Fructose-induced Hyperuricemia: Observations in Normal Children and in Patients with Hereditary Fructose Intolerance and Galactosemia

Abstract

Extract: After the infusion of fructose, 0.25 g/kg body wt, the mean peak plasma uric acid level was 5.4 ± 0.7 (SEM) mg/100 ml in six normal children and was not significantly increased compared with that of the mean basal value of 4.1 ± 0.5 mg/100 ml. The mean blood inorganic phosphate (P_i) levels were significantly less than the mean fasting value after fructose. Blood glucose, lactic acid, and fructose levels were significantly increased after fructose, but serum magnesium levels did not change.

In two patients with hereditary fructose intolerance (HFI) the peak blood uric acid levels were 12.1 and 7.6 mg/100 ml, respectively, after fructose. In both patients the blood glucose concentrations decreased 69 and 26 mg/100 ml below the fasting levels after fructose. The serum P_i level decreased 2.3 and 1.2 mg/100 ml below fasting values, decrements greater than the mean decrement in serum P_i of 0.8 ± 0.2 mg/100 ml which occurred in six normal children.

The mean uric acid excretion, expressed as milligrams per mg urinary creatinine, was 0.6 ±0.1 (SEM) before fructose in the normal children and increased significantly to 1.0 ±0.1 mg/mg creatinine after fructose. In two patients with HFI the uric acid excretion increased four- to fivefold after fructose administration; the increased uric acid excretion in HFI exceeded that of normal children.

In three patients with galactosemia, increases in blood uric acid levels after galactose ingestion were similar to those in normal children after fructose, but less than those in patients with HFI after fructose. The serum P_i levels decreased less in galactosemic patients after galactose administration than in patients with HFI after fructose infusion.

These studies support the hypothesis that fructose-induced hyperuricemia results from degradation of adenosine monophosphate. This effect appears to be specific for fructose. The lack of hyperuricemia in galactosemia patients after galactose ingestion may be explained by the observation that galactose is phosphorylated more slowly than fructose.

Speculation: Fructose administration in individuals predisposed to hyperuricemia and gout may induce urate overproduction by decreasing intrahepatic P_i and ATP content and ultimately lead to enhanced nucleotide catabolism. The pathogenesis of increased urate production in glycogen storage disease, type I, may be similar to that proposed for fructose-induced hyperuricemia.