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Chitosan supplementation and fat absorption in men and women
RESEARCH Current Research
Chitosan Supplementation and Fat Absorption in Men and Women MATTHEW D. GADES; JUDITH S. STERN, ScD
ABSTRACT Objective Chitosan is a primary ingredient in dietary weight-loss supplements. Its claimed activity is the binding and trapping of dietary fat, leading to fat excretion and weight loss without caloric restriction. We tested the fat-trapping capacity of a chitosan product in men and women. Design Participants (12 men, 12 women) were instructed to follow customized diet plans (five meals/day for 12 days). Oral charcoal markers defined two 4-day experimental periods. Two capsules were taken five times per day before each meal during the supplement period (2.5 g chitosan/day) and not during the control period. Feces were collected from day 2 to day 12. Feces from each period were pooled and analyzed for fat content. Results For men (mean⫾standard deviation⫽24.8⫾5.1 years, body mass index [BMI; calculated as kg/m2] 26.6⫾4.5) the average daily was 137⫾31 g fat and 3,256⫾624 kcal. For women (23.3⫾5.0 years, BMI 24.1⫾3.5) average daily 89⫾16 g fat and 2,110⫾195 kcal. Each two-capsule dose was consumed with 28⫾11 g fat in males and 18⫾7 g in females (range ⫽10-76 g/dose). Fecal fat excretion increased with chitosan by 1.8⫾2.4 g/day in males, P⫽.02, and did not increase with chitosan (0.0⫾1.4 g/day, P⫽.99) in females. Conclusions The fat trapped was clinically insignificant. For men, it would take more than 7 months to lose 1 pound of body fat. For women, no fat was trapped. This product, as with other similar products, fails to meet claims. J Am Diet Assoc. 2005;105:72-77.
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hitosan-based supplements are marketed and sold as weight-loss products. The central claim of these products is that they bind to or “trap” dietary fat, preventing fat absorption and causing fat excretion. This
M. D. Gades is a graduate student and J. S. Stern is a distinguished professor of Nutrition and Internal Medicine, Department of Nutrition, University of California Davis, Davis, CA. Address correspondence to: Judith S. Stern, ScD, Department of Nutrition, University of California Davis, 3150B Meyer Hall, Davis, CA 95616. E-mail: jsstern@ ucdavis.edu Copyright © 2005 by the American Dietetic Association. 0002-8223/05/10501-0013$30.00/0 doi: 10.1016/j.jada.2004.10.004
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claim may be based, in part, on the fact that chitosan has fat-binding properties in vitro (1,2) and increases fecal fat excretion in rats and mice when they are fed high amounts (3% to 15% wt/wt of the diet) (3,4). However, there is little evidence to support the claims that, in humans, chitosan causes clinically significant fat malabsorption and that it subsequently leads to weight loss. After passage of the Dietary Supplement Health and Education Act of 1994, dietary supplements are no longer subject to premarket approval by the US Food and Drug Administration. While the Act does prohibit claims that a dietary supplement can diagnose, prevent, mitigate, treat, or cure a specific disease (unless approved), it does not prohibit claims that a supplement can alter body structure or function if such claims are truthful and can be substantiated (5). However, many supplements sold today have structure and function claims that cannot be substantiated. A study by the Federal Trade Commission in 2002 reported that a marked disparity between the marketing or use claims for dietary supplements and the available peer-reviewed scientific evidence to support them is common (6). In the case of one chitosan product, the disparity between claims and evidence was egregious enough that legal action was taken against the manufacturer by the Federal Trade Commission (7). Despite the lack of supporting evidence, and some evidence to the contrary, chitosan-based dietary products continue to flourish and be touted as safe natural products to “trap the fat.” The earliest studies evaluating the effects of chitosan in humans, reviewed by Ernst and colleagues, reported enhanced weight loss, but these studies are considered seriously flawed and their results unreliable, as both we and Ernst noted (8,9). In those studies, an energyrestricted diet was used and the trapping of even 100% of the fat in their diets could not approach the energetic deficit required to explain the weight loss observed. Two other studies found no effect of chitosan on weight loss (10,11). Fecal fat excretion is a more direct measure of the effects of chitosan because any fat not absorbed must be excreted. Three studies, including two performed by our laboratory, found no effect or clinically insignificant effect of chitosan on fecal fat excretion (8,12,13). The largest reported effect of chitosan on fecal fat excretion in humans to date is a mean increase of 3.63 g (⫾4.06 g standard deviation [SD]) per day in 24 subjects taking 6.3 g chitosan per day (14). Even this amount is not clinically significant for substantial weight loss, and it is far less than what most consumers would expect from a product called “fat trapper.” Our purpose in this study was to address the general
© 2005 by the American Dietetic Association
question of chitosan’s efficacy by testing the effect of a particular chitosan product on fecal fat excretion in men and women. The studies to date measuring fecal fat excretion with chitosan are limited by the fact that they test only specific formulations, and that when women have been tested, their results are combined with men. Although there may be no physiological basis to expect a difference in effect between men and women, we have added women. Women are as likely or more likely than men to purchase and use weight-loss supplements. It is therefore desirable to test the product in both men and women. Women generally require a lower energy intake than men. By adding women, we included subjects with lower total fat intakes because we designed the diets to contain the same percent of energy from fat as used in men. We also used equal numbers of men and women and analyzed the results to look for sex differences. Chitosan supplement formulations are similar but not identical. Chitosan itself is the product of chemical deacetylation of the raw material chitin, and the degree of deacetylation in the product varies with reaction conditions (15). The degree of deacetylation and the molecular weight of the chitosan polymer impact the physical properties of chitosan including viscosity in solution and fatbinding capacity (15,16). In addition, chitosan may be combined with one or more compounds designed to enhance fat-binding activity. Ascorbic acid and fiber are examples (17,18). The product we tested contains both malic acid and psyllium. It therefore has the potential to perform differently than those formulations previously tested. METHODS The methods we used in this study are based on those used in our previously published studies (8,12). Our research protocol was approved by Human Subjects Review Committee at the University of California, Davis. To recruit participants, flyers calling for healthy volunteers between 21 and 40 years of age and briefly describing the nature of the study were posted around the University of California, Davis campus. Sixty-eight people responded by either e-mail or telephone. Additional detailed information about the study was given to these respondents and their height, weight, age, and self-reported activity level information were obtained. Exclusion criteria included food allergies and sensitivities; gastrointestinal, liver, eating, or immune disorders; type 1 or type 2 diabetes; being on lipid-lowering drugs; having a body mass index (BMI, calculated as kg/m2) ⬍19, and being unable to perform any of the tasks required of subjects. Of the 68 respondents, 39 were interviewed by one of the investigators in the presence of a registered dietitian. Thirtytwo of those interviewed were approved to participate; of those, 27 actually began the study (13 males, 14 females). A 24-hour dietary recall was used for both subjective and objective evaluations in the interviews. Selection criteria included interviewees having meal patterns, food choice selections, and fat content of their customary diet similar to that used in the study diet. Total calculated energy intake to maintain weight had to exceed 2,400 kcal/day in men and 1,800 kcal/day in women to ensure that at the necessary level of fat intake the percent of energy from fat
Figure 1. Experimental design of a 12-day study of subjects on a high-fat diet taking chitosan. The control period lasted days 2-6. Chitosan was taken daily from day 6-10. The appearance of charcoal in the feces separated the control from the chitosan period.
would not be excessive based on current health recommendations. The study lasted 12 days (see Figure 1). The meal plan was followed every day. Food was provided to each volunteer. All feces were collected from days 2 through 12 using a commode specimen collection system (CMS/ Fisher Healthcare, Houston, TX) and specimen collection bags. On days 2, 6, and 10, subjects drank 100 mL of a 10% activated charcoal solution (Actidose-Aqua, Paddock Labs, Minneapolis, MN) before breakfast. This charcoal served as a fecal marker, which, in addition to the time and date recorded on each sample, permitted the assignment of feces to the control and chitosan 4-day pools for subsequent analysis. On days 1, 6, and 12 volunteers were weighed, without shoes and wearing light clothing, on a digital scale. Each person was weighed at approximately the same time of day on each occasion. On days 6, 7, 8, and 9, volunteers consumed two capsules of Fat Magnet (Natural Balance Inc, Castle Rock, CO), taken as directed before each of the five meals on each day. Each two-capsule dose contained 500 mg chitosan, 200 mg psyllium husk, 40 mg malic acid, and 20 mg aloe vera. Total intake per day was 10 capsules of Fat Magnet for each subject, a total of 2.5 g chitosan per day. The fat content of the control and chitosan fecal pools were analyzed using the gravimetric modification of the Van de Kamer method (19,20). This analysis was independently performed by the National Institutes of Health-funded Clinical Nutrition Research Unit Assessment Laboratory at the University of California, Davis. Diet plans were designed individually for each volunteer. All diet plans consisted of five meals per day, each of which was constructed to contain at least 15 g fat per meal in men and at least 10 g fat per meal in women. Total daily energy intake for each diet was set to that required for maintenance for each person, based on height, weight, age, and activity level using the Harris and Benedict equations (21). Food items were selected by the volunteers from a list of 230 food items that were available at a local supermarket. Nutrition information used for each food item was taken from the food label or from a standard reference for those without a corresponding food label (22). Three unique daily diet plans were designed for each subject and cycled four times during the
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Table 1. Anthropometric data for men and women participating in a study of the fat-trapping capacity of chitosana Men (nⴝ12) b
Age (y) BMIc Height (cm) Body weight day 1 (kg) Body weight day 6 (kg) Body weight day 12 (kg)
Women (nⴝ12)
MeanⴞSD
Range
MeanⴞSD
Range
24.8⫾5.1 26.6⫾4.5 180.1⫾9.8* 85.4⫾10.1* 85.4⫾10* 85.0⫾10.3*
21-36 22.7-36.1 166.7-197.3 74.9-108.4 74.5-108.8 72.7-109.2
23.3⫾5 24.2⫾3.4 166.7⫾5.4 67.3⫾9.4 67.0⫾9.8 67.0⫾9.9
21-39 20-31 156.1-176 55.6-83.1 55.2-84.5 55.9-85.3
a
Chitosan supplements were taken daily on days 6, 7, 8, and 9 of this study. SD⫽standard deviation. c BMI is calculated as kg/m2. *P⬍.05; men vs women. b
study. Volunteers were instructed that they could eat additional servings of approved food items with any of the five meals if desired. Total energy intake was thus not restricted. Volunteers were instructed not to take vitamins, minerals, or other dietary supplements during the study. Participants recorded daily fecal collection times and noted the presence or absence of charcoal marker in the feces. Daily diet sheets listed the required foods grouped by meal and the macronutrient and energy content of each food to facilitate food substitution if necessary. Next to food items and chitosan doses were spaces to record the time at which each was consumed. Additional spaces were also provided to record additional food items and the time that they were consumed. At the bottom of each sheet was a statement that was signed by each volunteer at the end of each day. The statement read, “I attest that this is an accurate and complete representation of all foods I consumed on this the [blank] day of [blank], 2003, Signature: [blank].” Food intake analysis was based on the completed daily diet sheets that recorded the foods actually eaten by each subject. The contribution of the chitosan supplement toward daily fiber intake (2.5 g/day chitosan and 1.0 g/day psyllium) is not included in the dietary intake results. For meal analysis, a meal is defined as an episode of eating with an intermeal interval of at least 30 minutes. During the supplement period, a sixth meal was consumed on 10 occasions overall (in addition to the five meals per day⫻24 subjects⫻4 days⫽480 meals that were planned). No extra capsules were taken with any of those 10 meals, five of which contained fat. Because the purpose of this study was to measure the fat not absorbed in association with chitosan, those 10 meals are not included in the meal analysis, but they are included in the daily totals. During the supplement period, one female subject omitted one meal, as well as the chitosan dose that was to have gone with it. Three subjects that began the study do not appear in any of the results presented here. One male subject did not complete the study protocol due to unrelated illness. One female subject collected too few fecal samples to distinguish the two experimental periods. In a second female subject, the appearance of the fecal charcoal marker was too indistinct to distinguish the two experi-
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mental periods. Feces from these three subjects were not analyzed and none of their data are included. Data were evaluated using Student’s paired t test to compare the baseline and treatment periods. To compare men and women, Student’s unpaired t test was used. To compare body weights at three time points, repeated measures one-way analysis of variance was used. Statistical analyses were performed with Graphpad Prism 3.0 (Graphpad Software Inc, San Diego, CA). Values are expressed as mean⫾SD. A P value ⱕ.05 was considered statistically significant. RESULTS Characteristics of the 12 men and 12 women subjects are shown in Table 1. The men were taller and heavier, but BMI and age were not different from women. The combined mean BMI (⫾SD) was 25.4⫾4.1 and combined mean age (⫾SD) was 24.0⫾5.0 years. Weight did not change during the course of the study in men or women. In both men and women, food intake did not differ between the control and supplement periods (Table 2). Men ate more than women did, but the macronutrient composition of their diets was the same for men as for women. The average diet composition was 15% energy from protein, 38% from fat, and 47% from carbohydrates in men and 15% from protein, 38% from fat, and 48% from carbohydrates for women. When scaled by total energy intake, cholesterol intake was the same (men: 0.145⫾.092 mg/kcal, women: 0.126⫾.075 mg/kcal), and fiber intake not including the dietary supplement was the same (men: 7.2⫾1.9 mg/kcal, women: 7.3⫾2.7 mg/kcal). The average nutrient composition of each meal taken with chitosan during the supplement period is listed in Table 2. The fat intake per dose of chitosan ranged from 10 to 76 g in men, and from 10 to 60 g in women. Of the 240 meals eaten with chitosan by men, only two had less than 15 g of fat (10 g and 14 g). In women, none of the 239 meals eaten with chitosan had less than 10 g fat. Total fecal mass was increased with chitosan in men but not in women (Figure 2A). Daily fecal mass in men was 170⫾38 g (control) and 234⫾50 g (chitosan), a difference of 63⫾44 g/day (P⬍.005). In women, daily fecal mass was 114⫾31 g (control) and 137⫾37 g (chitosan), a difference of 23⫾41 g/day (P⫽.08). The effect of chitosan on
Table 2. Daily dietary intakes of energy, total fat, saturated fat (sat fat), cholesterol (chol), and fiber (not including the supplement) for 12 men and 12 women without (control) and with chitosan for the 4-day control and 4-day chitosan treatment periods as well as per each dose of chitosan n
Energy (MJ)
Energy (kcal)
Total fat (g)
Sat fat (g)
Chol (mg)
Fiber (g)
4™™™™™™™™™™™™™™™™™™™™™™™™™™ mean⫾standard deviation ™™™™™™™™™™™™™™™™™™™™™™™™™™3 Men Per daya Per dayb Per doseb Women Per daya Per day Per doseb
Control Chitosan Chitosan
48 48 240
13.57⫾2.47 13.67⫾2.77 2.72⫾1.00
3,244⫾591 3,269⫾661 650⫾238
137⫾30 138⫾32 27.6⫾11
51⫾13 51⫾13 10.2⫾5.3
458⫾297 464⫾270 92.7⫾124
23⫾8 25⫾8 4.6⫾3.9
Control Chitosan Chitosan
48 48 239
8.83⫾0.82 8.82⫾0.82 1.74⫾0.60
2,112⫾197 2,108⫾196 417⫾143
89⫾16 88⫾15 17.6⫾7.1
36⫾11 36⫾11 7.1⫾4.4
275⫾173 264⫾164 52.6⫾72
16⫾6 17⫾6 2.9⫾2.8
a
The n per day represent the 4 days of either control or chitosan period multiplied by 12 subjects per sex for 48 individual data points for men and for women. The n per dose represent 4 days of either control or chitosan period multiplied by 12 subjects per sex and by 5 meals per day for 240 individual data points except in women where one dose was missed by one subject on one occasion for a total of 239.
b
fecal fat excretion was different between men and women (P⫽.03) (Figure 2B). In men, daily fecal fat excretion was 5.0⫾1.5 g (control) and 6.9⫾2.7 g (chitosan), a difference of 1.8⫾2.4 g/day (P⫽.02). This very small fecal fat increase in men was statistically significant but far too small to be clinically significant. In women daily fecal fat excretion was 3.7⫾2.0 g (control) and 3.7⫾1.8 g (chitosan), a difference of 0.0⫾1.4 g/day (P⫽.99). DISCUSSION The results we report with this particular chitosan supplement are similar to those that have been reported previously for other chitosan supplements. Four other published studies measured the change in fecal fat excretion in people taking a chitosan supplement. Guerciolini and colleagues (13) gave 2.67 g chitosan per day to seven men and five women and measured a nonsignificant increase of 0.27 g fecal fat per day (n⫽12) (13). In our first study we gave 5.25 g chitosan per day (Fat Trapper, Enforma Natural Products) to seven men and found a 0.1 g/day nonsignificant decrease in fecal fat excretion (8). In our second study, we gave 4.5 g of chitosan per day (Absorbitol, Natrol) to 15 men and found an increase in fecal fat excretion of 1.1 g/day (12). Aranda and colleagues (14) gave 6.3 g of chitosan per day to 16 men and eight women and reported a 3.63⫾4.06 g/day increase in fecal fat excretion (n⫽24). In this study, 2.5 g chitosan/ day increased the fecal excretion of fat by 1.8 g/day in 12 men and 0.0 g/day in 12 women. When we combine the data for men and women in this study we find an overall fecal fat increase of 0.96 g/day (n⫽24, P⫽.04). However, it would be inappropriate to combine fecal fat results because a sex effect was observed. To control for the differing doses of chitosan used in these studies, in vivo fat-binding capacities may be compared. When the grams of fat bound per gram of chitosan consumed are calculated, the group of men in the current study gives the highest value of any study, with 0.72 g fat bound per gram of chitosan consumed. Second rank is Aranda and colleagues in with 0.58 g/g (14). Third is Gades and Stern (12) with 0.24 g/g. Fourth is Guerciolini
and colleagues (13) with 0.10 g/g. Fifth is the group of women in the current study with 0.02 g/g and last is Gades and Stern (8) with ⫺0.02 g/g. There is an overall agreement between these studies even though each used a different product, except Aranda and colleagues’ (14) and Gades and Stern’s (12), which used the same product. One difficulty in comparing these results between studies is that in Aranda and colleagues (14), the fecal collection method was a complete collection for only 48-hour periods. Fecal collection is an unpleasant task that when done only acutely will likely promote fecal retention and constipation. This seriously hinders the reliability of any data based on acute fecal collections in some subjects. A better alternative was used by Guerciolini and colleagues (13), who collected for 7-day periods and used a crossover design. The longer collection period ensures that any disruption of bowel movements in the first days has time to resolve. We collected continuously for 11 days and used oral charcoal, which appeared in the feces to demark the 4-day experimental periods. This method has the added benefit that the boundaries of the experimental periods are better defined, increasing the reliability of fecal fat excretion data in studies using that method. In our study, although the effect of chitosan on fecal fat excretion in men was small, it is unclear why women differed, with, on average, no effect at all. We designed the diets for participants so that each meal would have a load of fat that would more than saturate the chitosan dose based on available in vitro and in vivo published results. Specifically, Nauss and colleagues (1) reported that chitosan is able to bind to in vitro 4 to 5 g lipids per gram of chitosan. Based on the studies of Kanauchi and colleagues (17), the maximum fat-binding capacity of chitosan when given in massive doses to rats was 3.4 g/g. Although the amount of fat consumed per dose of chitosan in our study was less in women than in men, it was still high in women, with an average of 18 g and a minimum of 10 g fat per meal. Each meal, therefore, had an average of 36 and a minimum of 20 g fat per gram of chitosan in women. Fat was thus present in the meals at a more than
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Figure 2. Fecal mass and fecal fat excretion in 12 men and 12 women without and with chitosan. (A) Fecal mass in grams per day. (B) Fecal fat excretion in grams per day. Men and women are grouped separately. Mean⫾standard deviation for the 4-day control and chitosan treatment periods are indicated with bars; intra-subject differences between periods are indicated with scattergrams having bars for means. *P⬍.05 control vs chitosan.
fivefold excess of the theoretical binding capacity of the chitosan dose even in women. In discussing why, in our previous work, we found no effect of chitosan on fecal fat excretion, Aranda and colleagues (14) suggest that the fat intake was too high, that it might have “overwhelmed” the fiber, rendering it inactive. This statement appears to contradict what has been well established concerning the kinetics of substrate binding in general (23) and has no support from either in vivo or in vitro chitosan studies (16). In addition, given the fact that the American diet is typically high in fat, such an assertion calls into question whether this product could ever work for those likely to buy it. Based on our findings, it is not likely that the amount of fat present with each dose of chitosan was either too much or too little or that it contributed to the difference between men and women. Although nonzero in men, the impact of this chitosan supplement on fat excretion is clinically insignificant. If the small amount of fat excreted in the feces was not simply compensated for with a small increase in food intake over time, and if that net energy loss led to fat loss, it would take more than 7 months to lose 1 lb of body fat due to fat malabsorption in men taking chitosan. No amount of time could lead to any body fat loss in women taking chitosan at the rate measured here.
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1.8 g fat malabsorbed⫻9 kcal ⁄ g fat ⫽16.2 kcal malabsorbed ⁄ day (3.500 kcal ⁄ lb bodyfat) ⁄ (16.2 kcal ⁄ day) ⫽216 days per pound fat in men CONCLUSIONS This study reinforces the importance of testing dietary supplements in people in order to substantiate claims. The claims made for chitosan and fat malabsorption have been based primarily on combining chitosan in a buffer and fat and chitosan in a beaker, stirring the liquids, and measuring clumping of fat. This has been interpreted to be “malabsorption” in the gastrointestinal tract. Studies done in rodents, which document fat malabsorption, give the animals huge doses of chitosan— up to 4.5% by weight of the diet. In contrast, the small amount of fat malabsorbed in humans with chitosan was clinically insignificant in males (1.8 g/day) and nonexistent in females. The authors now have evidence using three different commercial products [this study; (8,12)] that the claims that chitosan is a fat-trapping weight-loss aid are not merely unsubstantiated, they are false.
This work was supported, in part, by a gift from the Consumer Justice Center, Laguna Nigel, CA and the UC Davis Clinical Nutrition Research Unit, National Institutes of Health DK35747 Nutritional Assessment Laboratory. References 1. Nauss JL, Thompson JL, Nagyvary J. The binding of micellar lipids to chitosan. Lipids. 1983;18:714-719. 2. Muzzarelli RAA. Interactions of chitin, chitosan, Nlauryl chitosan and N-dimethylaminopropyl chitosan with olive oil. Carbohyd Polym. 2000;43:263-268. 3. Deuchi K, Kanauchi O, Imasato Y, Kobayashi E. Decreasing effect of chitosan on the apparent fat digestibility by rats fed on a high-fat diet. Biosci Biotechnol Biochem. 1994;58:1613-1616. 4. Han LK, Kimura Y, Okuda H. 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. 5. US Food and Drug Administration. Dietary Supplement Health And Education Act of 1994. Available at: http://vm.cfsan.fda.gov/⬃dms/dietsupp.html. Accessed February 26, 2004. 6. Federal Trade Commission. Weight-loss advertising: An analysis of current trends. Federal Trade Commission. Available at: http://www.ftc.gov/bcp/reports/ weightloss.pdf. Accessed January 26, 2003. 7. US District Court. FTC v. Enforma Natural Products, Inc., Andrew Grey, and Fred Zinos. Available at: http://www.ftc.gov/os/2000/04/enformazinos.htm. Accessed June 19, 2000. 8. Gades MD, Stern JS. Chitosan supplementation does not affect fat absorption in healthy males fed a highfat diet, a pilot study. Int J Obes Relat Metab Disord. 2002;26:119-122. 9. Ernst E, Pittler M. Chitosan as a treatment for body weight reduction? A meta-analysis. Perfusion. 1998; 11:461-465. 10. Pittler MH, Abbot NC, Harkness EF, Ernst E. Randomized, double-blind trial of chitosan for body weight reduction. Eur J Clin Nutr. 1999;53:379-381. 11. Ho SC, Tai ES, Eng PH, Tan CE, Fok AC. In the absence of dietary surveillance, chitosan does not re-
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duce plasma lipids or obesity in hypercholesterolaemic obese Asian subjects. Singapore Med J. 2001;42:6-10. Gades MD, Stern JS. Chitosan supplementation and fecal fat excretion in men. Obes Res. 2003;11:683-688. Guerciolini R, Radu-Radulescu L, Boldrin M, Dallas J, Moore R. Comparative evaluation of fecal fat excretion induced by orlistat and chitosan. Obes Res. 2001;9:364-367. Barroso Aranda J, Contreras F, Bagchi D, Preuss HG. Efficacy of a novel chitosan formulation on fecal fat excretion: A double-blind, crossover, placebo-controlled study. J Med. 2002;33:209-225. Prashanth KVH. Solid state structure of chitosan prepared under different N-deacetylating conditions. Carbohyd Polym. 2002;50:27-33. No HK, Lee KS, Meyers SP. Correlations between physicochemical characteristics and binding capacities of chitosan products. J Food Sci. 2000;55:11341137. Kanauchi O, Deuchi K, Imasato Y, Shizukuishi M, Kobayashi E. Mechanism for the inhibition of fat digestion by chitosan and for the synergistic effect of ascorbate. Biosci Biotechnol Biochem. 1995;59:786790. Gallaher DD, Gallaher CM, Mahrt GJ, Carr TP, Hollingshead CH, Hesslink R Jr, Wise J. 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. Seligson D. Standard Methods of Clinical Chemistry. New York, NY: Academic Press; 1958. Braddock LI, Fleisher DR, Barbero GJ. A physical chemical study of the van de Kamer method for fecal fat analysis. Gastroenterology. 1968;55:165-172. Frances J, Zeman DMN. Applications of Clinical Nutrition. Englewoods Cliffs, NJ: Prentice Hall; 1988. Bowes AP, Pennington JAT, Church HN. Bose & Church’s Food Values of Portions Commonly Used. 17th ed. Philadelphia, PA: Lippincott; 1998. Segel IH. Enzyme Kinetics. Wiley Classics Library edition. New York, NY: Wiley-Interscience; 1993.
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Chitosan Supplementation and Fat Absorption in Men and Women MATTHEW D. GADES; JUDITH S. STERN, ScD
ABSTRACT Objective Chitosan is a primary ingredient in dietary weight-loss supplements. Its claimed activity is the binding and trapping of dietary fat, leading to fat excretion and weight loss without caloric restriction. We tested the fat-trapping capacity of a chitosan product in men and women. Design Participants (12 men, 12 women) were instructed to follow customized diet plans (five meals/day for 12 days). Oral charcoal markers defined two 4-day experimental periods. Two capsules were taken five times per day before each meal during the supplement period (2.5 g chitosan/day) and not during the control period. Feces were collected from day 2 to day 12. Feces from each period were pooled and analyzed for fat content. Results For men (mean⫾standard deviation⫽24.8⫾5.1 years, body mass index [BMI; calculated as kg/m2] 26.6⫾4.5) the average daily was 137⫾31 g fat and 3,256⫾624 kcal. For women (23.3⫾5.0 years, BMI 24.1⫾3.5) average daily 89⫾16 g fat and 2,110⫾195 kcal. Each two-capsule dose was consumed with 28⫾11 g fat in males and 18⫾7 g in females (range ⫽10-76 g/dose). Fecal fat excretion increased with chitosan by 1.8⫾2.4 g/day in males, P⫽.02, and did not increase with chitosan (0.0⫾1.4 g/day, P⫽.99) in females. Conclusions The fat trapped was clinically insignificant. For men, it would take more than 7 months to lose 1 pound of body fat. For women, no fat was trapped. This product, as with other similar products, fails to meet claims. J Am Diet Assoc. 2005;105:72-77.
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hitosan-based supplements are marketed and sold as weight-loss products. The central claim of these products is that they bind to or “trap” dietary fat, preventing fat absorption and causing fat excretion. This
M. D. Gades is a graduate student and J. S. Stern is a distinguished professor of Nutrition and Internal Medicine, Department of Nutrition, University of California Davis, Davis, CA. Address correspondence to: Judith S. Stern, ScD, Department of Nutrition, University of California Davis, 3150B Meyer Hall, Davis, CA 95616. E-mail: jsstern@ ucdavis.edu Copyright © 2005 by the American Dietetic Association. 0002-8223/05/10501-0013$30.00/0 doi: 10.1016/j.jada.2004.10.004
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claim may be based, in part, on the fact that chitosan has fat-binding properties in vitro (1,2) and increases fecal fat excretion in rats and mice when they are fed high amounts (3% to 15% wt/wt of the diet) (3,4). However, there is little evidence to support the claims that, in humans, chitosan causes clinically significant fat malabsorption and that it subsequently leads to weight loss. After passage of the Dietary Supplement Health and Education Act of 1994, dietary supplements are no longer subject to premarket approval by the US Food and Drug Administration. While the Act does prohibit claims that a dietary supplement can diagnose, prevent, mitigate, treat, or cure a specific disease (unless approved), it does not prohibit claims that a supplement can alter body structure or function if such claims are truthful and can be substantiated (5). However, many supplements sold today have structure and function claims that cannot be substantiated. A study by the Federal Trade Commission in 2002 reported that a marked disparity between the marketing or use claims for dietary supplements and the available peer-reviewed scientific evidence to support them is common (6). In the case of one chitosan product, the disparity between claims and evidence was egregious enough that legal action was taken against the manufacturer by the Federal Trade Commission (7). Despite the lack of supporting evidence, and some evidence to the contrary, chitosan-based dietary products continue to flourish and be touted as safe natural products to “trap the fat.” The earliest studies evaluating the effects of chitosan in humans, reviewed by Ernst and colleagues, reported enhanced weight loss, but these studies are considered seriously flawed and their results unreliable, as both we and Ernst noted (8,9). In those studies, an energyrestricted diet was used and the trapping of even 100% of the fat in their diets could not approach the energetic deficit required to explain the weight loss observed. Two other studies found no effect of chitosan on weight loss (10,11). Fecal fat excretion is a more direct measure of the effects of chitosan because any fat not absorbed must be excreted. Three studies, including two performed by our laboratory, found no effect or clinically insignificant effect of chitosan on fecal fat excretion (8,12,13). The largest reported effect of chitosan on fecal fat excretion in humans to date is a mean increase of 3.63 g (⫾4.06 g standard deviation [SD]) per day in 24 subjects taking 6.3 g chitosan per day (14). Even this amount is not clinically significant for substantial weight loss, and it is far less than what most consumers would expect from a product called “fat trapper.” Our purpose in this study was to address the general
© 2005 by the American Dietetic Association
question of chitosan’s efficacy by testing the effect of a particular chitosan product on fecal fat excretion in men and women. The studies to date measuring fecal fat excretion with chitosan are limited by the fact that they test only specific formulations, and that when women have been tested, their results are combined with men. Although there may be no physiological basis to expect a difference in effect between men and women, we have added women. Women are as likely or more likely than men to purchase and use weight-loss supplements. It is therefore desirable to test the product in both men and women. Women generally require a lower energy intake than men. By adding women, we included subjects with lower total fat intakes because we designed the diets to contain the same percent of energy from fat as used in men. We also used equal numbers of men and women and analyzed the results to look for sex differences. Chitosan supplement formulations are similar but not identical. Chitosan itself is the product of chemical deacetylation of the raw material chitin, and the degree of deacetylation in the product varies with reaction conditions (15). The degree of deacetylation and the molecular weight of the chitosan polymer impact the physical properties of chitosan including viscosity in solution and fatbinding capacity (15,16). In addition, chitosan may be combined with one or more compounds designed to enhance fat-binding activity. Ascorbic acid and fiber are examples (17,18). The product we tested contains both malic acid and psyllium. It therefore has the potential to perform differently than those formulations previously tested. METHODS The methods we used in this study are based on those used in our previously published studies (8,12). Our research protocol was approved by Human Subjects Review Committee at the University of California, Davis. To recruit participants, flyers calling for healthy volunteers between 21 and 40 years of age and briefly describing the nature of the study were posted around the University of California, Davis campus. Sixty-eight people responded by either e-mail or telephone. Additional detailed information about the study was given to these respondents and their height, weight, age, and self-reported activity level information were obtained. Exclusion criteria included food allergies and sensitivities; gastrointestinal, liver, eating, or immune disorders; type 1 or type 2 diabetes; being on lipid-lowering drugs; having a body mass index (BMI, calculated as kg/m2) ⬍19, and being unable to perform any of the tasks required of subjects. Of the 68 respondents, 39 were interviewed by one of the investigators in the presence of a registered dietitian. Thirtytwo of those interviewed were approved to participate; of those, 27 actually began the study (13 males, 14 females). A 24-hour dietary recall was used for both subjective and objective evaluations in the interviews. Selection criteria included interviewees having meal patterns, food choice selections, and fat content of their customary diet similar to that used in the study diet. Total calculated energy intake to maintain weight had to exceed 2,400 kcal/day in men and 1,800 kcal/day in women to ensure that at the necessary level of fat intake the percent of energy from fat
Figure 1. Experimental design of a 12-day study of subjects on a high-fat diet taking chitosan. The control period lasted days 2-6. Chitosan was taken daily from day 6-10. The appearance of charcoal in the feces separated the control from the chitosan period.
would not be excessive based on current health recommendations. The study lasted 12 days (see Figure 1). The meal plan was followed every day. Food was provided to each volunteer. All feces were collected from days 2 through 12 using a commode specimen collection system (CMS/ Fisher Healthcare, Houston, TX) and specimen collection bags. On days 2, 6, and 10, subjects drank 100 mL of a 10% activated charcoal solution (Actidose-Aqua, Paddock Labs, Minneapolis, MN) before breakfast. This charcoal served as a fecal marker, which, in addition to the time and date recorded on each sample, permitted the assignment of feces to the control and chitosan 4-day pools for subsequent analysis. On days 1, 6, and 12 volunteers were weighed, without shoes and wearing light clothing, on a digital scale. Each person was weighed at approximately the same time of day on each occasion. On days 6, 7, 8, and 9, volunteers consumed two capsules of Fat Magnet (Natural Balance Inc, Castle Rock, CO), taken as directed before each of the five meals on each day. Each two-capsule dose contained 500 mg chitosan, 200 mg psyllium husk, 40 mg malic acid, and 20 mg aloe vera. Total intake per day was 10 capsules of Fat Magnet for each subject, a total of 2.5 g chitosan per day. The fat content of the control and chitosan fecal pools were analyzed using the gravimetric modification of the Van de Kamer method (19,20). This analysis was independently performed by the National Institutes of Health-funded Clinical Nutrition Research Unit Assessment Laboratory at the University of California, Davis. Diet plans were designed individually for each volunteer. All diet plans consisted of five meals per day, each of which was constructed to contain at least 15 g fat per meal in men and at least 10 g fat per meal in women. Total daily energy intake for each diet was set to that required for maintenance for each person, based on height, weight, age, and activity level using the Harris and Benedict equations (21). Food items were selected by the volunteers from a list of 230 food items that were available at a local supermarket. Nutrition information used for each food item was taken from the food label or from a standard reference for those without a corresponding food label (22). Three unique daily diet plans were designed for each subject and cycled four times during the
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Table 1. Anthropometric data for men and women participating in a study of the fat-trapping capacity of chitosana Men (nⴝ12) b
Age (y) BMIc Height (cm) Body weight day 1 (kg) Body weight day 6 (kg) Body weight day 12 (kg)
Women (nⴝ12)
MeanⴞSD
Range
MeanⴞSD
Range
24.8⫾5.1 26.6⫾4.5 180.1⫾9.8* 85.4⫾10.1* 85.4⫾10* 85.0⫾10.3*
21-36 22.7-36.1 166.7-197.3 74.9-108.4 74.5-108.8 72.7-109.2
23.3⫾5 24.2⫾3.4 166.7⫾5.4 67.3⫾9.4 67.0⫾9.8 67.0⫾9.9
21-39 20-31 156.1-176 55.6-83.1 55.2-84.5 55.9-85.3
a
Chitosan supplements were taken daily on days 6, 7, 8, and 9 of this study. SD⫽standard deviation. c BMI is calculated as kg/m2. *P⬍.05; men vs women. b
study. Volunteers were instructed that they could eat additional servings of approved food items with any of the five meals if desired. Total energy intake was thus not restricted. Volunteers were instructed not to take vitamins, minerals, or other dietary supplements during the study. Participants recorded daily fecal collection times and noted the presence or absence of charcoal marker in the feces. Daily diet sheets listed the required foods grouped by meal and the macronutrient and energy content of each food to facilitate food substitution if necessary. Next to food items and chitosan doses were spaces to record the time at which each was consumed. Additional spaces were also provided to record additional food items and the time that they were consumed. At the bottom of each sheet was a statement that was signed by each volunteer at the end of each day. The statement read, “I attest that this is an accurate and complete representation of all foods I consumed on this the [blank] day of [blank], 2003, Signature: [blank].” Food intake analysis was based on the completed daily diet sheets that recorded the foods actually eaten by each subject. The contribution of the chitosan supplement toward daily fiber intake (2.5 g/day chitosan and 1.0 g/day psyllium) is not included in the dietary intake results. For meal analysis, a meal is defined as an episode of eating with an intermeal interval of at least 30 minutes. During the supplement period, a sixth meal was consumed on 10 occasions overall (in addition to the five meals per day⫻24 subjects⫻4 days⫽480 meals that were planned). No extra capsules were taken with any of those 10 meals, five of which contained fat. Because the purpose of this study was to measure the fat not absorbed in association with chitosan, those 10 meals are not included in the meal analysis, but they are included in the daily totals. During the supplement period, one female subject omitted one meal, as well as the chitosan dose that was to have gone with it. Three subjects that began the study do not appear in any of the results presented here. One male subject did not complete the study protocol due to unrelated illness. One female subject collected too few fecal samples to distinguish the two experimental periods. In a second female subject, the appearance of the fecal charcoal marker was too indistinct to distinguish the two experi-
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mental periods. Feces from these three subjects were not analyzed and none of their data are included. Data were evaluated using Student’s paired t test to compare the baseline and treatment periods. To compare men and women, Student’s unpaired t test was used. To compare body weights at three time points, repeated measures one-way analysis of variance was used. Statistical analyses were performed with Graphpad Prism 3.0 (Graphpad Software Inc, San Diego, CA). Values are expressed as mean⫾SD. A P value ⱕ.05 was considered statistically significant. RESULTS Characteristics of the 12 men and 12 women subjects are shown in Table 1. The men were taller and heavier, but BMI and age were not different from women. The combined mean BMI (⫾SD) was 25.4⫾4.1 and combined mean age (⫾SD) was 24.0⫾5.0 years. Weight did not change during the course of the study in men or women. In both men and women, food intake did not differ between the control and supplement periods (Table 2). Men ate more than women did, but the macronutrient composition of their diets was the same for men as for women. The average diet composition was 15% energy from protein, 38% from fat, and 47% from carbohydrates in men and 15% from protein, 38% from fat, and 48% from carbohydrates for women. When scaled by total energy intake, cholesterol intake was the same (men: 0.145⫾.092 mg/kcal, women: 0.126⫾.075 mg/kcal), and fiber intake not including the dietary supplement was the same (men: 7.2⫾1.9 mg/kcal, women: 7.3⫾2.7 mg/kcal). The average nutrient composition of each meal taken with chitosan during the supplement period is listed in Table 2. The fat intake per dose of chitosan ranged from 10 to 76 g in men, and from 10 to 60 g in women. Of the 240 meals eaten with chitosan by men, only two had less than 15 g of fat (10 g and 14 g). In women, none of the 239 meals eaten with chitosan had less than 10 g fat. Total fecal mass was increased with chitosan in men but not in women (Figure 2A). Daily fecal mass in men was 170⫾38 g (control) and 234⫾50 g (chitosan), a difference of 63⫾44 g/day (P⬍.005). In women, daily fecal mass was 114⫾31 g (control) and 137⫾37 g (chitosan), a difference of 23⫾41 g/day (P⫽.08). The effect of chitosan on
Table 2. Daily dietary intakes of energy, total fat, saturated fat (sat fat), cholesterol (chol), and fiber (not including the supplement) for 12 men and 12 women without (control) and with chitosan for the 4-day control and 4-day chitosan treatment periods as well as per each dose of chitosan n
Energy (MJ)
Energy (kcal)
Total fat (g)
Sat fat (g)
Chol (mg)
Fiber (g)
4™™™™™™™™™™™™™™™™™™™™™™™™™™ mean⫾standard deviation ™™™™™™™™™™™™™™™™™™™™™™™™™™3 Men Per daya Per dayb Per doseb Women Per daya Per day Per doseb
Control Chitosan Chitosan
48 48 240
13.57⫾2.47 13.67⫾2.77 2.72⫾1.00
3,244⫾591 3,269⫾661 650⫾238
137⫾30 138⫾32 27.6⫾11
51⫾13 51⫾13 10.2⫾5.3
458⫾297 464⫾270 92.7⫾124
23⫾8 25⫾8 4.6⫾3.9
Control Chitosan Chitosan
48 48 239
8.83⫾0.82 8.82⫾0.82 1.74⫾0.60
2,112⫾197 2,108⫾196 417⫾143
89⫾16 88⫾15 17.6⫾7.1
36⫾11 36⫾11 7.1⫾4.4
275⫾173 264⫾164 52.6⫾72
16⫾6 17⫾6 2.9⫾2.8
a
The n per day represent the 4 days of either control or chitosan period multiplied by 12 subjects per sex for 48 individual data points for men and for women. The n per dose represent 4 days of either control or chitosan period multiplied by 12 subjects per sex and by 5 meals per day for 240 individual data points except in women where one dose was missed by one subject on one occasion for a total of 239.
b
fecal fat excretion was different between men and women (P⫽.03) (Figure 2B). In men, daily fecal fat excretion was 5.0⫾1.5 g (control) and 6.9⫾2.7 g (chitosan), a difference of 1.8⫾2.4 g/day (P⫽.02). This very small fecal fat increase in men was statistically significant but far too small to be clinically significant. In women daily fecal fat excretion was 3.7⫾2.0 g (control) and 3.7⫾1.8 g (chitosan), a difference of 0.0⫾1.4 g/day (P⫽.99). DISCUSSION The results we report with this particular chitosan supplement are similar to those that have been reported previously for other chitosan supplements. Four other published studies measured the change in fecal fat excretion in people taking a chitosan supplement. Guerciolini and colleagues (13) gave 2.67 g chitosan per day to seven men and five women and measured a nonsignificant increase of 0.27 g fecal fat per day (n⫽12) (13). In our first study we gave 5.25 g chitosan per day (Fat Trapper, Enforma Natural Products) to seven men and found a 0.1 g/day nonsignificant decrease in fecal fat excretion (8). In our second study, we gave 4.5 g of chitosan per day (Absorbitol, Natrol) to 15 men and found an increase in fecal fat excretion of 1.1 g/day (12). Aranda and colleagues (14) gave 6.3 g of chitosan per day to 16 men and eight women and reported a 3.63⫾4.06 g/day increase in fecal fat excretion (n⫽24). In this study, 2.5 g chitosan/ day increased the fecal excretion of fat by 1.8 g/day in 12 men and 0.0 g/day in 12 women. When we combine the data for men and women in this study we find an overall fecal fat increase of 0.96 g/day (n⫽24, P⫽.04). However, it would be inappropriate to combine fecal fat results because a sex effect was observed. To control for the differing doses of chitosan used in these studies, in vivo fat-binding capacities may be compared. When the grams of fat bound per gram of chitosan consumed are calculated, the group of men in the current study gives the highest value of any study, with 0.72 g fat bound per gram of chitosan consumed. Second rank is Aranda and colleagues in with 0.58 g/g (14). Third is Gades and Stern (12) with 0.24 g/g. Fourth is Guerciolini
and colleagues (13) with 0.10 g/g. Fifth is the group of women in the current study with 0.02 g/g and last is Gades and Stern (8) with ⫺0.02 g/g. There is an overall agreement between these studies even though each used a different product, except Aranda and colleagues’ (14) and Gades and Stern’s (12), which used the same product. One difficulty in comparing these results between studies is that in Aranda and colleagues (14), the fecal collection method was a complete collection for only 48-hour periods. Fecal collection is an unpleasant task that when done only acutely will likely promote fecal retention and constipation. This seriously hinders the reliability of any data based on acute fecal collections in some subjects. A better alternative was used by Guerciolini and colleagues (13), who collected for 7-day periods and used a crossover design. The longer collection period ensures that any disruption of bowel movements in the first days has time to resolve. We collected continuously for 11 days and used oral charcoal, which appeared in the feces to demark the 4-day experimental periods. This method has the added benefit that the boundaries of the experimental periods are better defined, increasing the reliability of fecal fat excretion data in studies using that method. In our study, although the effect of chitosan on fecal fat excretion in men was small, it is unclear why women differed, with, on average, no effect at all. We designed the diets for participants so that each meal would have a load of fat that would more than saturate the chitosan dose based on available in vitro and in vivo published results. Specifically, Nauss and colleagues (1) reported that chitosan is able to bind to in vitro 4 to 5 g lipids per gram of chitosan. Based on the studies of Kanauchi and colleagues (17), the maximum fat-binding capacity of chitosan when given in massive doses to rats was 3.4 g/g. Although the amount of fat consumed per dose of chitosan in our study was less in women than in men, it was still high in women, with an average of 18 g and a minimum of 10 g fat per meal. Each meal, therefore, had an average of 36 and a minimum of 20 g fat per gram of chitosan in women. Fat was thus present in the meals at a more than
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Figure 2. Fecal mass and fecal fat excretion in 12 men and 12 women without and with chitosan. (A) Fecal mass in grams per day. (B) Fecal fat excretion in grams per day. Men and women are grouped separately. Mean⫾standard deviation for the 4-day control and chitosan treatment periods are indicated with bars; intra-subject differences between periods are indicated with scattergrams having bars for means. *P⬍.05 control vs chitosan.
fivefold excess of the theoretical binding capacity of the chitosan dose even in women. In discussing why, in our previous work, we found no effect of chitosan on fecal fat excretion, Aranda and colleagues (14) suggest that the fat intake was too high, that it might have “overwhelmed” the fiber, rendering it inactive. This statement appears to contradict what has been well established concerning the kinetics of substrate binding in general (23) and has no support from either in vivo or in vitro chitosan studies (16). In addition, given the fact that the American diet is typically high in fat, such an assertion calls into question whether this product could ever work for those likely to buy it. Based on our findings, it is not likely that the amount of fat present with each dose of chitosan was either too much or too little or that it contributed to the difference between men and women. Although nonzero in men, the impact of this chitosan supplement on fat excretion is clinically insignificant. If the small amount of fat excreted in the feces was not simply compensated for with a small increase in food intake over time, and if that net energy loss led to fat loss, it would take more than 7 months to lose 1 lb of body fat due to fat malabsorption in men taking chitosan. No amount of time could lead to any body fat loss in women taking chitosan at the rate measured here.
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1.8 g fat malabsorbed⫻9 kcal ⁄ g fat ⫽16.2 kcal malabsorbed ⁄ day (3.500 kcal ⁄ lb bodyfat) ⁄ (16.2 kcal ⁄ day) ⫽216 days per pound fat in men CONCLUSIONS This study reinforces the importance of testing dietary supplements in people in order to substantiate claims. The claims made for chitosan and fat malabsorption have been based primarily on combining chitosan in a buffer and fat and chitosan in a beaker, stirring the liquids, and measuring clumping of fat. This has been interpreted to be “malabsorption” in the gastrointestinal tract. Studies done in rodents, which document fat malabsorption, give the animals huge doses of chitosan— up to 4.5% by weight of the diet. In contrast, the small amount of fat malabsorbed in humans with chitosan was clinically insignificant in males (1.8 g/day) and nonexistent in females. The authors now have evidence using three different commercial products [this study; (8,12)] that the claims that chitosan is a fat-trapping weight-loss aid are not merely unsubstantiated, they are false.
This work was supported, in part, by a gift from the Consumer Justice Center, Laguna Nigel, CA and the UC Davis Clinical Nutrition Research Unit, National Institutes of Health DK35747 Nutritional Assessment Laboratory. References 1. Nauss JL, Thompson JL, Nagyvary J. The binding of micellar lipids to chitosan. Lipids. 1983;18:714-719. 2. Muzzarelli RAA. Interactions of chitin, chitosan, Nlauryl chitosan and N-dimethylaminopropyl chitosan with olive oil. Carbohyd Polym. 2000;43:263-268. 3. Deuchi K, Kanauchi O, Imasato Y, Kobayashi E. Decreasing effect of chitosan on the apparent fat digestibility by rats fed on a high-fat diet. Biosci Biotechnol Biochem. 1994;58:1613-1616. 4. Han LK, Kimura Y, Okuda H. 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. 5. US Food and Drug Administration. Dietary Supplement Health And Education Act of 1994. Available at: http://vm.cfsan.fda.gov/⬃dms/dietsupp.html. Accessed February 26, 2004. 6. Federal Trade Commission. Weight-loss advertising: An analysis of current trends. Federal Trade Commission. Available at: http://www.ftc.gov/bcp/reports/ weightloss.pdf. Accessed January 26, 2003. 7. US District Court. FTC v. Enforma Natural Products, Inc., Andrew Grey, and Fred Zinos. Available at: http://www.ftc.gov/os/2000/04/enformazinos.htm. Accessed June 19, 2000. 8. Gades MD, Stern JS. Chitosan supplementation does not affect fat absorption in healthy males fed a highfat diet, a pilot study. Int J Obes Relat Metab Disord. 2002;26:119-122. 9. Ernst E, Pittler M. Chitosan as a treatment for body weight reduction? A meta-analysis. Perfusion. 1998; 11:461-465. 10. Pittler MH, Abbot NC, Harkness EF, Ernst E. Randomized, double-blind trial of chitosan for body weight reduction. Eur J Clin Nutr. 1999;53:379-381. 11. Ho SC, Tai ES, Eng PH, Tan CE, Fok AC. In the absence of dietary surveillance, chitosan does not re-
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