Medically reviewed on Feb 12, 2018
Common Name(s): Chitosan , chitin
There is some evidence of the effect of chitosan on lowering cholesterol and body weight, but the effect is unlikely to be of clinical importance. To some extent, chitosan is used in the emergency setting to control bleeding. Chitosan has been used in various drug delivery systems. Antimicrobial and other effects are being evaluated for use in dentistry.
Chitosan has been administered at wide-ranging doses in clinical studies. In studies evaluating weight loss, 2.4 g/day is commonly used.
None well established.
Information regarding safety and efficacy in pregnancy and lactation is lacking.
Data are limited. Potentiation of the anticoagulant effect of warfarin was reported in a patient receiving chitosan 2.4 g/day.
The potential for allergy exists in individuals allergic to shellfish. Clinical trials report few adverse events, generally limited to flatulence and constipation.
Chitosan's toxicity profile is relatively low.
Chitin is a cellulose-like biopolymer found mainly in exoskeletons of marine invertebrates and arthropods, such as shrimp, crabs, or lobsters. Chitin can also be found in fungi (mushroom exoskeleton) and yeasts. Chitosan is deacylated chitin. “Squid pens,” waste shell by-products of squid processing, are a renewable and inexpensive source of chitosan. 1 , 2 , 3 , 4
Chitin consists mainly of unbranched chains of beta-(1 → 4)-2-acetamido-2-deoxy-D-glucose (=N-acetyl-d-glucosamine). It is similar to cellulose, in which the C-2 hydroxyl groups are replaced by acetamido residue. Chitin is practically insoluble in water, dilute acids, and alcohol, with variation depending on product origin. 1 Chitosan, the partially deacetylated polymer of N-acetyl-D-glucosamine, is water-soluble. 4
Rheology, flocculation, and film-formation testing have been performed with chitosan, demonstrating its usefulness in medical and analytical applications. 4 Biodegradable and biocompatible properties of chitosan films have been studied with positive outcomes. In vitro and in vivo degradation tests of chitin and chitosan have been evaluated, as well as chitosan film chemistry on electrically charged metal plates. 9 , 10 , 11
N-carboxymethylchitosan solubility and structure have been reported, along with the ability to chelate metal ions and to enhance binding of dyes. Other chemical aspects involving chitin or chitosan include optical isomer separation, mass-spectrometric analysis, polyelectrolyte and sulfation studies, adherence to liposomes, and properties of chitosan microspheres. 12 , 13 , 14 , 15 , 16 , 17 , 18
Uses and PharmacologyAntibacterial (dental) effects
Chitosan dental chewing gum, mouthwashes, and gels have been investigated for antibacterial action. Chitosan adheres to salivary pellicles (negatively charged protein film), reduces plaque, increases salivary secretion, and exerts antibacterial action effective in managing chronic periodontitis. 19 , 20 , 21 , 22 , 23
Positively charged amino groups in chitosan bind to negatively charged lipid and bile components, preventing their absorption by the body. 1Animal data
Extensive animal studies have been published demonstrating the effects of chitosan on lipid concentrations in affected rats, very low-density lipoprotein, and high density lipoprotein levels. 26 , 27 , 28 , 29 , 30 , 31 In a recent study, chitosan derived from white mushroom exoskeleton (fungal chitosan) decreased body weight gain and fat mass development in mice fed a high-fat diet. 32Clinical data
A Cochrane meta-analysis of quality, randomized, controlled clinical trials found a small effect of chitosan on total cholesterol (−0.2 mmol/L; 95% confidence interval [CI] = −0.3 to −0.1). 1 Results of trials published since the meta-analysis are conflicting. Some trials reported no cholesterol-lowering effect of chitosan compared with placebo, 33 , 34 while another reported an effect for chitosan at 4 weeks but no further effect at 12 weeks. 35
The Cochrane meta-analysis found a statistically significant but clinically insignificant effect for chitosan on body weight (−1.7 kg; 95% CI = −2.1 to −1.3 kg). 1 Positive, small changes in fasting blood glucose and blood pressure were also noted. 1 The clinical importance of the effect has also been questioned by other reviewers. 36 , 37
Bandages impregnated with chitosan and chitosan granules have been approved by the FDA for use in emergency settings to control blood loss. 41 Experiments conducted in pigs 41 and in the emergency department 42 have shown that topical application of chitosan granules controls bleeding in less than 3 minutes, where pressure alone failed. 42 Suggested mechanisms of action include mucoadhesion, platelet activation, vasoconstriction, and ionic action on red blood cells. 41 , 42
Chitosan (0.1% solution) has been effectively used as an alternative for sodium hyaluronate in long-term, postsurgical ophthalmic management (3 years). 47
Chitosan 2 g added to an oxalate-rich meal had no effect on urinary oxalate excretion, despite oxalate being negatively charged. 48 An antioxidant effect of chitosan has been demonstrated in vitro. 49
Application of chitosan in the pharmaceutical industry is documented. Its ability to mask bitter tastes in oral pharmaceuticals has been reported. 50 There are numerous reports of chitosan being employed in various types of drug delivery systems, including intranasal, transdermal, and site-specific delivery mechanisms, as well as in hydrogels, microspheres, liposomes, matrix forms, and conjugate forms. 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63
Chitosan has been administered in cholesterol reduction and weight loss clinical studies in wide-ranging doses of 0.24 to 15 g daily (median, 3.7 g/day) for 4 to 24 weeks. 1 , 33 , 34 , 35 Chitosan has been administered to patients with renal failure undergoing long-term hemodialysis without any apparent adverse events. 64
Information regarding safety and efficacy in pregnancy and lactation is lacking.
Data are limited. Potentiation of the anticoagulant effect of warfarin was reported in a patient receiving chitosan 2.4 g/day. Interference with vitamins A, D, E, and K absorption by chitosan was the suspected mechanism. 65 However, absorption of vitamins A, D, or E were unaffected by chitosan in a clinical trial. 34
Clinical trials report few adverse events. 1 At 6.75 g/day for 8 weeks, no adverse hematological effects were found for chitosan. 34 Adverse reactions included flatulence and constipation. 37 A case of rhabdomyolysis occurred with a combination preparation containing chitosan; however, other components of the product were considered more likely to be responsible for the effects. 66
Chitosan's toxicity profile is relatively low. Dietary chitosan reportedly affects calcium metabolism in animals. 67
Bibliography1. Jull AB, Ni Mhurchu C, Bennett DA, Dunshea-Mooij CA, Rodgers A. Chitosan for overweight or obesity. Cochrane Database Syst Rev . 2008;(3):CD003892.
2. Budavari S, ed. The Merck Index: An Encyclopedia of Chemicals, Drugs, and Biologicals . 11th ed. Rahway, NJ: Merck & Co. Inc; 1989.
3. Furda I, Brine CJ, ed. New Developments in Dietary Fiber: Physiological, Physicochemical, and Analytical Aspects . New York, NY: Plenum Press;1990;67-82.
4. Shepherd R, Reader S, Falshaw A. Chitosan functional properties. Glycoconj J . 1997;14(4):535-542.
5. Nauss JL, Thompson JL, Nagyvary J. The binding of micellar lipids to chitosan. Lipids . 1983;18(10):714-719.
6. Skaugrud O. Chitosan makes the grade. Manuf Chem . 1989;60:31,33,35.
7. Onsoyen E, Skaugrud O. Adding benefits to cosmetic formulations by tailormade chitosans. Seifen, Oele, Fette, Wachse . 1991;117:633-637.
8. Naidoo NT. Natural cosmetic constituents: seaweed, chitosan and rice. S Afr Pharm J . 1992;59:131-132
9. Cao ZS, Lu FQ. Studies on preparation of medical biodegradable films of chitosan. Chin J Pharm . 1996;27:14–16.
10. Tomihata K, Ikada Y. In vitro and in vivo degradation of films of chitin and its deacetylated derivatives. Biomaterials . 1997;18(7):567-575.
11. Ikeda H, Yamamura, S, Takayama K, Nagai T. Physicochemical properties of chitosan film prepared on a metal plate loaded with electric charge. Chem Pharm Bull . 1996;44(7):1372-1375.
12. Muzzarelli RA, Ilari P, Petrarulo M. Solubility and structure of N-carboxymethylchitosan. Int J Biol Macromol . 1994;16(4):177-180.
13. Muzzarelli R, Delben F, Ilari P, Tomasetti M. N-(carboxylmethyl)chitosan, a versatile chitin derivative. Chim oggi . 1993;11:31-35.
14. Malinowska I, Rózylo JK. Separation of optical isomers of amino acids on modified chitin and chitosan layers. Biomed Chromatogr . 1997;11(5):272-275.
15. Lopatin S, Ilyin MM, Pustobaev VN, Bezchetnikova ZA, Varlamov VP, Davankov VA. Mass-spectrometric analysis of N-acetylchitooligosaccharides prepared through enzymatic hydrolysis of chitosan. Anal Biochem . 1995;227(2):285-288.
16. Holme KR, Perlin AS. Chitosan N-sulfate. A water-soluble polyelectrolyte. Carbohydr Res . 1997;302(1-2):7-12.
17. Henriksen I, Smistad G, Karlsen J. Interactions between liposomes and chitosan. Int J Pharm . 1994;101(3):227-236.
18. Berthold A, Cremer K, Kreuter J. Influence of crosslinking on the acid stability and physicochemical properties of chitosan microspheres. STP Pharm Sci . 1996;6(5):358-364.
19. Akncbay H, Senel S, Ay ZY. Application of chitosan gel in the treatment of chronic periodontitis. J Biomed Mater Res B Appl Biomater . 2007;80(2):290-296.
20. Hayashi Y, Ohara N, Ganno T, et al. Chewing chitosan-containing gum effectively inhibits the growth of cariogenic bacteria. Arch Oral Biol . 2007;52(3):290-294.
21. Hayashi Y, Ohara N, Ganno T, Ishizaki H, Yanagiguchi K. Chitosan-containing gum chewing accelerates antibacterial effect with an increase in salivary secretion. J Dent . 2007;35(11):871-874.
22. van der Mei HC, Engels E, de Vries J, Dijkstra RJ, Busscher HJ. Chitosan adsorption to salivary pellicles. Eur J Oral Sci . 2007;115(4):303-307.
23. Bae K, Jun EJ, Lee SM, Paik DI, Kim JB. Effect of water-soluble reduced chitosan on Streptococcus mutans, plaque regrowth and biofilm vitality. Clin Oral Investig . 2006;10(2):102-107.
24. Knapczyk J, Macura AB, Pawlik B. Simple tests demonstrating the antimycotic effect of chitosan. Int J Pharm . 1992;80(1-3):33-38.
25. Petronio M, Mansi A, Gallinelli C, Pisani S, Seganti L, Chiarini F. In vitro effect of natural and semi-synthetic carbohydrate polymers on Chlamydia trachomatis infection. Chemotherapy . 1997;43(3):211-217.
26. Ryzhenkov V, Solov'eva MA, Remezova OV, Okunevich IV. Hypolipidemic effect of sulfated polysaccharides [in Russian]. Vopr Med Khim . 1996;42(2):115-119.
27. Sugano M, et al. Nutr Rep Int . 1978;18(5):531-37.
28. Sugano M, Fujikawa T, Hiratsuji Y, Nakashima K, Fukuda N, Hasegawa Y. A novel use of chitosan as a hypocholesterolemic agent in rats. Am J Clin Nutr . 1980;33(4):787-793.
29. Michihiro S, et al. Lab Nutr . 1988.
30. Birketvedt G. Clin Rep . 1991.
31. Chobot V, Kremenák J, Opletal L. Phytotherapeutic aspects of disease of the circulatory system. 4. Chitin and chitosan [in Czech]. Ceska Slov Farm . 1995;44(4):190-195.
32. Neyrinck AM, Bindels LB, De Backer F, Pachikian BD, Cani PD, Delzenne NM. Dietary supplementation with chitosan derived from mushrooms changes adipocytokine profile in diet-induced obese mice, a phenomenon linked to its lipid-lowering action. Int Immunopharmacol . 2009;9(6):767-773.
33. Lehtimäki T, Metso S, Ylitalo R, et al. Microcrystalline chitosan is ineffective to decrease plasma lipids in both apolipoprotein E epsilon 4 carriers and non-carriers: a long-term placebo-controlled trial in hypercholesterolaemic volunteers. Basic Clin Pharmacol Toxicol . 2005;97(2):98-103.
34. Tapola NS, Lyyra ML, Kolehmainen RM, Sarkkinen ES, Schauss AG. Safety aspects and cholesterol-lowering efficacy of chitosan tablets. J Am Coll Nutr . 2008;27(1):22-30.
35. Jaffer S, Sampalis JS. Efficacy and safety of chitosan HEP-40 in the management of hypercholesterolemia: a randomized, multicenter, placebo-controlled trial. Altern Med Rev . 2007;12(3):265-273.
36. Saper RB, Eisenberg DM, Phillips RS. Common dietary supplements for weight loss. Am Fam Physician . 2004;70(9):1731-1738.
37. Pittler MH, Ernst E. Dietary supplements for body-weight reduction: a systematic review. Am J Clin Nutr . 2004;79(4):529-536.
38. 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(6):364-367.
39. Gades MD, Stern JS. Chitosan supplementation and fat absorption in men and women. J Am Diet Assoc . 2005;105(1):72-77.
40. Gades MD, Stern JS. Chitosan supplementation and fecal fat excretion in men. Obes Res . 2003;11(5):683-688.
41. Millner RW, Lockhart AS, Bird H, Alexiou C. A new hemostatic agent: initial life-saving experience with Celox (chitosan) in cardiothoracic surgery. Ann Thorac Surg . 2009;87(2):e13-e14.
42. Brown MA, Daya MR, Worley JA. Experience with chitosan dressings in a civilian EMS system. J Emerg Med . 2009;37(1): 1-7.
43. Rao S, Sharma CP. Use of chitosan as a biomaterial: studies on its safety and hemostatic potential. J Biomed Mater Res . 1997;34(1):21-28.
44. Kratz G, Arnander C, Swedenborg J, et al. Scand J Plast Reconstr Surg Hand Surg . 1997;31(2):119-123.
45. Tsipouras N, Rix CJ, Brady PH. Passage of silver ions through membrane-mimetic materials, and its relevance to treatment of burn wounds with silver sulfadiazine cream. Clin Chem . 1997;43(2):290-301.
46. Costain DJ, Kennedy R, Ciona C, McAlister VC, Lee TD. Prevention of postsurgical adhesions with N,O-carboxymethyl chitosan: examination of the most efficacious preparation and the effect of N,O-carboxymethyl chitosan on postsurgical healing. Surgery . 1997;121(3):314-319.
47. Li Y, Cheng JW, Wei RL, et al. Intraocular pressure and endothelium cell counts after cataract surgery with chitosan and sodium hyaluronate (Healon GV): 3-year follow-up results of a randomised clinical trial. Adv Ther . 2008;25(5):422-429.
48. Wolf J, Asplin JR, Goldfarb DS. Chitosan does not reduce post-prandial urinary oxalate excretion. Urol Res . 2006;34(4):227-230.
49. Anraku M, Fujii T, Furutani N, et al. Antioxidant effects of a dietary supplement: reduction of indices of oxidative stress in normal subjects by water-soluble chitosan. Food Chem Toxicol . 2009;47(1):104-109.
50. Roy GM. Taste masking in oral pharmaceuticals. Pharma Tech . 1994;18:84,86,88,90,92,94,96-99.
51. Tozaki H, Komoike J, Tada C, et al. Chitosan capsules for colon-specific drug delivery: improvement of insulin absorption from the rat colon. J Pharm Sci . 1997;86(9):1016-1021.
52. Aiedeh K, Gianasi E, Orienti I, Zecchi V. Chitosan microcapsules as controlled release systems for insulin. J Microencapsul . 1997;14(5):567-576.
53. Aspden TJ, Illum L, Skaugrud O. Chitosan as a nasal delivery system: evaluation of insulin absorption enhancement and effect on nasal membrane integrity using rat models. Eur J Pharm Sci . 1996;4(1):23-31.
54. Mi F, Wong TB, Shyu SS. Sustained-release of oxytetracycline from chitosan microspheres prepared by interfacial acylation and spray hardening methods. J Microencapsul . 1997;14(5):577-591.
55. Patashnik S, Rabinovich L, Golomb G. Preparation and evaluation of chitosan microspheres containing bisphosphates. J Drug Target . 1997;4(6):371-380.
56. Vasudev SC, Chandy T, Sharma CP. Development of chitosan/polyethylene vinyl acetate co-matrix: controlled release of aspirin-heparin for preventing cardiovascular thrombosis. Biomaterials . 1997;18(5):375-381.
57. Schipper N, Olsson S, Hoogstraate JA, deBoer Ag, Varum KM, Artursson P. Chitosans as absorption enhancers for poorly absorbable drugs 2: mechanism of absorption enhancement. Pharm Res . 1997;14(7):923-929.
58. Kotzé AF, Luessen HL, de Leeuw BJ, de Boer BG, Verhoef JC, Junginger HE. N-trimethyl chitosan chloride as a potential absorption enhancer across mucosal surfaces: in vitro evaluation in intestinal epithelial cells (Caco-2). Pharm Res . 1997;14(9):1197-1202.
59. Huo Z, Sinha R, McNeela EA, et al. Induction of protective serum meningococcal bactericidal and diphtheria-neutralizing antibodies and mucosal immunoglobulin A in volunteers by nasal insufflations of the Neisseria meningitidis serogroup C polysaccharide-CRM197 conjugate vaccine mixed with chitosan. Infect Immun . 2005;73(12):8256-8265.
60. Christensen KS, Cohen AE, Mermelstein FH, et al. The analgesic efficacy and safety of a novel intranasal morphine formulation (morphine plus chitosan), immediate release oral morphine, intravenous morphine, and placebo in a postsurgical dental pain model. Anesth Analg . 2008;107(6):2018-2024.
61. Stoker DG, Reber KR, Waltzman LS, et al. Analgesic efficacy and safety of morphine-chitosan nasal solution in patients with moderate to severe pain following orthopedic surgery. Pain Med . 2008;9(1):3-12.
62. Säkkinen M, Marvola J, Kanerva H, Lindevall K, Ahonen A, Marvola M. Are chitosan formulations mucoadhesive in the human small intestine? An evaluation based on gamma scintigraphy. Int J Pharm . 2006;307(2):285-291.
63. Mady MM, Darwish MM, Khalil S, Khalil WM. Biophysical studies on chitosan-coated liposomes. Eur Biophys J . 2009;38(8):1127-1133.
64. Jing SB, Li L, Ji D, Takiguchi Y, Yamaguchi T. Effect of chitosan on renal function in patients with chronic renal failure. J Pharm Pharmacol . 1997;49(7):721-723.
65. Huang SS, Sung SH, Chiang CE. Chitosan potentiation of warfarin effect. Ann Pharmacother . 2007;41(11):1912-1914.
66. Mansi IA, Huang J. Rhabdomyolysis in response to weight-loss herbal medicine. Am J Med Sci . 2004;327(2):129.
67. Wada M, Nishimura Y, Watanabe Y, Takita T, Innami S. Accelerating effect of chitosan intake on urinary calcium excretion by rats. Biosci Biotechnol Biochem . 1997;61(7):1206-1208.
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