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SCIENTIFIC STATEMENT

Consumption of cereal fiber, mixtures of whole grains and bran, andwhole grains and risk reduction in type 2 diabetes, obesity, andcardiovascular disease1–4

Susan S Cho,5 Lu Qi,6 George C Fahey Jr,7 and David M Klurfeld8*

5NutraSource, Clarksville, MD; 6Department of Nutrition, Harvard School of Public Health, Boston, MA; 7Department of Animal Sciences, University of

Illinois, Urbana, IL; and 8USDA/Agricultural Research Service, Beltsville, MD.

ABSTRACTBackground: Studies of whole grain and chronic disease have oftenincluded bran-enriched foods and other ingredients that do not meet thecurrent definition of whole grains. Therefore, we assessed the literatureto test whether whole grains alone had benefits on these diseases.Objective: The objective was to assess the contribution of bran orcereal fiber on the impact of whole grains on the risk of type 2diabetes (T2D), obesity and body weight measures, and cardiovas-cular disease (CVD) in human studies as the basis for establishingan American Society for Nutrition (ASN) position on this subject.Design: We performed a comprehensive PubMed search of humanstudies published from 1965 to December 2010.Results: Most whole-grain studies included mixtures of wholegrains and foods with $25% bran. Prospective studies consistentlyshowed a reduced risk of T2D with high intakes of cereal fiber ormixtures of whole grains and bran. For body weight, a limitednumber of prospective studies on cereal fiber and whole grainsreported small but significant reductions in weight gain. ForCVD, studies found reduced risk with high intakes of cereal fiberor mixtures of whole grains and bran.Conclusions: The ASN position, based on the current state of thescience, is that consumption of foods rich in cereal fiber or mixturesof whole grains and bran is modestly associated with a reduced riskof obesity, T2D, and CVD. The data for whole grains alone arelimited primarily because of varying definitions among epidemio-logic studies of what, and how much, was included in that foodcategory. Am J Clin Nutr 2013;98:594–619.

INTRODUCTION

The prevalence of type 2 diabetes (T2D)9 and obesity has beenincreasing in the United States (1–3). Today, two-thirds of USadults (1) and nearly 1 in 3 children are overweight or obese (4).Intake of calories over physiologic needs has been linked toincreasing T2D, obesity, cardiovascular disease (CVD), andother chronic conditions (5).

The 2005 and 2010 Dietary Guidelines for Americans (DGA)recommend that whole grains account for at least half of 6 to 11

daily grain servings (6, 7) to reduce the risk of chronic diseases,including T2D, obesity, and heart disease. The NHANES 1999–2004 found that the daily consumption of whole-grain servingswas less than one-third of recommended intakes: only 1.5% ofchildren aged 1–3 y, 4.3% of adolescents, 4.8% of adults aged19–50 y, and 6.4% of adults .50 y meet the recommended 3–5servings per day (8, 9). The National Health Interview Survey2000 showed that the average American consumes only one-halfof the recommended intake of dietary fiber; .84% of Americanadults do not meet recommended intakes established by theInstitute of Medicine (10, 11). Increased consumption of wholegrains and cereal fiber–rich foods such as bran can contribute to

FROM THE AMERICAN SOCIETY FOR NUTRITION

1 This statement was peer reviewed and approved by the American Society for

Nutrition’s (ASN’s) Reviews, Papers, and Guidelines Committee and approved

by ASN’s Board of Directors. The statement did not undergo editorial peer

review by the editors of The American Journal of Clinical Nutrition.2 This project was funded by an unrestricted educational grant from CJ

CheilJedang, Garuda International, and the Kellogg Company.3 The opinions expressed in this article are those of the authors and not

necessarily those of the USDA, the Agricultural Research Service, or any of

the authors’ affiliations.4 Author disclosures: SS Cho, research support from Garuda International,

Innophos, JRS, Kellogg, Roquette; consultancy for CJ CheilJedang, Corn

Products International, Cyvex Nutrition, Optimum Nutrition, Pacific Rain-

bow, RFI Ingredient, and Shangdong Longlive. L Qi, no disclosures to re-

port. GC Fahey, research support from Roquette America Inc, Ingredion,

Abbott Nutrition, Del Monte, and Hartz Mountain; consultancy for Ingre-

dion, Novus lnternational, Procter & Gamble, Perfect Companion Group,

Pronaca, Nova Foods, NuPec, Dae Han Feed Co Ltd, Milk Specialties Co,

and Watt Publishing Co. DM Klurfeld, was a member of Unilever North

America Scientific Advisory Board at the time this work was performed.9 Abbreviations used: CVD, cardiovascular disease; DGA, Dietary Guide-

lines for Americans; FDA, US Food and Drug Administration; NHS, Nurses’

Health Study; RCT, randomized controlled trial; T2D, type 2 diabetes; WC,

waist circumference.

*Address correspondence to DM Klurfeld, USDA/Agricultural Research

Service, Human Nutrition Program, 5601 Sunnyside Avenue, Beltsville, MD

20705-5138. E-mail: [email protected].

First published online June 26, 2013; doi: 10.3945/ajcn.113.067629.

594 Am J Clin Nutr 2013;98:594–619. Printed in USA. � 2013 American Society for Nutrition

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improved fiber intake by Americans. The 2010 DGA recom-mend whole grains as a source of dietary fiber but do notmention other sources of dietary fiber. Furthermore, the DGA donot recommend dietary fiber to reduce the risk of chronic dis-eases despite the conclusion statements in the USDA NutritionEvidence Library that whole grains and cereal fiber intake areassociated with reduced risk of obesity and CVD (7, 12).

A change in the working definition of whole grains hascontributed to the confusion on the health effects of whole grainsand their components. Research conducted by nutritional epi-demiologists from the University of Minnesota and HarvardUniversity provided much of the early data in this area; however,these investigators used different definitions of a whole grain intheir studies (13–15). For example, some studies included brownbread and wheat germ in the whole-grain category and othersdid not (16, 17). In addition, there were no USDA databasesavailable at that time to calculate how much whole grain was ina serving of the various products, and the studies provided noinformation that this was accounted for. But the most prob-lematic inclusion in the whole-grain category was bran cereals.In the 1990s, foods with $25% whole grains and bran, as wellas high-fiber bran cereals, were included in the whole-grainworking definition (13–15). Today, high-fiber bran cereals areexcluded (18, 19). Definitions of whole grain vary depending onthe context and purpose. Research from the 1990s (13–15)supported the benefits of bran as an integral part of the healthbenefits of whole grains. According to this definition establishedin the 1990s, foods with $25% whole-grain or bran content by

weight were classified as whole grain. Of note, however, thedefinition commonly used in the scientific community is not thesame as that on food labels, which exclude foods with $25%bran. To establish a whole-grain health claim under the Food andDrug Administration Modernization Act, the definition ofa whole-grain food is one that contains $51% whole-grain in-gredients by weight per reference amount customarily consumed(18, 19). In 2006, the US Food and Drug Administration (FDA)provided additional guidance that describes specific sources ofwhole grains (20). Accordingly, examples of whole-grain foodsand ingredients in the Expert Panel report of the USDA/Healthand Human Services DGA include brown rice, oatmeal, wholeoats, bulgur (cracked wheat), popcorn, whole rye, graham flour,and whole wheat (21). This list includes some low-fiber foodsbut does not include bran-rich foods that are excellent sources offiber.

Compared with refined-grain foods, foods made with wholegrains are purported to contain fewer starches and calories andmore micronutrients and phytochemicals that may offer signif-icant health advantages (22). Whole grains are composed of bran,germ, and starchy endosperm. Bran is a concentrated source offiber, vitamins, minerals, and phytonutrients, which together arethought to provide many of the health benefits of whole grains(22). The use of bran-concentrated or -enriched foods likely canprovide consumers with more choices for healthy foods, promotehealthful dietary practices, and help individuals meet publichealth recommendations for the intake of whole grains and dietaryfiber without consumption of excess calories.


FIGURE 1. Flow diagram of systematic review on type 2 diabetes.

WHOLE-GRAIN, BRAN, AND FIBER INTAKE AND RISK OF DISEASE 595

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As the basis of an American Society for Nutrition positionstatement, this systematic review seeks to determine whetherbran, cereal fiber, and whole-grain intakes have an effect on thedevelopment of T2D, obesity, and heart disease.

METHODS

Approach and methodology

A comprehensive PubMed (http://www.ncbi.nlm.nih.gov/pubmed) search of the scientific literature for articles publishedfrom January 1965 to December 2010 was performed. For T2D,the following search strategy was used: (whole grain OR wholegrains OR whole-grain OR cereal fiber OR cereal fiber OR grainfiber OR grain fiber OR bran OR brans) AND (diabetes). Thisstrategy identified 614 human studies. Twenty additional recordswere identified through other sources. After removing duplicatesand nonrelevant articles, 66 abstracts were selected for moredetailed review. Finally, we selected 15 prospective studies and13 cross-sectional studies that met predetermined inclusion andexclusion criteria described below and shown in Figure 1 (23).For obesity and measures of body weight, the PubMed search ofthe following terms—whole grain OR whole grains OR whole-grain OR cereal fiber OR cereal fiber OR grain fiber OR grainfiber OR bran OR brans AND body weight OR body weight gainOR body mass index OR BMI z score OR obesity OR over-weight OR adiposity OR waist circumference OR waist-to-hip

ratio (WHR)—identified 538 articles. Seven additional recordswere identified from other sources, such as review articles. Afterremoving duplicates and nonrelevant articles, 43 studies werereviewed in detail. From these, 19 studies (5 prospective and 14cross-sectional) were selected on the basis of our inclusion andexclusion criteria described below and as shown in Figure 2(23). For CVD, search terms—(whole grain OR whole grainsOR whole-grain OR cereal fiber OR cereal fiber OR grain fiberOR grain fiber OR bran OR brans) AND (heart disease OR car-diovascular disease OR myocardial infarction OR hypertensionOR arterial disease OR stroke OR blood pressure)—identified894 human studies. Fifteen additional papers were identifiedthrough other sources. After removing duplicates and non-relevant articles, 85 abstracts were reviewed, from which weselected 22 prospective and 12 cross-sectional studies by usingthe inclusion and exclusion criteria described below and asshown in Figure 3 (23).

When assessing the contribution of whole grains alone, ouranalysis included only those studies that used the current defi-nition of a whole grain as established by the FDA (ie, foods thatcontain $51% whole-grain ingredients by weight per referenceamount customarily consumed).

Inclusion criteria

We included controlled feeding trials (intervention period of$1 y) and observational studies reporting risk and risk factors of

FIGURE 2. Flow diagram of systematic review on obesity. RCT, randomized controlled trial.

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T2D or CVD. For obesity outcomes, we used risk of obesity orweight-related endpoints, such as BMI, weight gain, waist cir-cumference (WC), and waist-to-hip ratio.

Exclusion criteria

Editorials, meta-analyses, reviews, and studies published inlanguages other than English were excluded. Articles related tototal, soluble, and insoluble fibers with no data on cereal fiberwere excluded. Short-term feeding studies (,1 y) were alsoexcluded because they do not reflect the long-term health impactof these grain components as consumed by the population.

Rating scientific evidence

We used the evidence grading system shown in Table 1. Thissystem is similar to that used by prominent organizations such asthe American Diabetes Association (24) or recommended byother experts (25). The assigned grade reflects the totality of theevidence on a particular subject and was established by con-sensus of the writing group.

RESULTS

A total of 15, 5, and 22 prospective cohort studies wereavailable for summarization for T2D, obesity/body weightmeasures, and CVD, respectively. Cross-sectional studies (13reports on T2D, 14 reports on obesity, and 12 studies on CVD) are

also presented as supportive data in Appendixes A–K. We foundno long-term ($1 y duration), randomized controlled trials(RCTs) that assessed the impact of cereal fiber, mixtures ofwhole grains or brain, or whole grains that represent intakes ofthese grain components as consumed by the population. Thus,all of the studies identified were observational, either pro-spective or cross-sectional.

The majority of whole-grain studies have investigated mix-tures of whole grains and $25% bran rather than whole grainsalone. Many studies reported that the inverse associations be-tween intake of mixtures of whole grains and bran or wholegrains alone and risks of T2D, CVD, or reduced weight gaindisappeared or were attenuated after adjustment for cereal fiberor bran, suggesting that cereal fiber and bran account for muchof the whole-grain effects.

T2D

A number of well-designed, large, prospective cohort studiesshowed a consistent inverse association between consumption ofcereal fiber or mixtures of whole grains and bran and the riskof T2D. Prospective studies consistently showed a reduced risk ofT2D with high intakes of cereal fiber (10 of 11 reports showed an18–40% risk reduction) or mixtures of whole grains and bran (5of 6 reports showed a risk reduction of 21–40%); one prospectivestudy on whole grains (meeting the FDA definition excluding$25% bran) reported a risk reduction of 32–37% in females.

FIGURE 3. Flow diagram of systematic review on cardiovascular disease (CVD).



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Studies on cereal fiber

The results of 11 reports are listed in Table 2: 10 reports from8 independent prospective cohorts, each of which reportedquintile or quartile analysis of cereal fiber consumption (16, 17,26–33), and one additional study based on regression analysis(34). All of the studies using quintile or quartile analysis ofcereal fiber consumption showed consistent associations be-tween intake of cereal fiber and risk reduction of T2D (16, 17,26–33). The Melbourne Collaborative Cohort Study was theonly epidemiologic report that failed to show an associationbetween cereal fiber and risk of T2D (34). The Melbourne Col-laborative Cohort’s primary purpose was to study the relationbetween glycemic index and risk of T2D. Fiber and cereal fiberconcentrations were reported for each quartile of glycemic index.Relative risk from cereal fiber was assessed on the basis of a10-g/d intake, not fiber intake quartiles.

Most of the studies followed groups of mixed ethnicity, butKrishnan et al (33) reported that cereal fiber intake was inverselyassociated with risk of T2D, with an incidence rate ratio of 0.82(95% CI: 0.70, 0.96; P-trend = 0.01) in a prospective cohortstudy in 59,000 US black women. A stronger association wasseen among black women with a BMI (in kg/m2) ,25: the in-cidence rate ratio for the highest compared with lowest quintilewas 0.41 (95% CI: 0.24, 0.72; P-trend = 0.003). Nine-yearfollow-up in the Atherosclerosis Risk in Communities Study(32) found that cereal fiber intake was inversely associated with

the risk of T2D in whites and African Americans, but the re-lation was significant only in whites (HR: 0.956; 95% CI: 0.925,0.987 for 1 g cereal fiber/d). The weaker association in AfricanAmericans may be due to fewer individuals and lower statisticalpower or a smaller difference in cereal fiber intake amountsbetween the highest and the lowest consuming groups. Datafrom cross-sectional studies are consistent with the findingsfrom prospective studies (Appendix A; 35–39).

Evidence level B was assigned for the association betweencereal fiber intake and risk reduction of T2D.

Studies on mixtures of whole grains and bran

Most of the studies (16, 26, 35, 36, 40–50) on whole grainsincluded foods with$25% bran in the whole-grain category. Sixprospective cohort studies on whole-grain intake and reductionin risk of T2D are summarized in Table 3 (16, 26, 40–43). All ofthese investigations (6 of 6 studies) followed different pop-ulations and included added bran in the whole-grain food cate-gory; thus, “whole grains” in these studies were “mixtures ofwhole grains and bran” (16, 26, 40–43). One study (16) alsoincluded wheat germ in the whole-grain definition (Table 3). Thestudy by Kochar et al (41) was limited to whole-grain breakfastcereals. These studies showed a significant inverse associationbetween intake of mixture of whole grains and bran and theincidence of T2D.

TABLE 1

Evidence grading system

Level of evidence (refers to the body of evidence) Description

A: strong Clear evidence from at least one large, well-conducted, generalizable, RCT1 that is

adequately powered with a large effect size and is free of bias or other concerns

or

Clear evidence from multiple RCTs or many controlled trials that may have few

limitations related to bias, measurement imprecision, inconsistent results, or other

concerns

B: moderate Evidence obtained from multiple, well-designed, conducted, and controlled prospective

cohort studies that have used adequate and relevant measurements and that gave similar

results from different populations

or

Evidence obtained from a well-conducted meta-analysis of prospective cohort studies

from different populations

C: limited Evidence obtained from multiple prospective cohort studies from diverse populations that

have limitations related to bias, measurement imprecision, or inconsistent results or have

other concerns

or

Evidence from only one well-designed prospective study with few limitations

or

Evidence from multiple well-designed and conducted cross-sectional or case-controlled

studies that have very few limitations that could invalidate the results from diverse

populations

or

Evidence from a meta-analysis that has design limitations

D: inadequate Evidence from studies that have one or more major methodologic flaws or many minor

methodologic flaws that result in low confidence in the effect estimate

or

Insufficient data to support a hypothesis

or

Evidence derived from clinical experience, historical studies (before-after), or

uncontrolled descriptive studies or case reports

1RCT, randomized controlled trial.

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A few studies were able to analyze the effects of cereal fiber,whole grains, and/or bran in the same population. The associa-tions of mixtures of whole grains and bran were attenuated ordisappeared after adjustments for other dietary factors such asdietary fiber or cereal fiber/magnesium (16, 26, 40). These datasuggest that dietary fiber and magnesium account for much of therisk reduction associated with intake of mixtures of whole grainsand bran.

In the study by Meyer et al (26), women in the highest intakequintile of mixtures of whole grains and bran had an adjusted RRof 0.79 (95% CI: 0.65, 0.96; P-trend = 0.0089) for T2D relativeto those in the lowest quintile. Cereal fiber and dietary magne-sium, 2 components of whole grains, were strongly related toT2D diabetes: RRs in the highest quintiles were 0.64 (95% CI:0.53, 0.79; P-trend = 0.0001) for cereal fiber and 0.67 (95% CI:0.55, 0.82; P-trend = 0.0003) for dietary magnesium. The as-sociation of mixtures of whole grains and bran was not sig-nificant after the models were adjusted for cereal fiber andmagnesium (RR: 0.93; 95% CI: 0.75, 1.16; P-trend = NS).Cereal fiber and dietary magnesium had significant inverserelations with T2D, even after simultaneous adjustment forgrains, and cereal grains: RRs were 0.71 (95% CI: 0.56, 0.89;P-trend = 0.0017) in the highest quintiles of cereal fiber and0.76 (95% CI: 0.62, 0.95; P-trend = 0.048) in dietary mag-nesium intakes (data not shown).

Similarly, Fung et al (40) showed that the benefit seenwith mixtures of whole grains and bran disappeared when thedata were adjusted for cereal fiber, magnesium, and glycemicload.

In the Finnish Mobile Clinic Health Examination Survey,Montonen et al (16) found that consumption of whole grains andcereal fiber was associated with a reduced risk of T2D. The RRsbetween the highest and lowest quartiles were 0.65 (95% CI:0.36, 1.18; P-trend = 0.02) for whole grains and 0.39 (95% CI:0.20, 0.77; P-trend = 0.01) for cereal fiber. However, this inverserelation between high intake of whole grains and T2D wassimilar but not significant (RR in the highest quartile: 0.67; 95%CI: 0.32, 1.38; NS) after adjustment for intake of saturated fat,antioxidant vitamins (vitamins E and C, b-carotene), vitaminB-6, folic acid, flavonoids, and magnesium. After further ad-justment for cereal fiber, the RR in the highest quartile of wholegrain intake was 1.14 (NS). The association of cereal fiber re-mained significant after additional adjustment for saturated fat,antioxidant vitamins, vitamin B-6, folic acid, flavonoids, andmagnesium. The authors suggested an independent associationbetween cereal fiber intake and T2D.

It is noteworthy that the whole-grain intake amounts in Finnishcohorts is significantly higher than those in the US cohorts; thehighest and the lowest intake group consumed 236 and 79 g ofmixtures of whole grains and bran, respectively. Despite the

TABLE 2

Prospective cohort studies of cereal fiber: risk of T2D1

Author, year

(reference) Study name

No. of

participants Age Follow-up

No. of

cases

Cereal fiber intake

RR 95% CI P-trendHighest Lowest

y y g/d

de Munter et al,

2007 (17)

NHS I and II 161,737 F 36–65 12–18 6486 12.0 1.1 0.64 0.54, 0.76 ,0.001

Meyer et al,

2000 (26)

IWHS 35, 988 F 55–69 6 1141 9.43 2.66 0.64 0.53, 0.79 0.0001

0.712 0.56, 0.89 0.002

Montonen et al,

2003 (16)

FMCHES 4316 M + F 40–69 10 156 29 6 11 12 6 3.4 0.39 0.20, 0.77 0.01

Salmeron et al,

1997 (27)

NHS 66,173 F 40–65 6 523 7.5 2.0 0.72 0.58, 0.90 0.001

Hu et al,

2001 (28)

NHS 84,941 F 30–55 16 3300 NA NA 0.60 0.53, 0.67 ,0.001

Schulze et al,

2004 (29)

NHS II 91,249 F 24–44 8 741 8.8 3.1 0.64 0.48, 0.86 0.004

Salmeron et al,

1997 (30)

HPFS 42,759 M 40–75 6 915 10.2 2.5 0.70 0.51, 0.96 0.007

Schulze et al,

2007 (31)

EPIC-Potsdam study 25,067 M + F 35–65 7 844 16.6 6.6 0.72 0.56, 0.93 0.02

Stevens et al,

2002 (32)

ARIC study 12,251 M + F

(W and AA)

45–64 9 1447 W: 5.1 6 3.6 W: 2.7 6 1.7 0.75 0.60, 0.92 ,0.05

AA: 4.0 6 2.6 AA: 2.8 6 1.6 0.86 0.65, 1.15 NS

All = W + AA 0.79 ,0.05

Krishnan et al,

2007 (33)

BWHS 59,000 F, AA 21–69 8 1938 8.3 6 2.5 1.5 6 0.7 0.82 0.70, 0.96 0.01

Hodge et al,

2004 (34)

MCCS 36,787 M + F 40–69 4 365 Every 10 g 0.97 0.79, 1.20 NS

1RRs are for the comparisons between highest quintile or quartile compared with that of the lowest. AA, African Americans; ARIC, Atherosclerosis Risk

in Communities; BWHS, Black Women’s Health Study; EPIC-Potsdam, European Prospective Investigation into Cancer and Nutrition–Potsdam; FMCHES,

Finnish Mobile Clinic Health Examination Survey; HPFS, Health Professionals Follow-Up Study; IWHS, Iowa Women’s Health Study; MCCS, Melbourne

Collaborative Cohort Study; NA, not available; NHS, Nurses’ Health Study; P-trend = P value for trend test across all levels of exposure; T2D, type 2 diabetes;

W, whites.2Multivariable model plus adjustment for cereal grains and magnesium.



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differences in major sources of whole grains (rye in Finland andwheat in the United States), trends for inverse associations weresimilar between the 2 countries. Data from cross-sectional studiesare consistent with the findings from prospective studies (Ap-pendixes B and C; 35, 36, 44–50).

Evidence level B was fulfilled for the association betweenintake of mixtures of whole grains and bran and risk reduction ofT2D.

Studies on whole grains

Two studies (17, 51) met the whole-grain definition criteriadefined by the FDA. Evidence for the association between whole-grain intake and T2D risk reduction was shown in one large, well-designed prospective cohort of females only [Nurses’ HealthStudy (NHS)], (Table 4; 17). No prospective study in males wasfound. Although the NHS was a carefully designed and well-conducted study, the absence of any confirmatory prospectivestudy limits the confidence that whole grains reduce the in-

cidence of T2D. Nonetheless, the data from the NHS allow oneto make a comparison between the benefit of whole graincompared with cereal fiber in reducing the risk of diabetes.Daily intakes of bran, cereal fiber, and whole grains were 9.6–12g, 12 g, and 36.9–45.6 g in the highest quintiles and 0.6–1.1 g,1 g, and 3.2–5.5 g in the lowest quintiles, respectively. These datasuggest that daily intakes of 8–11 g of cereal fiber and 34–40 gof whole grains provide comparable RR values. One cross-sectional study showed no association with risk factors related toT2D (Appendix D; 51).

Evidence for the association between whole-grain intake anddevelopment of T2D was considered as level C.

Obesity and body weight measures


The 2 prospective studies (52, 53) relating cereal fiber tovarious body weight measures are listed in Table 5. These 2

TABLE 3

Prospective cohort studies of mixtures of whole grains and bran: risk of T2D1

Author, year


No of

participants

Age at

baseline Follow-up

No. of

cases

Intake of mixtures of

whole grains and bran


y y

Fung et al,

2002 (40)

HPFS 42,898 M 40–75 #12 1197 3.2 servings/d 0.4 servings/d 0.70 0.57, 0.85 0.0006

0.982 0.76, 1.26 NS

Kochar et al,

20073 (41)

PHS 21,152 M 39.7–85.9 19.1 1958 $7 servings/wk 0 servings/wk 0.60 0.50, 0.71 ,0.0001

Liu et al,

2000 (42)

NHS 75,521 F 38–63 10 1879 2.70 servings/d 0.13 servings/d 0.73 0.63, 0.85 ,0.0001

Meyer et al,

2000 (26)

IWHS 35,988 F 55–69 6 1141 .17.5 servings/wk ,3.0 servings/wk 0.79 0.65, 0.96 0.0089

0.934 0.75, 1.16 NS

van Dam et al,

2006 (43)

BWHS 41,186 F 21–69 8 1964 1.29 servings/d 0.03 servings/d 0.69 0.60, 0.79 ,0.0001

Montonen et al,

2003 (16)

FMCHES5 4316 M + F 40–69 10 156 302 g/d 79 g/d 0.64 0.36, 1.15 0.02

0.676 0.32, 1.38 NS

1.147 0.66, 2.49 NS

1BWHS, Black Women’s Health Study; FMCHES, Finnish Mobile Clinic Health Examination Survey; HPFS, Health Professionals Follow-Up Study;

IWHS, Iowa Women’s Health Study; NHS, Nurses’ Health Study; PHS, Physicians’ Health Study; T2D, type 2 diabetes.2Multivariable model after further adjustment for cereal fiber, magnesium, and glycemic load.3Limited to breakfast cereals with $25% of whole grains and bran.4Multivariable model plus adjustment for cereal fiber intake.5 Included germs in the whole-grain definition.6Multivariable model after adjustments for intakes of other dietary factors including saturated fat, antioxidant vitamins (vitamins E and C, b-carotene),

vitamin B-6, folic acid, flavonoids, and magnesium.7Multivariable model after further adjustment for cereal fiber

TABLE 4

Prospective cohort studies on whole grains: risk of T2D1

Author, year (reference) Study name

No. of

participants Age Follow-up

No. of

cases

Whole-grain

intake2


y y g/d

de Munter et al,

2007 (17)

NHS I 73,327 F 37–65 12–18 4747 36.9 3.2 0.63 0.57, 0.69 ,0.001

NHS II 88,410 F 26–46 12–18 1739 45.6 5.5 0.68 0.57, 0.81 ,0.001

1RRs are for the comparison between the extreme quintiles. NHS, Nurses’ Health Study; T2D, type 2 diabetes.2The definition of whole grain met the US Food and Drug Administration criteria.

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prospective cohort studies in males and females showed sig-nificant inverse associations between cereal fiber intake andbody weight measures. However, the absolute reduction inweight gain from cereal fiber consumption was 0.39 kg betweenthe highest intake groups. The study by Du et al (53) also re-ported a small change in body weight, 77 g/y per daily intake of10 g cereal fiber. Although these differences were significant, itis difficult to evaluate their biological significance due to min-imal differences in absolute body weights.

A total of 4 of 4 cross-sectional reports (36, 39, 54, 55)summarized in Appendix E reported inverse associations be-tween cereal fiber intake and body weight measures. The dif-ferences in BMI, body weights, or WC between the highest andthe lowest intakes were large enough to have biological signif-icance.

We assigned evidence level B/C for an inverse associationbetween cereal fiber intake and various body weight measures.


Most studies on whole grains included $25% bran in thedefinition of whole-grain foods (36, 44, 45, 47, 48, 52, 54, 56–62). One study reported both definitions of whole grains (52),and another study (57) confined the evaluation to breakfast ce-reals with $25% whole grains and bran. The prospective reportscomparing whole grains and bran with measures of body weightare listed in Table 6 (52, 56, 57). All of the 3 large prospectivecohort studies in both men and women (52, 56, 57) and a smallprospective cohort study in children (58) reported consistentinverse correlations between intakes of mixtures of whole grainand bran and BMI, weight gain, body weight, or risk of obesity.Despite consistent inverse associations, these prospective studiesshowed minimal differences in absolute body weight or bodyweight gain between the highest and the lowest intake groups:The studies by Koh-Banerjee et al (52), Liu et al (56), andBazzanzo et al (57) reported body weight gain differences of0.52, 0.39, and 0.35–0.42 kg, respectively, during 8- to 13-yfollow-up periods. It is difficult to assess the health impact ofsuch minimal differences.

However, Liu et al (56) reported that, over a 12-y period, thereductions in risk of obesity and weight gain of $25 kg were19% and 23%, respectively. Also, Bazzano et al (57) reported

that, compared with the lowest consumers, the highest con-sumers of breakfast cereals with $25% whole grains and branhad a 23% lower risk of weight gain of $10 kg (RR: 0.78; 95%CI: 0.64, 0.96; P = 0.01). Steffen et al (58) reported a reductionin BMI of 7.2% during the 2-y follow up period in the highestconsumers of mixture of whole grains and bran.

All of the cross-sectional studies with .1500 subjects each(36, 47, 48, 59, 60) were consistent with the inverse associationbetween intake of whole grains and bran and body weightmeasures (Appendixes F and G). The differences in BMI, bodyweight, or WC between the highest and the lowest intake werelarge enough and may have biological significance. The studiesreporting no associations (61, 62) or mixed results (44) had lownumbers of subjects and may not have had sufficient statisticalpower (Appendixes F and G).

Evidence level B/C was the grade for the association betweenintake of mixtures of whole grains and bran and measures of bodyweight.


One study defined whole grains as foods containing $10%whole grains or bran (63). There was one prospective study ina male cohort with a lengthy follow-up (Health ProfessionalsFollow-Up Study) (52; Table 7), and the remainder were cross-sectional studies (9, 55, 64; Appendix H). In the Health Pro-fessionals Follow-Up Study, the absolute reduction in weightgain (0.29 kg) in the highest intake group was minimal: weightgains over the 8-y follow-up period were 0.69 and 0.96 kg forthe highest and the lowest quintile category, respectively (P-trend = 0.002). Despite statistical significance, the differencesare likely not biologically meaningful.

The relation between whole grains and reduction in weightgain was weakened after adjustment for added bran and cerealfiber intakes but still persisted. A cross-sectional study by O’Neilet al (Appendix H; 9) showed that inverse associations betweenwhole-grain intake and body weight measures (BMI and WC)disappeared after adjustment for cereal fiber.

Because only one prospective study in men reported a minimaldifference in body weight gain between the highest and the lowestintake groups, evidence for the inverse association of wholegrains is considered level C/D.

TABLE 5

Prospective cohort studies on cereal fiber; body weight measures1

Author, year


No. of

participants, age

Study design,

follow-up

Cereal fiber intake

Endpoints

Body weight measures

(highest vs lowest)Highest Lowest P-trend

g/d

Koh-Banerjee

et al, 2004 (52)

HPFS 27,082 M,

aged 40–75 y

P, 8 y Change in

intake: 5.1

Change in

intake: 22.2

Body weight

change (kg/8 y)

+0.91 vs +1.30

(0.39-kg difference)

0.0004

Du et al, 2010 (53) Diogenes

Project

89,432 M + F,

aged 20–78 y

P, 6.5 y 12.6 6 4.6 9.3 6 3.5 Body weight change

(g/y) per 10 g

cereal fiber/d

277 (2127, –26) 0.01

WC change (cm/y)

per 10 g cereal

fiber/d

20.10 (20.18, 20.02) ,0.001

1Values in parentheses are 95% CIs. HPFS, Health Professionals Follow-Up Study; P, prospective; WC, waist circumference.



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TABLE6

Prospective

cohortstudiesonmixturesofwhole

grainsandbran:risk

ofobesityandbodyweightmeasures1

Author,year

(reference)

Studynam

e

No.of

participants,age

Follow

-up

Intakeofmixturesof

whole

grainsandbran

Endpoints

RR(95%

CI)orbodyweight

measure

(highestvslowest)

P-trend

Highest

Low

est

y

Liu

etal,

2003(56)

NHS

74,091F,

aged

38–63

y

12

Servings/1000

kcalper

day:

atbaseline,

1.62;change

inintakein

12y,

0.90

Servings/1000

kcalper

day:

atbaseline,

0.07;

change

inintakein

12y,

20.59

ORforweight

gain,

$25kg

in12y

0.77(0.59,1.01)

0.03

ORforBMI(inkg/m

2)$30

in12y

0.81(0.73,0.91)

0.0002

Weightgain(kg)

4.12vs4.51

,0.0001

2–4

Average

changes

inBMI

(kg/m

2)

0.46vs0.56

,0.0001

Average

changes

inweight(kg)

1.23vs1.52

,0.0001

Koh-Banerjee

etal,2004(52)

HPFS

26,082M,aged

40–75

y

8+27.0

g/d

211.0

g/d

Bodyweightchange

(kg/8

y)

+0.73vs+1.25

(difference:0.52)

,0.0001

Bazzanoet

al,

2005(57)

PHS2

17,881M

8$1serving/d

Rarely

Weightgain(kg)

1.13vs1.55

0.003

RRforBMI$25

0.83(0.71,0.98)

0.06

13

Weightgain(kg)

1.83vs2.18

0.08

RRforBMI$25

0.91(0.79,1.05)

0.13

RRforweight

gain$10kg

0.78(0.64,0.96)

0.01

Steffen

etal,2003(58)

MPSS

285M

+F,

meanage

of13y

2.1.5

servings/d

,0.5

servings/d

BMI(kg/m

2)

21.9

vs23.6

0.05

1HPFS,HealthProfessionalsFollow

-UpStudy;

MPSS,MinneapolisPublic

SchoolStudents;NHS,Nurses’HealthStudy;

PHS,Physicians’

HealthStudy.

2A

reportfrom

thePHSwas

limited

tobreakfastcerealswith$25%

whole

grainsandbran.

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CVD

Prospective studies consistently showed a reduced risk of CVDwith high intakes of cereal fiber (a risk reduction of 14–26% forCVD mortality and 22–43% for stroke) or mixtures of wholegrains and bran (a risk reduction of 7–52% for CVD mortality,CVD events, and heart failure). Only 1 of 2 prospective studiesshowed an inverse association between whole-grain intake andreduction in risk of CVD. Subtypes of stroke were not evaluatedin this review. Also, one study (63), which used the cutoff of10% whole-grain content to define whole-grain foods, is notincluded in the review.


A summary of the reports showing the relation between cerealfiber consumption and CVD or hypertension are provided inTable 8. Six of the 10 publications (65–74) on CVD were in-dependent studies, of which one study addressed hypertension.For the reports related to the incidence of CVD, a variety ofoutcome measures were reported. In general, a consistent butmodest risk reduction was seen in CVD mortality (65, 67) andstroke (69–71): risk reductions were in the range of 14–26% forCVD mortality and 22–43% for stroke. However, a non-significant risk reduction (RR: 0.70; 95% CI: 0.46, 1.06; NS) inCVD mortality was observed in subjects with T2D (66). The riskreductions for CVD events (68–70) and myocardial infarction(69, 73) were inconsistent. No studies showed adverse effects ofcereal fiber. Two cross-sectional studies reported mixed results(Appendix I; 39, 75).

The evidence level is B for the association between cereal fiberintake and reduction in risk of CVD.

In the study by Alonso et al (74), fiber from cereals was in-versely associated with a lower risk of hypertension (HR com-paring the fifth and first quintile: 0.60; 95%CI: 0.3, 1.0; P-trend =0.05). The relation with hypertension was stronger among in-dividuals over the age of 40 y than in younger people andstronger among males than in females. A cross-sectional studysupported the findings from a prospective study (75; AppendixI). Evidence is considered inadequate (level D) due to the lim-ited number of large, well-designed prospective studies.


A summary of 10 reports from 6 independent prospectivestudies showing a relation between consumption of mixtures ofwhole grains and bran and reduction in risk of CVD or hyper-tension is provided in Table 9 (13–15, 45, 76–81). Most of thereports (w80%) related to heart disease considered whole-grainfoods as products containing whole grains and $25% bran.

Reports from the Physicians’ Health Study (76, 79) limited theinvestigation to breakfast cereals containing whole grains and$25% bran. All 9 reports from 4 large and 1 small prospectivecohort studies showed significant inverse associations betweenintakes of mixtures of whole grains and bran and risks of CVDmortality, CVD events, and heart failure in both males and fe-males (Table 9; 13–15, 45, 76–79). However, the risk reductionfor ischemic stroke was not significant (77, 80).

Cross-sectional studies on risk factors for CVD in relation toconsumption of whole grains and bran reported mixed results(Appendix J; 36, 44, 47, 48, 50, 61, 82). Overall, moderateevidence (grade B) exists for the association between intake ofmixtures of whole grains and bran and reduction in risk of CVDbecause all large, prospective cohort studies showed relativelyconsistent associations and the number of studies was adequate.

Only one study (81; Table 9) reported an inverse associationbetween reduction in risk of hypertension and intakes of mixturesof whole grains and bran in women only, and cross-sectionalstudies generally found no association (36, 44, 45, 47, 48; Ap-pendix J). Thus, there is inadequate evidence to suggest thatconsumption of whole grains with added bran will affect theincidence of hypertension (evidence level D).


A summary of the reports showing a relation between whole-grain consumption and risk of CVD or hypertension is providedin Table 10 (66, 83, 84). The inverse association betweenwhole-grain intake and CVD risk was attenuated and becamenonsignificant after adjustment for dietary fiber, magnesium,and other dietary factors (83), indicating that dietary fiber andmagnesium account for whole-grain actions. The study by Heet al (66), which reported no association, was confined to diabeticwomen. One cross-sectional study (Appendix K; 51) reportedinconsistent associations of whole-grain or bran intake with riskfactors for CVD. Thus, there is limited evidence for the associa-tion between intake of whole grains and reduction in risk ofCVD (level C).

Flint et al (84) reported an inverse association between whole-grain intake and hypertension, with an RR of 0.81 (95% CI: 0.75,0.87; P , 0.0001) in the highest quintile compared with thelowest (Table 10). The inverse association was attenuated ordisappeared after adjustment for bran (RR: 0.88; 95% CI: 0.77,1.00; P = 0.04) or cereal fiber (RR: 0.93; 95% CI: 0.84, 1.05;NS). A cross-sectional study (51) reported no association withdiastolic blood pressure. Evidence for the association of whole-grain consumption with hypertension is considered inadequateto draw any conclusions (level D).

TABLE 7

Prospective cohort studies of whole grain: body weight measures

Author, year


No. of

participants, age Follow-up

Whole-grain intake

Endpoints

Highest vs

lowest P-trendHighest Lowest

Koh-Banerjee

et al, 2004 (52)

HPFS1 27,082 M,

aged 40–75 y

8 y Change in intake:

+15.6 g/d

Change in intake:

217.8 g/d

Body weight

change

(kg/8 y)

+0.69 vs +0.96

(difference: 0.27)

0.002

1HPFS, Health Professionals Follow-Up Study.



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TABLE8

Prospective

cohortstudiesoncereal

fiber:risk

ofCVD

andhypertension1

Author,year

(reference)

Studynam

e

Noof

participants

Age

Follow

-up

Endpoints

No.of

cases

Cerealfiber

intake

RR

95%

CI

P-trend

Highest

Low

est

yy

g/d

Eshak

etal,

2010(65)

JCCSECR

58,730M

+F,

general

population

40–79

14.3

CVD

mortality

inmen

2080

.2.1

,1.4

0.862

0.64,

0.99

0.042

0.893

0.65,

1.01

0.060

CVD

mortality

inwomen

.1.7

,1.1

0.772

0.59,

0.98

0.031

0.763

0.59,

0.97

0.044

Heet

al,

2010(66)

NHS

7822F,

diabetic

30–55

26

CVD

mortality

295

32.6

g4.8

g0.70

0.46,

1.06

NS

Pietinen

etal,

1996(67)

ATBCstudy

21,930M,general

population

50–69

6.1

CHD

death

581

26.3

8.8

0.74

0.57,

0.96

0.01

Pietinen

etal,

1996(67)

ATBCstudy

21,930M

50–69

6.1

Coronaryevent

1399

26.3

8.8

0.91

0.77,

1.09

NS

Wolk

etal,

1999(68)

NHS

68,782F

37–64

10

CHD

events

591

7.7

2.2

0.63

0.49,

0.81

0.002

Liu

etal,

2002(69)

NHS

39,876F

$45

5.8

CVD

events

570

6.5

3.0

1.11

0.84,

1.46

NS

Mozaffarian

etal,2003(70)

CHS

3588M

+F

$65

8.6

CVD

events

811

.6.3

,1.7

0.79

0.62,

0.99

0.02

Mozaffarian

etal,2003(70)

CHS

3588M

+F

$65

8.6

Totalstroke

392

.6.3

,1.7

0.78

0.64,

0.95

,0.05

Ohet

al,

2005(71)

NHS

78,799F

30–55

18

Totalstroke

1020

5.7

1.4

0.66

0.52,

0.83

0.001

Ascherio

etal,

1996(72)

HPFS

43,738M

40–75

8Totalstroke

328

CF:NA

(total

fiber:28.9)

CF:NA

(total

fiber:12.4)

0.57

0.36,

0.92

0.03

Liu

etal,

2002(69)

NHS

39,876F

$45

5.8

MI

177

6.5

3.0

0.91

0.56,

1.47

NS

Rim

met

al,

1996(73)

HPFS

43,757M

40–75

6Fatal

andnonfatalMI

734

9.7

2.2

0.71

0.54,

0.92

0.01

Alonsoet

al,

2006(74)

SUN

follow

-upstudy

5880M

+F

.20

.2

Hypertension

180

NA

NA

0.60

0.3,1.0

0.05

1ATBC,Alpha-Tocopherol,Beta-CaroteneCancerPrevention;CF,cerealfiber;CHD,coronaryheartdisease;CHS,CardiovascularHealthStudy;

CVD,cardiovasculardisease;HPFS,HealthProfessionals

Follow

-UpStudy;JC

CSECR,JapaneseCollaborative

Cohort

StudyforEvaluationofCancerRisks;

MI,

myocardialinfarction;NA,notavailable;NHS,Nurses’HealthStudy;SUN,TheSeguim

iento

Universidad

deNavarra.

2Multivariable

model.

3Multivariable

model

plusfurther

adjustmentforfiber.

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DISCUSSION

This review focused on the observational studies linkingconsumption of whole grains, mixtures of whole grains and bran,or cereal fiber intake with risk reduction for T2D, obesity, orCVD. The strength of evidence from observational studies is notas strong as that from intervention trials (23, 85); however, wecould not identify any long-term (.1 y) RCTs that used cerealfiber, mixtures of whole grains and bran, or whole grains. Al-though there are many controlled trials that used a specific fiber,whole grain, or bran on putative intermediate biomarkers, nonemeasured disease endpoints. All such studies were of short-termduration, recruited small numbers of subjects, or participantswere given controlled portions of the foods that do not mimicordinary daily consumption. Unfortunately, it is difficult toconduct long-term, adequately powered randomized trials ofconsumption on cereal fiber, bran, and whole grains because ofthe difficulty in controlling food intake over long-enough pe-riods to show a difference in outcomes between groups, eventhough they are needed to make sound recommendations.Clinical trials have compared whole with refined grains, butnone studied whole grains compared with bran or cereal fiber. In

addition, a study on a single grain or a mixture of 1–2 grainsdoes not necessarily assess the impact of the whole-grain foodcategory as consumed by the population. Thus, observationalstudies have to be used for decision making concerning potentialassociations of grain components with health. A well-designedobservational study may be more persuasive than poorly con-trolled and performed or otherwise very limited randomizedtrials (86). However, observational studies have several limitationsas follows: 1) not all confounders can be controlled, 2) protocols(including food-frequency questionnaires) of each observationalstudy are different, and 3) food composition tables may notaccurately reflect individual foods consumed by participants of thestudy.

We considered that the data from large prospective studies aresuperior to and more reliable than those from cross-sectionalstudies. Thus, we have rated the strength of scientific evidence onthe basis of the quality, quantity, and consistency of results fromlarge prospective studies and have simply presented cross-sectionalsummaries as supporting data in Appendixes A–K.

We found that most RCTs and meta-analyses of RCTs did notcapture the impact of major whole grains, such as wheat and corn,

TABLE 9

Prospective cohort studies on mixtures of whole grain and bran: risk of CVD and hypertension1

Author, year


No. of

participants Age Follow-up Endpoints

No. of

cases

Whole-grain intake


y y servings

Jacobs et al,

1998 (13)

IWHS 31,284 F 55–69 9 Mortality from IHD 438 3.2 0.2/d 0.70 0.50, 0.98 0.02

Jacobs et al,

1999 (14)

IWHS 31,284 F 55–69 9 CVD mortality 1097 3.2 0.2/d 0.82 0.63, 1.06 0.03

Liu et al,

2003 (76)

PHS2 86,190 M 40–84 5.5 CVD Mortality 3114 $1.0 Rarely 0.80 0.66, 0.97 0.008

Sayhoun et al,

2006 (45)

NA 535 M + F 60–98 12–15 CVD Mortality 89 .1.94 #0.56/d 0.48 0.25, 0.96 0.04

Liu et al,

1999 (15)

NHS 75,521 F 38–63 10 CHD, fatal and

nonfatal MI

761 2.7 0.13/d 0.753 0.59, 0.95 0.01

0.794 0.62, 1.01 0.07

Steffen et al,

2003 (77)

ARIC study 11,940 M + F 45–64 11 Incident CAD 535 3.0 0.1/d 0.72 0.53, 0.97 0.05

Steffen et al,

2003 (77)

ARIC study 11,940 M + F 45–64 11 Heart failure 1140 .1/d — 0.93 0.87, 0.99 ,0.05

Nettleton et al,

2008 (78)

ARIC study 14,153 M + F 45–64 13 Heart failure,

hospitalized

1140 Per difference of 1 serving/d 0.93 0.87, 0.99 ,0.05

Djousse et al,

2007 (79)

PHS2 21,376 M 40–86 19.6 Heart failure 1018 $1 0/wk 0.72 0.59, 0.88 ,0.001

Liu et al,

2000 (80)

NHS 75,521 F 38–63 10 Ischemic stroke 352 2.7 0.13/d 0.645 0.47, 0.89 0.04

0.696 0.50, 0.98 0.08

Steffen et al,

2003 (77)

ARIC study 11,940 M + F 45–64 11 Ischemic stroke 214 3.0 0.1/d 0.75 0.46, 1.22 NS

Wang et al,

2007 (81)

WHS 28,926 F $45 10 Hypertension 8722 5.0 0.28/d 0.89 0.82, 0.97 0.007

1Age, age at baseline; ARIC, Atherosclerosis Risk in Communities; CAD, fatal and nonfatal myocardial infarction, coronary artery disease death, and

stroke; CHD, coronary heart disease; CVD, cardiovascular disease; IHD, ischemic heart disease; IWHS, Iowa Women’s Health Study; MI, myocardial

infarction; NA, not applicable; NHS, Nurses’ Health Study; PHS, Physicians’ Health Study; WHS, Women’s Health Study.2Reports from PHS were limited to breakfast cereals with $25% whole grains and bran.3Multivariable model adjusted for age, BMI, cigarette smoking, alcohol intake, parental or family history of myocardial infarction before age 60 y, self-

reported hypertension or hypercholesterolemia, menopausal status, hormone replacement usage, protein intake, aspirin use, multiple vitamin or vitamin E use,

vigorous activity, total energy intake, and dietary fatty acid classes.4Multivariable model after further adjustment for dietary fiber, folate, and vitamins E and B-6.5After adjustments for age and smoking.6Multivariable model, after further adjustments for other known CVD risk factors.



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consumed in the United States. Health Canada rejected healthclaims for whole grains and heart disease risk reduction, becausethe studies on minor whole grains such as oat and barley showedrisk reductions for heart disease but there were not enough data onmajor grains such aswheat and corn (87). Also, no long-termRCTsare available. Thus, observational studies may more accuratelyreflect the impact of whole grains as consumed by the population.

There is reasonable evidence for an inverse association of intakeof cereal fiber or mixtures of whole grains and bran and risk re-ductions for T2D and CVD (Table 11). However, the relation isless convincing for whole grains by themselves when using thecurrently accepted definition. The evidence (evidence level B/C)for the association between intakes of cereal fiber or mixtures ofwhole grains and bran and body weight measures is not as strongas those for T2D and CVD. This is partly due to the fact that theabsolute amounts of body weight changes were relatively smalldespite significant differences between the highest and the lowestintake groups, and it is difficult to assess clinical benefits relatedto such small differences. Despite minimal differences in absoluteweight gain, the studies reporting risks of obesity (OR: 0.81; 95%CI: 0.73, 0.91; P-trend = 0.0002; 56), weight gain of $25 kg(OR: 0.77; 95% CI: 0.59, 1.01; P = 0.03; 56), or weight gain of$10 kg (RR: 0.78; 95% CI: 0.64, 0.96; P = 0.01; 57), or BMI(21.9 compared with 23.6; P , 0.05; 58) presented stronger ev-idence for mixtures of whole grains and bran.

With regard to risk reduction for CVD, evidence for the as-sociation with cereal fiber intake is considered moderate (evi-dence level B) due to consistent inverse associations noted forCVD mortality and stroke. Evidence for whole grains and bran isconsidered moderate (evidence level B) due to consistent inverseassociations found across different populations. However, evi-dence for whole grains, per se, is considered limited (66, 84).Overall, the evidence for whole grains alone is limited or verylimited for reduction in risk of T2D, CVD, or obesity/bodyweight measures.

The inverse associations for the consumption of whole grains ormixtures of whole grains and bran and the risk of T2D, bodyweight measures, or CVDwere attenuated or disappeared after themodels were adjusted for cereal fiber, magnesium, bran, and/orother dietary components in whole grains (9, 26, 40, 52, 83, 84).The data indicated that the inverse relation between whole-grainintake and chronic conditions may be partly due to cereal fiber andbran in whole grains, and that cereal fiber and/or bran may accountfor much of the risk reduction associated with whole grains.

Our review supports the summary from the Life SciencesResearch Office (88), which stated that the associations betweenwhole-grain intake and risk reduction for T2D and CVD areinconclusive when the definition of whole grain does not includeadded bran. Similar conclusions were reached by the EuropeanFood Safety Authority (89), which rejected health claims relatedto whole grains (blood cholesterol concentration, carbohydratemetabolism and insulin sensitivity, low glycemic index, weightcontrol, and weight management, among others). These con-clusions may be due, in part, to the following factors: 1) very fewstudies had a long follow-up period; 2) different types of wholegrains may have different physiologic roles, thus it is difficult toreach a conclusion from studies investigating the effects of onetype of whole grain; and 3) the limited number of studies in-vestigated whole-grain effects alone (ie, most whole-grainstudies are confounded by the inclusion of bran cereals). It is

TABLE 10

Prospective cohort studies on whole grains: risk of CVD and hypertension1

Author, year


No. of

participants Age Follow-up Endpoints

No. of

cases

Whole-grain

intake


y y g/d

Jensen et al,

2004 (83)

HPFS 42,850 M 40–75 14 CHD 1818 42.4 3.5 0.822 0.70, 0.96 0.01

0.843 0.71, 0.98 0.02

0.854 0.71, 1.02 0.06

He et al,

2010 (66)

NHS 7822 F with T2D 30–55 26 CVD specific mortality 295 32.6 4.8 0.70 0.46, 1.06 NS

Flint et al,

2009 (84)

HPFS 31,648 M 40–75 18 Hypertension 9227 46.0 3.3 0.81 0.75, 0.87 ,0.0001

0.885 0.77, 1.00 0.04

0.946 0.84, 1.05 NS

1RRs are for the comparison between the extreme quintiles. CHD, coronary heart disease; CVD, cardiovascular disease; HPFS, Health Professionals

Follow-Up Study; NHS, Nurses’ Health Study; T2D, type 2 diabetes.2Multivariable model including adjustment for added bran, added germ, age, energy intake, smoking, alcohol, physical activity, family history of

myocardial infarction, vitamin E supplement use, and intakes of fats, fruit, vegetables, and fish.3Multivariable model plus BMI.4Multivariable model plus BMI plus dietary fiber, magnesium, and other nutrients.5Multivariable model including adjustment for bran.6Multivariable model including adjustment for cereal fiber.

TABLE 11

Summary of evidence level1

T2D Obesity CVD Hypertension

Cereal fiber B B/C B D

Mixtures of whole

grains and bran

B B/C B D

Whole grains C C/D C D

1CVD, cardiovascular disease; T2D, type 2 diabetes.

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noteworthy that recent reviews or meta-analyses reporting healthbenefits of whole grains include bran-rich foods in the whole-grain definition (90). Because this study simply accepted thevarious categorizations of whole grain by the individual researchstudies, it is not considered as a definitive summary of evidencesupporting the current DGA recommendations for whole grainsas defined by the FDA. The European Food Safety Authorityreport also identified the problem of inconsistent definitions ofwhole grains in published research studies (89).

It is recommended that large-scale, long-term RCTs be con-ducted to verify the results from observational studies. Fundingand logistical challenges associated with this are huge, but this isthe best opportunity to conclusively show health benefits fromwhole grains. In addition, more observational studies withupdated databases and whole-grain definitions that exclude brancereals and other foods previously included in the whole-graincategory are recommended to show health benefits of wholegrains per se. Future research should be able to differentiate theimpact of whole grains from that of whole grains with added bran.

ASN POSITION

Based on the current state of the science, there is moderateevidence that consumption of foods rich in cereal fiber or mix-tures of whole grains and bran is associated with a reduced risk ofobesity (level of evidence: B/C), T2D (level of evidence: B), orCVD (level of evidence: B). The data for whole grains alone arelimited primarily because of varying definitions among epide-miologic studies of what, and how much, was included in thatfood category (level of evidence: C for T2D or CVD and C/D forobesity).

We thank Richard Kahn for helpful discussions, particularly related to de-

velopment of the evidence grading system.

The authors’ responsibilities were as follows—All authors contributed

substantially to the development of this statement and reviewed and ap-

proved the final manuscript.

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APPENDIX A

Cross-sectional studies of cereal fiber: risk factors for T2D1

Author, year

(reference) Study name No. of participants Age

Cereal fiber intake

Endpoints

ORs or risk factor mean values

P-trendHighest Lowest Highest Lowest

y g/d

McKeown et al,

2004 (35)

FOS 2834 M + F 26–82 20.4 (.13) 0.90 (,1.5) OR (95% CI)

of MetS

0.62 (0.45, 0.86) 1.0 (reference) 0.002

HOMA-IR 6.5 6.8 0.02

6.52 6.92 0.003

Newby et al,

2007 (36)

BLSA 1516 M + F 27–88 9.5 2.2 Fasting glucose

(mmol/L)

5.52 6 0.0533 5.55 6 0.05 NS

10.4 2.4 2-h glucose

(mmol/L)

6.48 6 0.21 8.05 6 0.21 0.02

11.6 2.5 Fasting insulin

(mmol/L)

73.0 6 4.0 68.9 6 4.0 NS

2-h insulin

(mmol/L)

413 6 38.2 438 6 38.8 NS

Qi et al,

2006 (37)

NHS 902 F 30–55 10.0 (.8.6) 3.5 (,4.4) Plasma adiponectin

(mg/mL)

7.9 6.9 0.01

Qi et al,

2005 (38)

HPFS 780 M 40–75 10.0 ($8.6) 3.5 (,4.4) Plasma adiponectin

(mg/mL)

17.3 14.0 0.003

16.74 14.5 0.063

Lairon et al,

2005 (39)

SUVIMAX 5961 M + F 35–60 M: .10.6 M: ,5.3 OR (95% CI) of

elevated fasting

glucose

1.37 (0.79, 2.39) 1.0 NS

F: .7.7 F: ,3.9

1BLSA, Baltimore Longitudinal Study of Aging; FOS, Framingham Offspring Study; HPFS, Health Professionals Follow-Up Study; MetS, metabolic

syndrome; NHS, Nurses’ Health Study; SUVIMAX, Supplementation en Vitamines et Mineraux Antioxidants; T2D, type 2 diabetes.2After adjustment for whole grains.3Mean 6 SEM (all such values).4Multivariable model plus adjustment for magesium.

APPENDIX B

Cross-sectional studies of mixtures of whole grains and bran: risk of T2D or MetS1

Author, year


No. of

participants

Age at

baseline

Whole-grain intake

OR 95% CI P-trendHighest Lowest

y

Esmaillzadeh

et al, 20052 (44)

TLGS 827 M + F 18–74 229 g/d 6 g/d MetS: 0.68 MetS: 0.60, 0.78 0.01 for MetS

T2D: 0.84 T2D: 0.73, 0.99 NS for T2D

McKeown et al,

2004 (35)

FOS 2834 M + F 26–82 20.4 servings/wk 0.90 servings/wk MetS: 0.67 0.48, 0.91 0.01

Sahyoun et al,

2006 (45)

NA (community-living

persons in Boston)

535 M + F 60–98 2.9 servings/d 0.31 servings/d MetS: 0.46 0.27, 0.79 0.005

1 FOS, Framingham Offspring Study; MetS, metabolic syndrome; NA, not applicable; TLGS, Teheran Lipid and Glucose Study; T2D, type 2 diabetes.2 Included germs in the definition of whole grain.

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APPENDIX

C

Cross-sectional

analysisofmixturesofwhole

grainsandbran:risk

factors

forT2D1

Author,year

(reference)

Studynam

e

No.of

participants

Ageat

baseline

Whole-grain

intake

Riskfactor

Highest

Low

est

Endpoints

Highest

Low

est

P-trend

y

Sahyounet

al,

2006(45)

NA

535M

+F

60–98

2.9

servings/d

0.31servings/d

Fastingglucose

(mg/dL)

108.5

114.9

0.01

Liese

etal,

2003(46)

IRAS

978M

+F

40–69

Studyofmeanwhole

grain

intake=0.8

60.7

servings/d

ISb:0.082

0.001

Fastinginsulin

b:20.065

0.02

IS2

b:0.041

NS

Fastinginsulin2

b:20.031

NS

Lutsey

etal,

2007(47)

MESA

5496M

+F

45–84

1.39servings/d

0.02servings/d

Fastinginsulin(m

U/L)

5.16

5.37

0.002

Fastingglucose

(mg/dL)

97.6

99.0

0.08

HOMA-IR

(mU/L

3mmol/L)

1.53

1.68

0.02

McK

eownet

al,

2002(48)

FOS

2941M

+F

26–82

20.5

servings/wk

0.90servings/wk

Fastingglucose

(mmol/L)

5.22

5.32

0.05

5.243

5.303

NS

2-h

glucose

(mmol/L)

5.823

5.843

NS

Fastinginsulin(pmol/L)

195

210

0.001

1983

2073

0.002

2024

2064

NS

2015

2055

NS

2-h

insulin(pmol/L)

561

605

0.02

5683

5923

NS

Glycatedhem

oglobin

(%)

5.243

5.263

NS

New

byet

al,

2007(36)

BLSA

1516M

+F

27–88

45.4

g/d

0.56g/d

Fastingglucose

(mmol/L)

5.49

5.49

NS

50.6

g/d

1.1

g/d

2-h

glucose

(mmol/L)

7.32

8.24

0.006

51.5

g/d

2.2

g/d

Fastinginsulin(m

mol/L)

71.8

71.6

NS

51.7

g/d

2.4

g/d

2-h

insulin(m

mol/L)

414

479

NS

Pereira

etal,

1998(49)

CARDIA

3627Black

andwhiteadults

40–75

.9servings/wk

0–2servings/wk

Fastinginsulin(uU/m

L)

,0.05

Year0

10.3

10.8

Year7

11.3

12.4

,0.05

Steffen

etal,

2003(50)

NA

285M

+F

.1.5

servings/d

,0.5

servings/d

IS(m

g$kg21$min

21)

13.3

11.5

0.01

Fastinginsulin(m

U/L)

13.8

16.7

0.07

Fastingglucose

(mg/dL)

99.3

99.4

NS

1Lutsey

etal(47)included

branmuffin.BLSA,B

altimore

LongitudinalStudyofAging;CARDIA

,CoronaryArteryRiskDevelopmentin

YoungAdults;FOS,Framingham

Offspring

Study;

IRAS,Insulin

Resistance

AtherosclerosisStudy;IS,insulinsensitivity;MESA,Multi-Ethnic

StudyofAtherosclerosis;NA,notavailable;T2D,type2diabetes.

2Multivariable

model

afterfurther

adjustmentsfordietary

fiber,magnesium,BMI,andwaistcircumference.

3Multivariable

model

afterfurther

adjustmentforBMI.

4After

further

adjustmentforintakeofmagnesium.

5After

further

adjustmentforintakeofdietary

fiber.



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APPENDIX D

Cross-sectional study of whole grains: risk factors for T2D1

Author, year


No. of

participants Age

Whole-grain intake

Risk factors

Risk factors

P-valueHighest Lowest Highest Lowest

y g/d

Jensen et al,

2006 (51)

HPFS and

NHS II

938 M + F 25–75 43.8 8.2 Hb A1c (%) 5.49 5.50 NS

Insulin (uIU/L) 11.3 13.2 NS

Fasting glucose (mg/dL) 86.1 86.8 NS

1Hb A1c, glycated hemoglobin; HPFS, Health Professionals Follow-Up Study; NHS, Nurses’ Health Study; T2D, type 2 diabetes.

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APPENDIX

E

Cross-sectional

studiescomparingcereal

fiber:risk

ofobesityandbodyweightmeasures1

Author,year

(reference)

Studynam

e

No.of

participants

Age

Cerealfiber

intake,

g/d

Endpoints

Bodyweightmeasures

(ORorhighestvslowest)

P-trend

Highest

Low

est

yg/d

McK

eownet

al,

2009(54)

FHS

434M

+F

60–80

9.3

2.4

BMI(kg/m

2)

25.4

vs27.3

0.01

(%bodyfat)

31.5

vs34.7

0.004

New

byet

al,

2007(36)

BLSA

1516M

+F

27–88

9.5

2.2

BMI(kg/m

2)

24.3

60.2

vs25.7

60.2

,0.0001

Weight(kg)

71.4

60.8

vs75.6

60.7

0.004

9.7

2.3

WC(cm)

84.2

60.6

vs87.5

60.8

,0.0001

Laironet

al,2005(39)

SUVIM

AX

study

12,741M

+F

35–60

M:.10.6

M:,5.3

OR

(95%

CI)forBMI$25

0.70(0.55,0.90)

0.003

F:.7.7

F:,3.9

OR

(95%

CI)forWHR.0.95

0.99(0.78,1.26)

NS

vandeVijver

etal,2009(55)

NLCS

4237M

+F

55–69

Increased

intakeby

1g/d

Weightgain

Decreasein

BMIby0.04

inmen;NSin

women

P,

0.01formen;

NSforwomen

1BLSA,Baltimore

Longitudinal

StudyofAging;FHS,Framingham

HeartStudy;

NLCS,NetherlandsCohortStudy;SUVIM

AX,Supplementationen

Vitam

ines

etMinerauxAntioxidants;WC,waist

circumference;WHR,waist-to-hip

ratio.



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APPENDIX F

Cross-sectional studies on mixtures of whole grains and bran: risk of obesity and body weight measures1

Author, year


No. of

participants Age

Whole-grain intake

Endpoints

RR or OR

(highest vs lowest) P-trendHighest Lowest

y

Esmaillzadeh

et al, 2005 (44)

TLGS1 827 M + F 18–74 229 g/d 6 g/d OR (95% CI) for

abdominal

adiposity2

0.90 (0.79, 0.96) 0.04

OR (95% CI)

for obesity

0.71 (0.54, 1.09) NS

Good et al,

2008 (59)

NHANES 2092 F $19 $1 serving/d 0 servings/d RR for BMI

$25 kg/m21.47 (1.12, 1.94) for

women consuming

no whole grains

0.013

1TLGS, Teheran Lipid and Glucose Study.2Abdominal adiposity (waist circumference .102 cm for men and .88 cm for women).

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APPENDIX

G

Cross-sectional

studiesofmixturesofwhole

grainsandbran:bodyweight

measures1

Author,year

(reference)

Studynam

e

No.of

participants

Age

Whole-grain

intake

Endpoints

Bodyweight

measures

(highestvslowest)

P-trend

Highest

Low

est

y

McK

eownet

al,2009(54)

FHS

434M

+F

60–80

2.86servings/d

0.21servings/d

BMI(kg/m

2)

25.8

vs26.8

0.08,NS

(%bodyfat)

32.1

vs34.5

0.02

(%trunkfatmass)

39.4

vs43.0

0.02

New

byet

al,2007(36)

BLSA

1516M

+F

27–88

46.0

g/d

0.65g/d

BMI

24.8

vs.25.5

,0.001

Weight(kg)

72.6

vs75.0

0.004

49.3

g/d

0.94g/d

WC(cm)

85.0

vs87.4

0.002

McK

eownet

al,2002(48)

FOS

2941M

+F

26–82

2.9

servings/d

0.13servings/d

BMI(kg/m

2)

26.4

vs26.9

0.06

WHR

0.91vs0.92

0.005

Lutsey

etal,2007(47)

MESA

5496M

+F

45–84

1.39servings/d

0.02servings/d

BMI(kg/m

2)

27.6

vs28.2

,0.0001

McK

eownet

al,2010(60)

FHS

2834M

+F

32–83

2.93(2.04–12.7)servings/d

0.14(0.00–0.30)

servings/d

WC(cm)

93.7

vs97.0

,0.001

BMI(kg/m

2)

26.3

vs27.4

,0.001

VAT(cm

3)

1676vs1864

,0.001

SAT(cm

3)

2739vs2756

NS

Sahyounet

al,2006(45)

NA

(community-living

personsin

Boston)

535M

+F

60–98

.1.94servings/d

#0.56servings/d

BMI(kg/m

2)

25.2

vs26.4

0.03

Masters

etal,2010(61)

IRAS

1015M

+F

40–60

2.00servings/d

0.04servings/d

BMI(kg/m

2)

28.2

vs28.8

BMI=NS,WC=NS

WC(cm)

89.9

vs91.7

Chenget

al,2009(62)

DONALD

Study

215M

+F

$2

48.9

g/1000kcal

26.3

g/1000kcal

(%bodyfat)

b=0.669

NS

1Lutsey

etal(47)included

branmuffin;Mastersetal

(61)included

high-fiber

brancereals;forNew

byetal

(36),notclearwhat

was

included

butappearedto

includebran.BLSA,Baltimore

Longitudinal

StudyofAging;DONALD,Dortmund

Nutritional

andAnthropometricLongitudinally

Designed

Study;FHS,Framingham

Heart

Study;

FOS,Framingham

Offspring

Study;

IRAS,InsulinResistance

AtherosclerosisStudy;

MESA,Multi-Ethnic

StudyofAtherosclerosis;NA,notapplicable;SAT,subcutaneousadipose

tissue;

VAT,visceraladipose

tissue;

WC,waistcircumference;WHR,waist-to-hip

ratio.



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APPENDIX

H

Cross-sectional

studiesofwhole

grain:bodyweightmeasures1

Author,year

(reference)

Studynam

eParticipants

Whole-grain

intake

Endpoints

Biomarkers

(highestvslowest)

P-trend

Highest

Low

est

O’N

eilet

al,

2010(9)

NHANES1998–2004

7039aged

19–50y;6237

aged

$51y

4.6

servings/d

0.1

servings/d

BMI:ages

19–50

y(kg/m

2)

27.7

vs.28.02

,0.05

28.1

vs.27.9

3NS

BMI:ages

$51y

(kg/m

2)

27.9

vs.28.72

,0.05

28.3

vs.28.6

3NS

WC:ages

19–50y(cm)

94.2

vs.94.6

2,0.05

95.1

vs.94.5

3NS

WC:ages

$51y(cm)

98.2

vs.100.62

,0.05

99.1

vs.100.43

NS

Zanovec

etal,

2010(64)

NHANES2000–2006

8799M

+F

aged

6–18y

4.6

servings/d

0.1

servings/d

WCandBMIzscore

Ages

6–12y:WC,64.1

vs66.7

cm;BMIzscore,

0.23vs0.52

WC,P,

0.05;

BMI

zscore,P,

0.05

Ages

13–18

y:WC,78.2

vs81.4

cm;BMIzscore,

0.18vs0.54

WC,P,

0.05;

BMI

zscore,P,

0.05

vandeVijver

etal,2009(55)b

NLCS

4237M

+F

aged

55–69

y

Increasedintakeby1g/d

Regressionanalysis

DecreaseofBMIby0.03

formen

and0.04forwomen

,0.01

1NLCS,NetherlandsCohortStudy;WC,waistcircumference.

2Multivariable

model.

3Multivariable

model

pluscereal

fiber.

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APPENDIX

I

Cross-sectional

studiesoncereal

fiber

intake:

risk

factors

forCVD1

Reference

Studynam

eNo.ofparticipants

Age

Cerealfiber

intake

Endpoints

RR

(highestvslowest)

95%

CI

P-trend

Highest

Low

est

yg/d

Laironet

al,2005(39)

SUVIM

AX

2532M

45–60

.10.6

,5.3

Hypertension:yes

vsno,year2

0.86

0.67,1.10

0.02

Riskofelevated

Hcy,year3

0.73

0.50,1.07

0.02

3429F

35–60

.7.7

,3.9

Riskofelevated

TC,year1

0.94

0.75,1.17

NS

Riskofelevated

TG,year1

1.09

0.79,1.50

NS

Lichtensteinet

al,1986(75)

Caerphilly

Heart

Disease

Study

2421M

45–49

Mean6

SD

cereal

fiber

intake=7.7

64.5

SBP2(m

mHg/g

cereal

fiber)

DBP2(m

mHg/g

cereal

fiber)

20.186

20.111

20.363,20.009

20.228,20.005

NA

NA

1CVD,cardiovasculardisease;DBP,diastolicbloodpressure;Hcy,homocysteine,NA,notavailable;SBP,systolicbloodpressure;SUVIM

AX,Supplementationen

Vitam

ines

etMinerauxAntioxidants;

TC,totalcholesterol;TG,triglycerides.

2Bloodpressure

inem

ployed

men.



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APPENDIX

J

Cross-sectional

studiesonmixturesofwhole

grain

andbran:risk

factors

forCVD1

Author,year

(reference)

Studynam

e

(country)

No.of

participants

Age

Whole-grain

intake

Endpoints

Riskfactors/biomarker(change6

SE)

P-trend

Highest

Low

est

Highest

Low

est

y

Esm

aillzadeh

etal,2005(44)

TLGS(Iran)

827M

+F

18–74

$143g/d

,10g/d

Riskofhypertension

OR:0.84(95%

CI:0.73,0.99)

1.0

0.03

New

byet

al,2007(36)

BLSA

(USA)

1516M

+F

27–88

45.6

g/d

0.63g/d

TC

(mmol/L)

5.496

0.06

5.716

0.06

0.02

54.8

g/d

3.9

g/d

LDL-C

(mmol/L)

2.966

0.06

3.166

0.06

0.04

45.4

g/d

0.62g/d

SBP(m

mHg)

128.3

61.0

129.2

61.0

NS

DBP(m

mHg)

79.2

60.7

79.8

60.6

NS

McK

eownet

al,2002(48)

FOS(U

SA)

2941M

+F

26–82

2.93servings/d

0.13servings/d

TC

(mmol/L)

5.09

5.20

0.06

LDL-C

(mmol/L)

3.04

3.16

0.02

HDL-C

(mmol/L)

1.23

1.20

NS

SBP(m

mHg)

123.1

124.4

NS

DBP(m

mHg)

73.8

75.6

NS

Esm

aillzadeh

etal,2005(44)

TLGS(Iran)

827M

+F

18–74

$143g/d

,10g/d

TC

(mg/dL)

1936

32006

2NS

LDL-C

(mg/dL)

1206

21286

2NS

TG

(mg/dL)

1356

81676

8,0.05

SBP(m

mHg)

1156

11156

1NS

DBP(m

mHg)

776

1816

1,0.05

Lutsey

etal,2007(47)

MESA

(USA)

5496M

+F

45–84

1.39servings/d

0.02servings/d

HDL-C

(mg/dL)

51.3

51.8

NS

LDL-C

(mg/dL)

117.0

118.1

NS

SBP(m

mHg)

125.0

126.3

NS

DBP(m

mHg)

71.6

72.2

NS

CRP(m

g/L)

3.02

3.56

,0.0001

Hcy

(mmol/L)

8.82

9.62

,0.0001

Masters

etal,2010(61)

IRAS(U

SA)

1015M

+F

40–60

2.00servings/d

0.04servings/d

CRP(m

g/L)

1.55(0.62–3.42)

1.75(1.02–4.11)

0.0409

Lutsey

etal,2006(82)

CATCH

(USA)

2695M

+F

15–20

1.07–6.14servings/d

,0.20servings/d

Hcy

(mmol/L)

MM2:

5.42

MM2:

5.93

MM2:0.002

MM3:

5.67

MM3:

5.78

MM3:

NS

Steffen

etal,2003(50)

NA

285M

+F

13–15

.1.5

servings/d

,0.5

servings/d

TC

(mg/dL)

148.6

62.92

152.7

63.14

NS

LDL-C

(mg/dL)

84.6

62.53

90.4

62.73

NS

Sahyounet

al,2006(45)

NA

535M

+F

60–98

.1.94servings/d

#0.56servings/d

TC

(mg/dL)

217.8

225.8

NS

LDL-C

(mg/dL)

139.0

147.3

NS

TG

(mg/dL)

106.6

111.7

NS

SBP(m

mHg)

147.9

148.8

NS

DBP(m

mHg)

82.5

84.4

NS

1Age,ageatbaseline;BLSA,B

altimore

LongitudinalStudyofAging;CATCH,C

hild

andAdolescentTrialforCardiovascularHealth;CRP,C-reactiveprotein;CVD,cardiovasculardisease;DBP,diastolic

bloodpressure;FOS,Framingham

Offspring

Study;Hcy,homocysteine;

HDL-C,HDLcholesterol;IRAS,InsulinResistance

AtherosclerosisStudy;

LDL-C,LDLcholesterol;MESA,Multi-Ethnic

Studyof

Atherosclerosis;MM2,multipleregressionmodel2adjusted

forage,sex,race,site,energyintake,sm

oking,vitam

insupplem

entuse,BMI,andintakeofwholegrains,refined

grains,fruit,vegetables,dairy,red

orprocessed

meat,andpoultry;MM3,

multiple

regressionmodel

3adjusted

forfactors

inMM2plusserum

folate

andvitam

insB-6

andB-12;

NA,notavailable;SBP,

systolicbloodpressure;TC,total

cholesterol;TG,triglycerides;TLGS,Teheran

Lipid

andGlucose

Study.

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APPENDIX K

Cross-sectional study on whole grains: risk factors for CVD1

Author, year

(reference)

Study name

(country)

No. of

participants

Age at

baseline Follow-up

Whole grain

intake

Endpoints

Biomarker

P-trendHighest Lowest Highest Lowest

y y g/d

Jensen et al,

2006 (51)

HPFS and NHS

II (USA)

938 M + F F: 25–42 NA 43.8 8.2 TC (mg/dL) 215.6 6 2.8 222.0 6 3.0 0.02

M: 40–75 LDL-C (mg/dL) 123.9 6 2.3 126.6 6 2.7 NS

DBP (mm Hg) 60.5 6 8.1 61.8 6 8.5 NS

1CVD, cardiovascular disease; DBP, diastolic blood pressure; HPFS, Health Professionals Follow-Up Study; LDL-C, LDL cholesterol; NA, not available;

NHS, Nurses’ Health Study; TC, total cholesterol.



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