Sunday, October 16, 2011

Dietary Supplements (Vitamins and Minerals): Killers or Life Extenders?

     This blog was triggered by an article in a medical journal and the subsequent media coverage. The article is "Dietary Supplements and Mortality Rate in Older Women, in Archives of Internal Medicine, Vol 171, (#18), Oct 10, 2011, pp 1625-1633. I also refer my readers to a blog I published in 2009 entitled "Nutrition".

     Let us begin with some basic definitions. A vitamin is a molecule that is necessary/essential for human life, but which our body cannot synthesize. For instance, neither humans nor guinea pigs have the enzymes necessary to synthesize ascorbic acid, aka Vitamin C, but all other animals can synthesize it. So only we and the guinea pig can get scurvy. The vitamins we need are present in our food if we eat a "well-balanced" diet, by definition, This includes Vitamins A, the whole B complex (1,2,6,12), Vitamin C,D, E, and folic acid.,  There are also eight amino acids essential for the synthesis of human protein, three essential fatty acids, and a host of elements (iron, iodine, calcium, cobalt, magnesium,copper, zinc, selenium,...) that we must ingest. If we ingest too little of the vitamin we get ill (scurvy, night blindness, pernicious anemia, iron-deficiency anemia, ...). The question is if too much of a vitamin or a supplement is injurious to our health. Very few studies have addressed this question, and our beliefs are not a substitute for clinical studies. Also, it would not be ethical to deliberately overdose human subjects, so we are left with experiments of nature, or retrospective diet histories.

     We do know that an excess of the fat-soluble vitamins (A,D, and E) is injurious to our health.Cod liver oil contains vitamin D and a daily spoonful is probably OK, but eating a polar bear's liver has given Eskimos vitamin D toxicity and even caused death. We also cannot generalize from animal studies: chromium and selenium can help control a lab rat's sugar level but there is no evidence than these elements can be used to treat or prevent diabetes in humans. We must always remember that ALL chemical substances are poisonous; it is only a matter of dose (digitalis, opium, water, salt, iodine, etc.).

     Let me first remind my readers that only animal cells contain Vitamin B-12 (cyanocobalamin) because only animal DNA requires Vitamin B-12 as a cofactor (along with folic acid) for its enzymatic synthesis. Vegetable DNA does not require Vitamin B-12 for its synthesis, and therefore no vegetable cells contain this vitamin. In other words, if you ate only vegetables (and this excludes fish) you would die from Vitamin B-12 deficiency after first suffering irreversible brain and peripheral nervous system damage. Vegetarians must take B-12 supplements, which may be synthesized in a lab, since the human body's enzymes have no way of determining the source of the Vitamin B-12 that it needs and uses.

     We also know from "experiments of nature", i.e. genetic/enzymatic defects that prevent the normal clearing of minerals, that an accumulation of certain elements can cause disease and death. For instance:  excess iron (hemochromatosis), excess copper (Wilson's Disease), etc. The question that remains is whether  an excessive intake of water-soluble vitamins, which are excreted unchanged in our urine, is beneficial or detrimental to human health. By excess, I mean a daily dose much greater than that needed to prevent vitamin-deficient disease. Based  on the problems caused by too much iron or too much copper or too much iodine (affects the thyroid gland) it is probably true that an excess of any mineral element in the diet can be injurious (lead being the most notable, especially for the developing nervous system in children).

     It is difficult to find any study that conclusively demonstrates than a dietary excess of any vitamin is either beneficial or injurious. We do know that it gives the user the most expensive urine in the world. The reason for the lack of good studies is that the human generation cycle is 25 years, and there are no good 25-year vitamin studies (not counting Framingham and beta-carotene) with a good control (i.e. no excess vitamin intake) group. But it seems to me that if you want to make a change in the human diet, it is up to the proposer of the change to demonstrate that no harm will come from adopting the change. Too often we assume that any intervention that is not obviously immediately dangerous will prove to be beneficial in the long run. In my opinion (and I emphasize opinion) everything  we ingest is potentially poisonous, so we should probably never eat the same meal two days in a row (and certainly not eat tuna fish more than twice a week) so as to distribute and minimize the effect of any dietary poisons. And except for a daily aspirin in some people, and a daily glass of wine in everyone, it is probably incorrect to assume that any substantial change in our diet will prove to be beneficial and overcome the result of millions of years of evolutionary pressure on our body's chemistry.

     And let's remember again that the theory that oxidative stress contributed to the shortening of life and the induction of cancers was tested by giving the anti-oxidants  Vitamin E to many American heart disease patients and giving beta-carotene to male Finnish smokers (who have the highest rates of heart attacks and lung cancer in the world). The patients given daily high doses of Vitamin E had an increased rate of heart attacks. The Finnish smokers given beta carotene had a higher rate of lung cancer. And let's not forget taht the Japanese, with their "healthy" fish and vegetable diet have such a high rate of stomach cancer that just as we recommend colonoscopies at age  50 to screen for colon cancer, the Japanese start upper endoscopies at age 40 to look for stomach cancer.







  1. I just remembered a curious study done about 20 years ago at Albert Einstein College of Medicine and published in the New England Journal of medicine: It was well-known that a deficiency of vitamin B6 could cause distal neuropathies, and that a dose of 50 to 100 mg/day was the RDA. A clinician thought that double doses of this vitamin would cure females who had carpal tunnel syndrome, so they were started on 200 mg/day of Vitamin B6.After 6 to 12 months, those on the double dose developed the SAME type of distal neuropathy that those who were deficient had. This clinical result has never been explained, but it clearly demonstrates one case where an excess of a water-soluble vitamin caused a medical problem.

  2. One of my colleagues reminded me of some research done at Memorial Sloan Kettering, although he did not have the reference at hand: some scientists grew cancer cells in culture, and then tried to find the LD50 for drugs to kill these cells in culture.They found that the addition of anti-oxidants to the culture INcreased the resistance of the cancer cells to the anti-cancer drugs.

  3. A recent article on the Journal of the Americal Medical Association (October, 2011) showed that men who increased the amount of vitamin E in their diet INcreased their risk of prostate cancer.

  4. And of course, we have the counter-intuitive fact that if a patient has calcium oxalate kidney stones, the proper dietary intervention is to INcrease the amount of calcium in the diet, instead of decreasing dietary calcium, which was formerly recommended for "obvious" reasons.

  5. An article just published in JAMA (Nov. 7, vol 308, pp 1752-60) described a 10 year interventional study of adult male doctors, administered by Harvard University. A daily multivitamin did NOT reduce the incidence of heart attacks, strokes, and cardiovascular deaths.