Glucosamine Sulfate
Chad Bradshaw
Background
Glucosamine is a simple endogenous compound composed of glucose and an amine. Endogenously, glucosamine acts in two ways:
Stimulates the manufacture of glycosaminoglycans (components of cartilage)
Promotes incorporation of sulfur into cartilage
Because of the latter, glucosamine sulfate is the best source of glucosamine.
Glucosamine is commercially derived from chitin, the specially processed exoskeleton of shrimp, lobsters, and crabs. There are no dietary sources of glucosamine.
Perhaps the most significant sign of glucosamine deficiency is osteoarthritis, a condition resulting from the lost ability of cartilage to act as a shock absorber. As a result, weight-bearing joints (hips, knees, joints of the hands) experience destruction of cartilage. The joints then become painful and deformed and their ability to move is retarded.
Glucosamine is useful therapeutically because of its actions:
Glucosamine retards the degradation of cartilage.
Glucosamine stimulates cartilage cells to synthesize building blocks of cartilage.
Glucosamine exhibits anti-inflammatory properties via the inhibition of proteolytic enzymes.
Because of these effects, glucosamine is most useful in the treatment and prevention of osteoarthritis.
Examining Glucosamine Preparations
The three common commercial forms of glucosamine are: glucosamine hydrochloride, glucosamine sulfate, and N-acetyl-glucosamine (NAG). Scientific evidence strongly supports the use of glucosamine sulfate and NOT the other forms.
Human studies show that glucosamine sulfate is almost 98% absorbed. It is then distributed in the body primarily to joint tissues where it is incorporated into the connective tissue matrix of cartilage, ligaments and tendons. While there have been no human studies utilizing NAG, there have been impressive studies involving glucosamine. Animal studies have further supported the fact that glucosamine is better absorbed than NAG and it s "more efficient precursor of macromolecular hexosamine (glycosaminoglycans) than N-acetylglucosamine. It is possible that N-acetylglucosamine does not penetrate the cell membranes and, as a result, is not available for incorporation into glycoproteins and mucopolysaccharides." (Vidal Y and Plana RR, et al., Articular cartilage pharmacology, I, In vitro studies on glucosamine and non steroidal anti-inflammatory drugs. Pharmacol Res Comm 10, 557-569, 1978.)
Absorption of N-acetylglucosamine is questionable in humans for several reasons:
NAG is quickly digested by intestinal bacteria.
NAG is a known binder of dietary lectins in the gut with the resultant lectin-NAG complex being excreted in the feces.
A large percentage of NAG is broken down by intestinal cells.
In fact, NAG and glucosamine sulfate are entirely different molecules. The structural differences (NAG has a portion of an acetic acid molecule attached to it) make the body handle the two compounds differently. Glucosamine sulfate absorption appears to be active, whereas no mechanism exists for the absorption of NAG.
The scientific literature does not support the use of glucosamine hydrochloride. Apparently, the sulfur component of glucosamine sulfate is crucial to its mechanism of action.
In short, the only form of glucosamine that should be used is glucosamine sulfate.
Why use glucosamine instead of NSAIDS (Non-Steroidal Anti-Inflammatory Drugs) for Osteoarthritis?
While aspirin very effectively relieves the pain and inflammation associated with osteoarthritis, large doses (2-4 grams/day) are needed. These amounts of aspirin almost certainly result in toxicities such as tinnitus and gastric irritation. Other NSAIDS may be more tolerable, but are also associated with GI upset, headaches, and dizziness. In addition, NSAIDS actually inhibit cartilage repair and accelerate cartilage destruction. Since osteoarthritis itself is caused by cartilage degeneration, NSAIDS actually worsen the condition. In summary, aspirin and other NSAIDS may suppress the symptoms but actually accelerate the progression of osteoarthritis.
Clinical Trials with Glucosamine Sulfate
Clinical trials have repeatedly shown that while offering very little anti-inflammatory and no direct analgesic effect, glucosamine sulfate is far superior in relieving pain and inflammation of osteoarthritis than NSAIDS. Glucosamine addresses the underlying problem of osteoarthritis (cartilage degeneration), whereas NSAIDS simply provide symptomatic relief and further contribute to the degenerative disease of osteoarthritis.
Glucosamine's effects are not seen immediately, but when they do appear, the effects are much better than NSAIDS. For example, one double-blind study compared glucosamine sulfate to ibuprofen. Pain scores for subjects taking ibuprofen decreased faster in the first 2 weeks than scores in the glucosamine sulfate group. However, at week 4, the glucosamine group's pain scores were better than the ibuprofen group. Physicians also rated their patients' overall responses as either good or fair. The physicians rated 44% of the glucosamine sulfate group as "good" and only 15% of the ibuprofen group (Pujalte et al.).
A Portuguese study (Tapadinhas MJ, et al.) brought to light some other important clinical pearls concerning glucosamine.
Glucosamine Sulfate versus Cartilage Extracts
Cartilage extracts such as purified chondroitin sulfate, sea cucumber, green-lipped mussel, and shark cartilage are also readily available nutritional supplements. While these agents are composed of repeating units of glucosamine (with attached sugar molecules), they are not absorbed or utilized as well as pure glucosamine sulfate. Pharmacokinetic studies show that up to 98% of oral glucosamine sulfate is absorbed, compared to between 0 and 8% of oral chondroitin sulfate. In addition, the benefits of glucosamine sulfate are highly documented. This is not the case with cartilage extracts.
Dosage
Safety Issues
Glucosamine sulfate has been shown to be exceptionally safe in both animal and human studies. Side effects (when they do occur) are limited to gastric upset, heartburn, diarrhea, nausea or indigestion. Most of the time, these symptoms can be avoided by taking glucosamine with a meal. Hypersensitivity to sulfa drugs or sulfite-containing foods does not indicate hypersensitivity to glucosamine sulfate. The sulfate form of sulfur is present in high concentrations in human blood anyway. No allergic reactions have been reported.
References
Jones, Kimberly and Michelle Giesler. Glucosamine: The Arthritis Cure?. Presentation handout, Pharmacy 100, UNC-CH School of Pharmacy, Fall 1997.
Murray, Michael T. Encyclopedia of Nutritional Supplements. Prima Publishing, 1996.