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February 4, 2008 — Consumption of soft drinks sweetened with sugar and fructose is strongly associated with an increased risk for gout, according to the results of a prospective cohort study reported in the February 1 Online First issue of the BMJ.
"In humans, acute oral or intravenous administration of fructose results in a rapid increase in serum levels of uric acid through accentuated degradation of purine nucleotides and increased purine synthesis," write Hyon K. Choi, MD, PhD, from the Arthritis Research Centre of Canada, Vancouver General Hospital, University of British Columbia in Vancouver, and Gary Curhan, MD, ScD, from the Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts. "This urate raising effect was found to be exaggerated in people with hyperuricaemia or a history of gout. It is unknown, however, if this acute effect is sustained on a long term basis and eventually translates into an increased risk of gout."
The goal of this 12-year follow-up study of health professionals was to assess the relationship between consumption of sugar-sweetened soft drinks and fructose and the risk for incident gout in a cohort of 46,393 men with no history of gout at enrollment. Validated food frequency questionnaires were used to determine intake of soft drinks and fructose. The primary endpoint was incident cases of gout based on American College of Rheumatology (ACR) survey criteria.
During the 12-year follow-up, there were 755 confirmed incident cases of gout, and increasing consumption of sugar-sweetened soft drinks was linked to an increasing risk for gout. Compared with intake of less than 1 serving of sugar-sweetened soft drinks per month, the multivariate relative risk (RR) for gout was 1.29 (95% confidence interval [CI], 1.00-1.68) for 5 to 6 servings per week, 1.45 (95% CI, 1.02 - 2.08) for 1 serving per day, and 1.85 (95% CI, 1.08-3.16) for 2 or more servings per day (P for trend = .002).
These associations were independent of dietary and other risk factors for gout, including body mass index, age, hypertension, diuretic use, alcohol intake, and history of chronic renal failure. There was no apparent relationship between diet soft drinks and risk for incident gout (P for trend = 0.99).
For increasing quintiles of fructose intake, the multivariate relative risks for gout were 1.00, 1.29, 1.41, 1.84, and 2.02 (95% CI, 1.49 - 2.75; P for trend < .001). In addition to fructose-sweetened soft drinks, other major sources of fructose intake, including total fruit juice and fructose-rich fruits (apples and oranges) were also associated with a higher risk for incident gout (P for trend < .05).
"Prospective data suggest that consumption of sugar sweetened soft drinks and fructose is strongly associated with an increased risk of gout in men," the study authors write. "Furthermore, fructose rich fruits and fruit juices may also increase the risk. Diet soft drinks were not associated with the risk of gout."
Limitations of the study include dietary consumption self-reported by questionnaire and restriction of study cohort to male health professionals, limiting generalizability.
"Our data provide prospective evidence that fructose poses a substantial risk for gout," the study authors conclude. "These data even suggest that the risk posed by free fructose intake could be at least as large as that by purine rich foods such as total meat consumption (relative risk between extreme fifths of intake 1.4126). Thus, the conventional low purine diet approach allowing fructose intake could potentially worsen the overall net risk of gout attacks."
The National Institutes of Health and TAP Pharmaceuticals supported this study in part. Professor Choi is the Mary Pack Arthritis Society of Canada chair in rheumatology. Professor Curhan has disclosed no relevant financial relationships.
BMJ. Published online February 1, 2008.
Gout is the most common inflammatory arthritis in men. Its prevalence has doubled in the United States within the past few decades and increased 61% from 1977 to 1997, the same period in which sugar-sweetened soft drinks represented the largest single source of calories in the US diet with yearly per capita use increasing from 0 to 29 kg. Fructose administration in humans is associated with a rapid increase in serum levels of uric acid, which are greater in those with gout. The study authors hypothesized that increased intake of sweetened fructose-containing drinks was linked to the incidence of gout.
This is a prospective evaluation of the association between intake of sugar-sweetened soft drinks, juice, and fruit intake and the incidence of gout in a cohort of healthy men without a previous history of gout.