Ethanol-Induced Hyperuricemia: Evidence for Increased Urate Production by Activation of Adenine Nucleotide Turnover

Consumption of alcoholic beverages is associated with hyperuricemia and gout. To determine the contributions to this process of increased production and decreased excretion of uric acid, we gave oral ethanol (1.8 g per kilogram of body weight every 24 hours) for eight days or intravenous ethanol (0.25 to 0.35 g per kilogram per hour) for two hours to six patients with gout. During the long-term oral study we observed the following: serum urate levels increased from 8.4±0.4 (mean ±S.E.) to 10.1 ±0.9 mg per deciliter; whole blood lactate reached a peak of 3.1 ±0.7 mM from a base line of 1.3±0.3 mM; and urinary oxypurines increased to 641 ±397 per cent of the base-line value. Urate clearance increased to 145±25 per cent of the base-line value. Daily uric acid turnover increased from 1010 mg per deciliter to 170±17 per cent of the base-line value. During short-term intravenous ethanol administration, serum urate levels, urate clearance, and urinary uric acid excretion were not substantially altered from the baseline period. Urinary oxypurine levels increased to 341 to 415 per cent of base-line values. Urinary radioactivity, originating from the adenine nucleotide pool labeled by [8–¹⁴C]adenine, increased to 127 to 149 per cent of baseline values. These data indicate that ethanol increases urate synthesis by enhancing the turnover of adenine nucleotides. (N Engl J Med. 1982; 307:1598–1602.), Alcohol consumption has traditionally been associated with hyperuricemia and, in susceptible persons, the precipitation of acute gouty arthritis.¹ Early studies indicated that a decrease in the renal excretion of uric acid could account for ethanolinduced hyperuricemia.²,³ The hyperuricemia and hypouricosuria were linked to ethanol-related elevations in blood lactate levels. Lactate competitively inhibits uric acid clearance by the proximal tubule⁴,⁵ and could diminish urate excretion. However, the possibility that ethanol intake may lead to an increase in uric acid production as an alternative or additional mechanism for hyperuricemia has been suggested from other observations.⁶,⁷ In the present study we have reexamined.