Healthy and Safe

October 25, 2007

There are over 480,000 published peer-reviewed research studies on food supplements or ingredients used in food supplements, and the vast majority of these show positive effects. There are only a small handful of studies that have shown negative effects, these generally being associated with high doses or synthetic forms of ingredients like vitamin A, beta-carotene and vitamin E.

In the case of vitamin A, there is no doubt that high doses of this fat soluble vitamin can be harmful and an upper safe level or maximum permitted level for this vitamin makes perfect sense.

There are three key studies showing negative effects of beta-carotene on diseased or high-risk patients, but these have all used synthetic beta-carotene, in the absence of natural carotenoid complexes found in natural carotenoid-rich fruits and vegetables which have been found to be potent cancer-fighting nutrients. Ironically, these natural ‘mixed carotenoids’ are disallowed by the Food Supplements Directive.

Finally, there are four key negative studies on vitamin E, all of them conducted with synthetic vitamin E, which comprises only one of the eight vitamin E forms found in nature, but in its esterified form. This form, alpha-tocopherol, the only vitamin E form allowed by the Directive, actually reduces the body’s absorption of gamma-tocopherol which is the key antioxidant form of vitamin E found in food sources.

By: Robert Verkerk, The Alliance for Natural Health, United Kingdom

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.

Again, uneasiness regarding the pill

July 31, 2006

The pill (contraception in pill form) drains the body of the antioxidants, vitamin E and Q10. This could mean that a supplement would make it much safer to take the pill.

More than 100 million women worldwide use the pill as contraception. The pill is believed to be remarkably safe, and it is easy to forget that it can have serious side effects. According to a Dutch report from 2003, users of the pill have a 3-6 times higher risk of developing blood clots in the veins, which is a dangerous condition. In addition, they have a 2-5 times higher risk of developing blood clots in the heart or of suffering from stroke. These numbers are the same for the modern forms of the pill, which have few other few side effects.

If the risk of disease is low, (because of being young and otherwise healthy) than a low percentage increased in risk does not so important. But why is there any increase at all? Light has been thrown on this question by researchers of the Albert Einstein College of Medicine in New York. They have proven that users of the pill have lower vitamin E and Q10 levels in their blood than women who do not take the pill. Vitamin E and Q10 are well known antioxidants.

This is nothing new. Already 15 years ago, researchers believed that vitamin E could reduce the risks associated with the pill. It was also known that the pill drains the body of antioxidants, which can be directly linked to an increased risk of blood clot formation. When one lacks vitamin E, the fats in the blood become oxidized, thereby stimulating the platelets to stick together causing the formation of blood clots. Logically, it was suggested that vitamin E should be combined with use of the pill.

The pill uses up the body’s vitamin E and Q10 reserves. This has been proven again, this time in a study where 15 users of the pill in their forties were compared with women in the same age group who did not take the pill. The differences found were statistically valid, and although this was a small study there were no doubts regarding the results. These results were known before the study was completed; the problem was that nobody had been paying any attention to them.

Unsolved problems
Why does the pill strain the bloods vitamin E and Q10 contents? The pill raises the body’s oestrogen levels. This is why the ovaries go into hibernation so that ovulation is inhibited. The body registers a hormone level high enough that the ovaries can take a break. Even normal (physiologic) levels of oestrogen stimulate the formation of free radicals and therefore cause an increased use of antioxidants. This has been shown in an American study of the cells which compose the inner walls of the blood vessels (endothelium cells). They also showed that free radicals resulting from the presence of oestrogen caused the cells to grow, causing the blood vessels to thicken. It is believed that this increases the risk of blood clots. It also indicates that antioxidants could prevent such side effects.

For practical purposes, women with an increased risk for side effects are advised not to take the pill. This includes women over the age of 35, women with high blood pressure, and so on. All women with an increased risk of blood clots should refrain from using the pill. This causes some amount of contemplation. Who knows if they are in the high risk group? Is their risk so low that a five fold increase in risk is acceptable?

Aside from these problems it is important to know that if you use the pill, your defence against the formation of free radicals is weakened. Even though this is well known, no one has, until recently, thought to reduce this risk with the use of antioxidants.

An important question follows: What is the long term prognosis for women who took the pill for many years when they were young? During the many years they took the pill, they had reduced levels of vitamin E and Q10 in their blood. In the short term, this increased the oxidation of the blood’s fats which increased the risk of blood clots. But does it cause problems in the long term like smoking and high blood pressure? As yet, we can only guess.

By: Vitality Council

1. Palan PR Magneson AT, Castillo M, Dunne J, Mikhail MS. Effects of menstrual cycle and oral contraceptive use on serum levels of lipid soluble antioxidants. Am J Obstet Gynecol. 2006 May;194(5):e35-8. Epub 2006 Apr 21
2. Felty Q. Estrogen-induced DNA synthesis in vascular endothelial cells is mediated by ROS signaling. BMC Cardiovasc Disord 2006 Apr 11;6:16
3. Ciavatti M, Renaud S. Oxidative status and oral contraceptive. Its relevance to platelet abnormalities and cardiovascular risk. Free Radic Biol Med. 1991;10(5):325-38
4. Saha A, Roy K, De K, Sengupta C. Effects of oral contraceptive norethindron on blood lipid and lipid peroxidation parameters. Acta Pol Pharm. 2000 Nov-Dec;57(6):441-7.
5. Tanis BC, Rosendaal FR. Venous and arterial thrombosis during oral contraceptive use: Risks and risk factors. Semin Vasc Med. 2003 Feb;3(1):69-84
6. Crook D, Godsland I. Safety evaluation of modern oral contraceptives. Effect on lipoprotein and carbohydrate metabolism. Contraception. 1998 Mar;57(3):189-201

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.

Vitamin C and E Protects Children Against Arteriosclerosis

September 1, 2003

Children and young people with increased cholesterol levels may reduce the risk of developing arteriosclerosis if they take a daily supplement of Vitamin C and E. This is the conclusion of a study published in Circulation, published by the American Heart Association.

15 children and young people of the age of 9 to 20 years were part of this study. Half of the children took a daily 500mg Vitamin C and 400i.e. (international units) Vitamin E supplement. The rest of the children took placebo. After 6 weeks the groups were switched.

After 6 weeks of active treatment the results showed a significant betterment of the inner wall of the artery. Vitamins alone do not reduce increased cholesterol, but the vitamins seem to be able to protect the blood vessels against sclerosis and thereby secure that the arteries remain their elasticity.

“This is the first time anyone has studied how antioxidants like Vitamin C and E can better circulatory function,” says the chairman of the Vitality Council, specialist doctor in general medicine, Claus Hancke.

“Even if it is a small study, the results are important for children with increased cholesterol. If they alternatively must have cholesterol lowering medicine for several years, the risk of serious side effects will be pretty high. It is therefore wise to give priority to diet changes and extra Vitamin C and E supplements as a first choice in therapy,” Claus Hancke says.

The American study also involved diet recommendations, but they did not follow those recommendations. Among other things the children got too much animal fat and too little fruit and vegetables. Therefore the doctors chose to combine the diet changes with Vitamin C and E supplementation.

The study is carried out at the University of California, under the supervision of Marguerite Engler, M.D.

By: Per Tork Larsen, DSOM

Circulation 2003;108:802