cardiovascular disease (ASCVD) is the leading cause of death
in the U.S. and in most developed countries. Many nutritional
factors contribute to risk for ASCVD including total and saturated
fat consumption, fruits and vegetables in the diet and dietary
fiber intake. This review will focus
on the relationship of dietary fiber
intake to risk for coronary heart disease (CHD) and ASCVD (which
includes, principally, CHD, cerebral vascular disease and peripheral
vascular disease). Fiber-rich foods
such as vegetables, fruits, whole-grain cereals and legumes
are rich sources of nutrients, phytochemicals and antioxidants.
For example, most high fiber foods contain soluble and
insoluble fiber, minerals, vitamins,
other micronutrients and phytochemicals. Cereals and legumes
also contain complex carbohydrates and unsaturated fatty acids.
Some high fiber foods are rich in
monounsaturated fatty acids, whereas others provide (n-3) fatty
acids. Legumes and certain vegetables provide oligosaccharides.
When assessing the health benefits of dietary fiber,
one should consider the potential effects
of associated nutrients, micronutrients and phytochemicals.
These interactions will be reviewed as we discuss relationships
of dietary fiber to ASCVD.
FIBER AND CORONARY HEART DISEASE
evidence for links between dietary fiber
and atherosclerotic cardiovascular disease (ASCVD) is very strong;it
arises from animal studies (Pilch 1987), epidemiologic observations
(Rimm et al. 1996) and a limited number of clinical trials (Anderson
1995a). In addition, there is a strong theoretical rationale
for this link, making the association a logical one. Trowell
(1972) proposed that a deficient fiber intake might contribute to the high prevalence of coronary
heart disease (CHD) among Western people and that a generous
fiber intake in other areas of the world was protective from
CHD. This hypothesis has gained widespread acceptance, but the
scientific data in its support have been limited. Recently,
Rimm et al. (1996) reported that higher levels of fiber
intake were associated with lower rates of myocardial infarctions
and death from CHD among U.S. male health professionals. This
prospective cohort study probably provides the most persuasive
support for the Trowell hypothesis linking dietary fiber intake to protection from coronary heart disease. Since
the report of Morris et al. (1977), epidemiologists have reported
a strong link between dietary fiber
intake and prevalence of CHD (Rimm et al. 1996). Vegetarian
populations have higher fiber intakes than nonvegetarian control populations (Beilin
1994, Kritchevsky et al. 1984) and experience better health
and fewer premature deaths (Anderson
1990). All cause mortality is significantly lower for vegetarian
than for age and gender matched nonvegetarian individuals (Kahn
et al. 1984, Lemon and Walden 1966); this reduction is related,
in part, to a significant reduction in CHD mortality (Kristein
et al. 1977, Ruys and Hickie 1976, Wynder 1959). Although the
health benefits associated with vegetarian diets can be attributed,
in part, to physical activity and other healthy lifestyle practices,
the increased dietary fiber intake appears to make a significant contribution (Anderson 1990, Rimm et al. 1996).
the past 20 years, numerous studies have examined the associat
on between dietary fiber intake and risk for CHD. Rather remarkably, all of these
studies suggest that there is a negative relationship when evaluating
dietary fiber intake with CHD. Seven
studies (Burr and Sweetman 1982, Hallfrisch et al. 1988, Khaw
and Barrett Connor 1987, Kromhout et al. 1982, Kushi et al.
1985, Liu et al. 1982, Morris et al. 1977) noted the negative
association specifically with dietary fiber;
the remainder used other markers of fiber
intake such as legume intake, salad intake, complex carbohydrate
or vegetable protein intake.
findings may depend on the epidemiologic design, which can be
ecological, cohort, case comparison or population-based. Ecological
studies are designed to assess the association between two variables,
comparing groups whose selection is based on a variable that
is not being studied, such as geographical location. Liu et
al. (1982) conducted a univariate analysis on data for both
men and women ages 3574 y from 20 economically advanced countries,
collecting data for the years 19651969. They found that fiber
intake, estimated from consumption of vegetables, fruits, grains
and legumes, yielded a significant inverse correlation with
CHD mortality rates. Cohort studies evaluate the association
between a risk factor and the incidence of a disease as compared
among two or more groups. These groups are determined on the
basis of levels of exposure to a particular variable. Morris
et al. (1977) published one of the first cohort studies on the
health implications of a high fiber
diet in cardiovascular disease. From 1956 to 1966, 7-d dietary
surveys were collected from 337 middle-aged men in London and
Southeast England. These men were reevaluated in 1976 to determine
those who had developed clinical coronary heart disease. From
this information, it was noted that dietary fiber
from cereals was independently associated with a lower rate
of disease. In 1973, Burr and Sweetnam (1982) recruited 10,943
subjects to test the hypothesis that risk of death from disease
can be reduced by a high intake of fiber.
After 7 y, no significant associations were found with fiber.
However, a lower mortality from cerebrovascular disease was
noted in subjects who regularly consumed whole-meal bread. A
1960 study by Kromhout (1982) enlisted the help of 871 middle-aged
men in the Netherlands to evaluate risk indicators for CHD.
After 10 y of follow-up, it was suggested that a diet of at
least 37 g of dietary fiber per day
may be protective against chronic diseases such as CHD. Case-comparison
studies assess the association between a disease state and risk
factors, comparing diseased vs. nondiseased subjects. The risk
factor data are often collected either concurrently or retrospectively.
Khaw and Barrett-Connor (1987) evaluated the relationship between
dietary fiber intake and 12-y mortality
rates from ischemic heart disease in a population-based cohort
of 859 men and women living in Southern California. They calculated
that every 6 g increase in daily fiber
consumption was associated with a 25% reduction in ischemic
heart disease mortality. Kushi and collaborators (Kushi et al.
1985) examined the relation between diet and mortality from
CHD in a prospective epidemiologic study of 1001 middle-aged
men. Intakes of fiber, vegetable protein
and starch were lower in those individuals who died from coronary
heart disease. However, these observations were not significant
after adjustment for other risk factors. In 1992, Bolton-Smith
et al. (1992) published results of a case-comparison study in
which 10,359 men and women ages 4059 who were patients of 260
general practitioners throughout Scotland were evaluated. Subjects
were divided into the categories of CHD-diagnosed, CHD-undiagnosed
and non-CHD. Food-frequency questionnaires were used to record
dietary habits. The results suggested that a high dietary fiber
intake may be cardioprotective in both males and females.
surveys assess the cross-sectional association between two variables
by comparing population groups. For example, one can measure
the prevalence, mean value or distribution of a particular characteristic
or disease in a population. Hallfrisch et al. (1988) used 7-d
diet records to estimate fiber intake for the 845 men participating in the Baltimore
Mean Longitudinal Study of Aging. On the basis of this information,
the researchers determined that a higher fiber
consumption was associated with lower levels of risk factors
for coronary artery disease, including systolic and diastolic
blood pressure, triglycerides and fasting plasma glucose. Recently,
He et al. (1995) studied 850 Chinese subjects to evaluate the
relationship of oats and buckwheat to cardiovascular disease.
Dietary intake of oats and buckwheat was determined via a dietary
questionnaire. Although oat intake was associated with a lower
body mass index (BMI), systolic and diastolic blood pressure
and HDL cholesterol, buckwheat intake was associated with lower
serum cholesterol, LDL cholesterol and a higher ratio of HDL
to total cholesterol.
several clinical trials have established an inverse relation
between fiber intake and CHD, two studies (Neal and Balm 1990, Rimm
et al. 1996) suggest that the intake of Cereal fiber
has the strongest negative association with CHD. This is somewhat
surprising because cereal fiber, in
most regions of the world reported in these studies, comes largely
from wheat intake. Wheat bran does not decrease serum cholesterol
and LDL cholesterol concentrations as effectively as does oat
bran or psyllium, sources of soluble fiber. Perhaps the phytochemicals specific to wheat bran (Slavin
1994) may have triglyceride-lowering effects
and CHD protective effects by mechanisms
not related to LDL cholesterol reductions. The triglyceride-lowering
effects of wheat bran are discussed in the next section.
the fact that some unknowns exist about the precise mechanism
mediating lipoprotein changes, substantial evidence supports
the role of fiber. Ecological, cohort,
casecomparison, population-based and most recently clinical
trials support the inverse relationship between dietary fiber in the diet and ASCVD.
OF DIETARY FIBER
cholesterol concentrations are surrogate markers for risk for
CHD because LDL have a central role in the pathogenesis of atherosclerosis
(Navab et al. 1996). Oxidation of LDL in the subendothelial
space of arteries sets the stage for macrophage uptake of LDL,
foam cell development, and ultimately fatty streak and atheroma
formation (Navab et al. 1996). Decreasing the LDL cholesterol
concentrations is one of the most effective means of decreasing
risk for coronary heart disease (Manson et al. 1992). Dietary
fiber, especially soluble,
viscous fibers effectively decrease serum cholesterol and LDL
cholesterol concentrations, which may contribute to their protective
role against CHD (Anderson et al.
1990). In addition to its favorable effects
on fasting and postprandial serum lipoproteins, as detailed
below, dietary fiber intake affects a number of other CHD risk factors. The
effects of fiber
intake on these factors such as hypertension, diabetes and obesity
are summarized below.
soluble or viscous fibers have hypocholesterolemic effects (Anderson et al. 1990, Glore
et al. 1994). In general, these soluble
fibers, such as psyllium, oat bran, guar and pectin, decrease
serum cholesterol and LDL cholesterol concentrations without
affecting serum triglycerides. Often, consumption of these soluble
fibers is accompanied by distinct reductions in serum HDL cholesterol
concentrations. For example, in studies of the effects
of dry beans on serum lipoprotein concentrations, we noted that
consumption of 100 g of dry beans per day, without other changes
in macronutrient consumption, was accompanied by a 16.1% net
reduction (bean change minus control change) in serum LDL cholesterol
concentrations and a 9.9% net reduction in serum HDL cholesterol
concentrations (Anderson 1995b).
models provide a suitable approach for comparing lipid-lowering
effects of dietary fibers under controlled
conditions. We have performed 30 such studies comparing 610
fibers in each study with 10 rats in each treatment (Anderson
et al. 1994, Anderson 1995a).
information about the effects of different
fibers on serum lipids of rats after 3 wk of consuming purified
diets providing 67% carbohydrate, 15% protein, 6% fat, 6% dietary
fiber, 1% cholesterol, 0.2% cholic
acid, vitamins and minerals (Anderson
1995a). In this model, psyllium had the largest cholesterollowering effect by decreasing serum cholesterol by 32%
and liver cholesterol by 52%. Oat gum and guar gum were slightly
less effective and decreased serum cholesterol by 22%, compared
with values for cellulose-fed rats. Pectin has been reported
to have a wide range of effects, depending on molecular weight and degree of methoxylation
(Ebihara et al. 1979, Jud and Truswell 1982), whereas oat bran
and soy fiber produce modest effects
(Anderson et al. 1994, Anderson
1995a). The serum triglyceride responses to these diets are
of interest and have not been discussed previously. In a pioneer
study in 1974, Heaton and Pomare (1979) reported that wheat
bran intake decreased serum triglyceride concentrations in humans.
Because wheat bran does not have a significant effect on serum
cholesterol concentrations, these observations have not been
carefully pursued. From our rat studies, it is clear that soluble
fibers such as psyllium, oat gum and pectin do not have significant
effects on serum triglycerides. However,
wheat bran was associated with a major triglyceride-lowering
effect; corn bran, with a limited number of observations, also
appears to lower serum triglycerides.
In humans, psyllium
and guar gum appear to be the most effective cholesterol-lowering
soluble fibers (Anderson
et al. 1990). The hypocholesterolemic effects
of psyllium (Olson et al. 1997), guar gum (Todd et al. 1990)
and oat bran (Ripsin et al. 1992) are well documented by meta-analyses.
Our 1990 analysis of 23 human studies described the effects
of guar gum supplementation on serum cholesterol. A median reduction
of 11% (range, from 3% to 38%) was noted with inclusion of guar
gum in the diet. Significant reductions in serum cholesterol
levels were found in 20 of the 23 studies evaluating guar gum
supplementation (Anderson et al. 1990).
Similarly, a 1992 meta-analysis by Ripsin et al. (1992) tested
the hypothesis that oat supplementation would lower serum cholesterol
levels. Ten clinical trials were evaluated, and a reduction
of 5.9 mg/dL ( 0.13 mmol/L) in total cholesterol was noted in
subjects consuming an oat supplement. However, the most significant
reductions were found in trials that used hypercholesterolemic
subjects with initially higher cholesterol levels. Pectin also
has significant hypocholesterolemic effects
(Anderson et al. 1990), whereas soy fiber
has a modest effect in humans (Lo
et al. 1986). A summary of 19 clinical studies evaluating the
effects of pectin supplementation
on serum cholesterol was included in our 1990 analysis. A median
reduction of 8% (range, 5 to 18%) in total cholesterol was noted
in subjects receiving pectin in their diet. A significant reduction
in total cholesterol was found in 13 of the 19 trials evaluated
(Anderson et al. 1990). Other less widely studied and used
soluble fibers, such as locust bean gum (Zavarol et al. 1983)
and konjac mannan (Anderson et al.
1990), have modest hypocholesterolemic effects.
effects of soluble fiber intake on specific lipoproteins is of great importance.
LDL cholesterol appears to be the most atherogenic lipoprotein
(Navab et al. 1996), but HDL cholesterol has an extremely important
counterbalancing effect (Gowri 1997). The atherogenicity of
triglyceride-rich particles is still debated, but postprandial
hypertriglyceridemia probably contributes to risk for CHD (Anderson
et al. 1995b). Because LDL particles carry 65% of the cholesterol
in serum, changes in total serum cholesterol values largely
follow changes in serum LDL cholesterol concentrations. Soluble
or viscous fibers have specific effects
on LDL cholesterol and exert only minimal effects
on other lipoprotein particles. In our metaanalysis of eight
studies conducted in a comparable manner, administration of
10.4 g of psyllium daily for 8 wk to hypercholesterolemic subjects
consuming an American Heart Association (AHA) Step I diet was
accompanied by a net reduction (psyllium minus placebo) of 6.7%
in LDL cholesterol ( P 0.0001) (Anderson,
J. W., unpublished observations).
Similarly, specific effects on LDL
cholesterol concentrations have also been noted in subjects
consuming oat bran (Ripsin et al. 1992).
psyllium and oat bran tend to decrease HDL cholesterol concentrations
slightly, these changes are not significant. Because HDL cholesterol
is an umbrella term for a variety of small lipoprotein particles,
namely, as well as apolipoprotein (apo) A-I (only) and apo A-I/A-II
particles (Silverman and Pasternak 1993), measurements of the
total HDL cholesterol concentration have serious limitations.
Recent studies indicate that specific interventions affect the
antiatherogenic HDL particles (HDL and apo A-I particles) selectively,
whereas other interventions tend to affect the neutral or atherogenic
HDL particles (apo A-I/A-II) (Silverman and Pasternak 1993).
Estrogens may increase concentrations of antiatherogenic HDL
particles, whereas alcohol may increase the less protective
particles (Silverman and Pasternak
The effects of dietary
fibers on the specific HDL subfractions are not well delineated.
In our meta-analysis (Anderson, J. W.,
unpublished observations), we noted that psyllium supplementation
slightly increased the serum apo-A-I concentrations and significantly
increasing the apo-A-I/apo-B ratio. Further studies are required
to understand the specific effects of soluble fibers on HDL
MECHANISMS FOR HYPOCHOLESTEROLEMIC EFFECTS
The cholesterol-lowering effects
of soluble or viscous fibers relate
to their gel-forming properties (Anderson
1995b). Soluble fibers, such
as gum acacia, which do not form viscous solutions in water,
appear to have minimal hypocholesterolemic effects
(Haskell et al. 1992).Similarly, hydrolyzed guar gum does not
have significant cholesterol-lowering benefits in humans
(Anderson et al. 1993). Soluble
fibers such as psyllium and oat bran appear to exert their principal
effects on cholesterol metabolism through decreases in bile
acid absorption. These soluble fibers
bind bile acids in the small intestine, alter micelle formation
and decrease their absorption in the small intestine. Consequently,
more bile acids are excreted with the feces. Oat bran, for example,
increases fecal bile acid loss more than twofold and increases
loss of deoxycholic acid (DCA) by 240% (Marlett et al. 1994).
Psyllium also increases bile acid excretion significantly and
selectively increases the fractional turnover of both chenodeoxycholic
acid (CDCA) and cholic acid (CA) (Everson et al. 1992). Acting
somewhat like bile-acid binding resins, these soluble
fibers deplete the bile salt pool and divert cholesterol synthesis
from lipoprotein precursors to bile acid synthesis. Short-chain
fatty acid (SCFA) effects on the liver may hamper the ability of the liver to
compensate for these changes in cholesterol synthetic needs
(Wright et al. 1990). Martlett et al. (1994) evaluated nine
normolipidemic young men fed a control diet with or without
oat bran for 2 mo. Serum CA and CDCA were measured using radiolabeled
carbon as a means to monitor bile acid kinetics. Results of
this study indicated that bile acid excretion and concomitant
increases in bile acid synthesis are primary contributors to
changes in cholesterol absorption. They found that, when subjects
consumed the oat bran diet, total daily fecal bile acid excretion
more than doubled, with a significant elevation in secondary
bile acid excretion as well. Although the total bile acid pool
was unchanged, the CA pool size decreased, whereas the DCA pool
doubled. This elevation in DCA is significant because DCA inhibits
primary bile acid synthesis by affecting hepatic cholesterol
7 hydroxylase activity and by inhibiting -hydroxyl-methyl glutarate
(HMG)-CoA reductase activity, the rate-limiting step in cholesterol
synthesis (Marlett etal. 1994). In addition, DCA serves as a
more effective inhibitor of cholesterol absorption than chenodeoxycholic
acid (CDCA) in healthy humans (Leiss
et al. 1984).
production in the colon, absorption into the portal vein and
effects on the liver appear to play
a minor regulatory role in attenuating hepatic cholesterol synthesis
(Anderson 1995c, Anderson and Chen 1979, Wright et al. 1990). After meals containing
soluble fibers, serum acetate levels
increase, reflecting more delivery of SCFA to the liver. Our
in vitro data suggest that propionate specifically inhibits
cholesterol and fatty acid synthesis in the liver (Wright et
al. 1990). It seems likely that the combination of bile acid
loss and mild attenuation of hepatic cholesterol synthesis results
in lower serum cholesterol and LDL cholesterol concentrations.
Although it could be tested,, this hypothesis has not been examined
carefully in humans.
fiber-rich foods are associated with significant protection
from CHD and viscous hydrolyzed fibers have hypocholesterolemic
effects, these effects may be minimized
if purified fibers are used. For example, guar gum has significant
cholesterol-lowering effects (Anderson et al. 1990), whereas hydrolyzed guar gum lacks this
effect (Anderson et al. 1993). Furthermore,
although soy proteins rich in soy isoflavones have significant
hypocholesterolemic effects (Anderson
et al. 1995a, Anthony et al. 1996, Wagner et al. 1997), purified
isoflavone supplements may lack this effect (Nestel et al. 1997).
Thus, hydrolysis of fibers and isoflavones to extract them for
use as supplements may alter their physiologic effectiveness.
FIBER EFFECTS ON NON LIPOPROTEIN
CHD RISK FACTORS
clinical trials have failed to provide persuasive evidence that
increased fiber intake is as sociated
with a decrease in blood pressure. However, epidemiologic studies
support the hypothesis that higher levels of dietary fiber intake are associated with lower levels of systolic
as well as diastolic blood pressure (Ascherio et al. 1992, Joffres
et al. 1987, Witteman et al. 1989). In addition, research with
vegetarian subjects, who have higher intakes of dietary fiber
than control subjects, has found that the vegetarians have lower
blood pressures than their matched controls (Sacks et al. 1975).
Median reductions of 3.5 mm Hg in systolic and 2.2 mm Hg in
diastolic blood pressure were noted in three controlled studies
using vegetarian diets (Wright et al. 1979). Similarly, Appel
et al. (1997) reported that a diet that is rich in fruits, vegetables
and low fat dairy foods can substantially lower blood pressure.
The DASH Collaborative Research Group enrolled 459 adult subjects
with systolic blood pressures 160 mm Hg and diastolic blood
pressures between 80 and 95 mm Hg. After 3 wk of consuming a
control diet, subjects were randomly allocated to a diet rich
in fruits and vegetables, a combination diet rich in fruits,
vegetables and low fat dairy foods, or a control diet for 8
wk. At the end of treatment, systolic and diastolic blood pressure
had dropped 5.5 and 3.0 mm Hg more, respectively, with consumption
of the combination diet and were 2.8 and 1.1 mm Hg higher, respectively,
with the fruit and vegetable diet compared with the control
diet. This reduction in blood pressure was most significant
in subjects with an initial systolic blood pressure 140 mm Hg,
diastolic blood pressure 90 mm Hg or both. Unfortunately, a
vast array of clinical trials has produced conflicting results,
making it difficult to form concrete recommendations concerning
use of dietary fiber as a means to
lower blood pressure. Although it appears that a negative correlation
exists, further research is required to understand the variation
in blood pressure response seen across human trials.
has been found to be an independent risk factor for coronary
heart disease (Manson et al. 1995, Solomon and Manson 1997).
Research supports the role that dietary fiber plays in controlling obesity by offering a prolonged
feeling of satiety. A study of 50 male college students was
designed to determine the effects
of a high fiber diet on subsequent
food intake. It was determined that adding 5.2 g of crude fiber to a meal significantly reduced food intake. In addition,
those subjects receiving the high fiber
meal felt significantly fuller than did the lower fiber
subjects immediately after eating (Porikos and Hagamen 1986).
A similar controlled study by Rigaud et al. (1987) enlisted
the help of 20 healthy young volunteers who received either
a high fiber supplement (7.3 g fiber
per day) or placebo (0.6 g fiber per day). Visual analog scales were used to evaluate
feelings of hunger immediately after each of three main meals.
Mean hunger ratings were significantly greater during the control
period compared with during fiber
treatment. Rytigg et al. (1989) conducted a 52-wk controlled
study to determine the effects of
a dietary fiber supplement on weight
maintenance and reduction in 90 female subjects with uncomplicated
excess weight of 110130% of ideal body weight. It was noted
that hunger feeling in the fiber group decreased significantly at all three meals compared
with placebo. These three studies offer support to the suggestion
that a diet rich in fiber can help
control appetite by increasing satiety. With the new United
States health standards, which indicate that a BMI 25 increases
CHD risk (NHLBI Communications 1998), it is prudent to reduce
weight, especially in the Western world where waistlines continue
Diabetes and hyperinsulinemia.
estimated 70-80 million persons in the United States have insulin
resistance. Insulin resistance is an important risk factor in
the development and progression of hypertension, dyslipidemia,
obesity, diabetes (Ferrannini et al. 1987, Lillioja et al. 1993,
Reaven 1988) and possibly CHD (Pyorala 1997, Stout 1990). A
diet rich in fiber has been shown
to improve insulin sensitivity (Anderson
et al. 1991, Fukagawa et al. 1990) and lower serum insulin concentrations
(Wolever and Jenkins 1986). A controlled, random allocation,
crossover, metabolic study (Anderson
et al. 1991) allocated 10 subjects with insulin-dependent diabetes
mellitus (IDDM) to a low carbohydrate, low fiber
(LCLF) or a high carbohydrate, high fiber
(HCHF) diet for 28 d at a time. The HCHF diet provided 35 g
dietary fiber/1000 kcal in the form
of whole-grain or bran cereals, dried beans, vegetables and
fruit. Compared with the LCLF diet, the HCHF diet reduced basal
insulin requirements and increased carbohydrate disposed of
per unit insulin. This study indicated that Type 1 diabetic
subjects were more sensitive to insulin when consuming a high
carbohydrate, high fiber diet than
when consuming a low carbohydrate, low fiber,
high fat diet. High carbohydrate, high fiber,
low fat diets have also been recommended for patients with Type
2 diabetes. A diet of 63-65% of energy from carbohydrates,
10-12% of energy from fat and 45 g/d of fiber for 2 wk was found to offer a significant benefit in
metabolic control in volunteers with noninsulin-dependent diabetes
mellitus (NIDDM). A similar improvement was not seen in a complementary
high carbohydrate, low fat diet that was low in fiber
(20 g/d) (O'Dea et al. 1989).
et al. (1990) studied 12 healthy individuals to examine the
effects of a HCHF diet. The HCHF diet
provided 68% of energy as carbohydrates and 33 g/1000 kcal of
dietary fiber compared with 43% of
energy as carbohydrates and 7g/1000 kcal of dietary fiber
for the control diet. The HCHF diet was followed for 21-28
d. The HCHF diet lowered fasting serum glucose levels from 5.3
0.2 to 5.1 0.1 mmol/L ( P 0.01) and insulin from 66.0
7.9 to 49.5 5.7 pmol/L ( P 0.01). In addition, glucose
disposal rates increased from 18.87 1.66 mol/(kg min) in those
consuming the control diet compared with 23.87 2.78 mol/(kg
min) ( P 0.02) for those provided the HCHF diet. From
these results, the authors concluded that a HCHF diet may improve
carbohydrate metabolism by enhancing peripheral sensitivity
to insulin in healthy adults. Results of these controlled research
trials have been supported by a cohort study of 65,713 women,
ages 40-65 y, involved in the Longitudinal Nurse's Health study.
Participants completed a dietary questionnaire in 1986 at which
time subjects were free from diagnosis of cardiovascular disease,
cancer or diabetes. After 6 y of follow-up, 915 cases of NIDDM
had been documented. It was determined that cereal fiber
intake was inversely associated with risk of diabetes when comparing
extreme quintiles. From this observation, the authors suggested
that grains should be consumed in a minimally refined form to
reduce the incidence of diabetes (Salmeron et al. 1997b). Similar
results for disease risk were also seen in adult males (Salmeron
et al. 1997a). Thus, dietary fiber
intake appears to decrease the risk for developing Type 2 diabetes.
difficult to delineate from other dietary factors in a high
fiber diet, it appears that dietary
fiber intake may affect blood coagulation
factors. Marchmann and collaborators (Marchmann et al. 1994)
conducted a dietary intervention study of healthy middle-aged
Danish men and women during which they received either a traditional
high fat diet or a diet that was low fat, and high fiber
(LFHF). The LFHF diet significantly decreased plasma factor
VII coagulant activity and increased plasma fibrinolytic activity.
This reduction in plasma factor VII may be physiologically important
because an 8% reduction in factor VIIc might reduce the risk
for CHD by 1520% over 5 y.
NON-FIBER PLANT COMPOUNDS AND CHD RISK
fruits, grains and legumes are important dietary sources of
phytochemicals, antioxidant vitamins and certain (n-3) fatty
acids. The potential role of these compounds is reviewed briefly
below; limited information exists on the specific effects of linolenic acid, a plant (n-3) precursor of longer-chain
(n-3) ``fish oils,'' and this subject has been reviewed elsewhere
(de Lorgeril et al. 1994, Harris 1997).
are biologically active plant compounds that are ``semi-essential''
but are not classified currently as vitamins or minerals (Kuhnau
1976). Howard and Kritchevsky (1997) reviewed the knowledge
relating CHD risk to three classes of phytochemicals, i.e.,
plant sterols, flavonoids and plant sulfur compounds. Each will
be briefly reviewed below for their potential role with respect
to risk for CHD. Plant foods contain a number of sterols that
differ from cholesterol by small differences in their side chains.
The most prominent ones are sitosterol, stigmasterol and campesterol;
the total amount of plant sterols in the Western diet approaches
the amount of dietary cholesterol (Howard and Kritchevsky 1997).
These plant sterols are poorly absorbed and appear to decrease
cholesterol absorption (Mattson et al. 1982). By this mechanism,
plant sterol intake may decrease serum cholesterol concentrations
by as much as 10%. A recent clinical study of hypercholesterolemic
individuals suggests that the daily intake of 1.92.6 g of sitosterol
in a margarine preparation over a 1-y period was associated
with a 10.2% reduction in serum cholesterol concentrations (Miettinen
et al. 1995). From the amounts of plant sterols required to
significantly decrease serum cholesterol concentrations, it
seems unlikely that the amounts of these sterols consumed by
average individuals would affect serum cholesterol concentrations
(Denke et al. 1994). The plant flavonoids are a variety of chemical
compounds that are derivatives of 2-phenyl-1-benzopyran-4-one;
they occur naturally in vegetables, fruits, tea and wine (Hertog
et al. 1993, Howard and Kritchevsky 1997). Major sources of
flavonoids in the diet are tea, red wine, onions and apples
(Hertog et al. 1993). Several epidemiologic studies indicate
that higher flavonoid intakes are associated with lower rates
of CHD (Hertog et al. 1993 and 1995, Knekt et al. 1996). These
flavonoids appear to decrease risk for CHD by several different
mechanisms. Soy proteins, rich in isoflavones, have significant
hypocholesterolemic effects (Anderson
et al. 1995d). Intakes of soy protein (Anderson
et al. 1995d) or green tea (Simons et al. 1995), probably acting
through their flavonoids, have a tendency to increase serum
HDL cholesterol concentrations. Catechins, soy isoflavones and
phenolic substances from red wine have important antioxidant
properties and apparently are transported by LDL so that they
protect against in vitro oxidation of LDL (Anderson
et al. 1998, Frankel et al. 1993, Simons et al. 1995). Soy isoflavones
and other flavonoids also appear to decrease platelet aggregation
(Wilcox and Blumenthal 1995) and blood clotting, thereby decreasing
the tendency to thrombosis (Gryglewski et al. 1987). Although
soy isoflavones are not well quantified in humans
(Nestel et al. 1997), studies in monkeys (Honore et al. 1997)
suggest that they exert favorable effects on blood vessel dilatation similar to the effects of estrogens; thus, flavonoids may decrease risk of
CHD through protective effects on
blood vessels. Sulfur-containing plant foods such as garlic
also have hypocholesterolemic effects and decrease the tendency to form arterial thromboses.
The allium family of vegetables, which includes onions, garlic
and leeks, provides a variety of sulfur compounds that have
been used for medicinal purposes for millennia (Howard and Kritchevsky
1997). Although two recent meta-analyses (Silagy and Neil 1994,
Warshsky et al. 1993) report significant hypocholesterolemic
effects of garlic intake, a recent
well-controlled clinical trial (Simons et al. 1995) failed to
detect a significant effect. Further clinical studies are required
to demonstrate more clearly the effect of garlic or garlic powder
intake on serum lipoproteins, platelet aggregation, coagulation
time and blood pressure (Howard and Kritchevsky 1997).
LDL-oxidation hypothesis for atherosclerosis, as outlined above,
supports the potential protective role of antioxidant-rich foods
and supplements. Briefly, considerable experimental and clinical
data suggest that oxidative modification of LDL contributes
to the initiation of the plaque formation in the subendothelial
space of blood vessels (Navab et al. 1996). Vitamin E, the major
antioxidant transported in the LDL particle, has the potential
to reduce oxidative modification of LDL through its potent chain-breaking
antioxidant action (Dieber-Rotheneder et al. 1992). Indeed,
early epidemiologic and observational studies (Gey 1991, Kardinaal
et al 1993, Regnstom et al. 1996, Riemersma et al. 1991) support
the hypothesis that a generous intake of vitamin E is associated
with a reduced risk for CHD. Three large epidemiologic cohort
studies (Knekt et al. 1996, Rimm et al. 1993, Stampfer et al.
1993) all reported significant reductions in risk for CHD events
with reductions ranging from 31 to 65% (Jha et al. 1995). The
recent report of Kushi et al. (1996) noted that CHD risk is
62% lower in women with the greatest vitamin E intake. Many
clinical studies (Abbey et al. 1993, DieberRotheneder et al.
1992, Fuller et al. 1996, Jialal et al. 1995, Princen et al.
1992, Reaven et al. 1995) document the association of vitamin
E supplementation with a significant reduction in the in vitro
oxidation of LDL. As Jha et al. (1995) summarized, the earlier
prospective clinical trials did not report significant benefits
for vitamin E supplementation. The Cambridge Heart Antioxidant
Study (CHAOS) (Stephens et al. 1996) was a double-blind placebo-controlled
study that randomized 2002 patients with angiographically proven
CHD. Half of the patients received either 400 or 800 IU
vitamin E; the remainder received placebo. Vitamin
E intake was associated with a significant 47% reduction in
CHD events (Stephens et al. 1996). Because of the conflicting
results of these earlier trials, definitive conclusions must
be delayed until additional trials are completed (Prince et
al. 1991). -Carotene is also an antioxidant vitamin that is
transported in LDL and has a potential to decrease LDL oxidation
(Esterbauer et al. 1991). Epidemiologic studies suggest that
there is an inverse relationship between carotene intake and
CHD risk (Gey et al. 1993, Jha et al. 1995, Kardinaal et al.
1993, Morris et al. 1977). Although carotene supplementation
does not significantly alter in vitro oxidation of LDL (Gaziano
et al. 1995, Princen et al. 1992), several clinical trials have
examined the effects of -carotene
on risk for CHD. Three major randomized trials (Hennekens et
al. 1996, Omenn et al. 1996, The Alpha-Tocopherol BC 1994) reported
no significant alterations in CHD mortality associated with
-carotene supplementation. Because of the concerns about increased
risk for lung cancer among smokers receiving -carotene (Omenn
et al. 1996, The Alpha-Tocopherol BC 1994), enthusiasm for this
supplement has waned (Hennekens et al. 1996). Vitamin C is also
a potent antioxidant vitamin that is water soluble.
Although not transported in the LDL particle, vitamin C protects
LDL from in vitro oxidation (Frei 1991, Jialal et al. 1990).
Vitamin C has the capacity to preserve vitamin E in the plasma
and also repair oxidative damage inflicted on vitamin E (Esterbauer
and Ramos 1995). Earlier studies (Enstrom et al. 1992, Gey et
al. 1993) suggested an inverse relationship between vitamin
C intake and CHD risk, whereas large prospective observational
studies have not been consistent (Jha et al. 1995). Three randomized
trials have also yielded conflicting results (Jha et al. 1995).
Thus, the independent effects of vitamin
C intake on risk for CHD are unclear. Although most attention
has focused on antioxidants and decreased oxidation of LDL,
various antioxidants have other vascular-protective effects.
Prince et al. (1991) summarize the following effects
of antioxidants that are unrelated to LDL oxidation: preservation
of endothelial-derived nitric oxide action; inhibition of leukocyte
adhesion; reduction of cellular oxidation damage; and inhibition
of plalelet activation and smooth muscle proliferation. The
available data suggest strongly that vitamin E intake is associated
with a protection from CHD. -Carotene and vitamin C may also
have protective effects. Further clinical
trials are required to assess the clinical importance of these
observations. Currently, at least eight prospective trials examining
the effects of antioxidant vitamin
supplementation on cardiovascular disease are in progress. These
studies, individually or in aggregate, should have the numerical
strength to provide more definitive answers to current questions
regarding the relationship of antioxidant vitamin intake and
OF DIETARY FIBER
dietary fibers are fermented in the colon to SCFA, methane,
carbon dioxide and hydrogen (Pomare et al. 1985). Oligosaccharides
and soluble fibers are almost completely
fermented in the colon, whereas some insoluble fibers such as
wheat bran are fermented only partially. Most starches and resistant
fibers that reach the colon are fermented completely. Because
of the different metabolic fates of SCFA and because of their
different metabolic effects, they deserve attention for their potential health
propionate and butyrate are the principal SCFA produced in the
human colon (Pomare et al. 1985). Simplistically, acetate traverses
the liver and enters the peripheral circulation (Bridges et
al. 1992). Propionate is extracted by the liver and affects
lipid metabolism (Bridges et al. 1992). Butyrate appears to
have health-promoting effects for
colonocytes and only a portion of butyrate leaves the colon
for extraction by the liver (Pomare et al. 1985).
SCFA production from different dietary fiber
sources and supplies information on the ratio of the individual
SCFA acetate, propionate and butyrate produced. The acetate/propionate/butyrate
ratios are affected by the substrate available to the bacterial
flora of the colon. In free-living humans consuming a typical Western diet, this acetate/propionate/butyrate
ratio of material in the colon is approximately 60:25:15. Starches
tend to increase the relative amount of acetate, whereas some
fibers, such as oat bran, tend to increase the relative amount
of propionate. MacZulak et al. (1993) used an animal model to
study the effect of diets high in fiber
on fecal microorganism output and microbial fermentation products.
In these studies, the male Wistar rats were divided into groups
of five and fed high fiber and fiber-free diets in varying
order for a 3to 4-wk period. The high fiber
diet contained 40% soy cake, 20% crude potato starch, 19% wheat
bran and 5% each of apple pectin and carob gum. The fiber-free
diet contained 24% soy protein and 65% wheat starch. It was
determined that total anaerobe fecal concentration was 70 times
higher in the feces after consumption of the high fiber
diet compared with that of the fiber-free
diet. It appears that the high fiber
diet provides substrates necessary for microbial fermentation
and growth in the cecum. In addition, the high fiber diet influenced the proportion of organic acid products
such that the acetate/proptionate/butyrate ratio was 69:21:10
with consumption of the high fiber
diet vs. 92:7:1 with the fiber-free
diet. These results represent an elevation in propionate and
butyrate production when subjects consume a diet rich in fiber sources. Sunvold et al. (1995) studied the in vitro
fermentation characteristics of several fiber
sources including cellulose, beet pulp, citrus pulp and citrus
pectin. The fiber substrates were incubated for 6, 12, 24 and 48 h with
human feces. Total SCFA production was greatest with citrus
pectin, followed by citrus pulp, beet pulp and cellulose. The
acetate/propionate/ butyrate ratios after 48 h were 55:27:18
for the beet pulp, 60:22:18 for the citrus pulp and 57:21.5:21.5
for the citrus pectin. These results indicate that the source
of dietary fiber does influence substrate
fermentability by gut microflora in humans.
In a similar trial, Wang and collaborators (Wang and Gibson
1993) studied the effects of the in
vitro fermentation of inulin and oligofructose by bacteria growing
in the human large intestine. Fermentation products were found
from slurries of mixed human fecal bacteria. The acetate/propionate/butyrate
ratio for inulin was 72:19:8 and for oligofructose was 78:14:8.
OF DIETARY FIBER
Bifidobacterium species account for 12-15% of the bacteria
present in the human colon (Okubo et al. 1994, Salyers et al.
1985). Many health benefits have been attributed to the bifidobacteria
(Hayakawa et al. 1990), and one goal of healthy nutrition is
to increase bifidobacteria counts in the human colon.
Intake of oligofructoses and inulin significantly increase the
percentage and total counts of bifidobacteria in the
human colon (Gibson et al. 1995).
soluble dietary fibers such as oligofructoses and inulin are
extensively fermented in the colon, they also have the potential
to increase the bifidobacteria counts of the colon. Only
limited information is available on the effects
of soluble fibers on human colonic
animals models, certain soluble fibers
such as guar gum (a galactomannan polymer) significantly increase
the bifidobacteria counts in the colon. It is
possible that galactose, like fructose, selectively stimulates
the growth of certain bifidobacteria species in the colon.
Okubo et al. (1994) examined the effects
of intake of partially hydrolyzed guar gum (PHGG) on bacterial
counts of feces from volunteer subjects fed control diets and
diets containing PHGG. After a 2-wk control period, nine subjects
consumed 7 g of PHGG in a beverage three times daily (21 g/d).
The percentage of bifidobacteria in the feces increased
from 14.7 to 31.7% after 1 wk and was 24.8% after 2 wk. Two
weeks after discontinuing intake of PHGG, the bifidobacteria
count of the fecal samples returned to pretreatment values.
The bifidobacteria counts were significantly higher during
wk 3 and 4 of PHGG ingestion than values at baseline or after
cessation of PHGG intake. Of interest, lactobacillus
counts also increased significantly with PHGG consumption, but
significant changes were not observed in the concentrations
of any other microflora.
fruits, whole-grain cereals and legumes are rich sources of
nutrients, phytochemicals and antioxidants. These fiber-rich
foods have been shown in animal, epidemiologic and clinical
trials to be protective against CHD. Dietary fiber
in particular exerts favorable effects on fasting and postprandial serum lipoproteins, which
are surrogate markers for risk for CHD. In humans,
psyllium and guar gum appear to be the most effective cholesterol-lowering
soluble fibers. However,
2 Representative values for acetate (A), propionate
(P), butyrate (B) and total short-chain fatty acid (SCFA) production
original organic matter) from different fiber
sources Fiber free 1 Cellulose 2 Beet
pulp 2 Citrus pulp 2 Citrus pectin 2 Oligofructose
3 Inulin 3 Total SCFA 0.04 4.76 5.43 5.56 Acetate 0.15 2.60
3.28 3.18 Propionate 0.04 1.29 1.20 1.19 Butyrate 0.07 0.87
0.95 1.19 A:P:B Ratio 92:7:1 55:27:18 60:22:18 57:21.5:21.5
bran has a significant triglyceride-lowering effect, which may
serve as an independent risk factor for ASCVD. In addition to
its effects on lipoproteins, dietary
fiber also has a positive influence
on blood pressure, obesity, insulin resistance and clotting
factors, which are all independent risk factors for CHD. When
evaluating the role of dietary fiber
in ASCVD risk, one must also consider the non-fiber
components of plant foods, including phytochemicals, antioxidant
vitamins and certain (n-3) fatty acids. Available data strongly
suggest that vitamin E intake is associated with a protection
from CHD, and -carotene and vitamin C may also have protective
effects. Like oligosaccharides, soluble
fibers are almost completely fermented in the colon to SCFA,
methane, carbon dioxide and hydrogen. The SCFA ratios of acetate/propionate/butyrate
vary and are influenced by substrate availability to the bacterial
flora of the colon. It is also of interest that dietary fiber,
like oligofructoses and inulin, has the potential to increase
the bifidobacteria counts of the colon. This elevation
in bifidobacteria offers health benefits independent
of those normally attributed to fiber-rich
foods. Inclusion of dietary fiber
in the diet offers benefits not only to the heart, but also
to overall health.
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