1: J Pharm Pharmacol. 1997 Jul;49(7):721-3.

Effect of chitosan on renal function in patients with chronic renal failure.

Jing SB, Li L, Ji D. Department of Nephrology, Jinling Hospital, Nanjing University, School of Medicine, P.R. China. Department of Industrial Chemistry, Chiba Institute of Technology , Japan .

The effects of chitosan have been investigated on eighty patients with renal failure undergoing long-term stable haemodialysis treatment. The patients were tested after a control treatment period of 1 week. Half were fed 30 chitosan tablets (45 mg chitosan/tablet) three times a day. Ingestion of chitosan effectively reduced total serum cholesterol levels (from 10.14 +/- 4.40 to 5.82 +/- 2.19 mM) and increased serum haemoglobin levels (from 58.2 +/- 12.1 to 68 +/- 9.0 g L-1). Significant reductions in urea and creatinine levels in serum were observed after 4 weeks of chitosan ingestion. The feeling of physical strength, the appetite and the sleep of patients in the treatment group had improved significantly after 12 weeks of ingestion, compared with those of patients in the control group. During the treatment period, no clinically problematic symptoms were observed. These data suggest that chitosan might be effective treatment for renal failure patients, although the mechanism of the effect should be investigated further.

Publication Types:

•  Clinical Trial

•  Controlled Clinical Trial

2: Biosci Biotechnol Biochem. 2001 Nov;65(11):2412-8.

Hydrolysis of a chitosan-induced milk aggregate by pepsin, trypsin and pancreatic lipase.

Ausar SF , Landa CA , Bianco ID . Center of Excellence in Products and Processes of Cordoba, Cordoba Science Agency, Santa Maria de Punilla, Argentine.

The addition of chitosan to whole milk results in dose dependent destabilization and coagulation of the casein micelles and milk fat. The present study evaluates how the presence of chitosan could affect the hydrolysis of this chitosan-induced aggregate by different gastrointestinal proteases (pepsin and trypsin) and by pancreatic lipase. The chitosan-milk aggregate was hydrolyzed by pepsin and trypsin, as evaluated by the UV absorbance of TCA-soluble peptides and by urea-PAGE. The kinetics and extent of hydrolysis were independent of the casein being soluble or aggregated. The release of soluble peptides from the aggregate was

independent of the presence of chitosan. A progressive inhibition of pancreatic lipase was observed in proportion to the increase in molecular weight of the chitosan employed to induce the formation of the aggregate. Interestingly, the presence of chitosan not only affected the initial velocity of the reaction, but also reduced its extent. The results indicate that a milk aggregate induced by chitosan was very well digested by gastric and intestinal proteases independently of the molecular weight of the chitosan used, and that the aggregate could retain the lipid-lowering effect of chitosan .

3: Proc Soc Exp Biol Med. 1988 Oct;189(1):13-20.

A comparison of the lipid-lowering and intestinal morphological effects of cholestyramine, chitosan, and oat gum in rats.

Jennings CD , Boleyn K , Bridges SR . Department of Pathology, University of Kentucky Medical Center, Lexington.

Cholestyramine, chitosan, and oat gum are lipid-lowering compounds. Cholestyramine use in humans may contribute to colonic adenocarcinoma; chitosan and oat gum are being studied in the rat to determine their potential for human use. To compare these compounds, we fed three groups of 10 male Sprague-Dawley rats one of the substances at 5% of diet with 1% cholesterol and 0.2% cholic acid; two other groups were fed cellulose with and without 1% cholesterol and 0.2% cholic acid. All groups had similar food intake and weight gains. Cholesterol feeding increased total liver lipids almost 3-fold and liver cholesterol concentration almost 10-fold. Cholestyramine, oat gum, and chitosan all significantly lowered liver cholesterol with cholestyramine feeding yielding levels identical to the noncholesterol-fed basal group. Chitosan and oat gum lowered liver cholesterol moderately. Cholestyramine and chitosan both significantly lowered serum cholesterol compared to the cellulose group. Oat gum was less effective. Hemoglobin and serum iron were similar in all groups except the oat gum group, which had decreased serum iron. Histological examination of small and large bowel with morphometry revealed statistically significant increases in both proximal and distal small bowel and distal large bowel mucosal thickness in the cholestyramine-fed group. No changes were noted in the proximal large bowel. Neither chitosan nor oat gum produced mucosal change other than an increase in the distal small bowel with the oat gum diet. Chitosan may have lipid-lowering effects similar to those of cholestyramine without the deleterious changes in intestinal mucosa.

4: EXS. 1999;87:293-304.

Clinical and biochemical evaluation of chitosan for hypercholesterolemia and overweight control.

Muzzarelli RA . Center for Innovative Biomaterials, University of Ancona, Italy.

After providing basic information on enzymes involved in cholesterol homeostasis, and on ma

nagement of hypertriglyceremia and hypercholesterolemia, with the aid of cholestyramine and fibric acid, this chapter examines the effects of the ingestion of chitosan. Dietary chitosan is effective on serum cholesterol and in atherosclerosis in normal and diabetic mice, and lends itself to the treatment of hypercholesterolemia in humans . It also exhibits antiulcer, antiarthritic, antihypertension and antiuricemic properties . The published human trials, analysed statistically, further indicate that chitosan is effective to control overweight when associated to a diet. This chapter discusses several issues raised against the use of chitosan, namely, depletion of zinc and liposoluble vitamins, as well as advantages such as enhanced absorption of nutrients and competitive inhibition of lipases. It also directs attention to the unexplored areas of fungal and algal chitosans, and the use of chitins instead of chitosans.

Publication Types:

•  Review

5: Eksp Klin Farmakol. 1992 Sep-Oct;55(5):44-7.

The hypolipidemic activity of natural substances

Okunevich IV , Kliueva NN , Solov'eva MA .

Experiments on guinea pigs and rats have revealed that thiazole derivatives of isoflavone has a beneficial effects on disturbed lipid and lipoprotein metabolism. New phospholipid complexes enriched with vitamins have been demonstrated to produce a hypolipidemic effect. Sulfated chitosans decrease lipid infiltration of the liver and elevate serum high density lipoprotein levels in rats.

6 : J Med Food. 2003 Winter;6(4):397-9.

In this work we evaluated the efficacy and safety of a bread formulation containing chitosan in dyslipidemic type 2 diabetic subjects. For this purpose a total of 18 patients were allowed to incorporate to their habitual diets 120 g/day of bread containing 2% (wt/wt) chitosan (chitosan group, n= 9) or standard bread (control group, n= 9). Before the study and after 12 weeks on the modified diet, the following parameters were evaluated: body weight, plasma cholesterol, high-density lipoprotein (HDL)-cholesterol, low-density lipoprotein (LDL)-cholesterol, triglyceride, and hemoglobin A(1c) (HbA(1c)). Compared with the control group, the patients receiving chitosan-containing bread decreased their mean levels of LDL-cholesterol and significantly increased their mean levels of HDL-cholesterol at the end of the study. There were no significant differences in the body weight, serum triglyceride, and HbA(1c). These results suggest that chitosan incorporated into bread formulations could improve the lipoprotein balance similar to typical biliary salts trappers, increasing the HDL- and lowering the LDL-cholesterol, without changing the triglyceride levels. These results warrant further studies over a longer period of time to evaluate if a persistent improvement in levels of lipoproteins can be attained with this strategy.

7 : Eur J Clin Nutr. 2003 May;57(5):721-5.

Chitosan decreases total cholesterol in women: a randomized, double-blind, placebo-controlled trial.

Bokura H , Kobayashi S . Department of Internal Medicine III, Shimane Medical University, Shimane, Japan.

BACKGROUND: Hypercholesterolemia is an important risk factor for cardiovascular disease. Orally administered chitosan binds lipids in the small intestine and reduces their absorption. Chitosan has been shown to decrease serum cholesterol in animal and human studies . This study investigated the effectiveness of chitosan in reducing serum cholesterol without concomitant diet therapy. METHODS: Ninety female volunteers (age 34-70 y) with confirmed mild to moderate hypercholesterolemia were enrolled into the study. They were randomly assigned to receive chitosan (1.2 g per day) or placebo in a double-blind manner. Serum lipids, body weight and adverse events were assessed at baseline and after 28 and 56 days of treatment. Subjects maintained their usual diet and documented the type and gross amount of food consumed. RESULTS: Eighty-four subjects (41 chitosan, 43 placebo) were included in the analysis. Chitosan significantly (F=3.19, P=0.04) reduced total cholesterol compared to placebo. In a subgroup of subjects with over 60 y of age, chitosan group significantly reduced total and LDL cholesterol (F=4.21, P=0.02, and F=3.46, P=0.04, respectively) compared with placebo. Adverse effects were few; no serious events were reported. CONCLUSION: Our results demonstrate that chitosan is safe and effective for lowering cholesterol . However, the effect of chitosan for decreasing cholesterol is mild.

Publication Types:

•  Clinical Trial

•  Randomized Controlled Trial

8: J Nutr Sci Vitaminol (Tokyo). 2002 Oct;48(5):379-83.

Plasma lipoprotein cholesterol in rats fed a diet enriched in chitosan and cholesterol.

Yao HT , Chiang MT . Department of Food Science, National Taiwan Ocean University, Taiwan, ROC.

To investigate the effect of dietary chitosan on plasma lipoprotein cholesterol metabolism, male Sprague-Dawley (SD) rats fed a cholesterol-enriched diet containing cellulose (CE) or chitosan (CS) were studied for 2 wk. Lower plasma total cholesterol, low-density lipoprotein (LDL) cholesterol and very-low-density lipoprotein (VLDL) cholesterol were observed in rats fed a diet containing chitosan. In addition, significantly higher high-density lipoprotein (HDL) cholesterol and HDL2 cholesterol were observed in rats after 2 wk of chitosan feeding. Rats fed the chitosan diet had increased triacylglycerol percentages and decreased free cholesterol, cholesteryl ester and phospholipid percentages in VLDL lipid composition. Chitosan significantly decreased the surface lipid proportions and increased the core lipid proportions in VLDL particles. In addition, the ratios of surface lipids to core lipids of the VLDL particles in rats fed a diet containing chitosan were significantly decreased. A significantly lower plasma apolipoprotein B (Apo B) concentration was observed in rats fed the chitosan diet as compared to those fed the cellulose diet. No significant difference in plasma triacylglycerols or glucose levels was observed between the two dietary groups. Results from this study suggest that chitosan may alter the VLDL particle size and also play an important role in the regulation of lipoprotein metabolism in rats.

9 : Arzneimittelforschung. 2002;52(1):1-7.

Cholesterol-lowering properties and safety of chitosan.

Ylitalo R , Lehtinen S , Wuolijoki E . Department of Pharmacological Sciences, University of Tampere, Tampere, Finland.

Chitosan (CAS 9012-76-4) is derived by alkaline deacetylation from chitin, an abundant polymeric product of natural biosynthesis especially in crustaceans. It is available in a primary, unorganised structure, but also in a microcrystalline form. As a dietary supplement, chitosan has been claimed to control obesity and to lower serum cholesterol. A variety of chitosan products have been freely available worldwide in health stores and pharmacies. This review summarises the current knowledge about cholesterol-lowering and safety properties of chitosan and focuses its possible application for the treatment of hypercholesterolaemia. Chitosan behaves as a polycationic(+) cellulose-like fibrillar biopolymer that forms films with negatively charged surfaces. It is not specifically hydrolysed by digestive enzymes in man, but limited digestion of chitosan due to bacterial flora and to the unspecific enzymes might occur. Negatively charged molecules in stomach attach strongly to the positive charged tertiary amino group (-NH3+) of chitosan. Therefore, chitosan reduces fat absorption from gastrointestinal tract by binding with anionic carboxyl groups of fatty and bile acids, and it interferes with emulsification of neutral lipids (i.e., cholesterol, other sterols) by binding them with hydrophobic bonds. In short-term animal studies the safety of chitosan has been good. There are only few studies with chitosan in humans. In man, dietary chitosan has been reported to reduce serum total cholesterol levels by 5.8-42.6% and low-density lipoprotein levels by 15.1-35.1%. In short-term trials up to 12 weeks, no clinically significant symptoms have been observed with chitosan compared to placebo. Mild and transitory nausea and constipation have been reported in 2.6-5.4% of subjects. Although chitosan has been clinically well tolerated, it cannot be recommended to people allergic to crustaceans.

Publication Types:

•  Review

•  Review, Tutorial

10 : Methods Find Exp Clin Pharmacol. 1999 Jun;21(5):357-61.

Decrease in serum LDL cholesterol with microcrystalline chitosan.

Wuolijoki E , Hirvela T , Ylitalo P . Finn-Medi Research Ltd., Department of Pharmacological Sciences, University of Tampere, Finland.

Peroral microcrystalline chitosan (MCCh; 3 capsules, each 400 mg b.i.d.) or placebo was given for 8 weeks in a double-blind manner to 51 healthy obese women just before routine hospital and home meals. Weight records, serum lipids (total, LDL and HDL cholesterol, triglycerides) and safety laboratory parameters were monitored before the trial and at 4, 6 and 8 weeks of treatment. In a subgroup of subjects with a body mass index > or = 30 who had not changed their eating habits, serum LDL cholesterol decreased 0.57 +/- 0.72 mmol/l (n = ll) at 4 weeks in the MCCh group and 0.10 +/- 0.60 mmol/l (n = 14) in the placebo group (p < 0.05). At 8 weeks, LDL cholesterol reduction was 0.48 +/- 0.91 mmol/l in the MCCh group and 0.26 +/- 0.57 mmol/l in the placebo group (p > 0.1). In all subjects, the reduction in LDL cholesterol at 4 weeks was 0.48 +/- 0.72 mmol/l (n = 24) in MCCh subjects and 0.18 +/- 0.58 mmol/l (n = 27) in placebo subjects (p = 0.057), and 0.52 +/- 0.69 mmol/l and 0.31 +/- 0.63 mmol/l, respectively, at 8 weeks (p > 0.1). MCCh did not significantly alter serum total and HDL cholesterol (p > 0.1), but slightly increased serum triglycerides compared to placebo (p = 0.015-0.06). No reductions in weight were observed in any treatment group. Chitosan was well tolerated and no serious adverse events or changes in safety laboratory parameters were noted including serum fat-soluble vitamins A and E, and serum Fe++ and transferrin.

Publication Types:

•  Clinical Trial

•  Randomized Controlled Trial

11: Int J Vitam Nutr Res. 2004 Jul;74(4):253-63.

Dietary fiber suppresses elevation of uric acid and urea nitrogen concentrations in serum of rats with renal dysfunction induced by dietary adenine.

Koguchi T , Koguchi H , Nakajima H . Department of Applied Biology and Chemistry, Faculty of Applied Bioscience, Tokyo University of Agriculture, Tokyo, Japan.

This study was conducted to examine the effects of several kinds of dietary fiber (DF) with different physical properties on the elevation of uric acid and urea nitrogen concentrations in serum of rats induced by dietary adenine. DF decreased an uptake of 14C-labeled adenine in the rat jejunum in vitro, but the reduction varied with the physical property of DF. Male Wistar rats (3 weeks old) were fed a diet with or without a 0.4% adenine and a 5% DF (cellulose, chitin, chitosan, or xanthan gum) for 20 days. Feeding of adenine in the fiber-free group elevated the concentrations of uric acid, creatinine, and urea nitrogen in serum, but decreased the excretions of these compounds into urine and increased the amounts of 2,8-dihydroxyadenine (2,8-DHA) in kidney and urine. The test DF was found to suppress the elevation of uric acid, creatinine, and urea nitrogen concentrations in serum induced by dietary adenine, and to mitigate the decreased excretions of these compounds into urine and the increased retention of 2,8-DHA in kidney and urine. This phenomenon was remarkable in the xanthan gum group. These results suggest that DF suppresses the elevation of uric acid and urea nitrogen concentrations in serum by attenuating the absorption of dietary adenine.

12: Nippon Yakurigaku Zasshi. 1995 Aug;106(2):123-33.

Pharmacological properties of chitosan-coated dialdehyde cellulose (chitosan DAC), a newly developed oral adsorbent (II). Effect of chitosan DAC on rats with chronic renal failure induced by adriamycin

Nagano N , Yoshimoto H , Nishitoba T . Pharmaceutical Research Laboratory, Kirin Brewery Co., Ltd., Gunma, Japan.

The effects of chitosan-coated dialdehyde cellulose (Chitosan DAC), a newly developed oral adsorbent of urea and ammonia, were examined in rats with progressive chronic renal failure (CRF) induced by adriamycin. CRF rats induced by repeated injections of adriamycin were fed a diet containing chitosan DAC (5% content) or Kremezin (5% content), an oral charcoal adsorbent (AST-120) under strict paired-feeding for four months. CRF rats that received both a normal diet and Kremezin showed progressive azotemia, hyperphosphatemia, hyperlipidemia, proteinuria, and anemia, and began to die from 9 weeks after feeding started. In contrast, chitosan DAC-treatment showed marked prolongation of the survival period and decreases in blood urea nitrogen, serum creatinine, and serum phosphate. In addition, chitosan DAC-treatment ameliorated anemia in CRF rats, although hyperlipidemia and proteinuria were not improved. Furthermore, fecal weight, fecal water content, fecal nitrogen and fecal sodium were markedly increased, and the apparent protein ratio was decreased in CRF rats fed a diet containing chitosan DAC for 9 weeks. In contrast, none of these effects were observed in CRF rats receiving Kremezin. These observations suggest the further possibility of using oral adsorbent therapy for CRF patients.

13: Nippon Yakurigaku Zasshi. 1995 Aug;106(2):113-22.

Pharmacological properties of chitosan-coated dialdehyde cellulose (chitosan DAC), a newly developed oral adsorbent (I). Effect of chitosan DAC in normal rats

Yoshimoto H , Nagano N , Nishitoba T . Pharmaceutical Research Laboratory, Kirin Brewery Co., Ltd., Gunma, Japan.

The effects of chitosan-coated dialdehyde cellulose (chitosan DAC), a newly developed oral adsorbent of urea and ammonia, were examined in an in vitro adsorption study and in normal rats. Chitosan DAC showed high adsorption capacity for urea and ammonia in an in vitro study using the diluted supernatant of rat gastrointestinal fluid. In contrast, Kremezin, an oral charcoal adsorbent (AST-120), had little influence on these substances. In normal rats fed diets containing chitosan DAC (1, 2, 3, 4, 5, 7, and 10% content) for three weeks, increases in fecal wet weight, fecal dry weight and fecal water content were observed in a dose-dependent manner. In addition, chitosan DAC feeding increased fecal excretion of nitrogen and electrolytes (sodium, potassium and chloride ions) and decreased the apparent protein ratio in a dose-dependent manner. There were no obvious effects in serum parameters except that increased levels of protein and albumin and decreased levels of blood urea nitrogen, cholesterol and glucose were observed in rats fed a high concentration of chitosan DAC. In conclusion, these findings suggest the possibility that chitosan DAC treatment might be effective for improving chronic renal failure.