FROM THE AMERICAN SOCIETY FOR NUTRITION
SCIENTIFIC STATEMENT
Consumption of cereal fiber, mixtures of whole grains and bran, and
whole grains and risk reduction in type 2 diabetes, obesity, and
cardiovascular disease1–4
Susan S Cho,5 Lu Qi,6 George C Fahey Jr,7 and David M Klurfeld 8*
5
NutraSource, 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.
ABSTRACT
Background: Studies of whole grain and chronic disease have often
included bran-enriched foods and other ingredients that do not meet the
current definition of whole grains. Therefore, we assessed the literature
to test whether whole grains alone had benefits on these diseases.
Objective: The objective was to assess the contribution of bran or
cereal fiber on the impact of whole grains on the risk of type 2
diabetes (T2D), obesity and body weight measures, and cardiovas-
cular disease (CVD) in human studies as the basis for establishing
an American Society for Nutrition (ASN) position on this subject.
Design: We performed a comprehensive PubMed search of human
studies published from 1965 to December 2010.
Results: Most whole-grain studies included mixtures of whole
grains and foods with $25% bran. Prospective studies consistently
showed a reduced risk of T2D with high intakes of cereal fiber or
mixtures of whole grains and bran. For body weight, a limited
number of prospective studies on cereal fiber and whole grains
reported small but significant reductions in weight gain. For
CVD, studies found reduced risk with high intakes of cereal fiber
or mixtures of whole grains and bran.
Conclusions: The ASN position, based on the current state of the
science, is that consumption of foods rich in cereal fiber or mixtures
of whole grains and bran is modestly associated with a reduced risk
of obesity, T2D, and CVD. The data for whole grains alone are
limited primarily because of varying definitions among epidemio-
logic studies of what, and how much, was included in that food
category. Am J Clin Nutr 2013;98:594–619.
INTRODUCTION
The prevalence of type 2 diabetes (T2D)9 and obesity has been
increasing in the United States (1–3). Today, two-thirds of US
adults (1) and nearly 1 in 3 children are overweight or obese (4).
Intake of calories over physiologic needs has been linked to
increasing T2D, obesity, cardiovascular disease (CVD), and
other 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
594 Am J Clin Nutr 2013;98:594–619. Printed in USA. Ó 2013 American Society for Nutrition
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 servings
was less than one-third of recommended intakes: only 1.5% of
children aged 1–3 y, 4.3% of adolescents, 4.8% of adults aged
19–50 y, and 6.4% of adults .50 y meet the recommended 3–5
servings per day (8, 9). The National Health Interview Survey
2000 showed that the average American consumes only one-half
of the recommended intake of dietary fiber; .84% of American
adults do not meet recommended intakes established by the
Institute of Medicine (10, 11). Increased consumption of whole
grains and cereal fiber–rich foods such as bran can contribute to
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: david.klurfeld@ars.usda.gov.
First published online June 26, 2013; doi: 10.3945/ajcn.113.067629.
 FROM THE AMERICAN SOCIETY FOR NUTRITION
WHOLE-GRAIN, BRAN, AND FIBER INTAKE AND RISK OF DISEASE
improved fiber intake by Americans. The 2010 DGA recom-
mend whole grains as a source of dietary fiber but do not
mention other sources of dietary fiber. Furthermore, the DGA do
not recommend dietary fiber to reduce the risk of chronic dis-
eases despite the conclusion statements in the USDA Nutrition
Evidence Library that whole grains and cereal fiber intake are
associated with reduced risk of obesity and CVD (7, 12).
A change in the working definition of whole grains has
contributed to the confusion on the health effects of whole grains
and their components. Research conducted by nutritional epi-
demiologists from the University of Minnesota and Harvard
University provided much of the early data in this area; however,
these investigators used different definitions of a whole grain in
their studies (13–15). For example, some studies included brown
bread and wheat germ in the whole-grain category and others
did not (16, 17). In addition, there were no USDA databases
available at that time to calculate how much whole grain was in
a serving of the various products, and the studies provided no
information 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 well
as high-fiber bran cereals, were included in the whole-grain
working definition (13–15). Today, high-fiber bran cereals are
excluded (18, 19). Definitions of whole grain vary depending on
the context and purpose. Research from the 1990s (13–15)
supported the benefits of bran as an integral part of the health
benefits of whole grains. According to this definition established
in the 1990s, foods with $25% whole-grain or bran content by
FIGURE 1. Flow diagram of systematic review on type 2 diabetes.
595
weight were classified as whole grain. Of note, however, the
definition commonly used in the scientific community is not the
same as that on food labels, which exclude foods with $25%
bran. To establish a whole-grain health claim under the Food and
Drug Administration Modernization Act, the definition of
a 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 of
whole grains (20). Accordingly, examples of whole-grain foods
and ingredients in the Expert Panel report of the USDA/Health
and Human Services DGA include brown rice, oatmeal, whole
oats, bulgur (cracked wheat), popcorn, whole rye, graham flour,
and whole wheat (21). This list includes some low-fiber foods
but does not include bran-rich foods that are excellent sources of
fiber.
Compared with refined-grain foods, foods made with whole
grains are purported to contain fewer starches and calories and
more 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 of
fiber, vitamins, minerals, and phytonutrients, which together are
thought to provide many of the health benefits of whole grains
(22). The use of bran-concentrated or -enriched foods likely can
provide consumers with more choices for healthy foods, promote
healthful dietary practices, and help individuals meet public
health recommendations for the intake of whole grains and dietary
fiber without consumption of excess calories.
596 CHO ET AL
As the basis of an American Society for Nutrition position
statement, this systematic review seeks to determine whether
bran, cereal fiber, and whole-grain intakes have an effect on the
development 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 published
from January 1965 to December 2010 was performed. For T2D,
the following search strategy was used: (whole grain OR whole
grains OR whole-grain OR cereal fiber OR cereal fiber OR grain
fiber OR grain fiber OR bran OR brans) AND (diabetes). This
strategy identified 614 human studies. Twenty additional records
were identified through other sources. After removing duplicates
and nonrelevant articles, 66 abstracts were selected for more
detailed review. Finally, we selected 15 prospective studies and
13 cross-sectional studies that met predetermined inclusion and
exclusion criteria described below and shown in Figure 1 (23).
For obesity and measures of body weight, the PubMed search of
the following terms—whole grain OR whole grains OR whole-
grain OR cereal fiber OR cereal fiber OR grain fiber OR grain
fiber OR bran OR brans AND body weight OR body weight gain
OR body mass index OR BMI z score OR obesity OR over-
weight OR adiposity OR waist circumference OR waist-to-hip
FIGURE 2. Flow diagram of systematic review on obesity. RCT, randomized controlled trial.
ratio (WHR)—identified 538 articles. Seven additional records
were identified from other sources, such as review articles. After
removing duplicates and nonrelevant articles, 43 studies were
reviewed in detail. From these, 19 studies (5 prospective and 14
cross-sectional) were selected on the basis of our inclusion and
exclusion criteria described below and as shown in Figure 2
(23). For CVD, search terms—(whole grain OR whole grains
OR whole-grain OR cereal fiber OR cereal fiber OR grain fiber
OR grain fiber OR bran OR brans) AND (heart disease OR car-
diovascular disease OR myocardial infarction OR hypertension
OR arterial disease OR stroke OR blood pressure)—identified
894 human studies. Fifteen additional papers were identified
through other sources. After removing duplicates and non-
relevant articles, 85 abstracts were reviewed, from which we
selected 22 prospective and 12 cross-sectional studies by using
the inclusion and exclusion criteria described below and as
shown in Figure 3 (23).
When assessing the contribution of whole grains alone, our
analysis included only those studies that used the current defi-
nition of a whole grain as established by the FDA (ie, foods that
contain $51% whole-grain ingredients by weight per reference
amount customarily consumed).
Inclusion criteria
We included controlled feeding trials (intervention period of
$1 y) and observational studies reporting risk and risk factors of
 FROM THE AMERICAN SOCIETY FOR NUTRITION
WHOLE-GRAIN, BRAN, AND FIBER INTAKE AND RISK OF DISEASE
FIGURE 3. Flow diagram of systematic review on cardiovascular disease (CVD).
T2D or CVD. For obesity outcomes, we used risk of obesity or
weight-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 in
languages other than English were excluded. Articles related to
total, soluble, and insoluble fibers with no data on cereal fiber
were excluded. Short-term feeding studies (,1 y) were also
excluded because they do not reflect the long-term health impact
of these grain components as consumed by the population.
Rating scientific evidence
We used the evidence grading system shown in Table 1. This
system is similar to that used by prominent organizations such as
the American Diabetes Association (24) or recommended by
other experts (25). The assigned grade reflects the totality of the
evidence 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 were
available for summarization for T2D, obesity/body weight
measures, and CVD, respectively. Cross-sectional studies (13
reports on T2D, 14 reports on obesity, and 12 studies on CVD) are
597
also presented as supportive data in Appendixes A–K. We found
no long-term ($1 y duration), randomized controlled trials
(RCTs) that assessed the impact of cereal fiber, mixtures of
whole grains or brain, or whole grains that represent intakes of
these 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 grains
alone. Many studies reported that the inverse associations be-
tween intake of mixtures of whole grains and bran or whole
grains alone and risks of T2D, CVD, or reduced weight gain
disappeared or were attenuated after adjustment for cereal fiber
or bran, suggesting that cereal fiber and bran account for much
of the whole-grain effects.
T2D
A number of well-designed, large, prospective cohort studies
showed a consistent inverse association between consumption of
cereal fiber or mixtures of whole grains and bran and the risk
of T2D. Prospective studies consistently showed a reduced risk of
T2D with high intakes of cereal fiber (10 of 11 reports showed an
18–40% risk reduction) or mixtures of whole grains and bran (5
of 6 reports showed a risk reduction of 21–40%); one prospective
study on whole grains (meeting the FDA definition excluding
$25% bran) reported a risk reduction of 32–37% in females.
598 CHO ET AL
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
1
RCT, randomized controlled trial.

Studies on cereal fiber
The results of 11 reports are listed in Table 2: 10 reports from
8 independent prospective cohorts, each of which reported
quintile 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 of
cereal 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 the
only epidemiologic report that failed to show an association
between cereal fiber and risk of T2D (34). The Melbourne Col-
laborative Cohort’s primary purpose was to study the relation
between glycemic index and risk of T2D. Fiber and cereal fiber
concentrations were reported for each quartile of glycemic index.
Relative risk from cereal fiber was assessed on the basis of a
10-g/d intake, not fiber intake quartiles.
Most of the studies followed groups of mixed ethnicity, but
Krishnan et al (33) reported that cereal fiber intake was inversely
associated 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 cohort
study in 59,000 US black women. A stronger association was
seen among black women with a BMI (in kg/m2) ,25: the in-
cidence rate ratio for the highest compared with lowest quintile
was 0.41 (95% CI: 0.24, 0.72; P-trend = 0.003). Nine-year
follow-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 African
Americans may be due to fewer individuals and lower statistical
power or a smaller difference in cereal fiber intake amounts
between the highest and the lowest consuming groups. Data
from cross-sectional studies are consistent with the findings
from prospective studies (Appendix A; 35–39).
Evidence level B was assigned for the association between
cereal 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 grains
included foods with $25% bran in the whole-grain category. Six
prospective cohort studies on whole-grain intake and reduction
in risk of T2D are summarized in Table 3 (16, 26, 40–43). All of
these 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 of
whole grains and bran” (16, 26, 40–43). One study (16) also
included wheat germ in the whole-grain definition (Table 3). The
study by Kochar et al (41) was limited to whole-grain breakfast
cereals. These studies showed a significant inverse association
between intake of mixture of whole grains and bran and the
incidence of T2D.
 FROM THE AMERICAN SOCIETY FOR NUTRITION
WHOLE-GRAIN, BRAN, AND FIBER INTAKE AND RISK OF DISEASE 599
TABLE 2
Prospective cohort studies of cereal fiber: risk of T2D1
Cereal fiber intake
Author, year No. of No. of
(reference) Study name participants Age Follow-up cases Highest Lowest RR 95% CI P-trend

y y g/d
de Munter et al, NHS I and II 161,737 F 36–65 12–18 6486 12.0 1.1 0.64 0.54, 0.76 ,0.001
2007 (17)
Meyer et al, IWHS 35, 988 F 55–69 6 1141 9.43 2.66 0.64 0.53, 0.79 0.0001
2000 (26) 0.712 0.56, 0.89 0.002
Montonen et al, FMCHES 4316 M + F 40–69 10 156 29 6 11 12 6 3.4 0.39 0.20, 0.77 0.01
2003 (16)
Salmerón et al, NHS 66,173 F 40–65 6 523 7.5 2.0 0.72 0.58, 0.90 0.001
1997 (27)
Hu et al, NHS 84,941 F 30–55 16 3300 NA NA 0.60 0.53, 0.67 ,0.001
2001 (28)
Schulze et al, NHS II 91,249 F 24–44 8 741 8.8 3.1 0.64 0.48, 0.86 0.004
2004 (29)
Salmerón et al, HPFS 42,759 M 40–75 6 915 10.2 2.5 0.70 0.51, 0.96 0.007
1997 (30)
Schulze et al, EPIC-Potsdam study 25,067 M + F 35–65 7 844 16.6 6.6 0.72 0.56, 0.93 0.02
2007 (31)
Stevens et al, ARIC study 12,251 M + F 45–64 9 1447 W: 5.1 6 3.6 W: 2.7 6 1.7 0.75 0.60, 0.92 ,0.05
2002 (32) (W and AA) 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, 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
2007 (33)
Hodge et al, MCCS 36,787 M + F 40–69 4 365 Every 10 g 0.97 0.79, 1.20 NS
2004 (34)
1
RRs 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.
2
Multivariable model plus adjustment for cereal grains and magnesium.

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 or
disappeared after adjustments for other dietary factors such as
dietary fiber or cereal fiber/magnesium (16, 26, 40). These data
suggest that dietary fiber and magnesium account for much of the
risk reduction associated with intake of mixtures of whole grains
and bran.
In the study by Meyer et al (26), women in the highest intake
quintile of mixtures of whole grains and bran had an adjusted RR
of 0.79 (95% CI: 0.65, 0.96; P-trend = 0.0089) for T2D relative
to those in the lowest quintile. Cereal fiber and dietary magne-
sium, 2 components of whole grains, were strongly related to
T2D 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 and
magnesium (RR: 0.93; 95% CI: 0.75, 1.16; P-trend = NS).
Cereal fiber and dietary magnesium had significant inverse
relations with T2D, even after simultaneous adjustment for
grains, and cereal grains: RRs were 0.71 (95% CI: 0.56, 0.89;
P-trend = 0.0017) in the highest quintiles of cereal fiber and
0.76 (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 seen
with mixtures of whole grains and bran disappeared when the
data were adjusted for cereal fiber, magnesium, and glycemic
load.
In the Finnish Mobile Clinic Health Examination Survey,
Montonen et al (16) found that consumption of whole grains and
cereal fiber was associated with a reduced risk of T2D. The RRs
between 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 inverse
relation between high intake of whole grains and T2D was
similar 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), vitamin
B-6, folic acid, flavonoids, and magnesium. After further ad-
justment for cereal fiber, the RR in the highest quartile of whole
grain 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, and
magnesium. The authors suggested an independent association
between cereal fiber intake and T2D.
It is noteworthy that the whole-grain intake amounts in Finnish
cohorts is significantly higher than those in the US cohorts; the
highest and the lowest intake group consumed 236 and 79 g of
mixtures of whole grains and bran, respectively. Despite the
600 CHO ET AL
TABLE 3
Prospective cohort studies of mixtures of whole grains and bran: risk of T2D1
Intake of mixtures of
whole grains and bran
Author, year No of Age at No. of
(reference) Study name participants baseline Follow-up cases Highest Lowest RR 95% CI P-trend

y y
Fung et al, HPFS 42,898 M 40–75 #12 1197 3.2 servings/d 0.4 servings/d 0.70 0.57, 0.85 0.0006
2002 (40) 0.982 0.76, 1.26 NS
Kochar et al, 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
20073 (41)
Liu et al, NHS 75,521 F 38–63 10 1879 2.70 servings/d 0.13 servings/d 0.73 0.63, 0.85 ,0.0001
2000 (42)
Meyer et al, IWHS 35,988 F 55–69 6 1141 .17.5 servings/wk ,3.0 servings/wk 0.79 0.65, 0.96 0.0089
2000 (26) 0.934 0.75, 1.16 NS
van Dam et al, BWHS 41,186 F 21–69 8 1964 1.29 servings/d 0.03 servings/d 0.69 0.60, 0.79 ,0.0001
2006 (43)
Montonen et al, FMCHES5 4316 M + F 40–69 10 156 302 g/d 79 g/d 0.64 0.36, 1.15 0.02
2003 (16) 0.676 0.32, 1.38 NS
1.147 0.66, 2.49 NS
1
BWHS, 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.
2
Multivariable model after further adjustment for cereal fiber, magnesium, and glycemic load.
3
Limited to breakfast cereals with $25% of whole grains and bran.
4
Multivariable model plus adjustment for cereal fiber intake.
5
Included germs in the whole-grain definition.
6
Multivariable 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.
7
Multivariable model after further adjustment for cereal fiber

differences in major sources of whole grains (rye in Finland and
wheat in the United States), trends for inverse associations were
similar between the 2 countries. Data from cross-sectional studies
are consistent with the findings from prospective studies (Ap-
pendixes B and C; 35, 36, 44–50).
Evidence level B was fulfilled for the association between
intake of mixtures of whole grains and bran and risk reduction of
T2D.
Studies on whole grains
Two studies (17, 51) met the whole-grain definition criteria
defined 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’ Health
Study (NHS)], (Table 4; 17). No prospective study in males was
found. Although the NHS was a carefully designed and well-
conducted study, the absence of any confirmatory prospective
study limits the confidence that whole grains reduce the in-
cidence of T2D. Nonetheless, the data from the NHS allow one
to make a comparison between the benefit of whole grain
compared with cereal fiber in reducing the risk of diabetes.
Daily intakes of bran, cereal fiber, and whole grains were 9.6–12
g, 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 data
suggest that daily intakes of 8–11 g of cereal fiber and 34–40 g
of whole grains provide comparable RR values. One cross-
sectional study showed no association with risk factors related to
T2D (Appendix D; 51).
Evidence for the association between whole-grain intake and
development of T2D was considered as level C.
Obesity and body weight measures
Studies on cereal fiber
The 2 prospective studies (52, 53) relating cereal fiber to
various body weight measures are listed in Table 5. These 2

TABLE 4
Prospective cohort studies on whole grains: risk of T2D1
Whole-grain
intake2
No. of No. of
Author, year (reference) Study name participants Age Follow-up cases Highest Lowest RR 95% CI P-trend

y y g/d
de Munter et al, NHS I 73,327 F 37–65 12–18 4747 36.9 3.2 0.63 0.57, 0.69 ,0.001
2007 (17) NHS II 88,410 F 26–46 12–18 1739 45.6 5.5 0.68 0.57, 0.81 ,0.001
1
RRs are for the comparison between the extreme quintiles. NHS, Nurses’ Health Study; T2D, type 2 diabetes.
2
The definition of whole grain met the US Food and Drug Administration criteria.

WHOLE-GRAIN, BRAN, AND FIBER INTAKE AND RISK OF DISEASE
TABLE 5
Prospective cohort studies on cereal fiber; body weight measures1
Author, year No. of Study design,
(reference) Study name participants, age follow-up Highest
Koh-Banerjee HPFS 27,082 M, P, 8 y
et al, 2004 (52) aged 40–75 y
Du et al, 2010 (53) Diogenes 89,432 M + F, P, 6.5 y
Project aged 20–78 y
1
Values in parentheses are 95% CIs. HPFS, Health Professionals Follow-Up Study; P, prospective; WC, waist circumference.
prospective cohort studies in males and females showed sig-
nificant inverse associations between cereal fiber intake and
body weight measures. However, the absolute reduction in
weight gain from cereal fiber consumption was 0.39 kg between
the 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 of
10 g cereal fiber. Although these differences were significant, it
is 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 and
the lowest intakes were large enough to have biological signif-
icance.
We assigned evidence level B/C for an inverse association
between cereal fiber intake and various body weight measures.
Studies on mixtures of whole grains and bran
Most studies on whole grains included $25% bran in the
definition 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 reports
comparing whole grains and bran with measures of body weight
are listed in Table 6 (52, 56, 57). All of the 3 large prospective
cohort studies in both men and women (52, 56, 57) and a small
prospective cohort study in children (58) reported consistent
inverse correlations between intakes of mixtures of whole grain
and bran and BMI, weight gain, body weight, or risk of obesity.
Despite consistent inverse associations, these prospective studies
showed minimal differences in absolute body weight or body
weight gain between the highest and the lowest intake groups:
The studies by Koh-Banerjee et al (52), Liu et al (56), and
Bazzanzo et al (57) reported body weight gain differences of
0.52, 0.39, and 0.35–0.42 kg, respectively, during 8- to 13-y
follow-up periods. It is difficult to assess the health impact of
such minimal differences.
However, Liu et al (56) reported that, over a 12-y period, the
reductions in risk of obesity and weight gain of $25 kg were
19% and 23%, respectively. Also, Bazzano et al (57) reported
FROM THE AMERICAN SOCIETY FOR NUTRITION
601
Cereal fiber intake
Body weight measures
Lowest Endpoints (highest vs lowest) P-trend
g/d
Change in Change in Body weight +0.91 vs +1.30 0.0004
intake: 5.1 intake: 22.2 change (kg/8 y) (0.39-kg difference)
12.6 6 4.6 9.3 6 3.5 Body weight change 277 (2127, –26) 0.01
(g/y) per 10 g
cereal fiber/d
WC change (cm/y) 20.10 (20.18, 20.02) ,0.001
per 10 g cereal
fiber/d
that, compared with the lowest consumers, the highest con-
sumers of breakfast cereals with $25% whole grains and bran
had 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 reduction
in BMI of 7.2% during the 2-y follow up period in the highest
consumers 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 association
between intake of whole grains and bran and body weight
measures (Appendixes F and G). The differences in BMI, body
weight, or WC between the highest and the lowest intake were
large enough and may have biological significance. The studies
reporting no associations (61, 62) or mixed results (44) had low
numbers of subjects and may not have had sufficient statistical
power (Appendixes F and G).
Evidence level B/C was the grade for the association between
intake of mixtures of whole grains and bran and measures of body
weight.
Studies on whole grains
One study defined whole grains as foods containing $10%
whole grains or bran (63). There was one prospective study in
a male cohort with a lengthy follow-up (Health Professionals
Follow-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 weight
gain (0.29 kg) in the highest intake group was minimal: weight
gains over the 8-y follow-up period were 0.69 and 0.96 kg for
the highest and the lowest quintile category, respectively (P-
trend = 0.002). Despite statistical significance, the differences
are likely not biologically meaningful.
The relation between whole grains and reduction in weight
gain was weakened after adjustment for added bran and cereal
fiber intakes but still persisted. A cross-sectional study by O’Neil
et al (Appendix H; 9) showed that inverse associations between
whole-grain intake and body weight measures (BMI and WC)
disappeared after adjustment for cereal fiber.
Because only one prospective study in men reported a minimal
difference in body weight gain between the highest and the lowest
intake groups, evidence for the inverse association of whole
grains is considered level C/D.
 602

TABLE 6
Prospective cohort studies on mixtures of whole grains and bran: risk of obesity and body weight measures1
Intake of mixtures of
whole grains and bran
Author, year No. of RR (95% CI) or body weight
(reference) Study name participants, age Follow-up Highest Lowest Endpoints measure (highest vs lowest) P-trend

y
Liu et al, NHS 74,091 F, aged 12 Servings/1000 Servings/1000 kcal per day: OR for weight gain, $25 kg 0.77 (0.59, 1.01) 0.03
2003 (56) 38–63 y kcal per day: at baseline, 0.07; change in 12 y
at baseline, in intake in 12 y, 20.59 OR for BMI (in kg/m2) $30 0.81 (0.73, 0.91) 0.0002
1.62; change in 12 y
in intake in Weight gain (kg) 4.12 vs 4.51 ,0.0001
2–4 12 y, 0.90 Average changes in BMI 0.46 vs 0.56 ,0.0001
(kg/m2)
Average changes 1.23 vs 1.52 ,0.0001
in weight (kg)
CHO ET AL

Koh-Banerjee HPFS 26,082 M, aged 8 +27.0 g/d 211.0 g/d Body weight change +0.73 vs +1.25 ,0.0001
et al, 2004 (52) 40–75 y (kg/8 y) (difference: 0.52)
Bazzano et al, PHS2 17,881 M 8 $1 serving/d Rarely Weight gain (kg) 1.13 vs 1.55 0.003
2005 (57) RR for BMI $25 0.83 (0.71, 0.98) 0.06
13 Weight gain (kg) 1.83 vs 2.18 0.08
RR for BMI $25 0.91 (0.79, 1.05) 0.13
RR for weight 0.78 (0.64, 0.96) 0.01
gain $10 kg
Steffen et al, 2003 (58) MPSS 285 M + F, 2 .1.5 servings/d ,0.5 servings/d BMI (kg/m2) 21.9 vs 23.6 0.05
mean age
of 13 y
1
HPFS, Health Professionals Follow-Up Study; MPSS, Minneapolis Public School Students; NHS, Nurses’ Health Study; PHS, Physicians’ Health Study.
2
A report from the PHS was limited to breakfast cereals with $25% whole grains and bran.

WHOLE-GRAIN, BRAN, AND FIBER INTAKE AND RISK OF DISEASE
TABLE 7
Prospective cohort studies of whole grain: body weight measures
Author, year No. of
(reference) Study name participants, age Follow-up
1
Koh-Banerjee HPFS 27,082 M, 8y
et al, 2004 (52) aged 40–75 y
1
HPFS, Health Professionals Follow-Up Study.
CVD
Prospective studies consistently showed a reduced risk of CVD
with high intakes of cereal fiber (a risk reduction of 14–26% for
CVD mortality and 22–43% for stroke) or mixtures of whole
grains and bran (a risk reduction of 7–52% for CVD mortality,
CVD events, and heart failure). Only 1 of 2 prospective studies
showed an inverse association between whole-grain intake and
reduction in risk of CVD. Subtypes of stroke were not evaluated
in this review. Also, one study (63), which used the cutoff of
10% whole-grain content to define whole-grain foods, is not
included in the review.
Studies on cereal fiber
A summary of the reports showing the relation between cereal
fiber consumption and CVD or hypertension are provided in
Table 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 of
outcome measures were reported. In general, a consistent but
modest risk reduction was seen in CVD mortality (65, 67) and
stroke (69–71): risk reductions were in the range of 14–26% for
CVD mortality and 22–43% for stroke. However, a non-
significant risk reduction (RR: 0.70; 95% CI: 0.46, 1.06; NS) in
CVD mortality was observed in subjects with T2D (66). The risk
reductions for CVD events (68–70) and myocardial infarction
(69, 73) were inconsistent. No studies showed adverse effects of
cereal fiber. Two cross-sectional studies reported mixed results
(Appendix I; 39, 75).
The evidence level is B for the association between cereal fiber
intake 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 and
stronger among males than in females. A cross-sectional study
supported the findings from a prospective study (75; Appendix
I). Evidence is considered inadequate (level D) due to the lim-
ited number of large, well-designed prospective studies.
Studies on mixtures of whole grains and bran
A summary of 10 reports from 6 independent prospective
studies showing a relation between consumption of mixtures of
whole grains and bran and reduction in risk of CVD or hyper-
tension is provided in Table 9 (13–15, 45, 76–81). Most of the
reports (w80%) related to heart disease considered whole-grain
foods as products containing whole grains and $25% bran.
FROM THE AMERICAN SOCIETY FOR NUTRITION
603
Whole-grain intake
Highest vs
Highest Lowest Endpoints lowest P-trend
Change in intake: Change in intake: Body weight +0.69 vs +0.96 0.002
+15.6 g/d 217.8 g/d change (difference: 0.27)
(kg/8 y)
Reports from the Physicians’ Health Study (76, 79) limited the
investigation to breakfast cereals containing whole grains and
$25% bran. All 9 reports from 4 large and 1 small prospective
cohort studies showed significant inverse associations between
intakes of mixtures of whole grains and bran and risks of CVD
mortality, CVD events, and heart failure in both males and fe-
males (Table 9; 13–15, 45, 76–79). However, the risk reduction
for ischemic stroke was not significant (77, 80).
Cross-sectional studies on risk factors for CVD in relation to
consumption of whole grains and bran reported mixed results
(Appendix J; 36, 44, 47, 48, 50, 61, 82). Overall, moderate
evidence (grade B) exists for the association between intake of
mixtures of whole grains and bran and reduction in risk of CVD
because all large, prospective cohort studies showed relatively
consistent associations and the number of studies was adequate.
Only one study (81; Table 9) reported an inverse association
between reduction in risk of hypertension and intakes of mixtures
of whole grains and bran in women only, and cross-sectional
studies generally found no association (36, 44, 45, 47, 48; Ap-
pendix J). Thus, there is inadequate evidence to suggest that
consumption of whole grains with added bran will affect the
incidence of hypertension (evidence level D).
Studies on whole grains
A summary of the reports showing a relation between whole-
grain consumption and risk of CVD or hypertension is provided
in Table 10 (66, 83, 84). The inverse association between
whole-grain intake and CVD risk was attenuated and became
nonsignificant after adjustment for dietary fiber, magnesium,
and other dietary factors (83), indicating that dietary fiber and
magnesium account for whole-grain actions. The study by He
et al (66), which reported no association, was confined to diabetic
women. One cross-sectional study (Appendix K; 51) reported
inconsistent associations of whole-grain or bran intake with risk
factors for CVD. Thus, there is limited evidence for the associa-
tion between intake of whole grains and reduction in risk of
CVD (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 the
lowest (Table 10). The inverse association was attenuated or
disappeared 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 with
diastolic blood pressure. Evidence for the association of whole-
grain consumption with hypertension is considered inadequate
to draw any conclusions (level D).
 604

TABLE 8
Prospective cohort studies on cereal fiber: risk of CVD and hypertension1
Cereal fiber intake
Author, year No of No. of
(reference) Study name participants Age Follow-up Endpoints cases Highest Lowest RR 95% CI P-trend

y y g/d
Eshak et al, JCCSECR 58,730 M + F, general 40–79 14.3 CVD mortality in men 2080 .2.1 ,1.4 0.862 0.64, 0.99 0.042
2010 (65) population 0.893 0.65, 1.01 0.060
CVD mortality in women .1.7 ,1.1 0.772 0.59, 0.98 0.031
0.763 0.59, 0.97 0.044
He et al, NHS 7822 F, diabetic 30–55 26 CVD mortality 295 32.6 g 4.8 g 0.70 0.46, 1.06 NS
2010 (66)
Pietinen et al, ATBC study 21,930 M, general 50–69 6.1 CHD death 581 26.3 8.8 0.74 0.57, 0.96 0.01
1996 (67) population
Pietinen et al, ATBC study 21,930 M 50–69 6.1 Coronary event 1399 26.3 8.8 0.91 0.77, 1.09 NS
1996 (67)
Wolk et al, NHS 68,782 F 37–64 10 CHD events 591 7.7 2.2 0.63 0.49, 0.81 0.002
1999 (68)
Liu et al, NHS 39,876 F $45 5.8 CVD events 570 6.5 3.0 1.11 0.84, 1.46 NS
2002 (69)
Mozaffarian CHS 3588 M + F $65 8.6 CVD events 811 .6.3 ,1.7 0.79 0.62, 0.99 0.02
CHO ET AL

et al, 2003 (70)

Mozaffarian CHS 3588 M + F $65 8.6 Total stroke 392 .6.3 ,1.7 0.78 0.64, 0.95 ,0.05
et al, 2003 (70)
Oh et al, NHS 78,799 F 30–55 18 Total stroke 1020 5.7 1.4 0.66 0.52, 0.83 0.001
2005 (71)
Ascherio et al, HPFS 43,738 M 40–75 8 Total stroke 328 CF: NA (total CF: NA (total 0.57 0.36, 0.92 0.03
1996 (72) fiber: 28.9) fiber: 12.4)
Liu et al, NHS 39,876 F $45 5.8 MI 177 6.5 3.0 0.91 0.56, 1.47 NS
2002 (69)
Rimm et al, HPFS 43,757 M 40–75 6 Fatal and nonfatal MI 734 9.7 2.2 0.71 0.54, 0.92 0.01
1996 (73)
Alonso et al, SUN follow- up study 5880 M + F .20 .2 Hypertension 180 NA NA 0.60 0.3, 1.0 0.05
2006 (74)
1
ATBC, Alpha-Tocopherol, Beta-Carotene Cancer Prevention; CF, cereal fiber; CHD, coronary heart disease; CHS, Cardiovascular Health Study; CVD, cardiovascular disease; HPFS, Health Professionals
Follow-Up Study; JCCSECR, Japanese Collaborative Cohort Study for Evaluation of Cancer Risks; MI, myocardial infarction; NA, not available; NHS, Nurses’ Health Study; SUN, The Seguimiento
Universidad de Navarra.
2
Multivariable model.
3
Multivariable model plus further adjustment for fiber.
 FROM THE AMERICAN SOCIETY FOR NUTRITION
WHOLE-GRAIN, BRAN, AND FIBER INTAKE AND RISK OF DISEASE 605
TABLE 9
Prospective cohort studies on mixtures of whole grain and bran: risk of CVD and hypertension1
Whole-grain intake
Author, year No. of No. of
(reference) Study name participants Age Follow-up Endpoints cases Highest Lowest RR 95% CI P-trend

y y servings
Jacobs et al, IWHS 31,284 F 55–69 9 Mortality from IHD 438 3.2 0.2/d 0.70 0.50, 0.98 0.02
1998 (13)
Jacobs et al, IWHS 31,284 F 55–69 9 CVD mortality 1097 3.2 0.2/d 0.82 0.63, 1.06 0.03
1999 (14)
Liu et al, PHS2 86,190 M 40–84 5.5 CVD Mortality 3114 $1.0 Rarely 0.80 0.66, 0.97 0.008
2003 (76)
Sayhoun et al, NA 535 M + F 60–98 12–15 CVD Mortality 89 .1.94 #0.56/d 0.48 0.25, 0.96 0.04
2006 (45)
Liu et al, NHS 75,521 F 38–63 10 CHD, fatal and 761 2.7 0.13/d 0.753 0.59, 0.95 0.01
1999 (15) nonfatal MI 0.794 0.62, 1.01 0.07
Steffen et al, 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
2003 (77)
Steffen et al, ARIC study 11,940 M + F 45–64 11 Heart failure 1140 .1/d — 0.93 0.87, 0.99 ,0.05
2003 (77)
Nettleton et al, ARIC study 14,153 M + F 45–64 13 Heart failure, 1140 Per difference of 1 serving/d 0.93 0.87, 0.99 ,0.05
2008 (78) hospitalized
Djoussé et al, PHS2 21,376 M 40–86 19.6 Heart failure 1018 $1 0/wk 0.72 0.59, 0.88 ,0.001
2007 (79)
Liu et al, NHS 75,521 F 38–63 10 Ischemic stroke 352 2.7 0.13/d 0.645 0.47, 0.89 0.04
2000 (80) 0.696 0.50, 0.98 0.08
Steffen et al, ARIC study 11,940 M + F 45–64 11 Ischemic stroke 214 3.0 0.1/d 0.75 0.46, 1.22 NS
2003 (77)
Wang et al, WHS 28,926 F $45 10 Hypertension 8722 5.0 0.28/d 0.89 0.82, 0.97 0.007
2007 (81)
1
Age, 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.
2
Reports from PHS were limited to breakfast cereals with $25% whole grains and bran.
3
Multivariable 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.
4
Multivariable model after further adjustment for dietary fiber, folate, and vitamins E and B-6.
5
After adjustments for age and smoking.
6
Multivariable model, after further adjustments for other known CVD risk factors.

DISCUSSION addition, a study on a single grain or a mixture of 1–2 grains

This review focused on the observational studies linking
consumption of whole grains, mixtures of whole grains and bran,
or cereal fiber intake with risk reduction for T2D, obesity, or
CVD. The strength of evidence from observational studies is not
as strong as that from intervention trials (23, 85); however, we
could not identify any long-term (.1 y) RCTs that used cereal
fiber, 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, none
measured disease endpoints. All such studies were of short-term
duration, recruited small numbers of subjects, or participants
were given controlled portions of the foods that do not mimic
ordinary daily consumption. Unfortunately, it is difficult to
conduct long-term, adequately powered randomized trials of
consumption on cereal fiber, bran, and whole grains because of
the difficulty in controlling food intake over long-enough pe-
riods to show a difference in outcomes between groups, even
though they are needed to make sound recommendations.
Clinical trials have compared whole with refined grains, but
none studied whole grains compared with bran or cereal fiber. In
does not necessarily assess the impact of the whole-grain food
category as consumed by the population. Thus, observational
studies have to be used for decision making concerning potential
associations of grain components with health. A well-designed
observational study may be more persuasive than poorly con-
trolled and performed or otherwise very limited randomized
trials (86). However, observational studies have several limitations
as follows: 1) not all confounders can be controlled, 2) protocols
(including food-frequency questionnaires) of each observational
study are different, and 3) food composition tables may not
accurately reflect individual foods consumed by participants of the
study.
We considered that the data from large prospective studies are
superior to and more reliable than those from cross-sectional
studies. Thus, we have rated the strength of scientific evidence on
the basis of the quality, quantity, and consistency of results from
large prospective studies and have simply presented cross-sectional
summaries as supporting data in Appendixes A–K.
We found that most RCTs and meta-analyses of RCTs did not
capture the impact of major whole grains, such as wheat and corn,
606 CHO ET AL
TABLE 10
Prospective cohort studies on whole grains: risk of CVD and hypertension1
Whole-grain
intake
Author, year No. of No. of
(reference) Study name participants Age Follow-up Endpoints cases Highest Lowest RR 95% CI P-trend

y y g/d
Jensen et al, HPFS 42,850 M 40–75 14 CHD 1818 42.4 3.5 0.822 0.70, 0.96 0.01
2004 (83) 0.843 0.71, 0.98 0.02
0.854 0.71, 1.02 0.06
He et al, NHS 7822 F with T2D 30–55 26 CVD specific mortality 295 32.6 4.8 0.70 0.46, 1.06 NS
2010 (66)
Flint et al, HPFS 31,648 M 40–75 18 Hypertension 9227 46.0 3.3 0.81 0.75, 0.87 ,0.0001
2009 (84) 0.885 0.77, 1.00 0.04
0.946 0.84, 1.05 NS
1
RRs 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.
2
Multivariable 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.
3
Multivariable model plus BMI.
4
Multivariable model plus BMI plus dietary fiber, magnesium, and other nutrients.
5
Multivariable model including adjustment for bran.
6
Multivariable model including adjustment for cereal fiber.

consumed in the United States. Health Canada rejected health
claims for whole grains and heart disease risk reduction, because
the studies on minor whole grains such as oat and barley showed
risk reductions for heart disease but there were not enough data on
major grains such as wheat and corn (87). Also, no long-term RCTs
are available. Thus, observational studies may more accurately
reflect the impact of whole grains as consumed by the population.
There is reasonable evidence for an inverse association of intake
of cereal fiber or mixtures of whole grains and bran and risk re-
ductions for T2D and CVD (Table 11). However, the relation is
less convincing for whole grains by themselves when using the
currently accepted definition. The evidence (evidence level B/C)
for the association between intakes of cereal fiber or mixtures of
whole grains and bran and body weight measures is not as strong
as those for T2D and CVD. This is partly due to the fact that the
absolute amounts of body weight changes were relatively small
despite significant differences between the highest and the lowest
intake groups, and it is difficult to assess clinical benefits related
to such small differences. Despite minimal differences in absolute
weight 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 for
CVD mortality and stroke. Evidence for whole grains and bran is
considered moderate (evidence level B) due to consistent inverse
associations 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 very
limited for reduction in risk of T2D, CVD, or obesity/body
weight measures.
The inverse associations for the consumption of whole grains or
mixtures of whole grains and bran and the risk of T2D, body
weight measures, or CVD were attenuated or disappeared after the
models were adjusted for cereal fiber, magnesium, bran, and/or
other dietary components in whole grains (9, 26, 40, 52, 83, 84).
The data indicated that the inverse relation between whole-grain
intake and chronic conditions may be partly due to cereal fiber and
bran in whole grains, and that cereal fiber and/or bran may account
for much of the risk reduction associated with whole grains.
Our review supports the summary from the Life Sciences
Research Office (88), which stated that the associations between
whole-grain intake and risk reduction for T2D and CVD are
inconclusive when the definition of whole grain does not include
added bran. Similar conclusions were reached by the European
Food Safety Authority (89), which rejected health claims related
to whole grains (blood cholesterol concentration, carbohydrate
metabolism and insulin sensitivity, low glycemic index, weight
control, and weight management, among others). These con-
clusions may be due, in part, to the following factors: 1) very few
studies had a long follow-up period; 2) different types of whole
grains may have different physiologic roles, thus it is difficult to
reach a conclusion from studies investigating the effects of one
type of whole grain; and 3) the limited number of studies in-
vestigated whole-grain effects alone (ie, most whole-grain
studies are confounded by the inclusion of bran cereals). It is
TABLE 11
Summary of evidence level1
T2D Obesity CVD Hypertension
Cereal fiber B B/C B D
Mixtures of whole B B/C B D
grains and bran
Whole grains C C/D C D
1
CVD, cardiovascular disease; T2D, type 2 diabetes.
 FROM THE AMERICAN SOCIETY FOR NUTRITION
WHOLE-GRAIN, BRAN, AND FIBER INTAKE AND RISK OF DISEASE
noteworthy that recent reviews or meta-analyses reporting health
benefits of whole grains include bran-rich foods in the whole-
grain definition (90). Because this study simply accepted the
various categorizations of whole grain by the individual research
studies, it is not considered as a definitive summary of evidence
supporting the current DGA recommendations for whole grains
as defined by the FDA. The European Food Safety Authority
report also identified the problem of inconsistent definitions of
whole 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. Funding
and logistical challenges associated with this are huge, but this is
the best opportunity to conclusively show health benefits from
whole grains. In addition, more observational studies with
updated databases and whole-grain definitions that exclude bran
cereals and other foods previously included in the whole-grain
category are recommended to show health benefits of whole
grains per se. Future research should be able to differentiate the
impact of whole grains from that of whole grains with added bran.
ASN POSITION
Based on the current state of the science, there is moderate
evidence that consumption of foods rich in cereal fiber or mix-
tures of whole grains and bran is associated with a reduced risk of
obesity (level of evidence: B/C), T2D (level of evidence: B), or
CVD (level of evidence: B). The data for whole grains alone are
limited primarily because of varying definitions among epide-
miologic studies of what, and how much, was included in that
food category (level of evidence: C for T2D or CVD and C/D for
obesity).
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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610 CHO ET AL
APPENDIX A
Cross-sectional studies of cereal fiber: risk factors for T2D1
Cereal fiber intake ORs or risk factor mean values
Author, year
(reference) Study name No. of participants Age Highest Lowest Endpoints Highest Lowest P-trend

y g/d
McKeown et al, FOS 2834 M + F 26–82 20.4 (.13) 0.90 (,1.5) OR (95% CI) 0.62 (0.45, 0.86) 1.0 (reference) 0.002
2004 (35) of MetS
HOMA-IR 6.5 6.8 0.02
6.52 6.92 0.003
Newby et al, BLSA 1516 M + F 27–88 9.5 2.2 Fasting glucose 5.52 6 0.0533 5.55 6 0.05 NS
2007 (36) (mmol/L)
10.4 2.4 2-h glucose 6.48 6 0.21 8.05 6 0.21 0.02
(mmol/L)
11.6 2.5 Fasting insulin 73.0 6 4.0 68.9 6 4.0 NS
(mmol/L)
2-h insulin 413 6 38.2 438 6 38.8 NS
(mmol/L)
Qi et al, NHS 902 F 30–55 10.0 (.8.6) 3.5 (,4.4) Plasma adiponectin 7.9 6.9 0.01
2006 (37) (mg/mL)
Qi et al, HPFS 780 M 40–75 10.0 ($8.6) 3.5 (,4.4) Plasma adiponectin 17.3 14.0 0.003
2005 (38) (mg/mL)
16.74 14.5 0.063
Lairon et al, SUVIMAX 5961 M + F 35–60 M: .10.6 M: ,5.3 OR (95% CI) of 1.37 (0.79, 2.39) 1.0 NS
2005 (39) elevated fasting
glucose
F: .7.7 F: ,3.9
1
BLSA, 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.
2
After adjustment for whole grains.
3
Mean 6 SEM (all such values).
4
Multivariable model plus adjustment for magesium.

APPENDIX B
Cross-sectional studies of mixtures of whole grains and bran: risk of T2D or MetS1
Whole-grain intake
Author, year No. of Age at
(reference) Study name participants baseline Highest Lowest OR 95% CI P-trend

y
Esmaillzadeh TLGS 827 M + F 18–74 229 g/d 6 g/d MetS: 0.68 MetS: 0.60, 0.78 0.01 for MetS
et al, 20052 (44) T2D: 0.84 T2D: 0.73, 0.99 NS for T2D
McKeown et al, FOS 2834 M + F 26–82 20.4 servings/wk 0.90 servings/wk MetS: 0.67 0.48, 0.91 0.01
2004 (35)
Sahyoun et al, NA (community-living 535 M + F 60–98 2.9 servings/d 0.31 servings/d MetS: 0.46 0.27, 0.79 0.005
2006 (45) persons in Boston)
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.
APPENDIX C
Cross-sectional analysis of mixtures of whole grains and bran: risk factors for T2D1
Whole-grain intake Risk factor
Author, year No. of Age at
(reference) Study name participants baseline Highest Lowest Endpoints Highest Lowest P-trend

y
Sahyoun et al, NA 535 M + F 60–98 2.9 servings/d 0.31 servings/d Fasting glucose (mg/dL) 108.5 114.9 0.01
2006 (45)
Liese et al, IRAS 978 M + F 40–69 Study of mean whole grain IS b: 0.082 0.001
2003 (46) intake = 0.8 6 0.7 servings/d
Fasting insulin b: 20.065 0.02
IS2 b: 0.041 NS
Fasting insulin2 b: 20.031 NS
Lutsey et al, MESA 5496 M + F 45–84 1.39 servings/d 0.02 servings/d Fasting insulin (mU/L) 5.16 5.37 0.002
2007 (47) Fasting glucose (mg/dL) 97.6 99.0 0.08
HOMA-IR (mU/L 3 mmol/L) 1.53 1.68 0.02
McKeown et al, FOS 2941 M + F 26–82 20.5 servings/wk 0.90 servings/wk Fasting glucose (mmol/L) 5.22 5.32 0.05
2002 (48) 5.243 5.303 NS
3
2-h glucose (mmol/L) 5.82 5.843 NS
Fasting insulin (pmol/L) 195 210 0.001
1983 2073 0.002
2024 2064 NS
5
201 2055 NS
2-h insulin (pmol/L) 561 605 0.02
5683 5923 NS
Glycated hemoglobin (%) 5.243 5.263 NS
Newby et al, BLSA 1516 M + F 27–88 45.4 g/d 0.56 g/d Fasting glucose (mmol/L) 5.49 5.49 NS
2007 (36) 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 Fasting insulin (mmol/L) 71.8 71.6 NS
51.7 g/d 2.4 g/d 2-h insulin (mmol/L) 414 479 NS
Pereira et al, CARDIA 3627 Black and white adults 40–75 .9 servings/wk 0–2 servings/wk Fasting insulin (uU/mL) ,0.05
1998 (49) Year 0 10.3 10.8
Year 7 11.3 12.4 ,0.05
Steffen et al, NA 285 M + F .1.5 servings/d ,0.5 servings/d IS (mg $ kg21 $ min21) 13.3 11.5 0.01
WHOLE-GRAIN, BRAN, AND FIBER INTAKE AND RISK OF DISEASE

2003 (50) Fasting insulin (mU/L) 13.8 16.7 0.07

Fasting glucose (mg/dL) 99.3 99.4 NS
1
Lutsey et al (47) included bran muffin. BLSA, Baltimore Longitudinal Study of Aging; CARDIA, Coronary Artery Risk Development in Young Adults; FOS, Framingham Offspring Study; IRAS, Insulin
Resistance Atherosclerosis Study; IS, insulin sensitivity; MESA, Multi-Ethnic Study of Atherosclerosis; NA, not available; T2D, type 2 diabetes.
2
Multivariable model after further adjustments for dietary fiber, magnesium, BMI, and waist circumference.
3
Multivariable model after further adjustment for BMI.
4
After further adjustment for intake of magnesium.
5
After further adjustment for intake of dietary fiber.
FROM THE AMERICAN SOCIETY FOR NUTRITION
611
612 CHO ET AL
APPENDIX D
Cross-sectional study of whole grains: risk factors for T2D1
Whole-grain intake Risk factors
Author, year No. of
(reference) Study name participants Age Highest Lowest Risk factors Highest Lowest P-value

y g/d
Jensen et al, HPFS and 938 M + F 25–75 43.8 8.2 Hb A1c (%) 5.49 5.50 NS
2006 (51) NHS II Insulin (uIU/L) 11.3 13.2 NS
Fasting glucose (mg/dL) 86.1 86.8 NS
1
Hb A1c, glycated hemoglobin; HPFS, Health Professionals Follow-Up Study; NHS, Nurses’ Health Study; T2D, type 2 diabetes.
APPENDIX E
Cross-sectional studies comparing cereal fiber: risk of obesity and body weight measures1
Cereal fiber intake, g/d
Author, year No. of Body weight measures
(reference) Study name participants Age Highest Lowest Endpoints (OR or highest vs lowest) P-trend

y g/d
McKeown et al, FHS 434 M + F 60–80 9.3 2.4 BMI (kg/m2) 25.4 vs 27.3 0.01
2009 (54) (% body fat) 31.5 vs 34.7 0.004
Newby et al, BLSA 1516 M + F 27–88 9.5 2.2 BMI (kg/m2) 24.3 6 0.2 vs 25.7 6 0.2 ,0.0001
2007 (36) Weight (kg) 71.4 6 0.8 vs 75.6 6 0.7 0.004
9.7 2.3 WC (cm) 84.2 6 0.6 vs 87.5 6 0.8 ,0.0001
Lairon et al, 2005 (39) SUVIMAX study 12,741 M + F 35–60 M: .10.6 M: ,5.3 OR (95% CI) for BMI $25 0.70 (0.55, 0.90) 0.003
F: .7.7 F: ,3.9 OR (95% CI) for WHR .0.95 0.99 (0.78, 1.26) NS
van de Vijver NLCS 4237 M + F 55–69 Increased Weight gain Decrease in BMI by 0.04 P , 0.01 for men;
et al, 2009 (55) intake by in men; NS in women NS for women
1 g/d
1
BLSA, Baltimore Longitudinal Study of Aging; FHS, Framingham Heart Study; NLCS, Netherlands Cohort Study; SUVIMAX, Supplementation en Vitamines et Mineraux Antioxidants; WC, waist
circumference; WHR, waist-to-hip ratio.
WHOLE-GRAIN, BRAN, AND FIBER INTAKE AND RISK OF DISEASE
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614 CHO ET AL
APPENDIX F
Cross-sectional studies on mixtures of whole grains and bran: risk of obesity and body weight measures1
Whole-grain intake
Author, year No. of RR or OR
(reference) Study name participants Age Highest Lowest Endpoints (highest vs lowest) P-trend

y
Esmaillzadeh TLGS1 827 M + F 18–74 229 g/d 6 g/d OR (95% CI) for 0.90 (0.79, 0.96) 0.04
et al, 2005 (44) abdominal
adiposity2
OR (95% CI) 0.71 (0.54, 1.09) NS
for obesity
Good et al, NHANES 2092 F $19 $1 serving/d 0 servings/d RR for BMI 1.47 (1.12, 1.94) for 0.013
2008 (59) $25 kg/m2 women consuming
no whole grains
1
TLGS, Teheran Lipid and Glucose Study.
2
Abdominal adiposity (waist circumference .102 cm for men and .88 cm for women).
APPENDIX G
Cross-sectional studies of mixtures of whole grains and bran: body weight measures1
Whole-grain intake
Author, year No. of Body weight measures
(reference) Study name participants Age Highest Lowest Endpoints (highest vs lowest) P-trend

y
McKeown et al, 2009 (54) FHS 434 M + F 60–80 2.86 servings/d 0.21 servings/d BMI (kg/m2) 25.8 vs 26.8 0.08, NS
(% body fat) 32.1 vs 34.5 0.02
(% trunk fat mass) 39.4 vs 43.0 0.02
Newby et al, 2007 (36) BLSA 1516 M + F 27–88 46.0 g/d 0.65 g/d BMI 24.8 vs.25.5 ,0.001
Weight (kg) 72.6 vs 75.0 0.004
49.3 g/d 0.94 g/d WC (cm) 85.0 vs 87.4 0.002
McKeown et al, 2002 (48) FOS 2941 M + F 26–82 2.9 servings/d 0.13 servings/d BMI (kg/m2) 26.4 vs 26.9 0.06
WHR 0.91 vs 0.92 0.005
Lutsey et al, 2007 (47) MESA 5496 M + F 45–84 1.39 servings/d 0.02 servings/d BMI (kg/m2) 27.6 vs 28.2 ,0.0001
McKeown et al, 2010 (60) FHS 2834 M + F 32–83 2.93 (2.04–12.7) servings/d 0.14 (0.00–0.30) servings/d WC (cm) 93.7 vs 97.0 ,0.001
BMI (kg/m2) 26.3 vs 27.4 ,0.001
VAT (cm3) 1676 vs 1864 ,0.001
SAT (cm3) 2739 vs 2756 NS
Sahyoun et al, 2006 (45) NA (community-living 535 M + F 60–98 .1.94 servings/d #0.56 servings/d BMI (kg/m2) 25.2 vs 26.4 0.03
persons in Boston)
Masters et al, 2010 (61) IRAS 1015 M + F 40–60 2.00 servings/d 0.04 servings/d BMI (kg/m2) 28.2 vs 28.8 BMI = NS, WC = NS
WC (cm) 89.9 vs 91.7
Cheng et al, 2009 (62) DONALD Study 215 M + F $2 48.9 g/1000 kcal 26.3 g/ 1000 kcal (% body fat) b = 0.669 NS
1
Lutsey et al (47) included bran muffin; Masters et al (61) included high-fiber bran cereals; for Newby et al (36), not clear what was included but appeared to include bran. BLSA, Baltimore Longitudinal
Study of Aging; DONALD, Dortmund Nutritional and Anthropometric Longitudinally Designed Study; FHS, Framingham Heart Study; FOS, Framingham Offspring Study; IRAS, Insulin Resistance
WHOLE-GRAIN, BRAN, AND FIBER INTAKE AND RISK OF DISEASE

Atherosclerosis Study; MESA, Multi-Ethnic Study of Atherosclerosis; NA, not applicable; SAT, subcutaneous adipose tissue; VAT, visceral adipose tissue; WC, waist circumference; WHR, waist-to-hip ratio.
FROM THE AMERICAN SOCIETY FOR NUTRITION
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APPENDIX H
Cross-sectional studies of whole grain: body weight measures1
Whole-grain intake
Author, year Biomarkers
(reference) Study name Participants Highest Lowest Endpoints (highest vs lowest) P-trend
2
O’Neil et al, NHANES 1998–2004 7039 aged 4.6 servings/d 0.1 servings/d BMI: ages 27.7 vs. 28.0 ,0.05
2010 (9) 19–50 y; 6237 19–50 y (kg/m2) 28.1 vs. 27.93 NS
aged $51 y BMI: ages $51 y 27.9 vs. 28.72 ,0.05
(kg/m2)
28.3 vs. 28.63 NS
WC: ages 19–50 y (cm) 94.2 vs. 94.62 ,0.05
95.1 vs. 94.53 NS
WC: ages $51 y (cm) 98.2 vs.100.62 ,0.05
99.1 vs. 100.43 NS
CHO ET AL

Zanovec et al, NHANES 2000–2006 8799 M + F 4.6 servings/d 0.1 servings/d WC and BMI z score Ages 6–12 y: WC, 64.1 WC, P , 0.05; BMI
2010 (64) aged 6–18 y vs 66.7 cm; BMI z score, z score, P , 0.05
0.23 vs 0.52
Ages 13–18 y: WC, 78.2 WC, P , 0.05; BMI
vs 81.4 cm; BMI z score, z score, P , 0.05
0.18 vs 0.54
van de Vijver NLCS 4237 M + F Increased intake by 1 g/d Regression analysis Decrease of BMI by 0.03 ,0.01
et al, 2009 (55)b aged 55–69 y for men and 0.04 for women
1
NLCS, Netherlands Cohort Study; WC, waist circumference.
2
Multivariable model.
3
Multivariable model plus cereal fiber.
APPENDIX I
Cross-sectional studies on cereal fiber intake: risk factors for CVD1
Cereal fiber intake
RR
Reference Study name No. of participants Age Highest Lowest Endpoints (highest vs lowest) 95% CI P-trend

y g/d
Lairon et al, 2005 (39) SUVIMAX 2532 M 45–60 .10.6 ,5.3 Hypertension: yes vs no, year 2 0.86 0.67, 1.10 0.02
Risk of elevated Hcy, year 3 0.73 0.50, 1.07 0.02
3429 F 35–60 .7.7 ,3.9 Risk of elevated TC, year 1 0.94 0.75, 1.17 NS
Risk of elevated TG, year 1 1.09 0.79, 1.50 NS
Lichtenstein et al, 1986 (75) Caerphilly Heart 2421 M 45–49 Mean 6 SD cereal fiber SBP2 (mm Hg/g cereal fiber) 20.186 20.363, 20.009 NA
Disease Study intake = 7.7 6 4.5 DBP2 (mm Hg/g cereal fiber) 20.111 20.228, 20.005 NA
1
CVD, cardiovascular disease; DBP, diastolic blood pressure; Hcy, homocysteine, NA, not available; SBP, systolic blood pressure; SUVIMAX, Supplementation en Vitamines et Mineraux Antioxidants;
TC, total cholesterol; TG, triglycerides.
2
Blood pressure in employed men.
WHOLE-GRAIN, BRAN, AND FIBER INTAKE AND RISK OF DISEASE
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APPENDIX J
Cross-sectional studies on mixtures of whole grain and bran: risk factors for CVD1
Whole-grain intake Risk factors/biomarker (change 6 SE)
Author, year Study name No. of
(reference) (country) participants Age Highest Lowest Endpoints Highest Lowest P-trend

y
Esmaillzadeh et al, 2005 (44) TLGS (Iran) 827 M + F 18–74 $143 g/d ,10 g/d Risk of hypertension OR: 0.84 (95% CI: 0.73, 0.99) 1.0 0.03
Newby et al, 2007 (36) BLSA (USA) 1516 M + F 27–88 45.6 g/d 0.63 g/d TC (mmol/L) 5.49 6 0.06 5.71 6 0.06 0.02
54.8 g/d 3.9 g/d LDL-C (mmol/L) 2.96 6 0.06 3.16 6 0.06 0.04
45.4 g/d 0.62 g/d SBP (mm Hg) 128.3 6 1.0 129.2 6 1.0 NS
DBP (mm Hg) 79.2 6 0.7 79.8 6 0.6 NS
McKeown et al, 2002 (48) FOS (USA) 2941 M + F 26–82 2.93 servings/d 0.13 servings/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 (mm Hg) 123.1 124.4 NS
DBP (mm Hg) 73.8 75.6 NS
Esmaillzadeh et al, 2005 (44) TLGS (Iran) 827 M + F 18–74 $143 g/d ,10 g/d TC (mg/dL) 193 6 3 200 6 2 NS
LDL-C (mg/dL) 120 6 2 128 6 2 NS
TG (mg/dL) 135 6 8 167 6 8 ,0.05
SBP (mm Hg) 115 6 1 115 6 1 NS
DBP (mm Hg) 77 6 1 81 6 1 ,0.05
Lutsey et al, 2007 (47) MESA (USA) 5496 M + F 45–84 1.39 servings/d 0.02 servings/d HDL-C (mg/dL) 51.3 51.8 NS
LDL-C (mg/dL) 117.0 118.1 NS
CHO ET AL

SBP (mm Hg) 125.0 126.3 NS

DBP (mm Hg) 71.6 72.2 NS
CRP (mg/L) 3.02 3.56 ,0.0001
Hcy (mmol/L) 8.82 9.62 ,0.0001
Masters et al, 2010 (61) IRAS (USA) 1015 M + F 40–60 2.00 servings/d 0.04 servings/d CRP (mg/L) 1.55 (0.62–3.42) 1.75 (1.02–4.11) 0.0409
Lutsey et al, 2006 (82) CATCH (USA) 2695 M + F 15–20 1.07–6.14 servings/d ,0.20 servings/d Hcy (mmol/L) MM2: 5.42 MM2: 5.93 MM2:0.002
MM3: 5.67 MM3: 5.78 MM3: NS
Steffen et al, 2003 (50) NA 285 M + F 13–15 .1.5 servings/d ,0.5 servings/d TC (mg/dL) 148.6 6 2.92 152.7 6 3.14 NS
LDL-C (mg/dL) 84.6 6 2.53 90.4 6 2.73 NS
Sahyoun et al, 2006 (45) NA 535 M + F 60–98 .1.94 servings/d #0.56 servings/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 (mm Hg) 147.9 148.8 NS
DBP (mm Hg) 82.5 84.4 NS
1
Age, age at baseline; BLSA, Baltimore Longitudinal Study of Aging; CATCH, Child and Adolescent Trial for Cardiovascular Health; CRP, C-reactive protein; CVD, cardiovascular disease; DBP, diastolic
blood pressure; FOS, Framingham Offspring Study; Hcy, homocysteine; HDL-C, HDL cholesterol; IRAS, Insulin Resistance Atherosclerosis Study; LDL-C, LDL cholesterol; MESA, Multi-Ethnic Study of
Atherosclerosis; MM2, multiple regression model 2 adjusted for age, sex, race, site, energy intake, smoking, vitamin supplement use, BMI, and intake of whole grains, refined grains, fruit, vegetables, dairy, red
or processed meat, and poultry; MM3, multiple regression model 3 adjusted for factors in MM2 plus serum folate and vitamins B-6 and B-12; NA, not available; SBP, systolic blood pressure; TC, total
cholesterol; TG, triglycerides; TLGS, Teheran Lipid and Glucose Study.
 FROM THE AMERICAN SOCIETY FOR NUTRITION
WHOLE-GRAIN, BRAN, AND FIBER INTAKE AND RISK OF DISEASE 619
APPENDIX K
Cross-sectional study on whole grains: risk factors for CVD1
Whole grain
intake Biomarker
Author, year Study name No. of Age at
(reference) (country) participants baseline Follow-up Highest Lowest Endpoints Highest Lowest P-trend

y y g/d
Jensen et al, HPFS and NHS 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
2006 (51) II (USA) 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
1
CVD, 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.