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If you don’t read any further, let me say that,

There are a couple of great books available that go into considerable depth on glucosamine and chondroitin sulfate, including The Arthritis Cure (St. Martin’s Press, 1997) and Glucosamine and Chondroitin (Avery, 1998), so I won’t spend a lot of your time and mine going into all of the details. However, when speaking, there are a few questions that keep popping up and so I’d like to share some information that I’ve collected over the past few years on this topic.

What is glucosamine and why do you include it in most of your formulas?

Glucosamine is a molecule created within the body by combining a simple sugar, glucose, with an amino acid, glutamine. Once glucosamine is formed, it is used directly by the body to form larger molecules called GAGs, or glycosaminoglycans. It is also used to create other larger molecules called glycoproteins and glycolipids. The molecules that we are interested in, the glycosaminoglycans, help to make up the body’s tendons, ligaments, bones, cartilage, synovial fluid, mucous membranes, structures in the eye, blood vessels, and heart valves.

There are many factors that come into play when determining how much of the body’s glucose, which is normally used by the body as fuel, is converted into glucosamine. Although glucose is abundant in all of our diets, because of our genetic make up, increased stress, lack of exercise, poor diets, and injuries, very little of it is actually used to stimulate new tissue growth and increase the body’s lubricating fluids. This is why

For those of you who like diagrams, as I do, the following is a simple flow chart describing the construction of cartilage.

1. Glucose + Glutamine = Glucosamine
   
   

2. Glucosamine or Galactosamine + Carboxylate and/or Sulfate ester (repeating disaccharide units) = Glycosaminoglycan (GAG)

3. (Chondroitin sulfates are one type of GAG)

4. Glycosaminoglycans + Protein = Proteoglycans

5. Proteoglycans + Chondrocytes + Collagen + Water = Cartilage

There are three forms of glucosamine being sold in the nutritional industry today. How are they different and which one is best for treating arthritis?

Presently, glucosamine sulfate, glucosamine hydrochloride, and N-acetyl glucosamine are used in joint rebuilding products. Another form, glucosamine iodide, has also been found to increase GAG production, but is not presently used in today’s formulations.

Studies have shown that both the glucosamine sulfate and hydrochloride forms support GAG synthesis. It has been found, however, that N-acetyl glucosamine does not increase the formation of these larger molecules within the joints, but might be more effective in the synthesis of mucosal glycoproteins that form the viscous layer of the mucosa found in the digestive tract, called the glycocalyx. This glycoprotein layer protects the underlying tissues from destruction by digestive acids, digestive enzymes, bacterial and viral pathogens, parasites, and toxins whether produced by the body or found in the environment. At the same time, it provides a selective absorptive surface that allows specific nutrients to pass through.

Some authorities on the autoimmune arthritides give good evidence that these conditions, including rheumatoid arthritis, psoriatic arthritis, the arthritis related to system lupus, and SjÖgren’s Syndrome, are caused by a hyper immune response secondary to a condition known as leaky gut syndrome. Leaky gut syndrome, a condition of increase gut permeability due to destruction of the integrity of the intestinal mucosa, allows improperly digest foods, toxins meant for elimination, and various pathogens that normally couldn’t pass through because of their size or because of the sticky mucosal layer, to cross directly into the blood stream. As the chronically stressed immune system attempts to eliminate this constant source of foreign invaders, at some point a defect occurs, and the system designed to protect us no longer differentiates between what is us and what is not us. And it begins to attack the normal, healthy tissues of our own body. These types of diseases are known as autoimmune. NAG supplementation can prove very useful in treating these types of disorders.

Now, as to the differences between glucosamine sulfate and glucosamine hydrochloride, both of these nutrients work well in addressing tissue regeneration. They are both highly absorbable and both have been found extremely beneficial in helping to relieve joint pain, maintain healthy cartilage, and increase joint function. Although most of the research was performed using the patented sulfate form, the early research used the glucosamine hydrochloride.

This same research found that both the sulfate and hydrochloride molecules were eliminated from the body as wastes. Some clinicians still believe that the sulfate molecule contributes necessary sulfur critical for the reconstruction of damaged tissues within the joints. Since we now know that the sulfate molecule is excreted, there is no way that the sulfate could provide the sulfur. It was also determined that the sulfur used by chondroblasts (cartilage cells) in creating new cartilage matrix is obtained from existing proteins in the cartilage, not from the sulfate molecule.

Since it has been determined that it is the glucosamine, and not the sulfate or hydrochloride, which benefits those with degenerative joint disease, what should be the determining factor? Success with glucosamine is dose-dependent, so obviously a product with the highest concentrations of glucosamine would be of most benefit. It is unfortunate that most manufacturers recommend a daily dose of only 1500 milligrams. Frequently, with higher doses, results can be achieved much more quickly. On many occasions, I have treated patients, who had taken the manufacturers recommended dose of glucosamine for many months with no results, that became completely pain-free within three or four weeks after doubling the daily dose to 3000 milligrams. Any stomach upset could usually be alleviated by taking it with meals, and once the desired results had been achieved, we recommended reducing the dose slowly over a six to eight week period of time down to 500 milligrams per day. Since using higher doses, I have found it easier to use the glucosamine hydrochloride, since it is more pure and usually less expensive than the glucosamine sulfate.

Most of the European studies, performed by Rota Labs in Italy, used a patented form of glucosamine sulfate, which is not available in the United States. All of the glucosamine sulfate available in the U.S. is synthesized from glucosamine hydrochloride with the addition of the sulfate molecule. This new molecule proved to be very unstable and tended to oxidize very quickly causing it to break down, turning brown, and quickly losing its effectiveness. To keep this from occurring, the manufacturers must stabilized the glucosamine sulfate with either sodium or potassium chloride. For those of you non-chemists, like me, sodium chloride is table salt. This might become an issue for those of you on a salt-restricted diet.

I’d like to share some interesting math performed by Wilke Resources, Inc., a distributor of glucosamine hydrochloride made by Pfanstiehl Laboratories, Inc. If an individual was to take 1,500 mgs of glucosamine daily, on a monthly basis, you would need 80 capsules of sulfate to equal 60 capsules of hydrochloride. Please remember, however, that for many individuals, especially for those with involved weight-bearing joints, 1,500 mgs may not be enough. It’s also important to remember that glucosamine is not an analgesic (pain-killer) nor an anti-inflammatory. The desired effects are achieved only after the damaged tissues become healthy again. This process can take a considerable amount of time.

Or combine the glucosamine with the CM Complex. We’ve discovered that we can achieve much greater results by reducing the required levels of glucosamine (one third to one half) and combining it with equal amounts of the CM Complex. They seem to work on very different levels in the body.

GLUCOSAMINE

HYDROCHLORIDE VS. SULFATE

Glucosamine Hydrochloride	Comparative Attribute	Glucosamine Sulfate (NaCl added)
99+%	Purity (as the specific salt)	80%
83.1%	Bio-Active Glucosamine (as the free base)	62.8%
1,500 mgs	Equivalent Dosage (based on active)	1,995 mgs

"How safe is glucosamine and can I take larger doses without any worry?"

Although in all of my years of experience with glucosamine, I’ve never seen anything other than an occasional stomach upset, there are a couple of issues that you need to be aware of. Although no cases have ever been reported, glucosamine, derived from the exoskeletons of shellfish, may cause a reaction in those of you who are allergic to shrimp, crab, or lobster. The better glucosamine products are over 99% pure glucosamine and, I’m sure won’t cause any reactions. However, there may be some less expensive glucosamine products being sold today that have residual proteins, which theoretically could be problematic. Another concern is that there is some evidence that glucosamine may effect insulin’s ability to regulate blood sugar levels. There are a couple of different theories as to how this might happen. One is that glucosamine somehow desensitizes cell membranes to the effects of insulin. Another is that glucosamine effects enzymes in the pancreas, where insulin is produced, and thereby decreases the secretion of insulin. These particular phenomenon are dependent on the amount of glucosamine ingested. Those of you who are diabetic or have difficulty regulating your blood sugar should monitor your blood sugar levels very closely when taking glucosamine. And, remember, by combining the glucosamine with the CM Complex, you’ll be able to reduce the levels of glucosamine and oftentimes attain even greater results.

As to the safety of glucosamine, other than if you’re diabetic or if you’re taking an inferior quality glucosamine and you’re allergic to shellfish, it is very safe and very well tolerated. Studies have shown extremely favorable results with no toxicity at very high levels of 5 to 6 grams (5,000 — 6,000 mgs) per day. Occasionally, with these higher doses, some individuals experience gastric upset. As I said earlier, this temporary side effect can usually be eliminated by taking the glucosamine with food, or by dividing it into smaller doses taken three or four times per day.