Sugar-sweetened beverages, urate, gout and genetic interaction.
The clinical manifestations of gout occur as a result of immune responses to monosodium urate crystals. Elevated serum levels of urate (hyperuricemia) are a prerequisite for the development of gout with reduced fractional renal excretion of uric acid (FEUA) an important cause. In New Zealand, Mãori and Pacific Island people have inherently raised urate levels with one consequence a higher prevalence of more severe gout. One characteristic metabolic effect of fructose, present in sugar-sweetened beverages (SSB), is raised urate from hepatic processing of fructose. Here we discuss, and place in a biological context evidence, linking consumption of SSB with hyperuricemia and gout, including the first review of recent ecological and clinical studies of the impact of fructose and SSB exposure in Pacific Island people. Both increased serum urate and increased FEUA are observed in clinical studies examining the effects of an acute fructose load. In contrast, chronic exposure to increased fructose in the diet also leads to increased serum urate concentrations, but reduced FEUA. Epidemiological studies have consistently associated SSB consumption with increased serum urate levels and increased risk of gout. Non-additive interaction of SSB consumption with a genetic variant of a uric acid transporter in serum urate levels and gout risk emphasizes the causality of SSB in gout. Taken together these data demonstrate the hyperuricemic effect of SSB and fructose, with biochemical pathways reasonably well understood. The evidence that dietary fructose increases urate is strong. The evidence summarized here is of sufficient weight to recommend reduction of SSB consumption, particularly in Pacific Island and Mãori people, to reduce the burden of gout.
T R
TR
Merriman
N
N
Dalbeth
R J
RJ
Johnson
D001628:Beverages / Q000009:adverse effects*; D019422:Dietary Sucrose / Q000009:adverse effects*; D059647:Gene-Environment Interaction; D006073:Gout / Q000097:blood / Q000453:epidemiology / Q000235:genetics*; D006801:Humans; D009520:New Zealand / Q000453:epidemiology; D012307:Risk Factors; D014527:Uric Acid / Q000097:blood*
D019422:Dietary Sucrose; D014527:Uric Acid