Glucosamine
  
Glucosamine
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.
Synonyms
2-acetamido-2-deoxyglucose, acetylglucosamine, Arth-X Plus®, chitosamine, D-glucosamine, enhanced glucosamine sulfate, Flexi-Factors®, glucosamine chlorohydrate, Glucosamine Complex®, glucosamine hydrochloride, glucosamine hydroiodide, Glucosamine Mega®, glucosamine N-Acetyl, glucosamine sulfate, glucosamine sulphate, Joint Factors®, N-acetyl D-glucosamine (NAG, N-A-G), Nutri-Joint®, Poly-NAG, Ultra Maximum Strength Glucosamine Sulfate®.
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.
Uses based on scientific evidenceGrade*Knee osteoarthritis (mild-to-moderate)
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 . Further trials are needed to confirm safety and effectiveness, and to test different formulations of glucosamine.
A
Osteoarthritis (general)
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. More research is needed in this area before a conclusion can be made.
B
Chronic venous insufficiency
"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.
C
Inflammatory bowel disease (Crohn's disease, ulcerative colitis)
Preliminary research reports improvements with N-acetyl glucosamine as an added therapy in inflammatory bowel disease. Further scientific evidence is necessary before a recommendation can be made.
C
Rheumatoid arthritis
Preliminary human research reports benefits of glucosamine in the treatment of joint pain and swelling in rheumatoid arthritis. 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 people with this disease.
C
Temporomandibular joint (TMJ) disorders
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.
C
* 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).
Uses based on tradition or theory
The below uses are based on tradition or scientific theories. They often have not been thoroughly tested in humans, and safety and effectiveness have not always been proven. Some of these conditions are potentially serious, and should be evaluated by a qualified healthcare provider.
AIDS, athletic injuries, back pain, bleeding esophageal varices (blood vessels in the esophagus), cancer, congestive heart failure, depression, diabetes, fibromyalgia, joint pain, knee pain, kidney stones, migraine headache, osteoporosis, pain, psoriasis, skin rejuvenation, spondylosis deformans (growth of bony spurs on the spine), would healing, immunosuppression, topical hypopigmenting agent (combination product containing multiple ingredients).
Dosing
The below doses are based on scientific research, publications, traditional use, or expert opinion. Many herbs and supplements have not been thoroughly tested, and safety and effectiveness may not be proven. Brands may be made differently, with variable ingredients, even within the same brand. The below doses may not apply to all products. You should read product labels, and discuss doses with a qualified healthcare provider before starting therapy.
Standardization
Standardization involves measuring the amount of certain chemicals in products to try to make different preparations similar to each other. It is not always known if the chemicals being measured are the "active" ingredients. Glucosamine is not considered a drug in the United States and is therefore not required to be tested for quality by any agency prior to sale. Therefore, glucosamine preparations in the United States may vary in quality among different manufacturers and from batch to batch within the same manufacturer. In parts of Europe, glucosamine sulfate is available as a prescription drug of defined chemical nature. Most studies of glucosamine taken by mouth have used glucosamine sulfate, although different glucosamine salts are available, including glucosamine hydrochloride and glucosamine hydroiodide.
Adults (18 years and older)
Osteoarthritis : In most available studies, 500 milligrams of glucosamine sulfate has been used, taken by mouth as tablets or capsules three times daily, for 30 to 90 days. Once daily dosing as 1.5 grams (1500 milligrams) has also been used. Limited research has used 1500 milligrams daily as a crystalline powder for oral solution, or 500 milligrams of glucosamine hydrochloride three times daily. Dosing of 20 milligrams per kilogram of body weight daily has also been recommended in some publications. One study used a dose of 2000 milligrams per day for 12 weeks.
Other forms of glucosamine studied for osteoarthritis include : intra-articular (joint injections) of 400 milligrams of glucosamine sulfate daily for 7 days, 400 milligrams of glucosamine sulfate intravenously (through the veins) daily for 7 days, and muscular injections of 400 milligrams twice weekly. Another kind of glucosamine that has been used is a topical form in combination with chondroitin for a 4 week period. Safety and effectiveness of these formulations are not clearly proven.
Glucosamine hydrochloride provides more glucosamine than glucosamine sulfate , although this difference likely does not matter when products are prepared to provide a total of 500 milligrams of glucosamine per tablet.
Children (younger than 18 years)
There is not enough scientific evidence to recommend the use of glucosamine in children. Preliminary research has been done using N-acetyl-glucosamine in a small number children with inflammatory bowel disease, at a dose of 3 to 6 grams daily for an average of two and a half years.
Research in children has shown that there could be a relationship between the ingestion of MSM (methylsulfonylmethane) and autism; whether it is beneficial or harmful is unclear. MSM is often marketed with glucosamine as a dietary supplement and at this time should be avoided in children.
Safety
The U.S. Food and Drug Administration does not strictly regulate herbs and supplements. There is no guarantee of strength, purity or safety of products, and effects may vary. You should always read product labels. If you have a medical condition, or are taking other drugs, herbs, or supplements, you should speak with a qualified healthcare provider before starting a new therapy. Consult a healthcare provider immediately if you experience side effects.
Allergies
Since glucosamine can be made from the shells of shrimp, crab, and other shellfish, people with shellfish allergy or iodine hypersensitivity may have an allergic reaction to glucosamine products. A serious hypersensitivity reaction including throat swelling has been reported with glucosamine sulfate.
Side Effects and Warnings
In most human studies, glucosamine sulfate at a dose of 500 milligrams three times daily (tablets or capsules) has been well tolerated for 30 to 90 days. In a 3-year study and several short-term trials, the number of adverse events in patients taking glucosamine was no different from placebo (sugar pill). There have been reports that in laboratory animals, doses as high as 5000 milligrams per kilogram taken by mouth, 3000 milligrams per kilogram injected into muscle, and 1500 milligrams per kilogram through the veins have not caused death.
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 no effects on blood sugar, while other research reports effects on insulin. 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 several human cases, abnormal increased 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. 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.
There are reported cases suggesting a link between glucosamine/chondroitin products and asthma exacerbations. Until there exists more reliable data, patients with a history of asthma should not use glucosamine supplements except under the strict supervision of a physician.
Preliminary data suggest that glucosamine may modulate the immune system, although the clinical relevance of this is not clear.
Pregnancy & Breastfeeding
Glucosamine is not recommend during pregnancy or breastfeeding due to lack of scientific evidence.
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