Effects of vitamin C supplementation on gout risk: results from the physicians' health study II trial

Am J Clin Nutr. 2022 May 16;nqac140. doi: 10.1093/ajcn/nqac140. Online ahead of print.


Background: Short-term randomized trials suggest that a 500 mg/day vitamin C supplement reduces serum urate, while observational studies show vitamin E is inversely associated with gout risk.

Objective: We evaluated the effect of supplemental vitamin C (pre-specified primary exposure) and vitamin E (pre-specified secondary exposure) on new diagnoses of gout.

Design: We performed a post-hoc analysis of data from the Physicians' Health Study II (PHS II), a randomized, double-blind, placebo-controlled factorial trial of randomized vitamin C (500 mg/day) and vitamin E (400 IU every other day). The primary outcome was new gout diagnoses, self-reported at baseline and throughout the follow-up period of up to 10 years.

Results: Among 14,641 randomized male physicians in our analysis, the mean age was 64 (SD, 9) years; 1% were Black and 6.5% had gout prior to randomization. The incidence rate of new gout diagnoses during follow-up was 8.0 per 1,000 person-years among those assigned vitamin C versus 9.1 per 1,000 person-years among those assigned placebo. The vitamin C assignment reduced new gout diagnoses by 12% (HR 0.88; 95% CI: 0.77, 0.99; P = 0.04). These effects were greatest among those with a BMI <25 kg/m2 (P-interaction = 0.01). Vitamin E was not associated with new gout diagnoses (HR: 1.05; 95% CI: 0.92, 1.19; P = 0.48).

Conclusion: Vitamin C modestly reduced the risk of new gout diagnoses among middle-aged male physicians. Additional research is needed to determine the effects of higher doses of vitamin C supplementation on serum urate and gout flares among adults with established gout. ClinicalTrials.gov Identifier: NCT00270647.

Keywords: gout; randomized trial; vitamin C; vitamin E.

Associated data

  • ClinicalTrials.gov/NCT00270647