Glucosamine Sulfate for joint pain - Does glucosamine sulfate have side effects?

Joint Power Rx Formulated by Ray Sahelian, M.D.
Because joint pain is so debilitating, glucosamine sulfate and chondroitin sulfate alone are often not enough. This powerful joint formula includes several additional herbal extracts and nutrients including MSM, CMO, boswellia serrata, turmeric, cat's claw extract, grape seed extract, and sea cucumber for optimal joint health.  

Joint Power Rx Supplement has:
Glucosamine sulfate (from shellfish) - glucosamine is a popular ingredient in many joint health products
Chondroitin sulfate - chondroitin is a popular ingredient in many joint health products
MSM nutrient which stands for methylsulfonylmethane
CMO complex also known as cetyl myristoleate
Boswellia serrata extract is used in Ayurvedic medicine
Turmeric is an herb that contains curcumin
Cat's claw extract comes from the Amazon jungle
Devil's claw is a plant widely used in South African traditional medicine,
Grape seed extracts have compounds called procyanidolic oligomers which are powerful antioxidants, perhaps much greater than vitamins C and E.
Sea cucumbers have a number of substances that have therapeutic value.

Efficacy of glucosamine sulfate treatment in patients with osteoarthritis
Pol Merkur Lekarski. 2007 Mar;22(129):204-7. Dudek A, Raczkiewicz-Papierska A, T?ustochowicz W.
Wojskowy Instytut Medyczny, Klinika Chorób Wewnetrznych i Reumatologii CSK MON w Warszawie.
Glucosamine sulfate is precursor of glucosamineglycans synthesis. The purpose of this study was to determine the efficacy of treatment of osteoarthritis patients with glucosamine sulfate (Artreum). Fifty patients with ostoearthritis of the knees (38 pts) or hips (12 pts) entered into study. All patients have been treated with 500 mg of glucosamine three times daily for 12 weeks. We found the significant improvement during treatment in 38 (80) pts. as measured by WOMAC scale and in 36 (70%) as measured by Lequesne'a scale. Self assessed pain improved in 35 (74%) of patients. The efficacy of the treatment was characterized as "good" by 60% of patients, and it was similar to physician assessment. No clinically significant adverse events were observed. In this study we found that glucosamine treatment causes significant improvement in functional status and pain in osteoarthritis patients.

Glucosamine sulfate side effects
Based on our current understanding, glucosamine sulfate has few side effects, and can be taken for extended periods, months and years. Thus far, after being on the market for quite a number of years, there have not been any reports in the medical literature of any significant glucosamine sulfate side effects. However, as with most nutrients and medicines, long term effects are not clearly known.

Glucosamine sulfate in the treatment of knee osteoarthritis symptoms: a randomized, double-blind, placebo-controlled study using acetaminophen as a side comparator.
Arthritis Rheum. 2007 Feb;56(2):555-67. Rheumatology Department, Fundación Jiménez Díaz-Capio, Madrid, Spain.
To assess the effects of the prescription formulation of glucosamine sulfate (1,500 mg administered once daily) on the symptoms of knee osteoarthritis during a 6-month treatment course. Three hundred eighteen patients were enrolled in this randomized, placebo-controlled, double-blind trial in which acetaminophen, the currently preferred medication for symptomatic treatment of osteoarthritis, was used as a side comparator. Patients were randomly assigned to receive oral glucosamine sulfate 1,500 mg once daily, acetaminophen 3 gm/day, or placebo. The primary efficacy outcome measure was the change in the Lequesne index after 6 months. Secondary parameters included the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and response according to the Osteoarthritis Research Society International criteria. At baseline, the study patients had moderately severe osteoarthritis symptoms (mean Lequesne index approximately 11 points). Glucosamine sulfate was more effective than placebo in improving the Lequesne score, with a final decrease of 3.1 points, versus 1.9 with placebo. The 2.7-point decrease with acetaminophen was not significantly different from that with placebo. Similar results were observed for the WOMAC. There were more responders to glucosamine sulfate (39%) and acetaminophen (33%) than to placebo (21%). Safety was good, and was comparable among groups. The findings of this study indicate that glucosamine sulfate at the oral once-daily dosage of 1,500 mg is more effective than placebo in treating knee osteoarthritis symptoms.

Glucosamine sulfate reduces osteoarthritis progression in postmenopausal women with knee osteoarthritis: evidence from two 3-year studies.
Menopause. 2004 Mar-Apr;11(2):138-43. WHO Collaborating Center for Public Health Aspect of Osteoarticular Disorders, Liege, Belgium.
To investigate the effect of glucosamine sulfate on long-term symptoms and structure progression in postmenopausal women with knee osteoarthritis. This study consisted of a preplanned combination of two three-year, randomized, placebo-controlled, prospective, independent studies evaluating the effect of glucosamine sulfate on symptoms and structure modification in osteoarthritis and post-hoc analysis of the results obtained in postmenopausal women with knee osteoarthrits. Of 414 participants randomized in the two studies, 319 were postmenopausal women. After 3 years, postmenopausal participants in the glucosamine sulfate group showed no joint space narrowing, whereas participants in the placebo group experienced a narrowing of -0.33 mm. Percent changes after 3 years in the WOMAC index showed an improvement in the glucosamine sulfate group [-14%] and a trend for worsening in the placebo group (5%). This analysis, focusing on a large cohort of postmenopausal women, demonstrated for the first time that a pharmacological intervention for osteoarthrits has a disease-modifying effect in this particular population, the most frequently affected by knee osteoarthritis.

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.
Osteoarthritis Cartilage. 2003 Jan;11(1):1-5. WHO Collaborating Center for Public Health Aspect of Osteoarticular Disorders, Liege, Belgium.
To investigate the relationship between baseline radiographic severity of knee osteoarthritis and the importance of long-term joint space narrowing. Measurements of mean joint space width (JSW), was assessed by a computer-assisted method, and performed at baseline and after 3 years, on weightbearing anteroposterior knee radiographs. In the placebo group, baseline JSW was significantly and negatively correlated with the joint space narrowing observed after 3 years. In the lowest quartile of baseline mean JSW (<4.5mm), the JSW increased after 3 years by (mean (S.D.)) 3.8% (23.8) in the placebo group and 6.2% (17.5) in the glucosamine sulfate group. The difference between the two groups in these patients with the most severe OA at baseline was not statistically significant (P=0.70). In the highest quartile of baseline mean JSW (>6.2mm), a joint space narrowing of 14.9% (17.9) occurred in the placebo group after 3 years while patients from the glucosamine sulfate group only experienced a narrowing of 6.0% (15.1). Patients with the most severe OA at baseline had a RR of 0.42 to experience a 0.5mm joint space narrowing over 3 years, compared to those with the less affected joint. In patients with mild OA, i.e. in the highest quartile of baseline mean JSW, glucosamine sulfate use was associated with a trend towards a significant reduction in joint space narrowing.

Glucosamine and cholesterol
The effect of glucosamine sulfate on the blood levels of cholesterol or triglycerides--a clinical study
Ugeskr Laeger. 2007 Jan 29;169(5):407-10. Østergaard K, Hviid T, Hyllested-Winge JL. Slidgigtinstituttet A/S, Ishøj.
This study was conducted in order to determine if glucosamine sulfate taken by patients as treatment for chronic joint pain influences the fasting blood levels of cholesterol and triglycerides. A 3 months', post-marketing, randomised, double-blinded, placebo-controlled, clinical trial was performed with parallel groups of 66 patients over 40 years of age with joint pain of long duration receiving either recommend dosage (1500 mg per day) of glucosamine sulfate or placebo. The primary outcome measures were cholesterol levels (total cholesterol, LDL (low density lipoprotein)-cholesterol and HDL (high density lipoprotein)-cholesterol) and triglycerides in fasting blood (plasma levels). Secondary outcome measures were self reported side-effects. No significant differences between the glucosamine sulfate group and the placebo group with respect to cholesterol and triglycerides were observed. There were no differences between the treatment groups with respect to side-effects. This study demonstrates that glucosamine sulfate does not significantly influence blood levels of cholesterol or triglycerides.

Glucosamine oral bioavailability and plasma pharmacokinetics after increasing doses of crystalline glucosamine sulfate in man.
Osteoarthritis Cartilage. 2005 Dec;13(12):1041-9. Clinical Pharmacology Department, Rotta Research Laboratorium/Rottapharm, Monza, Italy.
Pharmacokinetic data on glucosamine are scant, limiting the understanding of glucosamine sulfate mechanism of action in support of its treatment effects in osteoarthritis. This study investigated the oral pharmacokinetics and dose-proportionality of glucosamine after administration of the patented crystalline glucosamine sulfate in man. Twelve healthy volunteers received three consecutive once-daily oral administrations of glucosamine sulfate soluble powder at the doses of 750, 1,500, and 3,000 mg, in an open, randomised, cross-over fashion. Glucosamine was rapidly absorbed after oral administration and its pharmacokinetics were linear in the dose range 750-1,500 mg, but not at 3,000 mg, where the plasma concentration-time profiles were less than expected based on dose-proportionality. Plasma levels increased over 30-folds from baseline and peaked at about 10 microM with the standard 1,500 mg once-daily dosage. Glucosamine distributed to extravascular compartments and its plasma concentrations were still above baseline up to the last collection time. Glucosamine elimination half-life was only tentatively estimated to average 15 h. Glucosamine is bioavailable after oral administration of crystalline glucosamine sulfate, persists in circulation, and its pharmacokinetics support once-daily dosage. Steady state peak concentrations at the therapeutic dose of 1,500 mg were in line with those found to be effective in selected in vitro mechanistic studies.

Glucosamine sulfate questions
Q. Would a glucosamine sulfate chondroitin sulfate supplement be better than just glucosamine sulfate by itself?
   A. Yes, we believe the addition of chondroitin can help glucosamine work better.

Q. Q. Would a glucosamine sulfate msm supplement work better better than just glucosamine sulfate by itself?
   A. Yes, we believe the addition of msm can help glucosamine sulfate work better.

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