Glucosamine: What is it?

I have suffered from knee pain for years. This could be attributed to congenital or developmental defects (never developed the full amount of cartilage in my knees) or the years of serving in the infantry or even football and martial arts. Whatever the reason for the pain, I wanted relief. I found that glucosamine alleviates these pains. But why??

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, ChitoSeal, Clo-Sur PAD, D-glucosamine, disease modifying drugs for osteoarthritis (DMOAD), 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-N-acetyl glucosamine (pGlcNAc), Poly-NAG, Syvek Patch, 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.

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 . 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)

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

"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)

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.

Diabetes (and related conditions)

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)

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.

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 strong recommendation can be made.

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 strong recommendation can be made.

Pain (leg pain)

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.

 Rheumatoid arthritis

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

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.

High cholesterol

Glucosamine does not appear to alter LDL or HDL levels in patients with chronic joint pain or diabetes.

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, fibromyalgia, kidney stones, migraine headache, immunosuppression, osteoporosis, pain, psoriasis, skin rejuvenation, spondylosis deformans (growth of bony spurs on the spine), topical hypopigmenting agent (combination product containing multiple ingredients), wound healing.

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.

Adults (18 years and older)
In most available studies, 500 milligrams of glucosamine sulfate has been taken by mouth as tablets or capsules three times daily for 30 to 90 days. Once daily dosing as 1.5 grams (1,500 milligrams) has also been used. Limited research has used 1,500 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 2,000 milligrams per day for 12 weeks.
Another kind of glucosamine that has been used is a topical form in combination with chondroitin for a four-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.
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. However, some research suggests that there is not enough shrimp allergen in glucosamine supplements to trigger reactions in patients who are allergic to shrimp. Nevertheless, caution is warranted. A serious hypersensitivity reaction including throat swelling has been reported with glucosamine sulfate. There are reported cases suggesting a link between glucosamine/chondroitin products and asthma exacerbations.
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.
Pregnancy and Breastfeeding
Glucosamine is not recommended during pregnancy or breastfeeding due to lack of scientific evidence.

Selected references

1. Albert SG, Oiknine RF, Parseghian S, et al. The effect of glucosamine on Serum HDL cholesterol and apolipoprotein AI levels in people with diabetes. Diabetes Care 2007 Nov;30(11):2800-3.
2. Audimoolam VK, Bhandari S. Acute interstitial nephritis induced by glucosamine. Nephrol Dial Transplant 2006 Jul;21(7):2031.
3. Clegg DO, Reda DJ, Harris CL, et al. Glucosamine, chondroitin sulfate, and the two in combination for painful knee osteoarthritis. N Engl J Med 2006 Feb 23;354(8):795-808.
4. Dudek A, Raczkiewicz-Papierska A, T?ustochowicz W. [Efficacy of glucosamine sulfate treatment in patients with osteoarthritis] Pol Merkur Lekarski 2007 Mar;22(129):204-7.
5. Herrero-Beaumont G, Ivorra JA, Del Carmen Trabado M, et al. 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.
6. Mehta K, Gala J, Bhasale S, et al. Comparison of glucosamine sulfate and a polyherbal supplement for the relief of osteoarthritis of the knee: a randomized controlled trial [ISRCTN25438351]. BMC Complement Altern Med 2007 Oct 31;7:34.
7. Miller MR, Mathews RS, Reeves KD. Treatment of painful advanced internal lumbar disc derangement with intradiscal injection of hypertonic dextrose. Pain Physician 2006 Apr;9(2):115-21.
8. Muniyappa R, Karne RJ, Hall G, et al. Oral glucosamine for 6 weeks at standard doses does not cause or worsen insulin resistance or endothelial dysfunction in lean or obese subjects. Diabetes 2006 Nov;55(11):3142-50.
9. Nakamura H, Masuko K, Yudoh K, et al. Effects of glucosamine administration on patients with rheumatoid arthritis. Rheumatol Int 2007 Jan;27(3):213-8.
10. Ossendza RA, Grandval P, Chinoune F, et al. [Acute cholestatic hepatitis due to glucosamine forte]. Gastroenterol Clin Biol 2007 Apr;31(4):449-50
11. Østergaard K, Hviid T, Hyllested-Winge JL. [The effect of glucosamine sulphate on the blood levels of cholesterol or triglycerides--a clinical study]. Ugeskr Laeger 2007 Jan 29;169(5):407-10.
12. Ostojic SM, Arsic M, Prodanovic S, et al. Glucosamine administration in athletes: effects on recovery of acute knee injury.Res Sports Med 2007 Apr-Jun;15(2):113-24.
13. Theodosakis J. A randomized, double blind, placebo controlled trial of a topical cream containing glucosamine sulfate, chondroitin sulfate, and camphor for osteoarthritis of the knee. J Rheumatol 2004;31(4):826-827.
14. Thie NM, Prasad NG, Major PW. Evaluation of glucosamine sulfate compared to ibuprofen for the treatment of temporomandibular joint osteoarthritis: a randomized double blind controlled 3 month clinical trial. J Rheumatol 2001;28(6):1347-1355.
15. Villacis J, Rice TR, Bucci LR, et al. Do shrimp-allergic individuals tolerate shrimp-derived glucosamine? Clin Exp Allergy 2006 Nov;36(11):1457-61.