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

Abstract

ExtractAfter the infusion of fructose, 0.25 g/kg body wt, the mean peak plasma uric acid lerel was 5.4 0.7 ( S E M ) mg/100 ml in six normal children and was not significantly increased compared with that of the mean basal kalue of 4.1 0.5 mg/100 ml. The mean blood inorganic phosphate ( P , ) 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 ( H F I ) 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, 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 i 0.1 ( S E M I 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 , 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. SpeculationFructose 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 1, may be similar to that proposed for fructose-induced hyperuricemia.

Oral fructose absorption in obese children with non‐alcoholic fatty liver disease

“…Uric acid is produced as a result of fructose ingestion . Transient increases in uric acid have been noted following an oral fructose challenge in adults, and are particularly pronounced in adults with gout and in children of adults with gout .…”

“…Transient increases in uric acid have been noted following an oral fructose challenge in adults, and are particularly pronounced in adults with gout and in children of adults with gout . Intravenous fructose infusions increase uric acid levels in normal children, and when administered to children with hereditary fructose intolerance, uric acid increases fourfold . Moreover, hyperuricaemia is an independent risk factor for adult and paediatric NAFLD .…”

Ketohexokinase C blockade ameliorates fructose-induced metabolic dysfunction in fructose-sensitive mice

“…In HFI, mutations in the aldolase B gene (aldob) lead to deficiency in aldolase B activity and the accumulation of Fru1-P. This results in marked phosphate and adenosine triphosphate (ATP) depletion and subsequent uric acid generation following fructose ingestion, which are much greater than those observed in healthy individuals (9). The depletion of phosphate sequestered in Fru1-P leads to glycogen accumulation (10) as well as competitive inhibition of glycogen phosphorylase b and phosphoglucomutase by Fru1-P (11).…”

Galactosemia: How Does Long-Term Treatment Change the Outcome?

“…In galactosemia, the same effect may be inferred for galactose from the observed fall of serum P! [21] and rise of serum urate [9,21] after a galactose load. (Galactose toler ance tests are potentially dangerous and should not be done in a galactosémie child.)…”