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Scientific Name(s): Cyamopsis psoralioides DC., Cyamopsis tetragonolobus (L.) Taub.
Common Name(s): Guar, Guar flour, Indian cluster bean, Jaguar gum
Guar gum is a food additive/thickener. It has been shown to reduce serum cholesterol and appears to have positive effects on blood glucose. It may be useful in reducing recurrence of anal fissures and mitigating postprandial hypotension. Guar gum should not be used to promote weight loss.
Guar gum has been administered in amounts from 7.5 to 21 g/day in clinical trials for weight loss. For constipation in children, 1 study used partially hydrolyzed guar gum 3 g/day for patients 4 to 6 years of age, 4 g/day for patients 6 to 12 years of age, and 5 g/day for patients 12 to 16 years of age. Guar gum 8 to 36 g/day and 100 to 150 g/day of dried beans or legumes have been suggested to lower low-density lipoprotein (LDL) cholesterol by 5% to 10%.
Contraindications have not yet been identified.
Information regarding safety and efficacy in pregnancy and lactation is lacking.
Large amounts of guar gum (10 g or more daily) may decrease metformin serum concentrations and should be avoided.
Guar gum may cause GI obstruction. The most common adverse effects are abdominal pain, cramps, diarrhea, and flatulence.
There is no published evidence of toxicity with the use of guar gum.
- Fabaceae (bean)
The guar plant is a small nitrogen-fixing annual that bears pods, each containing a number of seeds. Native to tropical Asia, the plant grows throughout India and Pakistan and has been cultivated in the southern US since the beginning of the 20th century.1 Another name for this species is C. psoralioides DC.
Guar gum is a dietary fiber obtained from the endosperm of the bean, which can account for more than 40% of the seed weight. It is separated and ground to form commercial guar gum. Guar beans may be eaten as green beans, used as fertilizer, or fed to cattle.2
Guar gum is reported to contain 75% soluble fiber, 7.6% insoluble fiber, 2% crude protein, 0.78% fat, 0.54% ash, and 9.6% moisture.2 Synonyms are Cyamopsis psoralioides DC.
Guar gum has been used for centuries as a thickening agent for foods and medicines. The largest market for guar gum is the food industry, where guar gum is known as food additive code E412.2 Guar gum continues to find extensive use for these applications as well as in the paper, textile, and oil drilling industries.
Guar is a galactomannan polysaccharide that forms a viscous gel when placed in contact with water. It forms solutions that range from slightly acidic to neutral pH. Even at low concentrations (1% to 2%), guar gum forms gels in water. The viscosity of these gels is generally unaffected by the pH of the solution.
Food grade guar gum contains approximately 80% guaran (a galactomannan composed of D-mannose and D-galactose units) with an average molecular weight of 220 kDa. The overall ratio of mannose to galactose is approximately 2:1.3 However, guar gum is not a uniform product and its viscosity may vary in proportion to the degree of galactomannan cross-linking.
Because of this physical composition, guar gum–based matrix tablets are currently being evaluated as a method of administering sustained-release drugs, including diltiazem,4, 5 and for colonic drug delivery of corticosteroids to patients with inflammatory bowel disease.6
Uses and Pharmacology
In a 60-day study of Wistar rats, diets containing 10% and 20% weight/weight guar gum resulted in lower serum cholesterol, triacylglycerol, and LDL cholesterol levels as well as higher high-density lipoprotein (HDL) cholesterol levels.3 Rats fed guar gum had significantly lower lymph flow compared with rats fed cellulose (3.88 ± 1.31 and 11.9 ± 1.1 mL, respectively; P < 0.005). Additionally, rats fed guar gum had significantly reduced transport of cholesterol (4.6 ± 1.77 and 18.1 ± 1.1 mg, respectively; P < 0.0005), triacylglycerols (66.8 ± 35.3 and 297 ± 27 mg, respectively; P < 0.05), and phospholipids (13.7 ± 6.7 and 36 ± 2.5 mg, respectively; P < 0.05).7 Triglycerides in the plasma and liver were lower in rats that were fed fructose and given supplemental guar gum hydrolysate.8
Guar gum has been shown to have positive effects on cholesterol at doses ranging from 12 to 15 g/day. Most short-term studies (less than 1 year) in patients with mild to moderate hypercholesterolemia have demonstrated a decrease in serum total cholesterol levels by approximately 6.5% to 15% and LDL cholesterol by between 10.5% and 25% without any effect on triglycerides or HDL cholesterol levels.9, 10, 11, 12, 13 A long-term study in 40 patients illustrated that the effects of guar gum on total cholesterol and LDL cholesterol were sustained with continued use over a period of 24 months.14 A comprehensive review of the lipid-lowering effects of guar gum described a general hypothesis for the mechanism of this action: Guar reduces cholesterol absorption and increases bile excretion, leading to increased hepatic turnover of cholesterol. It has been suggested that the effects of guar on LDL cholesterol metabolism are similar to those of bile-sequestering agents.15
Guar gum also has been used as an adjunct to more conventional lipid-lowering therapy. Coadministration with lovastatin resulted in a larger decrease in total cholesterol levels (44%) compared with lovastatin alone (34%) after 18 weeks of treatment.16 Placebo-controlled trials have used a number of methods in an attempt to mask guar gum’s unpleasant flavor, including uncoated granules,17 powders, crispbreads, and other flavored formulas.18
In a study of 141 patients with metabolic syndrome, guar gum 3.5 g given 3 times daily was found to improve LDL cholesterol and apolipoprotein B following 6 months of treatment.19
The ability of guar to alter viscosity20 and thus affect GI transit results in delayed absorption of glucose and may contribute to its hypoglycemic activity.
In a study of Wistar rats, diets containing 10% and 20% weight/weight guar gum were associated with lower glucose levels after 30 days of feeding compared with other diets assessed. However, after 60 days of feeding, blood glucose levels were relatively higher in all diet groups, with no effect noted with guar gum.3 In another study of healthy rats, intragastric administration of guar gum and glucose was associated with a smaller peak increment in plasma glucose, insulin, and glucagon-like peptide 1 concentration.21 Guar gum hydrolysate was found to improve glucose intolerance in rats given fructose-based diets on day 28 of administration.8
In diabetic rats fed a 5% guar gum diet for 8 weeks, a significant improvement in hemoglobin A1c (HbA1c) was noted (12.4%) compared with that of rats receiving a basal diet (14.4%, P < 0.05). Additionally, the weight of the kidney was less in the group receiving guar gum compared with the group receiving a basal diet (2.76 vs 3.51 g, respectively; P < 0.05). Urinary albumin excretion was highest in the basal diet group and intermediate in the guar gum diet group.22
In another study, rats with streptozotocin-induced diabetes fed a diet containing 20% guar gum experienced a greater reduction in glucose levels after 28 days of administration compared with those receiving glibenclamide 2 mg/kg.23
Guar reduces postprandial glucose and insulin levels in healthy subjects20 and in patients with type 2 diabetes mellitus.24, 25, 26, 27, 28, 29 No reduction in plasma C-peptide levels was observed, suggesting that guar gum attenuates insulin concentration in peripheral venous blood by increasing the hepatic extraction of insulin.29 These effects on glucose and insulin seem to be most pronounced when large amounts of guar gum are added to the diet, and when the fiber is administered with the glucose or food.30 However, when dietary fats and proteins are not adequately controlled in the diabetic diet, the addition of guar was shown to have little effect on postprandial glucose or C-peptide responses.31
In a study of 141 overweight, hypertensive patients, guar gum 3.5 g 3 times daily was associated with a significant reduction in fasting plasma glucose of 10 mg/dL after 4 months (P = 0.009) and 12 mg/dL after 6 months (P = 0.009). Additionally, HbA1c significantly decreased by 0.7% after 6 months of therapy (P < 0.001).32
The effects of 48 weeks of guar gum were assessed in a single-blind, placebo-controlled study of 15 patients with type 2 diabetes mellitus. Specifically, all patients received placebo for 8 weeks (placebo period 1) followed by 48 weeks of guar gum 15 g/day or placebo divided into 3 doses and then another 8-week placebo period (placebo period 2). HbA1c levels were lower during guar gum treatment compared with placebo period 1, with no change during placebo period 2. Fructosamine levels were lower after treatment with guar gum compared with the end of placebo period 1; however, upon stopping guar gum, the fructosamine level began to increase as noted in placebo period 2. Additionally, C-peptide response increased after 48 weeks of treatment with guar gum. However, even after stopping guar gum for 8 weeks, C-peptide levels were higher at the end of placebo period 2 compared with placebo period 1 and after 16 weeks of guar gum.33
Preparations containing guar gum have been used extensively to promote normal GI motility and to maintain fecal bulk.34 Guar preparations may delay gastric emptying time or GI transit, but these effects seem to be related to the type of meal and diet.
A 5% partially hydrolyzed guar gum diet in mice attenuated dextran sulfate sodium–induced colitis. After 2 weeks of prefeeding with guar gum, a reversal in shortening of the colon occurred. Additionally, disease activity index scores (ie, measuring weight loss, stool consistency, blood in stool) were lower in mice receiving guar gum compared with the controls.35
Oral rehydration solution, supplemented with guar gum, may reduce the duration of diarrhea in young children.36 Also, the addition of enzymatically modified guar gum to enteral formulas has been shown to increase GI transit time, increase fecal nitrogen excretion,37 and reduce diarrhea38 without any effects on normal absorption of glucose, amino acids, or fat, or any adverse effects on hematological, hepatic, or renal function.39 In a study of children with alternating diarrhea and constipation, Optifibre (partially hydrolyzed guar gum) improved these symptoms.40 Daily administration of partially hydrolyzed guar gum (3 g/day for patients 4 to 6 year of age, 4 g/day for patients 6 to 12 years of age, and 5 g/day for patients 12 to 16 years of age) for 4 weeks was as effective as lactulose at improving bowel movement frequency per week, stool consistency, and percentage of participants with abdominal pain and stool withholding.41
In a randomized, double-blind, placebo-controlled study, 60 women 18 to 65 years of age experiencing less than 3 bowel movements per week were randomized to receive 3 weeks of supplementation with 5 g/day of inulin and partially hydrolyzed guar gum given 3 times daily or placebo. An increase in bowel movement frequency and patient satisfaction occurred in both groups and was not statistically significant. Treatment with inulin and guar gum was associated with a decrease in the total Clostridium species (5.23 ± 0.67 cells/mcL at baseline compared with 4.76 ± 0.92 cells/mcL after treatment, P = 0.046), whereas women treated with placebo experienced an increase in total Clostridium sp. (5.14 ± 0.92 cells/mcL at baseline compared with 5.50 ± 0.91 cells/mcL after treatment, P = 0.047). The findings were statistically significant when comparing inulin/guar gum with placebo (P = 0.045).42
Seventy-seven patients with small intestinal bacterial overgrowth were randomized to receive 1,200 mg/day of rifaximin or 1,200 mg/day of rifaximin plus 5 g/day of partially hydrolyzed guar gum for 10 days. The eradication rate of small intestinal bacterial overgrowth was 62% in the group given rifaximin alone compared with 87% in the per-protocol group given rifaximin plus guar gum (P = 0.017) and 85% in the intention-to-treat group given rifaximin plus guar gum (P = 0.036). Clinical improvement was noted in 87% of patients receiving rifaximin alone compared with 91% in those receiving rifaximin plus guar gum (P = 0.677).43
A prospective, open-label study evaluated the effect of guar gum on colonic transit time (CTT) in adults (n = 39) with chronic constipation; bisacodyl or glycerin suppositories were allowed for rescue therapy during the study period. Daily partially hydrolyzed guar gum (5 mg) for 4 weeks significantly improved CTT, straining, and weeks with pain, specifically in patients with baseline slow transit time (P = 0.016, P < 0.001, and P = 0.027, respectively). The number of complete spontaneous bowel movements, spontaneous bowel movements, weeks with bloating, number of days/week taking laxatives, and stool form were significantly improved in patients with either slow or normal baseline transit times. No serious adverse events were reported.63
At 12 months after standard therapy with topical nitroglycerin 0.4% ointment for chronic anal fissure, patients who received oral supplementation of partially hydrolyzed guar gum (PHGG) 5 g/day for 10 months (7 cycles of 4 weeks spaced by 2-week intervals) achieved higher success rates (58.5% vs 38.3%; P = 0.019) and lower recurrence (14.5% vs 30.2%; P = 0.0047) than those without PHGG maintenance therapy.64
Because bulk-forming fibers may impart a feeling of fullness, they have been used to help curb appetite. Satiety is believed to be secondary to delayed gastric emptying.2, 44
Research reveals no animal data regarding the use of guar gum for weight loss.
The results of 1 small study suggested that guar gum may have a more profound effect on satiety when added to a meal rich in fat than when added to a low-fat meal.45 A meta-analysis presented the combined results of 20 randomized controlled trials in which guar gum (average daily dose, 9 to 30 g) was compared with placebo.46 It was shown conclusively that guar gum is not effective in reducing body weight. Additionally, a number of studies using a partially hydrolyzed form of guar gum, which has no viscosity or bulking effect, have found no effect on appetite47 or weight maintenance.48 Although evidence for the effectiveness of fiber products as appetite suppressants is lacking, they remain popular ingredients in over-the-counter weight loss preparations.
In a study of 141 patients with metabolic syndrome, guar gum 3.5 g given 3 times daily was found to significantly decrease waist circumference after 4 months of treatment (−4.6 cm, P = 0.011). Waist circumference was decreased even further after 6 months of treatment (−5.2, P < 0.004).19
Guar gum has been reported to have varied effects on blood pressure.
Research reveals no animal data regarding the use of guar gum for blood pressure levels.
One small study of 10 elderly subjects showed a reduction in postprandial hypotension (PPH) (defined as a decrease in systolic blood pressure greater than 20 mm Hg occurring within 2 hours of the end of a meal).49 These data were corroborated in a double-blind, randomized, placebo-controlled, crossover trial in 22 older women in South Korean community senior centers in which significant differences in postprandial systolic blood pressure were noted between the guar gum (9 g pre-meal intervention) and control groups with the greatest difference (18.2 mm Hg; P = 0.004) observed at 45 minutes after eating. Additionally, the incidence of PPH was 18.2% vs 72.7% in the guar gum and control groups, respectively (P < 0.001). No significant changes were noted in postprandial diastolic blood pressure during the 120-minute follow up.65 Conversely, guar supplementation for 2 weeks was shown to reduce blood pressure by 9% in moderately overweight men.50 However, in a study of 141 hypertensive overweight patients, guar gum reduced systolic blood pressure after 2 months of supplementation (3.5 g 3 times daily); however, there was no difference after 4 and 6 months of supplementation.32 In another study of 141 patients with metabolic syndrome, guar gum 3.5 grams 3 times daily was associated with an improvement in systolic blood pressure (−5.3 mm Hg, P < 0.001) after 4 months of treatment. However, this effect was not assessed in further study visits, and no effect on diastolic blood pressure was noted.19
Intrahepatic cholestasis and pruritus in pregnancy
Research reveals no animal data regarding the use of guar gum for intrahepatic cholestasis and pruritus in pregnancy.
In 2 double-blind studies, guar gum diminished or prevented worsening of pruritus in 96 pregnant women with intrahepatic cholestasis. This outcome is related to bile acid concentration, which remained unchanged in guar gum–treated patients but increased in placebo recipients.51, 52 The authors suggest that guar gum is a safe alternative and possible treatment option in these patients.
Guar gum has been administered in amounts from 7.5 to 21 g daily in clinical trials for weight loss.53 For constipation in children, 1 study used partially hydrolyzed guar gum 3 g/day for patients 4 to 6 years of age, 4 g/day for patients 6 to 12 years of age, and 5 g/day for 12 to 16 years of age.41 Guar gum 8 to 36 g/day and 100 to 150 g/day of dried beans or legumes have been suggested to lower LDL cholesterol by 5% to 10%.2
Pregnancy / Lactation
Information regarding safety and efficacy in pregnancy and lactation is lacking. Guar gum is not teratogenic and does not affect reproduction in rats.54
Guar gum reduces the absorption of metformin, which may decrease the antihyperglycemic effect.53 The effect of ingestion of 10 g of guar gum on a single 1,700 mg dose of metformin was studied in 6 healthy subjects.53 Guar gum decreased metformin serum levels between 1.5 and 5 hours after administration. The metformin area under the curve was decreased 39% and the absorption rate decreased over the first 6 hours following coadministration of guar gum.
In the colon, guar gum is fermented to short-chain fatty acids. Both guar and its resultant by-products do not appear to be absorbed by the gut. The most common adverse effects are GI-related, including abdominal pain, cramps, diarrhea, and flatulence.55 Approximately 50% of people taking guar experience flatulence, which usually occurs early in treatment and resolves with continued use. A dose of approximately 3 g 3 times daily, not to exceed 15 g/day, can minimize GI effects.2, 56
Guar gum may affect the absorption of coadministered drugs. Slowed absorption of digoxin, acetaminophen, and bumetanide and decreased absorption of metformin, penicillin V, and some formulations of glyburide have been reported.57 Bezafibrate, glipizide, and glyburide58 are generally unaffected by coadministration.9
Guar gum in a weight-loss product was implicated as causing esophageal obstruction in a patient who exceeded the recommended dosage.59 In a review, 18 cases of esophageal obstruction, 7 cases of small bowel obstruction, and possibly 1 death were associated with the use of Cal-Ban 3000, a guar gum–containing diet pill.60 The water-retaining capacity of the gum can cause it to swell 10- to 20-fold and may lead to luminal obstruction, particularly when an anatomic predisposition exists. Guar should be taken with large amounts of liquid.
Occupational asthma has been observed among people working with guar gum.61, 62 One case report suggests a possible anaphylactic reaction to a meal substitute containing guar gum in which the patient tested positive in a skin test.62
There is little or no information regarding toxicity with the use of guar gum.
- Cyamopsis psoralioides DC
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Dietary guar gum reduces lymph flow and diminishes lipid transport in thoracic duct-cannulated rats. Lipids. 2011;46(8):789-793.216118508. Suzuki T, Hara H. Ingestion of guar gum hydrolysate, a soluble and fermentable nondigestible saccharide, improves glucose intolerance and prevents hypertriglyceridemia in rats fed fructose. J Nutr. 2004;134(8):1942-1947.152843809. Todd PA, Benfield P, Goa KL. Guar gum. A review of its pharmacological properties, and use as a dietary adjunct in hypercholesterolaemia. Drugs. 1990;39(6):917-928.216446710. Knopp RH, Superko R, Davidson M, et al. Long-term blood cholesterol-lowering effects of a dietary fiber supplement. Am J Prev Med. 1999;17(1):18-23.1042974811. Jensen CD, Haskell W, Whittam JH. Long-term effects of water-soluble dietary fiber in the management of hypercholesterolemia in healthy men and women. Am J Cardiol. 1997;79(1):34-37.902473212. Hunninghake DB, Miller VT, LaRosa JC, et al. Long-term treatment of hypercholesterolemia with dietary fiber. Am J Med. 1994;97(6):504-508.798570813. Blake DE, Hamblett CJ, Frost PG, Judd PA, Ellis PR. Wheat bread supplemented with depolymerized guar gum reduces the plasma cholesterol concentration in hypercholesterolemic human subjects. Am J Clin Nutr. 1997;65(1):107-113.898892114. Salenius JP, Harju E, Jokela H, Riekkinen H, Silvasti M. Long term effects of guar gum on lipid metabolism after carotid endarterectomy. BMJ. 1995;310(6972):95-96.783373515. Turner PR, Tuomilehto J, Happonen P, La Ville AE, Shaikh M, Lewis B. Metabolic studies on the hypolipidaemic effect of guar gum. Atherosclerosis. 1990;81(2):145-150.215745016. Uusitupa MI, Miettinen TA, Happonen P, et al. Lathosterol and other noncholesterol sterols during treatment of hypercholesterolemia with lovastatin alone and with cholestyramine or guar gum. Arterioscler Thromb. 1992;12(7):807-813.131973517. Aro A, Uusitupa M, Voutilainen E, Korhonen T. 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Lakhdar A, et al. Fibre and patients with diabetes [letter]. Br Med J (Clin Res Ed). 1988;296(6634):1471.283730727. Kirsten R, Heintz B, Nelson K, Oremek G, Speck U. Influence of two guar preparations on glycosylated hemoglobin, total cholesterol and triglycerides in patients with diabetes mellitus. Int J Clin Pharmacol Ther Toxicol. 1992;30(12):582-586.133544128. Landin K, Holm G, Tengborn L, Smith U. Guar gum improves insulin sensitivity, blood lipids, blood pressure, and fibrinolysis in healthy men. Am J Clin Nutr. 1992;56(6):1061-1065.144265829. Gatenby SJ, Ellis PR, Morgan LM, Judd PA. Effect of partially depolymerized guar gum on acute metabolic variables in patients with non-insulin-dependent diabetes. Diabet Med. 1996;13(4):358-364.916261230. Nuttall FQ. Dietary fiber in the management of diabetes. Diabetes. 1993;42(4):503-508.838413131. Sels JP, De Bruin H, Camps MH, et al. Absence of guar efficacy in complex spaghetti meals on postprandial glucose and C-peptide levels in healthy control and non-insulin-dependent diabetes mellitus subjects. Horm Metab Res Suppl. 1992;26:52-58.133705932. Cicero AF, Derosa G, Manca M, Bove M, Borghi C, Gaddi AV. Different effect of psyllium and guar dietary supplementation on blood pressure control in hypertensive overweight patients: a six-month, randomized clinical trial. Clin Exp Hypertens. 2007;29(6):383-394.1772905533. Groop PH, Aro A, Stenman S, Groop L. Long-term effects of guar gum in subjects with non-insulin-dependent diabetes mellitus. Am J Clin Nutr. 1993;58(4):513-518.839748434. Rajala SA, Salminen SJ, Seppänen JH, Vapaatalo H. Treatment of chronic constipation with lactitol sweetened yoghurt supplemented with guar gum and wheat bran in elderly hospital in-patients. Compr Gerontol A. 1988;2(2):83-86.285254035. Naito Y, Takagi T, Katada K, et al. Partially hydrolyzed guar guym down-regulates colonic inflammatory response in dextran sulfate sodium-induced colitis in mice. J Nutr Biochem. 2006;17(6):402-409.1621433136. Alam NH, Meier R, Schneider H, et al. Partially hydrolyzed guar gum-supplemented oral rehydration solution in the treatment of acute diarrhea in children. J Pediatr Gastroenterol Nutr. 2000;31(5):503-507. 1114443437. Lampe JW, Effertz ME, Larson JL, Slavin JL. Gastrointestinal effects of modified guar gum and soy polysaccharide as part of an enteral formula diet. JPEN J Parenter Enteral Nutr. 1992;16(6):538-544.133736238. Homann HH, Kemen M, Fuessenich C, Senkal M, Zumtobel V. Reduction in diarrhea incidence by soluble fiber in patients receiving total or supplemental enteral nutrition. JPEN J Parenter Enteral Nutr. 1994;18(6):486-490.760272239. Alam NH, Meier R, Rausch T, et al. Effects of a partially hydrolyzed guar gum on intestinal absorption of carbohydrate, protein and fat: a double-blind controlled study in volunteers. Clin Nutr. 1998;17(3):125-129.1020532940. Paul SP, Barnard P, Edate S, Candy DCA. Stool consistency and abdominal pain in irritable bowel syndrome may be improved by partially hydrolysed guar gum. J Pediatr Gastroenterol Nutr. 2011;53(5):582-583.2183295041. Üstündağ G, Kuloğlu Z, Kirbaş N, Kansu A. Can partially hydrolyzed guar gum be an alternative to lactulose in treatment of childhood constipation? Turk J Gastroenterol. 2010;21(4):360-364.2133198842. Linetzky Waitzberg D, Alves Pereira CC, Logullo L, et al. Microbiota benefits after inulin and partially hydrolized guar gum supplementation: a randomized clinical trial in constipated women. Nutr Hosp. 2012:27(1):123-129.2256631143. Furnari M, Parodi A, Gemignani L, et al. Clinical trial: the combination of rifaximin with partially hydrolysed guar gum is more effective than rifaximin alone in eradicating small intestinal bacterial overgrowth. Aliment Pharmacol Ther. 2010;32(8):1000-1006.2093704544. Yen M, Ewald MB. Toxicity of weight loss agents. J Med Toxicol. 2012;8(2):145-152.2235129945. French SJ, Read NW. Effect of guar gum on hunger and satiety after meals of differing fat content: relationship with gastric emptying. Am J Clin Nutr. 1994;59(1):87-91.827940946. Pittler MH, Ernst E. Guar gum for body weight reduction: meta-analysis of randomized trials. Am J Med. 2001;110(9):724-730.1140375747. Heini AF, Lara-Castro C, Schneider H, Kirk KA, Considine RV, Weinsier RL. Effect of hydrolyzed guar fiber on fasting and postprandial satiety and satiety hormones: a double-blind, placebo-controlled trial during controlled weight loss. Int J Obes Relat Metab Disord. 1998;22(9):906-909.975625048. 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