Nutrients: Dietary Fiber, Atherosclerosis, and Cardiovascular Disease

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nutrients

Communication
Dietary Fiber, Atherosclerosis,
and Cardiovascular Disease
Ghada A. Soliman
Department of Environmental, Occupational and Geospatial Health Sciences, City University of New York,
Graduate School of Public Health and Health Policy, 55 West 125th St, New York, NY 10027, USA;
ghada.soliman@sph.cuny.edu; Tel.: +1-646-364-9515

Received: 25 March 2019; Accepted: 20 May 2019; Published: 23 May 2019 

Abstract: Observational studies have shown that dietary fiber intake is associated with decreased
risk of cardiovascular disease. Dietary fiber is a non-digestible form of carbohydrates, due to the lack
of the digestive enzyme in humans required to digest fiber. Dietary fibers and lignin are intrinsic to
plants and are classified according to their water solubility properties as either soluble or insoluble
fibers. Water-soluble fibers include pectin, gums, mucilage, fructans, and some resistant starches.
They are present in some fruits, vegetables, oats, and barley. Soluble fibers have been shown to lower
blood cholesterol by several mechanisms. On the other hand, water-insoluble fibers mainly include
lignin, cellulose, and hemicellulose; whole-grain foods, bran, nuts, and seeds are rich in these fibers.
Water-insoluble fibers have rapid gastric emptying, and as such may decrease the intestinal transit
time and increase fecal bulk, thus promoting digestive regularity. In addition to dietary fiber, isolated
and extracted fibers are known as functional fiber and have been shown to induce beneficial health
effects when added to food during processing. The recommended daily allowances (RDAs) for total
fiber intake for men and women aged 19–50 are 38 gram/day and 25 gram/day, respectively. It is worth
noting that the RDA recommendations are for healthy people and do not apply to individuals with
some chronic diseases. Studies have shown that most Americans do not consume the recommended
intake of fiber. This review will summarize the current knowledge regarding dietary fiber, sources of
food containing fiber, atherosclerosis, and heart disease risk reduction.

Keywords: dietary fiber; soluble fiber; insoluble fiber; functional fiber; food groups; cardiovascular
disease; the chemical composition of fiber

1. Introduction
Heart disease is the leading cause of morbidity and mortality in the United States. Cerebrovascular
disease (stroke) was the 5th leading cause of death in 2016, according to the National Vital Statistics [1].
To date, statins have been the most effective treatment for lowering blood Low-Density Lipoprotein
cholesterol (LDL-C), the major risk factor for atherosclerotic cardiovascular disease [2]. Statins inhibit
the 3-hydroxy-3-methylglutaryl-coenzyme A (HMG CoA) Reductase enzyme, which is the last step in
the endogenous cholesterol biosynthesis, and thereby decrease blood cholesterol levels. In clinical trials,
non-statin drugs had a little utility in the reduction of blood cholesterol due either to tolerability factors
or a lack of health outcome [3]. However, statin treatment is costly and is associated with side effects,
particularly when high doses are needed. Furthermore, statin non-adherence and discontinuation rates
remain high, and many at-risk patients do not achieve optimal LDL-Cholesterol lowering effect with
statin as monotherapy [4]. Recently, dietary fiber has been recommended as a dietary change that can
be incorporated in addition to statin therapy to increase its efficacy, improve health outcome, and to
lower the prescribed dose for statins. A recent meta-analysis of three randomized controlled trials
revealed that the addition of dietary gel-forming viscous soluble fiber doubled the efficacy of statins [5].

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Additionally, NHANES cross-sectional Data (2003–2006) showed that intake of whole grain, which is
rich in dietary fiber, was associated with enhanced effects of statins in lowering blood cholesterol [6].
Historically, crude fibers have been extracted from animal feeds in Germany since 1850 [7]. The benefits
of dietary fiber in lowering lipid and cholesterol levels were reported in South African Bantu in 1954 [8].
Observations of the impact of dietary fiber on lipid metabolism were reported in cockerel in 1964 [9].
Fisher et al. (1964) fed cockerel a 5% pectin-supplemented diet for a year and a half and found that
these avian sequestered and excreted two times more cholesterol and three times more lipid than
cockerel fed the standard diet [9]. The purpose of this review is to highlight the importance of dietary
fiber in lowering blood cholesterol and to shed light to the value of soluble gel-forming fiber as an
adjuvant to statins in lowering blood cholesterol, which is a hallmark of cardiovascular disease.

2. Chemistry and Metabolism of Fiber


Dietary fibers are a complex group of carbohydrates and lignin that are not hydrolyzed by human
enzymes and, therefore, are not digested or absorbed in the human body [10]. Dietary fiber is intact in
plants and is composed of a complex polymer of phenylpropanoid subunits. Soluble fiber is the edible
part of the plant that is resistant to digestion but could be partially or totally fermented by colonic
bacteria to short-chain fatty acids in the large intestine. Meanwhile, insoluble fiber passes through the
digestive tract intact [11].
Insoluble fiber includes cellulose, some hemicellulose, and lignin. Cellulose is a long linear
polymer made of β (1–4)-linked glucose units, and the hydrogen bond between glucose residues
gives the 3-dimensional structure of cellulose. Hemi-cellulose is formed of both hexose and pentose
sugars with the backbone linked by β (1–4) bonds, while the side chain includes galactose, arabinose,
and glucuronic acid linked via β (1–2) and β (1–3) bonds. On the other hand, lignin is formed of phenol
polymers that are highly branched with strong intramolecular bonds [11].
Soluble fiber encompasses pectin, gums, mucilage extracted from psyllium husk, β-glucan,
and fructans, as well as some hemicellulose. Pectin is a heterogeneous polysaccharide and is
composed of unbranched chains of α (1–4)-linked D-galacturonic acid backbone, with chains of pentose
and hexoses attached to the backbone. Gums are secreted at the site of plant injury and contain
galactose backbone linked by β (1–3) and β (1–6) bonds with side chains of arabinose, glucuronic acid,
methyl-glucuronic acid or galactose. Mucilage, found in the plant psyllium, is structurally similar to
gums, and is viscous, gel-forming water-soluble fiber containing up to 80% soluble polysaccharide.
On the other hand, β-glucans are formed of homopolymers of glucose subunits, while fructans are
polymers of fructose including oligofructoses and inulin.
Soluble fiber is resistant to hydrolysis by small intestinal enzymes in humans but is fermented
by bacteria to short-chain fatty acids (SCFA) in the large intestine. The production of SCFA leads to
alterations in the intestinal microbiota, which contributes to the hypocholesterolemic effects of soluble
fiber [12]. Dietary fiber adds bulk to the diet, adsorbs and sequesters cholesterol, and thus decreases
hepatic absorption and increases excretion through bile and fecal lipids and bile acids.

3. Dietary Fiber and Functional Fiber


Dietary fibers including soluble and insoluble fibers refer to ingredients in plants including
non-digestible carbohydrates and lignin. The plant cell wall consists of a primary and secondary
wall, which represents most of the content of dietary fiber. Dietary fibers are classified based on their
solubility in hot water, water holding capacity (hydration), and viscosity [7,13]. As mentioned above,
soluble fibers include viscous fibers such as β-glucans, fructans (inulin, fructooligosaccharides), gum,
pectin, mucilage, and non-viscous fibers such as hemicellulose. Soluble fibers absorb water, leading to
gel formation, which increases food transit time, delays gastric emptying, decreases nutrient absorption,
and slows digestion. Food sources of soluble fiber include vegetables such as carrots, broccoli, onion,
and artichokes, and fruits including bananas, berries, apples, and pears, as well as legumes, oats,
and barley (Table 1). The insoluble fibers include some hemicellulose, cellulose, and lignin. Unlike
Nutrients 2019, 11, 1155 3 of 11

soluble fiber, the insoluble fiber decreases transit time and increases fecal bulk, and thus helps to
relieve constipation. The insoluble fibers are found in whole grain, wheat, bran, nuts, and seeds, as
well as in some fruits and vegetables. While both soluble and insoluble fibers are undigestible, and
can be fermented by bacteria using its own enzymes to hydrolyze the fiber, soluble fibers are much
more easily fermentable by the gut bacteria, and thus have some prebiotic functions and provide a
source of short-chain fatty acids. As such, short-chain fatty acids are rapidly absorbed from the large
intestine and can be oxidized for energy production. Absorption of short-chain fatty acids such as
propionic acid has been shown to decrease cholesterol synthesis in the liver, leading to decreased
blood cholesterol and increased sodium and water absorption into the colonic mucosal cells [14,15].
Short-chain fatty acids also increase the acidification of colon luminal environment, in turn, the acidic
pH decreases the solubility of the free bile acids, and increases excretion of bile and at the same time
decreases the conversion of free bile acids to secondary bile acids which are more toxic.

Table 1. Select sources of dietary fiber in the food groups.

Fiber Content in The


Food Item * NDB ID Grams/Cup
Food Groups **
1. Grain Corn bran, crude 20015 60
Barley, hulled 20004 31.8
Rye flour, dark 20063 30
Wheat bran, crude 20077 24
Rice bran, crude 20060 24.8
Bulgur, dry 20021 17.5
Oats 20038 16
Sorghum grain 20067 12.9
Cereal, ready to eat (granola) 08037 10.9
Cornmeal, self-rising 20324 10.7
Wild rice, raw 20088 9.9
Pasta, whole grain 20135 9.2
Couscous, dry 20028 8.7
Rice, brown, long grain 20036 6.7
2. Protein Foods Beans, kidney, all types 16027 45.8
Soybeans, mature, roasted 16410 30.4
Peas, green, split, raw 16085 43
Seeds, sesame seed 12029 21.6
Lentils, pink or red, raw 16144 20
Nuts, almond, oil roasted 12065 16.5
Peanuts, oil roasted 16389 13.5
Chickpeas (garbanzo beans) canned 16360 10.6
3. Fruits Passion fruit, purple, raw 09231 24.5
Blueberries, canned, heavy syrup, drained 09353 15
Figs, dried, uncooked 09094 14.6
The Fiber Content in
Food Item * NDB ID Grams/Cup
the Food Groups
3. Fruits Peaches, dried, sulfured, uncooked 09246 13
(Continued) Plums, dried (prunes), uncooked 09279 12.4
Raisins, seeded 09299 11.2
Apricots, dried, sulfured, stewed with added sugar 09034 11.1
Avocado, raw 09037 10.1
Prunes (dried plum) 09293 9.4
Guava, common, raw 09139 8.9
Oranges, raw with peel 09205 7.7
Plantain, green, raw 09542 5.9
Nutrients 2019, 11, 1155 4 of 11

Table 1. Cont.

The Fiber Content in


Food Item * NDB ID Grams/Cup
the Food Groups
Kiwi fruit, green, raw 09148 5.4
Blueberry, raw 09050 3.6
Apple, granny smith, raw 09502 3.1
Strawberry, raw 09316 3
Peaches, yellow, raw 09236 2.3
Plum, raw 09279 2.3
4. Vegetables Potatoes, mashed, dehydrated granules 11380 14.2
Mixed vegetables 11579 9.3
Sweet potatoes, cooked, boiled 11510 8.2
Edamame, frozen, prepared 11212 8.1
Artichokes, frozen, cooked, boiled, drained 11703 7.7
Collard, cooked, boiled 11162 7.6
Tomato (sun-dried) 11955 6.6
Brussel Sprouts, frozen, chopped 11093 6.4
Corn (yellow, dried) 35183 5.8
Broccoli, frozen, chopped 11093 5.5
Squash, winter, hubbard, raw 11489 4.5
Carrots, cooked (frozen) 11131 4.8
Pea, raw 09252 4.3
Gums, guar, seed gums 42281 21
* Nutrient Database (NDB) source of data is the US Department of Agriculture, USDA Food Composition Databases;
Software developed by the National Agricultural Library v.3.9.5.1_2019-01-29. ** Classification of the Food Groups:
Grains, Food Group, Fruits, Vegetables, and Dairy) [16,17].

On the other hand, functional fibers refer to nondigestible carbohydrates that are either extracted
and isolated or synthesized and manufactured, and they have been shown to confer beneficial health
effects in humans. Functional fibers include β-glucans, cellulose, chitins and chitosan, fructans,
gums, lignin, pectin, polydextrose and polyols, psylliums, resistant dextrins, and resistant starches [7].
Prebiotics are a class of functional fiber that selectively stimulate the activity or growth of beneficial
health-promoting bacteria in the colon, mainly lactobacilli and bifidobacteria, and thereby improve the
host’s health [18]. To be classified as prebiotics, the fiber ingredients should be resistant to hydrolysis
by human enzymes; therefore, they should not be digested or absorbed, they should be resistant
to gastric acidity, and able to be fermented by the gut microbiota, and also they should selectively
stimulate the activity or growth of healthy intestinal bacteria [18]. Examples of prebiotics include
galacto-oligosaccharides, fructooligosaccharides (fructans), and lactulose. The total fiber consumption
is the sum of intakes of dietary fiber and functional fiber.

4. Recommended Dietary Fiber Intakes


The recommended Dietary Reference Intake (DRI) daily allowance in men aged 19–50 years is
38 g/day and women 25 g/days, and for men ages > 51 is 31 g/day and women ages > 51 is 21 g/day.
The recommendation for children ages 1–3 is 19 g/day and ages 4–8 is 25 g/day. For boys, ages 9–13,
the DRI recommendations are 31 g/day, and 38 g/days for ages 14–18. For girls ages 9–18, the DRI
recommendations are 26 g/day. Although dietary fibers have been shown have several beneficial
health effects, the average daily intake for most Americans is 15 g/day, which is much lower than
the recommended amount [19]. There is no upper tolerable level for fiber intake, but the tolerance
varies by individual, and the most common side effects from overconsumption are bloating and
abdominal discomfort.
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5. Fiber, Blood Cholesterol, and Atherosclerosis

5.1. Animal Studies


Studies in rats showed that administration of isomaltodextran was associated with decreased
fat absorption compared to the control vehicle, and this effect was observed for up to 6 hours [20].
The authors attributed the mechanism to increased micelle stabilization and enlarged particle size.
Our group showed in guinea pigs that animals fed pectin, guar gum, and psyllium exhibited increased
LDL-ApoB 100 turnover, which led to the upregulation of hepatic LDL receptors, leading to faster
catabolism and clearance [21–25]. Additionally, the hypocholesterolemic effect of fiber was due to the
decreased number of secreted VLDL particles, and decreased cholesteryl ester transfer protein (CETP)
activity leading to reduced cholesteryl ester in VLDL particles that are transferred to LDL, and at the
same time enhanced VLDL and LDL apo B 100 turnover [21]. Studies conducted in several animal
models showed the beneficial effects of dietary fibers in the reduction of heart disease risk or reduction
in cardiovascular disease mortality. For example, Lo et al. (1987) showed that dietary fiber isolated
from soybean was effective in preventing atherosclerosis in rabbits [26].
Similarly, Beakey et al. (1988) reported that grapefruit pectin reduced atherosclerosis in miniature
swine [27]. McCall et al (1992) compared the intake of low-cholesterol cellulose (LCC), high-cholesterol
psyllium (HCP), and high-cholesterol cellulose (HCC) in African green monkeys for 3.5 years and
reported that both LCC and HCP significantly reduced blood cholesterol than HCC and that dietary
psyllium decreased total blood cholesterol by decreasing LDL cholesterol synthesis [28,29]. Roach and
Topping et al. (1990, 1992) reported that the combination of oat bran and fish oil decreased blood
cholesterol levels in rats [30,31]. In addition, Wilson and colleagues found that barley and insoluble
fibers had a hypocholesterolemic effect in Syrian Gold Hamsters [32–34]. Similarly, several investigators
have documented the beneficial effects of certain types of dietary fiber in reducing blood cholesterol
in mice [35–41]. Taken together, studies in animal models reveal the importance of both soluble
and insoluble fibers in lowering blood cholesterol, attenuating atherosclerosis, and decreasing heart
disease risk.

5.2. Human Studies

5.2.1. Observational Studies


Several cohort studies have investigated the intake of dietary fiber and coronary heart disease,
as well as cardiovascular disease, in the U.S. and globally [42–53]. These studies documented a
protective effect of dietary fiber on the reduction of heart disease. Pereira et al. (2004) conducted a
meta-analysis of ten cohort studies with 6–10 years follow-up [44]. The group reported an inverse
relationship between dietary fiber intake and the risk of cardiovascular disease with a Relative Risk
(RR) of 0.84 (95% CI, 0.70–0.99). However, an additional 10 gram per day increment of fiber intake
was not statistically significant, with a relative risk of 1.0 (95% CI 0.88–1.13). Similarly, Threapleton
and colleagues (2013) performed a meta-analysis study to determine the dose–response relationship
between dietary fiber intake and the risk of cardiovascular disease [54]. The investigators reported that
the pooled protective effect for each 7 g/day increase in fiber intake was RR = 0.91 (CI 0.87 to 0.94).
However, higher doses of fiber had a larger confidence interval around the mean, and the results were
less reliable [54]. Additionally, Buil-Cosiales and colleagues (2014) documented that the intake of fiber
from fruit was associated with decreased all-cause mortality in the Prevencion con Dieta Mediterranea
(PREDIMED) study (Hazard Ratio 0.59, 95% CI = 0.44, 0.78) [55]. Over the last three decades, several
investigators have reported the benefits of dietary fiber from a variety of food sources in decreasing
the risk of cardiovascular diseases [54,56–64]. Therefore, based on the evidence, it appears that fiber
consumption with moderation is recommended.
The main limitations of observational studies include bias [65] and confounding variables [66],
as well as showing associations and correlations rather than causation. Selection bias can be encountered
Nutrients 2019, 11, 1155 6 of 11

in cohort studies due to informative censoring and measurement errors, and can be found in case-control
studies due to inappropriate selection of controls. At the same time, confounding may occur due
to the co-existence of exposures leading to the same health outcome. Confounding is difficult
to account for unless all common causes of exposure and their link to the disease outcomes are
known. Therefore, randomized control trials studies are conducted to address the causality of fiber
in reducing cardiovascular disease and mortality and to eliminate confounders, measurement errors,
and selection bias.

5.2.2. Randomized Control Trials


As mentioned above, observational studies have suggested that the intake of dietary fiber was
associated with decreased risk of heart disease. Randomized control trials are employed to determine
the causality of dietary fiber on improving the lipid profile. As such, several randomized control trials
investigated the effects of different fibers on atherosclerosis and heart disease. Li et al. compared the
intake of quinoa-enriched bread (20 g quinoa flour) to the intake of refined wheat in 37 overweight
healthy men aged 35–70 years with BMI > 25kg/m2 in a four-week crossover design with four weeks
washout period. The authors reported that after four weeks, blood cholesterol and blood glucose were
lower than the baseline in both groups, but there was no difference between the participant’s groups
which consumed quinoa versus the group that consumed 100% refined wheat. The authors attributed
the lack of significance to the short follow-up period [67]. Another randomized controlled crossover
trial for five weeks in 30 participants with mild hypercholesterolemia compared the intake of β-glucan
with a control diet and reported the reduction of total cholesterol with β-glucan groups, but no effect
on cholesterol synthesis or absorption. The authors speculated that lowering blood cholesterol levels
were attributed to increased bile acid synthesis [68]. Similarly, a randomized, controlled, open-label,
parallel group study in Asian Indians compared the intake of 3 grams of soluble fiber from oats with a
control group maintaining a routine diet for four weeks in healthy adults male and female participants
(blood cholesterol 200 mg/dL-240 mg/dL) [69]. The investigators reported a significant reduction in
total blood cholesterol in the intervention group versus the control group, which consumed athe usual
diet (8.1% versus 3.1%, p < 0.02), as well as LDL-cholesterol (11% vs. 4.1%, p < 0.04). Taken together,
the results from these short-term studies showed a trend of decreased total and LDL cholesterol and
improved cardiovascular biomarkers.
The variability in outcome was attributed to the short-term nature of the studies. Therefore,
longer-term intervention was suggested to confirm these findings. Yen et al. investigated the
long-term (8 weeks) effects of a diet-controlled study on supplementation with functional fibers,
isomalto-oligosaccharides, in 13 subjects with constipation. The protocol consisted of four weeks placebo
and two periods of four-week supplementation (total of 8 weeks) with isomalto-oligosaccharides, and a
four-week post period. The investigators reported improved colonic microflora profile during treatment
only and reduced LDL-cholesterol and total cholesterol during the intervention, as well as during the
follow-up period [70]. A 6-month randomized controlled intervention study with a one-year follow-up
investigated the impact of rice bran extract consumption in post-menopausal Vietnamese women
(n = 30/group). The participants in the intervention group received 50 mg of acylated steryl glucosides
(PSG) brown rice bran extract (6 capsules), while the placebo group received six capsules of corn oil.
The results showed a significant reduction in LDL cholesterol in the intervention group compared to
the placebo group (from 163 ± 25.3 mg/dL vs. 135.9 ± 26.8mg/dL), and decreased TNF α, inflammatory
marker (from 6.6 ± 5.5% to 4.72 ± 6 respectively [71]. Another long-term one-year pre-post intervention
trial in 66 participants with hyperlipidemia found that following a plant-based diet for one year led to
a significant reduction in blood pressure and LDL cholesterol that was maintained at the one-year
follow-up [72]. The plant-based diet consisted of a diet high in soy protein (22.5 g/1000 kcal), viscous
fibers (10 gm/1000gram), and almond (23 gm/1000g). Similar findings were reported in other studies in
which participants consumed a plant-based diet with the addition of monounsaturated fatty acids or
two levels of dietary advice to promote hypercholesterolemia control [72–76]. Taken together, based on
Nutrients 2019, 11, 1155 7 of 11

the long-term randomized control trials, there is strong evidence to indicate that intake of dietary
soluble fiber is associated with improved lipid profile, inflammatory markers, and improved health.

6. Other Fiber Functions


Dietary fiber has several protective effects against chronic diseases, including cardiovascular
disease, diabetes, metabolic syndrome, inflammatory bowel syndrome, diverticular disease, obesity,
and colorectal cancer in the age-adjusted analysis [77–84]. For example, insoluble fiber binds to and
adsorb scarcinogens, mutagens, and toxins, and therefore, prevents their harmful effects to the body,
by preventing the toxins absorption and targeting them for elimination [83,85,86]. Other fiber properties
include delayed colonic transit time, prolonged post-meal satiety and satiation, and induction of
cholecystokinin satiety hormone [87,88]. The Academy of Nutrition and Dietetics position on fiber
intake is to increase consumption of whole grains, fruits and vegetables, nuts and legumes, and that
dietary fiber is associated with risk reduction of type 2 diabetes, cardiovascular disease, and select
cancer types [89].

7. Summary
Dietary fiber can be used as a dietary change to complement statin monotherapy in lowering total
and LDL-Cholesterol and to reduce the prescribed dose of statin, decrease the side effects, and improve
drug tolerability. Soluble and insoluble dietary fibers in whole foods have multiple non-nutritive
health effects that help improve the lipoprotein profiles, and have no caloric value, and thus could
be part of a healthy eating pattern. The abundance of dietary fiber in whole grain, protein food,
fruits, and vegetables, makes them attractive targets for disease prevention and reduction of risk of
atherosclerosis and cardiovascular disease.

Author Contributions: G.S. researched, designed, analyzed, interpreted the results and wrote the manuscript.
Funding: The investigator’s work and publication costs are funded by an institutional start-up fund.
Conflicts of Interest: The authors declare no conflict of interest.

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