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Cited by 913Antioxidant Activity and Oxidative StressCardiovascular Health and Risk FactorsVitamin C and Antioxidants Research

Vitamins E and C in the Prevention of Cardiovascular Disease in Men: The Physicians' Health Study II Randomized Controlled Trial

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Sesso, Howard D.·2008·JAMA
DOI 10.1001/jama.2008.600PMC PMC2586922
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Abstract

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.

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  • Recent large-scale epidemiological studies reported preventive effects of antioxidant supplementations including vitamins E, C, and beta carotene rich in fruits and vegetables on cardiovascular disease, whereas other studies showed no beneficial effects, and in some cases a decrease in cardiovascular protection was observed.

    “Intriguingly, recent large-scale epidemiological studies reported the preventive effects of antioxidant supplementations including vitamins E, C, and beta carotene rich in fruits and vegetables on cardiovascular disease, whereas no beneficial effects were shown in other studies, and in some cases a decrease in cardiovascular protection with these supplementations was observed [103,104,105].”

    From NO-Rich Diet for Lifestyle-Related Diseases (2015) · cites this paper as [105]

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Research works printed but not linked: 2

  1. [46]Low-dose aspirin and vitamin E in people at cardiovascular risk: a randomised trial in general practice Lancet 2001 35789 95 11197445
  2. [59]Standing Committee on the Scientific Evaluation of Dietary Reference Intakes -Food and Nutrition Board Dietary Reference Intakes for Vitamin C, Vitamin E, Selenium, and Beta-carotene, and Other Carotenoids Washington, DC National Academy Press 2000

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Authors
Sesso, H. D.
Affiliations
Brigham and Women's Hospital (US)
Corresponding author
Sesso, Howard D.
ORCID
Sesso, Howard D.
Venue
JAMA
Publisher
American Medical Association (AMA)
Published
2008-11-12
Volume
300
Issue
18
Pages
2123
ISSN
  • 0002-9955 (ISSN-L)
  • 0098-7484
DOI
10.1001/jama.2008.600
PMC
PMC2586922
OpenAlex
W2021294790
Cited by
913
References
62
Citations by year
2026: 25 · 2025: 31 · 2024: 42 · 2023: 28 · 2022: 36 · 2021: 43 · 2020: 45 · 2019: 27 · 2018: 38 · 2017: 50 · 2016: 47 · 2015: 60 · 2014: 76 · 2013: 80 · 2012: 79
FWCI
40.58
Type
journal article
Language
en
Open access
Locations
  • JAMA (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Heart, Lung, and Blood Institute (HL-34595, HL 26490, R01 HL026490, R01HL034595)
  • National Cancer Institute (CA97193, R01CA040360, CA 34944, R01 CA034944, R01CA097193, CA 40360)
Topics
  • Health Sciences › Medicine › Biochemistry › Antioxidant Activity and Oxidative Stress
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Health and Risk Factors
  • Health Sciences › Nursing › Nutrition and Dietetics › Vitamin C and Antioxidants Research
Keywords
vitamin E supplementation, vitamin C supplementation, cardiovascular disease prevention, major cardiovascular events, myocardial infarction, stroke, cardiovascular mortality, men, antioxidant supplements, cardiovascular risk reduction, hormone replacement therapy, coronary artery disease, coronary revascularization, coronary angioplasty, coronary artery bypass grafting
MeSH terms
Aged, Antioxidants, Ascorbic Acid, Cardiovascular Diseases, Double-Blind Method, Follow-Up Studies, Humans, Male, Middle Aged, Vitamin E, Vitamins, Dietary Supplements, alpha-Tocopherol

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