NFI - SISA

Vitamins E and C in the prevention of cardiovascular disease in men: the Physicians' Health Study II randomized controlled trial

Sesso HD, Buring JE, Christen WG, Kurth T, Belanger C, MacFadyen J, Bubes V, Manson JE, Glynn RJ, Gaziano JM.
JAMA. 2008 Nov 12;300(18):2123-33

I risultati degli studi clinici che hanno valutato gli effetti degli antiossidanti e della vitamina C ed E nella riduzione del rischio cardiovascolare sono contrastanti. Pochi di questi studi inoltre hanno preso in considerazione soggetti di sesso maschile inizialmente a basso rischio di Malattia cardiovascolare e nessuno studio ha esaminato l’effetto della sola vitamina C, non associata alla vitamina E o ad altri antiossidanti. Questo gruppo di ricerca di Boston ha reclutato 14.641 medici di sesso maschile, partecipanti al Physicians’ Health Study II, di età media di 64 anni, che hanno assunto 400 UI di vitamina E a giorni alterni, 500 mg di vitamina C quotidianamente o entrambe le vitamine in associazione. Negli 8 anni di osservazione sono stati registrati 1.245 eventi cardiovascolari maggiori, sui quali né la vitamina E e nemmeno la vitamina C hanno mostrato alcun effetto. Nessuna delle due vitamine ha inoltre influenzato la mortalità totale, ma la vitamina E è risultata associata ad un aumento del rischio di Ictus emorragico (HR=1,74, p=0,04). Anche nel gruppo trattato con l’associazione delle due vitamine non sono stati evidenziati significativi effetti sugli eventi cardiovascolari. Questi dati confermano quanto già emerso da studi precedenti che hanno escluso l’efficacia delle vitamine C ed E, da sole o in associazione, nella prevenzione del rischio cardiovascolare.

CONTEXT: Basic research and observational studies suggest vitamin E or vitamin C may reduce the risk of cardiovascular disease. However, few long-term trials have evaluated men at initially low risk of cardiovascular disease, and no previous trial in men has examined vitamin C alone in the prevention of cardiovascular disease. OBJECTIVE: To evaluate whether long-term vitamin E or vitamin C supplementation decreases the risk of major cardiovascular events among men. DESIGN, SETTING, AND PARTICIPANTS: The Physicians' Health Study II was a randomized, double-blind, placebo-controlled factorial trial of vitamin E and vitamin C that began in 1997 and continued until its scheduled completion on August 31, 2007. There were 14,641 US male physicians enrolled, who were initially aged 50 years or older, including 754 men (5.1%) with prevalent cardiovascular disease at randomization. INTERVENTION: Individual supplements of 400 IU of vitamin E every other day and 500 mg of vitamin C daily. MAIN OUTCOME MEASURES: A composite end point of major cardiovascular events (nonfatal myocardial infarction, nonfatal stroke, and cardiovascular disease death). RESULTS: During a mean follow-up of 8 years, there were 1245 confirmed major cardiovascular events. Compared with placebo, vitamin E had no effect on the incidence of major cardiovascular events (both active and placebo vitamin E groups, 10.9 events per 1000 person-years; hazard ratio [HR], 1.01 [95% confidence interval {CI}, 0.90-1.13]; P = .86), as well as total myocardial infarction (HR, 0.90 [95% CI, 0.75-1.07]; P = .22), total stroke (HR, 1.07 [95% CI, 0.89-1.29]; P = .45), and cardiovascular mortality (HR, 1.07 [95% CI, 0.90-1.28]; P = .43). There also was no significant effect of vitamin C on major cardiovascular events (active and placebo vitamin E groups, 10.8 and 10.9 events per 1000 person-years, respectively; HR, 0.99 [95% CI, 0.89-1.11]; P = .91), as well as total myocardial infarction (HR, 1.04 [95% CI, 0.87-1.24]; P = .65), total stroke (HR, 0.89 [95% CI, 0.74-1.07]; P = .21), and cardiovascular mortality (HR, 1.02 [95% CI, 0.85-1.21]; P = .86). Neither vitamin E (HR, 1.07 [95% CI, 0.97-1.18]; P = .15) nor vitamin C (HR, 1.07 [95% CI, 0.97-1.18]; P = .16) had a significant effect on total mortality but vitamin E was associated with an increased risk of hemorrhagic stroke (HR, 1.74 [95% CI, 1.04-2.91]; P = .04). CONCLUSIONS: In this large, long-term trial of male physicians, neither vitamin E nor vitamin C supplementation reduced the risk of major cardiovascular events. These data provide no support for the use of these supplements for the prevention of cardiovascular disease in middle-aged and older men. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00270647.