The study authors acknowledged previous trials demonstrated heart health benefits associated vitamin C and E, but instigated the study because of what they perceived as a need to verify the benefits via a large cohort study.
The study ran for an average period of eight years and assessed nearly 15,000 male, American physicians aged 50 or over when the trial began in 1997. Five per cent had heart disease issues.
The randomised, double-blind, placebo-controlled study found vitamin E and C supplementation did not prevent heart disease.
“In this large, long-term trial of male physicians, neither vitamin E nor vitamin C supplementation reduced the risk of major cardiovascular events,” the authors wrote.
“These data provide no support for the use of these supplements for the prevention of cardiovascular disease in middle-aged and older men.”
The study drew criticism from the Washington DC-based industry trade groups, the Natural Products Association (NPA) and the Council for Responsible for Nutrition (CRN).
The NPA’s vice president of scientific and regulatory affairs, Daniel Fabricant, PhD, wondered which criteria had been employed to select the study’s dosage levels of 500mg for vitamin C and 400IU for vitamin E.
“On the second page of the study, it references nine pooled studies that when using 700 milligrams per day of vitamin C showed a 25 per cent reduction in the occurrence of cardiovascular disease,” Fabricant said. “Yet this study only used 500mg per day.”
Vitamin intake from food sources was not controlled and the fact the sample was taken from the medical fraternity, who were more likely to live healthily, confounded the study, he said.
“It is essentially a drug study but one without a positive control, which is necessary to ensure the experimental design can produce a positive result even if the intervention was unable to.”
The CRN’s vice president of scientific and regulatory affairs, Andrew Shao, PhD, was more positive, noting: “This study raises an interesting set of scientific challenges as to why the benefits found in observational studies have not been confirmed in this kind of trial.”
But he highlighted an ongoing industry bugbear with trials that sought to measure whether or not dietary supplements could cure or prevent disease when the function was much more about the promotion of health.
“Consumers should not take vitamins expecting that vitamins alone will prevent cardiovascular disease, but they should continue to take vitamins for the general health benefits they provide,” Shao said.
Participants in the ten-year trial were administered 500mg of vitamin C every day and 400IU of vitamin E every second day. Beta-carotene was also administered in doses of 50mg on alternate days but this was stopped in 2003.
The CV events being monitored were nonfatal myocardial infarction, total stroke, cardiovascular death, congestive heart failure, total mortality, angina, or coronary revascularisation.
CVD events were measured at 10.8 and 10.9 per 1000 people in both active and placebo groups
There was no adverse effect registered for bleeding including hematuria, easy bruising, and epistaxis as well as gastrointestinal tract symptoms such as peptic ulcers, constipation, diarrhea, gastritis.
There was also no increase in other adverse events such as fatigue, drowsiness, skin discoloration, rashes and migraine, hematuria, easy bruising, and epistaxis for both active vitamins E and C compared with placebo.
However they did note an increase in hemorrhagic stroke with vitamin E use.
Journal of the American Medical Association
2008;300(18):2123-2133. Published online November 9, 2008 (doi: 10.1001/jama.2008.600)
“Vitamins E and C in the Prevention of Cardiovascular Disease in Men: The Physicians' Health Study II Randomized Controlled Trial”
Authors: Howard D. Sesso, ScD, MPH; Julie E. Buring, ScD; William G. Christen, ScD; Tobias Kurth, MD, ScD; Charlene Belanger, MA; Jean MacFadyen, BA; Vadim Bubes, PhD; JoAnn E. Manson, MD, DrPH; Robert J. Glynn, ScD; J. Michael Gaziano, MD, MPH