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

 

References
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.

jama.ama-assn.org

Early old age without vitamins and minerals

January 15, 2007

Without sufficient vitamins and minerals, old age comes too early. This is because the organism ignores the future when resources are limited. If it needs to, it does what is best for the present.

Keep an eye on Bruce Ames, the American biochemist and professor from Berkeley University. He is the man behind the worldwide renown Ames test, a quick method of establishing whether or not substances in food and the environment are cancerous, which is to say whether or not they cause mutation. He is also the author of uncountable numbers of scientific articles and has proposed some very important hypothesises in the field of nutrition. In 1999 President Clinton handed him the “American Nobel prise,” the National Medal of Science, for his contributions. At an age of 78, Ames is still extremely active.

Ames is among those who insist that there is, in uncountable ways, relationships between shortages of vitamins and minerals and cancer, mutations, and aging. But earlier than others, he also sought to explain these relationships bio chemically. It is highly important that we turn to long term studies involving thousands of people for these biomechanical mechanisms to be tested. When Ames invented his mutation test, he simplified detection of cancerous substances with one blow. Long term animal studies became unnecessary. Now he also wants to make long term human studies unnecessary in the study of nutritional deprivation.

The relationship between nutritional deprivation and cancer has been documented with extensive references in last November’s Proceedings of the National Academy of Science. For example, mutations, cancer, and early aging are seen early in association with magnesium deficiency. Vitamin D deficiency is believed to be the reason for 29% of all cancer in men. There is a relationship between deficiency of n-3 fatty acids from fish oil and malignant melanoma (skin caner), between selenium deficiency and cancer, and between potassium deficiency and heart disease. Lack of the B vitamin folic acid, vitamin B12, thiamine, and niacin also are associated with mutations and cancer. Even iron deficiency leads to mutations.

If all of this, and more, is an expression of a causal relationship, then nutrient deficiency should naturally be combated. Deficiency is, as we all know, extremely widespread. We receive large amounts of carbohydrates and fats, but few vitamins and minerals. One in every two Americans receive less magnesium than recommended, 90% receive too little vitamin E, 30% receive too little vitamin C, and so on… and so on.

Mutations can wait
If these many nutrient deficiencies are really the reasons for cancer, aging, and mutation, than what is the explanation? According to Ames, cells, and therefore the organs that they compose, prioritise when they temporarily or permanently lack something. A cell which as a result of a deficiency cannot accomplish all of its tasks, choose, for example, to prioritise the production of energy over the reparation of mutations. Correspondingly, scarce resources cause the organism to prioritise the production of red blood cells over the production of white blood cells, which is to say over immune system maintenance. The principle behind this is the same as when blood is directed to vital organs, such as the heart and lung, after blood loss. The organism must survive now, even though the price is weakening in the long term.

Prioritising is nonetheless only one reason for mutation and aging. A more direct connection is that nutrient deficiencies cause problems for the cells’ energy factories, the mitochondria. They are weakened by vitamin B (biotin) deficiency, pantoic acid deficiency, riboflavin deficiency, B6 deficiency, among others. Without these nutrients, the mitochondria cannot produce the enzymes necessary for energy production. Without energy nothing works in the cell, including the defence against mutation

Ames and others are now trying to find out how much nutrients we need to hold the number of mutations to a minimum and to keep the our mitochondria intact. This is not easy, but it is easier than undertaking expensive, and in many ways, uncertain, decade(s) long population studies. Also, who would finance such expensive studies?

In recent years we have seen a number of studies of supplementary vitamins E and C, selenium, beta-carotene, and vitamin A. Many of these were poorly done, more have been misinterpreted, and some have been proven. Few have become wiser. Is this the way forward? Or has Ames again shown a better shortcut?

While we wait for better knowledge, we should, according to Ames, take reasonable supplements of vitamins and minerals. Everything points towards that this is wise. And there are no risks.

By: Niels Hertz, MD

Reference:
Ames B. Low micronutrient intake may accelerate the degenerative diseases of aging through allocation of scarce micronutrients by triage. PNAS 2006; 103:17589-94.

www.pnas.org

Magnesium benefits asthmatics

January 8, 2007

Almost everyone gets far less magnesium in their diet than people got in the past. It seems that this greatly worsens life for asthmatics. But the problem has hardly been investigated.

One has to take magnesium seriously. It is a vital mineral, but many people get far less than the 3-400 milligrams a day that are considered adequate. Before the industrialization, we got an average of approx. 500 mg a day (some have said 1,000). Today, many get less than 250.

Several reports in recent years have linked magnesium deficiency to asthma and allergies. In 1994, for example, an English study showed that the more magnesium asthmatics got, the better their lung function. Those who received 500 mg a day had 25% better lung function than those who received 400 – judged by the amount of air you can exhale in one second.

Asthma was not very common in the past. Today, it is a fearsome widespread disease. Approx. every tenth Danish school child has asthma. In Aberdeen and Philadelphia, every fourth child at the age of eight has it. The frequency in Denmark has more than tripled since the 1970s, and no one has any reasonable explanation. What if magnesium deficiency is part of the cause?

During an asthma attack, the bronchi contract so that the air can neither get out nor in – especially not out. But as early as 1912, the famous physician Trendelenburg – it was he who suggested that you should have your legs up in the air if the blood pressure drops – showed that magnesium has the opposite effect. It dilates the bronchi. It was on cows, but in 1936 it was also detected on humans.

Still, only two randomized studies have actually been made to investigate the effect on asthma. One (from 1997) showed that magnesium reduces symptoms. The second (from 2003) showed nothing, which was probably due to the patients receiving so much medication that there was nothing to improve.

Less allergy
Now a team of Brazilian doctors has made a third attempt. They studied 37 children and adolescents (7-19 years) with persistent moderate asthma and allergies. All received medical treatment in the form of an asthma spray with a bronchodilator in addition to adrenal cortex hormone. In addition, they had an acute-acting spray for use in aggravation.

In 18 of the children, this treatment was supplemented with 300 mg of magnesium daily for two months. The rest received placebo (“calcium pills”). Who got what, was decided by secret drawing of lots.

Magnesium helped. Those who received magnesium had significantly fewer days of asthma exacerbation during the two months (12 and 17, respectively). Despite this, they also had significantly fewer days in which to resort to the acute-acting spray (7 and 12, respectively). Although the experiment was small, the differences were statistically extremely reliable. In addition, those who were treated responded far less to the traditional skin prick tests used to examine for allergies. They actually became less allergic! Finally, one could directly measure that their bronchial mucosa was far less irritable.

The conclusion is obvious: Trendelenburg’s old discovery holds water with great certainty. But magnesium is a very cheap mineral (a prolonged-release tablet with 360 mg costs a little over a penny), which no one can patent. Who will pay for further research?

Niels Hertz, MD


Referencer:

1. Gontijo-Amaral C et al. Oral magnesium supplementation in asthmatic children: A double-blind placebo controlled trial. European Journal of Clinical Nutrition 2007: 61:54-60.
2. Britton J et al. Dietary magnesium, lung function, wheezing, and airway hyperreactivity in a random adult population. Lancet 1994;344:357-62

www.nature.com/ejcn/index.html
www.thelancet.com