Category: Criticism of dietary supplements

“Multivitamins”. What are they?

Claus Hancke

August 5. 2024

“Multivitamins have no effect”, “Multivitamins do not prolong life”, Multivitamins are a waste of money” and other similar headlines we have now seen in the past weeks in various
Danish newspapers and other media.

The observational study
All these headlines are based on an observational study from the United States that has been published June 26. this year.

An observational study is a study in which researchers “observe” different data, such as cohort studies and cross-sectional studies.

Observational studies are a relatively cheap research method because they do not require an intervention into the behavior of an experimental group. More simply, they involve observing how the selected data are distributed in relation to a certain behaviour such as taking a supplement and a certain outcome such as quality of life or mortality.

In the current study (Multivitamin use and mortality risk in 3 prospective US cohorts, JAMA Network Open. 2024;7(6):e2418729), data from three such observational studies were used. From the data, it was concluded that there is no significant effect of multivitamin use on life expectancy, which is the factor that has been focused on in the study.

Strangely enough, the focus is on life expectancy even though the authors themselves write in the introduction that the population’s motivation for taking multivitamins is to prevent disease.

But the incidence of disease does not appear in the data we see presented in the article in JAMA (Journal of the American Medical Association). The authors focus only on the length of life. They actually use the word mortality, but it is rather meaningless, since the mortality is approx.100% for us humans.

The investigation has been heavily hyped by the mainstream media, so we have to take it seriously., We need to clear away the worst misunderstandings.

The strange thing is that if this study had shown that multivitamins were healthy and good for us, it would not have been accepted for publication precisely because it was an observational study. Because such observational studies rank low on the scale of evidence in scientific studies.

The reason is that observational studies have quite a few sources of error, sources of bias. The data in the study come from people themselves, who have answered the questions that the researchers have asked. Moreover, the study is neither half, nor fully or double blinded, so it requires extreme objectivity from researchers. But for now, let’s ignore study quality, bias and the usual researcher bias when we talk about vitamins.

Let’s look at what these “multivitamin pills” really are.

When I write like that, it’s because these standard multivitamin pills from the supermarket are also not my cup of tea. Most multivitamin pills contain a wide range of vitamins and minerals, typically 100% of the recommended daily dose, in Denmark also called the RI (reference intake). This RI dose is far too small for some substances (vitamin C, vitamin D, selenium, etc.), while, especially for iron, it is far too large. Other ”multivitamins contain largely unabsorbable salts of some of the substances (magnesium, selenium etc.)

Briefly about iron
Those who have heard my lectures for the past 30 years also know that you should not buy vitamin pills with iron, unless you have been diagnosed with iron deficiency or are pregnant in the last trimester.

The body normally loses about 2 mg of iron per day. Since most multivitamin pills contain about 14 mg of iron, there is a theoretical net surplus of 12 mg of iron each day. And this iron accumulates in a protein, the phase reactant ferritin.

In this way, over the years, simply by taking multivitamin pills, you can build up a supply of iron in this ferritin. Iron is one of the most powerful catalysts for the formation of free radicals (ROS), which, in excess, can cause great damage to cell membranes and DNA in particular.

If a small child is brought to the emergency room because he has eaten a whole jar of ordinary multivitamin pills from the supermarket, then the doctor worries primarily about one thing; it is the intake of the large amount of iron.

Iron is easy and quick to raise the level in the body if you lack it, but incredibly difficult to get rid of if you have have too much. It must be done with intravenous treatment with substances such as Desferoxamine or EDTA, both of which bind iron. But it is difficult and slow. The age-old bloodletting method is almost faster.

Serum Ferritin is an important marker, and if it is above 200 µg/l, there is an increased risk of cardiac vascular diseases and cancer. So you have to be careful with iron. It is a double-edged sword.

Summa summarum: Never take multivitamin pills with iron, unless you have been diagnosed with iron deficiency in the form of low S-Ferritin.

Back to the study
When you consider that a cohort of people has been taking these multivitamin pills for years, then you suspect that they have obtained both good and bad ingredients. Honestly, it is completely impossible to come up with a qualified assessment when you (and the researchers) really have no idea what the people answering questionnaires have consumed.

I could easily formulate a multivitamin pill that mainly has a negative effect on the body. The pill will be cheap. With sufficient advertising money, it would probably be sold by the large supermarket chains, which look at price, discounts and shelf life.

I could use sodium selenite as the selenium. It is quite cheap, and I could declare it as selenium. It just that it’s hardly absorbed into the body. So the effect that can halve the incidence of heart disease and death, well, it will not occur.

I could use chromium chloride as chromium. It is quite cheap, but it is also quite inactive in comparison to chromium yeast, in which chromium chloride is converted to GTF chromium (glucose tolerance factor), which stabilizes blood sugar. Chromium chloride does not have this effect, but can be declared as chromium on the packaging, and then most people think that they get enough.

Every single one of the ingredients found in multivitamin pills can be declared in this way, even if the ingredient is in a (often cheap) form that has no positive biological effect. As I wrote above, you can easily construct a very cheap pill with a fine declaration, but without any kind of positive effect.

This is not to say that there are only such “junk pills” in the study. I just want to illustrate that when you have not defined the quality or content of what the study participants have actually eaten, it is more than difficult to form an overview of something as varied as the term “multivitamin pills”.

And when the product being studied is not a well-defined product, it is, to put it mildly, frivolous to conclude anything health related from the given data, and the authors are content with concluding, that they saw no difference in mortality risk in the two groups.

Let me end by saying that vitamins and minerals rarely help anything.
– You just mustn’t lack them.

The most important thing is, of course, a healthy diet, and where this fails in terms of content, you should supplement with vitamins and minerals of good quality.

Take care of yourself and others.

Claus Hancke
Specialist in general medicine

Much ado about nothing

Claus Hancke

February 12, 2019

One could justifiably use the above-mentioned Shakespeare title about a newly published article (1) that supposedly shows that antioxidant supplements reduce the effectiveness of chemotherapy and radiation therapy in postmenopausal women.

Please note that this assertion is by no means proven; there is much research that points in both directions.

The above-mentioned journal article does not contribute to clarification of the issue, not least because of the weak design of the study.

The data in the study came from interviews of postmenopausal women in two regions in Germany. The researchers used data from the “Mamma Carcinoma Risk Factor Investigation,” a study that was first published more than 10 years ago to report on the risk factors associated with postmenopausal hormone therapy.

Despite the known weaknesses of the interview study, the Danish TV2 reported the results of the study as a great sensation and with a headline that announced:

“New research: Dietary supplements can spread breast cancer.
German researchers have learned that antioxidant supplements can worsen breast cancer in women. The Danish Cancer Society is concerned.
For many years, there have been discussions as to whether antioxidant supplements are good for human health or not. And now a German study makes it clear that they are definitely dangerous for women with breast cancer.”

No, no, and no again.

There is no evidence for the dramatic TV2 news statements.

The German study does not make anything clear.

And the journal article authors’ own conclusion is much more cautious than the TV2 news report.

The journal article authors write:

“Our data do not support an overall association of postdiagnosis supplement use with prognosis in postmenopausal breast cancer survivors. Our results, together with other clinical and experimental evidence, suggest that during breast cancer treatment, antioxidants should potentiall be used with caution.”

In their journal article, the authors do not even advise against the use of antioxidants during chemotherapy and radiation therapy. They just urge caution.

Normally, German research results are shrugged off in Denmark, and interview-format studies get the same treatment. But, this time, the German interview study could be used to advance specific points of view, and so it was.

There are many things in this German study that grab the attention of the alert reader, and a close reading of the study reveals that the authors are biased, not least in their selection of earlier research on the topic.

An interview study, with no blinding of at all, is certainly not the most valid form of research and cannot be compared with prospective randomized controlled trials (RCT’s).

In the German study, the researchers asked some 2000 breast cancer patients whether they took antioxidant supplements before and/or after the time of their diagnosis with breast cancer and/or during their chemotherapy and radiation therapy.

The women in the study were to answer yes if they had just taken one or another supplement three days a week for a year at a given point in time. A “current user” was any woman who used supplement postdiagnosis within the 6 months before the first follow-up interview.

The term “supplement” and the term “antioxidant” are used quite sloppily but with a noticeable consistency. Whenever the researchers discuss the study, the usage, or the statistics, they use the term “supplements.” Whenever they discuss the chemotherapy or the radiation therapy, however, they use the term “antioxidants” without specifying what the term “antioxidants” covers.

In other words, the researchers have had to extend the definition of antioxidants with other supplements in order to achieve sufficient statistical power and thereby just barely sneak over the line into statistical significance.

About this, the authors write in their article:

“The main exposures of interest included postdiagnosis use (no postdiagnosis use, postdiagnosis use, current use) of any type of supplement; specific supplements, such as magnesium and calcium; and supplement group, such as antioxidants, in which there was adequate statistical power to conduct analyses. Only a few women reported postdiagnosis use of multivitamins, vitamins A, C, E, zinc, and selenium, and therefore they were collectively evaluated together as antioxidants in all of our analyses.”

Above and beyond the fact that the researchers have jumbled everything together in a big group that they call “antioxidants,” there is also a total lack of information about daily dosages, single dosages, and preparation types.

This study has a weak design and has unclear results. Therefore, the authors are careful to settle for a cautious conclusion, which speaks for itself.

The misinformation occurs when the Danish media then trumpet the study conclusion as the definitive truth.

Any serious researcher would avoid making such bombastic statements.

Litt:

  1. Jung AY et al. Antioxidant supplementation and breast cancer prognosis in postmenopausal women undergoing chemotherapy and radiation therapy. Am J Clin Nutr 2019;109:69–78.
  2. Flesch-Janys D, Slanger T, Mutschelknauss E, Kropp S, Obi N, Vettorazzi E, Braendle W, Bastert G, Hentschel S, Berger J. Risk of different histological types of postmenopausal breast cancer by type and regimen of menopausal hormone therapy. Int J Cancer 2008;123(4):933–41.

Contradictions about vitamins

Claus Hancke

 April 26, 2012

One may wonder about the Danish newspapers’ poor interest in the latest vitamin report. First of all, the report predicts dead to those who take vitamin pills, secondly, the turn-over for vitamins is one and a half billion kroner a year. The subject must interest many.

Here the report itself will not be discussed. It is already commented. On the other hand, attention must be paid to a very serious issue concerning the marketing of the report: The contradictory statements that a prominent researcher has used the report to make.

The statements are from chief physician Christian Gluud from Rigshospitalet. He has previously said peculiar things. It’s hard to forget how he on television declared antioxidants (like vitamin E and vitamin C) to be carcinogenic, even when they occur in fruit and vegetables. However, in fruit and vegetables there was, he believed, “a lot of other substances that might either correct the potential damage caused by the antioxidants or that could completely neutralize them.”

You might consider this amusing statement the next time you eat broccoli. It is thus an antidote to vitamins, you are eating!

Currently, Gluud said on TV that his latest study, which combined the results of different trials, is based on trials with commonly recommended vitamin doses. And yet, in almost all trials, there were used from five to twenty times the recommended dose or more.

Gluud has further said (the news program Deadline 2.4.2012) that his group has revealed that, for example, the antioxidants Vitamin C and selenium are directly life threatening, as they increase mortality by 4%. And yet, his report frees both of the two antioxidants for this accusation.

In the TV2 news (22.3.2012) Gluud said that “it’s quite common vitamin pills in very common doses that give the increased mortality.” But in an interview with Medwatch.dk he said the opposite: He could not comment on that subject – that multivitamins increase mortality – because no one had studied it!

If you ask chief physician Gluud, you may obviously get the answer that his current state of mind indicates. One moment, common vitamin pills are dangerous poisons, the next, it is not known, and at one time, selenium and vitamin C are poisonous, but at another time and towards another audience – those who read the report – they are harmless.

The contradictions do not prevent Gluud from hoping that the report will have “a practical and industry related consequence,” as he says. What that means is easy to understand. Gluud is/has been chairman of a lobby group that has sought to influence the European Commission to prevent the free sale of vitamins. They must be made into drugs, which in practice will push small vitamin companies out of the lucrative market, which alone in Europe is more than $ 20 billion a year.

When a researcher is politicizing, he invariably throws a dubious light over his research, justly or not. Worse, however, is when the researcher is facing the public, on a topic of great importance, against better knowledge.

In doing so makes him disqualified.

By. Niels Hertz, M.D

New slander against antioxidants

Niels Hertz

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

False Propaganda Against Vitamins

Niels Hertz

November 30, 2005

A frightening warning in an article in the Danish newspaper, Ekstra Bladet, claims that people will get sick from taking Vitamin B and injure their hearts by consuming Vitamin E. These claims are twisted and false.

Condescending evaluations of vitamin supplements are quite common. They rarely come from experts, but often from people who know something about something else and therefore think they know something about everything.

As a rule, it is stated that the vitamins only provide expensive urine and do not help against anything at all. Sometimes this message is spread rather too thickly.
The vitamins are poisonous! As the other day in a large published article in the newspaper Ekstra Bladet: You get sick from nutritional supplements, the headline stated. Further down, it became clear that you would not only get sick. You would die!

Whenever these kinds of statements appear, people get scared. They cannot imagine that anyone will write anything in Ekstra Bladet if it is not true. But unfortunately there are writers who don’t bother with that. This is evident from the mentioned article, which is mainly based on two gross, false claims. Here we comment on them in reverse order.

“The last new thing was the B vitamin folic acid, which should also be able to protect against heart disease. Recently, a large Norwegian study showed that folic acid did not make users less prone to heart disease. On the contrary, they got sick from the pills”.

Is that right? No. It is wrong. In the Norwegian randomised trial (it was called NORVIT), approx. 900 people who had had blood clots in the heart were supplemented with 0.8 mg of folic acid per day for 3-4 years. The table shows the relative mortality and incidence of heart clots in those who received folic acid and those who received inactive pills (placebo.)

……………………..………..……Folic acid……Placebo
Blood clot in the heart…….57,9…………….59,2
Total mortality………………….28,7…………….31,7

As seen, the overall mortality was 9% lower if folic acid was given instead of placebo. The risk of blood clots was also reduced. How does that agree with the fact that people “got sick (meaning heart disease) from the pills”? The answer is that it is not true. Admittedly, none of the differences were statistically significant. It was a trend. But that is not the same as the study showing the opposite of the trend.

And now to the first claim. It is about vitamin E. It was claimed that vitamin E should protect against heart disease, it says, but “when the major scientific studies came, it turned out that it… gave… heart failure, bleeding and an increased risk of dropping dead”.

Heart failure. That claim must come from the HOPE-TOO study, the only one of the many studies with a total of well over 100,000 participants in which heart failure has been found to be caused by vitamin E treatment.

4,000 people with severe atherosclerosis participated in HOPE-TOO. Those who received vitamin E (400 IU/day) had slightly more often weakened heart. The difference was statistically uncertain, i.e. that it could be accidental. The absence of heart failure in all the other studies suggests the same.

On the other hand, a slightly reduced risk of lung cancer was found in HOPE-TOO, and it was reliable. But since this has not been found in other studies either, it is unreasonable to mention it. It could be random anyway.

Another peculiarity of HOPE-TOO was that even though the participants were given 25 times the recommended amount of vitamin E, it could not be seen in the blood tests. On average, the participants had very little vitamin E in their blood, despite the large supplements. The concentration in the blood (17.6 mmol/l) was even at the lower end of the normal range (12-42 mol/l). Either the participants have not taken the vitamins, or they have e.g. taken them on an empty stomach so that they were not absorbed from the intestine. So where does the vitamin E study end up?

In other words: Here a single, guaranteed misleading, result from one small experiment is misused – as “fact”. It is cheating and distortion. And for the record: That you should start bleeding, let alone die from vitamin E in the mentioned doses, is out of thin air. In contrast, the vitamin prevents, in animal experiments, gastric bleeding caused by aspirin.

Professor Maret Traber, Oregon State University, is considered one of the world’s leading vitamin E researchers. She recommends vitamin E for a number of chronic health problems, including heart disease. Louis Ignarro, who received the Nobel Prize in 1998 for his research on blood vessels, unequivocally recommends vitamin E and C for the prevention of atherosclerosis. It works, he says.

Of course, what even such big celebrities think is no argument in itself. It is the substance that counts. Yet. If you are free to choose your advisers, you are likely to prefer the most knowledgeable – and the most reliable.

By: Niels Hertz  MD

References:
1. A. Astrup. Du bliver syg af kosttilskud. Sund og Slank. Ekstra Bladet. 26.11.05.
2. The HOPE and HOPE-TOO Trial Investigators. Effects of long-term vitamin E supplementation on cardiovascular events and cancer. JAMA 2005;293:1338-47.
3. Bonaa KH. NORVIT: Randomized trial of homocysteine-lowering with B-vitamins for secondary prevention of cardiovascular disease after acute myocardial infarction. Program and Abstracts from the European Society of Cardiology Congress 2005; September 3-7, 2005; Stockholm, Sweden. Hot Line II. Iflg. Linda Brooks. NORVIT: The norwegian vitamin trial. Medscape Sept. 2005. (Not published in printed media.)

Ridiculous vitamin pills?

Claus Hancke

June 21, 2005

In (Danish) Morning-TV they laugh about the Americans’ enriched foods. But American researchers take vitamins serious.

Now, the TV News channel TV2’s nutrition expert, Orla Zinck, has once again been on morning TV. He had returned from the United States, bringing some of the American’s ridiculous, vitamin-enriched foods. There is of course plenty of healthy food.

The light ironic tone remained. You could understand, for example, that all you get from taking extra vitamin C is severe diarrhea. You have to stay permanently in the toilet. It’s not true, but it sounds funny. And when you ridicule what you oppose, you make it sound like you’re right ….

Elsewhere in the world it is taken a little more seriously. Below follows what is thought at one of the world’s most recognized universities, Harvard University in the USA. Harvard has an official website on vitamins: www.hsph.harvard.edu/nutritionsource/vitamins.html. It is intended for e.g. doctors, who can probably assess the seriousness a little better than the majority of Danish Morning TV’s viewers.

The website opens with a statement: “If you eat healthy, do you need to take vitamins? Not many years ago, most experts would have answered emphatically “No”. Today there is solid documentation that a daily vitamin pill makes sense for most adults”.

But what new has happened? asks the article. Yes, it has been discovered that vitamins do not just prevent deficiency diseases such as scurvy and beriberi. Several of them are also likely to prevent heart disease, cancer, osteoporosis and other chronic diseases – if you get more than what is needed to avoid deficiency disease! The Harvard website concentrates on this new knowledge.

One section is about the B vitamin folic acid. It appears that folic acid not only prevents atherosclerosis and heart disease, but also cancer (in the colon and breast). Apparently it also negates the greatly increased breast cancer risk that women get from alcohol in even moderate amounts.

In the US, many foods are fortified with folic acid, but the article supports that you also take supplements so that you reach at least 400 micrograms per day. “Vitamin supplements are becoming more and more important”, it says.

Vitamin B12 is recommended in a daily dose of 6 micrograms, so far more than is normally recommended. It is mentioned that many elderly people have a B12 deficiency and, as a result, impaired memory. They may be disoriented and perhaps hallucinating in addition to having sensory disturbances in the feet. Sometimes people mistakenly think they have Alzheimer’s.

Regarding vitamin C, it is said that a pattern is emerging regarding the effect, and “as more knowledge is gained, an intake of 2-300 mg per day seems to be a goal worth striving for” , is it called. This is 3-4 times as much as Danes get in their diet and twice as much as in a regular diet, supplemented with a multivitamin pill.

Vitamin E is recommended in a dose of 400 units – or more – per day. It is 20 times as much as in the diet or in a multivitamin pill. This will very conceivably prevent heart disease, it is said.

Regarding vitamin D, it is mentioned that the optimal intake is 25 micrograms (1,000 units) per day. That is five times what is in a “full daily dose” vitamin pill. The purpose is to prevent the tendency to fall, osteoporosis and presumably cancer.

Through Danish TV2’s Morning TV, you get the impression that only uninformed people take vitamin pills, and it was made into something that was a bit laughable in the broadcast.

But the experts from one of the world’s leading universities, from which a stream of vitamin research emanates, think there is nothing to laugh about.

By: Vitality Council

References:
1. (Danish) Good Morning TV, 16 June 2005.
2. Harvard University, USA; official website about vitamins:
www.hsph.harvard.edu/nutritionsource/vitamins.html

The Emperor’s New Clothes: HOPE-TOO

Claus Hancke

April 5, 2005

Reputable American researchers claim that even large amounts of natural Vitamin E do not benefit established atherosclerosis. But their study do not reveal it. The participants got almost no Vitamin E.

Perhaps somebody have heard about the praised American HOPE study from 2000. It was to reveal that natural Vitamin E would not make any difference for people with atherosclerosis. This was a disappointment, and with it the issue could then have been dismissed.

That is not how it went. The HOPE study, which lasted 4,5 years and included 9,000 participants was prolonged with 2,5 years. They wanted to be absolutely sure, they said. In the follow-up study called HOPE-TOO only 4,000 people participated. Some did not want to participate, others had died, and others only wanted to be examined, but did not want any medication.

Half of the participants took 400 units natural Vitamin E daily (alpha-tocopherol), while the rest took placebo. They certainly had serious atherosclerosis: Every other one had had a heart attack, just as many suffered from angina pectoris (atherosclerosis ), and more than every third had diabetes.

The HOPE study showed that Vitamin E did not cause more or less cancer, more or less heart attacks, strokes, deaths or anything else. HOPE-TOO showed the same result, though with a single addition: Those who took Vitamin E slightly more often had heart failure; that is to say a decreased functioning of the heart.

The difference was so small that it could very well have been coincidental, even though it was statistically significant. Nevertheless the authors took the opportunity to strongly warn against dietary supplements. But yet they might as well have taken the opportunity to recommend them. They found that Vitamin E protected against lung cancer!

This finding, which was also statistically significant, was rejected, as an “error.” This conclusion was preceded by a lengthy discussion, in which reference is made to studies with beta-carotene, which as we all know, is something completely different.

No clothes on
But there is a far more serious surprise, which totally overshadows this biased opinion: During the whole study the participants did not have any more Vitamin E in their blood than all other people, who do not take supplements. The average value was 17,6 μmol/l. The normal value is 12 – 42. Despite the Vitamin E they only just managed to get their minimal need covered.

Before the study the participants actually had even lower values, averaging 10 μmol/l. This fits well with the fact that they were seriously ill, overweight heart patients who were kept on a low fat diet. A low fat diet may lead to deficiency of vitamin E.

Here we may also find the explanation of the low blood values. Vitamin E can only be absorbed from the intestine when fat is present. If you eat non-fat foods you might as well not take Vitamin E, even when you take 20 – 40 times the recommended dosage.

One is reminded of the Emperor’s New Clothes. HOPE-TOO has no clothes on. It claims to examine the effects of mega doses of Vitamin E, but the participants are only seemingly getting it. Strangely enough nobody has pointed out this almost ridiculous mistake before. In particular one wonders, why the authors themselves have not seen this mistake. Could it be that they do not know the normal values of Vitamin E in the blood?

This is not completely out of the question although it sounds strange. There are many examples of superficiality in scientific research. You do not have to look any further than the official commentary in the same issue of JAMA, which published the HOPE-TOO study. Here doctor Greg Brown by and large agrees with the conclusion of the study. He was also in charge of a similar study from 2001, which was supposed to show if antioxidants prevent atherosclerosis in the coronary arteries. This study concluded that antioxidants did not prevent atherosclerosis, even though the figures showed in black and white that the antioxidants halved the growth of atherosclerosis in the coronary arteries, compared to placebo.

By: Vitality Council

References:
1. The HOPE and HOPE-TOO Trial Investigators. Effects of long-term vitamin E supplementation on cardiovascular events and cancer. JAMA 2005;293:1338-47.
2. B Greg Brown. Is there any hope for vitamin E? JAMA 2005;293:1387-90.
3. Greg Brown et al. Simvastatin and niacin, antioxidant vitamins, or the combination for the prevention of coronary disease. N Engl J Med 2001;345:1583-92.

jama.ama-assn.org
content.nejm.org
www.iom.dk

Folic Acid is Still Healthy

Claus Hancke

December 11, 2004

New media storm has no basis in the scientific data. To the long list of cheap and trashy attacks on dietary supplements another one can be added for folic acid, which is a recent hit-and-run victim of the Danish newspaper B.T. with its screaming headline: ”Supplement can cause cancer.”

To make such a sensational claim, this tabloid ignored the authors’ very clear statement that it may only be a statistical fluke. But we have seen this kind of cut-and-slash media coverage before.

The article actually covers an old study from 1967, which was dug up from its grave and published in the British Medical Journal. [1] It seems that some 3,000 women participated in this study, which was not double-blind controlled.

Instead, the supplements were given to the subjects using six different tablets, separately colored, and taken from numbered drawers. Of these 3,000 women, 31 died from breast cancer during the 37 years that had passed, and of these 31, 6 women got 0.2 mg folic acid, 8 got 5 mg folic acid, and 17 got a placebo.

Clearly, no statistical certainty follows from this result, which means that it may only be an accidental incident. The study was supported financially by the pharmaceutical company, GlaxoSmithKline.

As mentioned, the authors themselves stated that the result may be accidental.

Many earlier scientific studies had shown the contrary to be true. In fact, the official comment by the professors Oakley and Mandel in the British Medical Journal [2] clearly dissociates them from the media-sensationalized conclusion, when they write that these earlier studies taken together actually demonstrate that higher supplementation of folic acid would decrease, rather than increase, the risk of cancer.

Furthermore, they draw attention to the fact that every single year folic-acid enrichment of American foods alone saves more people from blood clots in the brain and heart than the number of people dying from traffic accidents in the USA.

Be wary of this study, which is old. Its proponents are trying to have their cake and eat it too because when old scientific studies speak of the benefits of dietary supplements or natural medicine, they are often accused of being based upon an ”old standard,” and of not ”living up to the present standard.”

In decency the same can be said about old studies that are negative towards dietary supplements. These days a lot are dragged out from the old moth bag.

The problem is not so much these old studies, as it is the media, which smell sensationalism and thereby frighten the population from taking these supplements that are so important, when taken properly. But proper use demands information, and the population is not allowed to be informed.

By: Vitality Council

References:
1. Charles D, Ness AD, Campbell D, Smith GD, Hall MH. Taking folate in pregnancy and risk of maternal breast cancer. BMJ 2004:329:1375-6.
2. Ockley GP, Mandel JS. Commentary: Folic acid fortification remains an urgent health priority. BMJ 2004;349;1376.

bmj.bmjjournals.com
www.iom.dk

Vitamin E or false product description

Claus Hancke

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

 

References:
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.

A Dangerous Cocktail

Claus Hancke

October 3, 2004

Politicizing researchers and lazy journalists are a dangerous cocktail.
It is very disgraceful that the Danish Radio’s TV news presented such a one-sided story about antioxidants, as happened at 6:30 p.m. yesterday, where it declared without any reservation that 9 people out of 1,000 taking antioxidants will die from them!

Just the day before, the Danish (state owned) Radio / Television received a press release from the Vitality Council, which was criticizing the story and emphasized that possible harmful effects can only be caused by taking beta-carotene in large (therapeutic) dosages.

This old news can in no way be used to generalize about other antioxidants. The postulated general overmortality refers to two studies, in which beta-carotene was used in such great amounts that the test persons became yellow.

The Vitality Council also emphasized in its press release that according to the Lancet study, selenium, a potent antioxidant, is able to halve the risk of several kinds of cancer. This result was not at all mentioned in the TV news.

Furthermore, even the official comment in The Lancet dissociated from that which was the only extract on TV from the study: The postulated overmortality. The Lancet comment is written by two statisticians, who are seriously criticizing the statistical preparation of the material, and they state that the conclusion about overmortality is not convincing.

Another critical point out of many is that the Cochrane group removed a study on selenium, which it had announced as being a ”high quality” study, before the calculation on average.

The reason given for removing the study was that it would be given more weight in the random-effects model than in the fixed-effect meta-analysis. The removed high-quality study showed that selenium clearly reduced mortality!

It is not very good science to ignore figures that you do not like.

The TV news journalists have been hunting for some sort of scandal and one-sidedly accepted the very dramatic statements of Christian Gluud, M.D., which went much further than what the study material could ever support.

The Lancet has saved its skin by its serious comment, but the writers have cast a bad shadow over the Cochrane institution.

By: Vitality Council

References:
1. TVA 2.nd October 2004, 6:30.
2. Press release from Vitality Council 1.st October 2004.
3. Goran Bjelakovic, Dimitrinka Nikolova, Rosa G Simonetti, Christian Gluud, Antioxidant supplements for prevention of gastrointestinal cancers: a systematic review and meta-analysis, Lancet 2004;364:1219-28.

www.lancet.com
www.cochrane.dk/index.htm
www.iom.dk