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An Intriguing Study That Should Get Your Attention
  Below is the summary from a thought provoking preclinical study. While clinical relevance is at this time unclear the paper does provide a window on the field of glycobiology. What is important about this paper is that it demonstrates that N-acetyl-D-glucosamine plays a regulatory role and is not just a component of structural molecules. The summary is referenced and the reader is encouraged to read the whole paper. If we had no COX-2 would we need COX-2 inhibitors?
COX-1 (cyclooxygenase 1) is generally always present in tissues. COX-2 however is an enzyme induced as part of the inflammatory process. A study at the Scripps Clinic investigated the ability of glucosamine and N-acetyl-D-glucosamine to inhibit IL-1beta-induced COX-2 expression in normal human articular chondrocytes1. N-acetyl-D-glucosamine suppressed the production of IL-1beta-induced cyclooxygenase-2 and IL-6. The constitutively expressed cyclooxygenase-1, however, was not affected by the sugar. N-acetyl-D-glucosamine-mediated inhibition of the IL-1beta stimulation of the human chondrocyte was specific and identifies a novel mechanism of inhibition of inflammation in the human joint. See table below. Table 1: N-Acetyl-D-glucosamine effect on chondrocytes expression of COX-2, and COX-1.
The ability of glucosamine and N-acetyl-D-glucosamine to inhibit IL-1beta-induced NO production in human articular chondrocytes was also investigated. At a 10 mM concentration N-acetyl-D-glucosamine's ability to inhibit IL-1beta-induced NO production was 5 times greater than that of glucosamine. However both molecules inhibited NO production in a dose dependent manner. Table 2: The effect of various sugars on IL-1ß induced NO Production
The observed suppression of IL-1beta-induced NO production is associated with inhibition of inducible NO synthase mRNA and protein expression. The inhibitory effect of N-acetyl-D-glucosamine on NO production was specific, since monosaccharides, such as glucose, glucuronic acid, and N-acetylmannosamine, do not have this activity. Furthermore, the dimeric and the trimeric polymers of N-acetyl-D-glucosamine did not inhibit NO production. The investigators question the clinical relevance of their findings arguing that it is unlikely that tissue levels of N-acetyl-D-glucosamine in vivo would reach the levels they used in their in vitro experiments. However, the doses of N-acetyl-D-glucosamine used by Salvatore2 in the treatment of inflammatory bowel disease in children, 3 to 6 grams of N-acetyl-D-glucosamine daily, could reach concentrations in tissue similar to those used in the human chondrocyte experiments. For example a 50 kilogram person has an extra cellular fluid volume of 8.7 litres. Three grams of N-acetyl-D-glucosamine placed in 8.7 liters of water would result in a solution concentration of (3 grams/(221 grams per mole X 8.7 liters) equal to 1.6 mM. At a dose of 6 grams the concentration could reach 3 mM which is high enough according to the data presented to significantly reduce NO production. 1 Shikhman, A. R., K. Kuhn, et al. (2001). "N-acetylglucosamine prevents IL-1 beta-mediated activation of human chondrocytes." J Immunol 166(8): 5155-60. 2 Salvatore, S., R. Heuschkel, et al. (2000). "A pilot study of N-acetyl glucosamine, a nutritional substrate for glycosaminoglycan synthesis, in paediatric chronic inflammatory bowel disease." Aliment Pharmacol Ther 14(12): 1567-79. | |
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Notice: The information is intended to provide the reader with a comprehensive understanding of the science underlying the role of glucosamine and N-acetylglucosamine in the mammalian body. The scientific information on this site has been compiled from many different scientific sources. No specific therapeutic claims are made for any product. The information provided on this site is for general information purposes only and is not intended to qualify, supplement or replace that of your medical professional. These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease. Your healthcare giver should undertake diagnosing and treating your medical condition.
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