Vitamins E and C in the Prevention of Prostate and Total Cancer in Men: The Physicians' Health Study II Randomized Controlled Trial

Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02120, USA.
JAMA The Journal of the American Medical Association (Impact Factor: 35.29). 01/2009; 301(1):52-62. DOI: 10.1001/jama.2008.862
Source: PubMed


Many individuals take vitamins in the hopes of preventing chronic diseases such as cancer, and vitamins E and C are among the most common individual supplements. A large-scale randomized trial suggested that vitamin E may reduce risk of prostate cancer; however, few trials have been powered to address this relationship. No previous trial in men at usual risk has examined vitamin C alone in the prevention of cancer.
To evaluate whether long-term vitamin E or C supplementation decreases risk of prostate and total cancer events among men.
The Physicians' Health Study II is a randomized, double-blind, placebo-controlled factorial trial of vitamins E and C that began in 1997 and continued until its scheduled completion on August 31, 2007. A total of 14,641 male physicians in the United States initially aged 50 years or older, including 1307 men with a history of prior cancer at randomization, were enrolled.
Individual supplements of 400 IU of vitamin E every other day and 500 mg of vitamin C daily.
Prostate and total cancer.
During a mean follow-up of 8.0 years, there were 1008 confirmed incident cases of prostate cancer and 1943 total cancers. Compared with placebo, vitamin E had no effect on the incidence of prostate cancer (active and placebo vitamin E groups, 9.1 and 9.5 events per 1000 person-years; hazard ratio [HR], 0.97; 95% confidence interval [CI], 0.85-1.09; P = .58) or total cancer (active and placebo vitamin E groups, 17.8 and 17.3 cases per 1000 person-years; HR, 1.04; 95% CI, 0.95-1.13; P = .41). There was also no significant effect of vitamin C on total cancer (active and placebo vitamin C groups, 17.6 and 17.5 events per 1000 person-years; HR, 1.01; 95% CI, 0.92-1.10; P = .86) or prostate cancer (active and placebo vitamin C groups, 9.4 and 9.2 cases per 1000 person-years; HR, 1.02; 95% CI, 0.90-1.15; P = .80). Neither vitamin E nor vitamin C had a significant effect on colorectal, lung, or other site-specific cancers. Adjustment for adherence and exclusion of the first 4 or 6 years of follow-up did not alter the results. Stratification by various cancer risk factors demonstrated no significant modification of the effect of vitamin E on prostate cancer risk or either agent on total cancer risk.
In this large, long-term trial of male physicians, neither vitamin E nor C supplementation reduced the risk of prostate or total cancer. These data provide no support for the use of these supplements for the prevention of cancer in middle-aged and older men. Identifier: NCT00270647.

26 Reads
  • Source
    • "Antioxidants, as well as numerous cardioprotective strategies for reducing lethal reperfusion injury, have been administered in patients with AMI [50]. Although the scientific rationale, epidemiologic data, and retrospective studies have been persuasive, prospective, randomized, placebo-controlled trials have so far failed to verify the actual benefit of antioxidant vitamins in human diseases [51-54]. Among the possible contributory factors likely to account for this discrepancy,the lack of consideration of basic aspects, such as the pharmacokinetic properties of antioxidant vitamins, will be discussed later. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Background: Acute myocardial infarction (AMI) is the leading cause of mortality worldwide. Oxidative stress has been involved in the ischemia-reperfusion injury in AMI. It has been suggested that reperfusion accounts for up to 50% of the final size of a myocardial infarct, a part of the damage likely to be prevented.Therefore, we propose that antioxidant reinforcement through vitamins C and E supplementation should protect against the ischemia-reperfusion damage, thus decreasing infarct size.The PREVEC Trial (Prevention of reperfusion damage associated with percutaneous coronary angioplasty following acute myocardial infarction) seeks to evaluate whether antioxidant vitamins C and E reduce infarct size in patients subjected to percutaneous coronary angioplasty after AMI. Methods/design: This is a randomized, 1:1, double-blind, placebo-controlled clinical trial.The study takes place at two centers in Chile: University of Chile Clinical Hospital and San Borja Arriarán Clinical Hospital.The subjects will be 134 adults with acute myocardial infarction with indication for percutaneous coronary angioplasty.This intervention is being performed as a pilot study, involving high-dose vitamin C infusion plus oral administration of vitamin E (Vitamin-treatment group) or placebo (Control group) during the angioplasty procedure. Afterward, the Vitamin-treatment group receives oral doses of vitamins C and E, and the Control group receives placebo for 84 days after coronary angioplasty.Primary outcome is infarct size, assessed by cardiac magnetic resonance (CMR), measured 6 and 84 days after coronary angioplasty.Secondary outcomes are ejection fraction, measured 6 and 84 days after coronary angioplasty with CMR, and biomarkers for oxidative stress, antioxidant status, heart damage, and inflammation, which will be measured at baseline, at the onset of reperfusion, 6 to 8 hours after revascularization, and at hospital discharge. Discussion: The ischemia-reperfusion event occurring during angioplasty is known to increase myocardial infarct size. The cardioprotective benefits of high doses of vitamin C combined with vitamin E have not been fully explored. The PREVEC Trial seeks to determine the suitability of the therapeutic use of vitamins C and E against the reperfusion damage produced during angioplasty.Patient recruitment opened in February 2013. The trial is scheduled to end in March 2016. Trial registration: ISRCTN56034553.
    Trials 05/2014; 15(1):192. DOI:10.1186/1745-6215-15-192 · 1.73 Impact Factor
  • Source
    • "However, human studies are needed to confirm such therapeutic effects of protective nutrients. In the same context, it is important to be mindful that long-term effects of excessive antioxidant intake in the form of supplements have been questioned (Gaziano et al. 2009; Soni et al. 2010). In addition, a multitude of bioactive food components occur in the food supply, and some of these bioactive constituents likely share the same molecular targets. "
    [Show abstract] [Hide abstract]
    ABSTRACT: The paradigm of human risk assessment includes many variables that must be viewed collectively in order to improve human health and prevent chronic disease. The pathology of chronic diseases is complex, however, and may be influenced by exposure to environmental pollutants, a sedentary lifestyle, and poor dietary habits. Much of the emerging evidence suggests that nutrition can modulate the toxicity of environmental pollutants, which may alter human risks associated with toxicant exposures. In this commentary, we discuss the basis for recommending that nutrition be considered a critical variable in disease outcomes associated with exposure to environmental pollutants, thus establishing the importance of incorporating nutrition within the context of cumulative risk assessment. A convincing body of research indicates that nutrition is a modulator of vulnerability to environmental insults; thus, it is timely to consider nutrition as a vital component of human risk assessment. Nutrition may serve as either an agonist or an antagonist (e.g., high-fat foods or foods rich in antioxidants, respectively) of the health impacts associated with exposure to environmental pollutants. Dietary practices and food choices may help explain the large variability observed in human risk assessment. We recommend that nutrition and dietary practices be incorporated into future environmental research and the development of risk assessment paradigms. Healthful nutrition interventions might be a powerful approach to reduce disease risks associated with many environmental toxic insults and should be considered a variable within the context of cumulative risk assessment and, where appropriate, a potential tool for subsequent risk reduction.
    Environmental Health Perspectives 02/2012; 120(6):771-4. DOI:10.1289/ehp.1104712 · 7.98 Impact Factor
  • Source
    • "Because most chronic diseases are of multi-causal origin, the supplementation with a single antioxidant seems unreasonable. The negative results of respective interventional trials with single or few antioxidants , as for example in SELECT (Selenium and vitamin E Cancer Prevention Trial; (Lippman et al., 2009)) or PHS- II (Physicans' Health Study II; (Gaziano et al., 2009)) are not surprising. Consequently, it was stated that " single-agent interventions, even in combinations, may be an ineffective approach to primary prevention in average-risk populations " (Gann, 2009). "
    [Show abstract] [Hide abstract]
    ABSTRACT: The powerful action of antioxidants in preventing premature lipid oxidation in food suggests that the same compounds, when consumed with the daily diet, could unfold antioxidative/anti-aging effects in the human body. Therefore, it has been hypothesized that antioxidants are helpful in preventing various diseases. More detailed chemical and physiological examination of antioxidants shows, however, that the extrapolation of in vitro data to in vivo behavior may be misleading. Indeed, such a procedure fails to take into account the mismatch between most in vitro models (e.g., cell cultures) and in vivo systems. For example, the physiological relevance of pro-oxidative and other physiological activities of antioxidants have been largely underestimated. Actually, contrary to the antioxidant hypothesis, clinical trials testing the health benefits of dietary antioxidants have reported rather mixed or negative results. Many clinical studies have not taken into account the nutrikinetic and nutridynamic nature of antioxidants. Further, oxidative stress is not only an inevitable event in a healthy human cell, but responsible for the functioning of vital metabolic processes, such as insulin signaling and erythropoietin production. In the light of recent physiological studies it appears more advisable to maintain the delicate redox balance of the cell than to interfere with the antioxidant homeostasis by a non-physiological, excessive exogenous supply of antioxidants in healthy humans.
    Critical reviews in food science and nutrition 02/2012; 52(2):162-71. DOI:10.1080/10408398.2010.499481 · 5.18 Impact Factor
Show more


26 Reads
Available from