Fructose-rich beverages and risk of gout in women

Abstract

Context: Fructose-rich beverages such as sugar-sweetened soda and orange juice can increase serum uric acid levels and, thus, the risk of gout, but prospective data on the relationship are limited.

Objective: To examine the relationship between intake of fructose-rich beverages and fructose and the risk of incident gout among women.

Design, setting, and participants: In the Nurses' Health Study, a US prospective cohort study spanning 22 years (1984-2006), we analyzed data from 78,906 women with no history of gout at baseline who provided information on intake of beverages and fructose through validated food frequency questionnaires.

Main outcome measure: Incident cases that met the American College of Rheumatology survey criteria for gout.

Results: During 22 years of follow-up, we documented 778 confirmed incident cases of gout. Increasing intake of sugar-sweetened soda was independently associated with increasing risk of gout. Compared with consumption of less than 1 serving per month of sugar-sweetened soda, the multivariate relative risk of gout for 1 serving per day was 1.74 (95% confidence interval [CI], 1.19-2.55) and for 2 or more servings per day was 2.39 (95% CI, 1.34-4.26) (P<.001 for trend). The corresponding relative risks for orange juice were 1.41 (95% CI, 1.03-1.93) and 2.42 (95% CI, 1.27-4.63) (P = .02 for trend). The absolute risk differences corresponding to these relative risks were 36 and 68 cases per 100,000 person-years for sugar-sweetened soda and 14 and 47 cases per 100,000 person-years for orange juice, respectively. Diet soft drinks were not associated with the risk of gout (P = .27 for trend). Compared with the lowest quintile of fructose intake, the multivariate relative risk of gout in the top quintile was 1.62 (95% CI, 1.20-2.19; P = .004 for trend) (risk difference of 28 cases per 100,000 person-years).

Conclusion: Among this cohort of women, consumption of fructose-rich beverages is associated with an increased risk of incident gout, although the contribution of these beverages to the risk of gout in the population is likely modest given the low incidence rate among women.

Figure 1. Mechanism of Fructose-Induced Hyperuricemia

Fructose induces uric acid production by increasing ATP degradation to AMP, a uric acid precursor. The phosphorylation of fructose to fructose-l-phosphate causes ATP to be degraded to ADP. Fructose-l- phosphate traps inorganic phosphate, and ADP is converted back to ATP by using inorganic phosphate. The net result is reduced levels of intracellular ATP and inorganic phosphate (Pi) combined with a buildup of AMP, which also leads to increased IMP concentration. Elevated AMP and IMP levels activate the catabolic pathways leading to increased synthesis of uric acid, accounting for hyperuricemia. (See text for details).