P OLYSACCHARIDES :D IETARY F IBER

8.3.3 P OLYSACCHARIDES :D IETARY F IBER

8.3.3.1 Observational Studies

Inverse associations between the intake of whole-grain foods or dietary fiber and CVD morbidity and mortality have been demonstrated in several observational

studies. 35 Some of theses studies will be evaluated in the following, starting with whole-grain foods. In one study, the dietary habits of postmenopausal women from

Carbohydrates and the Risk of Cardiovascular Disease

Iowa were investigated in 1986 and the incidence of CVD was followed for 9 years. 36 The mean weekly intake was 6.4 slices of dark bread, 1.9 cups of whole- grain breakfast cereals, and 2.5 servings of other whole-grain foods, and the intake of whole-grain foods ranged from 1.5 to 22.5 servings per week. A striking inverse relation between the whole-grain intake and the incidence of ischemic heart disease (IHD) was found. The age- and energy-adjusted relative risks from the lowest to the highest intake by quintiles were 1.0, 0.84, 0.58, 0.45, and 0.60. After adjustment of potentially confounding variables, the risk of IHD death was reduced by about one third in those eating >1 serving of a whole-grain product per day, compared with those who reported rarely eating any whole-grain products. In contrast, no association between the total refined-grain intake and risk of IHD death was found.

The association between the intake of whole-grain bread and CVD mortality was investigated among Norwegian subjects. 37 The men reported a mean intake of

6.3 slices of bread per day using 23% whole-grain flour, while the women consumed

3.9 slices per day containing 26% whole-grain flour. A whole-grain bread score was calculated and ranged from 0.05 (one slice per day made with 5% whole-grain flour) to 5.4 (nine slices per day made with 60% whole-grain flour). In total, five whole- grain intake categories were formed and the hazard ratios for total mortality in CVD were inverse and graded across the categories (from 1 to 0.63).

Several studies have dealt with the association between dietary fiber intake and risk for cardiovascular disease. The intake of dietary fiber and risk of coronary heart disease were followed for 10 years among women in the Nurses’ Health

Study. 38 In total, 68,782 women were included in the analysis and the age-adjusted relative risk for major CHD events was 0.53 for women in the highest quintile of total dietary fiber intake (median, 22.9 g/day) compared with women in the lowest quintile (median, 11.5 g/day). Among different sources of dietary fiber, only cereal fiber was strongly associated with a reduced risk of CHD. Male health profession-

als have been followed in a similar study. 39 Their food habits were assessed using

a 131-item food frequency questionnaire. During 6 years of follow-up there were 511 nonfatal cases of myocardial infarction (MI) and 229 coronary deaths. The age-adjusted relative risk of myocardial infarction for the top quintile of total dietary fiber intake was 0.64 (median intake, 28.9 g/day) compared with men in the lowest quintile (median intake, 12.4 g/day). Cereal fiber was most strongly associated with a reduced risk of MI compared with other fiber sources, like vegetables and fruits. Thus, the same associations were found for male health professionals as for female health professionals. In one of the earliest studies in the field, the CHD incidence in men working at London transport or banks was

also found to be lower in those eating more cereal fibers. 40 Elderly people were the focus in another study from the U.S., and the aim was to assess whether fiber consumption from fruit, vegetable, and cereal sources was associated with the

incidence of CVD. 41 Using a 99-item food frequency questionnaire, the average intake of the different fibers was calculated: cereal fiber, 4.2 g/day; fruit fiber, 5.2

g/day; vegetable fiber, 6.9 g/day; and total fiber, 16.2 g/day. The main foods contributing to cereal fiber intake were dark breads and bran cereals; to fruit fiber intake, apples, oranges, and bananas; and to vegetable fiber intake, beans, broccoli, peas, corn, and cauliflower. During 9 years, the incidence of combined stroke,

Functional Food Carbohydrates

ischemic heart disease death, and nonfatal myocardial infarction was followed. Neither fruit fiber, vegetable fiber, nor total fiber was associated with the incidence

of CVD, while cereal fiber consumption, adjusted for several parameters, was inversely associated with incident CVD, with 21% lower risk in the highest quintile

intake compared with the lowest quintile. Thus, all these studies show that the intake of fiber, especially cereal fiber, is associated with a lower risk for CVD.

Observational studies have also evaluated the relation between intake of soluble fiber relative to insoluble fiber and its association with CVD risk. In the study on

female health professionals, an inverse relation between both soluble and insoluble fiber and the risk of CVD and MI was found, but after multivariate adjustments the

associations were no longer significant. 42 Pietinen et al. 43 investigated smoking men included in the Alpha-Tocopherol, Beta Carotene (ATBC) Cancer Prevention Study

(21,930 subjects). They filled in a 276-food-item dietary questionnaire and the incidence of CHD was followed for 6 years. The median intake of dietary fiber in the highest quintile was 34.8 g/day and in the lowest quintile 16.1 g/day. In age- and treatment-adjusted analysis, water-soluble fiber was more strongly associated with reduced coronary death than water-insoluble fiber, and cereal fiber also had a stronger association than vegetable and fruit fiber. A 10-g larger daily intake of fiber appeared to lower the risk of coronary death by 17%. A study was conducted in Italy comparing subjects who had had a nonfatal acute myocardial infarction with

a control group. 44 Compared with the lowest tertile, the odds ratio (OR) of risk of acute myocardinal infarction in the highest tertile was 0.72 for total fiber, 0.64 for

soluble fiber (significant), 0.77 for insoluble fiber, 0.71 for cellulose, 0.82 for veg- etable fiber, 0.64 for fruit fiber (significant), and 1.1 for cereal fiber. In this popula- tion, cereal fiber was derived chiefly from refined grains, and this may explain the lack of protection found for this type of fiber.

In a meta-analysis, Anderson 45 evaluated the strength of the association between dietary fiber-rich foods and risk for CHD. For total dietary fiber, 82%

and, for whole grains, 75% of the studies in the meta-analysis showed a significant inverse association to the risk for CHD (Figure 8.2). For cereals, fruits, and

vegetables, the association was less pronounced. In the meta-analysis, the risk ratio for CHD comparing the highest to the lowest groups of intake was 0.73 for dietary fiber and 0.71 for intake of whole grains. Thus, dietary fiber was associated with a significant reduction of the risk for CHD of approximately 27%. Also, fruit and vegetable consumption was associated with a significant reduction of CHD risk (23 and 14%, respectively), while for cereals, no significant association was found. This may be related to the fact that most of the cereals consumed were refined and low in dietary fiber.

8.3.3.2 Intervention Studies

Many intervention studies have been made investigating the effects of dietary fibers on different variables related to CVD. The main interest has been focused on effects

of soluble fibers, and thus on foods rich in soluble fibers. First, some studies investi- gating mixtures of dietary fibers or food fiber concentrates will be reviewed, followed by studies using only one fiber preparation (psyllium, oats, barley, guar gum, pectin).

Carbohydrates and the Risk of Cardiovascular Disease

18 16 Total

Inverse association 14 Significant inverse association

s 12 udie

10 er of st 8

umb N 6

Vegetables Total fiber FIGURE 8.2 Number of observational studies reporting an association between dietary fiber-

Whole grains

Cereals

Fruits

rich foods and risk for CHD. (Adapted from Anderson, J.W., Proc. Nutr. Soc., 62, 135, 2003.) 8.3.3.2.1 Effects of Mixtures of Dietary Fibers

In one study, subjects with increased plasma cholesterol values were given a daily supplement of 15 g of soluble fiber from psyllium, pectin, guar gum, and locust

bean gum during 6 months. 46 The fibers were mixed in water and consumed with each of three major daily meals. In comparison with the control group given acacia gum, the total and LDL cholesterol values were significantly lower in the test group. After 8 weeks, the reductions in comparison with baseline were 6.4 and 10.5%, respectively, and about the same reductions were found at weeks 16 and 24. In another study, a combination of soluble fibers from psyllium, oats, and barley was

given to men with hypercholesterolemia. 47 They consumed the fibers as a breakfast cereal (50 g containing 12 g of soluble fiber) for 6 weeks. In comparison with a

control group given a breakfast cereal based on wheat, the total cholesterol and LDL cholesterol levels fell significantly in the test group, with 3.2 and 4.4%, respectively.

In yet another study, hypercholesterolemic subjects consumed soluble fibers (gum arabic:pectin = 4:1) mixed in apple juice for 12 weeks using doses of 0, 5, or 15

g/day. 48 No differences in blood lipid levels were found between the treatments, and even increases in blood lipids were observed. A combination of soluble and insoluble fibers has also been investigated. 49 The soluble fibers were guar gum and pectin, and the insoluble fibers were soy fiber, pea fiber, and corn bran, and they were given to hypercholesterolemic subjects consuming 20 g of the fibers daily for 15 to 36 weeks. The supplement was mixed with a beverage and was consumed before breakfast and dinner. Intake of the fiber supplement significantly decreased the levels of LDL cholesterol (–9.7%), total cholesterol (–6.5%), and apolipoprotein B (–12.6%) compared with the placebo at week 15. There was a tendency to smaller reductions toward the end of the treatment period. Another fiber combination of oat beta-glucan and psyllium (4 servings per day, 8 g of soluble fiber) and a control diet

Functional Food Carbohydrates

were compared in a randomized crossover study of subjects with increased plasma cholesterol values. 50 Compared with the control diet, the high-fiber diet reduced total cholesterol by 2.1% and, applying the Framingham cardiovascular disease risk equation to the data, gave a calculated reduction in risk of 4.2%. The reduction in risk, although small, is likely to be significant on a population basis. Thus, many studies using supplementation by a combination of soluble fibers in daily doses of

5 to 20 g have shown positive effects on blood lipid levels. 8.3.3.2.2 Effects of Different Single Dietary Fiber-Rich Foods 8.3.3.2.2.1 Psyllium

Psyllium has been extensively investigated in relation to its effects on CVD, and over 40 human studies were found in a Medline search using the search terms psyllium and cholesterol. Psyllium seed husk is derived from Plantago ovata and contains a mixture of polysaccharides such as arabinoxylans; 100 g of seed husk

contains about 71% soluble dietary fiber and 15% insoluble fiber. 51 Psyllium prep- arations have been commercially available for over 60 years, and their physiological

properties are thought to be due to the gel-forming ability. 3 In a long-term study, men and women with hypercholesterolemia were given an American Heart Associ- ation (AHA) Step I diet for 8 weeks and thereafter randomly assigned to receive either 10.2 g of psyllium (n = 197) or a cellulose placebo (n = 51) daily for 26

weeks. 52 The fibers were mixed in liquid and were taken immediately before break- fast and dinner. Serum total and LDL cholesterol were 4.7 and 6.7% lower, respec- tively, in the psyllium group than in the placebo group. In a study by Bell et al., 53 psyllium was incorporated into a breakfast cereal also containing oat bran, sugar beet fiber, and wheat bran. The cereal was consumed once daily for 6 weeks by subjects with increased blood cholesterol values. The daily intake of soluble fiber from the cereal was 5.8 g, whereof 50% was from psyllium. Compared to a control group that consumed cornflakes, the total cholesterol and LDL cholesterol levels were reduced significantly in the psyllium group. The effects of psyllium (15 g/day)

have also been studied in diabetes type 2 patients for 6 weeks. 54 In comparison with cellulose placebo treatment, the total and LDL cholesterol in the test group were reduced significantly, 2.7 and 7.2%, respectively. Furthermore, significant increases of HDL cholesterol and a decrease in triglycerides were observed in the test group.

As in the study of Anderson et al., 52 the fiber preparations were mixed in water and taken before regular meals three times per day. A dose–response study was made by Davidson et al. 55 using psyllium seed husk given in daily doses of 0, 3.4, 6.8, or

10.2 g for 24 weeks. The fibers were included in different foods like ready-to-eat cereals, bread, pasta, and snack bars. A change in LDL cholesterol (–5.3% in

comparison to control) after 24 weeks consumption was only shown for the group that took the highest dose of psyllium husk — 10.2 g/day. The reduction in LDL cholesterol was more pronounced in the beginning of the intervention (week 4) for

all groups. Davidson et al. 55 also investigated the lipid-lowering effect of psyllium in hypercholesterolemic children (6 to 18 years). They were given psyllium for 6 weeks and, after a 6-week washout period, a control cereal. Consumption of psyllium gave a 7% reduction in LDL cholesterol compared with the control cereal. Williams

et al. 56 have also used psyllium as a treatment for hypercholesterolemic children.

Carbohydrates and the Risk of Cardiovascular Disease

The children consumed 6.4 g of soluble fiber from psyllium per day during 12 weeks and, compared to a control group, their total cholesterol and LDL cholesterol levels

decreased. A meta-analysis of eight controlled trials showed that psyllium supple- mentation was well tolerated and resulted in an additional 7% reduction in LDL cholesterol in hypercholesterolemic individuals already consuming a low-fat diet. 57 An earlier meta-analysis of data from 12 studies of subjects with increased choles-

terol levels who consumed psyllium in a low-fat diet showed similar results. 58 The total cholesterol and LDL cholesterol were reduced an average of 5 and 9%, respec- tively, in comparison with a control diet. Gender, age, and menopausal status did not affect the response.

Thus, many existing studies have shown that psyllium seed husk can reduce the total and LDL cholesterol levels significantly, and meta-analysis of the studies has

confirmed this. More dose–response studies are needed to evaluate how much psyl- lium is needed to be consumed to get a significant cholesterol-lowering effect.

8.3.3.2.2.2 Oats The cholesterol-lowering properties of oats have also been studied extensively. More than 50 human studies were found in a Medline search by including human studies conducted after 1980 and using the search terms oats and cholesterol. It is generally agreed that the main cholesterol-lowering compound in oats is the soluble fiber component, beta-glucan. Beta-glucans are composed of β-(1-4)-linked glucose units separated every two to three units by a single β-(1-3)-linked glucose. The beta- glucans in the oat kernel are distributed throughout the endosperm and are located in the endosperm cell walls. In different oat varieties harvested in Sweden in three different years, the beta-glucan content varied from 3.5 to 5.7% of the dry matter. 59 Oat bran is defined by the American Association of Cereal Chemists as a material fractionated so that the oat bran fraction is not more than 50% of the starting material, with a total beta-glucan content of at least 5.5% (dry weight basis) and a total dietary fiber content of at least 16.0% (dry weight basis), and with at least one third of the total dietary fiber being soluble fiber. 60

To further purify the beta-glucans, different techniques have been used. In an EU project (QLK1-CT-2000-00535), concentrates with a content of 25% oat beta- glucans have been prepared (R. Öste and A. Öste Triantafyllou, EP 1124441). The manufacturing process includes dry or wet milling of the flakes at 60˚C followed by an enzymatic reaction step using beta-amylase. In this way, maltose and beta- limit dextrins, the main carbohydrate species in the final product, are formed from starch. After the enzymatic step, insoluble fibers can be optionally separated using

a decanting step. However, the beta-glucans are somewhat degraded during the concentration process. In the starting material (oat bran), 30% of the beta-glucan had a molecular weight under 200,000, but in the final concentrate, all beta-glucans had a molecular weight below 200,000. The molecular weight distribution of beta-

glucans in oat-based foods has also been investigated by Åman et al. 61 Oats, rolled oats and oat bran concentrates, extruded flakes, macaroni, muffins, and porridge

contained beta-glucans with a high average molecular weight, while pasteurized apple juice, fresh pasta, and a tea cake contained degraded beta-glucans.

Functional Food Carbohydrates

The molecular weight of the beta-glucans may be of importance for the choles- terol-lowering effects. In one study, an intake of 5.9 g of beta-glucan from oat bran incorporated in bread and cookies did not have any significant effect on blood lipids, while an intake of 5 g of beta-glucans mixed in orange juice significantly lowered

LDL cholesterol compared with a control group. 62 The molecular weight of the beta- glucans was lower in the bread than in the cookies and the preparation mixed with orange juice. However, the molecular weight is probably not the only important factor for the cholesterol-reducing potential. In another trial, an oat drink containing beta-glucans of rather low molecular weight (peak molecular weight, 82,400; Bili-

aderis, unpublished) was compared with a control drink low in beta-glucans. 63 The intake of oat drink (3.8 g of beta-glucans/day) resulted in significantly lower total

cholesterol (6%) and LDL cholesterol (6%) levels compared to the control drink, and thus had the expected quantitative cholesterol-lowering effects, compared with less processed products. One explanation for the results could be that the beta- glucans were in a soluble form. In another human study, the solubility of the beta-

glucans used was measured. 64 After the addition of an oat bran concentrate to food products like bread, tea cake, muesli, muffins, macaroni, pasta, and apple drink, the

solubility was analyzed after extraction of the ground sample in water at 37˚C for

2 h. It was found that the solubility of the beta-glucans in the products was rather low (about 50%), but the daily dose of soluble beta-glucans consumed by hyperc- holesterolemic subjects (2.7 g) was still high enough to decrease the blood choles- terol levels significantly compared to a control diet. The molecular weight and the solubility of the beta-glucans used in human studies have seldom been documented, and this makes it difficult to compare results from different studies in relation to the doses used. However, several investigators have addressed the task to make overall evaluations on the relation between oat beta-glucan intake and its cholesterol-low- ering effects. A large meta-analysis of oat products and their lowering effects of

plasma cholesterol was made by Ripsin et al. 65 The studies included in the analysis varied in study design, oat products, doses of oats, control products, and subjects with different initial cholesterol levels, gender, and age, and the influence of these parameters was assessed in the meta-analysis. The criteria for inclusion in the meta- analysis were that the study was controlled and randomized and that the control product should have a very low soluble fiber content. Moreover, the trial should also include a dietary assessment and measurement of the body weight. Twelve trials

were included in the calculation of the summary effect size. 65 Most of the trials used

a parallel design, and the length of the treatment phase varied between 18 days and

12 weeks. The summary effect size for a change in total cholesterol was found to

be –0.13 mmol/l. The initial cholesterol level was highly predictive of the reduction in total cholesterol level, while age and gender could not predict the response to oats. The dose–response effect was also evaluated, and after dividing the material in an intake of <3 and 3 g of soluble fiber, the interaction was statistically significant.

Mälkki 66 also evaluated the dose–response effect of oats. She identified 53 clinical trials, and 37 of them showed significant reductions in blood cholesterol levels after

consumption of oat products, while in 10 studies no significant effects were detected. The dose–response effect was not very obvious.

Carbohydrates and the Risk of Cardiovascular Disease

It is known that the cholesterol-lowering effect is larger in subjects with increased cholesterol levels. Ripsin et al. 65 indicated that if the initial cholesterol levels were over 5.9 mmol/l, the reduction was larger. Önning 67 compared 17 studies on hyperlipidemic subjects. The total cholesterol level at the end of the intervention period in the control group was between 5.9 and 7.4 mmol/l. The change in total cholesterol in the oat group in comparison with the control group varied from 0 to –13% and in LDL cholesterol from 0 to –16.5%. The studies with the largest reductions incorporated the oats in hot cereals, muffins, and beverages, while in the studies with small reductions the oats were given in cold cereals and also in bread. Thus, there are several problems concerning the estimate of the lipid-lowering effects of different oat products, but incorporation of the oats in a hydrated form seems to have a more positive effect. Additional studies are needed to relate the chemical and physicochemical characterization of the oat product to the cholesterol-lowering capacity.

8.3.3.2.2.3 Barley Barley usually contains beta-glucans in about the same amount as oats (3.5 to 5.9% of the dry matter), but higher amounts have been detected in some varieties (up to

11%). 68 Barley may have cholesterol-reducing effects similar to those of oats, but very few human studies have been done. In one animal study, hamsters consumed barley in doses of 0, 25, 50, and 75% of the diet, and the total cholesterol concen-

tration was reduced but no dose–response relationship was found. 69 No differences in the cholesterol-lowering effects between barley and oats were observed in another study on hamsters, where the cereals were given in three doses: 2, 4, and 8 g/100

g of diet. 70 Chicken has also been fed beta-glucans from barley, and the effect on the blood cholesterol concentration was followed. 71 A nonwaxy (Franubet) and a waxy (Washonupana) starch genotype with the same content of beta-glucans were compared, and it was shown that only the waxy genotype had an effect on the blood cholesterol. This was probably due to the waxy genotype having a higher viscosity when mixed with water, a greater average degree of polymerization, and lower endogenous beta-glucanase activity. 72

Six studies were found in a Medline search on the effect of barley on blood cholesterol by including human studies done after 1980 and using the search terms barley and cholesterol. Keogh et al. 73 gave a highly concentrated barley beta-glucan preparation (75% beta-glucans) to hypercholesterolemic men in a crossover trial. The beta-glucan intake was 8 to 12 g/day, depending on body weight, and the preparation was incorporated in different foods taken throughout the day (bread, waffles, muffins, cakes, in dishes). The diet was controlled during the whole study period (7-day diet rotation) and, in the control diet, the beta-glucans were exchanged with glucose. Eighteen subjects completed the study, and the average intake of beta- glucans was 10 g/day. The total cholesterol level fell 1.3% and the LDL cholesterol level fell 3.8% over the 4-week beta-glucan period, but no significant differences between the beta-glucan and the control period were found. The lack of effect could

be due to structural changes in the beta-glucans during the isolation process or during the incorporation of the preparation in foods (freezing, storage, baking). In an earlier study, however, barley fiber was more effective in reducing the blood cholesterol

Functional Food Carbohydrates

level than wheat fiber. 74 Twenty-one men with mild hypercholesterolemia consumed barley fiber incorporated in bread, muesli, spaghetti, and biscuits (total of about 8

g of beta-glucan/day) for 4 weeks. In comparison with the wheat foods, the barley foods gave significantly lower total cholesterol (6%) and LDL cholesterol (7%)

levels, while the HDL cholesterol and triglyceride levels did not differ. A similar result was also obtained in a recent study by Behall et al. 75 Eighteen men with increased cholesterol levels consumed a controlled diet (AHA Step I) for 2 weeks, and then the same diet for 5 weeks in a Latin square design, but about 20% of the

energy intake was exchanged with brown rice/whole wheat, 1 / 2 barley, and 1 / 2 brown rice/whole wheat or barley (<0.4, 3, and 6 g soluble fiber per 2800 kcal, respectively).

The barley (flakes, flour, pearled) was incorporated into foods like pancakes, spice cake, no-bake cookies, hot cereal, toasted flakes, steamed pilaf, and muffins. The total cholesterol and LDL cholesterol levels were significantly lower after the high-

soluble-fiber diet than after the low- or medium-fiber diets. Newman et al. 76 found that a diet with high amounts of barley (corresponding to 42 g of dietary fiber daily) gave decreased cholesterol levels for subjects that had high pretreatment cholesterol levels, but not for subjects with average pretreatment cholesterol levels. Barley flour that contained 10.7% beta-glucan was incorporated in breads, cookies, muffins, and bars, and the subjects were asked to consume one serving of three test products daily and otherwise follow their normal meal pattern. In another study in Japan, replacement of 30% of the carbohydrates in the diet with barley gave significantly

lower total and LDL concentrations in young female subjects. 77 Thus, most of the studies published on barley and blood lipids indicate that barley, like oats, has positive effects on the blood lipid pattern.

8.3.3.2.2.4 Guar Gum Guar gum is the ground endosperm of seeds from the guar plant (Cyamopsis tet- ragonoloba ), and the main component is galactomannan. Guar gum is the natural gum that produces the highest viscosity, and many human studies on its effect on lipid metabolism have been conducted. A Medline search using the search terms guar gum and cholesterol showed that nearly 70 studies have been published since 1980. Its effects on glucose, lipid metabolism, and blood pressure were investigated

in healthy men by Landin et al. 78 The dose of guar gum was 10 g and it was taken three times a day for 6 weeks. In comparison with a placebo, the guar gum decreased the blood cholesterol and triglyceride levels and blood pressure significantly. Thirty grams of guar gum was taken daily for 6 weeks in a double-blind, placebo-controlled,

crossover study. 79 The subjects had primary hyperlipidemia, and their total choles- terol, LDL cholesterol, and intermediate-density lipoprotein levels were decreased about 10% when they consumed guar gum. The effect of guar gum on LDL metab- olism seemed to be related to an increased LDL apolipoprotein B fractional catab- olism. Modified guar gum has also been studied, and in one study partially depoly- merized guar gum decreased the total cholesterol levels by 10%, which is a reduction

similar to that found earlier for high molecular weight guar gum. 80 The effects of solid or liquid guar gum and preparations with high or medium viscosity on lipid metabolism were followed in hypercholesterolemic subjects. 81 Both solid and liquid guar gum preparations lowered the total and LDL cholesterol, but the high-viscosity

Carbohydrates and the Risk of Cardiovascular Disease

preparation gave a larger reduction in blood lipid levels than the medium-viscosity preparation. In yet another study, hypercholesterolemic men were given granulated

guar gum (15 g/day) or placebo for 12 weeks in a crossover trial. 82 After 6 weeks’ consumption of guar gum, the total and LDL cholesterol levels were significantly

decreased compared with the placebo, but after 12 weeks the difference was no longer statistically significant. The hypocholesterolemic effect of guar gum seems

to decrease during prolonged dietary supplementation. However, most studies on guar gum have noted significant reductions in serum cholesterol (mean, 11.2%) and

LDL cholesterol (mean, 17.7%). 3 The doses given in the studies varied between 6 to 26 g/day, but in most of the studies a dose of over 10 g/day was used. Other gums (xanthan, locust bean, karaya, acacia, arabic) also significantly lower the cholesterol levels, but the effects are slightly less than those reported with guar gum.

8.3.3.2.2.5 Pectin Pectic substances are a complex group of acidic polysaccharides consisting mainly

of galacturonic acid, rhamnose, arabinose, and galactose residues. 83 Also for pectin, several human studies have been done and about 25 studies were found in a Medline search by using the search terms pectin and cholesterol. One observational study especially focused on pectin. Here, the influence of pectin on the progression of atherosclerosis was studied in a cohort of subjects free of heart disease aged

40 to 60 years (n = 573). 84 A significant inverse association between the intima- media thickness of the common carotid arteries and the intake of pectin was found. The ratio of total to HDL cholesterol was inversely related to the intake of pectin, and also to total fiber and viscous fiber intake. Pectin can be included in the diet as a supplement, but also as fruits, which often contain much pectin. In another study, subjects with hypertension were given guava fruits before meals during 12

weeks, and the effect on the blood lipids and blood pressure was followed. 85 In comparison with a group that was not given guava, the total cholesterol, HDL cholesterol, triglycerides, and blood pressure decreased significantly. An intake of another pectin-rich fruit (100 g of prunes daily) and its effect on blood lipids and bile acid excretion were investigated in men with mild hypercholesterolemia. 86 LDL cholesterol in plasma and the concentration of lithocholic acid in feces were significantly lower after the prune diet in comparison with the control diet (grape- fruit juice). Consumption of apple powder (52 g daily) for 4 weeks by subjects with type 2 diabetes did, however, not decrease the total cholesterol and LDL

cholesterol levels significantly. 87 The apple powder was added to bread and seven slices were consumed per day. The apple powder would be expected to contain

approximately 10.9% pectic substances, which corresponds to a daily intake of

5.7 g. When pectin isolated from grapefruit was given to hypercholesterolemic subjects, the plasma cholesterol and LDL cholesterol decreased 7.6 and 10.8%, respectively. 88 In another study on male hyperlipidemic subjects, the total choles- terol and LDL cholesterol levels were reduced 2 and 4%, respectively, by a pectin supplement, but the reductions were not significant compared to those after a

cornflakes control diet. 89 The pectin was added to a ready-to-eat breakfast cereal consumed once daily for 6 weeks. The breakfast cereal also contained oat bran,

sugar beet fiber, and wheat bran. The daily intake of soluble fiber in the pectin

Functional Food Carbohydrates

group was 6 g, whereof about 3 g was from pectin. Challen et al. 90 gave healthy volunteers 36 g of pectin per day during 3 weeks, which resulted in significantly

lower serum cholesterol concentrations (5.18 mmol/l) in comparison with a control (5.73 mmol/l), but had no effects on the platelet aggregation, platelet fatty acid concentration, blood clot lysis time, and bleeding times. The influence of pectins on the fibrin network was also investigated. Dietary pectin influenced the fibrin network in hypercholesterolemic men (more permeable, lower tensile strength)

but did not change the fibrinogen concentration. 91 Moreover, male hyperlipidemic subjects were given either pectin (15 g/day) or acetate (6.8 g/day) and the effects

on the fibrin network were followed. 92 Both supplements gave significant and similar changes on the fibrinogen network (more permeable, lower tensile strength), and thus the effect of pectin on the fibrin network could partially be mediated by acetate.

Several studies have also been done with different kinds of pectins. Dongowski and Lorentz 93 gave diets containing pectin with different degrees of methylation (34.5, 70.8, and 92.6%) to rats for 3 weeks. The concentration of bile acids in the plasma decreased when pectin was given, and with increasing degree of methylation more bile acids were excreted with the feces. A study on hamsters indicated that the viscosity of the pectin was important for the cholesterol-lowering effect. 94

According to Anderson et al., 3 most clinical studies on pectin noted a significant reduction in serum cholesterol after pectin supplementation, with a mean decrease of 12.4%. The doses given were 2 to 50 g/day, with most of the studies using a dose of 15 g/day.

8.3.3.3 Cholesterol-Lowering Mechanisms of Dietary Fiber

Several mechanisms have been proposed for the cholesterol-lowering effects of dietary fiber. The main hypothesis is that they decrease the intestinal uptake of bile

acids. Bile acids (mainly cholic acid and chenodeoxycholic acid) are produced in the liver from cholesterol and they are excreted into the bile. When food enters the intestine, bile acids flow into the duedenum and mix with the contents. By active transport, over 90% of the bile acids are reabsorbed from the intestine and transported back to the liver (enterohepatic circulation). Decreasing the bile acid reuptake will lead to an increased use of cholesterol for bile acid synthesis, and in this way, the blood cholesterol values will be reduced. Several types of dietary fiber have been shown to increase the fecal excretion of chenodeoxycholic acid. In subjects with an ileostomy, intake of oat bran bread led to an increased excretion of chenodeoxycholic

acid and total bile acids in comparison with a wheat flour bread. 95 The median (range) bile acid excretions were 851 (232 to 1550) and 606 (101 to 980) mg/day

in the oat bran and wheat flour periods, respectively. However, barley bread did not increase the bile acid excretion significantly in comparison to the wheat flour bread, but instead the excretion of total cholesterol was significantly higher (583 and 494

mg/day, respectively). In another study on ileostomy patients, either pectin (15 g) or wheat bran (16 g) was given and excretion of bile acids and cholesterol from the small intestine was studied. 96 Pectin significantly increased the bile acid excretion

Carbohydrates and the Risk of Cardiovascular Disease

35% and the net cholesterol excretion 14%, but an intake of wheat bran did not change these parameters.

The composition of the bile can also be influenced by a dietary fiber intake. Hillman et al. 97 gave fiber components like pectin (12 g), cellulose (15 g), or lignin

(12 g) to healthy subjects daily for 4 weeks, and the effect on the biliary composition was followed. The fiber components gave different effects on the bile acid compo-

sition, probably mainly related to changes in the colonic metabolism of the fiber components. Pectin significantly decreased the mean percentage of cholic acid from

42.8 to 39%, and cellulose increased the mean percentage of chenodeoxycholic acid from 33.6 to 35.4%. Lignin had no significant effect on the bile acid composition.

The effects on the blood lipids were also followed, but no significant changes were observed in these normolipidemic subjects. 98

In animals, the main outcome of fiber action is a lowering of hepatic cholesterol pools as a result of more cholesterol being diverted to bile acid synthesis and lower

cholesterol delivery to the liver through chylomicron remnants. 99 The activity of major regulatory enzymes of cholesterol homeostasis are increased (3-hydroxy-3- methylglutaryl coenzyme A reductase and Cyp 7) — the former to compensate for sterol loss in the liver and the latter to produce more bile acids to balance the depletion of bile acid pools. In addition, acyl–coenzyme A cholesterol:acyltrans- ferase activity is decreased because of low availability of free cholesterol. Further- more, hepatic LDL receptors are upregulated to reestablish a cholesterol balance in the liver. In addition, the VLDL apolipoprotein B synthesis rate is decreased and the conversion of VLDL to LDL is reduced. The combination of all of these mech- anisms is the probable cause of the consistent hypocholesterolemic effect induced

by soluble fiber. 99 Furthermore, soluble fiber can decrease the gastric emptying, prolong glucose absorption, and increase insulin sensitivity. These changes can also

have an effect on the liver metabolism of lipids (cholesterol, fatty acids). Dietary fiber can also interfere with the dietary fat absorption by binding the bile acids

necessary for micelle formation. Furthermore, some fibers are fermented in the colon and the short-chain fatty acids produced may influence the cholesterol metabolism in the liver, but at present only a few human studies on this point exist and more studies are needed to estimate this effect.

The method of fiber administration seems also to have an influence on the cholesterol-lowering effect. Psyllium fibers (7.3 to 7.6 g daily) were taken either with meals or between meals for 2 weeks. 100 In comparison with a wheat bran control, the total, LDL, and HDL cholesterol were reduced 8, 11, and 7%, respectively, if the psyllium was taken with meals, while when it was taken between meals no cholesterol-lowering effect was observed. It is therefore important to include the soluble fiber in each meal, and in most of the controlled studies, it is taken with a meal at least twice daily.

8.3.3.4 Cholesterol-Lowering Effects of Dietary Fiber in Comparison with Other Food Components

Brown et al. 101 evaluated the cholesterol-lowering effect of different soluble dietary fibers and made a meta-analysis of controlled trials (25 trials of oat products, 17 of

Functional Food Carbohydrates

psyllium, 7 of pectin, 18 of guar gum). The intake of soluble fiber was associated with a small but significant decrease in total cholesterol (–0.045 mmol/l/g of fiber) and LDL cholesterol (–0.057 mmol/l/g of fiber). The different soluble fibers’ effect on the cholesterol levels did not differ significantly (Table 8.3). As a comparison, other meta-analyses and also studies on barley are included in Table 8.3. Brown et al. 101 concluded that increasing the intake of soluble fiber can only make a limited contribution to dietary therapy to lower cholesterol. Jenkins and Kendall 102 compared the ability of different food components to reduce the LDL cholesterol (Table 8.4). Consumption of 5 to 10 g of viscous fiber daily can reduce the LDL cholesterol by approximately 5%. The same reduction can also be obtained with an intake of 1 to

3 g of plant sterols or 25 g of soy protein daily. Changing the amount of saturated

TABLE 8.3 Doses of Fiber Preparations Used in Dietary Studies and Resulting Lowering Effect of Mean Blood Cholesterol (mmol/l/g)

Blood Cholesterol-

Dietary Fiber Amount, Mean

Lowering Effect,

Source (Range), g/day

mmol/l/g

Brown et al., 101 meta-analysis

Anderson et al., 57 meta-analysis Oats

10.2 a –0.023

5.0 (1.5–13.0) b –0.037

Brown et al., 101 meta-analysis

3 (1.2–7.6) b –0.043

Ripsin et al., 65 meta-analysis

Barley 8 c –0.016

McIntosh et al. 74

9.9 (8–12) c –0.008

Keogh et al. 73

Behall et al. 75 Guar gum

6 b –0.065

Brown et al., 101 meta-analysis Pectin

17.5 (6.6–30.0) b –0.026

Brown et al., 101 meta-analysis a Psyllium.

4.7 (2.2–9.0) b –0.070

b Soluble fiber. c Beta-glucan.

TABLE 8.4 Ability of Different Food Components to Lower the Blood LDL Cholesterol Level

Component Approximate LDL Cholesterol Reduction

5–10 g of viscous fiber per day 5% 1–3 g of plant sterols per day

5% 25 g of soy protein per day

5% <7% of the energy intake from saturated fat

10% Source : Adapted from Jenkins, D.J.A. and Kendall, C.W.C., J. Am. Coll. Nutr., 18, 559, 1999.

Carbohydrates and the Risk of Cardiovascular Disease

fat to below 7% of the energy intake will lead to lower LDL cholesterol levels by approximately 10%. A reduction of LDL cholesterol by 5% is estimated to have clinical relevance on a population basis, but a combination of different dietary components known to improve the LDL cholesterol values can probably give an even better result. Intake of a diet low in saturated fat and high in plant sterols (1.2 g/1000 kcal), soy protein (16.2 g/1000 kcal), viscous fibers (8.3 g/1000 kcal), and almonds (16.6 g/1000 kcal) lowered the LDL cholesterol similarly to statins (35%),

a very efficient cholesterol-lowering agent. 103 The viscous fibers used were psyllium husk and beta-glucans from oats and barley. No significant differences in blood pressure, HDL cholesterol, or triglycerides were seen in comparison with subjects only consuming a low-saturated-fat diet. The calculated coronary artery disease risk was significantly reduced by 32% (Framingham 10-year cardiovascular disease risk).