Glucosamine has hardly been evaluated in conditions other than osteoarthritis. Hence is is not clear whether glucosamine is helpful in those with damage to cartilage or joints due to musculoskeletal injuries. Glucosamine appears to help rebuild cartilage in osteoarthritis patients, but it is unlikely that it would help joints where the cartilage has been surgically removed. Similarly, glucosamine has not be tested in autoimmune diseases involving joints, such as lupus and rheumatoid arthritis. Those with artificial joints are not likely to be helped by glucosamine since they have no cartilage.
Glucosamine sulfate or Glucosamine hydrochloride?
Glucosamine is available as glucosamine sulfate or glucosamine hydrochloride (glucosamine hcl). A review of the scientific literature shows glucosamine is likely to be helpful for many patients with osteoarthritis. Almost all of the studies done with glucosamine have used the sulfate form since a company in Europe funded the studies, and we know that it works. However, the hydrochloride form has been used by doctors for many years and it seems to work just as well. The hydrochloride form is cheaper. The positive effects of glucosamine reducing joint pain are often noticed within a few weeks.
Glucosamine and allergies:
Those who are allergic to sulfates may take glucosamine hydrochloride and not glucosamine sulfate, and they should avoid chondroitin sulfate. Glucosamine is derived from shrimp, oyster and crab shells and chondroitin is derived from cartilage of cows, pigs and sharks. There is no synthetically made glucosamine on the market.
Combining Glucosamine with Drugs:
Glucosamine may be taken together with acetaminophen or NSAIDs such as ibuprofen and naproxen. After glucosamine starts working in a few weeks, hopefully the dose of the other drugs can be reduced or eliminated. We are not aware of glucosamine interacting with other medicines. It appears that glucosamine, chondroitin and other arthritis herbs are safer than the pain relief medicines.
Glucosamine Side Effects - Long term safety:
Based on our current understanding, glucosamine 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 side effects. However, as with most nutrients and medicines, long term effects are not clearly known. It is best pregnant women not take glucosamine until more is known about this interaction.
Glucosamine and Diabetes:
The dose of glucosamine, one or two grams a day, is minimal as a sugar source compared to the amounts of carbohydrates found in the foods we consume. One study indicates that glucosamine is safe in diabetics.
In a study published in Archives of Internal Medicine, 38 elderly patients with type 2 diabetes were divided into two groups. The first group took 1500 mg of glucosamine a day combined with 1200 mg chondroitin sulfate. Chondroitin is another supplement often used in combination with glucosamine to treat osteoarthritis. The other group took placebo pills. Two-thirds of the dose was taken in the morning and one-third in the evening. The study lasted for 90 days. Blood studies were done to evaluate blood sugar levels and also levels of haemoglobin A1c, a specific blood marker that can tell us average blood sugar levels over long periods of time. There was no statistically significant rise in haemoglobin A1c levels in those who took glucosamine.
Timing of Glucosamine ingestion:
It's difficult to say when the best time or frequency is to take glucosamine, whether with or without food, but a good option is to take glucosamine before meals. All 1,500 mg a day can be taken at one time or split in two or three divided doses throughout the day.
Can glucosamine pills be absorbed from the stomach and end up in cartilage?
Yes. After oral administration of glucosamine sulfate (GS), 90% is absorbed. (Sulfate means that the glucosamine is attached to sulfur and oxygen atoms).
In a study done in Italy, two healthy male volunteers were given 250 mg of oral GS, tagged with radioactive carbon 14 as a tracer, in the morning on an empty stomach. The radioactive GS was found an hour later in blood and then later in other tissues. The researchers state "GS very rapidly diffuses in most tissues and organs and that it has a special tropism (attraction) for articular tissue (cartilage) and for bone." These volunteers were also given GS intravenously (IV) and intramuscularly (IM). The amount of GS in blood after oral administration was only a quarter of the amount available by IV and IM. Therefore oral administration is effective, but not as good as IV or IM. When oral GS is absorbed, it first goes to the liver where a large portion gets broken down into similar molecules such a carbon dioxide, urea and water.
Glucosamine Research Update:
Evidence continues to mount that glucosamine, while generally safe, is not effective in treating osteoarthritis of the knee. In the latest study, Dr. Tim McAlindon and colleagues from Tufts-New England Medical Center in Boston randomly assigned 205 adults with painful knee osteoarthritis to take glucosamine (1.5 grams per day) or a placebo for 12 weeks. Ninety-three participants in each group completed the trial. At the end of the study there were no significant differences between glucosamine and placebo in terms of changes in pain scores. There were also no marked differences between glucosamine and placebo in terms of stiffness, physical function and use of painkillers, the team reports in the American Journal of Medicine.
The effect of glucosamine-chondroitin supplementation on glycosylated haemoglobin levels in patients with type 2 diabetes mellitus: a placebo-controlled, double-blinded, randomized clinical trial.
Scroggie D.A., Albright A., Harris M.D., Wilford Hall Medical Center, Lackland Air Force Base, Lackland, TX. Arch Intern Med. 2004 Apr 12; 164(7):807
With increasing use of glucosamine-containing supplements for the treatment of osteoarthritis, there is increasing concern in the medical community about possible toxic effects. The present study was undertaken to determine whether glucosamine supplementation altered haemoglobin A1c concentrations in patients with well-controlled diabetes mellitus.
OBJECTIVE: To evaluate possible effects of glucosamine supplementation on glycemic control in a selected population of patients with type 2 diabetes mellitus.
DESIGN: Placebo-controlled, double-blinded, randomized clinical trial. Patients were typically elderly patients, evenly divided between men and women. Most of the patients were being treated with 1 or 2 drugs for glycemic control. In daily doses for 90 days, patients received either placebo or a combination of 1500 mg of glucosamine hydrochloride with 1200 mg of chondroitin sulfate.
Main Outcome Measure: Haemoglobin A1c levels before and after 90 days of therapy.
RESULTS: There were 4 withdrawals from the glucosamine-treated group. Three were related to co-morbidities (myocardial infarction, congestive heart failure, and atrial fibriliation) and 1 to a possible adverse reaction (excessive flatus). No other patient reported any adverse effects of glucosamine therapy. Post treatment haemoglobin A1c concentrations were not significantly different between groups, nor were there any significant differences within groups before and after treatment.
CONCLUSION: This study demonstrates that oral glucosamine supplementation does not result in clinically significant alterations in glucose metabolism in patients with type 2 diabetes mellitus.
Randomised, double-blind, placebo-controlled glucosamine discontinuation trial in knee osteoarthritis.
Arthritis Rheum. 2004 Oct 15; 51(5):738-45.
To assess the efficacy of glucosamine sulfate in knee osteoarthritis (OA). A 4-center, 6-month, randomized, double-blind, placebo-controlled glucosamine discontinuation trial was conducted in 137 current users of glucosamine with knee OA who had experienced at least moderate improvement in knee pain after starting glucosamine. Study medication dosage was equivalent to the dosage of glucosamine taken prior to the study (maximum 1,500 mg/day). Follow up continued for 6 months or until disease flare, whichever occurred first. The primary outcome was the proportion of disease flares in the glucosamine and placebo groups using an intent-to-treat analysis. Secondary outcomes included time to disease flare; analgesic medication use; severity of disease flare; and change in pain, stiffness, function and quality of life in the glucosamine and placebo groups.
RESULTS: Disease flare was seen in 28 (42%) of 66 placebo patients and 32 (45%) of 71 glucosamine patients. In the Cox regression analysis, after adjustment for sex, study site and OA radiographic severity, time to disease flare was not significantly different in the glucosamine compared with placebo group. At final study visit, acetaminophen was used in 27% and 21% of placebo and glucosamine patients, respectively, nonstereoidal antiinflammatory drugs (NSAIDs) were used in 29% and 30%, and both were used in 20% and 21%. No differences were found in severity of disease flare or other secondary outcomes between placebo and glucosamine patients.
CONCLUSION: In patients with knee OA with at least moderate subjective improvement with prior glucosamine use, this study provides no evidence of symptomatic benefit from continued use of glucosamine sulfate.
Effects of glucosamine hydrochloride on the production of prostaglandin E2, nitric oxide and metalloproteases by chondrocytes and synovioctyes in osteoarthritis. Clin Exp Rheumatoi. 2004 May-Jun;22(3):293-9.
To determine the response of glucosamine hydrochloride on chondrocytes and synoviocytes in terms of prostaglandin E2 (PGE2), nitric oxide (NO) and matrix metalloproteases (MMPs). Chondrocytes and synoviocytes were prepared from joint specimens of patients who underwent total knee arthroplasty for osteoarthritis (OA). Chondroctes from patients with femoral neck fracture were served as a normal control. Culture cells were stimulated by 5 ng/ml of IL-1beta and treated with various concentration of glucosamine hydrochloride. Glucosamine hydrochloride at a concentration of 100 microg/ml suppressed PGE2 production and partly suppressed NO production. Glucosamine also suppressed the production of MMPs from normal chondrocytes and synoviocytes but not from OA chondrocytes.
CONCLUSION: Glucosamine sulfate reduces osteoarthritis progression in post-menopausal women with knee osteoarthritis: evidence from two 3-year studies.
Bruyere O. WHO Collaborating Center for Public Health Aspect of Osteoarticular Disorders, Liege, Belgium.
Menopause. 2004 Mar-Apr;1 1(2):13-43
OBJECTIVE: To investigate the effect of glucosamine sulfate on long-term symptoms and structure progression in post-menopausal women with knee osteoarthritis (OA).
DESIGN: This study consisted of a pre-planned combination of two three-year, randomized, placebo-controlled, prospective, independent studies evaluating the effect of glucosamine sulfate on symptoms and structure modification in OA and post-hoc analysis of the results obtained in post-menopausal women with knee OA. Minimal joint space width was assessed at baseline and after 3 years from standing anteroposterior knee radiographs. Symptoms were scored by the algo-functional WOMAC index at baseline and after 3 years. All primary statistical analyses were performed in intention-to-treat, comparing joint space width and WOMAN changes between groups by ANOVA.
RESULTS: Of 414 participants randomized in the two studies, 319 were post-menopausal women. At baseline, glucosamine sulfate and placebo groups were comparable for demographic and disease characteristics, both in the general population and in the post-menopausal women subset. After 3 years, post-menopausal participants in the glucosamine sulfate group showed no joint space narrowing [joint space change of +0.003 mm (95% CI, -0.09 to 0.11)], whereas participants in the placebo group experienced a narrowing of -0.33 mm. Percent changes after 3 years in the WOMAC worsening in the placebo group.
CONCLUSION: This analysis, focusing on a large cohort of post-menopausal women, demonstrated for the first time that a pharmacological intervention with glucosamine for OA has a disease-modifying effect in this particular population, the most frequently affected by knee OA.
Effect of glucosamine supplementation on fasting and non-fasting plasma glucose and serum insulin concentrations in healthy individuals.
Osteoarthritis Cartilage. 2004 Jun;12(6):506-11
OBJECTIVE: To test the hypothesis that glucose intolerance does not occur when healthy adults consume normal, recommended dosages of glucosamine sulfate.
METHODS: Healthy adults (N=19) ingested 1500 mg of glucosamine sulfate or placebo (double blind) each day for 12 weeks. Three-hour oral glucose tolerance tests (OGTT) were performed using 75 g of dextrose. These occurred before the start of supplementation, at 6 weeks, and at the completion of supplementation (12 weeks).
RESULTS: There were no significant diffrences between fasted levels of serum insulin or blood glucose. Glucosamine sulfate supplementation did not alter serum insulin or plasma glucose during the OGTT. There were no significant differences within or between treatments, ages or gender. Glycated haemoglobin measurements at the three time points showed no significant changes over time, within or between treatments, ages or gender. The lack of significant changes may have been due to large standard deviations in the data.
CONCLUSION: The data suggests that glucosamine supplementation, with normal recommended dosages, does not cause glucose intolerance in healthy adults. This cannot be determined conclusively, however, until further studies are conducted using alternative types of testing.
The effect of glucosamine supplementation on people experiencing regular knee pain. Braham R. University of Western Australia. Crawley, Western Australia 6009. Br J Sports
Med. 2003 Feb;37(1):45-9; discussion 49.
OBJECTIVE: The purpose of this study was to examine the effects of oral glucosamine supplementation on the functional ability and degree of pain felt by individuals who had regular knee pain, most likely due to previous articular cartilage damage, and possibly osteoarthritis.
METHODS: Subjects were randomly supplemented with either glucosamine (n=24) or placebo (P) (lactose) (n=22) for 12 weeks at a dose of 2,000 mg per day. Over this period, four testing sessions were conducted, with changes in knee pain and function assessed by clinical and functional tests, (joint line palpation, a 3 metre “duck walk” and a repeated, walking stair climb), two questionnaires (the Knee Injury and Osteoarthritis Outcome Score [KOOS] and the Knee Pain Scale [KPS]) and participant subjective evaluations.
RESULTS: The clinical and functional test scores improved with time but there were no significant differences between the two groups. The questionnaire results also recorded a significant main effect for time, but the glucosamine group was found to have significantly better KOOS quality of life scores at week eight and 12, and lower KPS scores are week eight than the placebo group.
CONCLUSIONS: These results suggest that glucosamine supplementation can provide some degree of pain relief and improved function in persons who experience regular knee pain, which may be caused by prior cartilage injury and/or osteoarthritis. The trends in the results also suggest that, at a dosage of 2,000 mg per day, the majority of improvements are present after eight weeks.
Glucosamine sulfate reduces osteoarthritis progression in post-menopausal women with knee arthritis: evidence from two 3-year studies.
Menopause. 2004 Mar-Apr;11(2):138-43.
OBJECTIVE: To investigate the effect of glucosamine sulfate on long-term symptoms and structure progression in post-menopausal women with knee osteoarthritis (OA).
DESIGN: 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 OA and post-hoc analysis of the results obtained in post-menopausal women with knee OA. Minimal joint space width was assessed at baseline and after 3 years from standing anteroposterior knee radiographs. Symptoms were scored by the aglo-functional WOMAC index at baseline and after 3 years. All primary statistical analyses were performed in intention-to-treat, comparing joint space width and WOMAC changes between groups by ANOVA.
RESULTS: Of 414 participants randomized in the two studies, 319 were post-menopausal women. At baseline, glucosamine sulfate and placebo groups were comparable for demographic and diseasae characteristics, both in the general population and in the post-menopausal women subset. After 3 years, post-menopausal participants in the glucosamine sulfate group showed no joint space narrowing [joint space change of +0.003 mm], whereas participants in the placebo group experienced a narrowing on -0.33 mm. Percent changes after 3 years in the WOMAC index showed an improvement in the glucosamine sulfate group and a trend for worsening the placebo group.
CONCLUSION: This analysis, focusing on a large cohort of post-menopausal women, demonstrated for the first time that a pharmacological intervention for OA has a disease-modifying effect in this particular population, the most frequently affected by knee OA.
Effect of glucosamine supplementation on fasting and non-fasting plasma glucose and serum insulin concentrations in healthy individuals.
Osteoarthritis Cartilage. 2004 Jun;12(6):506-11.
OBJECTIVE: To test the hypothesis that glucose intolerance does not occur when healthy adults consume normal, recommended dosages of glucosamine sulfate.
METHODS: Healthy adults (N=19) ingested 1500 mg of glucosamine sulfate or placebo (double blind) each day for 12 weeks. Three-hour oral glucose tolerance tests (OGTT) were performed using 75 g of dextrose. These occurred before the start of supplementation, at 6 weeks, and at the completion of supplementation (12 weeks).
RESULTS: There were no significant differences between fasted levels of serum insulin or blood glucose. Glucosamine sulfate supplementation did not alter serum insulin or plasma glucose during the OGTT. There were no significant differences within or between treatments, ages or gender. Glycated haemoglobin measurements at the three time points showed no significant change over time, within or between treatments, ages or gender. The lack of significant changes may have been due to large standard deviations in the data.
CONCLUSION: The data suggests that glucosamine supplementation, with normal recommended dosages, does not cause glucose intolerance in healthy adults. This cannot be determined conclusively, however, until further studies are conducted using alternative types of testing.
Glucosamine and MSM work better together for arthritis.
Clinical Drug Investigations, June 2004.
A study published in Clinical Drug Investigations, made big news in July 2004. The study found that the combination of glucosamine and methylsulfonylmethane - better known as MSM - is more effective against osteoarthritis than either nutrient alone. Although the individual nutrients did improve pain and swelling in patients’ affected joint, the combined therapy was more effective than MSM or glucosamine alone in reducing these symptoms and improving the function of joints. In a clinical trial conducted at the Institute of Medical Sciences in Hyderabad, India, 118 patients with mild to moderate osteoarthritis were treated three times daily with either 500 milligrams of glucosamine, 500 milligrams of MSM, a combination of both, or an inactive placebo. After 12 weeks of treatment, the average pain score had fallen from 1.74 to 0.65 in the glucosamine-only group. In MSM-only participants, it fell from 1.53 to 0.74. However, in the combination group, it fell from 1.7 to 0.36. The researchers also found that the combination treatment had a faster effect on pain and inflammation compared to glucosamine alone. All of the treatments were well tolerated. “it can be concluded,” the researchers say, “that the combination of MSM with glucosamine provides better and more rapid improvement in patients with osteoarthritis.”
The effect of glucosamine-chondroitin supplementation on gluocsylated haemoglobin levels in patients with type 2 diabetes mellitus: a placebo-controlled, double-blinded, randomized clinical trial.
Arch Intern Med. 2004 Apr 12;164(7):807
BACKGROUND: With increasing use of glucosamine-containing supplements for the treatment of osteoarthritis, there is increasing concern in the medical community about possible toxic effects. The present study was undertaken to determine whether glucosamine supplementation altered haemoglobin A1c concentrations in patients with well-controlled diabetes mellitus.
OBJECTIVE: To evaluate possible effects of glucosamine supplementation on glycemic control in a selected population of patients with type 2 diabetes mellitus.
DESIGN: Placebo-controlled, double-blinded, randomized clinical trial.
SETTING: Outpatient, diabetes monitoring clinic.
PATIENTS: Patients were typically elderly patients, evenly divided between men and women. Most of the patients were being treated with 1 or 2 drugs for glycemic control.
INTERVENTION: in daily doses for 90 days, patients received either placebo or a combination of 1500 mg of glucosamine hydrochloride with 1200 mg of chondroitin. Main Outcome Measure Haemoglobin A1c levels before and after 90 days of therapy.
RESULTS: There were 4 withdrawals from the glucosamine-treated group. Three were related to co-morbidities (myocardial infarction, congestive heart failure, and atrial fibrillation) and 1 to a possible adverse reaction (excessive flatus). No other patient reported any adverse effects of glucosamine therapy, and no patient had any change in their diabetes management. Mean haemoglobin A1c concentrations were not significantly different between groups prior to glucosamine therapy. Post treatment haemoglobin A1c concentrations were not significantly different between groups, nor were there any significant differences within group before and after treatment.
CONCLUSIONS: This study demonstrates that oral glucosamine supplementation does not results in clinically significant alterations in glucose metabolism in patients with type 2 diabetes mellitus.
Glucosamine and MSM work better together for arthritis:
We all know the benefits of glucosamine and chondroitin for arthritis. Now it seems there’s another nutrient that could be helpful in combination with glucosamine. This nutrient is known as MSM - which stands for Methylsulfonylmethane. In the June 2004 issue of the journal Clinical Drug investigations, scientists report that although the individual agents did not improve pain and swelling in arthritic joints, the combined therapy was more effective than the singly nutrients in reducing symptoms and improving the function of joints. In a clinical trial conducted at Nizam’s Institute of Medical Sciences in Hyderabad, India, 118 patients with mild to moderate osteoarthritis were treated three times daily with either 500 milligrams of glucosamine, 500 milligrams of methylsulfonylmethane, a combination of both, or an inactive placebo. After 12 weeks of treatment, the average pain score had fallen from 1.74 to 0.65 in the glucosamine-only group. In MSM-only participants, it fell from 1.53 to 0.74. However, in the combination group, it fell from 1.7 to 0.36.