Document Detail

Vitamins E and C in the prevention of cardiovascular disease in men: the Physicians' Health Study II randomized controlled trial.
MedLine Citation:
PMID:  18997197     Owner:  NLM     Status:  MEDLINE    
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: Identifier: NCT00270647.
Howard D Sesso; Julie E Buring; William G Christen; Tobias Kurth; Charlene Belanger; Jean MacFadyen; Vadim Bubes; JoAnn E Manson; Robert J Glynn; J Michael Gaziano
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Publication Detail:
Type:  Journal Article; Randomized Controlled Trial; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2008-11-09
Journal Detail:
Title:  JAMA     Volume:  300     ISSN:  1538-3598     ISO Abbreviation:  JAMA     Publication Date:  2008 Nov 
Date Detail:
Created Date:  2008-11-12     Completed Date:  2008-11-18     Revised Date:  2014-09-17    
Medline Journal Info:
Nlm Unique ID:  7501160     Medline TA:  JAMA     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2123-33     Citation Subset:  AIM; IM    
Data Bank Information
Bank Name/Acc. No.:
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MeSH Terms
Antioxidants / administration & dosage,  therapeutic use*
Ascorbic Acid / administration & dosage,  therapeutic use*
Cardiovascular Diseases / epidemiology,  prevention & control*
Dietary Supplements*
Double-Blind Method
Follow-Up Studies
Middle Aged
Vitamin E / administration & dosage,  therapeutic use*
Vitamins / administration & dosage,  therapeutic use*
alpha-Tocopherol / administration & dosage,  therapeutic use
Grant Support
CA 34944/CA/NCI NIH HHS; CA 40360/CA/NCI NIH HHS; CA 97193/CA/NCI NIH HHS; HL 26490/HL/NHLBI NIH HHS; HL 34595/HL/NHLBI NIH HHS; R01 CA097193/CA/NCI NIH HHS; R01 CA097193-01/CA/NCI NIH HHS; R01 CA097193-02/CA/NCI NIH HHS; R01 CA097193-03/CA/NCI NIH HHS; R01 CA097193-04/CA/NCI NIH HHS; R01 CA097193-05/CA/NCI NIH HHS; R01 CA097193-06A1/CA/NCI NIH HHS; R01 CA097193-07/CA/NCI NIH HHS
Reg. No./Substance:
0/Antioxidants; 0/Vitamins; 1406-18-4/Vitamin E; H4N855PNZ1/alpha-Tocopherol; PQ6CK8PD0R/Ascorbic Acid
Comment In:
Evid Based Nurs. 2009 Apr;12(2):48   [PMID:  19321825 ]
JAMA. 2009 Apr 1;301(13):1335-6; author reply 1336-7   [PMID:  19336703 ]
JAMA. 2009 Apr 1;301(13):1336; author reply 1336-7   [PMID:  19336705 ]
JAMA. 2009 Apr 1;301(13):1335; author reply 1336-7   [PMID:  19336704 ]
Ann Intern Med. 2009 Apr 21;150(8):JC4-12   [PMID:  19391226 ]

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