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Glucosamine is a natural compound made in the body from glucose (blood sugar) and a nitrogen-containing amine molecule. In the body, glucosamine stimulates the manufacture of glycosaminoglycans (GAGs), structural support molecules in cartilage, tendons, and ligaments.
In groundbreaking research conducted over fifty years ago at the World Health Organization (WHO), it was found that as people age, they lose the ability to manufacture sufficient levels of glucosamine.
Without adequate glucosamine, cartilage loses its gel-like nature and ability to act as a shock absorber. Glycosaminoglycans (GAGs) serve as the structural scaffolding of cartilage and are critical to maintaining the high water content of cartilage and other joint components. Without sufficient glucosamine, joints start to degenerate (break down). Glucosamine also exerts some action on inflammatory processes.
After discovering glucosamine's link to joint health, intensive scientific research has shown a rationale and role for glucosamine supplementation in supporting joint health. Glucosamine is recommended as a "first-line" approach to joint health issues by medical organizations in many parts of the world.
Glucosamine sulfate is the best form of glucosamine and the key dietary supplement to promote joint health. Numerous double-blind studies in humans have shown GS to produce significant improvements in pain, indexes of joint function, and blood markers of cartilage health. Typically, these benefits are seen after 2 to 4 weeks of use, but there is some evidence that the longer GS is used, the greater the joint health benefits.
The two longest placebo-controlled trials were three years in duration. The results from these studies showed, quite convincingly, that GS slowed down the progression of cartilage breakdown associated with aging or mechanical stress on joints, as noted by improvements in X-rays and clinical evaluation. Results also showed a significantly reduced number of total joint replacements in those who took GS in these studies even as much as 5 years after they stopped taking GS.
GS may be a preventive measure against cartilage degeneration, especially in athletes subjected to joint strain, such as runners or those involved in soccer, football, basketball, or other weight-bearing sports. GS may also help aid in recovering from minor acute joint sprains and strains. One double-blind study showed the the protective action of GS on cartilage in soccer players taking 1,500 or 3,000 mg per day for 3 months by demonstrating an increase in a blood marker for cartilage synthesis and a reduced ratio showing cartilage breakdown.
There are no food sources of glucosamine. It is only available as a dietary supplement. Most commercially available sources of glucosamine are derived from chitin – the exoskeleton of shrimp, lobsters, and crabs. A vegan form produced from a corn-based microbial fermentation is also available.
Glucosamine sulfate (GS) has been extensively researched, with over 300 scientific investigations and 30 double-blind studies highlighting its effectiveness. It is the preferred form of glucosamine and has been widely embraced by millions worldwide.
Registered as an aid in joint health in over 70 countries, GS has demonstrated remarkable qualities.
Human studies focusing on the absorption and distribution of GS reveal an impressive absorption rate of up to 98%. Once absorbed, it primarily targets joint tissues for the production of cartilage, ligaments, and tendons. This underscores its crucial role in supporting joint health.
Because one of the primary effects of glucosamine sulfate (GS) is to promote the manufacture of glycosaminoglycans (GAGs), a lack of sulfur may mean less GAG synthesis when glucosamine hydrochloride (GHCL) is used.
Therefore, it is unlikely that GHCL alone will show the same excellent clinical results achieved with GS because it lacks this critical element.
Results from double-blind studies have shown that GHCL is no more effective than a placebo in promoting joint health. One double-blind, placebo-controlled human study examined the effects of GHCL on knee health in human subjects. Subjects received either 500 mg of GHCL or a placebo three times daily for 10 weeks. Results showed the difference between the two groups was not statistically significant.
In one of the most extensive studies with GHCL, 1,583 patients with knee pain and poor joint function were randomized to receive each day for 24 weeks either 1,500 mg of GHCL, 1,200 mg of chondroitin sulfate, both GHCL and chondroitin sulfate (same dosages as the single arms), 200 mg of celecoxib, or placebo. Results showed that in patients with moderate-to-severe pain at the beginning of the study, the response rate was significantly higher in subjects who took both GHCL and chondroitin sulfate compared to the placebo (79.2% vs. 54.3%). However, there was no benefit over placebo in the groups getting GHCL or chondroitin sulfate.
N-acetylglucosamine (NAG) differs from glucosamine sulfate (GS) in that instead of an attached sulfur molecule, it has a portion of an acetic acid molecule. As a result, GS and NAG are handled differently by the body. While glucosamine is easily absorbed, NAG is not. The absorption of NAG by humans is poor for several reasons:
In addition to the question of absorption, joint tissue cannot use NAG as well as it does glucosamine. These absorption and utilization issues indicate NAG is highly unlikely to possess the same benefits to joint health as GS. Companies selling NAG claim that NAG is a better form of glucosamine for joint health, but scientific data do not support these claims.
The standard dosage for GS is 1500 mg/day, and taking it as a single dosage may produce better results. Also, athletes or people subjecting their joints to more significant wear and tear may need to increase the dosage to 3,000 mg to support cartilage health.
Glucosamine Sulfate has an excellent safety record. It has been concluded that side effects are no different from placebo, are rare, and are generally limited to mild gastrointestinal irritation.
Glucosamine is often discussed with chondroitin sulfate (CS). However, based on the extensive clinical evidence, only glucosamine sulfate (GS) has consistently proven its clinical effectiveness when used as a standalone agent. Numerous studies have shown that combining Glucosamine Hydrochloride (GHCL) and chondroitin sulfate is effective, and GS alone offers the most robust clinical benefits.
Furthermore, research indicates that combining GS with chondroitin sulfate does not provide significantly greater benefits than GS alone. However, when GS or GS+CS is combined with methylsulfonylmethane (MSM), it may offer additional beneficial effects. Similarly, using MSM with GHCL can enhance the benefits of GHCL by providing essential sulfur.
Sulfur plays a critical role in the therapeutic effects of GS, and substituting it is likely to reduce the efficacy of supplemental glucosamine. This nutrient is vital for joint tissue, as it stabilizes the connective tissue matrix of cartilage, tendons, and ligaments. Additionally, sulfur helps protect against cartilage degeneration. Thus, maintaining adequate sulfur content in glycosaminoglycans (GAGs) is crucial to prevent cartilage deterioration.
Overall, the extensive research on glucosamine sulfate underscores its importance in supporting joint health and its significant role in promoting overall well-being.
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By Dr. Michael Murray, N.D. 
