Orthomolecular Medicine- Big Talk, Little Evidence, Real Risk

One of the most impressive-sounding labels for an unproven alternative therapy is Orthomolecular Medicine. And the origin of the term, coined by Nobel laureate Linus Pauling, gives it added gravitas. As it turns out, though, it’s just a fancy way of claiming that there are medical benefits to giving high doses of vitamins above and beyond the ordinary, and quite small amounts necessary for normal health. Proponents of this concept argue that many diseases are due to undetected vitamin or mineral deficiencies, usually attributed to the unspecified evils of modern life or industrial agriculture. They also seem to follow the philosophy that if a little is good, more is better in arguing that extremely high doses of essential micronutrients can treat or prevent illness.

It is culturally difficult to argue against the benefits of vitamins, or to suggest they might cause harm. The memory of a time in which people in Western societies were routinely deficient in micronutrients, and when supplementation provided seemingly miraculous benefits, is still accessible. And there are still places in the world in which the poor not only do not have our nutrient-excess health problems but in which vitamin deficiencies are still common, and supplementation can be beneficial. Recent surveys suggest vitamins are seen as generally benign even by doctors, who commonly use them as placebo therapy.

However, the grand claims made in the 1970s by Pauling and others about the benefits of megadoses of vitamins have had a long time to prove themselves, and they have so far failed to do so. In human medicine, the loosely-organized set of theories called Orthomolecular Medicine has passed through the classic stages of CAM research:

1. An untested idea

2. An idea with support from a few random in vitro and animal model studies

3. An idea with a few supportive findings in small, poorly designed clinical studies

4. An idea clearly debunked in larger and better-designed studies but whose proponents cling to it tenaciously despite the lack of evidentiary support because they see themselves as visionaries ignored or oppressed by the unimaginative and venal mainstream medical establishment.

In veterinary medicine, as usual, not all of the stages are well-represented. The closest I have been able to find to Stage 3 are some case reports and papers from the 1970s that are long on grand theorizing and short on data by Dr. Wendell Belfield. These are balanced by a number of in vitro and animal model studies showing the implausibility or potential dangers megadoses of vitamins, but to my knowledge well-designed, adequately powered clinical trials have not been done to definitively prove or disprove any of the claims orthomolecular practitioners make. In my opinion, this is as it should be since the basic plausibility, the in vitro data, and the data from human medicine all argue against wasting resources on something so unlikely to prove safe and effective, but it is always nice to be able to show with solid data that likely nonsense truly is nonsense.

Since there do not appear to be definitive studies, I have put together some information of a cautionary nature about some commonly advocated vitamin therapies. This is certainly not a comprehensive literature review, nor do I claim it is the final word on megadose vitamin therapy. I have selected cautionary research to illustrate the potential risks of orthomolecular therapies and to remind everyone why the burden of proof is properly on proponents of this approach to justify their extravagant claims. It is also important to emphasize that the use of vitamins in high doses to prevent or treat disease is essentially using these compounds as drugs. They are not “nutritional” therapies when given above the recognized necessary amounts but active pharmaceuticals, and as such any possible benefits will come with associated risks and side effects.


Vitamin A

As a fat-soluble vitamin, Vitamin A can accumulate over time, making reaching dangerous levels more likely. As for most vitamins, there are clear benefits to appropriate amounts, and supplementation sometimes shows benefit for people in impoverished environments with inadequate nutrition, but the evidence does not support benefits for supplementation of healthy people with adequate diets or clear benefits for treating non-deficiency diseases.

Excessive dietary Vitamin A can worsen osteoporosis and raise the risk of hip fractures.

A nice summary of the risks of Vitamin A, including neurologic disease, birth defects, and osteoporosis.

A Cochrane Review that presents mixed evidence for the possible benefit of Vitamin A for reducing mortality in children with measles.  However, another review found no benefit for non-measles pneumonia.

A Chochrane Review showing Vitamin A does not reduce transmission of HIV from mother to offspring.

A Cochrane Review that found no value in Vitamin A for preventing lower respiratory tract infections in children, and even a few studies showing and increase risk with supplementation.


Vitamin C

The original megavitamin Linus Pauling promoted obsessively in his later years. The most extensively studied claims of orthomolecular practitioners are those relating to Vitamin C, and these are the claims that have been most soundly disproven. In addition, recent evidence illustrates the real risks of large doses of Vitamin C.

Vitamin C can interfere with the effectiveness of chemotherapy.

A pair of detailed reviews and refutations of a couple of papers purporting to finally show some value to megadoses of Vitamin C . First Post Second Post 

A paper showing Vitamin C not helpful, and potentially exacerbating for hypertrophic osteodystrophy in dogs.

No evidence oral Vitamin C improves immune system parameters in dogs.

Cochrane Reviews-Evidence does not support Vitamin C for prevention or treatment of the common cold and is generally absent or of unreliable quality for the use of Vitamin C in prevention or treatment of pneumonia, tetanus, and asthma.


Vitamin D

There is a great deal of interest in the potential of this vitamin to reduce cancer risk. However, the evidence so far is mixed, with some studies showing a decreased risk (e.g. colon cancer), little or no change in risk (e.g. breast, prostate, and others), and even some increase in risk (e.g. pancreatic cancer among smokers). Excessive amounts can cause kidney stones, abnormal heart rhythms, and other serious side effects. This is one substance for which I think there is justification to conducting further research.


Vitamin E

In this study, Vitamin E use increased the risk of lung cancer.

A pair of studies that showed Vitamin E had no protective benefit for prostate cancer and increased the risk of heart failure.


Multivitamins and Miscellaneous

A systematic review and meta-analysis published in the Lancet that suggests not only do antioxidants and Vitamin A and E supplements not prevent cancer, they may actually increase mortality risk.

A large study that found no benefit to multivitamin supplements for older women.

Neurologic toxicity with oral supplementation of Vitamin B6 in dogs.

Extensive research into orthomolecular claims in neurologic and psychiatric disease has found no evidence of benefit.

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10 Responses to Orthomolecular Medicine- Big Talk, Little Evidence, Real Risk

  1. Bartimaeus says:

    From the references you provided for the various vitamins and some new work published in Nature last week (http://www.nature.com/nature/journal/vaop/ncurrent/full/nature08268.html) a lot of evidence is building that some reasonable level of micro nutrients is necessary for good health, but excessive amounts are either unnecessary or even harmful.
    The money quote from that link;

    “These data…raise the possibility that antioxidants may have dichotomous activities with respect to tumorigenesis-that is, suppressing tumorigenesis by preventing oxidative damage to DNA, and promoting tumorigenesis by allowing survival of cells that are metabolically impaired. …Lastly, randomised trials have demonstrated both anti-neoplastic and neoplastic effects of antioxidants, with neoplastic effects associated with patients at higher risk owing to smoking and alcohol consumption, or patients undergoing chemo- or radiation therapy. Our work provides a biological rationale for these findings, as antioxidant activity may promote the survival of pre-initiated tumor cells in unnatural matrix environments and thus enhance malignancy.”

    It seems that some of the patients who are at the highest risk emotionally to the promoters of orthomolecular medicine and similar treatments are those who are most likely to suffer the unwanted effects of excess levels of vitamins and antioxidants.

  2. skeptvet says:

    Absolutely! Thanks for pulling that quote out of the study. It illustrates exactly the no-free-lunch-in-physiology principle that CAM proponents can’t seem to accept.Everything has a downside, every benefit comes with risks, and this is just as true of those rare CAM therapies that actuallly do something as it is of mainstream scientific medicine.

  3. Rita says:

    Whilst we’re on the subject of vitamins, what’s the story on vitamin D, exposure to sunlight and animals? So many animals are kept indoors – pets in flats, (dogs often walked at night, or in less-than-sunny places) horses in boxes (exercised outdoors, but often not for long, and somtimes not every day) etc (I assume factory farmed animals are supplemented) – is there any stuff about on this?

  4. skeptvet says:

    Dogs and cats have very inefficient activation of Vitamin D by UV light in their skin due to an enzyme which interferes with the process. It makes sense since, under normal conditons, very little UV light would get through their coats anyway, so such a process wouldn’t be reliable. They need to get their Vit D from diet. Not sure about horses and cattle, as it’s outside my field, but I would guess the same is true of haired mammals generally. Here are a couple of papers on the subject.

    Morris JG. Ineffective vitamin D synthesis in cats is reversed by an inhibitor of 7-dehydrocholestrol-delta7-reductase. J Nutr. 1999 Apr;129(4):903-8.

    Similar info for dogs:
    Hazewinkel, H.A.W., How, K. L., Bosch, R., Goedegebuure, S. A. & Voorhout, G. (1987) Inadequate photosynthesis of vitamin D in dogs. In Nutrition, Malnutrition, and Dietetics in the Dog and Cat. Proceedings of an international symposium held at Hanover, Sept 3 to 4 1987. English edition edited by A.T.B. Edney, published by British Veterinary Association in collaboration with the Waltham Centre for Pet Nutrition.

  5. Rita says:

    Many thanks for the reply – I wonder if it applies to pigs, who are not notably hairy (although wild boars are, of course) and rather wish to protect themselves from the sun with mud etc…………..

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  8. Austin says:

    You’re using dogs to refute the benefits of vitamin C? Do you realize dogs produce their own vitamin C? Do you know in what amounts they do so when healthy? When sick?

  9. skeptvet says:

    When people claim benefits for Vit C supplementation in dogs, it is necessary to evaluate claims for these benefits in dogs. As you point out, humans (and guinea pigs) are exceptions among mammals in not being able to synthesize Vit C, so there is even less reason to believe dramatic benefits will be obtained by supplementing it. As of now, the evidence for such benefits is non-existent in dogs and very weak for humans, though there is some interesting, though preliminary, research involving thiamine and Vit C and steroid combinations for sepsis in people.

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