Jurnal dislipidemia

REVIEW

Cereal grains and legumes in the prevention ofcoronary heart disease and stroke: a review of theliterature

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 to2000. Since then, several key studies have been published. Five studies have examined the relationship between wholegrainconsumption, 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 a40% reduction in risk for those who eat wholegrain food habitually vs those who eat them rarely. Notwithstanding the fact thatfibre is an important component of wholegrains, many studies have not shown an independent effect of fibre alone on CHDevents. Thus in terms of CHD prevention, fibre is best obtained from wholegrain sources. Wholegrain products have strongantioxidant activity and contain phytoestrogens, but there is insufficient evidence to determine whether this is beneficial in CHDprevention. Soluble fibre clearly lowers cholesterol to a small but significant degree and one would expect that this wouldreduce CHD events. There have been a small number of epidemiological studies showing soy consumption is associated withlower rates of heart disease. Countering the positive evidence for wholegrain and legume intake has been the Nurses HealthStudy in 2000 that showed women who were overweight or obese consuming a high glycaemic load (GL) diet doubled theirrelative risk of CHD compared with those consuming a low GL diet. Although the literature relating GL with CHD events issomewhat 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 shouldbe used. Promotion of carbohydrate foods should be focused on wholegrain cereals because these have proven to be associatedwith health benefits. There is insufficient evidence about whether the addition of other components of wholegrains such aspolyphenolics or minerals (such as magnesium or zinc) would improve the health benefits of refined grain foods and this needsinvestigation. Whether adding bran to refined carbohydrate foods can improve the situation is also not clear, and it was foundthat added bran lowered heart disease risk in men by 30%. This persisted after full adjustment (including GL) suggesting, at leastin 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 normal-

weight 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

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 inReceived 9 May 2005; revised 19 December 2005; accepted 28 February

2006; 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.

European Journal of Clinical Nutrition (2006) 60, 1145–1159& 2006 Nature Publishing Group All rights reserved 0954-3007/06 $30.00

www.nature.com/ejcn

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 recom-

mended grains coming from enriched or wholegrain pro-

ducts. 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 ‘exploit-

ing 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

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 di-

gested 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), cardiovas-

cular disease and stroke, combined with key words describ-

ing whole grains, cereal grains, dietary fibre, soy and

Table 1 Selected components in wholegrains and their postulated mechanismsa

Component Antioxidant Tumourgrowth suppressor

Enzymemodulator

Bindingscavenger

Chemicalinactivator

Lipid-lowering Gut modifier Hormonaleffects

Dietary fibre O O O OOligosaccharides O O O OFlavonoids O O OInositols OLignin On-3 fatty acids O OPhenolics O O OPhytates OPhytoestrogens O O OProtease inhibitors OSaponins OSelenium O OTocopherols O OZinc O O

aSource: Slavin et al. (1999).

Cereal grains and legumes in the prevention of CHD and stroke: a reviewI Flight and P Clifton

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European Journal of Clinical Nutrition

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 cardio-

vascular 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

trend¼0.01). 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

Table 2 Compositional differences between whole and refined wheata

Component Whole wheat Refined wheat

Bran (%) 14 o0.1Germ (%) 2.5 o0.1Total dietary fibre (%) 13 3Insoluble dietary fibre (%) 11.5 1.9Soluble dietary fibre (%) 1.1 1.0Protein (%) 14 14Fat (%) 2.7 1.4Starch and sugar (%) 70 83Total minerals 1.8 0.6

Selected mineralsZinc (mg/g) 29 8Iron (mg/g) 35 13Selenium (mg/g) 0.06 0.02

Selected vitaminsVitamin B-6 (mg/g) 7.5 1.4Folic acid (mg/g) 0.57 0.11

Phenolic compoundsFerulic acid (mg/g) 5 0.4b-tocotrienol (mg/g) 32.8 5.7

Phytate phosphorus (mg/g) 2.9 0.1

aSource: Slavin et al., 1999.


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Table 3 Effect of wholegrain intake on CHD risk – prospective epidemiologic studiesa

Author Participants(no.)

Population sample Outcome variable Follow-up(years)

Relative risk (95% CI) Comments

Fraser et al. (1992) 31 208 US Seventh Day Adventists CHD events 8 0.56 (0.35–0.89) For usual consumption of whole wheat rather thanwhite bread, inverse but not significant for CHDdeath

Jacobs et al. (1998) 34 492 Iowa sample from drivinglicenses

CHD death 9 0.70 (0.50–0.98) For the highest vs lowest quintile of whole grainintake

Jacobs et al. (1999) 38 740 Iowa sample from drivinglicenses

CHD death 9 0.82 (0.66–1.01) For those in the highest vs lowest quintile of wholegrain intake; similar reductions were seen for CHD,stroke and other CVD deaths, although the findingwas weakest for stroke

Liu et al. (1999) 75 521 US nurses CHD events 10 0.72 (0.54–0.91) For the highest vs lowest quintile of whole grainintake

Liu et al. (2000a) 75 521 US nurses Ischaemic stroke 12 0.69 (0.50–0.98) For ischaemic stroke in the highest vs lowestquintile of wholegrain intake

Jacobs et al. (2001) 33 848 Norwegians sampled inthree counties

CVD death 14 0.77 (0.60–0.98) Between high and low wholegrain break intakescores

Liu et al. (2003) 86 190 US physicians CVD death (MI andstroke)

6 0.80 (0.66–0.97) For men who ate wholegrain breakfast cereals(4or¼1 serving/day) compared to those whorarely or never consumed whole grain cereal, withreductions in CHD death but not stroke

Mozaffarian et al.(2003)b

3588 US residents aged 465 yearswithout CVD at baseline

CVD event 9 0.76 (0.64–0.90) For dark bread (specific comparison not specified);breakfast cereals unrelated

Steffen et al. (2003) 11 940 US samples in four cities CHD event,ischaemic stroke

11 0.72 (CHD)(0.53–0.97)0.75 (stroke)

(0.46–1.22)

For the highest vs lowest quintile of wholegrainintake, although the findings for stroke did notreach statistical significance; findings were similarin black and white subjects

Bazzano et al. (2003) 9776 US population-based sample CHD event 19 0.80 (0.63–1.01) Unspecified risk reduction when data wereanalysed by food source of cereal fibre, similar toCHD risk reduction for cereal fibre (20% reductionper 4.5 g cereal fibre per 1735 kcal/day)

Abbreviations: CHD, coronary heart disease; CVD, cardiovascular disease; MI, myocardial infarction; CI, confidence interval.aAdapted from Anderson (2002) and Jacobs and Gallaher (2004).bThis 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.

Cerealgrainsand

legumes

inthe

preventionof

CHD

andstroke:a

reviewIFlightand

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EuropeanJournalofClinicalN

utrition

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 substan-

tially 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 review-

ing 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, P¼0.04 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, P¼0.38 for

trend). However, the inverse relation remained (even though

not statistically significant) suggesting that other constitu-

ents may confer additional protection. The authors acknowl-

edge 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, P¼ 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 creat-

ing the possibility for attenuation of the true HR.

Mozaffarian et al. (2003) followed 3588 men and women

aged 65þ 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 second-

ary 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, specifi-

cally 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, P¼0.0002 for trend) for total strokes and

1.56 (95% CI, 1.05–2.33; P¼0.02 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; P¼0.13 for trend) for total stroke and

0.74 (95% CI, 0.54–1.02, P¼0.13 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;


1149


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 hypercholestero-

laemia. 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 confound-

ing 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 associa-

tion 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 proces-

sing 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 Baseline cohort Person-years of follow-up CHD events (RR) CHD deaths (RR)

World Health Organization (1988)Men 9521 39 230 0.83 0.54Women 10 555 43 872 3.52 —

Knekt et al. (1994)Men 2712 24 599 0.95 0.82Women 2481 23 643 0.75 0.44

Kushi et al. (1996) (women only) 30 180 294 620 — 0.49Pietinen et al. (1996) (men only) 21 141 121 813 1.02 0.94Rimm et al. (1996a) (men only) 41 574 383 206 0.77 0.68Folsom et al. (1997)

Men 5240 45 861 0.68 0.90Women 6481 58 199 1.95 —

Wolk et al. (1999) (women only, 1980 inception) 81 415 513 915 1.69 1.34Wolk et al. (1999) (women only, 1986 inception) 61 706 607 049 0.66 0.61Liu et al. (2002) (women only) 37 272 190 755 0.93 0.03Total number of participants 31 0278 2 346 762

Pooled (95% confidence intervals) 0.90 (0.77–1.07) 0.75 (0.63–0.91)P-value for relative riskb 0.23 0.003P-value for heterogeneityc 0.02 0.30

aAdapted 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.bP-value, test for no association.CP-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.


1150


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; P¼0.06 for trend) and a non-

significant 11% lower risk of death from CHD (RR, 0.89, 95%

CI, 0.76–1.02; P¼0.10 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 rando-

mized double-blind, placebo-controlled primary prevention

trial designed to test the efficacy of daily supplementation

with antioxidant vitamins and minerals at non-pharmaco-

logical 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 select-

ing 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

(P¼0.05). 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

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 co-

workers 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 (n¼443

who received fibre advice, n¼436 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,

Table 5 Comparison of clinical and biochemical indices for the highestand lowest quintiles of dietary fibre intake for men and womenparticipating in the SU.VI.MAX studya

Variable Gender Difference (%) highest vslowest total dietary fibre

intake quintile

Fibre sourceassociationb

BMI Men �4.9 TDF, CF, FF VFWomen �1.3

Systolic pressure(mm Hg)

Men �3.8 TDF, CF

Women �2.2

Plasma cholesterol Men �3.2Women þ0.1

Plasmatriacylglycerols(mmol/l)

Men �16.2 TDF

Women �10.0

Plasma glucose(mmol/l)

Men �5.2 CF

Women �2.3

Abbreviations: BMI, body mass index; CF, cereal fibre; FF, fruit fibre; TDF, total

dietary fibre; VF, vegetable fibre.aSource: (Lairon et al., 2003).bComparison 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).


1151


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; ques-

tionnaire 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 (n¼3559) 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 (n¼7481) consumed on

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 nonsignifi-

cant 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 whole-

grain 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 whole-

grains, 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-amylase-

hydrolysed 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).

Table 6 Mortality from CHD in men who received advice to eat morecereal fibre compared with those who did not in the Diet andReinfarction Trial (DART) 1983-2000a

Follow-upperiod (years)

Number of CHDdeaths advice/no advice

Adjustedhazardb (CI)

0–2 109/86 1.35 (1.02, 1.80)2–5 85/73 1.27 (0.93, 1.75)5–10 100/111 0.96 (0.73, 1.26)10þ 83/91 0.94 (0.70, 1.27)Overall 377/361 1.11 (0.96, 1.29)

aadapted from Ness et al. (2002).bAdjusted for history of myocardial infarction, angina, hypertension at

baseline, X-ray evidence of cardiomegaly, pulmonary congestion or pulmo-

nary oedema at baseline, and treatment (at entry) with b-blockers, other

antihypertensives, digoxin/antiarrythmics, or anticoagulants.

Abbreviations: CHD, coronary heart disease; CI, confidence interval.


1152


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 anddisease

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 (RR¼0.63) between flavonoid intake and sub-

sequent 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.


1153


Unsaturated fatty acids and wholegrains

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.

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 concentra-

tions. 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 (P¼0.0008). Plasma entero-

lactone 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 be-

tween 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

(P¼ 0.03 for trend) and CVD-related (P¼0.04 for trend)

death decreased linearly across quartiles of serum enterolac-

tone concentration (Vanharanta et al., 2003).

Conclusion

Wholegrains, particularly from rye, contain phytoestrogens

but whether this is beneficial for CHD prevention is not yet

clear.

Wholegrains as part of a prudent diet

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 interac-

tions 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 Profes-

sionals’ 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 trend¼0.03)

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 trend¼0.02) for the Western pattern.

Similar associations were found in the Health Profes-

sionals’ 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).

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


1154


consumption was significantly and inversely associated with

risk of CHD (P¼0.002 for trend) and CVD (P¼0.02 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 4þ times per

week were 1.0, 0.8 and 0.5, respectively, after adjustment for

non-dietary factors (P for trend¼0.01). 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 relation-

ship between soy food intake and risk of total CHD (P for

trend¼0.003) 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 (RR¼0.14;

95% CI, 0.04–0.48 for the highest vs the lowest quartile of

intake; P for trend¼0.001) (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 postmeno-

pausal 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 isoflavone-

poor 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 antiox-

idants.

Hale et al. (2002) tested 80 mg of a soy isoflavone

concentrate in 29 healthy menopausal women and demon-

strated 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 vasculardisease

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


1155


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 carbohydrate-

containing 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 (Foster-

Powell et al., 2002), whereas intact grains have a low GI. In

the studies relating wholegrain consumption to protection

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 carbohy-

drate per serve (such as most vegetables).

Acknowledgements

This study was supported in part by BRI Australia Ltd.

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