Glucosamine (Regenasure®)
About the Quality of Glucosamine in Dietary Supplements
Glucosamine is a widely used ingredient that occurs naturally in the body of warm-blooded animals, and forms an important building block of joint cartilage. Glucosamine may help build tissue that holds water providing cartilage thickness and giving it a cushioning effect.
Dozens of scientific studies with animals and humans have clearly demonstrated that dietary supplementation of glucosamine in combination with chondroitin, another building block of cartilage, benefits connective tissues. The best-known clinical study is the 4-year one known as the Glucosamine/chondroitin Arthritis Intervention Trial (GAIT), conducted at 16 sites across the United States. This double-blind, placebo-controlled study was sponsored by the government funded National Institute of Health (NIH), and was published in 2005 in the New England Journal of Medicine. This study, which enrolled nearly 1,600 patients, showed that when Glucosamine and Chondroitin were used in combination, they resulted in relief of knee pain in nearly 79% of patients with moderate to severe osteoarthritis; significantly more than either the placebo control group, or patients that were treated with a common NSAID drug.
Quality
Nearly all glucosamine originates in China and nearly all is produced from shellfish.
The quality of glucosamine varies and is sometimes not of the expected purity. Several consumer studies have brought to light that glucosamine products sold in stores contain between 0% and 115% of the glucosamine claimed on the labels. This is not to say that manufacturers add less than the desired amount on purpose, but rather that the glucosamine used is of dubious quality.
Another problem with commonly used glucosamine is that people who are shellfish intolerant may respond adversely to shellfish-derived glucosamine, even though the chemical process should eliminate almost any proteins present in the source material.
Glucosamine Sulfate or Glucosamine HCL?
Pure glucosamine molecules are chemically unstable, and manufacturers of glucosamine products must therefore purchase a stabilized form of this molecule, which is done by converting it into a salt. Typical forms of glucosamine salts are [glucosamine.HCl], better known as glucosamine hydrochloride, and [glucosamine.SO4.2KCl], or glucosamine sulfate. There is a fair amount of controversy about which salt form is easiest assimilated by the body, although in reality both salts, in the pure form, deliver equally effective amounts of the desired glucosamine to joint cartilage. The explanation is straightforward; in the acidic environment of the stomach, the stable glucosamine salt molecule is quickly ionized into a positively charged glucosamine ion and a negatively charged chloride or sulfate ion. Only the pure glucosamine relates to the observed benefits relative to osteoarthritis.
There is another important difference between the two forms, however, and that is the weight of the glucosamine molecule. One molecule of glucosamine chloride contains approximately 80% pure glucosamine, while one molecule of glucosamine sulfate contains only about 60%.
Regenasure® Vegetarian Glucosamine
Regenasure® glucosamine is a patented vegetarian form of glucosamine, i.e., a non-shellfish, non-animal derived form of this popular ingredient. The stabilized chemical form of this molecule is the hydrochloride salt, as this form yields the most glucosamine per unit weight.
Nevertheless a major disadvantage of this vegetarian glucosamine is that it costs about two to three times as much as the more popular animal-derived forms of glucosamine.
Regenasure® glucosamine is pharmaceutical grade and therefore of the highest possible purity, and is produced by means of a unique and patented fermentation process. Regenasure® glucosamine is obtained from corn and this important fact is a major benefit to people and pets allergic to shellfish.
The Role of Glucosamine in the Body
Glucosamine is an amino monosaccharide found in chitin, glycoproteins and glycosaminoglycans (formerly known as mucopolysaccharides) such as hyaluronic acid and heparan sulfate.
Biochemically, glucosamine is involved in glycoprotein metabolism. Glycoproteins, known as proteoglycans, form the ground substance in the extra-cellular matrix of connective tissue. Proteoglycans are polyanionic substances of high-molecular weight and contain many different types of heteropolysaccharide side-chains covalently linked to a polypeptide-chain backbone. These polysaccharides make up to 95% of the proteoglycan structure. In fact, chemically, proteoglycans resemble polysaccharides more than they do proteins.
The polysaccharide groups in proteoglycans are called glycosaminoglycans or GAGs. GAGs include hyaluronic acid, chondroitin sulfate, dermatan sulfate, keratan sulfate, heparin and heparan sulfate. All of the GAGs contain derivatives of glucosamine or galactosamine.
Glucosamine derivatives are found in hyaluronic acid, keratan sulfate and heparan sulfate. Chondroitin sulfate contains derivatives of galactosamine.
The glucosamine-containing glycosaminoglycan hyaluronic acid is vital for the function of articular cartilage. GAG chains are fundamental components of aggrecan found in articular cartilage. Aggrecan confers upon articular cartilage shock-absorbing properties. It does this by providing cartilage with a swelling pressure that is restrained by the tensile forces of collagen fibers. This balance confers upon articular cartilage the deformable resilience vital to its function.
The actions of supplemental glucosamine have yet to be clarified. It may play a role in the promotion and maintenance of the structure and function of cartilage in the joints of the body. Glucosamine may also have anti-inflammatory properties.
In the early stages of degenerative joint disease, aggrecan biosynthesis is increased. However, in later stages, aggrecan synthesis is decreased, leading eventually to the loss of cartilage resiliency and to most of the symptoms that accompany osteoarthritis.
During the progression of osteoarthritis, exogenous glucosamine may have a beneficial role. But note: glucosamine is available commercially as a nutritional supplement in three different forms, i.e. glucosamine hydrochloride or glucosamine HCl, glucosamine sulfate and N-acetyl-glucosamine.
Glucosamine sulfate has been subject of some studies published by American Journal of Natural Medicine where it is cited to have been effective in at least 20 double-blind trials. Other studies have shown that glucosamine sulfate is absorbed by body for at least the 90% of the total amount taken, indipendently if administered intramuscularly or orally.
It is known that, in vitro, chondrocytes do synthetize more aggregan when the culture medium is supplemented with glucosamine. N-acetylglucosamine is found to be less effective in these in vitro studies. Glucosamine has also been found to have antioxidant activity and to be beneficial in models of experimental arthritis.
Two recent meta-analyses have confirmed that glucosamine is useful in the treatment of osteoarthritis. One of these meta-analyses included all double-blind, placebo-controlled trials that lasted four weeks or longer. This meta-analysis also included trials that studied the effects of chondroitin sulfate. In all, there were l3 of these studies (six involving glucosamine and seven involving chondroitin sulfate).
All l3 studies found positive results in hip or knee osteoarthritis. The authors of the meta-analysis judged a trial positive if there was 25% or more improvement in the treatment group compared with placebo. Very significant improvement was associated with both glucosamine (39.5%) and chondroitin sulfate (40.2%), compared with placebo.There has been one study demonstrating an apparent synergistic effect using glucosamine and chondroitin together*. The combination was more effective than either substance alone in inhibiting progression of degenerative cartilage lesions in an experimental study.
In another recent meta-analysis of nine randomized, controlled trials of glucosamine, glucosamine was significantly superior to placebo in seven of the studies and was superior to ibuprofen and equal to ibuprofen in the other two studies.
Recently, a long-term, randomized placebo-controlled trial of glucosamine sulfate's effects on osteoarthritis ended with the conclusion that the supplement halts progression of structural joint damage and reduces symptoms of those with osteoarthritis of the knee. The study involved 212 patients 50 years or older who received 1500 milligrams of glucosamine sulfate daily or placebo.
Radiographic evidence, at a three-year followup, showed joint space narrowing--the prime indicator of arthritic joint damage--in the placebo group consistent with what has been documented to be typical in untreated osteoarthritis. The glucosamine-supplemented subjects, on the other hand, showed only a non-significant increase in joint space at the same three-year followup.
It is probably not surprising that glucosamine may be helpful in osteoarthritis. Glucosamine is crucial for the construction of glycosaminoglycans (GAGs) in articular cartilage. Reduced GAG content in osteoarthritic cartilage matrix corresponds with the severity of osteoarthritis. Oral glucosamine appears to be capable of prompting the chondrocytes to secrete more GAGs. This knowledge, derived from animal and in vitro studies, has prompted clinical trials of glucosamine in osteoarthritis.
| GLUCOSAMINE |
| Main Actions: |
|
| Main Uses: | osteoarthitis, arthirtis, rheumatoid arthritis, psoriasic arthritis, cartlage disorders |
| Standard Dosage: | 1500 mg daily |
| Contraindiactions: | None known; however:
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| Drug Interactions: | Glucosamine may increase insulin resistance and consequently affect glucose tolerance. |
Glucosamine and Chondroitin Sulfate*
Thus far, it has been 20 years since glucosamine and chondroitin are used in Europe as adjuvants to traditional treatments of osteoarthritis both in humans and animals.
These substances are cited as nutrients contained in most of the food and listed in the same family of vitamins.
Glucosamine and chondroitin are natural occurring substances in humans and animals, especially in cartilages.
An healthy body synthetizes glucose from which it gets the needed glucosamine to maintain cartilages functioning. About the 90% of intaken glucosamine is absorbed; the 8-12% of this is distribuited into tissues, while the rest is cleared out as urinary execration and carbon dioxide. Only the 10% of intaken chondroitin sulfate is absorbed by the body though. So that in elderly people and/or if joint cartilage is injuried, the body cannot afford to synthetize enough glucosamine for its physiological necessities. Therefore, it's needed an external supplementation making up to this metabolic imbalance.
It's thought that glucosamine and chondroitin sulfate act by inhibiting enzymes that destroy cartilage and stimulating proteoglycans synthesis.
There are several studies that document the effects of glucosamine and chondroitin on more than 4000 individuals. In comparison to traditional NSAIDs they have the same effectiveness but lower toxicity. In addition, many studies have suggested that glucosamine and chondroitin sulfate effects hold over 4 weeks after having discontinued the treatment.
Bibliography
Deal CL, Moskowitz RW. Nutraceuticals as therapeutic agents in osteoarthritis. The role of glucosamine, chondroitin sulfate, and collagen hydrolysate. Rheum Dis Clin North Am. 1999; 25:379-395.
Drovanti A, Bignamini AA, Rovati AL. Therapeutic activity of oral glucosamine sulfate in osteoarthritis, a placebo-controlled double-blind investigation. Clin Ther. 1980; 3:260-272.
Houpt JB, McMillan R, Wein C, Paget-Dello SD. Effect of glucosamine hydrochloride in the treatment of pain of osteoarthritis of the knee. J Rheumatol. 1999; 26:2423-2430.
Leffler CT, Philippi AF, Leffler SG, et al. Glucosamine, chondroitin, and manganese ascorbate for degenerative joint disease of the knee or low back: a randomized double-blind, placebo-controlled pilot study. Mil Med. 1999; 64:85-91.
McClain DA, Crook, ED. Hexosamines and insulin resistance. Diabetes. 1996; 45:l003-l006.
Noack W, Fischer, M., Forster, KK, et al. Glucosamine sulfate in osteoarthritis of the knee. Osteoarthritis Cartilage. 1994; 2:51-59.
Pujalte JM, Llavore EP, Ylescupidez FR. Double-blind evaluation of oral glucosamine sulfate in the basic treatment of osteoarthritis. Curr Med Res Opin. 1980; 7:110-114.
Reichelt A, Forster K, Fisher M, et al. Efficacy and safety of intramuscular glucosamine sulfate in osteoarthritis of the knee. A randomized, placebo-controlled, double-blind study. Arzneimittelforschung. 1999; 44:75-80.
Setnikar I, Giacchetti C, Zanolo G. Pharmacokinetics of glucosamine in the dog and in man. Arzneimittelforschung. 1986; 36:729-735.
Setnikar I, Palumbo R, Canali S, Zanolo G. Pharmacokinetics of glucosamine in man. Arzneimittelforschung.1993; 43:1109-1113.
Towheed TE, Anastassiades TP. Glucosamine and chondroitin for treating symptoms of osteoarthritis. Evidence is widely touted but incomplete. JAMA. 2000; 283:1483-1484.
Towheed TE, Anastassiades TP. Glucosamine therapy for osteoarthritis. Editorial. J Rheumatol l999; 26:2294-2297.
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