Chondrointin is a natural glycosaminoglycan that is present mainly in the extracellular matrix surrounding cells and is most abundant in the cartilage, skin, blood vessels, ligaments, and tendons in every part of the body. Glycosaminoglycans of the joint cartilage are high-molecular-weight aggregates (proteoglycans) that aid the mechanical and elastic properties of the joint. Chondroitin sulfate helps in osteoarthritis as a result of its anti-inflammatory activity, stimulation of the synthesis of proteoglycans and hyaluronic acid, decrease of the catabolic activity of chondrocytes inhibiting some proteolytic enzymes and other substances that contribute to damage the cartilaginous matrix, reduction of the synthesis of nitric oxide, and apoptosis of articular chondrocytes

Glucosamine is a natural glucose derivative and an essential component of glycoproteins and proteoglycans.  It has been safely used to relieve osteoarthritis in humans. Glucosamine with chondroitin sulfate is a very popular anti-arthritic supplement, one of the most popular supplements other than vitamins and minerals.  This combined supplement is the only treatment which has repeatedly shown the ability to slow or halt joint space deterioration in osteo-arthritis.  The cost of three double strength tablets per day is about $12 and well worth the investment, both for pain relief and to prevent further joint damage.  A few people actually experience not just a cessation of joint space loss, but actually a small amount of recovery of previous loss.  

In a very preliminary open trial, the combination appeared to be very helpful for psoriasis.  It has also helped mucosal wound healing in some animal studies and beneficial effects on artificially induced liver injury, again in animal studies. 

Glucosamine and chondroitin should not be taken during pregnancy, just to be on the safe side.  In a streptozotocin-induced hyperglycemic apolipoprotein E-deficient mouse model, one study suggested the possibility of atherosclerosis in diabetics from glucosamine (Diabetes 2006 Jan;55(1):93-101).  However, other research suggests glucosamine may be a novel strategy for inducing cardioprotection, and that this appears to be mediated by an increase in protein O-GlcNAc levels (J Mol Cell Cardiol 2006 Feb;40(2):303-12).  Also, in apoE-null mice, glucosamine significantly reduced the atherosclerotic lesion in aortic root. (P < 0.05) These data suggest that macrovascular disease associated with hyperglycemia is unlikely due to glucosamine. In fact, glucosamine by increasing HSPG showed atheroprotective effects.  

Carrageenan- induced paw edema caused by the acute inflammation was slightly reduced and the level of granuloma formation caused by the subacute inflammation was strongly suppressed (Phyto Res 2005 Dec;19(12):1048-51).  Recent studies have shown that glucosamine also possesses immunosuppressive properties and is effective in prolonging graft survival in mice.  It had a positive therapeutic effect on experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (J Immunol 2005 Dec 1;175(11):7202-8).

New England Journal of Medicine Makes Glucosamine/Chondroitin Look Bad for Arthritis: In a 24-week DB PC Veteran Administration study, 1229 mild and 354 moderate-severe osteoarthritis knee patients took 1500 mg of glucosamine daily, 1200 mg of chondroitin sulfate daily, both glucosamine and chondroitin sulfate, 200 mg of celecoxib (Celebrex) daily, or placebo. Overall, it was reported that glucosamine and chondroitin sulfate were not significantly better than placebo in reducing knee pain by 20 percent. The data for mild arthritis was odd in that an amazing 60% of placebo patients improved. Meanwhile, glucosamine (64%) and chondroitin (66%) did better than the combination (62%) vs. just 70% for celecoxib. However, for patients with moderate-to-severe pain, glucosamine with chondroitin did very well (79% vs. 54%, P=0.002) and clearly better than the dangerous arthritis drug celecoxib (69%). Glucosamine, chondroitin sulfate, and the two in combination for painful knee osteoarthritis. Clegg DO, et al. University of Utah School of Medicine. . New Eng J Med 2006 Feb 23;354(8):795-808. Ed: As expected, the study led the news media to trash glucosamine-chondroitin while failing to point out that the combination did very well for those with moderate-to-serious pain, i.e., the most important patients.  They also failed to mentioned that Celebrex did worse in this important category.  Despite the study being totally funded by the public, it was published in the expensive NEJM which is a cash cow for the Massachusetts Medical Society.  Citizens and doctors without a subscription could not see the actual study.  Celebrex costs $128/mo vs. $12/mo for glucosamine/chondroitin.  According to this study, it would be necessary to treated 30 mild patients with Celebrex to help one more patient achieve a 20% decrease in mild pain than chondroitin at a cost of $40,000/year.  Celebrex also increases the rate of heart attacks (129% increase) and causes many stomach bleeds vs. no side-effects for glucosamine/chondroitin.  Glucosamine/chondroitin has repeatedly been shown in 1 to 4 year studies to slow joint space deterioration while Celebrex has not. The New England Journal of Medicine receives very large amounts of advertising income from pharmaceutical companies.  Researchers being paid by public monies should be required to publish their full reports on free, internet medical journals, not profit-oriented, industry-subsidized magazines like NEJM. 

Chondroitin Protected Joints Without Loss for Two Years: In a 2-year DB PC study of 300 patients with knee OA, those on 800 mg CS once daily for 2 years had no loss of joint space over the two year period vs. a loss of 0.14 mm after 2 years for placebo (P = 0.001). There was no significant differences in rates of adverse events between the two groups. Chondroitins 4 and 6 sulfate in osteoarthritis of the knee: a randomized, controlled trial. Michel BA, et al. University Hospital Zurich, Switzerland. . Arthritis Rheum. 2005 Mar;52(3):779-86.

Chondroitin Helped Osteoarthritis in Many DB Studies: A metanalysis of chondroitin found 16 studies with 7 double-blind studies used for metanalysis totalling 374 patients found over 50% improvement in arthritis pain. J Rheumatol 2000 Jan;27(1):205-11; The efficacy of 1200 mg of chondroitin sulfate (CS) as a single daily dose does not differ from that of 3 x 400 mg daily doses of CS and both were beneficial in 4-week 120-patient DB study. Bourgeois, Pitie Salpetriere Hospital, Paris, France. Osteoarthritis Cartilage 1998 May;6 Suppl A:25-30;  A 146-patient DB PC study from the University of Siena in Italy found patients treated with the NSAID showed prompt and plain reduction of clinical symptoms, which, however, reappeared after the end of treatment; in the chondroitin group, the therapeutic response appeared later in time but lasted for up to 3 months after the end of treatment. CS seems to have slow but gradually increasing clinical activity in OA; these benefits last for a long period after the end of treatment. J Rheumatol 1996 Aug;23(8):1385-91; Similar results in a 3- month DB study with two months of follow-up of 120 osteoarthritis of the hip patients. Rev Rhum Mal Osteoartic 1992 Jul-Sep;59(7-8):466-72; A meta-analysis found chondroitin a greater benefit but glucosamine also helpful although the quality of research not high and publication bias by manufacturers probable. JAMA 2000 Mar 15;283(11):1469-75; The amounts generally administered are glucosamine, 1500 mg, and chondroitin sulfate, 1200 mg, daily; 

Chondroitin Protects Knee Cartilage Without Loss for One Year: In a 120-patient Univ. of Liege study, patients with osteoarthritis of the knee who received 400 mg twice a day for two separate three month periods had no loss of joint space on x-ray after one year while placebo patients had a shrinkage of the joint space, evidence of deterioration. Intermittent treatment of knee osteoarthritis with oral chondroitin sulfate: a one-year, randomized, double-blind, multicenter study versus placebo. Uebelhart D, Malaise M, et al. Osteoarthritis Cartilage. 2004 Apr;12(4):269-76

Chondroitin May Help Psoriasis, Too: Eleven adult patients with knee osteoarthritis and long-standing, moderate to severe psoriasis resistant to conventional therapy were treated with chondroitin sulfate 800 mg per day of chondroitin sulfate for 2 months. Skin biopsies were obtained before and after treatment. All patients but one presented a dramatic improvement of the condition of the skin, with a reduction of swelling, redness, flaking, and itching (clearance of psoriasis in one patient), increase in the hydration and softening of the skin, and amelioration of scaling. Histopathologically, there was a statistically significant decrease in epidermal thickness, a decrease in the thickness between the stratum basale and the stratum granulosum, a significant improvement of the degree of psoriasis activity, and a decrease in the number of keratinocytes stained with Ki-67. Clinical and histopathological improvement of psoriasis with oral chondroitin sulfate: a serendipitous finding. Verges J, et al. Barcelona, Spain. . Dermatol Online J. 2005 Mar 1;11(1):31.

Chondroitin Might Help Low Back Pain: In a report of a poor quality, 6-month open trial of 25 patients with lower back pain (LBP), 13 of whom had coronary heart disease and 19 hypertension (n = 18), by the end of the 1st month on chondroitin, there was a significantly lower pain intensity, increased spinal motility, increased exercise tolerance. Excellent and good response to structum were observed in 71% patients. CHD characteristics did not change while arterial pressure went down noticiably. Structum in combined treatment of low back pain syndrome. Mazurov VI, et al. Ter Arkh. 2004;76(8):68-71. Ed: In general, Russian medical research is very poor quality and this report is no except.  It is included because it is the first to mention back pain.

Wound Healing in Maxillary Sinus Mucosa Helped by Chondroitin Sulfate Hydrogel: Rabbit study. Gilbert ME, et al. University of Utah. Laryngoscope. 2004 Aug;114(8):1406-9. Other studies have found palatal mucosa wound healiing accelerated in in vitro studies. 

Antioxidant and Antifibrogenic effects of the Glycosaminoglycans hyaluronic acid and Chondroitin-4-sulphate in Carbon tetrachloride-induced Liver Fibrogenesis. Rat study. Campo GM, et al. University of Messina, Italy. . Chem Biol Interact. 2004 Jul 20;148(3):125-38.

Review of Long-Term Studies Strongly Favors Glucosamine: In a review of all DB PC studies lasting at least one year, glucosamine sulfate was more effective than placebo in delaying structural progression in knee OA. The risk of disease progression was reduced by 54% (RR 0.46; p = 0.0011). The number-needed-to-treat was 9. The pooled effect sizes for pain reduction and improvement in physical function were 0.41 (p < 0.0001) and 0.46 (p < 0.0001) in favor of glucosamine sulfate. Glucosamine sulfate caused no more adverse effects than placebo.

Glucosamine Protects Knee Cartilage: In a World Health Organization coordinated international study of 414 patients with osteoarthritis of the knee treated in a DB PC study for 3 years, those on glucosamine had no narrowing of the joint space while those on placebo had a significant 0.33 mm narrowing, signifying continuing cartilage destruction. Those on glucosamine had a 14% improvement in pain symptoms, while those on placebo had a 5% worsening. Glucosamine sulfate reduces osteoarthritis progression in postmenopausal women with knee osteoarthritis: evidence from two 3-year studies. Bruyere O, Pavelka K, et al. Menopause. 2004;11(2):138-143. 

Glucosamine Helps: Stimulates cartilage cells to synthesize glycosaminoglycans and proteoglycans. It helps inflammatory, mechanical arthritis and immunolog-reactive arthritis although much less than indomethacin in animals. In 4-8 week DB trials, it was more effective than placebo (Osteoarthritis Cartilage 2:51, ’94), as effective as ibuprofen 400 TID from 2^nd week (Osteoarthritis Cartilage 2:61, ’94) and more effective by end of trial in Curr Med Res Opin 8:145, ’82. It is well tolerated. Chondroitin sulfate is reported to maintain viscosity in joints, stimulate cartilage repair and inhibits enzyme break down of cartilage (Drug Exp Clin Res 17:3 ’91). The two are often combined. Med Let 9/26/97

Glucosamine Disease Modifying in Osteoarthritis over Three Years: In a DB PC study of 1500 glucosamine QD vs. placebo in 212 patients for 3 years, there was progressive loss of joint space in controls but not in the glucosamine group (p=.003). No side-effect of significance were detected. Those with less severe OA had the most joint space deterioration on placebo. Correlation between radiographic severity of knee osteoarthritis and future disease progression. Results from a 3-year prospective, placebo-controlled study evaluating the effect of glucosamine sulfate. Bruyere O, et al. Univ Liege, Belgium. Lancet. 2001 Jan 27;357(9252):247-8

Glucosamine Beneficial in 2nd Three Year Study; Protects Cartilage: In comparison with piroxicam, a NSAID, glucosamine significantly improved arthritic symptoms after 12 weeks of therapy and remained effective 8 weeks after treatment was discontinued. The beneficial effects of long-term oral glucosamine therapy in preventing joint space narrowing and improving symptoms were shown in two 3-year placebo-controlled trials in a total of 414 patients with osteoarthritis. Statistically significant differences favoring glucosamine were noted in the per-protocol and intention-to-treat analyses for the primary endpoints for both joint structural changes and symptom modification. Glucosamine has a tolerability profile similar to that of placebo. Drugs Aging. 2003;20(14):1041-1060 

Glucosamine-Chondroitin-Manganese Helps Osteo in Two Studies: In a 93-patient DB PC study of 1000 mg glucosamine, 800 mg chondroitin, and 125 mg manganese citrate BID, researchers found no increase side-effects vs. placebo but a 52% improvement in arthritis pain was found vs. 28% on placebo. Osteoarthritis Cartilage 2000 Sep;8(5):343-50. A similar study of knee osteo in Marines found similar results. Mil Med 1999 Feb;164(2):85-91

Glucosamine-Chondroitin JAMA Meta-Analysis Favorable: Trials of glucosamine and chondroitin preparations for OA symptoms demonstrate moderate to large effects, but quality issues and likely publication bias suggest that these effects are exaggerated. Nevertheless, some degree of efficacy appears probable for these preparations. 14 DB studies of at least 4 weeks were found. Most studies were manufacturer supported. Boston Univ. JAMA 2000 Mar 15;283(11):1469-75

Glucosamine No Better in Three Studies: No benefit was found in 98 osteoarthritis of the knee patients in a 60-day DB of 500 mg TID. West J Med 2000 Feb;172(2):91-4; In a DB PC study of 205 for 12-weeks, no difference was noted. Am J Med. 2004 Nov 1;117(9):643-9; No difference was found in a 137-patient DB PC 6-month discontinuation study of patients who had improved on glucosamine 1500 mg alone. Ed: The combination may be better rather than glucosamine alone.  Also, even worthwhile treatment sometimes fail in placebo controlled trials.

Glucosamine Did as Well as Ibuprofen for Pain: Glucosamine 1500 mg/day helped as well as ibuprofen 1200 mg/day in a 4-week DB study of 178 Chinese OA of knee. Arzneimittelforschung 1998 May;48(5):469-74. 

Glucosamine Might Protect Against Atherosclerosis: Distinct effects of glucose and glucosamine on vascular endothelial and smooth muscle cells: Evidence for a protective role for glucosamine in atherosclerosis. Glucosamine significantly reduced the atherosclerotic lesion in aortic root in apoE-nul mice (P<0.05). Wenlan Duan, et al. Cardiovascular Diabetology 2005, 4:16. http://www.cardiab.com/content/4/1/16 free access

Meta-Analysis Supports Glucosamine for Arthritis: In a meta-analysis of all DB PC studies lasting at least one year through August, 2004, glucosamine sulfate was more effective than placebo in delaying structural progression in knee OA by 54% (pooled RR 0.46; p = 0.0011). The number-needed-to-treat was 9. The pooled effect sizes for pain reduction and improvement in physical function were 0.41 (p < 0.0001) and 0.46 (p < 0.0001). Glucosamine sulfate caused no more adverse effects than placebo.  Glucosamine long-term treatment and the progression of knee osteoarthritis: systematic review of randomized controlled trials. Poolsup N, et al. Silpakorn University, Nakhon-Pathom, Thailand. . Ann Pharmacother. 2005 Jun;39(6):1080-7.

Glucosamine-Chondroitin Helped Rheumatoid-Like Autoimmune Arthritis in Rats: In collagen-induced autoimmune arthritis (CIA), both the Arthritis Index and Histologic Index criteria showed a statistically significant reduction in the prevalence of CIA in rats pretreated with the glucosamine-chondroitin mixture (54%) compared to the combined control groups (96%, P = 0.001). The GCM treatment failed to alter T-cell proliferation and antibody production to bovine type-II collagen, indicating that its effects are not due to alteration of the antigen-specific immune response. Effect of pre-loading oral glucosamine HCl/chondroitin sulfate/manganese ascorbate combination on experimental arthritis in rats. Beren J, Hill SL, Diener-West M, Rose NR. Johns Hopkins. Exp Biol Med (Maywood). 2001 Feb;226(2):144-51; Also, in adjuvant arthritis. Inflamm Res. 2005 Mar;54(3):127-32.

Glucosamine-Chondroitin Better Than Either Alone in Horse Cartilage Study: Study with cartilage in vitro. DE DeChant et al. Equine Vet J. 2005 May;37(3):227-31; Similar, Osteoarthritis Cartilage. 2005 May;13(5):387-94.