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Long-term cholesterol-lowering effects of psyllium as an adjunct to diet therapy in the treatment of hypercholesterolemia.

BACKGROUND: Hypercholesterolemia is a major risk factor for coronary heart disease and nutrition management is the initial therapeutic approach. OBJECTIVE: This multicenter study evaluated the long-term effectiveness of psyllium husk fiber as an adjunct to diet in the treatment of persons with primary hypercholesterolemia. DESIGN: Men and women with hypercholesterolemia were recruited. After following an American Heart Association Step I diet for 8 wk (dietary adaptation phase), eligible subjects with serum LDL-cholesterol concentrations between 3.36 and 4.91 mmol/L were randomly assigned to receive either 5.1 g psyllium or a cellulose placebo twice daily for 26 wk while continuing diet therapy. RESULTS: Serum total and LDL-cholesterol concentrations were 4.7% and 6.7% lower in the psyllium group than in the placebo group after 24-26 wk (P < 0.001). Other outcome measures did not differ significantly between groups. CONCLUSIONS: Treatment with 5.1 g psyllium twice daily produces significant net reductions in serum total and LDL-cholesterol concentrations in men and women with primary hypercholesterolemia. Psyllium therapy is an effective adjunct to diet therapy and may provide an alternative to drug therapy for some patients.

Adult↗

Cholesterol 7 alpha-hydroxylase activity is increased by dietary modification with psyllium hydrocolloid, pectin, cholesterol and cholestyramine in rats.

Sources of dietary fiber known to alter cholesterol metabolism and/or bile acid pool size were fed to rats, and activity of the rate-limiting step in bile acid synthesis, cholesterol 7 alpha-hydroxylase, was measured. In the first experiment, semipurified diets containing 5% cellulose, psyllium hydrocolloid, pectin or oat bran as dietary fiber sources or 2% cholestyramine were fed to groups of 10 male Wistar rats for 4 wk. In the second experiment, groups of six rats were fed diets containing 5% cellulose, rice bran, oat bran or psyllium with and without 0.25% cholesterol. In the first experiment, the activity of cholesterol 7 alpha-hydroxylase (pmol.min-1.mg protein-1) was highest in the cholestyramine-treated group (95.6 +/- 3.6), followed by groups fed psyllium (35.5 +/- 3.5) or pectin (36.0 +/- 4.5), which exhibited more than twice the enzyme activity of groups fed cellulose (16.9 +/- 1.9) or oat bran (12.3 +/- 2.0). In the second experiment, feeding cholesterol resulted in significantly higher enzyme activity when cellulose (65%), oat bran (118%) and rice bran (60%) were fed, but no difference in activity was observed when cholesterol was added to the psyllium-containing diet. Higher activity of cholesterol 7 alpha-hydroxylase when pectin or psyllium rather than cellulose was fed may explain the almost twofold higher bile acid pool sizes previously reported in response to feeding either of these fibers. These data support the hypothesis that the hypocholesterolemic effect of soluble fibers is modulated through increased synthesis and therefore pool size of bile acids.

Animals↗

Psyllium reduces blood lipids in men and women with hyperlipidemia.

To see if a modest amount of soluble fiber reduced blood lipids in subjects with hyperlipidemia who were on a low-fat diet, 42 subjects (21 men, 21 women) consuming an American Heart Association step 2 diet took two servings of breakfast cereal daily for two 2-week periods in a randomized crossover trial. There were two types of test cereals, each providing 6.7 g psyllium fiber daily, and two types of wheat bran control cereals, matched for available carbohydrate and total fiber. Half the subjects tested each type of cereal, and the results were pooled because the psyllium cereals had similar effects on serum cholesterol levels. Comparing values at the end of 2 weeks, psyllium reduced serum total (6.33 +/- 0.12 mmol/L versus 6.76 +/- 0.12 mmol/L, p < 0.001), low-density lipoprotein (LDL; 4.36 +/- 0.11 mmol/L versus 4.73 +/- 0.12 mmol/L, p < 0.001) and high-density lipoprotein cholesterol levels (HDL; 1.10 +/- 0.05 mmol/L versus 1.14 +/- 0.05 mmol/L, p < 0.05) and the LDL/HDL cholesterol ratio (4.27 +/- 0.20 versus 4.48 +/- 0.22, p < 0.02) with no effect on triglycerides. There was no significant interaction between the effects of treatment and sex for any of the blood lipid variables. Women tended to have greater decreases in total, LDL, and HDL cholesterol levels than men, but the percent decrease in LDL/HDL ratio on psyllium was similar in men, 4.9%, and women, 4.7%. It is concluded that 6.7 g of psyllium fiber daily, with a low-fat diet, reduces serum cholesterol levels in both men and women with hyperlipidemia.

American Heart Association↗

Synergistic effects of psyllium in the dietary treatment of hypercholesterolemia.

We investigated psyllium fiber supplementation as a means of enhancing the cholesterol-lowering effect of the phase I American Heart Association diet. Fifty-nine subjects with total serum cholesterol (TC) levels ranging from 5.56 to 10.24 mmol/L (215 to 396 mg/dL) were given a 2-month dietary lead-in followed by 3 months of diet only (29 subjects) or diet supplemented with 20.4 g of psyllium daily (30 subjects). Unlike women, men had a significant decrease in levels of both TC (-8.0%) and low-density lipoprotein cholesterol (LDL-C) (-10.1%) during the dietary lead-in. Psyllium supplementation resulted in an additional 5.5% reduction in the TC levels as compared to diet alone. Psyllium supplementation combined with dietary lead-in resulted in an overall 17.3% decrease in the TC and a 20.0% decrease in LDL-C for men, with decreases of 7.7% and 11.6%, respectively, for women. Psyllium effectively enhances the cholesterol-lowering effect of the phase I diet.

Cholesterol↗

Occupational asthma in nurses handling psyllium.

Five nurses aged 31-55 years old had a history of asthmatic symptoms after being exposed to psyllium that they prepared and distributed to patients. They had been nurses for 9-20 years and had reported asthmatic symptoms related to work in the past 3-12 months. They reported symptoms of rhinoconjunctivitis and all were atopic but only one had a previous history of asthma. Four of the five tested subjects had an immediate skin reaction to a commercial psyllium extract. All had IgE antibodies to psyllium. At the time that they were investigated, four out of the five had a significant increase in bronchial responsiveness to methacholine (PC 20 less than 8 mg/ml). Inhalation challenges with psyllium caused isolated immediate (one subject) and dual reactions (three subjects). One subject exposed for only 1 min to the psyllium powder experienced a severe immediate bronchospastic reaction, which required intubation for 3 h with complete functional recovery thereafter. This experience illustrates the precautions necessary, with the inclusion of a cautious dose-response approach, even with an 'occupation-type' challenge in the laboratory.

Adult↗

Inhibitory effects of psyllium on rat mineral absorption were abolished by reduction of viscosity with partial hydrolysis.

Psyllium husk, a highly viscous fiber, has beneficial effects for health, but has been reported to inhibit absorption of calcium. The present study found the effects of fiber viscosity on calcium, magnesium, and zinc absorption with partially degraded psyllium preparations to be one fifth viscosity (LD-HP) and one seventieth viscosity (HD-HP) using normal and ovariectomized rats. Magnesium absorption was reduced with ingestion of intact psyllium (50 g/kg diet) for 4 weeks but this reduced absorption was increased with lower viscous psyllium preparations. Moreover, the absorption in the HD-HP group was higher than in the control group (100 g cellulose/kg diet) in ovariectomized rats. Changes in calcium and zinc absorption were similar to those in magnesium absorption. Cecal pH was reduced only in rats fed HD-HP in both normal and ovariectomized rats. These results indicate that reduction of psyllium viscosity tends to counter inhibitory effects on mineral absorption.

Animals↗

Effect of psyllium, calcium polycarbophil, and wheat bran on secretory diarrhea induced by phenolphthalein.

BACKGROUND: Fiber and water-holding agents are used for the treatment of constipation. In what may appear to be a paradox, they are sometimes also used for the treatment of diarrhea; it has been proposed that they sequester water from liquid stools and/or increase the ratio of fecal solids to fecal water and thereby improve stool consistency. The purpose of the present study was to test the validity of this hypothesis in normal subjects in whom secretory diarrhea was induced by phenolphthalein. METHODS: In random sequence, 9 subjects with phenolphthalein-induced diarrhea were treated with placebo, psyllium, calcium polycarbophil, or wheat bran. RESULTS: Calcium polycarbophil and wheat bran had no effect on fecal consistency or on fecal viscosity. By contrast, psyllium made stools firmer and increased fecal viscosity. In a dose-response study in 6 subjects, doses of 9, 18, and 30 g of psyllium per day caused a near linear increase in fecal viscosity. CONCLUSION: Psyllium, but not calcium polycarbophil or wheat bran, improves fecal consistency and viscosity in subjects with experimentally-induced secretory diarrhea.

Acrylic Resins↗

Anaphylaxis following psyllium ingestion.

Psyllium is a hydrophilic agent found in many bulk laxative preparations. We report the occurrence of an anaphylactic reaction in a patient after ingestion of a psyllium-containing laxative. IgE mediation of the reaction was suggested by a positive immediate skin test to psyllium, positive passive transfer skin test, lack of skin response during passive transfer with heat treated serum, and an elevated IgE (RAST) to psyllium seed.

Adult↗

Systemic anaphylaxis after ingestion of a psyllium-containing breakfast cereal.

Allergic reactions have been described as an occupational hazard among nurses and pharmaceutical workers who handle psyllium-containing laxatives. This study reports the case of a 38-year-old female nurse who ingested a bowl of psyllium-containing Heartwise Cereal (Kelloggs, Battle Creek, MI) and 25 minutes later developed severe systemic anaphylaxis manifested by hypotension, a feeling of constriction in the throat, hoarseness, dyspnea, wheezing, generalized pruritus, urticaria, and vomiting. She was treated with epinephrine, normal saline, diphenhydramine, and methylprednisolone, and recovered completely. Subsequent IgE immunoblot assay was strongly reactive to psyllium. Ingestion of psyllium-containing breakfast foods by sensitized individuals can be associated with life-threatening systemic anaphylaxis.

Adult↗

Randomized, double-blind, placebo-controlled, two-period crossover clinical trial of psyllium fiber in children with hypercholesterolemia.

A randomized, double-blind, placebo-controlled, crossover clinical trial was designed to test the efficacy of psyllium fiber in lowering elevated low-density lipoprotein cholesterol (LDL-C) levels in children 5 to 17 years of age. Subjects with LDL-C levels > 2.84 mmol/L (110 mg/dl) after at least 3 months of a low total fat, low saturated fat, low cholesterol diet were enrolled. Two ready-to-eat cereals, with water-soluble psyllium fiber (6 gm/day) and without, were prescribed for 4 to 5 weeks each, with an intervening 2-week washout phase. Reported compliance rates exceeded 80% in the 20 subjects who completed the study. Mean initial total cholesterol, LDL-C, high-density lipoprotein cholesterol, and triglyceride values were 5.23, 3.60, 1.18, and 2.22 mmol/L, respectively. Comparison of the mean changes (from baseline) in lipid values after the two periods of cereal consumption revealed no statistically nor clinically significant differences in total cholesterol, LDL-C, or high-density lipoprotein cholesterol values. Triglyceride levels, however, increased 0.68 mmol/L (26 mg/dl; p < 0.05) after the control cereal in comparison with the psyllium cereal. No significant differences were noted in the children's dietary intake (assessed by 7-day diet records) during the two study periods. Measures of growth (height, weight, and skin-fold thicknesses), and blood vitamin (folic acid; vitamins A, D, and E) and mineral (iron, zinc, and calcium) levels were not affected. In this study, psyllium fiber had no additional lowering effect on total cholesterol or LDL-C levels in children who were already following low total fat, low saturated fat, low cholesterol diets.

Adolescent↗

Effects of dietary cellulose and psyllium husk on monkey colonic microbial metabolism in continuous culture.

The effects of inoculating an in vitro continuous culture system with primate colon contents compared to fecal material, and the effect of feeding these cultures psyllium husk, a fermentable, or cellulose, a less fermentable, dietary fiber were tested. Modified 500-ml Bellco culture chambers were continuously infused with buffered medium containing vitamin mix, deoxycholate, urea, hemin, casein and mucin. Cultures were fed a mixture of minerals, sucrose, starch and either psyllium husk or cellulose twice daily. Chambers were inoculated with fecal or colonic samples obtained from adult male African green monkeys fed the respective fiber source in a purified diet for more than 3 yr. After a 5-d stabilization period, samples were collected for total viable anaerobe and aerobe counts, microbial beta-glucuronidase (EC 3.2.1.31) activity, volatile fatty acid (VFA) and ammonia nitrogen concentrations, dry matter, pH and oxidation-reduction potential. Inoculation with fecal material or colon contents produced similar results for the above mentioned characteristics; major differences were found due to the fiber treatments. Psyllium-fed cultures had lower pH (P less than 0.01) and higher VFA concentration (P less than 0.01) and beta-glucuronidase activity (P less than 0.10) than cellulose-fed cultures. The ratio of anaerobes to aerobes was lower (P less than 0.01) in psyllium-fed than in cellulose-fed cultures. These results indicate that feces can be used as an inoculum source for in vitro studies of changes in colonic microbial metabolism due to diet, and that dietary fiber source affects the colonic microbial population and metabolism.

Animals↗

Effects of dietary cellulose, psyllium husk and cholesterol level on fecal and colonic microbial metabolism in monkeys.

The effect of long-term feeding of dietary fiber and two levels of cholesterol on monkey colonic microbial metabolism was studied. Three groups of African green monkeys were fed for 3.5 yr purified diets containing 9.7% cellulose or psyllium husk and 0.8 mg cholesterol per kcal or 9.7% cellulose and 0.1 mg cholesterol per kcal. Total viable anaerobe and aerobe counts, microbial beta-glucuronidase activity, volatile fatty acid and ammonia nitrogen concentrations, dry matter and pH were determined in fecal and colonic samples. Compared to cellulose, psyllium husk feeding decreased (P less than 0.05) percentage dry matter, beta-glucuronidase (EC 3.2.1.31) activity and pH, and increased (P less than 0.05) ammonia nitrogen and volatile fatty acid output in feces and in colon contents. In all groups, colonic beta-glucuronidase activity was greater (P less than 0.05) than in fecal samples. Microbial beta-glucuronidase activity, pH or percentage dry matter in the ascending colon was not different from that in the transcending or descending segments. The ratio of anaerobic to aerobic bacteria was lower in colon contents from monkeys fed psyllium husk compared to those fed cellulose. Total viable bacterial counts were lower in monkeys fed low cholesterol compared to high cholesterol diets. The results suggest that chronic intake of dietary psyllium husk resulted in greater colonic microbial metabolism compared to cellulose feeding.

Animals↗

Dietary psyllium hydrocolloid and pectin increase bile acid pool size and change bile acid composition in rats.

Bile acid composition, synthetic rate and pool size were determined in rats fed diets containing 5 g cellulose, 5 g pectin or 5 g psyllium hydrocolloid/100 g diet using the washout technique. Bile acid pool sizes were similar for pectin- and psyllium-fed rats, and both were higher than the pool size for rats fed cellulose (5.48 +/- 1.22, 4.70 +/- 0.71 and 1.77 +/- 0.41 mumol/100 g body wt, respectively). Bile acid secretion rates showed a similar pattern [1730 +/- 496, 1551 +/- 252 and 572 +/- 88 nmol/(h.100 g body wt)], as did basal synthetic rates [129 +/- 25, 126 +/- 42 and 87 +/- 18 pmol/(h.100 g body wt)]. Individual and total bile acid pool sizes were generally higher in animals fed the pectin- or psyllium-supplemented diet compared with rats fed cellulose. Pectin or psyllium consumption resulted in a lower hydrophobicity of the bile acid pool and a lower ratio of circulating 12 alpha-hydroxylated to non-12 alpha-hydroxylated bile acids compared with cellulose consumption. This reduced hydrophobicity has been shown to reduce feedback inhibition of bile acid synthesis and may be responsible for the larger bile acid pool size. Changes in the location of reabsorption of bile acids may also be responsible for changes in the pool size and composition. These changes are characteristic of greater sterol excretion.

Animals↗

Artificial fiber complexes composed of cellulose and guar gum or psyllium may be better sources of soluble fiber for rats than comparable fiber mixtures.

Three fiber complexes composed of cellulose and the same weight of guar gum, cornstarch or psyllium were constructed as three-dimensional networks of cellulose fiber filled with the soluble components. Physiological properties of these fiber complexes were examined in comparison with a mixture of powdered cellulose and the corresponding polysaccharides at a ratio of 1:1 in rats. Another group of rats was fed a fiber-free diet. Body weight gain in the guar gum-cellulose mixture group, but not in guar gum-cellulose complex group, was lower than that of the fiber-free group. The cecal walls in the groups fed the guar gum-cellulose and psyllium-cellulose mixture diets were heavier than those in the corresponding fiber complex-fed groups. Weights of the small intestinal wall and ileal mucosa were also greater in the guar gum-cellulose mixture-fed group than in the guar gum-cellulose complex-fed and the fiber-free diet-fed groups. Fermentable energy in dietary fiber estimated from fecal energy excretion, short-chain fatty acid contents and in vitro short-chain fatty acid production rates in the cecum of the complex-fed groups were similar to those in the fiber mixture-fed groups. However, butyric acid content and production rate in the group fed the guar gum-cellulose complex were markedly higher than in the other groups. The lowering effects of guar gum-cellulose and psyllium-cellulose mixtures on plasma cholesterol concentration tended to be greater than those of guar gum-cellulose and psyllium-cellulose complexes. These findings demonstrate that the artificial fiber complexes supply soluble fibers without increasing mechanical stress to the intestines and decreasing cecal fermentation.

Animals↗

Dietary psyllium increases fecal bile acid excretion, total steroid excretion and bile acid biosynthesis in rats.

Psyllium, a source of dietary fiber rich in soluble components results in lower serum cholesterol concentration in several species. Suggested mechanisms for the hypocholesterolemic effect include a greater excretion of fecal bile acids and total steroids, and up-regulation of bile acid biosynthesis. The activity of cholesterol 7alpha-hydroxylase (7alphaOHase), the rate limiting enzyme in bile acid biosynthesis, is higher in rats fed 5% psyllium. Whether this higher activity corresponds to an increase in mRNA levels has not been determined. Four groups of 10 rats were fed a semipurified diet containing 5% cellulose (CEL; control), 5% cellulose plus 1% cholic acid (CCA), 5% cellulose plus 2% cholestyramine (CHY) or 5% psyllium hydrocolloid (PSY) for 3 wk. Liver cholesterol concentration, fecal bile acid and total steroid excretion, 7alphaOHase activity and 7alphaOHase mRNA levels were measured. Liver cholesterol content in rats fed CCA was significantly higher than in all other groups. Rats fed CHY and PSY had significantly lower liver cholesterol content than those fed CEL. Total fecal steroid and bile acid excretions were significantly greater in rats fed CCA, CHY and PSY than in those fed CEL. Activities and mRNA levels of 7alphaOHase in rats fed CHY and PSY were significantly higher than in rats fed CEL or CCA. These data indicate that feeding psyllium to rats increases fecal bile acid and total steroid excretion as well as 7alphaOHase activity and 7alphaOHase mRNA levels.

Animals↗

Correlation between echographic gastric emptying and appetite: influence of psyllium.

The correlation between ultrasonographic gastric emptying and appetite was studied. Echographic evaluation of gastric emptying by measurement of the antral vertical diameter and assessment of sensations of hunger and satiety using analogue visual scales were performed simultaneously in 12 healthy volunteers. Measurements were carried out after the intake of 10.8 g psyllium or placebo in a randomised, crossover, double blind trial. The correlation between echographic gastric emptying and sensations of hunger and satiety was excellent (p < 0.001) after the intake of either psyllium or placebo. Psyllium significantly delayed gastric emptying from the third hour after a meal. It increased the sensation of satiety and decreased hunger at the sixth hour after the meal. The association between echographic measurement and visual scales is a simple method of evaluating the relationship between the stomach and appetite. The pharmacodynamic effect of psyllium should be confirmed by longterm therapeutic trials.

Adolescent↗

Hypocholesterolemic effect of dietary psyllium in female rats.

We fed cholesterol-enriched (1% cholesterol and 0.2% cholic acid) semipurified diets containing either 3% cellulose or psyllium to 2 groups of female Wistar rats for a period of 8 weeks. The feeding of the cholesterol-enriched semipurified diets resulted in a progressive increase in plasma cholesterol levels in both groups during the 8 weeks of the experiment. The rats fed psyllium, however, had significantly lower plasma cholesterol concentrations than the animals fed cellulose throughout the experimental period (at 8 weeks, 8.92 +/- 4.42 and 16.47 +/- 8 mmol/l, respectively, means +/- SD, n = 14, p < 0.01). Most of the plasma cholesterol in both groups at the end of the study was located in the very low-density lipoprotein (VLDL) fraction (91%) and differences in total plasma cholesterol concentrations were predominantly reflected in differences in VLDL cholesterol. Plasma triglyceride concentrations were not significantly different between the 2 groups. Liver cholesterol concentrations paralleled the concentrations of plasma cholesterol and were significantly lower (p < 0.001) in the psyllium-fed rats (90.31 +/- 13.81 micromol/g liver) than in the cellulose-fed rats (60.49 +/- 15.25 micromol/g liver). Substitution of psyllium for cellulose resulted in an increase in the excretion of fecal bile acids by 26%, and this increase was predominantly caused by an increased excretion of beta-muricholic acid and the bile acids derived from beta-muricholic acid (omega-muricholic acid and hyodeoxycholic acid).

Animals↗

Psyllium therapy in the irritable bowel syndrome. A double-blind trial.

A randomized, double-blind trial of a psyllium preparation was initiated in 77 patients with painful irritable bowel syndrome. Sixty-patients finished and submitted symptom data for 8 weeks while taking placebo (n = 34) or psyllium (n = 26). Increase in normal stools and decrease in pain severity (p less than 0.05) occurred equally in both groups. Subjective improvement was reported by 24 of 34 patients on placebo and 20 or 26 on psyllium (p greater than 0.05). Five symptom variables were significantly correlated (p less than 0.05) with patient's subjective global assessment (R = 0.64). Discriminant analysis of Minnesota Multiphasic Personality Inventory variables yielded overall rates of correct prediction of 66.1% for whether patients got "much better" and 77.9% for whether they voluntarily dropped from the study. A major placebo effect occurs in patients with painful irritable bowel syndrome and is probably responsible for the efficacy of psyllium. Personality factors influence the magnitude of therapeutic response and whether patients discontinue treatment within 8 weeks.

Clinical Trials as Topic↗