Life Extension Magazine®

Issue: Apr 2000

In The News

Why some “Es” fail to work, progestin/estrogen combination increases breast cancer risk.

Scientifically reviewed by: Dr. Gary Gonzalez, MD, on January 2021.


Vitamin E has been extensively studied for its role in preventing heart attacks. Most studies show a significant reduction in coronary artery-related heart attack in people who supplement with vitamin E. Based on these positive reports, a 4.5 year study was conducted on a large group of people at high risk for heart attack because they already had cardiovascular disease or diabetes in addition to another risk factor. The purpose of this study was to ascertain if a soybean oil vitamin E supplement could reduce mortality or slow disease progression. This study was published in the January 20, 2000 issue of New England Journal of Medicine.

The results of this study showed that supplementation with 400 IU of alpha tocopherol acetate (from soybean oil) had no effect on cardiovascular outcomes compared to placebo. The researchers stated that one possible reason that this soybean oil vitamin E did not show any benefit might be because it was given alone, without other antioxidants that are known to have synergistic protective effects against cardiovascular disease.

The Life Extension Foundation has identified other reasons why this study failed to show a protective effect. First of all, the soybean oil-form of vitamin E used was a cheap kind often advertised for $1.99 a bottle (30 capsules) in pharmacies. Serious vitamin takers prefer cold-water dispersible dry powder vitamin E supplements in the form of alpha tocopherol succinate or acetate because the cold-water dispersible forms are efficiently absorbed even when taken on an empty stomach or with a low-fat meal. The non-cold water dispersible (oil) forms of vitamin E may be poorly absorbed unless taken with several grams of fats or oils. Most, if not all, of the high-risk patients in this study would be expected to be on low-fat diets and therefore may not have absorbed the oil-based vitamin E.

Cold-water dispersible vitamin E is twice as expensive as soybean oil E-acetate, but the cold-water dispersible forms are more efficiently absorbed. Both "acetate" and "succinate" vitamin E can come from natural sources. The importance to the consumer is how well the vitamin E absorbs into the blood stream. Cold-water dispersible vitamin E, whether in a succinate or acetate form, always comes in a white dry powder, while non-cold-water dispersible natural and synthetic acetate forms of vitamin E are always in a thick brown oil.

While 100 IU or more of supplemental vitamin E a day has been shown to reduce the risk of heart attacks in healthy people, those with pre-existing coronary artery disease often take 800 to 1600 IU a day, based on the pioneering work of the Shute brothers in the mid 1940s. Because of the severe disease states the people in this study were already in, they should have been given more than 400 IU a day vitamin E.

Most studies that seek to determine the efficacy of a drug or vitamin will measure blood levels of the agent being tested to verify patient compliance and absorption. This is critical because many agents do not properly absorb. This is especially true of E-acetate oil vitamin E capsules that should be taken with a high-fat meal for optimal absorption. In this study, there were no blood tests conducted to measure absorption of the E-acetate oil. There is also no indication that patients given the E-acetate oil were told to take it with a high-fat meal. Further, because of the severe disease states these people were already in, they may have been consuming a very low-fat diet. As was previously noted, there can be an absorption problem with E-acetate oil caps, while dry cold-water dispersible powder vitamin E supplements contain surfactants that enable them to be readily absorbed with or without food.


Another potential flaw in this study is that all participants were allowed to take a multi-vitamin supplement that could contain up to 100 IU of vitamin E. Since no blood tests where done to measure vitamin status, it could be that the placebo group was consuming a wide range of nutrients such as folic acid, vitamins B6, B12, B6, C and E. In other words, the placebo group may have fared as well as the group receiving the vitamin E because they were allowed to obtain adequate levels of cardiovascular-protecting nutrients independent of the study.

Still another concern with the validity of this study rests with the fact that these sick people were being given drugs that mimic many of vitamin E's known heart attack-preventing effects. One way vitamin E protects against heart attacks is to help prevent abnormal blood clot formation inside coronary arteries (anti-platelet action). Since both the vitamin E and control group were being given anti-platelet drugs, the beneficial anti-platelet effects may have been experienced in both groups and therefore, the placebo group may not have died at a greater rate than those taking vitamin E. Many of these people were prescribed "statin" cholesterol lowering drugs. Some statin drugs have antioxidant properties that help protect LDL cholesterol from oxidizing, which is another anti-heart attack effect of vitamin E. There were many other potential confounding factors relating to the drugs these sick people were taking that could have masked substantial components of vitamin E's beneficial effects, providing the vitamin was absorbed in the first place, which has yet to be determined.

The fact that vitamin E alone was used in this study is an example of the "one-drug" mentality that exists with conventional medicine today. Even though the researchers knew that other antioxidants could synergistically enhance the effects of vitamin E, they chose to conduct this long-term study using only a moderate dose of a questionable form of vitamin E. The article in New England Journal of Medicine did not reveal that the form of vitamin E used was alpha tocopherol E-acetate oil. The article only stated "vitamin E from natural sources." The Life Extension Foundation had to independently contact the researchers to ascertain what form of vitamin E was used. The researchers should have listed the form of vitamin E in the article, as this would have provided a key piece of information as to why the study failed to show any benefits.

The researchers state in their discussion that 400 IU a day of vitamin E is a high dose, when most alternative physicians recommend 800 to 1600 IU of vitamin E for therapeutic control of already existing cardiovascular disease. Since conventional cardiologists don't know that higher doses of vitamin E are required to treat cardiovascular disease patients, this article will have the unfortunate effect of causing some doctors to recommend against vitamin supplementation. This article, published in the prestigious New England Journal of Medicine, also provides a potent weapon for the pharmaceutical industry to dissuade heart disease patients from taking dietary supplements.

Progestin/estrogen combination increases breast cancer risk

In a study published in the Journal of American Medical Association, estrogen replacement with the concomitant administration of progestins was found to increase the risk of breast cancer.

Previously, when 90% of the world's data concerning hormone replacement and breast cancer was analyzed, it was determined that breast cancer risk increased with longer, recent use of HRT. These findings were more prevalent in lean women and with those who had less clinically advanced tumors. It was not determined what influence improved diagnostics had on these findings.

In the current follow up study, data from twenty-nine american screening centers was analyzed between the years of 1980 and 1995. A total of 46,355 postmenopausal women were studied, with an average age of 58. Data was obtained by responses to questionnaires.

Many women take progestins along with estrogen in order to lower the risk of uterine cancer associated with estrogen replacement. The women studied who took estrogen alone experienced a 20% higher incidence of breast cancer. However, women taking estrogen with progestin experienced a 40% higher rate. These rates were similar for women who received annual mammograms and for those who did not, but were not valid for overweight women. According to the study authors, with every year of HRT, the risk of breast cancer increases 8% for those using an estrogen-progestin combination and 1% for those using estrogen alone.

Concerning these findings, Journal of American Medical Association editorial writer Walter Willett remarked, "Although post-menopausal hormone use has important benefits, the study ... highlights the potential hazards and uncertainties that accompany such use."

"The commonly held belief that aging routinely requires pharmacological management has unfortunately led to neglect of diet and lifestyle as the primary means to achieve healthy aging."