Vitamin E: Heart Disease and Cancer Rates in High-Risk Older Patients

G. Douglas Andersen, DC, DACBSP, CCN

"The major finding of the HOPE trial including the initial trial and trial extension, is the lack of benefit for vitamin E in preventing cancer or major cardiovascular events after a prolonged period of treatment and observation. Furthermore, our studies raise concern about an increased risk of heart failure related to vitamin E."

The above quote made headlines around the world. The Heart Outcomes Prevention Evaluation (HOPE) was an international trial involving 267 centers and 9541 patients that lasted 64 months between December 1993 and April 1999. None of the patients were younger than 55 years old and their mean age was 66. The participants were in a group considered high risk for cardiovascular disease. This was defined as having a history of coronary artery disease, peripheral artery disease, stroke, or diabetes mellitus. 4761 patients took 400 IU of natural vitamin E daily for the duration of the study. 4780 participants took an identical placebo pill. The HOPE study was extended an additional 49 months from April 1999 until May of 2003. Called the Ongoing Outcomes, it was referred to as HOPE-TOO. 174 of the original 267 centers continued to participate. In the 174 centers, there were 3056 vitamin E patients and 3060 placebo patients left over from the initial HOPE trial. 2025 in the vitamin E group and 1969 in the placebo group agreed to continue the intervention. Please note that this study was double blinded. Neither the researchers nor patients knew who was taking the vitamin E.

Rather than give an opinion, a percentage, or an extrapolation like doubling the risk (see box), I thought that clinicians would prefer to look at the raw data when encountering patients' questions such as "Is vitamin E going to give me heart disease?"

Why I Dislike Hearing "Doubles Your Risk"
When I see or hear a report telling me my risk for something is doubled, I am always irritated at receiving spin. Because without raw data, doubling one’s risk means little. For example, increasing your risk from 1 out of a million to 2 out of a million doubles your risk as does increasing your risk from 1 out of 4 to 2 out of 4.

Total Patients Vitamin E Placebo
HOPE 4761 4780
HOPE-TOO 2025 1969

Cardiovascular Deaths Vitamin E Placebo
HOPE 482 475
HOPE-TOO 364 361
Total 846 836

Cancer Deaths Vitamin E Placebo
HOPE 156 178
HOPE-TOO 128 133
Total 284 311

Deaths from All Causes Vitamin E Placebo
HOPE 799 801
HOPE-TOO 620 604
Total 1419 1405

HOPE Cardiovascular Events Vitamin E Placebo
Unstable Angina 712 698
Heart Failure 641 578
Myocardial Infarction 724 686
Stroke 270 246
Total Events 2347 2208

HOPE-TOO Cardiovascular Events Vitamin E Placebo
Unstable Angina 565 547
Heart Failure 519 443
Myocardial Infarction 580 534
Stroke 208 191
Total Events 1872 1715

HOPE Cancer Incidents Vitamin E Placebo
Breast 25 29
Colorectal 69 54
Lung 69 96
Melanoma 15 18
Oral and Pharyngeal 9 18
Prostate 116 119
Total Incidents 303 331

HOPE-TOO Cancer Incidents Vitamin E Placebo
Breast 19 26
Colorectal 61 44
Lung 58 74
Melanoma 13 17
Oral and Pharyngeal 8 15
Prostate 91 101
Total Incidents 250 277

I predict this study will be used to advance the agendas on both sides of the supplement debate. It does appear that 400 IU of natural Vitamin E increases the rate of nonfatal heart disease in high risk older age populations. It also appears that 400 IU of natural Vitamin E decreases some cancers in high risk older age populations.

Knowing the raw data will give you insight as to how biased a given author is when this study is quoted to support an argument. For example, an author with an antisupplement bias can correctly state that in both the HOPE and HOPE-TOO trials there were more deaths from heart disease in people who took vitamin E than people who took placebos. Conversely, the author with the prosupplement bias can say that in both the HOPE and HOPE-TOO trials there were fewer deaths from cancer in those persons who took vitamin E. Looking at the overall death rates due to cardiovascular disease, cancer, and deaths from all causes, it appears that 400 IU of vitamin E is neither the toxic substance that some authors will claim it is, nor is it a panacea for health that other authors will state.


1Lonn, E., The HOPE and HOPE-TOO Trial Investigators. Effects of Long-term Vitamin E Supplementation on Cardiovascular Events and Cancer. JAMA. 2005; 293(11): 1338-1347.


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