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Glucosamine Sulfate: A Naturally Sulfated Compound in Joint Cartilage

Current price comparison for online sources: GS price info.
A best buy: 2000 750 mg. capsules of USP grade glucosamine from Pfanstiehl Laboratories (over 2 years' supply) for approximately $190 at Nutrasense.

Our bodies depend on glucosamine, an amino sugar, for the synthesis of connective tissue and cartilage. Glucosamine is used as the starting material for tendons and ligaments, mucous membranes in both the digestive and respiratory tracts, nails, skin, bone, eyes, heart valves, and synovial fluid in the joints. It also supports healthy mucous secretion of the digestive, respiratory, and urinary tracts. In its sulfated form, glucosamine provides cartilage with its structure, strength, and "shock absorbing" properties. Glucosamine takes up to 3-10 weeks of regular use to begin demonstrating an effect because the process of thickening synovial fluid to improve its cushioning effect can be a slow one. Chondroprotective agents including glucosamine and chondroitin protect and restore joint cartilage by:

  • Supporting and enhancing anabolic chondrocyte synthesis.
  • Supporting or enhancing the synthesis of synovial fluid, which is required tolubricate the joint.
  • Inhibiting free radical enzymes and autoimmune processes that degrade joint cartilage.
  • Removing blockages in blood vessels leading to the joint.

Dietary supplements of glucosamine sulfate (GS) have been demonstrated to be an easily absorbed source of glucosamine. For supplements, glucosamine may be chemically produced from scratch or glucosamine sulfate sources are isolated from shellfish chitin and converted to glucosamine sulfate. Glucosamine is widely distributed in animal tissues and humans have been ingesting glucosamine when they chewed "gristle" for thousands of years. It's also a natural component of chitin, a major structural component of the hard shells of clams, oysters, and other shellfish.

Researchers have found no contraindications for glucosamine sulfate. Commercial glucosamine sulfate is highly purified, not causing any reaction in most people allergic to shellfish. Persons allergic to sulfa drugs can still take glucosamine sulfate. "Sulfa" short for sulfonamide refers to an old-fashioned antibiotic and has no connection whatsoever with the organic compound glucosamine sulfate. Sulphur is an essential mineral. The sulfate form of sulfur is present in relatively high concentrations in human blood. GS is stabilized with one of two mineral salts: sodium chloride (NaCl) or potassium chloride (KCl). Although they both appear to effectively stabilize GS, the use of KCl as a stabilizer seems preferable since the average Western diet already provides far too much salt (NaCl) and not enough potassium. However, most of the research has been done with the NaCl-stabilized form.

Most regular glucosamine sulfate products available contain between 8% and 12% sodium, and 12% chloride by weight. A few people with high blood pressure are sensitive to sodium chlorides, so blood pressure should be monitored for a few weeks in hypertensive persons beginning glucosamine sulfate. A large, 3-year controlled trial found that people taking glucosamine had slightly lower blood glucose levels compared with people taking placebo. Until more is known, people taking glucosamine supplements for long periods may wish to have their blood sugar levels checked; people with diabetes are advised to consult with a doctor before taking GS and should monitor blood sugar levels while taking GS.

Orally ingested pure glucosamine sulfate has been found to be well-tolerated and free of side effects. In 1999 the first case of an allergic reaction to oral GS was reported. Allergic reactions to this supplement appear to be very rare.

There are no known contraindications to its use or drug interactions. Drugs and other medications appear to be compatible with glucosamine (a molecule always present in our bodies) and no adverse interactions have been reported.

Dietary supplements of pure glucosamine sulfate have been found to be well tolerated and free of side effects in most individuals. In rare instances, some gastrointestinal upset such as nausea or heartburn may occur. This is usually prevented by taking the supplement with meals. As a convenient source of glucosamine, oral supplements may continue to be used as long as necessary.

Alternate forms and complementary supplements for GS

Glucosamine sulfate is produced from glucosamine hydrochoride and is broken down to the same compound in the stomach. Either may be safely used as a supplement.

Two other compounds are often discussed with glucosamine: níacetyl glucosamine (NAG) and chondroitin.

A bit of chemistry here: glucosamine sulfate is produced by combining glucose with glutamine to form glucosamine through the action of the enzyme glucosamine synthetase. NAG is also produced this way. However, for NAG there is one more step: it is then acetylated to form n-acetyl glycosamine or NAG.

Over 20 double-blind studies have been conducted on glucosamine sulfate. NAG has not been nearly as rigorously tested. Glucosamine sulfate is a glucosamine molecule attached to a sulfur molecule. The sulfur molecule helps glucosamine metabolism. Glucosamine sulfate has a 98% absorption rate and when absorbed is distributed directly to join tissues. NAG, quite a different molecule, is not as easily absorbed and handled quite differently by the body. Glucosamine is a very small molecule compared to NAG. Itís like swallowing a flaxseed versus a whole grapefruit. Glucosamine sulfate is the preferred form because the sulfur molecule helps to metabolize any extra glucosamine and it links to other sulfur molecules in the joints which increases cartilage strength.

Chondroitin sulfate is often used as a complementary compound for glucosamine supplements. By itself glucosamine sulfate is a safe, effective remedy for painful joints. Some studies show improved effect when taken with chondroitin sulfate. Both substances work together to protect and rebuild cartilage. Glucosamine enhances the viscosity of synovial fluid, providing much needed lubrication, while chondroitin inhibits damaging enzymes and stimulates the transport of nutrients. Chondroitin sulfate is a constituent of shark cartilage, which helps to explain the beneficial effects that shark cartilage produces in arthritis patients. The chondroitin sulfates have been tested extensively in humans with outstanding success as anti-atherosclerotic agents. The FDA has ruled, however, that, since each chondroitin sulfate molecule is different than all other molecules, which makes it impossible to produce a precisely standardized product, it cannot be approved as a therapy.

More favorable response to oral intake of glucosamine HCl or sulfate has been observed compared with other glucosamine sources such as chondroitin sulfate or cartilage extracts. The much larger size of the molecules of these substances makes them more difficult to absorb than glucosamine sulfate.
N-acetylglucosamine (NAG), an acetylated form of glucosamine that participates in connective tissue metabolism, is also used as a dietary supplement. It is also an integral component of the mucous membranes of the body, particularly those in the digestive tract. Although N-acetylglucosamine appears to have value in supporting the health of the gastrointestinal tract, glucosamine sulfate appears to be a more efficient precursor of joint-associated connective tissue than NAG.

Why use glucosamine?

When our lubricating synovial fluid becomes thin, its ability to cushion is reduced. Glucosamine makes the synovial fluid thick and gelatinous, increasing its cushioning ability, lessening the friction and pain.

Degenerative joint disease (dgd or osteoarthritis)is common over age 60. It is also associated with certain occupations and sports such as ballet and football, and does occur in a joint after an injury or fracture or after excessive weight-bearing. In osteoarthritis (OA, or wear-and-tear arthritis), the normally shiny, slick cartilage becomes softened and dull. It begins to lose its elasticity, and its surface may become worn in spots. It also thins out, so it canít absorb as much synovial fluid. Consequently, the bones move closer together, and the joint space narrows. Eventually the cartilage may grow so thin in spots that the bones begin to rub against each other. Morning stiffness, soreness when beginning movement which eases somewhat as movement continues, and varying degrees of pain, from minor to intense are also common with DGD.

Glucosamine safer than NSAIDS or aspirin

Long term use of glucosamine is safer than aspirin or NSAIDS (ibuprofen, Motrin, Advil, etc). Recent research shows that NSAIDS drugs do suppress the painful symptoms more quickly but may also accelerate the progression of degenerative joint disease. Studies have shown that these drugs contribute to cartilage destruction and inhibit new cartilage formation. (F.M. Brooks et al. NSAID and osteoarthritis-help or hindrance? J. Rheumatol. 9:3-5, 1982.) Prolonged use of these anti-inflammatory drugs may also lead to gastro-intestinal bleeding or liver and kidney damage. On the other hand, glucosamine eases pain while actually promoting healing.

Glucosamine's role in body chemistry

Glucosamine is a key precursor of connective tissue. Connective tissue, a fibrous type of body tissue, has varied functions throughout the body. Our connective tissue system supports and connects internal organs, forms bones and the walls of blood vessels, attaches muscles to bones and replaces tissues of other types following injury. The two main components of connective tissue are collagen and proteoglycans. Collagen is the strong, fibrous protein that physically connects our tissues. Proteoglycans are large, complex modified sugar molecules that form the framework for collagen to follow. Their ability to hold water also gives connective tissues flexibility and resiliency.

Proteoglycans are the basic substance of joint cartilage. Glucosamine is the key building block of proteoglycans. As the pivotal ingredient for proteoglycan synthesis, the amount of available glucosamine controls the rate at which cartilage and connective tissue can be formed. The active role of glucosamine in cartilage metabolism is enhanced by sulfate as sulfur molecules are also required for the structure of proteoglycans.

Glucosamine is produced in the body when glucose, a simple sugar, combines with glutamine, an amine, through an enzymatically controlled reaction. The resulting aminomono-saccharide is then sulfated by the action of cellular enzymes to form glucosamine sulfate. Glucosamine and glucosamine sulfate are used to build the larger proteoglycan molecules such as glycosaminoglycans, mucopolysaccharides, hyaluronic acid, and chondritin sulfate which form various connective tissues. Its physiological function on joints is to stimulate the manufacture of glycosaminoglycans, which are key structural components of cartilage. Glucosamine also promotes the incorporation of sulfur into cartilage. Because of this effect, glucosamine sulfate may be the best source of glucosamine.

Because the rate-limiting step in connective tissue formation is the amount of glucosamine, dietary supplements of glucosamine sulfate have been studied and found to be a valuable source of glucosamine that is readily distributed to joint tissues. There is discussion over which of the two glucosamine salts, hydrochloride or sulfate, is preferred for the treatment of osteoarthritis. The answer is straightforward - both salts, in the pure form, deliver equally effective amounts of the desired glucosamine to joint cartilage.

Glucosamine sulfate is a small molecule that is very soluble in water and easily absorbed from the small intestine. As much as 98% absorption of an ingested amount has been demonstrated in scientific studies. Its easy diffusibility through biological membranes allows glucosamine sulfate to be quickly assimilated by joint structures and other tissues that require it.

Pure Glucosamine Sulfate is very hygroscopic and degrades rapidly (goes from white to off-white to tan to brown) when exposed to moisture. To avoid this problem, Glucosamine sulfate, as currently imported, is made from glucosamine HCl by adding either sodium or potassium sulfate and co-crystallizing the resulting mixture. Glucosamine sulfate supplements imported into the US is only 80% glucosamine with the remaining 20% being sodium or potassium. D-Glucosamine HCl provides a high purity, stable source of glucosamine that is readily absorbed by the body and is the most cost effective form of glucosamine available (see a comparison of glucosamine HCL and glucosamine sulfate.)

How to use supplementary glucosamine sulfate

As a source of glucosamine, the usual intake is one 500 mg capsule of glucosamine sulfate taken three times daily, for a total of 1,500 mg per day. Some reports indicate that obese individuals may need to take a bit more. Use of diuretics may reduce the benefits of Glucosamine Sulfate, therefore, slightly higher amounts of Glucosamine Sulfate may be needed in these instances.



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The statements in this article are informational and have not been evaluated by the Food and Drug Administration.