It’s been suggested for years that vitamin C might prevent gout, whether or not a person has a history of previous gout. Dietary and supplemental vitamin C intake have been inversely associated with gout in observational studies. A meta-analysis of clinical trials published in Arthritis Care & Research showed vitamin C supplementation lowered urate in adults without gout.
Howard D. Sesso, ScD, MPH, associate director of the Division of Preventive Medicine at Brigham and Women’s Hospital, and colleagues recently published the first data on this question based upon a large-scale, long-term randomized trial. In The American Journal of Clinical Nutrition, they report supplementation with 500 mg/day of vitamin C versus placebo was associated with a lower risk of new gout diagnosis, whereas 400 IU every other day of supplemental vitamin E had no effect on gout.
The researchers conducted a post hoc analysis of the Physicians’ Health Study II, a 2x2x2x2 factorial, randomized, double-blind, placebo-controlled trial conducted from July 1997 to August 2007 at the Brigham.
The trial examined the effects of vitamin C, vitamin E, a multivitamin, and beta-carotene on the risk of prostate cancer, cardiovascular disease, and eye disease in 14,641 U.S. male physicians who were 50 or older at baseline. They were followed for up to 10 years.
The post hoc analysis included data for participants randomized to:
- Vitamin C (n=7,329) or placebo (n=7,312)
- Vitamin E (n=7,315) or placebo (n=7,326)
Follow-up continued for a maximum of 10 years until the occurrence of gout, death, last known questionnaire return date, or the end of the vitamin C and vitamin E interventions on August 31, 2007, whichever came first.
Overall, vitamin C had a modest but statistically significant 12% reduction on the risk of gout:
- Overall—HR, 0.88 (P=0.04)
- Excluding men with prevalent gout—HR, 0.90 (P=0.23)
The effect of vitamin C also appeared to be greater among men with a normal body mass index:
- BMI <25—HR, 0.74
- BMI 25 to <30—HR, 0.85
- BMI ≥30—HR, 1.29 (P for interaction = 0.01)
There was no association between assignment to vitamin E versus placebo and newly diagnosed gout (HR 1.05; P=0.48). Excluding participants with gout at baseline did not alter the lack of effect.
Caveats for Clinicians
Vitamin C is generally well tolerated, but the small treatment effect in this study doesn’t yet support a population-wide recommendation for supplementation to reduce the risk of gout. Likewise, these results should not be interpreted as a reason to discontinue or replace urate-lowering therapies.