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
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 cardiovascular 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 epidemiologic 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
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 Rainbow, RFI Ingredient, and Shangdong Longlive. L Qi, no disclosures to report. GC Fahey, research support from Roquette America Inc, Ingredion,
Abbott Nutrition, Del Monte, and Hartz Mountain; consultancy for Ingredion, 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 Guidelines 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.
Am J Clin Nutr 2013;98:594–619. Printed in USA. Ó 2013 American Society for Nutrition
Downloaded from ajcn.nutrition.org at AMERICAN SOCIETY FOR NUTRITION on August 2, 2013
Susan S Cho,5 Lu Qi,6 George C Fahey Jr,7 and David M Klurfeld 8*
FROM THE AMERICAN SOCIETY FOR NUTRITION
WHOLE-GRAIN, BRAN, AND FIBER INTAKE AND RISK OF DISEASE
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 ingredients 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 significant 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.
FIGURE 1. Flow diagram of systematic review on type 2 diabetes.
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improved fiber intake by Americans. The 2010 DGA recommend 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 diseases 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 epidemiologists 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 problematic 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
595
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
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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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 wholegrain 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 overweight OR adiposity OR waist circumference OR waist-to-hip
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 cardiovascular 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 nonrelevant 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 definition of a whole grain as established by the FDA (ie, foods that
contain $51% whole-grain ingredients by weight per reference
amount customarily consumed).
FROM THE AMERICAN SOCIETY FOR NUTRITION
WHOLE-GRAIN, BRAN, AND FIBER INTAKE AND RISK OF DISEASE
597
T2D or CVD. For obesity outcomes, we used risk of obesity or
weight-related endpoints, such as BMI, weight gain, waist circumference (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 consensus 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
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 prospective or cross-sectional.
The majority of whole-grain studies have investigated mixtures of whole grains and $25% bran rather than whole grains
alone. Many studies reported that the inverse associations between 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.
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FIGURE 3. Flow diagram of systematic review on cardiovascular disease (CVD).
598
CHO ET AL
TABLE 1
Evidence grading system
Level of evidence (refers to the body of evidence)
A: strong
B: moderate
D: inadequate
1
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
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
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
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
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 between 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 Collaborative 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 incidence 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 relation 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 populations and included added bran in the whole-grain food category; 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.
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C: limited
Description
FROM THE AMERICAN SOCIETY FOR NUTRITION
599
WHOLE-GRAIN, BRAN, AND FIBER INTAKE AND RISK OF DISEASE
TABLE 2
Prospective cohort studies of cereal fiber: risk of T2D1
Cereal fiber intake
Author, year
(reference)
Krishnan et al,
2007 (33)
Hodge et al,
2004 (34)
Age
Follow-up
No. of
cases
NHS I and II
161,737 F
y
36–65
y
12–18
6486
IWHS
35, 988 F
55–69
6
1141
9.43
4316 M + F
40–69
10
156
29 6 11
NHS
66,173 F
40–65
6
523
7.5
NHS
84,941 F
30–55
16
3300
NHS II
91,249 F
24–44
8
HPFS
42,759 M
40–75
EPIC-Potsdam study
25,067 M + F
ARIC study
Study name
Lowest
RR
95% CI
P-trend
1.1
0.64
0.54, 0.76
,0.001
2.66
0.64
0.712
0.39
0.53, 0.79
0.56, 0.89
0.20, 0.77
0.0001
0.002
0.01
2.0
0.72
0.58, 0.90
0.001
NA
NA
0.60
0.53, 0.67
,0.001
741
8.8
3.1
0.64
0.48, 0.86
0.004
6
915
10.2
2.5
0.70
0.51, 0.96
0.007
35–65
7
844
16.6
6.6
0.72
0.56, 0.93
0.02
12,251 M + F
(W and AA)
45–64
9
1447
W: 2.7 6 1.7
AA: 2.8 6 1.6
59,000 F, AA
21–69
8
1938
0.75
0.86
0.79
0.82
0.60, 0.92
0.65, 1.15
BWHS
W: 5.1 6 3.6
AA: 4.0 6 2.6
All = W + AA
8.3 6 2.5
0.70, 0.96
,0.05
NS
,0.05
0.01
MCCS
36,787 M + F
40–69
4
365
0.97
0.79, 1.20
NS
FMCHES
Highest
g/d
12.0
12 6 3.4
1.5 6 0.7
Every 10 g
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 associations 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 magnesium, 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 association of mixtures of whole grains and bran was not significant 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 magnesium 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 adjustment for cereal fiber, the RR in the highest quartile of whole
grain intake was 1.14 (NS). The association of cereal fiber remained 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
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de Munter et al,
2007 (17)
Meyer et al,
2000 (26)
Montonen et al,
2003 (16)
Salmerón et al,
1997 (27)
Hu et al,
2001 (28)
Schulze et al,
2004 (29)
Salmerón et al,
1997 (30)
Schulze et al,
2007 (31)
Stevens et al,
2002 (32)
No. of
participants
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
(reference)
No of
participants
Age at
baseline
No. of
cases
Highest
HPFS
42,898 M
y
40–75
1197
3.2 servings/d
0.4 servings/d
PHS
21,152 M
39.7–85.9
19.1
1958
$7 servings/wk
NHS
75,521 F
38–63
10
1879
IWHS
35,988 F
55–69
6
BWHS
41,186 F
21–69
FMCHES5
4316 M + F
40–69
Follow-up
RR
95% CI
P-trend
0 servings/wk
0.70
0.982
0.60
0.57, 0.85
0.76, 1.26
0.50, 0.71
0.0006
NS
,0.0001
2.70 servings/d
0.13 servings/d
0.73
0.63, 0.85
,0.0001
1141
.17.5 servings/wk
,3.0 servings/wk
8
1964
1.29 servings/d
0.03 servings/d
0.79
0.934
0.69
0.65, 0.96
0.75, 1.16
0.60, 0.79
0.0089
NS
,0.0001
10
156
0.64
0.676
1.147
0.36, 1.15
0.32, 1.38
0.66, 2.49
0.02
NS
NS
y
#12
Lowest
302 g/d
79 g/d
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 (Appendixes 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 wholegrain intake and T2D risk reduction was shown in one large, welldesigned 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 wellconducted 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 crosssectional 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
Author, year (reference)
Study name
No. of
participants
de Munter et al,
2007 (17)
NHS I
NHS II
73,327 F
88,410 F
1
2
Age
y
37–65
26–46
Follow-up
No. of
cases
Highest
y
12–18
12–18
4747
1739
36.9
45.6
Lowest
RR
95% CI
P-trend
3.2
5.5
0.63
0.68
0.57, 0.69
0.57, 0.81
,0.001
,0.001
g/d
RRs are for the comparison between the extreme quintiles. NHS, Nurses’ Health Study; T2D, type 2 diabetes.
The definition of whole grain met the US Food and Drug Administration criteria.
Downloaded from ajcn.nutrition.org at AMERICAN SOCIETY FOR NUTRITION on August 2, 2013
Fung et al,
2002 (40)
Kochar et al,
20073 (41)
Liu et al,
2000 (42)
Meyer et al,
2000 (26)
van Dam et al,
2006 (43)
Montonen et al,
2003 (16)
Study name
FROM THE AMERICAN SOCIETY FOR NUTRITION
601
WHOLE-GRAIN, BRAN, AND FIBER INTAKE AND RISK OF DISEASE
TABLE 5
Prospective cohort studies on cereal fiber; body weight measures1
Author, year
(reference)
Cereal fiber intake
No. of
Study design,
Study name participants, age
follow-up
Highest
Lowest
Koh-Banerjee
HPFS
et al, 2004 (52)
Du et al, 2010 (53) Diogenes
Project
1
27,082 M,
aged 40–75 y
89,432 M + F,
aged 20–78 y
P, 8 y
P, 6.5 y
Endpoints
Body weight measures
(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
prospective cohort studies in males and females showed significant 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 reported 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 minimal 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 between cereal fiber intake and body weight measures. The differences in BMI, body weights, or WC between the highest and
the lowest intakes were large enough to have biological significance.
We assigned evidence level B/C for an inverse association
between cereal fiber intake and various body weight measures.
that, compared with the lowest consumers, the highest consumers 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 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 cereals 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
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 crosssectional studies (9, 55, 64; Appendix H). In the Health Professionals 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 (Ptrend = 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.
Downloaded from ajcn.nutrition.org at AMERICAN SOCIETY FOR NUTRITION on August 2, 2013
Values in parentheses are 95% CIs. HPFS, Health Professionals Follow-Up Study; P, prospective; WC, waist circumference.
2
285 M + F,
mean age
of 13 y
2
13
8
8
2–4
y
12
Follow-up
Rarely
$1 serving/d
,0.5 servings/d
211.0 g/d
.1.5 servings/d
Lowest
Servings/1000 kcal per day:
at baseline, 0.07; change
in intake in 12 y, 20.59
+27.0 g/d
Servings/1000
kcal per day:
at baseline,
1.62; change
in intake in
12 y, 0.90
Highest
OR for weight gain, $25 kg
in 12 y
OR for BMI (in kg/m2) $30
in 12 y
Weight gain (kg)
Average changes in BMI
(kg/m2)
Average changes
in weight (kg)
Body weight change
(kg/8 y)
Weight gain (kg)
RR for BMI $25
Weight gain (kg)
RR for BMI $25
RR for weight
gain $10 kg
BMI (kg/m2)
Endpoints
HPFS, Health Professionals Follow-Up Study; MPSS, Minneapolis Public School Students; NHS, Nurses’ Health Study; PHS, Physicians’ Health Study.
A report from the PHS was limited to breakfast cereals with $25% whole grains and bran.
MPSS
26,082 M, aged
40–75 y
17,881 M
74,091 F, aged
38–63 y
No. of
participants, age
Downloaded from ajcn.nutrition.org at AMERICAN SOCIETY FOR NUTRITION on August 2, 2013
1
Steffen et al, 2003 (58)
HPFS
Koh-Banerjee
et al, 2004 (52)
Bazzano et al,
2005 (57)
PHS2
NHS
Study name
Liu et al,
2003 (56)
Author, year
(reference)
Intake of mixtures of
whole grains and bran
TABLE 6
Prospective cohort studies on mixtures of whole grains and bran: risk of obesity and body weight measures1
0.03
0.0002
,0.0001
,0.0001
,0.0001
,0.0001
0.003
0.06
0.08
0.13
0.01
0.05
0.81 (0.73, 0.91)
4.12 vs 4.51
0.46 vs 0.56
1.23 vs 1.52
+0.73 vs +1.25
(difference: 0.52)
1.13 vs 1.55
0.83 (0.71, 0.98)
1.83 vs 2.18
0.91 (0.79, 1.05)
0.78 (0.64, 0.96)
21.9 vs 23.6
P-trend
0.77 (0.59, 1.01)
RR (95% CI) or body weight
measure (highest vs lowest)
602
CHO ET AL
FROM THE AMERICAN SOCIETY FOR NUTRITION
603
WHOLE-GRAIN, BRAN, AND FIBER INTAKE AND RISK OF DISEASE
TABLE 7
Prospective cohort studies of whole grain: body weight measures
Whole-grain intake
Author, year
(reference)
Koh-Banerjee
et al, 2004 (52)
1
Study name
1
HPFS
No. of
participants, age
27,082 M,
aged 40–75 y
Follow-up
Highest
8y
Change in intake:
+15.6 g/d
Lowest
Endpoints
Change in intake:
217.8 g/d
Body weight
change
(kg/8 y)
Highest vs
lowest
+0.69 vs +0.96
(difference: 0.27)
P-trend
0.002
HPFS, Health Professionals Follow-Up Study.
CVD
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 independent 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 nonsignificant 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 inversely associated with a lower risk of hypertension (HR comparing the fifth and first quintile: 0.60; 95% CI: 0.3, 1.0; P-trend =
0.05). The relation with hypertension was stronger among individuals 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 limited 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 hypertension 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.
Studies on whole grains
A summary of the reports showing a relation between wholegrain 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 association between intake of whole grains and reduction in risk of
CVD (level C).
Flint et al (84) reported an inverse association between wholegrain 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 wholegrain consumption with hypertension is considered inadequate
to draw any conclusions (level D).
Downloaded from ajcn.nutrition.org at AMERICAN SOCIETY FOR NUTRITION on August 2, 2013
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.
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 females (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; Appendix 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).
21,930 M, general
population
21,930 M
ATBC study
3588 M + F
3588 M + F
78,799 F
43,738 M
39,876 F
43,757 M
CHS
CHS
NHS
HPFS
NHS
HPFS
8.6
8.6
$65
$65
6
.2
.20
5.8
$45
40–75
8
40–75
18
5.8
$45
30–55
10
6.1
6.1
37–64
50–69
50–69
26
y
14.3
y
40–79
30–55
Follow-up
Age
Hypertension
Fatal and nonfatal MI
MI
Total stroke
Total stroke
Total stroke
CVD events
CVD events
CHD events
Coronary event
CHD death
CVD mortality
CVD mortality in women
CVD mortality in men
Endpoints
180
734
177
328
1020
392
811
570
591
1399
581
295
2080
No. of
cases
NA
9.7
CF: NA (total
fiber: 28.9)
6.5
5.7
.6.3
.6.3
6.5
7.7
26.3
26.3
32.6 g
.1.7
.2.1
Highest
g/d
0.36, 0.92
0.56, 1.47
0.91
0.63
1.11
0.79
0.78
0.66
0.57
0.91
0.71
0.60
2.2
3.0
,1.7
,1.7
1.4
CF: NA (total
fiber: 12.4)
3.0
2.2
NA
0.3, 1.0
0.54, 0.92
0.52, 0.83
0.64, 0.95
0.62, 0.99
0.84, 1.46
0.49, 0.81
0.77, 1.09
0.57, 0.96
8.8
,1.1
0.74
0.99
1.01
0.98
0.97
1.06
8.8
0.64,
0.65,
0.59,
0.59,
0.46,
95% CI
4.8 g
RR
0.862
0.893
0.772
0.763
0.70
,1.4
Lowest
Cereal fiber intake
Downloaded from ajcn.nutrition.org at AMERICAN SOCIETY FOR NUTRITION on August 2, 2013
0.05
0.01
NS
0.03
0.001
,0.05
0.02
NS
0.002
NS
0.01
0.042
0.060
0.031
0.044
NS
P-trend
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.
5880 M + F
39,876 F
NHS
SUN follow- up study
68,782 F
NHS
ATBC study
7822 F, diabetic
NHS
He et al,
2010 (66)
Pietinen et al,
1996 (67)
Pietinen et al,
1996 (67)
Wolk et al,
1999 (68)
Liu et al,
2002 (69)
Mozaffarian
et al, 2003 (70)
Mozaffarian
et al, 2003 (70)
Oh et al,
2005 (71)
Ascherio et al,
1996 (72)
Liu et al,
2002 (69)
Rimm et al,
1996 (73)
Alonso et al,
2006 (74)
58,730 M + F, general
population
JCCSECR
Study name
No of
participants
Eshak et al,
2010 (65)
Author, year
(reference)
TABLE 8
Prospective cohort studies on cereal fiber: risk of CVD and hypertension1
604
CHO ET AL
FROM THE AMERICAN SOCIETY FOR NUTRITION
605
WHOLE-GRAIN, BRAN, AND FIBER INTAKE AND RISK OF DISEASE
TABLE 9
Prospective cohort studies on mixtures of whole grain and bran: risk of CVD and hypertension1
Author, year
(reference)
Age
Follow-up
Endpoints
IWHS
31,284 F
y
55–69
y
9
Mortality from IHD
IWHS
31,284 F
55–69
9
PHS2
86,190 M
40–84
NA
535 M + F
60–98
NHS
75,521 F
38–63
10
ARIC study 11,940 M + F 45–64
Whole-grain intake
No. of
cases Highest
Lowest
RR
95% CI
P-trend
servings
438
3.2
0.2/d
0.70
0.50, 0.98
0.02
CVD mortality
1097
3.2
0.2/d
0.82
0.63, 1.06
0.03
5.5
CVD Mortality
3114
$1.0
Rarely
0.80
0.66, 0.97
0.008
12–15
CVD Mortality
89
.1.94
#0.56/d
0.48
0.25, 0.96
0.04
761
2.7
0.13/d
11
CHD, fatal and
nonfatal MI
Incident CAD
535
3.0
0.1/d
0.753 0.59, 0.95
0.794 0.62, 1.01
0.72 0.53, 0.97
0.01
0.07
0.05
ARIC study 11,940 M + F 45–64
11
Heart failure
1140
.1/d
—
ARIC study 14,153 M + F 45–64
13
1140
PHS2
21,376 M
40–86
19.6
Heart failure,
hospitalized
Heart failure
1018
$1
NHS
75,521 F
38–63
10
Ischemic stroke
352
ARIC study 11,940 M + F 45–64
11
Ischemic stroke
10
Hypertension
WHS
28,926 F
$45
0.93
0.87, 0.99 ,0.05
0.93
0.87, 0.99 ,0.05
0/wk
0.72
0.59, 0.88 ,0.001
2.7
0.13/d
214
3.0
0.1/d
0.645 0.47, 0.89
0.696 0.50, 0.98
0.75 0.46, 1.22
0.04
0.08
NS
8722
5.0
0.28/d
0.89
0.007
Per difference of 1 serving/d
0.82, 0.97
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, selfreported 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
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. Although 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 periods 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
addition, a study on a single grain or a mixture of 1–2 grains
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 controlled 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,
Downloaded from ajcn.nutrition.org at AMERICAN SOCIETY FOR NUTRITION on August 2, 2013
Jacobs et al,
1998 (13)
Jacobs et al,
1999 (14)
Liu et al,
2003 (76)
Sayhoun et al,
2006 (45)
Liu et al,
1999 (15)
Steffen et al,
2003 (77)
Steffen et al,
2003 (77)
Nettleton et al,
2008 (78)
Djoussé et al,
2007 (79)
Liu et al,
2000 (80)
Steffen et al,
2003 (77)
Wang et al,
2007 (81)
Study name
No. of
participants
606
CHO ET AL
TABLE 10
Prospective cohort studies on whole grains: risk of CVD and hypertension1
Whole-grain
intake
Author, year
(reference)
Study name
No. of
participants
Age
Follow-up
Endpoints
Jensen et al,
2004 (83)
HPFS
42,850 M
y
40–75
y
14
CHD
He et al,
2010 (66)
Flint et al,
2009 (84)
NHS
7822 F with T2D
30–55
26
CVD specific mortality
HPFS
31,648 M
40–75
18
Hypertension
No. of
cases
Highest
Lowest
RR
95% CI
P-trend
g/d
1818
42.4
3.5
295
32.6
4.8
9227
46.0
3.3
0.822
0.843
0.854
0.70
0.70,
0.71,
0.71,
0.46,
0.81
0.885
0.946
0.75, 0.87
0.77, 1.00
0.84, 1.05
0.96
0.98
1.02
1.06
0.01
0.02
0.06
NS
,0.0001
0.04
NS
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 reductions 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 evidence for mixtures of whole grains and bran.
With regard to risk reduction for CVD, evidence for the association with cereal fiber intake is considered moderate (evidence 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, evidence 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 conclusions 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 investigated 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
Cereal fiber
Mixtures of whole
grains and bran
Whole grains
1
T2D
Obesity
CVD
Hypertension
B
B
B/C
B/C
B
B
D
D
C
C/D
C
D
CVD, cardiovascular disease; T2D, type 2 diabetes.
Downloaded from ajcn.nutrition.org at AMERICAN SOCIETY FOR NUTRITION on August 2, 2013
1
FROM THE AMERICAN SOCIETY FOR NUTRITION
WHOLE-GRAIN, BRAN, AND FIBER INTAKE AND RISK OF DISEASE
10.
11.
12.
13.
14.
15.
16.
17.
ASN POSITION
Based on the current state of the science, there is moderate
evidence that consumption of foods rich in cereal fiber or mixtures 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 epidemiologic 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 development of the evidence grading system.
The authors’ responsibilities were as follows—All authors contributed
substantially to the development of this statement and reviewed and approved the final manuscript.
18.
19.
20.
21.
22.
23.
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noteworthy that recent reviews or meta-analyses reporting health
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607
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609
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APPENDIX A
Cross-sectional studies of cereal fiber: risk factors for T2D1
Cereal fiber intake
Author, year
(reference)
McKeown et al,
2004 (35)
Newby et al,
2007 (36)
Lairon et al,
2005 (39)
FOS
2834 M + F
BLSA
1516 M + F
Age
y
26–82
27–88
Highest
Lowest
9.5
2.2
10.4
2.4
11.6
2.5
902 F
30–55 10.0 (.8.6)
3.5 (,4.4)
HPFS
780 M
40–75 10.0 ($8.6)
3.5 (,4.4)
5961 M + F
35–60
Highest
g/d
20.4 (.13) 0.90 (,1.5) OR (95% CI)
of MetS
HOMA-IR
NHS
SUVIMAX
Endpoints
M: .10.6
M: ,5.3
F: .7.7
F: ,3.9
P-trend
0.62 (0.45, 0.86) 1.0 (reference)
Fasting glucose
(mmol/L)
2-h glucose
(mmol/L)
Fasting insulin
(mmol/L)
2-h insulin
(mmol/L)
Plasma adiponectin
(mg/mL)
Plasma adiponectin
(mg/mL)
OR (95% CI) of
elevated fasting
glucose
Lowest
0.002
6.5
6.52
5.52 6 0.0533
6.8
6.92
5.55 6 0.05
0.02
0.003
NS
6.48 6 0.21
8.05 6 0.21
0.02
73.0 6 4.0
68.9 6 4.0
NS
413 6 38.2
438 6 38.8
NS
7.9
6.9
0.01
17.3
14.0
0.003
16.74
1.37 (0.79, 2.39)
14.5
1.0
0.063
NS
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
(reference)
Study name
No. of
participants
TLGS
827 M + F
Esmaillzadeh
et al, 20052 (44)
McKeown et al,
FOS
2834 M + F
2004 (35)
Sahyoun et al,
NA (community-living 535 M + F
2006 (45)
persons in Boston)
1
2
Age at
baseline
Highest
Lowest
y
18–74
229 g/d
6 g/d
OR
95% CI
P-trend
26–82
MetS: 0.68 MetS: 0.60, 0.78 0.01 for MetS
T2D: 0.84 T2D: 0.73, 0.99 NS for T2D
20.4 servings/wk 0.90 servings/wk MetS: 0.67
0.48, 0.91
0.01
60–98
2.9 servings/d
0.31 servings/d
MetS: 0.46
0.27, 0.79
0.005
FOS, Framingham Offspring Study; MetS, metabolic syndrome; NA, not applicable; TLGS, Teheran Lipid and Glucose Study; T2D, type 2 diabetes.
Included germs in the definition of whole grain.
Downloaded from ajcn.nutrition.org at AMERICAN SOCIETY FOR NUTRITION on August 2, 2013
Qi et al,
2006 (37)
Qi et al,
2005 (38)
Study name No. of participants
ORs or risk factor mean values
BLSA
CARDIA
NA
Newby et al,
2007 (36)
Pereira et al,
1998 (49)
Steffen et al,
2003 (50)
285 M + F
3627 Black and white adults
1516 M + F
2941 M + F
40–75
27–88
26–82
45–84
0.31 servings/d
Lowest
0.56 g/d
1.1 g/d
2.2 g/d
2.4 g/d
0–2 servings/wk
,0.5 servings/d
.1.5 servings/d
0.90 servings/wk
0.02 servings/d
45.4 g/d
50.6 g/d
51.5 g/d
51.7 g/d
.9 servings/wk
20.5 servings/wk
1.39 servings/d
Study of mean whole grain
intake = 0.8 6 0.7 servings/d
2.9 servings/d
y
60–98
40–69
Highest
Whole-grain intake
Age at
baseline
Glycated hemoglobin (%)
Fasting glucose (mmol/L)
2-h glucose (mmol/L)
Fasting insulin (mmol/L)
2-h insulin (mmol/L)
Fasting insulin (uU/mL)
Year 0
Year 7
IS (mg $ kg21 $ min21)
Fasting insulin (mU/L)
Fasting glucose (mg/dL)
2-h insulin (pmol/L)
2-h glucose (mmol/L)
Fasting insulin (pmol/L)
Fasting insulin
IS2
Fasting insulin2
Fasting insulin (mU/L)
Fasting glucose (mg/dL)
HOMA-IR (mU/L 3 mmol/L)
Fasting glucose (mmol/L)
IS
Fasting glucose (mg/dL)
Endpoints
10.3
11.3
13.3
13.8
99.3
10.8
12.4
11.5
16.7
99.4
,0.05
0.01
0.07
NS
0.02
NS
NS
0.002
0.08
0.02
0.05
NS
NS
0.001
0.002
NS
NS
0.02
NS
NS
NS
0.006
NS
NS
,0.05
b: 20.065
b: 0.041
b: 20.031
5.16
5.37
97.6
99.0
1.53
1.68
5.22
5.32
5.243
5.303
3
5.82
5.843
195
210
2073
1983
2024
2064
5
201
2055
561
605
5683
5923
5.243
5.263
5.49
5.49
7.32
8.24
71.8
71.6
414
479
0.01
P-trend
0.001
114.9
Lowest
b: 0.082
108.5
Highest
Risk factor
WHOLE-GRAIN, BRAN, AND FIBER INTAKE AND RISK OF DISEASE
Downloaded from ajcn.nutrition.org at AMERICAN SOCIETY FOR NUTRITION on August 2, 2013
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.
FOS
McKeown et al,
2002 (48)
5496 M + F
978 M + F
IRAS
MESA
535 M + F
No. of
participants
NA
Study name
Lutsey et al,
2007 (47)
Sahyoun et al,
2006 (45)
Liese et al,
2003 (46)
Author, year
(reference)
APPENDIX C
Cross-sectional analysis of mixtures of whole grains and bran: risk factors for T2D1
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
Author, year
(reference)
Study name
Jensen et al,
2006 (51)
HPFS and
NHS II
1
No. of
participants
Age
938 M + F
y
25–75
Highest
Lowest
Risk factors
Risk factors
Highest
Lowest
P-value
Hb A1c (%)
Insulin (uIU/L)
Fasting glucose (mg/dL)
5.49
11.3
86.1
5.50
13.2
86.8
NS
NS
NS
g/d
43.8
8.2
Hb A1c, glycated hemoglobin; HPFS, Health Professionals Follow-Up Study; NHS, Nurses’ Health Study; T2D, type 2 diabetes.
Downloaded from ajcn.nutrition.org at AMERICAN SOCIETY FOR NUTRITION on August 2, 2013
4237 M + F
55–69
35–60
g/d
2.2
2.4
Lowest
9.7
2.3
M: .10.6
M: ,5.3
F: .7.7
F: ,3.9
Increased
intake by
1 g/d
9.5
9.3
y
60–80
27–88
Highest
Age
Cereal fiber intake, g/d
BMI (kg/m2)
(% body fat)
BMI (kg/m2)
Weight (kg)
WC (cm)
OR (95% CI) for BMI $25
OR (95% CI) for WHR .0.95
Weight gain
Endpoints
P-trend
0.01
0.004
,0.0001
0.004
,0.0001
0.003
NS
P , 0.01 for men;
NS for women
Body weight measures
(OR or highest vs lowest)
25.4 vs 27.3
31.5 vs 34.7
24.3 6 0.2 vs 25.7 6 0.2
71.4 6 0.8 vs 75.6 6 0.7
84.2 6 0.6 vs 87.5 6 0.8
0.70 (0.55, 0.90)
0.99 (0.78, 1.26)
Decrease in BMI by 0.04
in men; NS in women
WHOLE-GRAIN, BRAN, AND FIBER INTAKE AND RISK OF DISEASE
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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.
NLCS
van de Vijver
et al, 2009 (55)
12,741 M + F
1516 M + F
BLSA
SUVIMAX study
434 M + F
No. of
participants
FHS
Study name
Lairon et al, 2005 (39)
McKeown et al,
2009 (54)
Newby et al,
2007 (36)
Author, year
(reference)
APPENDIX E
Cross-sectional studies comparing cereal fiber: risk of obesity and body weight measures1
FROM THE AMERICAN SOCIETY FOR NUTRITION
613
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
(reference)
Esmaillzadeh
et al, 2005 (44)
Good et al,
2008 (59)
1
Age
TLGS1
827 M + F
y
18–74
NHANES
2092 F
$19
Highest
229 g/d
$1 serving/d
Lowest
Endpoints
6 g/d
OR (95% CI) for
abdominal
adiposity2
OR (95% CI)
for obesity
RR for BMI
$25 kg/m2
0 servings/d
TLGS, Teheran Lipid and Glucose Study.
Abdominal adiposity (waist circumference .102 cm for men and .88 cm for women).
RR or OR
(highest vs lowest)
0.90 (0.79, 0.96)
0.71 (0.54, 1.09)
1.47 (1.12, 1.94) for
women consuming
no whole grains
P-trend
0.04
NS
0.013
Downloaded from ajcn.nutrition.org at AMERICAN SOCIETY FOR NUTRITION on August 2, 2013
2
Study name
No. of
participants
DONALD Study
215 M + F $2
Endpoints
48.9 g/1000 kcal
26.3 g/ 1000 kcal
0.04 servings/d
BMI (kg/m2)
WC (cm)
(% body fat)
BMI = NS, WC = NS
28.2 vs 28.8
89.9 vs 91.7
b = 0.669
NS
0.08, NS
0.02
0.02
,0.001
0.004
0.002
0.06
0.005
,0.0001
,0.001
,0.001
,0.001
NS
0.03
P-trend
25.8 vs 26.8
32.1 vs 34.5
39.4 vs 43.0
24.8 vs.25.5
72.6 vs 75.0
85.0 vs 87.4
26.4 vs 26.9
0.91 vs 0.92
27.6 vs 28.2
93.7 vs 97.0
26.3 vs 27.4
1676 vs 1864
2739 vs 2756
25.2 vs 26.4
Body weight measures
(highest vs lowest)
WHOLE-GRAIN, BRAN, AND FIBER INTAKE AND RISK OF DISEASE
Downloaded from ajcn.nutrition.org at AMERICAN SOCIETY FOR NUTRITION on August 2, 2013
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
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.
1
Cheng et al, 2009 (62)
Masters et al, 2010 (61)
NA (community-living 535 M + F 60–98
persons in Boston)
IRAS
1015 M + F 40–60 2.00 servings/d
5496 M + F 45–84
2834 M + F 32–83
Lutsey et al, 2007 (47)
MESA
McKeown et al, 2010 (60) FHS
Sahyoun et al, 2006 (45)
2941 M + F 26–82
McKeown et al, 2002 (48) FOS
BLSA
Lowest
0.21 servings/d
Whole-grain intake
BMI (kg/m2)
(% body fat)
(% trunk fat mass)
46.0 g/d
0.65 g/d
BMI
Weight (kg)
49.3 g/d
0.94 g/d
WC (cm)
2.9 servings/d
0.13 servings/d
BMI (kg/m2)
WHR
1.39 servings/d
0.02 servings/d
BMI (kg/m2)
2.93 (2.04–12.7) servings/d 0.14 (0.00–0.30) servings/d WC (cm)
BMI (kg/m2)
VAT (cm3)
SAT (cm3)
.1.94 servings/d
#0.56 servings/d
BMI (kg/m2)
1516 M + F 27–88
Highest
Newby et al, 2007 (36)
Age
y
434 M + F 60–80 2.86 servings/d
Study name
No. of
participants
McKeown et al, 2009 (54) FHS
Author, year
(reference)
APPENDIX G
Cross-sectional studies of mixtures of whole grains and bran: body weight measures1
FROM THE AMERICAN SOCIETY FOR NUTRITION
615
NHANES 2000–2006
NLCS
Zanovec et al,
2010 (64)
van de Vijver
et al, 2009 (55)b
4237 M + F
aged 55–69 y
8799 M + F
aged 6–18 y
7039 aged
19–50 y; 6237
aged $51 y
Participants
2
0.1 servings/d
0.1 servings/d
Lowest
Increased intake by 1 g/d
4.6 servings/d
4.6 servings/d
Highest
Whole-grain intake
Regression analysis
WC and BMI z score
WC: ages $51 y (cm)
WC: ages 19–50 y (cm)
BMI: ages
19–50 y (kg/m2)
BMI: ages $51 y
(kg/m2)
Endpoints
28.3 vs. 28.63
94.2 vs. 94.62
95.1 vs. 94.53
98.2 vs.100.62
99.1 vs. 100.43
Ages 6–12 y: WC, 64.1
vs 66.7 cm; BMI z score,
0.23 vs 0.52
Ages 13–18 y: WC, 78.2
vs 81.4 cm; BMI z score,
0.18 vs 0.54
Decrease of BMI by 0.03
for men and 0.04 for women
27.7 vs. 28.0
28.1 vs. 27.93
27.9 vs. 28.72
2
Biomarkers
(highest vs lowest)
Downloaded from ajcn.nutrition.org at AMERICAN SOCIETY FOR NUTRITION on August 2, 2013
NLCS, Netherlands Cohort Study; WC, waist circumference.
Multivariable model.
3
Multivariable model plus cereal fiber.
1
NHANES 1998–2004
Study name
O’Neil et al,
2010 (9)
Author, year
(reference)
APPENDIX H
Cross-sectional studies of whole grain: body weight measures1
NS
NS
NS
,0.01
WC, P , 0.05; BMI
z score, P , 0.05
NS
WC, P , 0.05; BMI
z score, P , 0.05
,0.05
,0.05
,0.05
,0.05
P-trend
616
CHO ET AL
Caerphilly Heart
Disease Study
Lichtenstein et al, 1986 (75)
45–49
35–60
3429 F
2421 M
y
45–60
Age
2532 M
No. of participants
,3.9
.7.7
Mean 6 SD cereal fiber
intake = 7.7 6 4.5
,5.3
g/d
Lowest
.10.6
Highest
Cereal fiber intake
Hypertension: yes vs no, year 2
Risk of elevated Hcy, year 3
Risk of elevated TC, year 1
Risk of elevated TG, year 1
SBP2 (mm Hg/g cereal fiber)
DBP2 (mm Hg/g cereal fiber)
Endpoints
0.86
0.73
0.94
1.09
20.186
20.111
RR
(highest vs lowest)
0.67,
0.50,
0.75,
0.79,
20.363,
20.228,
1.10
1.07
1.17
1.50
20.009
20.005
95% CI
0.02
0.02
NS
NS
NA
NA
P-trend
WHOLE-GRAIN, BRAN, AND FIBER INTAKE AND RISK OF DISEASE
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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.
SUVIMAX
Study name
Lairon et al, 2005 (39)
Reference
APPENDIX I
Cross-sectional studies on cereal fiber intake: risk factors for CVD1
FROM THE AMERICAN SOCIETY FOR NUTRITION
617
FOS (USA)
TLGS (Iran)
MESA (USA)
IRAS (USA)
CATCH (USA)
NA
NA
McKeown et al, 2002 (48)
Esmaillzadeh et al, 2005 (44)
Lutsey et al, 2007 (47)
Masters et al, 2010 (61)
Lutsey et al, 2006 (82)
Steffen et al, 2003 (50)
Sahyoun et al, 2006 (45)
535 M + F
285 M + F
1015 M + F
2695 M + F
5496 M + F
827 M + F
2941 M + F
827 M + F
1516 M + F
No. of
participants
60–98
13–15
40–60
15–20
45–84
18–74
26–82
y
18–74
27–88
Age
0.04 servings/d
,0.20 servings/d
,0.5 servings/d
#0.56 servings/d
2.00 servings/d
1.07–6.14 servings/d
.1.5 servings/d
.1.94 servings/d
0.02 servings/d
,10 g/d
$143 g/d
1.39 servings/d
0.13 servings/d
,10 g/d
0.63 g/d
3.9 g/d
0.62 g/d
Lowest
2.93 servings/d
$143 g/d
45.6 g/d
54.8 g/d
45.4 g/d
Highest
Whole-grain intake
TC (mg/dL)
LDL-C (mg/dL)
TC (mg/dL)
LDL-C (mg/dL)
TG (mg/dL)
SBP (mm Hg)
DBP (mm Hg)
Risk of hypertension
TC (mmol/L)
LDL-C (mmol/L)
SBP (mm Hg)
DBP (mm Hg)
TC (mmol/L)
LDL-C (mmol/L)
HDL-C (mmol/L)
SBP (mm Hg)
DBP (mm Hg)
TC (mg/dL)
LDL-C (mg/dL)
TG (mg/dL)
SBP (mm Hg)
DBP (mm Hg)
HDL-C (mg/dL)
LDL-C (mg/dL)
SBP (mm Hg)
DBP (mm Hg)
CRP (mg/L)
Hcy (mmol/L)
CRP (mg/L)
Hcy (mmol/L)
Endpoints
1.0
6 0.06
6 0.06
6 1.0
6 0.6
5.20
3.16
1.20
124.4
75.6
200 6 2
128 6 2
167 6 8
115 6 1
81 6 1
51.8
118.1
126.3
72.2
3.56
9.62
1.75 (1.02–4.11)
MM2: 5.93
MM3: 5.78
152.7 6 3.14
90.4 6 2.73
225.8
147.3
111.7
148.8
84.4
OR: 0.84 (95% CI: 0.73, 0.99)
5.49 6 0.06
2.96 6 0.06
128.3 6 1.0
79.2 6 0.7
5.09
3.04
1.23
123.1
73.8
193 6 3
120 6 2
135 6 8
115 6 1
77 6 1
51.3
117.0
125.0
71.6
3.02
8.82
1.55 (0.62–3.42)
MM2: 5.42
MM3: 5.67
148.6 6 2.92
84.6 6 2.53
217.8
139.0
106.6
147.9
82.5
5.71
3.16
129.2
79.8
Lowest
Highest
Risk factors/biomarker (change 6 SE)
Downloaded from ajcn.nutrition.org at AMERICAN SOCIETY FOR NUTRITION on August 2, 2013
0.03
0.02
0.04
NS
NS
0.06
0.02
NS
NS
NS
NS
NS
,0.05
NS
,0.05
NS
NS
NS
NS
,0.0001
,0.0001
0.0409
MM2:0.002
MM3: NS
NS
NS
NS
NS
NS
NS
NS
P-trend
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.
TLGS (Iran)
BLSA (USA)
Study name
(country)
Esmaillzadeh et al, 2005 (44)
Newby et al, 2007 (36)
Author, year
(reference)
APPENDIX J
Cross-sectional studies on mixtures of whole grain and bran: risk factors for CVD1
618
CHO ET AL
FROM THE AMERICAN SOCIETY FOR NUTRITION
619
WHOLE-GRAIN, BRAN, AND FIBER INTAKE AND RISK OF DISEASE
APPENDIX K
Cross-sectional study on whole grains: risk factors for CVD1
Whole grain
intake
Author, year
(reference)
Study name
(country)
No. of
participants
Age at
baseline
Jensen et al,
2006 (51)
HPFS and NHS
II (USA)
938 M + F
y
F: 25–42
M: 40–75
Follow-up
y
NA
Highest
Lowest
Biomarker
Endpoints
Highest
Lowest
P-trend
TC (mg/dL)
LDL-C (mg/dL)
DBP (mm Hg)
215.6 6 2.8
123.9 6 2.3
60.5 6 8.1
222.0 6 3.0
126.6 6 2.7
61.8 6 8.5
0.02
NS
NS
g/d
43.8
8.2
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.
Downloaded from ajcn.nutrition.org at AMERICAN SOCIETY FOR NUTRITION on August 2, 2013