Chitosan for Weight Loss and Cholesterol Lowering
By Robert J. Nardino, MD, FACP
"Never have to diet again!" these five words have captivated many people who have waged the battle of the bulging waistline. Even though the Dietary Supplement Health and Education Act prohibits specific health claims for substances classified as supplements, word about many products’ purported effectiveness gets around, especially when the issue is weight loss. Such claims have been attributed to chitosan, a product from the unlikely source of crustacean shells.
Mechanism of Action
Chitosan is derived from chitin, a polysaccharide found in the exoskeleton, or protective shell, of shellfish. Deacetylation of chitin results in a cationic biopolymer that is thought to bind negatively charged molecules like fatty acids and bile acids and has the property of being indigestible. Therefore, the presumptive mechanism of chitosan in combating obesity is to decrease the absorption of fat from the gastrointestinal tract, though there is conflicting evidence about the mechanism in humans.
In animal studies chitosan’s mechanism appeared to be inhibition of intestinal absorption.1,2 But in a study comparing the effects of chitosan and orlistat in 12 human volunteers, fecal fat excretion was significantly elevated in those taking orlistat but not in subjects receiving chitosan.3 This study employed a chitosan dose of 890 mg three times daily, and a standardized dietary fat content. A recent study in seven human volunteers fed a high-fat diet (> 120 g/d) also showed no increase in fecal fat excretion when the subjects were treated with 5.25 g/d of chitosan.4
There are few randomized controlled trials investigating the effectiveness of chitosan for weight reduction or cholesterol lowering.
A meta-analysis of five small Italian trials was performed in 1998; the mean difference in weight reduction between chitosan and placebo was 3.28 kg (7.2 lb), but methodological problems were identified.5
Pittler and colleagues at the University of Exeter recruited 34 volunteers (28 men, six women) to receive 1 g of chitosan (four capsules of 250 mg each) or placebo twice daily over a 28-day period.6 For inclusion, subjects needed to be between ages 18 and 60, and meet the criteria for body mass index (BMI), which were 23.9-28.5 for women and 25.0-29.9 for men. People with diabetes mellitus, intestinal disorders, concomitant medication use, or pregnancy were excluded. There was no dietary intervention; subjects were required to record their food intake in a diary.
Four patients withdrew from the study (two from each group) leaving 15 patients in each treatment arm. In both the chitosan and placebo groups, BMI was unchanged during the four-week period. Adherence to the study drug was high, with more than 90% in both groups. There were no changes in any serum measurement except for vitamin K levels, which increased significantly in the chitosan group. No serious adverse effects were reported.
In a Finnish study looking at the cholesterol-lowering effects of chitosan in 51 obese women, no weight loss advantage in the chitosan-treated women was observed.7 More recently, investigators in Poland recruited 50 women with BMI > 30 and randomized them to receive 1,500 mg of chitosan three times daily before meals. Each subject also was enrolled in a six-month program that included a 1,000 kcal diet and a group meeting every two weeks, plus recommendations about exercise and behavioral modification from a physician, psychologist, and dietitian. At the end of six months, weight loss was achieved in both the chitosan and placebo groups, but was significantly greater in the chitosan-treated patients (mean loss of 16 kg and 11 kg, respectively).8
The data in humans are scant and conflicting. The aforementioned Finnish study showed a small reduction in LDL cholesterol compared with placebo.7 In this trial, 51 women with BMI 28-35 received 1,200 mg of microcrystalline chitosan twice daily. Mean LDL decreased by 0.5 mmol (19 mg/dL), but was not statistically significant. A subset of women with BMI > 30 had a slightly more pronounced effect.
In a study of obese hypercholesterolemic subjects in Singapore, 1 g of chitosan (brand name Absorbitol) three times daily over four months showed no reduction of LDL; there was a small increase in HDL in the group receiving Absorbitol.9 In the Polish weight-loss study cited above, there was no difference in either total or LDL cholesterol between the chitosan and placebo groups.8
Animal studies suggesting the combination of chitosan with glucomannan might be more potent than chitosan alone led to a pilot study in 21 overweight subjects.10 They received 2.4 g/d of a supplement with equal content of chitosan and glucomannan. Total LDL and HDL cholesterol were lower at four weeks compared to baseline measurements. LDL cholesterol fell from a mean of 2.61 mmol/L at baseline to 2.36 mmol/L at 28 days (a decrease from 101 mg/dL to 91 mg/dL). As noted in other human studies of chitosan, fecal fat excretion did not increase.
A Japanese group showed that low molecular weight chitosan lowered serum glucose levels in a dose-dependent manner in diabetic mice.11 There also is interest in chitosan and its derivatives for use in novel drug delivery systems, wound healing, and anticoagulation.12
In a review of multiple studies, it was found that mild, transient nausea and constipation were reported in 2.6-5.4% of subjects.13 Swollen heels and wrists were observed in one study, but overall were not considered serious.7 Manufacturers recommend that fat-soluble vitamins (D, E, A, and K) should be consumed four hours before or after chitosan, on the assumption that fat excretion induced by chitosan could lead to malabsorption of these vitamins. However, the one study that measured serum levels of fat-soluble vitamins did not demonstrate any reduction of levels.6
Two manufacturers of chitosan products have been sanctioned for false claims of efficacy. The TRY-Lean Corp was warned by the Food and Drug Administration in 1999,14 and the makers of "Fat Trapper," Enforma Natural Products Inc was penalized by the Federal Trade Commision and required to pay fines and refunds in 2000.15 Despite this, products still have provocative names like "Fat Absorber," although the marketing emphasis is now on cholesterol lowering rather than weight loss.
Chitosan is marketed as a dietary supplement in the United States. It is marketed by numerous companies, usually in dosages of 500-1,000 mg per tablet. It is sometimes combined with vitamin C, as one of the animal studies showed a synergistic effect of vitamin C and chitosan with respect to inhibiting fat digestion.2 Table 1 shows a sampling of popular chitosan products.
Whether chitosan can reduce weight by itself is uncertain. The weight of the evidence seems to indicate it cannot, although the recent Polish study indicates that as part of a rigorous program of diet, exercise, and behavioral modification, chitosan may have adjunctive benefit. The data for cholesterol lowering also are mixed, although chitosan in combination with glucomannan shows some promise for this use.
Chitosan alone cannot be recommended as a weight loss agent. More study is needed to determine its role in the management of lipid disorders. As it appears safe, a trial for cholesterol lowering can be considered, perhaps for low-risk patients who are near their LDL goal. Because of its source, chitosan cannot be recommended for people who have an allergy to shellfish. v
Dr. Nardino is Program Director of the Internal Medicine Residency at the Hospital of St. Raphael and Assistant Clinical Professor of Medicine, Yale University School of Medicine, New Haven, CT.
1. Han LK, et al. Reduction in fat storage during chitin-chitosan treatment in mice fed a high-fat diet. Int J Obes Relat Metab Disord 1999;23:174-179.
2. Kanauchi O, et al. Mechanism for the inhibition of fat digestion by chitosan and for the synergistic effect of ascorbate. Biosci Biotechnol Biochem 1995;59:786-790.
3. Guerciolini R, et al. Comparative evaluation of fecal fat excretion induced by orlistat and chitosan. Obes Res 2001;9:364-367.
4. Gades MD, Stern JS. Chitosan supplementation does not affect fat absorption in healthy males fed a high-fat diet, a pilot study. Int J Obes Relat Metab Disord 2002;26:119-122.
5. Ernst E, Pittler MH. Chitosan as a treatment for body weight reduction? A meta-analysis. Perfusion 1998; 11:461.
6. Pittler MH, et al. Randomized, double-blind trial of chitosan for body weight reduction. Eur J Clin Nutr 1999;53:379-381.
7. Wuolijoki E, et al. Decrease in serum LDL cholesterol with microcrystalline chitosan. Methods Find Exp Clin Pharmacol 1999;21:357-361.
8. Zahorska-Markiewicz B, et al. Effect of chitosan in complex management of obesity. Pol Merkuriusz Lek 2002;13:129-132.
9. Ho SC, et al. In the absence of dietary surveillance, chitosan does not reduce plasma lipids or obesity in hypercholesterolaemic obese Asian subjects. Singapore Med J 2001;42:006-10.
10. Gallaher DD, et al. A glucomannan and chitosan fiber supplement decreases plasma cholesterol and increases cholesterol excretion in overweight normocholesterolemic humans. J Am Coll Nutr 2002;21:428-433.
11. Hayashi K, Ito M. Antidiabetic action of low molecular weight chitosan in genetically obese diabetic KK-Ay mice. Biol Pharm Bull 2002;25:188-192.
12. Hirano S. Chitin biotechnology applications. Biotechnol Annu Rev 1996;2:237-258.
13. Ylitalo R, et al. Cholesterol-lowering properties and safety of chitosan. Arzneimittelforschung 2002;52:1-7.
14. FDA Warning Letter to TRY-Lean, Corp., 1999.
15. Federal Tade Commission v. Enforma Natural Products, Inc., 2000.