Glucosamine Chondroitin MSM

product monograph

NPN: 80008779 3345-8 Class: Supplement

Ingredients (alphabetical) Medicinal: Chondroitin sulfate, glucosamine sulfate, MSM (methyl-sulfonyl-methane) Non-medicinal: Coating (dextrin, dextrose, lecithin, sodium carboxymethylcellulose, sodium citrate), croscarmellose sodium, microcrystalline cellulose, purified water, stearic acid, vegetable grade magnesium stearate Allergens Corn, shellfish, soy, starch Source Glucosamine from the hard shells of shell fish, Chondroitin sulfate from bovine trachea, MSM is a derivative of wood lignin. Uses Use as a symptomatic treatment for osteoarthritis. The more traditional glucosamine sulfate and chondroitin sulfate are used as restorative or anabolic agents for catilage [Bucci, 1994]. MSM provides some pain and anti-inflammatory relief, as well as sulfur for connective tissue enhancement. Recommended Amount Use 1 tablet TID. A workable reduced dosage can be tried for the maintenance phase based on the retention of treatment benefits. The dosage can gradually be reduced at the rate of 1 tablet per 3 months. Increase the dosage if pain returns. In the case of age-related osteoarthritis, it would probably be prudent to remain on at least 2 tablets per day indefinitely. Adverse Side Effects There are virtually no adverse side effects and no toxicity reported with glucosamine sulfate or chondroitin sulfate, both being endogenous to cartilage [Bucci, 1994]. Some have complained of initial gastric upset when using these substances, so recommend with meals. MSM is used at a reduced dose in this product compared to MSM used alone specifically for pain. MSM is not associated with adverse side effects. The overwhelming majority of people who have taken MSM have experienced no adverse effects. It has been taken in amounts greater than two grams for years without adverse effects [McCarty, 1994]. Taking too large an amount of MSM at one time can cause GI irritation with diarrhea and cramping, as well as minor headaches. This is resolved usually by dividing the daily amount or reducing the daily dose. Skin rashes have been reported with DMSO and therefore may be seen with MSM since it is a derivative of DMSO. Interactions There are no documented drug interactions with glucosamine sulfate salt or chondroitin sulfate. After many years of clinical use, MSM has not been found to adversely interact with any prescribed medication [McCarty, 1994]. DMSO has been found to counteract platelet aggregation. MSM as a derivative of DMSO has not been so studied but there is indication that it also will present a blood thinning effect. Those using coumadin or other blood thinning medication, including other natural blood thinning products like high doses of garlic, salmon oil, grape seed extract, and high doses of vitamin E, may be at risk of bleeding problems if using high doses of MSM. Precautions / Cautions The sulfate radical in the Glucosamine Sulfate salt is not as likely to cause allergy as is sulfite, but it may be possible, even

FOR PROFESSIONAL USE ONLY. This information is provided for educational purposes only and is not intended for self-diagnosis or self-treatment of a condition that should be interpreted by a qualified health care provider. While the information in this document has been carefully reviewed and reflects current clinical and scientific knowledge, it is subject to change.

UPDATED 10/01/2008 | Glucosamine Chondroitin MSM, 500/400/400 mg | NF0667T PAGE 1 OF 4 product monograph though sulfate is a metabolic necessity. The sulfate in chondroitin sulfate is covalently bound to the chondroitin and is not free to body fluids. Those allergic to shellfish have been concerned over a possible allergic reaction to glucosamine. Allergic reaction has not been reported as a practical concern, probably because the allergens are in the meat and the extraction process is able to denature any extraneous flesh protein. However, it must be recognized that individuals sometimes display profound sensitivity where it is not expected. If there is concern over possible allergic reaction, especially if anaphylactic reactions are possible, have the customer discuss the matter with their physician before commencing use. MSM has had a successful history of helping people without significant adverse effects. However, it is not yet fully known what might be the long-term effects in people using very large amounts. The experience of Dr Stanley W. Jacob, at the DMSO Clinic at the Oregon Health Sciences University in Portland, indicates that there are no special cautions [McCarty, 1994] other than those of prudent use associated with any substance that is still being explored and discovered without benefit of formal clinical trials. Concern has been expressed concerning those with a sulfa drug sensitivity, that a cross-sensitivity may be possible due to the sulfonyl group in MSM. Cross-sensitivity has not been widely reported but caution is advised. It is known that MSM will give false positive test results for elevated liver enzymes in liver function tests [McCarty, 1994]. Discontinuation of MSM should precede all liver testing by at least one week, with resumption following tests. Otherwise, MSM has been found to present no interference in blood chemistry tests. MSM has the potential for reducing platelet aggregation. See under Interactions. Clinical experience indicates that MSM is safe during pregnancy [McCarty, 1994]. However, it is recommended that pregnant women first discuss MSM with their physician before using MSM. Because MSM has the potential to raise one’s energy level, it is not recommended at bedtime. Contraindications None known. Pharmaceutical Commentary Glucosamine, itself, is a natural endogenous metabolite of cartilage and other connective tissue anabolic biochemistry. It is present in meat, fish, and poultry, but is only harvested commercially from the hard shells of shellfish, which are principally chitin (N-acetylglucosamine). Furthermore, humans are endowed with particular efficacy in absorbing glucosamine, as are other carnivorous mammals. These biological features constitute a straight forward and obvious rationale for using glucosamine supplementation in the clinical treatment of osteoarthritis. Indeed, early German clinical research, beginning in 1969, using glucosamine sulfate was predicated on the anabolic potential for cartilage renewal [McCarty, 1994]. Since these were uncontrolled studies they were not considered definitive. More impetus to pursue glucosamine became possible when an Italian pharmaceutical company introduced glucosamine sulfate in 500 mg tablets in the late 70s. Since its introduction in the early 1980s in commercial form, glucosamine has become highly regarded and a first-line treatment for osteoarthritis in many countries. International research has demonstrated that osteoarthritis could be arrested with glucosamine sulfate supplementation, if caught before the onset of irreversible joint damage. Significant reductions in joint pain, stiffness, tenderness, and swelling, as well as increased joint performance are the hallmarks of glucosamine sulfate. Even when researchers compared it to non-steroidal anti-inflammatory drug therapy (NSAID), like ibuprofen, glucosamine sulfate led to greater improvements in pain reduction and measurably better joint performance [Bucci, 1994] [McCarty, 1994]. Glucosamine hydrochloride has been introduced to offer an alternative approach. However, the sulfate moiety has important clinical value. Effective sulfur metabolism is imperative if osteoarthritis is to be arrested, and reversed where possible. Since reduced sulfur intake, and/or its synthesis into sulfate groups may be an important causative factor in a significant percent of arthritis, it seems prudent to use glucosamine sulfate with its preformed sulfate. Endogenously produced cartilage glycosaminoglycans (GAG’s), of which 66 percent is chondroitin sulfate, must be highly sulfated to electostatically bind water inside the cartilage. Cartilage hydration should be at 65 to 80 percent water. The first biochemical sign of failing cartilage is dehydration, and rehydration is integral to healing. Concerning chondroitin sulfate, because greater insights into the pathogenesis of osteoarthritis have revealed the critical role of the GAG’s and because chondroitin sulfate is a GAG, representing 66 percent of the GAG production, those seeking to

UPDATED 10/01/2008 | Glucosamine Chondroitin MSM, 500/400/400 mg | NF0667T PAGE 2 OF 4 product monograph enhance the clinical work with chondroproective agents have turned to chondroitin sulfate. Chondroitin sulfate demonstrates considerable tolerability and therapeutic efficacy. GAG’s in vitro, generally are able to inhibit certain enzymes present in the synovial fluid such as elastase from leukocytes, and hyaluronidase, thus offering a greater opportunity for preserving cartilage anabolic success by reducing inordinate cartilage catabolism [Conte, 1995] [Pipitone, 1991]. Chondroitin sulfate has been shown to inhibit up to 60% of the enzymatic action of elastase. Furthermore, chondroitin sulfate has demonstrated in vitro anti- inflammatory action by inhibiting the complement system. Chondroitin sulfate has always yielded clinical improvement regarding painful symptoms and limited joint function, and this is interpreted as proof of its anti-inflammatory action. Healthy cartilage is 65 to 80 percent water and hydration of the cartilage mass is directly controlled by the GAG’s. Chondroitin sulfate supplementation redresses cartilage dehydration, which is critical to arresting further decline and is almost certain to be a factor in any case of osteoarthritis [Theodosakis et al, 1997]. Since cartilage cannot have a direct blood supply, it depends on adequate nutritional supply via water borne nutrients transferred from the blood supplied synovial membrane. Dehydration of the cartilage mass imposes a reduced infiltration rate of nutrients to the cartilage chondrocytes, resulting in compromised ability to rebound and thrive under wear and tear. Chondroitin sulfate supplementation is considered a beneficial co-factor because it provides the immediate presence of the principal GAG of cartilage metabolism. Chondroitin sulfate will be produced by the influence of glucosamine, which is now recognized as the rate-limiting-factor in cartilage anabolic metabolism [McCarty, 1994]. However, there is a natural unpredictable lag time before the endogenous chondroitin sulfate supply is stable. In the compromised osteoarthritis joint, the pursuit of normalized cartilage metabolism is enhanced by ready-made molecules that are critical to the rehydration process. Many osteoarthritis sufferers have found a combined use to be beneficial. For those initiating treatment with glucosamine sulfate for the first time, it may be prudent to begin with the combination treatment. The absorption of chondroitin sulfate has been disputed, based on the relative size of the molecule. It is undoubtedly a very large structure for intact absorption. However, evidence does point to active pinocytosis with some enzymatic reductions in the size during the absorption process. Gastric juices do not seem able to digest chondroitin sulfate [Conte et al, 1995]. One may think of the reduced molecular fragments as modular segments that will present an economy of reconfiguration by the chondrocytes. The clinical efficacy of chondroitin sulfate as a sole treatment has been demonstrated on many occasions indicating that the absorption problem is largely academic [Theodosakis et al, 1997]. Chondroitin sulfate can be discontinued when significant pain reduction and improved joint function are achieved, these being the signs of greater anabolic rebound. Or the combination treatment can be continued as the treatment plan, later becoming a maintenance treatment at a reduced daily amount. Many consumers have come to believe that their chondroitin sulfate is indispensable and prefer to continue with it throughout the active treatment phase and then for their maintenance phase. MSM is a relatively new natural product and is known for pain reduction, as well as some decrease in inflammation. The daily amount of MSM in this product is offered to complement the pain reducing abilities of glucosamine and chondroitin sulfate. The potential for MSM to facilitate healing is thought to extend from a sulfur-donor action [Jacob et al, 2002]. Furthermore, since glucosamine sulfate alone has been an effective pain reducer that is as good as or greater than ibuprofen over time, a lower amount of MSM may be all that is needed to enhance the control of pain.

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References 3345-8 Bucci LR. Chondroprotective Agents Glucosamine Salts and Chondroitin Sulfate. Townsend Letters for Doctors, pp52-54, Jan 1994. Conte A, et al. Biochemical and Pharmacokinetic Aspects of Oral Treatment with Chondroitin Sulfate. Arzneim-Forsch 1995;45:918-925. Horvath K, et al. Toxicity of methylsulfonylmethane in rats. Food Chem Toxicol 2002;40(10):1459-1462. Jacob SW, Lawrence RM, Zucker M. The Miracle Of MSM: The Natural Solution For Pain. GP Putnam’s Son, New York NY, 1999. McCarty MF. The Neglect of Glucosamine as a Treatment for Osteoarthritis – A Personal Perspective. Medical Hypotheses 1994;42:323-327. Pipitone VR. Chondroprotection with Chondroitin Sulfate. Drugs In Experimental and Clinical Research 1991;17(1):3-7. Theodosakis J, et al. The Arthritis Cure. St Martin’s Press, New York NY, 1997.

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