Chitosan

Common Name(s): Chitosan , chitin

Uses

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.

Dosing

Chitosan has been administered at wide-ranging doses in clinical studies. In studies evaluating weight loss, 2.4 g/day is commonly used.

Contraindications

None well established.

Pregnancy/Lactation

Information regarding safety and efficacy in pregnancy and lactation is lacking.

Interactions

Data are limited. Potentiation of the anticoagulant effect of warfarin was reported in a patient receiving chitosan 2.4 g/day.

Adverse Reactions

The potential for allergy exists in individuals allergic to shellfish. Clinical trials report few adverse events, generally limited to flatulence and constipation.

Toxicology

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

History

Chitosan has been used in water purification plants to absorb greases, oils, metals, and toxic substances. Chitosan has been used in the cosmetic and fabric industry. 2 , 5 , 6 , 7 , 8

Chemistry

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 Pharmacology

Antibacterial (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

Chitosan also exerts action against candida and chlamydia. 24 , 25

Cholesterol-lowering effects and weight-loss

Positively charged amino groups in chitosan bind to negatively charged lipid and bile components, preventing their absorption by the body. 1

Animal 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. 32

Clinical 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

Other studies report on the effect of chitosan on fat absorption, again with conflicting results, 38 , 39 , 40 with some researchers suggesting a gender-specific response. 39

Hemostasis

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's characteristic as a film-forming and protective polysaccharide suggests a potential role in wound healing and burns. Its applications in this area have been investigated. 43 , 44 , 45 , 46

Other uses

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

Dosage

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

A chitosan 0.1% solution has been used in ophthalmology, 47 while 1% w/w solutions have been used as a mouthwash. 19 Chewing gums releasing 2% w/v in saliva have been used in dental studies. 20 , 21

Pregnancy/Lactation

Information regarding safety and efficacy in pregnancy and lactation is lacking.

Interactions

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

Adverse Reactions

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

Toxicology

Chitosan's toxicity profile is relatively low. Dietary chitosan reportedly affects calcium metabolism in animals. 67

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