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Pass the Joint

Does glucosamine heal or bypass damaged joints?

Glucosamine is a popular supplement for treating various joint problems, particularly osteoarthritis. Made in the body from a combination of glucose and the amino acid L-glutamine, glucosamine is preferred over the usual treatments for joint ills, such as nonsteroidal anti-inflamatory drugs, which do temporarily relieve joint pain but do nothing to ease the underlying problem.

In contrast, glucosamine, which is often combined with another natural substance, chondroitin sulfate, reportedly not only possess anti-inflamatory properties but also helps serve as a precursor for the actual building blocks of joints.

On the other hand, some studies have recently warned consumers of glucosamine supplements to beware of the possibility of interference with glucose metabolism in the body. This interference, in turn, promotes hyperglycemia, or excess glucose in the blood. The hyperglycemia, linked to insulin resistance, is considered by many clinicians to be the initial step in the onset of diabetes in predisposed people.

Several animal studies have suggested that glucosamine promotes glucose-based side effects by mimicking a metabolic pathway, which some researchers believe is the forerunner to full-blown insulin resistance. Some even suggest that glucosamine interferes with the passage of glucose into muscle. But that theory of glucosamine toxicity is a problem because it appears mostly in animal studies. A study of human subjects published last year showed no effects of a glucosamine infusion on either insulin activity or secretion,1 a result confirmed by a more recent study.2 The newer study featured 18 healthy nondiabetic subjects, consisting of an equal number of men and women, average age 24, who had a dose of glucosamine higher than that used in animal studies injected into one arm. The other arm acted as a control. The insulin was injected using a clamp technique to prevent systemic effects that might obscure clear results.

No subject showed any adverse effects on insulin-stimulated glucose uptake in the entire body or at the forearm level, and the authors point out the folly of applying the results of animal studies to human physiology. Another obvious clue to the safety of glucosamine is that while many people have used it to treat joint ills, there’s no report of glucose problems or diabetes onset, even after extended supplement use.

Another controversy concerning glucosamine is its mode of action. Most reviews say that it acts as a building block for a substance called glycosaminoglycan (GAG) in the body. GAG is the raw material from which joints are built and maintained. With age the body becomes less efficient at synthesizing that vital joint material, which means its internal joint structures degrade faster than it can rebuild them, and it becomes predisposed to such wear-and-tear diseases as osteoarthritis.

Studies show that while 90 percent of an oral dose of glucosamine is absorbed, most of it is degraded in the liver, leaving only 26 percent available for absorption into the blood. Despite that, even large oral doses of glucosamine don’t affect blood serum concentrations. If blood levels of glucosamine don’t increase appreciably, then it follows that not enough can enter the joint space to act as a true substrate for GAG synthesis. But many people have reported joint improvement after using glucosamine (it takes several weeks to observe results)’so how does glucosamine help? A new study offers an explanation of the apparent paradox.3

The sulfate portion of glucosamine imparts the joint-healing effects, say the study authors. Sulfate is essential for GAG synthesis, and when sulfate isn’t readily available, GAG synthesis in cartilage is inhibited.

That same study revealed that glucosamine offers an effective transport system for entry of inorganic sulfate into the joint space and thereby acts as a substrate for GAG and subsequent cartilage synthesis and repair. Interestingly, when straight sulfate is used for the same purpose, it doesn’t work. In large enough doses to work, straight sulfate acts as a laxative. On the other hand, sulfate blood levels do increase with consumption of either a mixed meal or a protein load. The protein effect is due to the presence of sulfur-containing amino acids, such as methionine and cysteine.

The authors also point out that even a 6,000-milligram oral dose of glucosamine fails to increase the blood plasma level of glucosamine. They note that ‘this should allay any concern that standard oral doses of glucosamine [which are less than one-tenth of this] could incur insulin resistance.’ As proof of their contention that the sulfate portion of glucosamine is the active factor, the authors cite previous studies that found glucosamine ineffective for treating joint/cartilage problems. Those studies didn’t use glucosamine sulfate but other supplemental forms of glucosamine not containing the sulfate portion.

Another interesting finding was that acetaminophen (one popular brand name is Tylenol) interferes with glucosamine sulfate by reducing blood sulfate levels, so taking glucosamine sulfate with acetaminophen would block its effects. Sulfate also speeds the exit of acetaminophen from the body, lowering its analgesic, or pain-killing, effect. The interference of acetaminophen with glucosamine sulfate activity may explain why some people who use acetaminophen to relieve immediate joint pain don’t experience its benefits.

Based on the new explanation of how glucosamine works to help mitigate joint and cartilage pain while promoting healing, I’d conjecture that adding a readily available, safe form of sulfate to an existing glucosamine/chondroitin formula would make it work even better. In fact, I’ve provided such a formula to several world-class athletes I’ve worked with in the past, including boxing champion Oscar de La Hoya. The best formula I’ve found is called Glucosamine Gold by Westco Innovative Nutrition. For more information call (310) 204-6686.

Editor’s note: Muscle-Link’s glucosamine and chondroitin sulfate supplement is Flex Stak. Visit for more information..
1 Monauni, T., et al. (2000). Effects of glucosamine infusion on insulin secretion and insulin action in humans. Diabetes. 49:926-935.
2 Pouwels, M.J., et al. (2001). Short-term glucosamine infusion does not affect insulin sensitivity in humans. J Clin Endocrino Metab. 86:2099-2103..
3 Hoffer, L.J., et al. (2001). Sulfate could mediate the therapeutic effect of glucosamine sulfate. Metabolism. 50:767-770.

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