Cereals, legumes, and chronic disease risk reduction: evidence

from epidemiologic studies1–3

Lawrence H Kushi, Katie A Meyer, and David R Jacobs Jr

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ABSTRACT There is growing evidence that cereals and period that indeed, Daniel and his group appeared “fairer and fat-
legumes play important roles in the prevention of chronic dis- ter in flesh” than the others, and so they were provided the diet
eases. Early epidemiologic studies of these associations focused of pulses rather than the diet of meat.
on intake of dietary fiber rather than intake of grains or legumes. More recently, the role that cereals and legumes may play in the
Generally, these studies indicated an inverse association between etiology of chronic diseases was highlighted by hypotheses put
dietary fiber intake and risk of coronary artery disease; this forth by Burkitt and Trowell (2), who suggested that dietary fiber
observation has been replicated in recent cohort studies. Studies may be beneficial for preventing several diseases that are common
that focused on grain or cereal intake are fewer in number; these in Western societies. Based on observations of diet and disease in
tend to support an inverse association between intake of whole Africa compared with the United Kingdom and other industrial-
grains and coronary artery disease. Studies on the association of ized nations, they proposed that the refining of grains and lack of
dietary fiber with colon and other cancers have generally shown dietary fiber may be important in diseases such as large bowel can-
inverse relations, but whether these relations are attributable cer (3), coronary artery disease (4), and diabetes (5, 6).
to cereals, other fiber sources, or other factors is less clear. These observations stimulated substantial research into the
Although legumes have been shown to lower blood cholesterol association of dietary fiber intake with these diseases. Much of
concentrations, epidemiologic studies are few and inconclusive this research has focused on understanding the mechanisms by
regarding the association of legumes with risk of coronary artery which dietary fibers may influence the etiology of these diseases.
disease. It has been hypothesized that legumes, in particular Thus, there is a substantial body of literature showing that dietary
soybeans, reduce the risk of some cancers, but epidemiologic fibers, in particular soluble fibers, decrease blood cholesterol con-
studies are equivocal in this regard. Overall, there is substantial centrations and may thereby modify the risk of coronary artery
epidemiologic evidence that dietary fiber and whole grains are disease (7) and that dietary fiber may affect risk of large bowel
associated with decreased risk of coronary artery disease and cancers through mechanisms such as altering bile acid metabo-
some cancers, whereas the role of legumes in these diseases lism, increasing fecal bulk, or decreasing gut transit time (8).
appears promising but as yet inconclusive. Am J Clin Nutr Recently, attention has also focused on the possible roles of
1999;70(suppl):451S–8S. factors other than fiber that are contained in cereals and legumes
and that may alter the risk of chronic diseases. Examples include
KEY WORDS Dietary fiber, whole grains, legumes, cere- vitamin E; B vitamins such as folic acid and minerals such as
als, coronary artery disease, cardiovascular disease, cancer, selenium that have not been added to refined flour products; and
chronic disease risk, chronic disease prevention compounds with estrogenic activity, such as isoflavones or lig-
nans (9). Because many of these factors occur together in nature
and are relatively concentrated in whole foods, there has been
INTRODUCTION interest in the possible differences between whole and refined
The observation that diets low in meat and high in cereals and grains in relation to chronic disease risk. In addition, cereal
legumes are beneficial for health has recently become a topic of grains and their products are among the most commonly con-
scientific interest, but was noted at least as far back as the Old sumed items and are a staple in most human diets. Given the
Testament. In the first chapter of the Book of Daniel (1), Daniel importance of cereals as a food, and the potential mechanisms
beseeched King Nebuchadnezzar’s prince of eunuchs not to feed
him the king’s meat and wine, but to feed him a diet of pulses
(cereals and legumes) instead. The prince of eunuchs, concerned 1
From the Division of Epidemiology, University of Minnesota School of
that Daniel and his friends would look callow in comparison
Public Health, Minneapolis.
with others, feared the King would be displeased. To this, Daniel 2
Supported by in part by the National Institutes of Health (grant no.
proposed that he and his friends be fed the pulse diet for 10 days, CA-39742).
after which their countenance could be compared with that of 3
Address reprint requests to LH Kushi, Division of Epidemiology, Univer-
others who were fed the king’s meat. In this earliest of recorded sity of Minnesota School of Public Health, 1300 South Second Street, Suite
feeding experiments, it was observed after the intervention 300, Minneapolis, MN 55454–1015. E-mail: [email protected].

Am J Clin Nutr 1999;70(suppl):451S–8S. Printed in USA. © 1999 American Society for Clinical Nutrition 451S
452S KUSHI ET AL

relating cereal intake to decreased risk of chronic diseases, a it was observed that men in the highest quintile of dietary fiber
number of epidemiologic studies have examined the association intake had a relative risk of myocardial infarction of 0.64 (95%
of these factors with disease risk. This article reviews the recent CI: 0.47, 0.87) compared with men in the lowest quintile of
evidence from epidemiologic studies relating dietary fiber, intake (17). In further analyses, this association was found to
whole grains, or legumes to the risk of chronic diseases. hold true primarily for insoluble fibers and not soluble fibers,
and for cereal fiber more strongly than for fiber from vegetables
or fruit. The other study was a follow-up of participants in the
DIETARY FIBER AND HEART DISEASE Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study (16).
Although the major focus of most epidemiologic studies of In this study, dietary fiber was inversely associated with coro-
diet and heart disease has been the role of dietary lipids, there is nary artery disease incidence; this association was strongest for
also a substantial epidemiologic history of investigations regard- soluble fiber and vegetable fiber sources, but was present for
ing dietary fiber. After the initial observations of Trowell (4), insoluble fiber and cereal and fruit fibers as well.
several prospective cohort studies investigated the association of Preliminary analyses in a third, large, prospective epidemio-
dietary fiber with heart disease (Table 1). The earliest of these, a logic study suggest that dietary fiber is inversely associated with

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10- to 20-y follow-up of 337 British male bank and bus employ- risk of death from coronary artery disease (L Kushi et al, unpub-
ees, reported a striking inverse association of total and cereal lished observations, 1998). In this prospective study of 31 284
fiber intake with coronary artery disease incidence (10, 18). postmenopausal women in Iowa, the relative risk of death from
Other studies conducted in Netherlands (11); Framingham, MA coronary artery disease was 0.76 (95% CI: 0.55, 1.05) among
(19); and Rancho Bernardo, CA (13) reported inverse associa- women in the highest quintile of dietary fiber intake compared
tions between coronary artery disease and dietary fiber or carbo- with those in the lowest quintile. As in the study of male health
hydrates from sources other than sugar or starch. However, in professionals, this association was stronger with insoluble than
only one of these studies (13) was the association with dietary soluble fiber and with fiber from cereals than fiber from vegeta-
fiber controlled for energy intake. bles, fruit, or legumes. In this study and 2 other prospective
In epidemiologic studies of diet, total energy intake is usually cohort studies (16, 17), these associations were apparent after
a confounder of diet-disease associations because intakes of controlling for total energy intake. Taken together, these
almost all dietary factors are highly correlated with energy intake prospective cohort studies provide remarkably consistent evi-
(20). This is simply because the more food one eats, the more of dence that dietary fiber is likely to be inversely associated with
most dietary components one eats. It is also known that physical risk of heart disease.
activity is inversely associated with heart disease risk and, in pop-
ulation studies, is a primary determinant of total energy intake
(21). Thus, in studies in which dietary fiber intake is not con- DIETARY FIBER AND CANCER
trolled for energy intake, it is not clear whether observed inverse
associations between fiber intake and heart disease risk are in part Colorectal cancer
attributable to differences in energy expenditure. This is under- As noted previously, the hypothesis that dietary fiber may
scored by the observation that in most prospective epidemiologic decrease the risk of colorectal cancer was initially proposed by
studies of diet and heart disease, total energy intake is inversely Burkitt (3). Since then, dietary fiber has been among the more
associated with risk of heart disease (10–13, 19). frequently investigated dietary factors in studies of the etiology
One of the first prospective studies to examine the association of colorectal cancer. Most of the analytic epidemiologic studies
of dietary fiber with coronary artery disease while controlling for on this topic have been case-control studies, and these have been
energy intake was a study of brothers in Ireland and Boston (12). the subject of reviews (25, 26). In one such review, it was noted
In this study, dietary fiber intake assessed in the late 1950s and that 11 of 17 case-control studies of dietary fiber and colon can-
early 1960s was inversely associated with risk of death from cer found an inverse association (25).
coronary artery disease after 20 y of follow-up, with men in the Howe et al (27) published one summary of these case-con-
highest third of dietary fiber intake having a relative risk of coro- trol studies, based on a combined analysis of original data from
nary mortality of 0.57 compared with men in the lowest third. In 13 such studies. This combined analysis included 5255 subjects
2 other prospective studies, one conducted in Caerphilly, Wales with colorectal cancer and 10 349 control subjects from studies
(15) and the other a follow-up of participants in the placebo arm conducted in Argentina, Australia, China, Singapore, Belgium,
of the Lipid Research Clinics Coronary Primary Prevention Trial Greece, Spain, Canada, and the United States. Overall, there was
(14), inverse associations between dietary fiber intake and coro- a strong inverse association of dietary fiber intake with risk of
nary artery disease were observed. However, unlike the findings colorectal cancer. The relative risks of colorectal cancer for sub-
of the Ireland-Boston Diet-Heart Study (12) or the Rancho jects in the lowest quintile to subjects in the highest quintile of
Bernardo study (13), these associations were attenuated and no fiber intake were 1.0, 0.79, 0.69, 0.63, and 0.53 (P trend < 0.0001).
longer significant after controlling for energy intake. This association remained after adjustment for other dietary fac-
In the 1980s, several large prospective studies of diet and dis- tors that are correlated with fiber intake and may influence the risk
ease were established. Because enough time passed for these of this cancer, such as vitamin C and b-carotene. This inverse
studies to have accrued reasonable numbers of events, several association was highly consistent; it was observed in all but one
reports about the associations between dietary factors and heart (28) of the individual case-control studies included in this analy-
disease risk in these studies have been published (16, 17, 22–24). sis and was found in case subsets, including subjects with cancers
In 1996, investigators from 2 of these studies reported associa- of the right-sided colon, left-sided colon, and rectum.
tions between dietary fiber and heart disease risk. In one of these The combined analysis by Howe et al (27) was based on stud-
studies, a 6-y follow-up of 43 757 male US health professionals, ies that had been completed before 1989. Since then, several
 CEREALS, LEGUMES, AND CHRONIC DISEASE RISK 453S

TABLE 1
Relative risk (RR) of coronary heart disease (CHD), comparing high and low dietary fiber intakes, in prospective epidemiologic studies1
Age range Study CHD
Study and location Cohort at baseline period events Comparison RR (95% CI)2 P trend
y n
Total dietary fiber
Morris et al (10), 337 M 30–67 1956–1976 45 events Highest compared 0.323,4 < 0.0055
United Kingdom with lowest third
Kromhout et al (11), 871 M 40–59 1960–1970 37 deaths Highest compared ~0.263,6 NS
Zutphen, Netherlands with lowest fifth
Kushi et al (12), 1001 M of 29–72 1959–1982 148 deaths Highest compared 0.57 (0.33, 0.97) < 0.05
Boston and Ireland Irish descent with lowest third
Khaw and Barrett-Connor

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(13), Bernardo, CA
Men 356 50–79 1972–1985 42 deaths Per 6-g increment 0.85 (0.64, 1.11) 0.15
Women 503 50–79 1972–1985 23 deaths Per 6-g increment 0.67 (0.45, 1.00) 0.05
Combined 859 50–79 1972–1985 65 deaths Per 6-g increment 0.79 (0.63, 0.98) 0.03
Humble et al (14), 1801 M 35–60 1973–1983 249 events Highest compared ~0.64 (0.43, 1.00)3 0.003
United States with lowest fifth
Fehily et al (15), 2423 M 45–59 1979–1988 153 events NS
Caerphilly, Wales
Pietinen et al (16), 21 930 M, 50–69 1985–1993 1399 events Highest compared 0.84 (0.71, 1.01) 0.03
Finland, smokers with lowest fifth
581 deaths Highest compared 0.68 (0.52, 0.88) < 0.001
with lowest fifth
Rimm et al (17), 43 757 M, health 40–75 1986–1992 734 events Highest compared 0.64 (0.47, 0.87) 0.004
United States professionals with lowest fifth
511 nonfatal MI Highest compared 0.65 (0.49, 0.88) 0.02
with lowest fifth
229 deaths Highest compared 0.45 (0.28, 0.72) < 0.001
with lowest fifth
Kushi7, Iowa 31 284 F 55–69 1986–1995 375 deaths Highest compared 0.76 (0.55, 1.05) 0.05
with lowest fifth
Soluble fiber
Pietinen et al (16), 21 930 M, 50–69 1985–1993 1399 events Highest compared 0.79 (0.66, 0.94) 0.004
Finland smokers with lowest fifth
581 deaths Highest compared 0.61 (0.46, 0.79) < 0.001
with lowest fifth
Rimm et al (17), 43 757 M, health 40–75 1986–1992 734 events Per 10-g increment 1.07 (0.57, 2.02)
United States professionals
Kushi7, Iowa 31 284 F 55–69 1986–1995 375 deaths Highest compared 0.79 (0.58, 1.08) 0.30
with lowest fifth
Insoluble fiber
Pietinen et al (16), 21930 M, 50–69 1985–1993 1399 events Highest compared 0.86 (0.72, 1.02) 0.07
Finland smokers with lowest fifth
581 deaths Highest compared 0.71 (0.55, 0.93) 0.002
with lowest fifth
Rimm et al (17), 43 757 M health 40–75 1986–1992 734 events Per 10-g increment 0.75 (0.59, 0.94)
United States professionals
Kushi7, Iowa 31 284 F 55–69 1986–1995 375 deaths Highest compared 0.70 (0.50, 0.96) 0.05
with lowest fifth
Cereal fiber
Morris et al (10), 337 M 30–67 1956–1976 45 events Highest compared 0.20 3,4
United States with lowest third
Pietinen et al (16), 21 930 M, 50–69 1985–1993 1399 events Highest compared 0.94 (0.79, 1.12) 0.32
Finland smokers with lowest fifth
581 deaths Highest compared 0.77 (0.59, 1.00) 0.03
with lowest fifth
Rimm et al (17), 43 757 M, health 40-75 1986–1992 734 events Highest compared 0.71 (0.54, 0.92) 0.007
United States professionals with lowest fifth
Kushi7, Iowa 31 284 F 55–69 1986–1995 375 deaths Highest compared 0.64 (0.46, 0.89) 0.002
with lowest fifth
(Continued)
454S KUSHI ET AL

TABLE 1 (Continued)
Age range Study CHD
Study and location Cohort at baseline period events Comparison RR (95% CI)2 P trend
y n
Vegetable fiber
Pietinen et al (16), 21 930 M, 50–69 1985–1993 1399 events Highest compared 0.84 (0.71, 1.00) 0.003
Finland smokers with lowest fifth
581 deaths Highest compared 0.73 (0.57, 0.93) < 0.001
with lowest fifth
Rimm et al (17), 43 757 M, health 40–75 1986–1992 734 events Highest compared 0.83 (0.64, 1.08) 0.05
United States professionals with lowest fifth
Kushi7, Iowa 31 284 F 55–69 1986–1995 375 deaths Highest compared 0.96 (0.71, 1.31) 0.71
with lowest fifth

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Fruit fiber
Pietinen et al (16), 21 930 M, 50–69 1985–1993 1399 events Highest compared 0.90 (0.75, 1.07) 0.11
Finland smokers with lowest fifth
581 deaths Highest compared 0.82 (0.63, 1.07) 0.03
with lowest fifth
Rimm et al (17), 43 757 M, health 40–75 1986–1992 734 events Highest compared 0.81 (0.62, 1.06) 0.10
United States professionals with lowest fifth
Kushi7, Iowa 31 284 F 55–69 1986–1995 375 deaths Highest compared 1.06 (0.76, 1.47) 0.89
with lowest fifth
1
MI, myocardial infarction.
2
Adjusted for multiple CHD risk factors unless otherwise noted.
3
Estimated from information provided in the study publication.
4
Crude RR.
5
Men who developed CHD consumed significantly lower amounts of dietary fiber per 1000 kcal (4.184 MJ) than men who did not develop CHD (P < 0.005).
6
RR adjusted for age only.
7
L Kushi et al, unpublished observations, 1998.

other case-control studies have supported an inverse association (36) and the other in Dutch civil servants (37), also failed to
between dietary fiber intake and risk of colorectal cancer. For observe an association of dietary fiber with colon cancer risk.
example, in a study conducted in Washington State, Meyer and The discrepancy between case-control studies and cohort stud-
White (29) observed that in both men and women, those with ies on this topic is somewhat perplexing. It may be a result of
colon cancer were likely to consume lower amounts of dietary differential recall of dietary habits by case subjects compared
fiber than were the population-based control subjects. The risk of with control subjects in the case-control studies. For example,
colon cancer among subjects in the highest quartile of dietary case subjects may have modified their diet because of their dis-
fiber consumption was about one-half that of subjects in the low- ease, and their current dietary patterns could influence their
est quartile, which was similar to the estimate made in the com- recall of past dietary habits. Alternatively, case subjects may be
bined analysis. In a case-control study conducted in Russia, more likely than control subjects to recall dietary factors that
Zaridze et al (30) noted similar inverse associations of cellulose they think are associated with their condition. The discrepancy
intake with risk of colorectal cancer. In a large multicenter case- may also be attributable to other dietary factors that are associ-
control study, Slattery et al (31) also observed inverse associa- ated with fiber intake, such as fruit and vegetables or red meat.
tions of dietary fiber with colon cancer risk. Thus, although not Both vegetables and fruit (38) and red meat (25, 39) have been
all case-control studies support an inverse association of dietary consistently associated with colon cancer risk in studies, includ-
fiber intake with risk of colon cancer (28, 32), overall such stud- ing cohort studies. Overall, the studies about fiber and colon
ies provide substantial support for this association. cancer provide modest support for an association between
There have been relatively fewer prospective cohort studies of dietary patterns involving higher fiber intake and reduced risk
dietary fiber and colon cancer and these studies are more equiv- of colon cancer.
ocal with respect to this association. The prospective studies on
this association include the Nurses’ Health Study (33) and the Other cancers
Iowa Women’s Health Study (34). In these studies there was The potential association of dietary fiber with breast cancer
some suggestion that high intakes of dietary fiber may be asso- has also been investigated in numerous epidemiologic studies. In
ciated with lower colon cancer risk, but the relative risks for high 1990, Howe et al (40) reported the results of a combined analy-
compared with low intakes were modest at <0.8–0.9 and were sis of data from 10 case-control studies of breast cancer; the
not significant. In the Health Professionals Follow-up Study, a authors found a modest decrease in breast cancer risk (0.85) with
prospective study in men, a possible inverse association between an increase of 20 g dietary fiber/d. Some of the more recent case-
dietary fiber and colon cancer was no longer observed after control studies of dietary fiber and breast cancer reported an
adjustment for potential confounding factors (35). Two other inverse association (41) and others reported no association (42,
prospective studies, one in Japanese-American men in Hawaii 43). Prospective cohort studies have provided a similar view of
 CEREALS, LEGUMES, AND CHRONIC DISEASE RISK 455S

the possible association between dietary fiber and breast cancer. intake from lowest to highest intake were 1.0, 0.92, 0.69, 0.61,
In the Nurses’ Health Study, there was little suggestion that and 0.70 (P trend = 0.02) after adjustment for multiple coronary
dietary fiber is associated with risk of breast cancer (44), a find- disease risk factors. This inverse association was also seen for
ing similar to that seen in the Iowa Women’s Health Study (45) consumption of dark bread and whole-grain breakfast cereal.
and in a cohort of postmenopausal women in New York (46). The inverse association with whole-grain intake could not be
Only one such study, a nested case-control study in a Canadian attributed solely to dietary fiber intake. Although adjustment for
population, supported a decreased risk of breast cancer with dietary fiber intake attenuated the relative risk estimates, the
increased intake of dietary fiber (47). Overall, these studies sug- association was still apparent (relative risks from lowest to high-
gest that if there is an association of dietary fiber with risk of est intake: 1.0, 0.96, 0.75, 0.68, and 0.77 (P trend = 0.12).
breast cancer, it is likely to be a modest one. Interestingly, there was no association of refined-grain intake
Regarding other cancer sites, relatively few studies have with risk of coronary artery disease death in the Iowa study (rela-
reported on dietary fiber intake. One review highlighted the con- tive risk = 0.97 for highest compared with lowest quintile of intake)
sistent inverse associations between fiber intake and pancreatic (64). In the Alpha-Tocopherol, Beta-Carotene Cancer Prevention
cancer that were observed in 5 of 6 case-control studies (48). Study, there was also no association between coronary death and

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Five of these studies (49–53) were conducted under the auspices cereal products other than rye products (16). These observations
of the International Agency for Research on Cancer and used suggest that there may be differences in the health benefits of
similar methods to allow pooling of data. In the combined analy- whole-grain compared with refined-grain intake, and that benefits
sis of these pooled data, the relative risks of pancreatic cancer seen with whole grains are not simply a result of substitution for
from lowest to highest quartiles of fiber intake were 1.0, 0.66, higher meat or fat intakes. As described by Slavin et al (8), there
0.56, and 0.42 (P trend < 0.01) (54). For cancers of other sites, are several potential compounds (in addition to dietary fiber) with
reviews indicate relatively little evidence of an association with associated mechanisms by which whole-grain intake may reduce
fiber intake, either because few studies have been reported or the the risk of chronic diseases such as cancer and heart disease.
findings have been null or inconsistent (55, 56). Because there has been little focus on cereal or grain intake per
se in epidemiologic studies, most studies have not collected
dietary data in a manner that allows separation of cereal con-
WHOLE GRAINS AND CHRONIC DISEASE sumption into whole-grain and refined-grain intake. A review by
Although there has been substantial interest in the role that Jacobs et al (65) identified 14 case-control studies of cancer that
dietary fiber may play in chronic disease risk, there has been com- included information on dietary exposures associated with whole-
paratively little focus on cereals and whole grains, which are major grain intake. Examples of these exposures included whole-grain
contributors to dietary fiber intake in most diets (57). This lack of bread or pasta (66, 67), whole-meal bread (68), brown bread (69),
focus is not simply a result of attention to nutrients or chemical or nonwhite bread (70). In this review, 4 of 5 case-control studies
compounds rather than foods or food groups; for example, there of colorectal cancer indicated inverse associations with whole-
have been numerous studies of vegetables, fruit, and cancer risk, a grain intake; odds ratios were generally <0.75 when comparing
topic of several reviews published in the past decade (38, 58, 59). high with low whole-grain intake. All 7 case-control studies of
There are relatively few studies of whole grains and coronary stomach cancer found inverse associations with whole-grain
artery disease (60, 61). In one of these, a prospective study of Sev- intake, with odds ratios ranging from 0.37 to 0.79 when compar-
enth-day Adventists, consumption of whole-wheat bread was asso- ing high with low intake. The other 2 case-control studies, on
ciated with significantly reduced risk of nonfatal coronary artery endometrial cancer, also suggested inverse associations with
disease compared with consumption of white bread (relative risk: whole-grain intake.
0.45; 95% CI: 0.28, 0.71) (60). In the Alpha-Tocopherol, Beta- In addition to the studies included in the review by Jacobs et
Carotene Cancer Prevention Study, consumption of rye products al (65), there have been several other case-control studies of can-
was associated with decreased risk of coronary artery disease, with cer that have published information on risk associated with
relative risks from lowest to highest quintiles of rye intake of 1.0, whole-grain intake. For example, one of the case-control studies
0.87, 0.86, 0.79, and 0.75 (P trend = 0.02) (24). Rye is not only an of pancreatic cancer that was mentioned previously with regard
important source of fiber, but in Finland, the whole grain, rather to fiber intake also included information on both whole- and
than the refined grain, is usually consumed. Similarly, consumption refined-grain intakes (50). At least 4 other case-control studies of
of breakfast cereals was associated with a lower risk of coronary pancreatic cancer also included information on whole-grain
disease in the Health Professionals Follow-up Study (relative risk: intake (71–74). Two of these studies reported inverse associa-
0.83; 95% CI: 0.69, 0.99), but information was not presented as to tions of whole-grain intake with risk of pancreatic cancer (odds
whether the cereals were made of whole or refined grains (62). ratios of 0.44 and 0.70 for high and low intake, respectively; 71,
Finally, in a cohort study of British vegetarians (63), daily con- 74), whereas 1 reported no association (72). An additional large
sumption of whole-meal bread was associated with a nonsignifi- case-control study of colon cancer reported an inverse associa-
cant reduction in risk of coronary mortality of 0.85 (95% CI: 0.68, tion with whole-grain intake in men, but not women (31). At
1.06); however, consumption of bran cereals was not associated least 2 case-control studies of breast cancer with information on
with reduced mortality from coronary artery disease. whole-grain intake have also been published; one of these
Recent analyses from the Iowa Women’s Health Study also reported an inverse association with whole-grain intake (75)
suggest that whole-grain intake is inversely associated with coro- whereas the other found essentially no association (76). Addi-
nary mortality (64). In this study, 387 of 34 492 women enrolled tional case-control studies of ovarian cancer (77), soft tissue sar-
in the study in 1986 and eligible for follow-up had died of coro- coma (78), and non-Hodgkin lymphoma (79) also reported
nary artery disease after 9 y of follow-up. The relative risks of inverse associations with whole-grain intake; in these studies,
coronary artery disease death among quintiles of whole-grain odds ratios comparing high with low intakes ranged from 0.40 to
456S KUSHI ET AL

0.75. Many of these studies are included in an updated review of role of soyfoods and phytoestrogens in chronic disease preven-
the association between whole-grain intake and cancer (80). tion, this article will not discuss the topic further.
Several of these and other case-control studies of cancer have The role of legumes in cancer prevention is unclear. Most
also reported on risk associated with intake of refined grains. In reviews on this topic generally indicate that among epidemiologic
contrast to the generally inverse associations seen with whole- studies, about as many studies suggest an inverse association as a
grain intake, refined grains tend to be associated with increased positive association between intake of legumes and cancer risk
risk of cancer across these studies. For example, among the case- (38). In a recent report concerning the association of legumes
control studies of colorectal cancer, refined-grain foods such as with cancer risk, it was noted that 58 epidemiologic studies have
pasta (66, 81) or starchy foods and flour products (82) were asso- examined this association (91). Of these, 29 reported a decreased
ciated with increased risk of colorectal cancer. In the large case- risk with higher intake whereas 22 reported an increased risk.
control study of colon cancer, refined-grain products were also Overall, no conclusions concerning the role of legumes in cancer
associated with increased risk (31). Similarly, white bread intake risk could be reached based on this literature (91).
was positively associated with pancreatic cancer risk in 3 studies
(71–74). Six of the 7 case-control studies of stomach cancer that

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were included in the review by Jacobs et al (65) on whole grains SUMMARY AND CONCLUSIONS
also reported associations with refined-grain foods (69, 70, 83–86). There is substantial evidence that increased consumption of
In these studies, various refined-grain foods, including white dietary fiber is associated with reduced risk of coronary artery
bread (83, 85, 86), pasta (69, 84, 85), or rice (presumed to be disease. This has been observed in the majority of prospective
white) (84, 85) were associated with increased risk of stomach cohort studies that have published information on this associa-
cancer. Only in a study conducted in Sweden was a refined-grain tion, although in some of these studies the association was weak-
food (white bread) not associated with stomach cancer risk (70). ened by adjustment for energy intake and cardiovascular risk
There have been relatively few prospective studies of refined factors. Whether dietary fiber intake is also inversely associated
or whole-grain foods and cancer risk. In one prospective study with risk of cancer, particularly large bowel cancer, is less clear.
conducted in Japan, intakes of rice and wheat, both of which are Although there have been relatively consistent findings of an
usually consumed as refined grains, were inversely associated inverse association between dietary fiber intake and risk of colo-
with risk of colorectal cancer (87). In this same cohort, these rectal cancer in case-control studies, the several prospective
foods were not associated with risk of stomach cancer. cohort studies on this topic have not confirmed these findings.
Overall, these studies indicate that consumption of whole- There is some interest in the possible role that whole-grain
grain foods is associated with reduced risk of a variety of cancers foods may play in reducing the risk of chronic diseases. In com-
and coronary artery disease, whereas refined-grain foods may be parison with the focus on dietary fiber, however, this topic has
associated with increased risk. Differences in disease risk asso- been relatively understudied. According to reviews, studies that
ciated with whole-grain compared with refined-grain foods sug- have reported on the associations of whole grains with cancer
gest that these findings are not due simply to the substitution of risk appear to almost uniformly indicate reduced risk associated
high-carbohydrate foods for high-fat or animal foods and also with increased intake of whole grains (65, 80). Whether this is
suggest that people can reliably distinguish refined from whole- attributable to dietary fiber, some other factor that is present in
grain foods. The observations in the Iowa Women’s Health Study greater abundance in whole grains, or a combination of such fac-
regarding the associations with coronary artery disease (64) also tors is not clear. However, whole grains contain numerous com-
suggest that these findings cannot be attributed solely to dietary pounds with biological activities that may lower the risk of
fiber intake. The findings do suggest that increased consumption chronic diseases, and the concentrations of many of these com-
of cereal products may reduce the risk of these diseases, but pounds are greatly diminished during the refining process.
these cereal products should be consumed as whole grains rather There is considerable interest in the role that legumes may
than the more commonly available refined grains. Recent find- play in the prevention of chronic diseases. Much of this interest
ings from the Nurses’ Health Study (88) and the Health Profes- has focused recently on the role of soyfoods, which appear to
sionals Follow-up Study (89) that linked the glycemic index of have hypocholesterolemic properties and may influence estrogen
foods with risk of type 2 diabetes underscore the possibility that metabolism and thereby decrease the risk of hormone-dependent
there may be other beneficial health effects of whole-grain foods cancers. However, there have been relatively few studies that
that are not yet widely recognized. have focused on elucidating the effects of legumes on disease
risk, and the epidemiologic studies that have addressed this ques-
tion have often focused on the roles of other foods or nutrients
LEGUMES AND CHRONIC DISEASE and therefore have collected limited information on legume
Along with whole grains, legumes constitute another food intake. Many of these studies are reviewed elsewhere in this sup-
group that has been relatively understudied in an epidemiologic plement. More work is needed in this area before the nature of
context. Whereas legumes are also a source of dietary fiber—the associations with cancer, heart disease, or other chronic condi-
relatively high soluble-fiber content of peas and beans was tions can be more clearly understood.
shown to lower blood cholesterol concentrations in feeding stud- Overall, the evidence regarding grains, dietary fiber, and
ies (7)—their effects on coronary artery disease have been inves- legumes supports the broad dietary guidelines that have been pro-
tigated in only a few studies. Similarly, although there has been mulgated by various agencies and committees. Indeed, research
substantial interest in the role that soyfoods may play in the pre- findings suggest that recommendations to consume whole grains
vention of cancer (90) or heart disease (7), there is relatively lit- deserve greater prominence than is currently provided in most
tle support from epidemiologic studies for this association. dietary recommendations. This shift in emphasis toward whole
Because other articles in this supplement focus on the possible grains and away from refined-grain breads, cereals, and pasta or
 CEREALS, LEGUMES, AND CHRONIC DISEASE RISK 457S

grain products that are otherwise undefined has been advocated 22. Kushi LH, Folsom AR, Prineas RJ, Mink PJ, Wu Y, Bostick RM.
by others (92). For example, the Dietary Guidelines for Ameri- Dietary antioxidant vitamins and death from coronary heart disease
cans (93) and the food guide pyramid (94) mention whole grains in postmenopausal women. N Engl J Med 1996;334:1156–62.
only in the text that accompanies the recommendations, and also 23. Ascherio A, Rimm EB, Giovannucci EL, Spiegelman D, Stampfer
M, Willett WC. Dietary fat and risk of coronary heart disease in men:
only in the context of dietary fiber intake. Although dietary fiber
cohort follow up study in the United States. BMJ 1996;313:84–90.
appears to be one component of whole grains that is associated
24. Stampfer MJ, Hennekens CH, Manson JE, Colditz GA, Rosner B,
with reduced risk of coronary artery disease, other factors, such Willett WC. Vitamin E consumption and the risk of coronary disease
as vitamin E and phytoestrogenic lignans, may also play impor- in women. N Engl J Med 1993;328:1444–9.
tant roles in the consistently observed inverse associations of 25. Potter JD. Nutrition and colorectal cancer. Cancer Causes Control
whole-grain intake with risk of chronic diseases. 1996;7:127–46.
26. Trock B, Lanza E, Greenwald P. Dietary fiber, vegetables, and colon
cancer: critical review and meta-analyses of the epidemiologic evi-
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