Stephen P Juraschek1, J Michael Gaziano2,3, Robert J Glynn4,5, Natalya Gomelskaya4, Vadim Y Bubes4, Julie E Buring4,6, Robert H Shmerling7, Howard D Sesso2,4,6. 1. Division of General Medicine, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA. 2. Division of Aging, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA. 3. Massachusetts Veterans Epidemiology Research and Information Center (MAVERIC), VA Boston Healthcare System, Boston, MA, USA. 4. Division of Preventive Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA. 5. Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA. 6. Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA. 7. Division of Rheumatology and Clinical Immunology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA.
Abstract
BACKGROUND: Short-term randomized trials suggest that a 500 mg/d vitamin C supplement reduces serum urate, whereas observational studies show vitamin E is inversely associated with gout risk. OBJECTIVES: We evaluated the effect of supplemental vitamin C (prespecified primary exposure) and vitamin E (prespecified secondary exposure) on new diagnoses of gout. METHODS: We performed a post hoc analysis of data from the Physicians' Health Study II, a randomized, double-blind, placebo-controlled factorial trial of randomized vitamin C (500 mg/d) 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 ≤10 y. RESULTS: Of 14,641 randomly assigned male physicians in our analysis, the mean age was 64 ± 9 y; 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 1000 person-years among those assigned vitamin C compared with 9.1 per 1000 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/m 2 (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). CONCLUSIONS: Vitamin C modestly reduced the risk of new gout diagnoses in 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 in adults with established gout.The Physicians' Health Study II is registered at clinicaltrials.gov (identifier: NCT00270647).
BACKGROUND: Short-term randomized trials suggest that a 500 mg/d vitamin C supplement reduces serum urate, whereas observational studies show vitamin E is inversely associated with gout risk. OBJECTIVES: We evaluated the effect of supplemental vitamin C (prespecified primary exposure) and vitamin E (prespecified secondary exposure) on new diagnoses of gout. METHODS: We performed a post hoc analysis of data from the Physicians' Health Study II, a randomized, double-blind, placebo-controlled factorial trial of randomized vitamin C (500 mg/d) 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 ≤10 y. RESULTS: Of 14,641 randomly assigned male physicians in our analysis, the mean age was 64 ± 9 y; 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 1000 person-years among those assigned vitamin C compared with 9.1 per 1000 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/m 2 (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). CONCLUSIONS: Vitamin C modestly reduced the risk of new gout diagnoses in 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 in adults with established gout.The Physicians' Health Study II is registered at clinicaltrials.gov (identifier: NCT00270647).
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