Dietary supplements for prolonging the life of the test did not stand up

Josh Mitteldorf, LIFE EXTENSION SUPPLEMENTS: A REALITY CHECK

Translated by Evgenia Ryabtseva, portal "Eternal Youth" http://vechnayamolodost.ruStephen Spindler, a professor of biochemistry at the University of California at Riverside, has been arguing for many years that taking dietary supplements, plant extracts and nutraceuticals by healthy adults is generally ineffective, while some of them can actually negatively affect life expectancy.

In his article Review of the literature and suggestions for the design of rodent survival studies for the identification of compounds that increase health and life span, published in 2012 in the journal AGE (in open access), almost 50 experimental papers on increasing the lifespan of mice were analyzed. Almost all of them ended in failure.

As part of one of the recently published works of the Spindler group (Influence on Longevity of Blueberry, Cinnamon, Green and Black Tea, Pomegranate, Sesame, Curcumin, Morin, Pycnogenol, Quercetin, and Taxifolin Fed Iso-Calorically to Long-Lived, F1 Hybrid Mice)  separate experiments were conducted to study the effects of extracts of blueberry, pomegranate, green and black tea, cinnamon, sesame, curcumin, morin, pycnogenol, quercetin and taxifolin with the usual caloric content of the diet of experimental mice. The authors claim that in previous works of other researchers, the increase in the life expectancy of experimental animals is explained not by the consumption of phytonutrients with anti-inflammatory and antioxidant effects, but by a decrease in the caloric content of the diet by replacing part of it with delicious, but not nutritious fruits.

One of the topics discussed in Spindler's articles is devoted to the fact that a low-calorie diet is the only mechanism that gives stable results, as well as to the fact that many of the approaches considered capable of increasing life expectancy implicitly limit the intake of nutrients into the body (which remains without the attention of researchers). However, there are a huge number of compounds that need such experiments, and each study in mice is so expensive that Spindler suggested using gene expression profiles to simplify the identification of candidates for further research.

Another approach is to simultaneously test a variety of compounds that are part of the "cocktail" to increase life expectancy. The argument in favor of this approach is the well–known fact that eating fruits and vegetables contributes to maintaining good health and longevity - see, for example, a recent article in The American Journal of Clinical Nutrition (Bellavia et al., Fruit and vegetable consumption and all-cause mortality: a dose-response analysis), in which based on 13-year observations of a cohort of more than 70 thousand people, a significant difference in life expectancy and the probability of death depending on the consumption of vegetables and fruits is shown.. Therefore, it is possible that in order to obtain tangible results, it is necessary to use a complex combination of biologically active substances.

At the end of last year, Spindler published in the AGE journal the results of his experiments (Lifespan effects of simple and complex nutraceutical combinations fed isocalorically to mice), in which commercial combination drugs were added to the feed of hybrid mice to "prolong life". The results obtained are sobering for those of us who take carefully selected dietary supplements every day, including for the author of the article who recommends taking such drugs on his website Aging Advice.

ResultsSeven of the eight graphs published in the article demonstrating the lifespan of mice look like this.

The graph shows that the dynamics of mortality of mice whose food was enriched with dietary supplements exactly corresponds to the dynamics of mortality of mice kept on a standard diet.

(The results obtained for the experimental group and the control group are almost identical. Therefore, if it were not for the confidence in the integrity of the researcher, he could be suspected of data manipulation. However, the author of this review is confident that in the case of Spindler, the reproducibility of the results is due to his competence in all aspects of working with mice and planning experiments. The staff of his laboratory have a lot of experience and apply methods of keeping, feeding, providing water, maintaining temperature and light conditions, which make it possible to eliminate most of the usual scatter of data for laboratory experiments. Even the selection of the mouse line is based on the results of in-depth analysis.)

One of the eight experimental groups demonstrated even a slight shortening of life expectancy compared to the control group:

The results obtained do not support the hypothesis that simple or complex combinations of nutraceuticals, including antioxidants, effectively delay the onset and slow down the progression of the main causes of death in mice. The results do not contradict the data obtained during epidemiological studies, according to which dietary supplements do not have a positive effect, and in some cases are even harmful to healthy people.

Which compounds have been analyzed?During the study, mice were divided into 8 experimental groups that received different combinations of dietary supplements, one control group that received a standard diet, and one "positive control" group that was kept on a low-calorie diet (and lived longer).

Some components of the combinations obtained by different groups coincided. The full list of components is very large, so only the main items are listed below:

• aspirin,
• alpha lipoic acid;
• blueberry extract,
• carnitine,
• carnosine,
• coenzyme Q10 (ubiquinol),
• dehydroepiandrosterone,
• ginkgo biloba,
• green tea,
• melatonin,
• various minerals,
• N-acetylcysteine,
• pomegranate extract,
• quercetin,
• resveratrol,
• S-adenosyl methionine,
• silymarin (milk thistle),
• vitamin A complex,
• B vitamins,
• vitamin C,
• vitamin D3,
• Vitamin E,
• vitamin K2.

Two of these compounds (metformin and melatonin) have reliably demonstrated their ability to increase life expectancy in earlier experiments on mice. Spindler does not comment on this fact and the question remains open. There is also reliable data obtained in human studies, according to which vitamin D and aspirin reduce mortality from any cause – see the review by Josh Mittendorf Vitamin D and Aspirin: Fast track to a longer life.

The study did not analyze the effects of prescription-only medications that had previously demonstrated the ability to increase the lifespan of mice, such as deprenil, metformin and rapamycin. The first two of them, according to the author, are quite suitable for use by most people.

Fish oil is responsible for shortening life expectancyWhy was there a shortening of life expectancy (by about 9%) in experiment No. 8?

Spindler suggests that the reason for this may be the reaction of mice to omega-3 fatty acids (fish oil). He cites data that has not yet been published, according to which fish oil taken separately reduces life expectancy. Another possible explanation is the well-known fact that some plant compounds have effects similar to those of mammalian hormones, and that an uncontrolled overdose of plant extracts can seriously disrupt metabolism.

Warning: Mice are not peopleSome aspects of the aging metabolism of mice are similar to what is happening in the human body, while others are very different.

One of the fundamental differences is that aging mice die mainly from cancer, while older people die from diseases of the cardiovascular system, cancer and Alzheimer's disease. In the body of aging mice, as well as in the body of aging people, the concentration of hormones that stimulate inflammatory processes that destroy healthy tissues and increase the risk of cancer increases (Belloni et al., Suppressing an Anti-Inflammatory Cytokine Reveals a Strong Age-Dependent Survival Cost in Mice // PLOS ONE, 2010). Therefore, the reasons for the ineffectiveness of ingredients with anti-inflammatory properties (such as omega-3 fatty acids and aspirin) are particularly unclear. Unlike humans, telomere shortening does not occur in aging mice, so we can hope that telomerase activators (such as extracts of silymarin, astragalus, ashwagandha, bakop) are beneficial for humans, despite being useless for mice.

The zero results partially obtained in the work of the Spindler group can be explained by the content of antioxidant vitamins in the tested combinations, which, according to existing data, generally reduce life expectancy. This can neutralize the positive effects of other ingredients that could have a positive effect when applied individually. The same applies to fish oil, which is part of one of the ineffective combinations.

What do we have in the end?The results of epidemiological studies indicate that small doses of nonsteroidal anti-inflammatory drugs (ibuprofen, aspirin), as well as large doses of vitamin D reduce mortality.

Experiments on rodents have demonstrated that melatonin, metformin and deprenil increase life expectancy. There is also data obtained by Russian scientists, according to which Skulachev ions (SkQ) can be added to this list, but this drug is not yet on the market.

There are also individual examples and theoretical background, testifying in favor of telomerase activators: astragalosides, silymarin extract and other plants, carnosine, etc. It is possible that these compounds are more effective against humans than against mice, but there is no reliable evidence of this yet.

All other data are speculative. Many of the dietary supplements may help some people and not help others. Spindler also emphasizes that the likelihood of harm to health is a concern. None of us would be pleased to know that the dietary supplements we take can actually shorten our lives.

03.04.2014