INHIBITION OF PROTEIN GLYCATION AND ADVANCED GLYCATION END-PRODUCTS BY ASCORBIC-ACID AND OTHER VITAMINS AND NUTRIENTS

Nonenzymatic glycation, the reaction of glucose and other reducing sug ars with protein, reversibly produces Amadori products and over a long period irreversible advanced glycation end products. In diabetes, the se reactions are greatly accelerated and are important in the pathogen esis of diabetic complications. In vitro glycation was studied with bo vine albumin as the model protein. A mixture of 25 mM glucose/fructose was used as the glycating agent. The Amadori product was quantitated by thiobarbituric acid colorimetry after hydrolysis. Advanced glycatio n endproducts were measured by their intrinsic fluorescence. A number of vitamins and nutrients were found to be potent inhibitors of both t he glycation reaction and the subsequent end products. The nutrients w ere effective at physiological concentrations and exhibited dose-respo nse relationships. The inhibitors included ascorbic acid, tocopherol, pyridoxal, niacinamide, sodium selenite, selenium yeast, and carnosine . A significant correlation was found between the inhibition of glycat ion and the inhibition of AGE formation (P <0.001). One of the nutrien ts, ascorbic acid, was used in a pilot study. Eighteen normal subjects , 7 college age and 10 middle age, were supplemented with 1,000 mg of ascorbic acid in the form of Re-Natured Vitamin C(R) for a period of 4 weeks. Serum protein glycation was decreased an average of 46.8% (P < 0.01). These results underline the importance of nutrition in diabetes and indicate the possibility of therapeutic use of these nutrients fo r the prevention of diabetic complications. (C) Elsevier Science Inc. 1996