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Human and Clinical Nutrition
High blood uric acid (hyperuricaemia) is the strongest determinant risk factor for gout, an inflammatory arthritis caused by uric acid crystals, and its prevalence is higher in males compared with females(1). Hyperuricaemia is also common in patients who develop diabetes(2), obesity(3), hyperglycaemia(4,5), hypertension(6)and stroke(7), although it is often unattended until their first, if any, gout attack. Gout prevalence increased approximately from 0·5 to 3 % between 1960 and 2010 in the USA(8)and other areas(9)accompanied by a parallel increase in the number of individuals with hyperuricaemia(10,11). The fact that 25-34 years is the age group with the highest blood uric acid level(12)may suggest that hyperuricaemia precedes the development of metabolic syndromes(13). Interestingly, allopurinol, a uric acid-lowering agent used in gout therapy, has a protective effect on hypertension, which suggests that excess uric acid synthesis is a causal factor for developing hypertension(14).
Some dietary factors including purines, alcohol and fructose(15-18)also elevate blood uric acid levels - for example, chronic exposure to fructose can lead to the development of hyperuricaemia(19). Fructose phosphorylation by fructokinase causes intracellular phosphate depletion, leading to the activation of deaminase, which converts adenosine monophosphate to inosine monophosphate. The consumption of ATP activates transformation of inosine monophosphate to inosine, the precursor of uric acid metabolism. Chronic hyperuricaemia may also up-regulate fructokinase expression, leading to the amplification of the lipogenic effects of fructose in human hepatocytes(20). Xanthine oxidoreductase (also called xanthine oxidase or xanthine dehydrogenase depending on proteolytic processing) catalyses the final step in uric acid production. Inhibition of this enzyme has been the target of uric acid-lowering drugs such as allopurinol(21). Studies in both healthy humans(22,23)and animal models(24)substantiate the importance of increased insulin resistance to hyperuricaemia, and vice versa, providing a link to excess fructose intake.
Quercetin is...