Plana worked exclusively with Glucosamine HCl and was able to show that Glucosamine HCl stimulates in a dose dependent manner soluble mucopolysaccharide release by "in vitro" cultured mouse fibroblasts. According to Plana, these results are in agreement with those reported by Karzel. He was also able to demonstrate agreement with Kim’s earlier work. Plana further showed that the dose-dependent enhancing activity of Glucosamine HCl not only contrasted to the dose-dependent depressing activity of non-steroidal anti-inflammatory drugs but also could diminish in a statistically significant way the depressing activity of the NSAID on protein and mucopolysaccharide synthesis.

1. In 1986 and 1993, Rotta Research published pharmacokinetic data on Glucosamine Sulfate in both dog and man. Close examination of this work shows the following:
   
   
1. The tagged glucosamine used in the testing was C¹⁴-tagged glucosamine hydrochloride, which was subsequently mixed with untagged glucosamine sulfate. The results, which are reported as glucosamine sulfate, should be reported as glucosamine hydrochloride.
   
   
2. The 1986 study also sheds light on what happens to orally administered glucosamine sulfate. Under paragraph 4.1 entitled "Physical properties of glucosamine" the authors establish that glucosamine has a pKa of 6.91 at 37 degrees C and state that orally consumed glucosamine is 100% ionized in stomach acid (pH 1-3). This means that glucosamine sulfate exists in the stomach as free glucosamine ions and sulfate ions in a vast sea of Chloride ions from the gastric (hydrochloric) acid. As the stomach contents move to the small intestine, the pH rises to approximately 6.8 and glucosamine now is 46% ionized and 54% not ionized. It is also not glucosamine sulfate. If any salt reforms, it will be the hydrochloride due to the overwhelming preponderance of chloride from the stomach acid. In fact, the "not ionized" portion is the neutral aminosugar glucosamine. This is fortunate because neutral compounds move through cell walls much more readily than do charged ions. Thus, neutral glucosamine moves from the small intestine into the blood stream where, at a pH of 7.4, 25% of the glucosamine is ionized and 75% is not ionized.
   
   
2. Fact from Fiction
   
   
   
   1. Based on the preceding, there is no valid science to claim that glucosamine sulfate is more readily absorbed from the gut than is glucosamine hydrochloride. What is absorbed in either case is glucosamine – the salt is irrelevant.
   
   
   2. As to the claim that the sulfate ion from the glucosamine is important to subsequent formation of sulfated mucopolysaccharides like chondroitin sulfate also has no basis in science. Sulfate ions are eliminated as waste products. The sulfur used in the synthesis of sulfated mucopolysaccharides comes from the protein sulfur linkages as old collagen breakdowns. If you want to supplement bioavailable sulfur, you would need to consume products like methionine and MSM (methysulfonylmethane) or just good old protein.
   
   
   3. The active ingredient in the treatment of osteoarthritis is glucosamine. Like many other drugs, the hydrochloride or sulfate acid salt is the delivery vehicle. Once it has entered the stomach, the salt’s job is done and it is the glucosamine that is released to perform its function.
      
      

1. The following table shows the differences between Glucosamine HCl and commercially available Glucosamine Sulfate • 2KCl (Glucosamine Sulfate is cocrystallized with 2 moles of potassium chloride or sodium chloride in order to maintain stability):