Much ado about nothing

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

 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

Press Release from the Danish Society for Orthomolecular Medicine (DSOM)

November 12, 2002

The Danish Society for Orthomolecular Medicine (DSOM):
Rumours that antioxidants should have no general effect on secondary prevention of heart disease originates from The Heart Protection Study published in July 2002 in the magazine The Lancet. The study was financed by e.g. the pharmaceutical companies Merck & Co. and Roche Vitamins.

The purpose of the study was, among others, to investigate Merck’s cholesterol lowering drug Zocor’s effect on various parameters such as blood clots in the heart and heart disease, etc. The study included 20,536 high-risk patients – ie. patients with known cardiovascular disease or dispositions for this – eg. diabetes.

The patients were randomized to 4 groups, of which 5000 patients received 600 mg vitamin E, 250 mg Vitamin C and 20 mg betacarotene. 5000 patients received both Zocor and vitamins. 5000 patients received Zocor only and 5,000 patients served as a joint control group. This means that the part of the study containing the vitamin group plus a joint control group comprised 10,000 people and not 20,536 persons as stated elsewhere.

Not surprisingly, the main result of the study showed that Zocor had a positive effect even at very low cholesterol values, which undoubtedly significantly increases the indication range for Zocor.

However, there are several criticisms, apart from the fact that the number of trial participants is exaggerated:

  • Dosage of vitamin E and vitamin C are not proportional to each other. The two vitamins are closely linked in the antioxidant protection of the cell. If there is an excess of one vitamin, it can have a pro-oxidant effect.
  • One will usually not give more than 100 – 200 mg of Vitamin E. Vitamin C should be given several times a day or as a prolonged-release preparation.
  • Vitamin C, as a single dose in a dose of 250 mg will only have an effect for a few hours. The half-life of vitamin C is approx. 4 hours, i.e. that from a daily dose alone you can not expect an effect at all – rather the opposite.
  • Beta-carotene has previously been tried alone in a major trial for lung cancer and smokers. Here, it appeared that this vitamin had a prooxidant effect with a prevalence of lung cancer in smokers as a result. The Heart Protection Study has not been able to confirm such an effect of an incorrectly unbalanced dosage.

The results of the study also coincide with the results found in the HOPE study, namely that there was no secondary preventive effect when consuming individual vitamins.

  • You can not study the effect of individual vitamins on diseases that have taken decades to develop. Vitamins act as co-factors and as antioxidants, they are involved in a complicated interaction with the body’s own enzymatic antioxidants in a way that we do not yet fully understand.
  • Individual vitamins or random combinations of two or three individual vitamins should not be perceived as a medicine that cures a disorder in the traditional sense, but as a method that can strengthen the body’s own antioxidant defenses.
  • You cannot simplify and define 3 different vitamins in an illogical mutual dosage for antioxidants generally. The antioxidant system reduces oxidized molecules. This is done according to the thermodynamic laws. The individual steps in this process, of which there are many, depend on the redox potential of the individual molecule. For example, urate is part of this chain. Urate is not an antioxidant in the traditional sense in everyday speech but possesses antioxidant properties just like albumin. A generalization is therefore completely incorrect.
  • The individual may have several or individual nutrient deficiencies. It is therefore not correct to study the effect of individual vitamins on chronic diseases.

Only in the last year has it become common knowledge that a substance such as Homocysteine (indicator of low B vitamins) has the greatest significance for risk and heart disease.

The content of the B vitamins: B12, B6, and folic acid in our food has decreased significantly since the Danish Ministry of Food began systematic studies of these in 1993. Thus 24% to 50% of the male population is at risk of deficiency diseases. Despite the private Nutrition Council’s stubborn adherence to the opposite, the Ministry of Food, Agriculture and Fisheries in Denmark is aware of this, but states that they are simply keeping an eye on developments.

The iron content of e.g. oatmeal has been reduced by 10% within just the last 5 years. The website of the British Ministry of Agriculture reports a 50% drop in selenium intake compared to 1983 and today.

………………………

By: Per Tork Larsen, M.D., DSOM

(No references)

rum.ctsu.ox.ac.uk/~hps
www.heartprotectionstudy.com/heartprotection/heartprotection/index.jsp
www.akudoc.dk
www.iom.dk