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.

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Ah.wocf: Clodronate. etidronate and pamidronate are bisphosphonates introduced in the treatment of hypercalcaemia and osteoporosis. Interestingly, they also inhibit development of experimental atherosclerosis and affect smooth muscle tone of isolated rat tail artery. We have studied in vitro whether these hydrophilic compounds 1) accumulate in the wall of the human artery, 2) influence human arterial tone, and 3) interfere with the vascular action of L-type Ca2+ antagonists. Human internal mammary artery rings were incubated with ''C-labelled bisphosphonates. After a 2-hr incubation, the ratios of artery-to-incubate concentrations with 4 and 40 pmolil of clodronate were, respectively, 3.020.5 (mean?S.E.M.) and 1.320.2, with 4 and 40 pmol/l of etidronate 7.4+-0.9 and 3.2?0.4, and with 0.4 and 4 pmol/l of pamidronate 4.7+0.7 and 3.920.8. Both tested bisphosphonates, clodronate and pamidronate, reduced the arterial contractile force induced by a-adrenergic stimulation with noradrenaline and membrane depolarization with high concentration of KCI. Clodronate also decreased the arterial contraction induced by cumulative addition of Ca2+ with KCI as the agonist, and had an additive inhibitory effect on this response with the L-type Ca2+-channel blocker nifedipine. The results demostrate that I ) bisphosphonates accumulate markedly in human artery, 2) clodronate and pamidronate reduce human arterial contactile force to a-adrenergic and depolarizing stimuli, and 3) as shown with clodronate, bisphosphonates may exert an additive inhibitory effect on human arterial contractions with an L-type Ca2+-channel blocker.