Glucosamine

Overview

Glucosamine is an amino-sugar that is naturally produced in humans. It is the key building block in the synthesis of glycosaminoglycans, hyaluronic acid and proteoglycans. These substances are the foundation of many of the body's tissues including tendons, ligaments, cartilage, collagen, basement membranes, mucous membranes of the digestive system, membranes in the respiratory tract, and synovial fluid in the joints. Proteoglycans are proteins that make up the connective tissue of cartilage giving joints their elasticity, strength, and resilience.

Tissues in the joints become damaged when lubricating synovial fluids in the joint spaces lose viscosity. Glucosamine normally synthesized, may be insufficient in quantity for repair. With the loss of cushioning, degeneration of bones and cartilage begins, accompanied by reduced flexibility of the joint. Glucosamine supplementation helps to make the synovial fluid thick and elastic.

Reports of rapid symptomatic response to glucosamine in osteoarthritis may be partially due to the promotion synthesis of cartilage proteoglycans. Glucosamine also stimulates synovial production of hyaluronic acid (HA). HA has anti-inflammatory and analgesic properties, and promotes anabolic behavior in chondrocytes. Concentration and molecular weight is decreased in osteoarthritis; glucosamine supplementation may provide long-term benefits, for repair of joint structures. (1)

Both glucosamine sulfate and glucosamine HCl hydrolyze in stomach acids, separating glucosamine from the carrier. Glucosamine is then readily available for absorption in the small intestine. Glucosamine sulfate is approximately 74 percent glucosamine (dependent on product quality) stabilized with a salt of potassium or sodium.

Glucosamine needs sulfur to be properly utilized; however, the concept that the sulfur components of glucosamine sulfate cross-link with other molecules for structural integrity is not supported by research study. Glucosamine uses the sulfur released from existing stores donated by protein molecules already available in the joint tissue.

Glucosamine appears to act synergistically with chondroitin sulfate without side effects. Chondroitin sulfate inhibits the deleterious effect of degradative enzymes on critical joint components. Manganese, vitamin C, and bromelain may improve effectiveness of glucosamine without the side effects typical to nonsteroidal anti-inflammatory drugs.

Dosage Info

Dosage Range

500-2,000mg daily.

Most Common Dosage

500mg, 3 times a day.

Dosage Forms

Capsules, tablets, liquids, and powders often in combination with chondroitin sulfate.

Adult RDI

None established

Adult ODA

None established

Active Forms

Glucosamine sulfate and hydrochloride.

Absorption

Glucosamine is easily absorbed from the gastrointestinal tract when taken orally.

Toxicities & Precautions

General

There is no known toxicity associated with glucosamine.

Individuals on sodium-restricted diets and those concerned about potassium intake should use glucosamine HCl instead of glucosamine sulfate.

Exercise results in reductions of the blood concentrations of glucosamine.

Side Effects

Glucosamine induced insulin resistance in skeletal muscle in animal studies. (2) , (3) It has been determined that glucosamine may lower cellular ATP levels and affect insulin action in fat cells by other mechanisms. (4) A study has reported that interstitial glucose and insulin levels are not reduced during glucosamine therapy. (5) To date, no evidence has been found to support that glucosamine has an effect on blood sugar regulation in humans.

Allergy

Some glucosamine products are created from shellfish. No allergic responses have been reported in individuals with a shellfish allergy. Supposedly, glucosamine derived from shellfish is purified and therefore should not cause a hypersensitive response. However, data does not exist to support or deny this claim. Until further information is available, individuals with a shellfish allergy should use glucosamine cautiously or use products that are derived from sources other than shellfish.

Functions in the Body

Macromolecule Biosynthesis:

Glucosamine is necessary for the biosynthesis of macromolecules including glycolipids, glycoproteins, hyaluronic acid, proteoglycans, and mucopolysaccharides, which are also called glycosaminoglycans (GAGs).

Anti-inflammatory Activity:

Glucosamine provides anti-inflammatory activity.

Clinical Applications

Gonarthritis

A 12-month study demonstrated that glucosamine sulfate has chondroprotective activity, with significant improvement after the first 3 months of therapy. (6) Results of various studies report that glucosamine sulfate may lead to long-lasting pain reduction and functional improvement by means of increasing anabolic mechanisms, reducing the activity of proteolytic enzymes and by its anti-inflammatory effect. (7)

Temporomandibular Joint Dysfunction

Studies report decreased joint noises, pain, and swelling after the administration of glucosamine and chondroitin sulfate in the treatment of TMJ. (8)

Kidney Stones

A mixture of glycosaminoglycans, including glucosamine, administered to 40 patients with idiopathic calcium-oxalate nephrolithiasis, reported a significant reduction in the formation of oxalate stone formation. (9)

Wound Healing

Glucosamine availability appears to be rate-limiting for hyaluronic acid synthesis. Administration during the first few days after surgery or trauma can enhance hyaluronic acid production in the wound, promoting swifter healing with potentially diminishing complications related to scarring. (10)

Osteoarthritis

Glucosamine functions as an anti-inflammatory and studies indicate that supplementation with glucosamine reduced inflammation. (11) , (12) , (13) , (14) Researchers found that glucosamine sulfate supplementation in patients improved symptoms of osteoarthritis and the arthritis did not progress as rapidly as it did in the placebo group. (15) , (16)

Symptoms and Causes of Deficiency

No glucosamine deficiency has been reported in humans.

Dietary Sources

Glucosamine does not occur in foods. Supplemental sources of glucosamine are derived from chitin, which is the processed exoskeleton of shrimp, lobster, and crab shells.

References

  1. View Abstract: McCarty MF. Enhanced Synovial Production of Hyaluronic Acid may Explain Rapid Clinical Response to High-dose Glucosamine in Osteoarthritis. Med Hypotheses. Jun1998;50(6):507-10.
  2. View Abstract: Kim YB, Zierath JR, Zhu JS, et al. Glucosamine Infusion in Rats Rapidly Impairs Insulin Stimulation of Phosphoinositide 3-kinase but does not Alter Activation of Akt/protein Kinase B in Skeletal Muscle. Diabetes. Feb1999;48(2):310-20.
  3. View Abstract: Virkamäki A, Yki Järvinen H. Allosteric Regulation of Glycogen Synthase and Hexokinase by Glucosamine-6-phosphate during Glucosamine-induced Insulin Resistance in Skeletal Muscle and Heart. Diabetes. May1999;48(5):1101-07.
  4. View Abstract: Chi MM, Heimberg H, Hresko RC, et al. Glucosamine-induced Insulin Resistance in 3T3-L1 Adipocytes is caused by Depletion of Intracellular ATP. J Biol Chem. Aug1998;273(32):20658-68.
  5. View Abstract: Holmäng A, Larsson BM, Lönroth P, et al. Induction of Insulin Resistance by Glucosamine Reduces Blood Flow but not Interstitial Levels of Either Glucose or Insulin. Diabetes. Jan1999;48(1):106-11.
  6. View Abstract: Franci B, Campagna S, Battisti E, et al. The Efficacy and Safety of Glucosamine Sulfate in the Treatment of Gonarthritis. Clin Ter. Mar1996;147(3):99-105.
  7. View Abstract: Vajaradul Y. Double-blind Clinical Evaluation of Intra-articular Glucosamine in Outpatients with Gonarthritis. Clin Ther. 1981;3(5):336-43.
  8. View Abstract: Shankland WE 2nd. The Effects of Glucosamine and Chondroitin Sulfate on Osteoarthritis of the TMJ: A Preliminary Report of 50 Patients. Cranio. Oct1998;16(4):230-35.
  9. View Abstract: Baggio B, et al. Effects of the Oral Administration of Glycosaminoglycans on Cellular Abnormalities Associated with Idiopathic Calcium Oxalate Nephrolithiasis. Eur J Clin Pharmacol. 1991;40(3):237-40.
  10. View Abstract: McCarty MF. Glucosamine for Wound Healing. Med Hypotheses. Oct1996;47(4):273-75.
  11. View Abstract: Vaz AL. Double-blind Clinical Evaluation of the Relative Efficacy of Ibuprofen and Glucosamine Sulphate in the Management of Osteoarthrosis of the Knee in Out-patients. Curr Med Res Opin. 1982;8(3):145-49.
  12. Muller-Fassbender H, et al. Glucosamine Sulfate Compared to Ibuprofen in Osteoarthritis of the Knee. Osteoarthritis and Cartilage. 1994;2(1):61-69.
  13. View Abstract: Qui GX, et al. Efficacy and Safety of Glucosamine Sulfate Versus Ibuprofen in Patients with Knee Osteoarthritis. Arzneimittelforschung. May1998;48(5):469-74.
  14. View Abstract: Reginster JY, Deroisy R, Rovati LC, et al. Long-term effects of glucosamine sulphate on osteoarthritis progression: a randomised, placebo-controlled clinical trial. Lancet. Jan2001;357(9252):251-6.
  15. View Abstract: Pavelka K, Gatterova J, Olejarova M, Machacek S, Giacovelli G, Rovati LC. Glucosamine Sulfate Use and Delay of Progression of Knee Osteoarthritis: A 3-Year, Randomized, Placebo-Controlled, Double-blind Study. Arch Intern Med. Oct2002;162(18):2113-23.
  16. View Abstract: Bruyere O, Pavelka K, Rovati LC, et al. Glucosamine sulfate reduces osteoarthritis progression in postmenopausal women with knee osteoarthritis: evidence from two 3-year studies. Menopause. Mar2004;11(2):138-43.