[Multivitamin Episode 2] Finland Shock? Copenhagen Shock? Mistakes in research on multivitamins | Dr. Esther Lyuh

about futility

Criticisms of multivitamins

Multivitamins, like other nutritional supplements, are criticized for the need to be taken. In a study of Los Angeles and Hawaii residents, three out of four found food was enough and one in four found multivitamin drugs helpful (Am J of Clin Nutr, 2007). Multivitamins contributed to an average increase of 8 percentage points in the percentage of nutrients lacking. In the United States, multivitamins are helpful for vitamin E, potassium, and calcium, which are insufficient for food, but vitamin A and iron are already consumed a lot as food, so there is a report that 10-15% of multivitamins may be consumed excessively

The most critical study of multivitamins, the first

But two of the most critical and shocking findings about multivitamins are: It is also a paper often cited by nutritionists. First, a multinational research institute led by the National Institute of Health in Finland conducted a study of 29,000 male smokers over the age of 50 for 5 to 8 years.  Surprisingly, taking 20 mg of beta-carotene from a multivitamin daily increased the risk of lung cancer by 18% compared to the placebo group. The results of this study were published in the media under the name Finnish shock. Until then, beta-carotene was known to help prevent cancer, such as lung cancer.

But found several problems with the study?

However, the results of this study were criticized for the unrealistically high dose of beta-carotene used in the experiment.  I was given 20mg daily because this dose is 10 times more than what is usually found in a commercial multivitamin. Another problem is that the beta-carotene used in the experiment at the time was synthetic. Beta-carotene has the same chemical structure but different isomers, meaning three-dimensional shapes, depending on whether it is synthetic or natural. Synthetic beta-carotene is trans, but natural beta-carotene is 20-50% cis. If it was a natural beta-carotene product derived from carrots or dunariella, etc., the results would have been different.

The most critical study of multivitamins, the second

The second study came in 2007 from Copenhagen, Denmark. A meta-analysis of 68 multivitamin-related papers published by researchers at the University of Copenhagen found that vitamin C and selenium neither increased nor decreased mortality, but beta-carotene reduced mortality by 7%, vitamin A by 16%, and vitamin E by 4%. Raised. The media dubbed the news the Copenhagen Shock and reported loudly that multivitamin consumption increased mortality.

But this also found several problems!

However, this result clearly reveals the disadvantages of meta-analysis, which statistically reanalyzes the results of other studies that have already been published, rather than conducting a new study.
First of all, the qualitative difference of the product was not considered at all. It is clear that poor quality products with excessive amounts of synthetic vitamin A or synthetic beta-carotene will produce poor results. In addition, the study subjects included many elderly participants suffering from serious diseases such as cancer or heart disease. Although it is clear that treatment received at hospitals and clinics, such as drugs and surgery, was more important than multivitamins in their deaths, we compared the increase and decrease in mortality by taking multivitamins alone. In addition, there were deaths by homicide or suicide during the study period, so the mortality rate was calculated including deaths unrelated to the result of nutrient intake. The age difference between the study subjects was also too large, from 18 to 103 years old. The health conditions of 18-year-olds and 103-year-olds are so different, but I tried to interpret the mortality rate as the same result. Also, the duration of administration and dose also varied too much. There are papers that administered once and observed for 3 months, and there are also papers that administered for 6 years and observed for 14 years.

Statistics to suit your taste

Even though the researchers turned the statistics to their liking, the initial analysis showed that vitamin C and selenium lowered mortality by more than 10%. Then, the research team arbitrarily subtracted 21 papers and ran the statistics again with only 47 papers.  The result is the Copenhagen Shock that many people know.

The attitude of some scholars with prejudice against nutritional supplements is concerning

I am concerned that some academics with a prejudice against nutritional supplements are trying to gain attention thanks to sensationalism in the media. The Copenhagen Study originally started with 815 papers. Here, 68 pieces were selected, and when the desired results were not produced here, 21 pieces were removed again. When the researchers re-analyzed the 21 papers that were excluded because of bias, the mortality rate was reduced by 9% in the vitamin intake group. Professor Ha Byung-geun of Indiana University in the United States criticized the Copenhagen study, saying, "The researcher's prejudice is so severe that it goes beyond the scope of medicine." Professor Meir Stampfer of Harvard University, a renowned nutritional epidemiologist, also said in an interview with the Associated Press that "the Copenhagen study was too disparate to draw appropriate conclusions."

Nutritional research needs to be done properly

A technique often used by research groups critical of vitamin supplements today is a meta-analysis, such as the Copenhagen Study. The task of statistically analyzing papers published by others. However, one of the big drawbacks of meta-analysis is that there is a saying 'waste in waste'. Translated literally, it means 'garbage in the trash'. It means that a well-designed study can be put together and a meta-analysis can reach a good conclusion. For a proper meta-analysis, the quality and dose of nutritional supplements must be similar, and the research conditions, such as the health status and age of the research subjects, must be analyzed by setting a similar range.  Ultimately, which papers are selected for analysis can have a decisive effect on the results of the meta-analysis. This means that prejudice, which selects only favorable papers to produce the desired results, can implicitly intervene.

Many doctors don't know much about nutrition.

Just as important as the prejudices of some medical communities, the problem is that many doctors are not very knowledgeable about nutrition. In medical school, the nutrition curriculum is very weak and medical students do not learn nutrition properly. When I was in medical school, I learned proper nutrition for about a week, and at least it was one credit. Many medical students don't value nutrition. A person's health cannot be achieved only with medications prescribed by doctors or surgery. Ignoring the most basic nutrition without properly studying it is not the right attitude as a doctor.

Why you don't have to skimp on research results

Because multivitamins are foods, not drugs, in nature, mortality and cancer rates associated with them will continue to fluctuate. Therefore, there is no reason to be happy with each of these results. I am not focusing on disease or death, but rather on improving functioning. The concept of making healthy people healthier.  It's easy to understand when you think of it this way. After taking care of fresh vegetables and fruits, I feel that my condition improves. Conversely, if you eat poorly, you will feel tired and frustrated. There is an answer to the experience that everyone can sympathize with in common sense.

Need to prove your experience?

It is a later task to observe tens of thousands of people for more than several years and determine what kind of disease occurs or not. The loophole of obsessive evidence-based medicine is right here. It's because it doesn't have to be verified with every paper to find out the truth. How will you prove these experiences? Any more reasons to prove it? Even in mathematics there are axioms that need not be proved. For example, 'Parallel lines never intersect in space'.

If you make up for the missing nutrients...

I think the same goes for nutrition. It is true that supplementing the lack of nutrients through nutritional supplements is more beneficial to health than starving in any form or eating poor meals It is not necessary to elucidate all the molecular mechanisms of these nutrients. It doesn't even have to come from a blood test. Changes in function do not come from blood tests, but are felt by myself. There's even less reason to prove a drop in mortality decades later. There is an answer to the refreshing feeling you feel after eating a good meal. That's why hundreds of millions of people take multivitamins every day.
Esther Lyuh, Doctor of Preventive Medicine, Seoul National University