Ebook Sports Nutrition: Fats and Proteins (Part 2)

10 Glucosamine and Chondroitin Sulfate Catherine G.R. Jackson CONTENTS 10.1 Introduction..................................................................................................187 10.2 Description of Products ...............................................................................188 10.2.1 Glucosamine.....................................................................................188 10.2.2 Chondroitin Sulfate..........................................................................189 10.3 Mechanisms..................................................................................................189 10.3.1 Glucosamine.....................................................................................189 10.3.2 Chondroitin Sulfate..........................................................................190 10.4 Review of Research Studies and Clinical Trials.........................................190 10.4.1 Glucosamine.....................................................................................190 10.4.2 Chondroitin Sulfate..........................................................................191 10.4.3 Combined Glucosamine and Chondroitin Sulfate...........................192 10.5 Side Effects ..................................................................................................194 10.5.1 Glucosamine.....................................................................................194 10.5.2 Chondroitin Sulfate..........................................................................194 10.6 Use in Sport and Exercise ...........................................................................194 10.7 Summary and Recommendations................................................................195 References..............................................................................................................196 10.1 INTRODUCTION Americans currently spend more money on natural remedies for osteoarthritis than for any other medical condition,1 thus producing an extremely large and lucrative market for the multi-billion-dollar supplement industry. Osteoarthritis is destined to become one of the most prevalent and costly diseases in our society. It is estimated that currently over 21 million adults in the U.S. suffer from osteoarthritis; it is predicted that this number will double over the next 20 years. Increasing age, female gender, and obesity are risk factors. It is also known that athletes of all types frequently live with chronic joint pain often associated with overuse injuries; they present an additional multi-million-dollar market for the supplements. Glucosamine and chondroitin sulfate have been widely publicized in the popular media as being capable of decelerating the degenerative processes, decreasing pain, and maintaining and improving joint function 187 188 Sports Nutrition: Fats and Proteins in osteoarthritis and other conditions where joint pain is the result. However, studies have not been able to confirm these statements. There are numerous anecdotal reports to which supplement manufacturers refer. However, the majority of clinical trials have small sample sizes, little or no follow-up, and are sponsored by the supplement manufacturers.2 Problems in evaluation of efficacy begin with classification of these agents, as they have been called drugs, nutriceuticals, food supplements, alternative therapy, homeopathic therapy, and complementary therapy. Individuals with joint pain now consume very large quantities of glucosamine and chondroitin primarily based on a great volume of media coverage as to their value. There is currently much controversy and confusion concerning the topic. In osteoarthritis the chondrocytes and aqueous matrix decrease with age, which results in poor-quality cartilage. Bones may become exposed and rub together, which creates damage and pain. With time, bones chip and fracture, which can lead to bone growth, producing increased pain and lack of mobility. The individual finds that this disrupts daily life and activity makes symptoms worse. Patients feel unwell and depressed. Active individuals may terminate exercise completely, which increases the risks of inactivity-related chronic diseases. Osteoarthritis affects approximately 12% of the U.S. population and is a common cause of age-related pain and physical disability. The condition itself, however, is poorly understood. The degenerative process is not slowed or reversed with current treatments, which include aspirin, acetaminophen, and nonsteroidal anti-inflamma-tory drugs (NSAIDs). Interestingly, the origin of pain caused by the condition is unclear and, upon investigation, is more often attributed to lesions or referred pain rather than articular problems, as there are no nerves in articular cartilage. The biochemistry of glucosamine has led to the suggestion that its use might stop and possibly reverse the degenerative process. However, evidence is questionable. Chard and Dieppe3 showed great insight into the problem by commenting that glucosamine may become the first agent about which we have more published systematic reviews, editorials, meta-analyses, and comments than primary research papers. They iden-tified only 24 primary research studies, but also found 9 reviews and numerous comments and editorials. Most primary research studies are poor, and positive results are invariably found in supplement manufacturer-sponsored research. Chard and Dieppe3 also concluded that there is more hype than magic, rationales for use are unclear, best dose and route of administration are unknown, and published work does not allow conclusions about efficacy or effectiveness. However, since it is safe, toxicity concerns cannot be raised. There is a need for regulation, as there could be long-term side effects, while the length of treatment is not known. Other uses of the drugs are to treat migraines,4 gastrointestinal disorders such as Crohn’s disease, ulcerative colitis, atherosclerosis, and capsular contracture in breast implants.5 10.2 DESCRIPTION OF PRODUCTS 10.2.1 GLUCOSAMINE Glucosamine is an amino monosaccharide (amine sugar) that can be found in chitin, glycoproteins, and the glycosaminoglycans (mucopolysaccharides), such as heparin Glucosamine and Chondroitin Sulfate 189 sulfate and hyaluronic acid. Other chemical designations are 2-amino-2-deoxy-beta-D-glucopyranose, 2-amino-2-deoxyglucose, and chitosamine.6 It is available over the counter as a nutritional supplement as glucosamine hydrochloride (glucosamine HCl), glucosamine sulfate, or N-acetyl-glucosamine. Research has used primarily the chlo-ride and sulfate salts, which are those most commonly purchased. The chemical structure of glucosamine is such that at physiologic and neutral pH the molecule has a positive charge. Negative anions are found in the salt forms, which neutralize the charge. In glucosamine sulfate the anion is sulfate, in glu-cosamine HCl the anion is chloride, and in N-acetylglucosamine the amino group is acetylated, which results in a neutral charge. All forms are water soluble. Nutri-tional supplements are usually derived from marine exoskeletons with the chitin extracted from seashells. There are also synthetic forms. Since glucosamine falls under the 1994 Dietary Supplement Health and Education Act (DSHEA) and is classified as a medicinal product, its manufacture is not regulated. As a result, there is no standardization of active ingredients, concentrations, or reporting requirements for labels. A consumer cannot know what is contained in the product as glucosamine is inherently unstable and must be combined with other ingredients for stability. Analysis of products consistently produces the result that many formulations do not contain ingredients listed on the label.7 10.2.2 CHONDROITIN SULFATE Chondroitin sulfate is a heteropolysaccharide identified as a glycosaminoglycan (GAG). GAGs form the ground substance in connective tissue’s extracellular matrix. The molecule itself is comprised of repeating linear units of D-galactosamine and D-glucuronic acid. It is found in human cartilage, cornea, bone arterial walls, and skin; this form is called chondroitin sulfate A (chondroitin 4-sulfate). Cartilage of humans, fish, and shark contains chondroitin sulfate C (chondroitin 6-sulfate). The two forms differ in the amino group of chondroitin sulfate A and in the sulfate group of chondroitin sulfate C. There is a B form called dermatan sulfate, which is found in heart valves, tendons, skin, and arterial walls. The molecular weights of all forms range from 5,000 to 50,000 daltons. It is available over the counter as a nutritional supplement, usually in an isomeric mixture of A and C forms. Nutritional supple-ments are derived from varied sources, such as pork by-products (ears, snout), bovine trachea cartilaginous rings, whale septum, and shark cartilage.6 10.3 MECHANISMS 10.3.1 GLUCOSAMINE Glucosamine is produced within the body in small amounts in reactions involving glucose and glutamic acid. It is a small molecule (molecular weight = 179.17) that is easily absorbed in vivo. Humans may decrease production with aging. It is not found in any common foods and cannot be obtained externally. If the body is not synthesizing the substance, it needs to be taken as a supplement. It is found in abundance in cartilage, with small amounts measured in tendons and ligaments; it is an essential substrate matrix that is a component of cartilage. 190 Sports Nutrition: Fats and Proteins It is still not clear what the actions are of glucosamine taken as a nutritional supplement. Purported effects are the promotion and maintenance of the structure and function of cartilage in the joints of the body. It has also been reported that glucosamine has anti-inflammatory effects. The biochemistry, however, has been known for quite some time. Glucosamine, a sugar and a sulfated amino monosac-charide, is involved in glycoprotein metabolism where it is found in proteoglycans as polysaccharide groups called GAGs. All GAGs contain derivatives of glucosamine or glactosamine. These polysaccharides comprise 95% of the ground substance in the intracellular matrix of connective tissue. One of the GAGs, hyaluronic acid, is essential for the function of articular cartilage and is responsible for shock absorbing and deformability functions.6 In vitro studies show that it can alter chondrocyte metabolism; it is not clear whether oral glucosamine can reach chondrocytes in vivo.8 Over 90% of the studies in glucosamine pharmacokinetics have used animal models. It has been shown that about 90% of the salt is absorbed from the small intestine and transported to the liver. The majority is then catabolized in the first pass; seldom is it detected in serum after oral ingestion. Free glucosamine is not usually detected in plasma.9,10 How much is taken into joints is not known for humans, while some uptake is seen in articular cartilage in animals. 10.3.2 CHONDROITIN SULFATE It is still not clear what the actions are of chondroitin sulfate when taken as a nutritional supplement. Purported effects are the promotion and maintenance of the structure and function of cartilage in the joints of the body. It has also been reported that chondroitin sulfate has anti-inflammatory and pain relief effects. The biochem-istry has been known for some time. Chondroitin sulfate is a GAG, previously described in the glucosamine mechanisms. It is essential for the structure and function of articular cartilage and provides the same properties as hyaluronic acid. While intra-articular injections of hyaluronic acid have been shown to relieve joint pain and improve mobility, the same has not yet been demonstrated for chondroitin sulfate. It is speculated that oral ingestion of chondroitin sulfate may lead to an increase in hyaluronic acid. Thus, cartilage breakdown would be inhibited.6 It has been shown that absorption is from the stomach and small intestine. High molecular weight forms are not significantly absorbed, while low molecular weight forms show significant absorption after oral ingestion. How much is taken into joints is not known for humans, while it is known that some does enter the joint space. 10.4 REVIEW OF RESEARCH STUDIES AND CLINICAL TRIALS 10.4.1 GLUCOSAMINE Glucosamine was looked at for use in reducing the symptoms of osteoarthritis as early as 1969.11 A number of years ago early studies showed, in 20 patients, that the use of glucosamine sulfate resulted in patients who experience lessening or disappearance of symptoms with use over 6 to 8 weeks12 with no adverse reactions. Barclay and associates13 reviewed the pharmacology and pharmacokinetics of glucosamine and Glucosamine and Chondroitin Sulfate 191 evaluated the available literature regarding safety and efficacy. Of the literature pub-lished between 1965 and 1997, three critically evaluated studies were found that reported a decrease in the symptoms of osteoarthritis. However, flaws in the research designs precluded making positive recommendations for improvements in the symp-toms of osteoarthritis with oral glucosamine use. Intramuscular glucosamine admin-istration, however, is effective.14 No statistically significant difference in glucosamine sulfate and placebo were found in managing pain, leading to the conclusion by one group that the supplement was no more effective than the placebo.15 A 12-week study of 2000 mg/day doses of glucosamine in subjects with articular cartilage damage and possible osteoarthritis showed self-reported improvement in symptoms. However, while clinical and functional test scores improved over the evaluation period in both the test and placebo groups, there were no significant differences between groups at the end of the study.16 The trend reported was that improvement could be seen after 8 weeks. A 3-year prospective, placebo-controlled study evaluating the effect of glucosamine sulfate use on joint space narrowing in knee osteoarthritis did not find statistically significant results in the most severe cases. However, patients with less severe radiographic knee osteoarthritis showed a trend toward significant reduction in joint space narrowing.17 It has been shown that a 3-year treatment of osteoarthritis with glucosamine sulfate use retarded the pro-gression of knee osteoarthritis as determined by a lesser joint space narrowing than in the placebo group.18 The authors suggested that this retardation of narrowing of joint space might modify and slow the disease process; however, joint space nar-rowing is not associated with pain. Positive results are difficult to demonstrate (glucosamine hydrochloride). The objec-tive measurement differences between groups are not usually statistically significant. Results are reported as positive trends19 in objective measurements. More often than not, however, patients report that they feel better than at the start of the trial.19 Glu-cosamine use was shown to preserve joint space in that significant narrowing did not occur. It was suggested that long-term use prevents joint structure changes and improves disease symptoms.20 However, a change in joint space is not necessarily associated with a change in pain levels. Some have reported overall positive results.21 Literature reviews usually conclude that glucosamine may not only provide symptomatic pain relief, but also have a role in chondroprotection.22 Even though no differences were found between the glucosamine and placebo groups, and positive results were modest, it was still concluded that glucosamine sulfate may be a safe and effective symptomatic slow-acting drug for osteoarthritis.23 Glucosamine can be administered orally, intravenously, intramuscularly, and intra-articularly. Reviews of primarily European and Asian literature have suggested that glucosamine sulfate use may provide pain relief, reduce tenderness, and improve mobility in patients with osteoarthritis.24 Studies in the U.S. do not support these conclusions. 10.4.2 CHONDROITIN SULFATE A number of years ago, based on in vitro studies, chondroitin sulfate was identified as a supplement that may provide chondroprotection.25 A multicenter randomized, double-blind, controlled study of 143 subjects with osteoarthritis that used three ... - tailieumienphi.vn