Glucosamine sulfate vs. NAG
Currently companies marketing N-acetyl-glucosamine, commonly referred to as "NAG," are misleading many physicians into believing that NAG is better absorbed, more stable, and is better utilized than glucosamine sulfate. These contentions are without support in the scientific literature. In fact, the literature contains just the opposite. Glucosamine sulfate is clearly the preferred form.
As mentioned above, detailed human studies on the absorption, distribution, and elimination of orally administered glucosamine sulfate have shown an absorption rate of as high as 98% and that once absorbed it is then distributed primarily to joint tissues where it is incorporated into the connective tissue matrix of cartilage, ligaments, and tendons, In addition, there are the impressive clinical studies on thousands of patients. In contrast, there has never been a double-blind study using NAG for any application. Nor have there ever been any detailed absorption studies on NAG in humans.
Further evidence of the superiority of glucosamine sulfate to NAG is offered by studies in laboratory animals. Over the years, numerous researchers have researchers have repeatedly demonstrated that glucosamine is superior to NAG in terms of absorption and utilization by at least a factor of 2:1.18-29 These researchers have concluded that glucosamine is a more efficient precursor of macromolecular hexosamine [glycosaminoglycans] than N-acetyl-glucosamine does not penetrate the cell membranes and, as a result, is not available for incorporation into glycoproteins and mucopolysaccharides.20
The absorption of NAG is quickly digested by intestinal bacteria; 2) NAG is a known binder of dietary lectins in the gut with the resultant lectin-NAG complex being excreted in the feces; and 3) a large percentage of NAG is broken down by intestinal cells.
NAG differs from glucosamine sulfate in that instead of a sulfur molecule, NAG has a portion of an acetic acid molecule attached to it. Glucosamine sulfate and NAG ware entirely different molecules and appear to be handled by the body differently. The body preferentially utilizes glucosamine sulfate compared to NAG. This preference is exhibited by the fact that the absorption of glucosamine sulfate is an active process.29 In other words, there are mechanisms in the body which are designed specifically for the absorption and utilization of glucosamine sulfate. No such mechanisms exist for NAG.
It is highly unlikely that NAG possesses the same kind of antiarthritic and antireactive properties that glucosamine sulfate has been shown to possess.30-31 In addition to the question of absorption, several studies have shown that the articular tissue is not able to utilize NAG as well as it does glucosamine.18-19
The marketing information on NAG will often use the term slow acetylators to describe a very small group of individuals with Crohn's disease and ulcerative colitis who are unable to convert glucosamine to NAG as fast as individuals without these diseases. Glucosamine and NAG are necessary in the manufacture of mucin, the glycoprotein lining of the intestinal tract.
Distributors of NAG hold up only one study as evidence that NAG is better. The study demonstrated that when intestinal cells from patients with Crohn's disease or ulcerative colitis were bathed in a solution containing a ratio of radioactive NAG:glucosamine of 10:1, the cells incorporated more NAG than the cells from individuals without these diseases.30 These results are expected due to the higher concentrations of NAG in the media artificially promoting passive diffusion to a greater extent than the active accumulation of glucosamine. How distributors of NAG can then use this information to claim that NAG is better than glucosamine sulfate is puzzling since the significance of this test tube study is unclear and other studies have demonstrated an increased utilization of glucosamine in these patients.33
The problem of acetylation of glucosamine is not a factor for most people as it is not a rate-limiting step in the manufacture of glycosaminoglycans, instead it is the manufacture of glucosamine. Another form of glucosamine presently being marketed is glucosamine hydrochloride (HCI). As with NAG, the research simply does not support the use of glucosamine HCI.
It appears the sulfur component of glucosamine sulfate may be critical to the beneficial effects noted. Sulfur is an essential nutrient for joint tissue where it functions in the stabilization of the connective tissue matrix of cartilage, tendons, and ligaments. As far back as the 1930's, researchers demonstrated that individuals with arthritis are commonly deficient in this essential nutrient.34 Restoring sulfur levels brought about significant benefit to these patients.35 Therefore, it appears the sulfur portion of glucosamine sulfate is extremely important and is another reason why glucosamine sulfate is the preferred form of glucosamine.
The standard dose for glucosamine sulfate is 500 mg three times per day. Obese individuals may need higher dosages based on their body weight (20 mg/kg body weight/day).
Glucosamine sulfate is extremely well-tolerated. In addition, there are no contra-indications or adverse interactions with drugs. Individuals taking diuretics may need to take higher dosages. Glucosamine sulfate may cause some gastrointestinal upset (nausea, heartburn, etc.) in rare instances. If this occurs, have the patient try taking it with meals.