Biologic/Organic/Pharmacologic Therapies: Glucosamine
Natural Standard Monograph
Background: Glucosamine is a natural compound that is found in healthy cartilage. Glucosamine sulfate is a normal constituent of glycoaminoglycans in cartilage matrix and synovial fluid.
Available evidence from randomized controlled trials supports the use of glucosamine sulfate in the treatment of osteoarthritis, particularly of the knee. It is believed that the sulfate moiety provides clinical benefit in the synovial fluid by strengthening cartilage and aiding glycosaminoglycan synthesis. If this hypothesis is confirmed, it would mean that only the glucosamine sulfate form is effective and non-sulfated glucosamine forms are not effective.
Glucosamine is commonly taken in combination with chondroitin, a glycosaminoglycan derived from articular cartilage. Use of complementary therapies, including glucosamine, is common in patients with osteoarthritis, and may allow for reduced doses of non-steroidal anti-inflammatory agents.
Uses based on scientific evidence
These uses have been tested in humans or animals. Safety and effectiveness have not always been proven. Some of these conditions are potentially serious, and should be evaluated by a qualified healthcare provider.
Knee osteoarthritis (mild-to-moderate) A
Based on human research, there is good evidence to support the use of glucosamine sulfate in the treatment of mild-to-moderate knee osteoarthritis. Most studies have used glucosamine sulfate supplied by one European manufacturer (Rotta Research Laboratorium), and it is not known if glucosamine preparations made by other manufacturers are equally effective. Although some studies of glucosamine have not found benefits, these have either included patients with severe osteoarthritis or used products other than glucosamine sulfate. The evidence for the effect of glycosaminoglycan polysulphate is conflicting and merits further investigation. More well-designed clinical trials are needed to confirm safety and effectiveness, and to test different formulations of glucosamine.
Osteoarthritis (general) B
Several human studies and animal experiments report benefits of glucosamine in treating osteoarthritis of various joints of the body, although the evidence is less plentiful than that for knee osteoarthritis. Some of these benefits include pain relief, possibly due to an anti-inflammatory effect of glucosamine, and improved joint function. Overall, these studies have not been well designed. Although there is some promising research, more study is needed in this area before a firm conclusion can be made.
Chronic venous insufficiency C
"Chronic venous insufficiency" is a syndrome that includes leg swelling, varicose veins, pain, itching, skin changes and skin ulcers. The term is more commonly used in Europe than in the United States. Currently, there is not enough reliable scientific evidence to recommend glucosamine in the treatment of this condition.
Diabetes (and related conditions) C
Early research suggests that glucosamine does not improve blood sugar control, lipid levels or apolipoprotein levels in diabetics. Additional research is needed in this area.
Inflammatory bowel disease (Crohn's disease, ulcerative colitis) C
Preliminary research reports improvements with N-acetyl glucosamine as an added therapy in inflammatory bowel disease. Further scientific evidence is necessary before a strong recommendation can be made.
Pain (leg pain) C
Preliminary human research reports benefits of injected glucosamine plus chondroitin in the treatment of leg pain arising from advanced lumbar degenerative disc disease. Further scientific evidence is necessary before a firm recommendation can be made.
Rehabilitation (after knee injury)
Glucosamine has been given to athletes with acute knee injuries. Although glucosamine did not improve pain, it did help improve flexibility. Additional research is needed to confirm these early findings.
Early human research reports benefits of glucosamine in the treatment of joint pain and swelling in rheumatoid arthritis. In other research, glucosamine did not exert anti-rheumatic effects, but it did improve symptoms of the disease. However, this is early information, and additional research is needed before a conclusion can be drawn. The treatment of rheumatoid arthritis can be complicated, and a qualified healthcare provider should follow patients with this disease.
Temporomandibular joint (TMJ) disorders C
There is a lack of sufficient evidence to recommend for or against the use of glucosamine (or the combination of glucosamine and chondroitin) in the treatment of temporomandibular joint disorders.
*Key to grades: A: Strong scientific evidence for this use; B: Good scientific evidence for this use; C: Unclear scientific evidence for this use; D: Fair scientific evidence against this use (it may not work); F: Strong scientific evidence against this use (it likely does not work).
Side Effects and Warnings
In most human studies, glucosamine sulfate has been well tolerated for 30 to 90 days.
Side effects may include upset stomach, drowsiness, insomnia, headache, skin reactions, sun sensitivity and nail toughening. There are rare reports of abdominal pain, loss of appetite, vomiting, nausea, flatulence (gas), constipation, heartburn and diarrhea. Based on several human cases, temporary increases in blood pressure and heart rate, as well as palpitations, may occur with glucosamine/chondroitin products. Based on animal research, glucosamine theoretically may increase the risk for eye cataract formation.
It remains unclear if glucosamine alters blood sugar levels. Several human studies suggest that glucosamine taken by mouth has no effects on blood sugar, while other research reports mixed effects on insulin. When glucosamine is injected, it appears to cause insulin resistance and endothelial dysfunction. Preliminary studies show no effect on mean hemoglobin A1c concentrations in patients with type 2 diabetes mellitus. Caution is advised in patients with diabetes or hypoglycemia and in those taking drugs, herbs or supplements that affect blood sugar. Serum glucose levels may need to be monitored by a healthcare provider and medication adjustments may be necessary.
In theory glucosamine may increase the risk of bleeding. Caution is advised in patients with bleeding disorders or taking drugs that may increase the risk of bleeding. Dosing adjustments may be necessary.
In several human cases, abnormally high amounts of protein were found in the urine of patients receiving glucosamine / chondroitin products. The clinical meaning of this is unclear. Glucosamine is removed from the body mainly in the urine, and elimination of glucosamine from the body is delayed in people with reduced kidney function. Acute interstitial nephritis, a condition that causes the kidneys to become swollen and possibly dysfunctional, has been reported in a patient taking glucosamine. Increased blood levels of creatine phosphokinase may occur with glucosamine/chondroitin, which may be due to impurities in some products. This may alter certain laboratory tests measured by healthcare providers.
Early data suggest that glucosamine may modulate the immune system, although the clinical relevance of this is not clear.
One patient developed liver inflammation (acute cholestatic hepatitis) after taking glucosamine forte.