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.

Clinical Context

Study Highlights

• Included were those in the follow-up study of health professionals, a longitudinal study of 51,529 male dentists, optometrists, osteopathic physicians, pharmacists, podiatrists, and veterinarians who were predominantly white (91%) and aged 40 to 75 years in 1986.
• Excluded were those with a history of gout.
• Participants completed a mailed questionnaire at baseline and every 2 years thereafter, with follow-up rate exceeding 90% for each 2-year period.
• A validated food frequency questionnaire was used to inquire about intake of more than 130 foods and beverages in the previous year, and intake was updated every 4 years.
• They were asked how frequently they consumed sweetened soft drinks and diet soft drinks, different types of fruit juices, and fruits.
• Range of frequency responses was from "never" to "6 or more times a day" with 9 frequency categories.
• Nutrient intakes were calculated by multiplying the frequency response by nutrient content of the specified portion sizes.
• Food intake was previously validated against 2 one-week diet records in this cohort.
• At baseline, orange juice, sugar-sweetened soft drinks, apples, raisins, and oranges contributed 54.2% of monosaccharide fructose.
• At baseline and at every 2 years, participants provided information on weight, regular drug use, and medical conditions, and body mass index was calculated.
• Incident cases of gout were ascertained with criteria of the ACR with 6 of 11 criteria being met.
• Questionnaire gout self-report was confirmed by medical record review of 50 cases with 94% concordance seen.
• Cox proportional hazards modeling was used to estimate risk for gout across categories of soft drink or fructose intake.
• At 12 years of follow-up of 46,393 men, 755 newly diagnosed cases of gout were reported that met ACR criteria.
• Increasing consumption of sweetened soft drinks was associated with increasing intake of caffeine, fructose, meats, and high-fat foods, and age and low-fat dairy intake tended to decrease.
• Increasing intake of sugar-sweetened soft drinks was associated with increasing risk for gout.
• The multivariate RR of gout for 5 to 6 servings of sugar-sweetened drinks a week was 1.29; for 1 serving a day, 1.45; and for 2 or more servings a day, 1.85 (P for trend = .002).
• Intake of diet soft drinks was not associated with increased risk for gout.
• Increasing fructose intake was also associated with increased risk for gout.
• Men in the highest fifth vs the lowest fifth of free fructose intake had an RR of 1.81 (P for trend < .001).
• After adjustment for other types of carbohydrates, RR was 2.02 (P for trend < .001).
• Higher total fructose intake was associated with increasing risk for gout, and the risk for a 5% increment in energy from fructose was 2.10, corresponding to an RR of 1.52.
• Total fruit juice intake was associated with increased risk for gout.
• Compared with men who consumed less than 1 glass of juice a month, the RR for consuming 2 or more glasses a day was 1.81.
• The corresponding RR for orange or apple juice consumption was 1.82.
• For intake of an orange or apple a day, the RR was 1.64, 1.55 for an orange alone, and 1.48 for an apple alone.
• No other individual fructose-rich foods were associated with risk for gout.

Pearls for Practice

• Consumption of sugar-sweetened soft drinks high in fructose, fruit juices, oranges, and apples are associated with an increased risk for gout in men.
• Intake of diet soft drinks is not associated with an increased risk for gout in men.

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