, lignan intake was
positively associated with serum enterolactone concentrations. The mean serum enterolactone concentration in the
highest quintile of lignan intake was 50% higher than in the
lowest quintile (Po0.001) (Kilkkinen et al., 2003).
Jacobs et al. (2002) conducted a crossover feeding study in
which 11 overweight, non-diabetic men and women ate, in
random order, wholegrain foods or refined grain foods. Serum
enterolactone concentrations were higher when eating the
wholegrain diet than with the refined grain diet by 6.2
(within person s.e. 1.7) nmol/l (P ¼ 0.0008). Plasma enterolactone concentrations were inversely related to plasma F2
isoprostane – an oxidized lipid believed to be a good marker of
oxidative stress and defence (Vanharanta et al., 2002).
In the Kuopio Ischaemic Heart Disease Risk Factor Study,
multivariate analyses showed significant associations between elevated serum enterolactone concentration and
reduced risk of CHD- and CVD-related mortality, but weaker
associations in relation to all-cause mortality. In the 1889
men aged 42–60 years, followed for an average of 12.2 years,
70 CHD-related, 103 CVD-related, and 242 all-cause deaths
occurred in participants free of prior CVD. In the Cox
proportional hazards regression model adjusting for the
most potent confounding factors, the risk of CHD-related
(P ¼ 0.03 for trend) and CVD-related (P ¼ 0.04 for trend)
death decreased linearly across quartiles of serum enterolactone concentration (Vanharanta et al., 2003).
Conclusion
Wholegrains, particularly from rye, contain phytoestrogens
but whether this is beneficial for CHD prevention is not yet
clear.
European Journal of Clinical Nutrition
Conclusion
Wholegrains are a source of valuable nutrients (Table 1). It is
clear that wholegrains are protective in relation to CHD,
whereas refined grains may have an adverse effect, although
the data for the latter is not as consistent.
Legumes
In a study of the 9632 men and women who participated in
the First National Health and Nutrition Examination Survey
(NHANES 1) Epidemiologic Follow-up Study (NHEFS) and
who were free of cardiovascular disease at their baseline
examination, Bazzano et al. (2001) found that legume
Cereal grains and legumes in the prevention of CHD and stroke: a review
I Flight and P Clifton
1155
consumption was significantly and inversely associated with
risk of CHD (P ¼ 0.002 for trend) and CVD (P ¼ 0.02 for
trend) after adjustment for established CVD risk factors. Over
an average of 19 years of follow-up, 1802 incident cases of
CHD and 3680 incident cases of CVD were found. Legume
consumption four times or more per week, compared with
less than once a week, was associated with a 22% lower risk
of CHD (relative risk, 0.78; 95% CI, 0.68–0.90) and an 11%
lower risk of CVD (relative risk, 0.89; 95% CI 0.80–0.98).
Frequency of legume intake was estimated using a 3-month
FFQ; participants were asked how often ‘dry beans and peas
like pinto beans, red beans, black-eye [sic] peas, peanuts and
peanut butter’ were usually consumed in the past 3 months
excluding periods of illness or dieting. Information on
portion size was not collected.
In an ecological study relating soy consumption to heart
disease mortality in 47 prefectures in Japan, a weak inverse
correlation was found in women only after adjusting for
covariates (Nagata, 2000). The study used 3 day food records
from 6000 households.
Sasazuki et al. (2001) examined a total of 632 cases aged
40–79 years, living in Fukuoka City or adjacent areas, with
their first episode of acute myocardial infarction (AMI) and
1214 controls matched for age, sex and residence. In women
only, tofu consumption was inversely related to the risk of
AMI; relative risks for eating tofu o2, 2–3 and 4 þ times per
week were 1.0, 0.8 and 0.5, respectively, after adjustment for
non-dietary factors (P for trend ¼ 0.01). Further analysis of
the independent relationship of three food groups (fruit, fish
and tofu) with AMI did not change the inverse association
with tofu observed for women.
In Chinese women in the Shanghai Women’s Health
Study, there was a clear monotonic dose–response relationship between soy food intake and risk of total CHD (P for
trend ¼ 0.003) with an adjusted RR of 0.25 (95% CI, 0.10–
0.63) observed for women in the highest vs the lowest
quartile of total soy protein intake. After a mean of 2.5 years
(162 277 person-years) of follow-up, 62 incident cases of
CHD (43 nonfatal myocardial infarctions and 19 CHD
deaths) were seen. The inverse association was more
pronounced for nonfatal myocardial infarction (RR ¼ 0.14;
95% CI, 0.04–0.48 for the highest vs the lowest quartile of
intake; P for trend ¼ 0.001) (Zhang et al., 2003).
Interventions with legumes
Wangen et al. (2001) found that 132 mg of isoflavones per
day, from high isoflavone soy protein, given for 3 months
lowered LDL cholesterol by 6.5% compared with low
isoflavone isolated soy protein. Study subjects were 18
normocholesterolemic and hypercholesterolemic postmenopausal women. A contrary finding was demonstrated by
Sanders et al. (2002) who contrasted a soy protein diet
containing 56 mg/day of isoflavones against one containing
2 mg/day for 17 days in 22 healthy young normolipidemic
subjects in a crossover design. Only HDL cholesterol rose, by
4%, with isoflavones.
Jenkins et al. (2002a) also found no effect on lipids of
isoflavone-enriched soy protein compared with isoflavonepoor soy protein (73 vs 10 mg) in 41 subjects in a crossover
study, but did find that 52 g of soy protein lowered total
cholesterol by 4% and also lowered systolic blood pressure in
men compared with a dairy-rich low-fat diet.
Zhan and Ho (2005) performed a meta-analysis of 23
recent trials involving 1381 subjects using soy with intact
isoflavones and found an LDL cholesterol-lowering of 5%.
The effect was independent of initial cholesterol level. Soy
containing 80 mg of isoflavone/day was more effective than
lower amounts. Ashton and Ball (2000) replaced 150 g of
meat per day with 290 g of tofu in 42 men in a randomized
crossover trial with periods of 1 month each. Total
cholesterol and triglyceride and the lag period of LDL
oxidation were significantly lowered by tofu. Jang et al.
(2001) randomized 76 men with heart disease to either
refined rice or a wholegrain/legume powder for 16 weeks and
showed that the wholegrain/legume diet reduced plasma
insulin and glucose by 14% and malondialdehyde and F2
isoprostane in diabetic subjects by 28%. The latter two
measures show that legumes contain bioavailable antioxidants.
Hale et al. (2002) tested 80 mg of a soy isoflavone
concentrate in 29 healthy menopausal women and demonstrated no effects on endothelial function compared with a
placebo, although there is some evidence that soy protein
isolate (regardless of isoflavone content) contributes to total
plasma antioxidant status, which potentially might protect
against heart disease (Swain et al., 2002).
Azadbakht et al. (2003) replaced half of the animal protein
(total protein 0.8 g/kg) with soy in the diet of 14 patients
with nephropathy for 7 weeks and found that the soy
lowered total cholesterol, triglyceride and LDL cholesterol as
well as urea nitrogen and urine protein levels.
Conclusion
Overall, the recent data have confirmed that soy protein (at
least 25 g/day) can lower LDL cholesterol to a small but
significant degree (5–6%). Isoflavones may play a small role
in cholesterol-lowering but may also play a separate role in
soy’s effects in lowering heart disease rates, as in the three
studies quoted. The USFDA has allowed a health claim for
soy (United States Food and Drug Administration (USFDA),
1999).
Glycaemic index, glycaemic load and vascular
disease
Glycaemic index is the glucose excursion above baseline over
2 h of 50 g of available carbohydrate in comparison with
either 50 g of glucose or 50 g of available carbohydrate from
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Cereal grains and legumes in the prevention of CHD and stroke: a review
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1156
white bread expressed as a percentage. Glycaemic load (GL)
is the product of amount of carbohydrate per serve and
glycaemic index (GI). Liu et al. (2000b) examined the
association between GL and heart disease in 75 521 women
in the Nurses Health Study. After 10 years of follow up, 761
incident cases were found and it was observed that the risk of
heart disease was twice as great in the women consuming the
highest GL diet. The association was only seen in women
with a BMI of greater than 23 kg/m2.
Carbohydrate intake varied from 144 to 226 g per day and
GI from 72 to 80 g per day (averaged across all carbohydratecontaining foods). Fibre intake varied from 14 to 18 g/day
and cereal fibre from 3 to 5 g/day. The women who
consumed a high GL diet ate more total fibre, more cereal
fibre and less fat but these components did not blunt the
effect of the high GI carbohydrates. Carbohydrate amount
was not related to disease risk but GI was related. The biggest
contributors to the GL in the study by Liu et al. (2000b) were
potato (8%) and cold breakfast cereal (4%).
In relation to stroke, carbohydrate itself was a risk factor, as
was GL but the latter was only significant in women with a
BMI greater than 25 kg/m2 (Oh et al., 2005). Cereal fibre was
inversely associated with risk of both haemorrhagic and
thrombotic stroke, with a 29–33% reduction in risk for
women in the highest quintile of intake compared to those
in the lowest.
Possible mechanisms for the increased risk resulting from a
high GL include reduction in HDL cholesterol (Ford and Liu,
2001; Liu et al., 2001; Amano et al., 2004), increased fasting
plasma triglycerides (Liu et al., 2001; Amano et al., 2004),
higher fasting insulin (Amano et al., 2004), increased CRP
(Liu et al., 2002) and glucose intolerance (Schulze et al.,
2004), with epidemiological associations being shown
between risk factors and either the GL of the diet or GI.
CRP is a marker of vascular disease but is also believed to play
an active role in the heart disease process (Zwaka et al., 2001;
Verma et al., 2002).
In dietary interventions, exchanging carbohydrate for fat
is well known to lower HDL cholesterol, increase fasting and
postprandial triglycerides and to increase fasting insulin
(Mensink and Katan, 1992; Garg et al., 1994; Turley et al.,
1998; Mensink et al., 2003), but whether this is adverse in
terms of cardiovascular risk is unknown and the only data in
support of the latter are the Nurses Health Study referred to
above (Liu et al. (2000b).
Glycaemic index has been shown to be unrelated to
cardiovascular mortality in the Zutphen study (van Dam
et al., 2000) and in a Cochrane meta-analysis (Kelly et al.,
2004) of 15 interventions looking at the GI of carbohydrates.
The latter concluded that the evidence to prove GI was
related to cardiovascular risk factors or improvement in
glucose control was weak. This conclusion is critical as many
wholegrain cereal products are wholemeal (ie they contain
milled rather than intact grains) and have a high GI (FosterPowell et al., 2002), whereas intact grains have a low GI. In
the studies relating wholegrain consumption to protection
European Journal of Clinical Nutrition
from vascular disease, the highest quintile of wholegrain
intake usually has a high GL (Jensen et al., 2004) so the
benefit of wholegrain is seen despite the high GL.
Conclusions
(1) the intake of wholegrain foods clearly protects against
heart disease and stroke but the exact mechanism is not
clear. Fibre, magnesium, folate and vitamins B6 and
vitamin E may be important.
(2) The intake of high GI carbohydrates (from both grain
and non-grain sources) in large amounts is associated
with an increased risk of heart disease in overweight and
obese women even when fibre intake is high, but this
requires further confirmation in normal-weight women.
Recommendation: Carbohydrate-rich foods should be
wholegrain and if they are not, then the lowest GI product
available should be consumed. Glycaemic index is largely
irrelevant for foods that contain small amounts of carbohydrate per serve (such as most vegetables).
Acknowledgements
This study was supported in part by BRI Australia Ltd.
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