Fructose and Uric Acid

High quantities of fructose in the diet are able to increase circulating VLDL-triglyceride levels because fructose metabolism by the liver increases the rate of de novo lipogenesis. One hypothesis suggests that these fatty acids contribute to insulin resistance because they are deposited in skeletal muscle tissue. However, of equal importance metabolically is the ability of fructose to raise uric acid concentrations. These is some evidence that these raised circulating levels of uric acid may then lead to the development of insulin resistance. This occurs because fructose can up-regulate nucleotide degradation, one of the products of which is uric acid. Uric acid is best known as a causative factor in the development of gout. Gout occurs when uric acid becomes supersaturated in extracellular fluid and crystallises in joints resulting in tissue inflammation. Normal plasma levels of uric acid are in the range of 4 to 7 mg/dL.

Fructose is able to increase uric acid production because high intakes of fructose cause a rapid degradation of purine nucleotides to uric acid in the liver. Fructose enters the liver and is phosphorylated to fructose 1-phosphate, in the process causing ATP to be converted to ADP. As fructose 1-phosphate accumulates it traps inorganic phosphate. Adenylate kinase and oxidative phosphorylation converts ADP back to ATP, but at the same time AMP increases in intracellular concentration because of the activity of adenylate kinase. The high AMP concentrations increase intracellular levels of IMP, and as they increase in concentration, dephosphorylation by 5’-nucleotidase triggers a cascade of dephosphorylation of nucleotides. The end result is an increase in the formation of uric acid. Research has shown that consumption of 4 or more sugar containing soft drinks per day significantly increases the risk of developing elevated levels of uric acid.

Elevated levels of uric acid are seen in a number of metabolic disorders, but it unclear as to whether the uric acid is the cause of the dysfunction or a symptom of it. Uric acid levels are raised in the metabolic syndrome, and an association between the two has been known for some time. Individuals with type 2 diabetes also have raised circulating levels of uric acid. Animal models that replicate the metabolic syndrome by feeding high amounts of fructose (60% of energy intake) cause elevated levels of triglycerides, increased blood pressure and insulin resistance. These characteristics of metabolic syndrome are alleviated by the administration of the uric acid lowering drugs allopurinol and benzbromarone. The blood pressure rises seen in the rats were caused by impaired nitric oxide dependent dilation, and this impaired nitric oxide response was correlated positively to the rise in uric acid seen in the plasma.

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1Angelopoulos, T. J., Lowndes, J., Zukley, L., Melanson, K. J., Nguyen, V., Huffman, A. and Rippe, J. M. 2009. The effect of high-fructose corn syrup consumption on triglycerides and uric acid. Journal of Nutrition. 139: 1242S-1245S

About Robert Barrington

Robert Barrington is a writer, nutritionist, lecturer and philosopher.
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