Gout and Hyperuricemia
Risk Factors for Gout
Hyperuricemia is the primary risk factor for gout, and is required, although not sufficient, for the progression of the disease. The risk of gout increases with age and is more common in men; increased risk is also associated with other medical conditions including hypertension, obesity, renal insufficiency, early menopause (hormone therapy can reduce this risk), hypercholesterolemia, and surgery. Some medications increase gout risk (which is reversible upon discontinuation), particularly loop and thiazide diuretics, but also anti-tuberculous drugs, cyclosporin, and levodopa.20,36-38 Aspirin has a dual effect on uric acid levels; low doses inhibit excretion and increase blood levels, while very high doses (>3,000 mg/day) reduce levels.20 At 75 mg/day in elderly patients, the increase in blood uric acid is about 6%.39
Uric acid levels are very sensitive to dietary influences. High-purine foods, particularly red meat, fish, and shellfish, have long been known to increase hyperuricemia and gout risk. Data from the Health Professionals Follow-up Study, which followed over 47,000 health professionals for 12 years, revealed that individuals with the highest intakes of beef, pork, or lamb (>1.9 servings/day) and seafood (>0.6 servings/day) increased their risk of gout by 77% and 53%, respectively.40 There were no associations between total protein intake, total animal protein (including dairy protein, poultry, and eggs) intake, or purine-rich vegetable intake and the incidence of gout.
Alcoholic beverages increase blood uric acid and gout risk.41,42 In one study, individuals who consumed one beer or one serving of spirits per day had 1.75 and 1.22 times the incidence of gout, respectively, than individuals who consumed less than one drink a month. Drinking over two beers/day increased gout risk by 2.5-fold.42 Wine does not appear to affect gout risk. Alcohol metabolism to acetate accelerates the breakdown of purine-containing nucleotides (like ATP) and raises blood uric acid.43 Alcohol can also lower body temperature in the extremities which may precipitate an acute attack independent of blood uric acid concentration (gout attacks can occur in alcoholics at lower blood urate levels than in non-alcoholics).44 Beer, despite having less alcohol per serving than the other beverages, is more hyperuricemic due to its high purine content.45
Fructose has been positively associated with both gout and hyperuricemia risk in some studies, but has had no significant effect in others. In the third National Health and Nutritional Examination Survey (NHANES III), 14,761 individuals over 20 years old who consumed one or more sweetened soft drinks per day had levels of blood uric acid that averaged 0.5 mg/dL higher than non-drinkers.46 By comparison, persons who consumed an equivalent amount of orange juice had blood uric acid levels that averaged only about 0.15 mg/dL higher than non-juice drinkers. An analysis of more recent NHANES data, however, failed to find any significant association between total fructose consumption and hyperuricemia risk. These results, in addition to the conflicting results of several metabolic studies of fructose in human volunteers, suggest the relationship between fructose and hyperuricemia may be sensitive to factors aside from just the amount of ingested sugar.16