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CHITOSAN FOR CHOLESTEROL MANAGEMENT
Mikio Kato, MD, FACS, FACOG Gene Mazzocco, MD, FACP Edward O. Dingilian, PE
The past decade has witnessed emergence of conclusive evidence that lowering serum cholesterol level can markedly and safely reduce the risk of coronary heart disease (CHD) events, including cardiac death, myocardial infarction, unstable angina, and stroke.1CHD expressed as myocardial infarction is the leading cause of death in American men and women (American Heart Association, 1997). Russian Federation reports three times more incidents of CHD compared to United States, or China, and United States has twice more than Japan (American Heart Association, 1999). Among immigrants who migrate from countries with low rates of death from CHD, the death rate is similar to that of their adoptive country after acculturation than to that of their native country.
The National Cholesterol Education Program (NCEP) has identified low-density lipoprotein cholesterol (LDL-C) as the primary target of cholesterol lowering therapy.2On the basis of epidemiological data, it has been predicted that each 1 percent reduction in the level of LDL cholesterol results in a reduction of 1.0 to 1.5 percent in the risk of cardiovascular events.3
Cholesterol is essential to body function and exists in the cell membranes of all body tissues. Cholesterol is needed to manufacture cell membranes, synthesize certain hormones and digest dietary fat and act as an insulator for neuronal axons. Dietary cholesterol mostly from animal and dairy products, is absorbed through the small intestine after being hydrolyzed by the pancreatic cholesterol esterase. Hydrolyzed cholesterol with digested dietary fat called triglycerides are transported to the bloodstream through the small intestinal wall after being coated with a protein called chylomicron lipoprotein. Chylomicron main function is to transport dietary triglyceride from the intestine to tissues throughout the body, also it provides the means to deliver hydrolyzed cholesterol from the intestine to the liver.
The bloodstream has other lipoproteins, each with its distinct metabolic role. These lipoproteins are classified primarily on the basis of their density. Chylomicron and very low density lipoprotein (VLDL) are the least dense, then intermediate density lipoprotein (IDL), low density lipoprotein (LDL), and the most dense being high density lipoprotein (HDL). Each of these lipoproteins have a range ratio of triglyceride to cholesterol content in their core. 60-70 percent of total bloodstream cholesterol is carried by LDL, 20-30 percent by HDL, and VLDL carries 10-15 percent. LDL cholesterol are often referred to as “bad” cholesterol because they can build up and harden in the arteries, and eventually choke off the supply of blood to the heart. HDL are referred to as “good” cholesterol, because they collect excess cholesterol and transport back to the liver.
VLDL are synthesized in the liver, the core being rich in triglyceride compared to cholesterol. VLDL transport triglyceride to tissues throughout the body, and carry the liver cholesterol into the bloodstream. LDL is the catabolic product of VLDL after VLDL lose most of their triglyceride content. LDL is smaller in size and denser compared to VLDL, the LDL core being mainly made up of cholesterol. IDL is the transitional intermediate between VLDL and LDL. HDL are the smallest and densest of the blood lipoproteins. HDL mostly originate in the liver and the rest in the intestine. HDL become cholesterol enriched as they collect cholesterol from body tissues. HDL acquired cholesterol is removed by the liver, or transferred to chylomicron remnants, or LDL, or recycled back to the bloodstream by incorporating in VLDL. Liver removed cholesterol may be excreted by bile after its conversion to bile acids. The American Heart Association reports that some experts believe HDL removes excess cholesterol from arteries.
Some 53 million Americans have high cholesterol levels. Current national guidelines list 200mg/dl of total cholesterol as desirable level, over 240mg/dl as high, and less than 35mg/dl of HDL as low. New guidelines unveiled by NIH recommend desirable total cholesterol to remain 200mg/dl, but add that 100mg/dl of LDL as optimal, 130-159mg/dl borderline high, 160mg/dl high, 190mg/dl as very high, and HDL raised from 35mg/dl to 40mg/dl.
Family history such as Tangier disease, hormonal influences, metabolic disorders like diabetes and obesity, alcohol, smoking, high fat diets, lack of physical activity are contributors to cholesterol disorders. In women, obesity is associated with triglyceride levels that are 35 to 45mg/dl higher than average, and HDL cholesterol levels that are 5 to 9 mg/dl lower.4 Women below the age 45 on oral contraceptives have higher serum cholesterol and triglyceride than women not taking them.5 Individuals with hyperthyroism sometimes may have elevated HDL as well as LDL.5 National Cholesterol Education Program (NCEP) lists diets to reduce LDL cholesterol levels. The recommended diets emphasize more fruits, vegetables, grains, legumes, fish, lean meats, low fat dairy products, and ample physical exercise. Cholesterol synthesis by the body is influenced by dietary consumption of cholesterol. While most research in this area was performed on rodents, it seems that as the dietary level of cholesterol increases, the body synthesis of cholesterol decreases. However, this effect mainly takes place in the liver.5
Physicians may consider medical therapy if dietary changes coupled with exercise fail to lower high cholesterol levels. Medical therapy includes several classes of prescription drugs. One class is resins that bind with bile acids in the gastro-intestinal tract and the liver cannot produce more bile acid, thereby less cholesterol is available to the blood. Another class of drugs decreases ability of the liver to produce triglycerides, which in turn reduce liver’s synthesis of VLDL, hence less LDL is present in the bloodstream. A recent class of cholesterol reducing drugs is represented by statins. Statins inhibit the body enzyme needed by the liver to synthesize cholesterol. Like any other drug, these medications are not for everyone, they can cause side effects, and patients must consult their physicians.
Limited human,7-11 rodent12,13, and outside the body research show dietary supplement “chitosan” taken orally over a period of time decreases LDL and increases HDL levels in the bloodstream. Chitosan is extracted from natural chitin found in shrimp, crab, and lobster shells. Chitosan when dissolves in gastric acid, it binds to digested dietary fats and partially inhibits absorption in the bloodstream.
Chitosan also forms micelles with cholesterol and dietary cholesterol in the alkaline fluids in the upper part of the intestine, resulting in the depression of the absorption of dietary cholesterol and the circulation to the liver.14
According to published literature the hypochlesterolemic effect of chitosan seems to vary, and in part depends on the chitosan purity, and other properties, ingested quantity and duration of the test. The mechanism as to how chitosan affects blood cholesterol levels in humans is not well defined, and is the subject of current research. Chitosan appears to be devoid of side effects in daily dosages averaging 1500mg-2500mg. However it is not recommended for those with shellfish allergies. Pregnant, lactating women, are also recommended not to use chitosan. Individuals of 14 years of age or less, and persons on medication are asked to consult their physician prior to using chitosan.
Since a large percentage of cholesterol disorders are attributed to dietary factors, lifestyle changes including
limiting saturated fats, increasing intake of soluble fiber, fresh fruits and vegetables, weight reduction and increased physical activity are the best choices for a healthy and long living.
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2. Summary of the second report of National Cholesterol Education Program (NCEP). Expert Panel on
detection, evaluation, and treatment of high blood cholesterol (Adult Treatment Panel II). JAMA 1993; 269:3015-3023
3. Brown GB et al: Simvastatin and niacin, antioxidant vitamins, or the combination for the prevention of coronary disease. N Engl J Med 2001; 345:1583-1592
4. Denke MA et al: Excess body weight. An under-recognized contributor to dyslipidemia in white American women. Arch Intern Med 1994: 154: 401
5. Thompson GR: Abnormalities of plasma lipoprotein transport. Plasma lipids and their role in disease 1999; p17-43
6. Wildman REC et al: Lipids. Advanced human nutrition 2000; p99-122
7. Maezaki Y et al: Hypocholesterolemic effect of chitosan in adult males. Biosci. Biotech. Biochem 1993; 53(9): 1439-1444
8. Macchi G: A new approach to the treatment of obesity: Chitosan’s effects on body weight reduction and plasma cholesterol’s levels. Acta Toxicol. Ther. 1996, vol XVII:303-320
9. Jing SB et al: Effect of chitosan on renal function in patients with chronic renal failure. J Pharm Pharmacol 1997; 49(7): 721-723
10. Muzzarelli RAA: Management of hypercholesterolemia and overweight by oral administration of chitosans. New biomedical materials 1998, p135-142
11. Wuolijoki E et al: Decrease in serum LDL cholesterol with microcrystalline chitosan Find. Exp Clin Pharm 1999; 21(5): 357-361
12. Han LK et al: Reduction in the fat storage during chitin-chitosan treatment in mice fed high diet. Int J Obes Relat Metab Disord 1999; 23(2): 174-179
13. Lian GM et al: Effect of high molecular weight chitosan on nutrient digestibility, blood lipids and fecal contents in rats. Advances in Chitin Science 1998; p299-306
14. Muzzarelli RAA: Chitosan based dietary foods. Carbohy. Polym 1996; 29: 309-316
Mikio Kato, MD, FACS, FACOG, Gene Mazzocco, MD, FACP
Edward O. Dingilian, PE, President, United Chitotechnologies, Inc., USA
Correspondence to: Edward O. Dingilian, PE, (e-mail: Edingilian@aol.com)
January 7, 2002