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ChondroCareª Glucosamine & Chondroitin Complex
Dietary Supplement

120 tablets

ChondroCareª is a comprehensive formula designed to support healthy joints by featuring glucosamine sulfate and chondroitin sulfate. Glucosamine is the basis for the formation of vital connective tissue substances such as proteoglycans and glycosamino-glycans (GAGs). Chondroitin sulfate supports healthy joint matrix formation. ChondroCare also features the valuable mineral synergists zinc, copper, manganese, and selenium for added support of joint tissues.

These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease.

Directions: Take 6 tablets daily or as directed by your health care practitioner.

Caution: Keep out of the reach of children.

Storage: Keep tightly closed in a cool, dry place.

Supplement Facts
Serving Size : 2 Tablets
Servings Per Container : 60
Per Serving (2 Tablets) Per Day (6 Tablets)
Amount % Daily Value Amount % Daily Value
Vitamin C 35 mg 58% 105 mg 175%
(as manganese ascorbate)
Zinc (as zinc glycinate ) 5 mg 33% 15 mg 100%
Selenium 100 mcg 143% 300 mcg 429%
(as selenium amino acid complex )
Copper (as copper lysinate ) 0.66 mg 33% 2 mg 100%
Manganese 7 mg 350% 20 mg 1000%
(as manganese ascorbate)
Glucosamine Sulfate KCl 500 mg ** 1500 mg **
Chondroitin Sulfate 400 mg ** 1200 mg **

**Daily Value not established.

Other Ingredients: Fibersol¨ 2 (maltodextrin with soluble fiber), cellulose, croscarmellose sodium, stearic acid, magnesium stearate, and silica.
Patented mineral amino acid chelates: U.S. Patent #4,599,152 Albion¨.

Glucosamine sulphate

A controlled clinical investigation in arthrosis Efficacy and tolerance of a new preparation of pure glucosamine sulphate, in injectable and oral form, were investigated in 30 patients with osteoarthrosis. Two groups of in-patients with chronic degenerative articular disorders received daily for 7 days either 400 mg glucosamine sulphate or a piperazine/chlorbutanol combination by intravenous or intramuscular injection. During the 2 following weeks, the patients receiving glucosamine had oral glucosamine capsules (6 x 250 mg daily); the other group had placebo. Efficacy was tested by semiquantitative scoring of pain at rest and during active and passive movements, as well as limitation of articular function, before and after 7 and 21 days of treatment. Patients were positively questioned daily for possible intolerance symptoms.

Haematology, circulatory data and urine analysis were tested before and after treatment. During both initial parenteral treatments, each symptom significantly improved, but to a faster and greater extent in the group treated with glucosamine. During the maintenance period, a further improvement was recorded in the patients treated with glucosamine, whereas in those on placebo the symptom scores increased almost to the pre-treatment level. This was considered the major difference between basic therapy, such as with glucosamine, and purely symptomatic treatment. Clinical and biological tolerance were excellent with both treatments, and no definitely drug-related complaints were recorded. It is suggested that parenteral and/or oral treatment with pure glucosamine sulphate should be considered as basic therapy for the management of primary or secondary degenerative osteoarthrosis disorders.DีAmbrosio E, Casa B, Bompasi R, et al. Glucosamine sulphate: a controlled clinical investigation in arthrosis. Pharmatherapeutica 2:504-508; 1981.

Double-blind clinical evaluation of oral glucosamine sulphate in the basic treatment of osteoarthrosis

The efficacy and tolerance of oral glucosamine sulphate were tested against placebo in a prospective double-blind trial in 20 out-patients with established osteoarthrosis. Two capsules of either glucosamine sulphate (250 mg) or placebo were administered 3-times daily over a period of 6 to 8 weeks. Articular pain, joint tenderness and restricted movement were semi-quantitatively scored 1 to 4 every 3 days, and individually averaged over the treatment period (overall composite score). Possible side-reactions were similarly scored upon positive questioning of the patients. Haematology, erythrocyte sedimentation rate, urine analysis and X-rays were recorded before and after treatment. Significant alleviation of symptoms was associated with the use of the active drug at the prescribed dose. Similarly, patients given glucosamine sulphate experienced earlier alleviation of symptoms compared with those who had placebo. The use of glucosamine sulphate also resulted in a significantly larger proportion of patients who experienced lessening or disappearance of symptoms within the trial period. No adverse reactions were reported by the patients treated with glucosamine, and no variation in laboratory tests was recorded.Pujalte JM, Llavore EP, Ylescupidez FR. Double-blind clinical evaluation of oral glucosamine sulphate in the basic treatment of osteoarthrosis. Curr Med Res Opin 7:110-114; 1980.

Oral glucosamine sulphate in the management of arthrosis: report on a multi-centre open investigation in Portugal

An open study was carried out by 252 doctors throughout Portugal to assess the effectiveness and tolerability of oral glucosamine sulphate in the treatment of arthrosis, Patients received 1.5 g daily in 3 divided doses over a mean period of 30-14 days. The results from 1208 patients were analyzed and showed that the symptoms of pain at rest, on standing and on exercise and limited active and passive movements improved steadily through the treatment period. The improvement obtained lasted for a period of 6 to 12 weeks after the end of treatment. Objective therapeutic efficacy was rated by the doctors as ิgoodี in 59% of patients, and ิsufficientี in a further 36%. These results were significantly better than those obtained with previous treatments (except for injectable glucosamine) in the same patients. Sex, age, localization of arthrosis, concomitant illnesses or concomitant treatments did not influence the frequency of responders to treatment. Oral glucosamine was fully tolerated by 86% of patients, a significantly larger proportion than that reported with other previous treatments and approached only by injectable glucosamine. The onset of possible side-effects was significantly related to pre-existing gastrointestinal disorders and related treatments, and to concomitant diuretic treatment.Tapadinhas MJ, Rivera IC, Bignamini AA. Oral glucosamine sulphate in the management of arthrosis: report on a multi-centre open investigation in Portugal. Pharmatherapeutica 3:157-168; 1982.

Double-blind clinical evaluation of the relative efficacy of ibuprofen and glucosamine sulphate in the management of osteoarthrosis of the knee in out-patients.

A double-blind trial was carried out in 40 out-patients with unilateral osteoarthrosis of the knee to compare the efficacy and tolerance of oral treatment with 1.5 g glucosamine sulphate or 1.2 g ibuprofen daily over a period of 8 weeks. Pain scores decreased faster during the first 2 weeks in the ibuprofen than in the glucosamine treatment group. Although the rate of decrease was slower, the reduction in pain scores was continued throughout the trial period in patients on glucosamine and the difference between the two groups turned significantly in favour of glucosamine at Week 8. No significant differences were observed in swelling or any of the other parameters monitored. Tolerance was satisfactory with both treatments, with only minor complaints being reported by 2 patients on glucosamine compared with 5 patients on ibuprofen.Vaz AL. Double-blind clinical evaluation of the relative efficacy of ibuprofen and glucosamine sulphate in the management of osteoarthrosis of the knee in out-patients. Curr Med Res Opin 8:145-149; 1982.

The influence of glucosamine on the antiexudative effect of nonsteroidal anti-inflammatory agents.

The study of the antiexudative activities of voltaren, indomethacin and piroxicam in combination with glucosamine on the model of carrageenan inflammation showed that the combination makes it possible to decrease the effective doses of nonsteroidal anti-inflammaroty drugs by 2-2.7 times with the preservation of the pronounced antiexudative activity. A diverse influence of aminosugar on the anti-inflammatory effect of nonsteroidal anti-inflammatory drugs depending on the sequence and routes of administration is connected with their membrane mechanisms and metabolic features of amino sugar.[The influence of glucosamine on the antiexudative effect of nonsteroidal anti-inflammatory agents] Zupanets IA, Drogovoz SM, Bezdetko NV, et al. Farmakol Toksikol (USSR) 54:61-3;1991

Pharmacokinetics of glucosamine in man.

The pharmacokinetics of glucosamine sulfate (CAS 29031-19-4) was investigated in 6 healthy male volunteers (2 per administration route) using 14C uniformly labelled glucosamine sulfate and administering it in single dose by intravenous (i.v.), intramuscular (i.m.) or oral route. The results show that after i.v. administration the radioactivity due to glucosamine appears in plasma and is rapidly eliminated, with an initial t1/2 of 0.28 h. 1-2 h after administration the radioactivity due to glucosamine disappears almost completely and is replaced by a radioactivity originating from plasma proteins, in which glucosamine or its metabolites are incorporated. This radioactivity reaches a peak after 8-10 h and then declines with a t1/2 of 70 h. About 28% of the administered radioactivity is recovered in the urine of the 120 h following the administration and less than 1% is recovered in the feces. After i.m. administration similar pharmacokinetic patterns are observed. After oral administration a proportion close to 90% of glucosamine sulfate is absorbed. Free glucosamine is not detectable in plasma. The radioactivity incorporated in the plasma proteins follows pharmacokinetic patterns which are similar to those after i.v. or i.m. administration, but its concentration in plasma is about 5 times smaller than that after parenteral administration. The AUC after oral administration is 26% of that after i.v., or i.m. administration. The smaller plasma levels of radioactivity after oral administration are probably due to a first pass effect in the liver which metabolizes a notable proportion of glucosamine into smaller molecules and ultimately to CO2, water and urea. The results confirm previous investigations in rats and dogs showing that also in man glucosamine sulfate is a prodrug for glucosamine that is well absorbed after oral administration and that, after i.v, i.m. or oral administration, diffuses into several tissues, including bones and articular cartilages.Setnikar I; Palumbo R; Canali S; Zanolo G. Pharmacokinetics of glucosamine in man. Arzneim Forsch (GERMANY) 43:1109-13; 1993.

Efficacy and safety of intramuscular glucosamine sulfate in osteoarthritis of the knee. A randomised, placebo- controlled, double-blind study.

Glucosamine sulfate (Dona, CAS 29031-19-4) is a drug used in the treatment of osteoarthritis. When orally given, it is more effective than placebo and at least as effective as non-steroidal anti-inflammatory drugs in relieving osteoarthritis symptoms. The aim of this multicentre, randomised, placebo-controlled, double-blind, parallel-group study was to assess the efficacy and safety of glucosamine sulfate intramuscularly given on the same parameters. 155 out-patients with knee osteoarthritis (Lequesneีs criteria), radiological stage between I and III, Lequesneีs severity index of at least 4 points and symptoms for at least 6 months, were treated with i.m. glucosamine sulfate (or placebo) 400 mg twice a week for 6 weeks. Clinic visits were performed at enrollment, after a 2-week baseline, at weekly intervals during treatment and 2 weeks after drug discontinuation. Responders to treatment were considered those patients with a reduction of at least 3 points in the Lequesne index, together with a positive overall judgement by the investigator. The Lequesne index was slightly over 10 points in average in both groups at the beginning of treatment. A significant decrease in the index was observed for glucosamine compared to placebo (3.3 vs. 2.0 points in average, respectively; p < 0.05, Studentีs t-test). The responder rate in the evaluable patients was 55% with glucosamine (n = 73) and only 33% (n = 69) with placebo (p = 0.012, Fisherีs Exact Test). According to the intention-to-treat approach, considering also drop-outs, these proportions were 51% vs. 30% (p = 0.(5).Reichelt A, Forster KK, Fischer M, et al. Efficacy and safety of intramuscular glucosamine sulfate in osteoarthritis of the knee. A randomised, placebo-controlled, double-blind study. ArzneimForschung 44:75-80; 1994.

Clinical research in osteoarthritis: design and results of short-term and long-term trials with disease-modifying drugs

Putative disease-modifying drugs are usually clinically used in osteoarthritis with two main aims: not only stopping or reducing the cartilage degenerative process after a long-term treatment, but also controlling the symptoms of the disease within a few days or weeks, thus avoiding or diminishing the use of symptomatic medications. Due to the difficulties of implementing the first aim, the latter aim was more often investigated, even if most often with inadequate study design and insufficient numbers of patients. We have recently carried out three double-blind, controlled, parallel groups, randomized, 4-6 week trials of glucosamine sulphate versus placebo or the NSAID ibuprofen on a total of 606 gonarthrosic out-patients. Movement limitation and pain were scored according to the Lequesne index, and the efficacy goals were strictly pre-determined. Access to other medications was not allowed. Glucosamine was significanlty more effective than placebo, while no difference was detected in comparison with the NSAID(p<0.025 and p=0.77, respectively: Fisher's two-tailed exact test). On the other hand, glucosamine was as well tolerated as placebo, while the percentage of patients suffering adverse drug reactions was higher in the ibbuprofen group (37% vs 7%;p<0.001). Long-term trials are in progress and several aspects are to be considered in their design: they must be double-blind, placebo-controlled, randomized, continued for a period of years and (most importantly) with the careful use of imaging and biochemical techniques capable of generating objective evaluation criteria Rovati LC. Clinical research in osteoarthritis: design and results of short-term and long-term trials with disease-modifying drugs. Int J Tissue React (SWITZERLAND) 14:243-251;1992.

Double-blind clinical evaluation of intra-articular glucosamine in outpatients with gonarthrosis.

Fifty-four outpatients with gonarthrosis participated in a double-blind clinical test with the aim of evaluating the efficacy and tolerance of intra-articular glucosamine in comparison with a 0.9% NaCI placebo. Each patient had one intra-articular injection per week for five consecutive weeks. Pain, active and passive mobility of the joint, swelling, and generalized and local intolerance symptoms were recorded before beginning the treatment, and four weeks after the last injection. Glucosamine reduced pain to a significantly greater extent than did placebo, and resulted in significantly more pain-free patients. The angle of joint flexion substantially increased after glucosamine treatment. Active mobility increased with both treatments, with a more favorable trend after glucosamine administration. Knee swelling did not decrease significantly after glucosamine, whereas it worsened (although no significantly) after placebo. There were no local or general intolerance symptoms during and after treatment. Glucosamine administration was able to accelerate the recovery of arthrosic patients, with no resulting side effects, and to partially restore articular function. In addition, the clinical recovery did not fade after treatment ended, but lasted for the following month, at least. These features are a definite improvement over antirheumatic drugs, the major drawbacks of which are action of short duration and side effects. Glucosamine therapy therefore deserves a selected place in the management of osteoarthrosis. Vajaradul Y. Double-blind clinical evaluation of intra-articular glucosamine in outpatients with gonarthrosis. Clin Ther 3:336-343; 1981.

Chondroitin sulfate

Chondroitin sulfate (CS) is found in many tissues in the body such as tendon, bone, and eye cornea. Additionally, CS is the most abundant GAG in articular cartilage. CS has been demonstrated in vitro to inhibit several degradative enzymes that destroy cartilage and exhibit anti-inflammatory activity. Therefore, authors postulate that CS has a protective effect rather than an anabolic effect as seen in GA.

Similar to GA studies, CS has been demonstrated in clinical trials to increase movement as well as decrease pain and use of NSAIDs in human OA patients (23-25). As in the case of GA, the therapeutic response to CS is gradual, appearing weeks after beginning of therapy. Exogenous GAGs require prolonged periods of treatment because the compounds must enter into the metabolism of the joint cartilage. Nevertheless, the clinical improvements persist after stopping treatment. As well, patients report few side effects.
The literature on bioavailability studies is conflicting. Baici et al reported statistically little change in serum GAG concentration after oral administration of CS in humans (18). However, the validity of methodology used in the Baici et al study was questioned (19). Conte et al demonstrated in two studies, of which one included radiolabeled CS, that 70% of oral doses were absorbed in rats and dogs (20,21). Radioactivity was associated with high, intermediate and low molecular mass polysaccharide compounds. Because CS is a large molecule, authors posit that it is partially absorbed in the gut after digestion with smaller molecules being preferentially absorbed (21,22). Conte et al also demonstrated an increased (10-20%) steady-state plasma level of CS when administered daily to human subjects after 2-3 days (21). After 5 days of daily CS administration, increases in hyaluronate and changes in GAG size were observed in synovial fluid samples from human subjects. Such results demonstrate that polysaccharides originating from oral GAGs are incorporated into tissues.

Synergy of Glucosamine and Chondroitin

Although studies report beneficial results from using the two GAGs singly, some authors speculate that combining the two GAGs are synergistic. Because glucosamine and chondroitin sulfate have beneficial but different mechanisms of action, combining these compounds produces a synergistic response in articular cartilage. Using the two GAGs together will:

1. stimulate chondrocyte and synoviocyte metabolism,
2. inhibit degradative enzymes.

Consequently, concomitant use of both GAGs may result in a net increase in cartilage synthesis thereby slowing progression of OA as well as reducing disease symptoms. Several studies in both animal and human models have administered CS and GA combined, but no comparisons to singularly administered GAGs have been made.

The available published studies offer promising results of improvement in affliction from osteoarthritis with treatment of exogenous GAGs. However, the evidence is met with controversy from mainstream medical practitioners. For example, GAGs are not recommended by the Arthritis Foundation. Despite mounting testimony that GAGs may have a role in management of osteoarthritis, their use is not recommended based on the available scientific studies due to serious design flaws or insufficient details. Studies are criticized for their small sample populations. Additionally, although no short-term toxicity has been reported, long-term safety of GAGs needs to be investigated. Although few side-effects in humans have been reported, GAG effects on patients with underlying diseases should be examined, especially diseases affecting coagulation. Thirdly, no studies have examined their use in other forms of arthritis or other connective tissue maladies.

Historically, most of the data on use of GAGs has been derived from European studies. Until last year, no studies had been published from the US. Das et al conducted the first clinical investigation in the USA of GAG use for treatment of OA (27). Philippi et al performed the first study of GAG use to treat degenerative joint disease of the knee or low back in athletic populations (28). Both studies demonstrate effectiveness of GAGs in treatment of OA in the knee. The second study did not show any statistical benefit in spinal degenerative joint disease. There was, however, a trend for some benefit and the authors suggest a follow-up trial with a larger sample base over a longer time period for further elucidation.

A protocol has been established for design and conduct of clinical trials in studies of OA (26).

Hopefully, more studies will examine the most effective dose and long-term effects of GAGs as well as their combination with traditional OA treatments. On-going animal research may demonstrate GAG efficacy in other forms of connective tissue diseases. In the interim, individuals are advised to follow standard treatment recommendations, such as weight control, exercise, adequate nutrition and thermotherapy. Nonetheless, use of GAGs, in conjunction with proper use of other medications, may provide additional relief from symptoms and protect cartilage from degradation.

Glucosamine and chondroitin sulfate are available over the counter in many commercial products: singly and combined. Because they are considered a natural product and a dietary supplement, GAGs are not evaluated nor regulated by the Federal Drug Administration (FDA) for purity which can vary tremendously depending on extraction techniques and analysis technology. Purity can determine effectiveness, especially considering that all research and clinical studies used purified substances. Information from University of Maryland School of Pharmacy has shown that analysis of several commercial GAG products do not meet label claims (29). Purchasers should therefore be careful to buy from a reputable manufacturer that uses pure substances and can validate their finished product

According to the studies, the standard daily dosage for glucosamine is 1000-1500 mg and 800-1200 mg of chondroitin sulfate divided into 2-3 dosages. A loading dose is recommended for a minimum of two months. Most individuals should see an improvement in eight weeks or less.

Thereafter, daily maintenance dosages may be reduced to 500 mg GA and 400 mg of CS or more, depending on disease status. Two other compounds that are frequently used with GAGs are manganese and ascorbic acid. Manganese is a mineral that serves as a cofactor in biochemical reactions in joint connective tissue metabolism, such as GAG synthesis. Deficiencies of manganese result in formation of abnormal bone and cartilage.

However, evidence of efficacy of manganese in osteoarthritis is lacking. Recall from previous sections of this series that ascorbic acid (vitamin C) is an important cofactor in collagen synthesis and deficiencies result in poor wound healing (see Part 3).

Questions raised by individuals with diabetes address the safety of GAG use. Although GA and CS are classed as carbohydrates, the body does not break them down into glucose. Consequently, they will not raise blood sugar levels by providing a source of glucose. Supplementation of glucosamine and chondroitin may be of importance to athletes, considering the stress to connective tissue during sports activities and the mounting frequency of soft tissue injuries over the last two decades (30). Nonetheless, consumers are urged to be cautious when choosing a product.

Studies tend to support the synergism of GA and CS and not all commercial products contain both. Additionally, because they are classified as a dietary supplement, the strength and purity of GAG products are not subject to FDA regulation or control. Therefore, look for a product from a reputable manufacturer that can provide analysis of quality

References

1. Brown SJ, Child RB, Day SH, Donnelly AE. Indices of skeletal muscle damage and connective tissue breakdown following eccentric muscle contractions. Eur J Appl Physiol 1997, 75:369-374.
2. Bayliss MT, Davidson C, Woodhouse SM, Osborne DJ. Chondroitin sulphation in human joint tissue varies with age, zone and topography. Acta Orthrop Scand (Supp 266) 1995, 66:22-25.
3. Kongtawelert P, Books PM, Ghosh P. Pentosan polysulfate (Cartrophen) prevents the hydrocortisone induced loss of hyaluronic acid and proteoglycans from cartilage of rabbit joints as well as normalizes the keratan sulfate levels in their serum. J Rheum 1989; 16:1455-1459.
4. Rogachefsky RA, Dean DD, Howell DS, Altman RD. Treatment of canine osteoarthritis with sodium pentosan polysulfate and insulin-like growth factor-1. Ann N Y Acad Sci. 1994, 732:392-4.
5. Sant GR. Interstitial cystitis. Curr Opin Obstet Gynecol 1997, 9(5):332-336.
6. Tardy-Poncet B, Tardy B, Grelac F, et al. Pentosan polysulfate-induced thrombocytopenia and thrombosis. Am J Hematol 1994, 45:252-257.
7. Gironell A, Altes A, Arboix A, et al. Pentosan polysulfate-induced thrombocytopenia: a case diagnosed with an ELISA test used for heparin-induced thrombocytopenia. Ann Hematol 1996, 73:51-52.
8. Davis WM. The role of glucosamine and chondroitin sulfate in the management of arthritis. Drug Topics 1998, April (suppl):3S-13S.
9. Anderson MA, Slater MR, Hammad TA. Results of a survey of small-animal practitioners on the perceived clinical efficacy and safety of an oral nutraceutical. Prev Vet Med 1999, 38:65-73.
10. Hanson RR, Smalley LR, Huff GK, et al. Oral treatment with a glucosamine-chondroitin sulfate compound for degenerative joint disease in horses: 25 cases. Equine Pract 1997, 19(9):16-20.
11. Lippiello L, Idouraine A, McNamara PS, et al. Cartilage stimulatory and antiproteolytic activity is present in sera of dogs treated with a chondroprotective agent. Canine Pract 1998, 23(6):10-12.
12. Reichelt A, Forster KK, Fisher M, et al. Efficacy and safety of intramuscular glucosamine sulfate in osteoarthritis of the knee. Arzneimittelforschung 1994, 44(1):75-80.
13. da Camara CC, Dowless GV. Glucosamine sulfate for osteoarthritis. Ann Pharmacol 1998, 32:580-587.
14. Vidal y Plana RR, Bizzarri D, Rovati AL. Articular cartilage pharmacology: I. In vitro studies on glucosamine and non-steroidal anti-inflammatory drugs. Pharmacol Res Commun. 1978,10(6):557-69.
15. Raiss R. Effect of D-glucosamine sulfate on experimentally injured articular cartilage. Comparative morphometry of the ultrastructure of chondrocytes. Fortschr Med. 1985, 27;103(24):658-62.
16. Senikar I, Giacchetti C, Zanolo G. Pharmacokinetics of glucosamine in man. Arzneimittelforschung 1986, 36:729-735.
17. Senikar I, Palumbo R, Canali S, et al. Pharmacokinetics of glucosamine in man. Arzneimittelforschung 1993, 43:1109-1113.
18. Baici A, Horler D, Moser B, et al. Analysis of glycosaminoglycans in human serum after oral administration of chondroitin sulfate. Rheumatol Int 1992, 12:81-88.
19. Lualdi P. Bioavailability of oral chondroitin sulfate. Rheumatol Int 1993, 13:39-40.
20. Conte A, de Bernardi M, Palmieri L, et al. Metabolic fate of exogenous chondroitin sulfate in man. Arzneimittelforschung 1991, 41:768-772.
21. Conte A, Volpi N, Palmieri L, et al. Biochemical and pharmacological aspects of oral treatment with chondroitin sulfate. Arzneimittelforschung 1995, 45:918-925.
22. Paroli E, Antonilli L, Biffoni M. A pharmacological approach to glycosaminoglycans. Drugs Exptl Clin Res 1991, 17:9-20.
23. Fleisch A, et al. A one-year randomized, double-blind placebo-controlled study with oral chondroitin sulfate in patients with knee osteoarthritis. Singapore: The Third International Congress of the Osteoarthritis Research Society, 1997:6.
24. Fioravanti A, Franci A, Anselmi F, et al. Clinical efficacy and tolerance of galactosaminoglucuronoglycan sulfate in the treatment of osteoarthritis. Drugs Exptl Clin Res 1991, 17:41-44.
25. Busci L, Poor G. Efficacy and tolerability of oral chondroitin sulfate as a symptomatic slow-acting drug for osteoarthritis in the treatment of knee osteoarthritis. Osteoarth Cartil 1998, suppl 6:31-36.
26. Altman R, Brandt K, Hochberg M, et al. Special Report: Design and conduct of clinical trials in patients with osteoarthritis. Osteoarth Cartil 1996, 4:217-243.
27. Das AK, Eitel J, Hammad T. Efficacy of a new class of glucosamine hydrochloride, sodium chondroitin sulfate and manganese ascorbate in the management of knee osteoarthritis: a randomized double-blind placebo-controlled clinical trial. Am Assoc Hip Knee Surg, 8th Annual Meeting, November 1998.
28. Philippi AF, Leffler CT, Leffler SG, et al. Glucosamine, chondroitin, and manganese ascorbate for degenerative joint disease of the knee or low back: a randomized, double-blind, placebo-controlled pilot study. Mil Med 164:85-91.
29. Newsweek, Feb 17, 1997, p. 54.
30. Perry JD. Exercise, injury and chronic inflammatory lesions. Br Med Bull 1992, 48:668-682.

These statements have not been evaluated by the Food and Drug Administration. These products are not intended to diagnose, treat, cure or prevent any disease.