N-acetyl glucosamine (NAG) is metabolized differently from other forms. It is selectively taken up by the liver and other tissues to make proteins, so it is less available to repair cartilage. Since pure glucosamine breaks down upon exposure to air and water, sodium chloride (salt) or potassium chloride is often used as a stabilizer in glucosamine sulfate, accounting for 30% of its weight. Sulfate accounts for 20% of the weight, so many glucosamine sulfate supplements are only half glucosamine.
Glucosamine HCL is 83% glucosamine, more stable than glucosamine sulfate and is sodium-free. Although many of the successful clinical trials used glucosamine sulfate, animal studies and cartilage culture studies all indicate that glucosamine HC1 is better than other forms of glucosamine for enhancing cartilage production.(1) Osteoarthritis Affects 80% of People over 50.
Painful osteoarthritis, characterized by joint degeneration, loss of cartilage and alterations of subchohondral bone, now affects more than 40 million Americans. This degenerative condition can affect virtually everyone who lives long enough. There is a 35% incidence in the knees as early as age 30 and the incidence increases dramatically with age, affecting 80% of persons over 50.(3) Add to that people with rheumatoid arthritis, tendonitis,bursitis, sports or any other joint injuries. Now standard treatment has focused on relieving the pain as much as possible, while the joints continue to deteriorate.
Cartilage Can Be Repaired and Rebuilt
Due to normal wear and tear, tissues are constantly being broken down and replaced or restructured. When aging, disease or injury makes conditions less than ideal, tissues are broken down faster than they can be regenerated. There is increased turnover of the cartilage matrix in osteoarthritis joints compared to normal joints. When the amount of matrix degraded by chondrocyticenzymes exceeds the amount of new matrix synthesized, the cartilage naturally degenerates. If this process is allowed to continue, destruction of cartilage is followed by hardening and formation of bone spurs in the joint margins. The result is pain, deformity and limited movement in the joint. However, research has shown that, by supplying the body with natural substances that inhibit cartilage breakdown and promote cartilage repair, damaged cartilage can be replaced by healthy new cartilage.(1-8) These effects have been confirmed by electron~micrography.(8)
Glucosamine . . . Both Precursor and Stimulant
Proteoglycans are a group of proteins that make up what is known as the ground substance of cartilage. This is what gives joints their strength and resilience. Glucosamine, a naturally occurring amino sugar made up of glucose and the amino acid glutamine, is both a precursor and a stimulant of proteoglycan synthesis. The availability of glucosamine is the key, rate-limiting step in GAG and proteoglycan synthesis. If sufficient glucosamine is available, then synthesis of proteoglycans can proceed.(2)Manganese is also an important cofactor in this process(4).
In several clinical studies, glucosamine has been shown to help relieve joint pain and stiffness of osteoarthritis. With continued use, it was even more effective than ibuprofen for joint pain. Tested against ibuprofen in an 8-week double-blind study involving 40 patients with unilateral degeneration of knee joints~, pain scores decreased faster in the ibuprofen group, but by the eighth week, glucosamine proved to be much more effective.(7)
Perhaps the most significant study on glucosamine and osteoarthritis comes from Pavia, Italy. There 80 patients were hospitalized for 30 days where they received rest and physical therapy, but no drugs. Half the patients were given glucosamine and the other half a placebo. As in other studies, big improvements were found in the glucosamine-treated group. Ten became symptom-free. No such improvements were seen in the control group. Near the end of the study, samples of cartilage were taken from a few of the subjects. When the cartilage samples were examined by scanning electron microscopy, damage and destruction of cartilage typical of osteoarthritis were found in the control subjects. Cartilage from the glucosamine-treated patients looked like it was from young, healthy people. Since all of the patients had severe osteoarthritis before the study, this study provided direct physical evidence of the ability of oral glucosamine to regenerate damaged cartilage.(l,8)
Glucosamine is easily and rapidly absorbed by the body. At physiological ph, 75% of glucosamine is not ionized and, therefore, easily crosses membranes. Absorption studies in both animals and humans indicate that glucosamine is rapidly absorbed and selectively taken up by articular cartilage.(2)
The Ground Substance... Chondroitin Sulfate
Chondroitin sulfate, a glycosaminoglycan (GAG) which is a type of proteoglycan, is predominant in the ground substance of cartilage, bone and blood vessels, but also occurs in other connective tissues. In test tubes, chondroitin sulfate stimulates the production of cartilage and arrests degradative enzymes that destroy it.(l) Clinical trials have demonstrated improved joint function and mobility, reduced pain and inflammation and an actual reversal of joint degeneration as detected by radiographs. This reversal includes observed improvement in the volume and quantity of the joint connective matrix and synovial fluid.(5) In addition to these improvements, another surprise benefit has been observed. Over long periods of supplementation, atherosclerotic changes took place and death from cardiovascular disease was nearly eliminated.(5) Remember chondroitin sulfate also forms the ground substance of blood vessels.
Since chondroitin is a very large molecule, some authorities claim that it cannot be absorbed and is of no value as a supplement. However, animal studies using radioactively tagged chondroitin sulfate have shown that, after being broken down into its components and absorbed, the metabolites are reassembled into new chondroitin sulfate molecules and added to the GAG supply needed to maintain healthy joints and other connective tissues.(6)
Standard Treatment Suppresses Symptoms and Worsens the Condition
Standard medical treatment for osteoarthritis is aspirin or other non-steroidal anti-inflammatory drugs (NSAIDs) which may relieve the pain, but do nothing to arrest the degenerative process. In fact, there is evidence that long-term use of NSAIDs can cause further joint damage and accelerate the progression of osteoarthritis by inhibiting synthesis of proteoglycans.Supplementary glucosamine and chondroitin sulfate may counteract this effect to some degree; however, use of NSAIDs should be discontinued as soon as possible.
Avoiding the Pain
The natural products, chondroitin sulfate and glucosamine HC1,are not analgesics in the same sense as aspirin, other NSAIDs and corticosteroids. Pain relief is seen with continued use as damaged tissues are repaired and rebuilt. In the comparison study with glucosamine and ibuprofen, it took 8 weeks for the glucosamine group to show less pain and more mobility than the ibuprofen group. However, their relief lasted for up to a month after the supplements were discontinued.(4,7) That doesn't happen with pain relief medications.
It may be possible to avoid, or at least postpone, joint degeneration indefinitely by taking these natural supplements prophylactically. It is definitely important to begin supplementation at the first sign of injury or degeneration. If the disease is allowed to progress until no cartilage remains, there is nothing left to repair.
REFERENCES
1. Bucci, Luke PhD, Pain Free, The Summit Group
2. Bucci, Luke, PhD, Nutrition Applied to Injury Rehabilitation and Sports Medicine, CRC Press.
3. Pizzorno, J. Natural Medicine Approach to Treating Osteoarthritis, Alt & Comp Ther, Jan/Feb, 1995;93-95.
4. McCarty, M, The Neglect of Glucosamine as a Treatment for Osteoarthritis -- A Personal Perspective, Medical Hypotheses(1994) 42j323-327. 5. Chondroitin Sulfate - Cartilage Compound Confounds Joint Problems, HCN, Spring/Summmer 1997.
6. Conte, A, et al, Biochemical and Pharmocokinetic Aspects of Oral Treatment with Chondroitin Sulfate, Arzneimittelforschung 45:8, 918-925, Aug. 1995.
7. Lopez, V, Double-blind clinical evaluation of the relative efficacy of ibuprofen and glucosamine sulfate in the management of osteoarthrosis of the knee in out-patients, Curr Med Res Opin,9:145-149, 1982
8. Drovanti, A, et al., Therapeutic activity of oral glucosaminesulfate in osteoarthrosis: A placebo-controlled double-blind investigation, Clin Ther 3(4);260-272, 1980.
2. Bucci, Luke, PhD, Nutrition Applied to Injury Rehabilitation and Sports Medicine, CRC Press.
3. Pizzorno, J. Natural Medicine Approach to Treating Osteoarthritis, Alt & Comp Ther, Jan/Feb, 1995;93-95.
4. McCarty, M, The Neglect of Glucosamine as a Treatment for Osteoarthritis -- A Personal Perspective, Medical Hypotheses(1994) 42j323-327. 5. Chondroitin Sulfate - Cartilage Compound Confounds Joint Problems, HCN, Spring/Summmer 1997.
6. Conte, A, et al, Biochemical and Pharmocokinetic Aspects of Oral Treatment with Chondroitin Sulfate, Arzneimittelforschung 45:8, 918-925, Aug. 1995.
7. Lopez, V, Double-blind clinical evaluation of the relative efficacy of ibuprofen and glucosamine sulfate in the management of osteoarthrosis of the knee in out-patients, Curr Med Res Opin,9:145-149, 1982
8. Drovanti, A, et al., Therapeutic activity of oral glucosaminesulfate in osteoarthrosis: A placebo-controlled double-blind investigation, Clin Ther 3(4);260-272, 1980.
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