New slander against antioxidants

March 13, 2007

A new article maintains that antioxidants cause death, but the article is based on a comparison of results from incomparable studies.

Once again a scientific article has created a commotion regarding antioxidants. It claims that they cause death. This has been heard, and disproved, before. Because of the common uncertainty regarding this subject, we are nonetheless forced to take a stand regarding this claim.

The man behind this claim is a Serbian professor from a university located in the town of Nis. One of the co-authors is a Danish physician who has, among other things, declared antioxidants to be poisonous and cancer causing on Danish TV. He even suggested that they are poisonous in the amounts found in vegetables.

The study is a so called Meta analysis. It combines as many old studies on antioxidants as possible and extracts a kind of average from their results. Small four week studies are blended up with larger studies which have gone on for up to 12 years. Studies where very small doses were used are blended up with studies on mega doses, studies using one antioxidant are blended up with studies on combinations of antioxidants (e.g. vitamin E, vitamin C, and selenium), and so on. Among the studies used, there are at least eight different combination treatments using vitamin E. This enormous mess alone causes the study to be somewhat questionable. One cannot calculate an average between apples and oranges.

This is not even the worst part. In an attempt to prove that vitamin E increases risk of death (the articles primary claim), the ignored studies where selenium was used together with vitamin E. The selenium studies often showed reduced mortality and lowered cancer risk. This was not good for the Meta analysis authors, it disturbed their theory. They eliminated 11 essential studies on vitamin E and selenium from the analysis.

Selenium was ignored, but that wasn’t enough. The still couldn’t prove that vitamin E is harmful. The numbers wouldn’t work. To solve this, the article uses the fact that the antioxidant beta-carotene, the yellow colouring in carrots, increases death rates in smokers. This is commonly accepted (although not completely certain). In two of the largest studies conducted on antioxidants, a very slightly increased death rate was found due to a combination of beta-carotene and vitamin E.

More peculiarities
Common sense lends to the conclusion that beta-carotene is the villain in these studies. This was known in advance. Combinations of vitamin E with e.g. vitamin C and/or selenium do not increase mortality. More likely the opposite is true. In the large and very thorough French SU.VI.MAX study, death rates in men fell by over a third when they received vitamin E and vitamin C as well as selenium (besides zinc and beta-carotene!). This introduced a new era because this was the first time in our part of the world that a large array of antioxidants was used in study; which is what most people recommend. The antioxidants in our food are an orchestra, not solo instruments. They must play together to work. In a Chinese study from Linxian the same thing was found: lower mortality after supplements of vitamins E and C, selenium, beta-carotene, and vitamin A.

But the article in question maintains that vitamin E causes death. The claim is built, along with the discussed “manoeuvres,” on the two aforementioned studies, because the other vitamin E studies are insignificantly small in comparison. In these studies vitamin E was used with beta-carotene, and vitamin E was blamed in the Meta analysis for the poor results.

This is like claiming that mineral water is deadly if someone dies after drinking water mixed with arsenic. This conclusion is insane. The arsenic is deadly, not the water. Even though A+B is dangerous, it can naturally not be claimed that both A and B are dangerous alone.

There are other peculiarities in the article. Among other things, in at least two of the studies used, mortality was calculated many years after the end of the study. This is comparable to blaming a traffic accident for back pain when the pain became apparent eight years after the traffic accident. This type of measure was apparently necessary to get the desired results.

It is very easy to make these arguments in a scientific journal. If not for the press, it would be ignored. The article is based on a comparison of a number of incomparable articles, and this makes it hardly worth the effort it takes to make it better. It has also been exposed to sharp criticism. It has been clearly dismissed by two unrelated statisticians and by a professor of nutrition at Harvard University, Meir Stampfer. Stampfer is world renown and among the leading figures in nutrition studies encompassing over 300,000 people. He says that he will continue taking his vitamin supplements, unfazed by the article. But he adds that the article can lead to misinterpretation of the information that we have.

This is unfortunately an all too real possibility. Not in the least because the analysis’s authors insistently do the same.

By: Niels Hertz MD


1. Bjelakovic G, Nikolova D, Gluud LL et al. Mortality in randomized trials of antioxidant supplements for primary and secondary prevention trials. JAMA 2007;297:842-857.
2. Virtamo J et al. ATBC Study Group. Incidence of cancer and mortality following alpha-tocoferol and beta carotene supplementation: A postintervention follow up. JAMA 2003;290:476-485.
3. Lee IM et al. Vitamin E in the primary prevention of cardiovascular disease and cancer. The Women’s Health Study. A randomized, controlled trial. JAMA 2005;294:56-65.

Vitamin E or false product description

November 12, 2004

Calculations on the basis of old studies leads to claim of increased mortality by antioxidants and vitamin E, but is in reality based on studies with beta-carotene.

Recently, researchers published a study on beta-carotene, but called it antioxidants. Now there is a new study of beta carotene, but this time it is called vitamin E. Both studies are so-called meta-analyzes, ie. calculations of previous research.

The two studies claim to show that respectively antioxidants and vitamin E increase mortality, but they are both based on the results of old beta-carotene tests. Since 1994, it has been known that beta-carotene can cause cancer and increase mortality in at least male smokers.

The latest meta-analysis originates from Johns Hopkins University in the USA. Here, the mortality rate in a total of 19 old treatment trials with vitamin E was investigated. Apparently, doses above 400 units per day slightly increased mortality, although it was decreased in the trial where the dose was the highest (2,000 units/day). There were 11 trials where more than 400 units were used per day. At a lower dose, there was a tendency for decreased mortality.

However, of the 11 trials, the so-called Heart Protection Study (HPS) from the year 2000 is by far the largest. In fact, so large that it completely dominates the calculation. In HPS, almost twice as many died as in all the other 10 trials combined – and more than four times as many as in the other trials with increased mortality. The problem with this is that in HPS, in addition to vitamin E, the treatment consisted of vitamin C and beta-carotene!

Of course, one cannot comment on the risk of vitamin E based on an experiment in which both vitamin E and C and beta-carotene were used. You can only comment on vitamin E and C and beta-carotene!

Also, in the trial in question (HPS), synthetic vitamin E was used. It consists of eight different chemical compounds, only one of which is found in nature. That makes it even more difficult to comment on vitamin E, which most people buy in its natural form.

There are many other objections to the new meta-analysis. If you e.g. arrange the numbers just a little differently, but still fairly, the excess mortality disappears entirely. That happens if you ignore the misleading HPS study and include trials using over 300 units instead of just over 400. That would be entirely plausible.

This and much else may be why several independent statisticians told the New York Times that they did not believe the conclusion.

One can debate whether there is a real need for these sometimes arbitrary concoctions of old experiments, which easily lead to misinterpretations. Far greater is the need for large-scale investigations into whether, for example, a combination of natural vitamin E and C prevents atherosclerosis in people who are not overwhelmingly atherosclerosis already. This is where one can expect an effect, but these experiments have not been carried out.

Sales of vitamin E are increasing in the United States, where many doctors in particular take it. The combination of vitamin E and C can be seen i.a. as a competitor to the tremendous expensive, but almost ineffective, prescription drugs for Alzheimer’s. According to a report earlier this year – also from Johns Hopkins – users of both of these vitamins have approx. 80% reduced risk of getting Alzheimer’s – compared to those who get only one of them or none at all.

Most recently, the Nobel laureate Louis Ignarro, based on his own experiments, strongly recommended the same combination as prevention against atherosclerosis.

By: Vitality Council


1) Metaanalysis: High-dosage vitamin E supplementation may increase all-cause mortality. Ann Int Med 2004;142.
2) Bjelakowic G, Nikolova D, Simonetti R G, Gluud C. Antioxidant supplements for prevention of gastrointestinal cancers: a systematic review and meta-analysis. The Lancet 2004;364:1219-28.
3) Ignarro L J et al. “Long Term Beneficial Effects of Physical Training and Metabolic Treatment on Atherosclerosis in Hypercholesterolemic Mice. PNAS 2004 (May 24).
4) Zandi PP et al. Reduced risk of Alzheimer disaease in users of antioxidant vitamin supplements. Arch Neurol 2004;61:82-88.
5) Gina Kolata: Large Doses of Vitamin E May Be Harmful. New York Times 11.11.04.