Orthomolecular medicine is a form of complementary and alternative medicine aimed at maintaining health through nutritional supplementation and based on the assertion that there is an optimum nutritional environment in the body and that diseases reflect deficiencies in this environment. Treatment for disease, according to this view, calls for the "correcting of imbalances or deficiencies based on individual biochemistry" by use of substances natural to the body, such as vitamins, minerals, amino acids, trace elements and fatty acids. Few medical or scientific experts support this approach; even the accuracy of calling the orthomolecular approach a form of medicine has been questioned since the 1970s.
The approach is sometimes referred to as megavitamin therapy because its practice evolved out of, and in some cases still uses, doses of vitamins and minerals many times higher than the recommended dietary intake. Orthomolecular practitioners may also incorporate a variety of other styles of treatment into their approaches, including dietary restriction, megadoses of non-vitamin nutrients and mainstream pharmaceutical drugs. Proponents argue that non-optimal levels of certain substances can cause health issues beyond simple vitamin deficiency and see balancing these substances as an integral part of health.
The term "orthomolecular" was coined by Linus Pauling to mean "the right molecules in the right amounts" (ortho is Greek for "right"). Proponents of orthomolecular medicine hold that treatment must be based on each patient's individual biochemistry.
The scientific and medical consensus is that the broad claims of efficacy advanced by advocates of orthomolecular medicine are not adequately tested as drug therapies. It has been described as a form of food faddism and even quackery. Proponents point to mainstream sources that have published research supporting the benefits of nutrient supplementation and to instances where conventional medicine uses vitamins as treatments for some diseases.
However, some vitamins have been linked to increased risk of cancer and death. The scientific consensus view is that for normal individuals, a balanced diet contains all necessary vitamins and minerals, and that routine supplementation is not necessary absent specific diagnosed deficiencies.
In the early 20th century, some doctors hypothesised that vitamins could cure disease, and supplements were prescribed in megadoses by the 1930s. Their effects on health were disappointing, though, and in the 1950s and 60s, nutrition was de-emphasised in standard medical curricula. Riordon's organization cite figures from this period as founders of their movement, although the word "orthomolecular" was coined by Linus Pauling only in 1967.
Amongst the individuals described posthumously as orthomolecularists are Max Gerson, who developed a diet that he claimed could treat diseases, which the American Medical Association's 1949 Council on Pharmacy and Chemistry found ineffective; and the Shute brothers, who attempted to treat heart disease with vitamin E. Several concepts now cited by orthomolecularists, including individual biochemical variation and inborn errors of metabolism, debuted in scientific papers early in the 20th century.
In 1948, William McCormick theorized that vitamin C deficiency played an important role in many diseases and began to use large doses in patients. In the 1950s, Fred R. Klenner also tried vitamin C megadosage as a therapy for a wide range of illnesses, including polio.Irwin Stone stated that organisms that do not synthesise their own vitamin C due to a loss-of-function mutation have a disease he called "hypoascorbemia". This term is not used by the medical community, and the idea of an organism-wide lack of a biosynthetic pathway as a disease was not endorsed by Stone's contemporaries.
In the 1950s, some individuals believed that vitamin deficiencies caused mental illness. Psychiatrists Humphry Osmond and Abram Hoffer gave people having acute schizophrenic episodes high doses of niacin, while William Kaufman used niacinamide. While niacin has no known efficacy in psychiatric disease, the use of niacin in combination with statins and other medical therapies has become one of several medical treatments for cardiovascular disease.
In the late 1960s, Linus Pauling introduced the expression "orthomolecular" to express the idea of the right molecules in the right amounts. Since the first claims of medical breakthroughs with vitamin C by Pauling and others, findings on the health effects of vitamin C have been controversial and contradictory. Pauling's claims have been criticised as overbroad.
Hoffer believed that particular nutrients could cure mental illness. In the 1950s, he attempted to treat schizophrenia with niacin, although proponents of orthomolecular psychiatry say that the ideas behind their approach predate Hoffer. According to Hoffer and others who called themselves "orthomolecular psychiatrists", psychiatric syndromes result from biochemical deficiencies, allergies, toxicities or several hypothetical contributing conditions which they termed pyroluria, histadelia and histapenia. These purported causes were said to be found during an "individual biochemical workup" and treated with megavitamin therapy and dietary changes including fasting. These diagnoses and treatments are not accepted by evidence-based medicine.
Orthomolecularists say that they provide prescriptions for optimal amounts of micronutrients after individual diagnoses based on blood tests and personal histories. Lifestyle and diet changes may also be recommended. The battery of tests ordered includes many that are not considered useful by medicine.
Orthomolecular medicine is practiced by few medical practitioners.
Another recent CAM survey reported that 12% of liver disease patients used the antioxidant silymarin, more than 6% used vitamins, and that "in all, 74% of patients reported using CAM in addition to the medications prescribed by their physician, but 26% did not inform their physician of their CAM use."
Even though the health benefits are not established, the use of high doses of vitamins is also common in people who have been diagnosed with cancer. According to Cancer Research UK, cancer patients should always seek professional advice before taking such supplements, and using them as a substitute for conventional treatment "could be harmful to [their] health and greatly reduce the chance of curing or controlling [their] cancer".
Medical and scientific reception
Orthomolecular therapies have been criticized as lacking a sufficient evidence base for clinical use: their scientific foundations are too weak, the studies that have been performed are too few and too open to interpretation, and reported positive findings in observational studies are contradicted by the results of more rigorous clinical trials. Accordingly, "there is no evidence that orthomolecular medicine is effective". Proponents of orthomolecular medicine strongly dispute this statement by citing studies demonstrating the effectiveness of treatments involving vitamins, though this ignores the belief that a normal diet will provide adequate nutrients to avoid deficiencies, and that orthomolecular treatments are not actually related to vitamin deficiency. The lack of scientifically rigorous testing of orthomolecular medicine has led to its practices being classed with other forms of alternative medicine and regarded as unscientific. It has been described as food faddism and quackery, with critics arguing that it is based upon an "exaggerated belief in the effects of nutrition upon health and disease." Orthomolecular practitioners will often use dubious diagnostic methods to define what substances are "correct"; one example is hair analysis, which produces spurious results when used in this fashion.
Proponents of orthomolecular medicine contend that, unlike some other forms of alternative medicine such as homeopathy, their ideas are at least biologically based, do not involve magical thinking, and are capable of generating testable hypotheses.Orthomolecular is not a standard medical term, and clinical use of specific nutrients is considered a form of chemoprevention (to prevent or delay development of disease) or chemotherapy (to treat an existing condition).
Despite a lack of evidence for its efficacy, interest in intravenous high dose vitamin C therapy has not been permanently extinguished, and some research groups continue to investigate whether it has an effect as a possible cancer treatment.
Similarly, the American Cancer Society comments that the current scientific evidence does not "support use of orthomolecular therapy for most of the conditions for which it is promoted." Some supplements have exhibited benefits for specific conditions, while a few have been confirmed to be harmful; the consumption of nutritious foods is the best recognized method to obtain vitamins, minerals, and nutrients crucial for good health.Barrie Cassileth, an adviser on alternative medicine to the National Institutes of Health, stated that "scientific research has found no benefit from orthomolecular therapy for any disease," and medical textbooks also report that there is "no evidence that megavitamin or orthomolecular therapy is effective in treating any disease."
A 1973 task force of the American Psychiatric Association unanimously concluded:
This review and critique has carefully examined the literature produced by megavitamin proponents and by those who have attempted to replicate their basic and clinical work. It concludes in this regard that the credibility of the megavitamin proponents is low. Their credibility is further diminished by a consistent refusal over the past decade to perform controlled experiments and to report their new results in a scientifically acceptable fashion. Under these circumstances this Task Force considers the massive publicity which they promulgate via radio, the lay press and popular books, using catch phrases which are really misnomers like "megavitamin therapy" and "orthomolecular treatment," to be deplorable.
In response to claims that orthomolecular medicine could cure childhood psychoses and learning disorders, the American Academy of Pediatrics labelled orthomolecular medicine a "cult" in 1976.
Proponents of orthomolecular medicine counter that some vitamins and nutrients are now used in medicine as treatments for specific diseases, such as megadose niacin and fish oil for dyslipidemias, and megavitamin therapies for a group of rare inborn errors of metabolism. A review in the Annals of Internal Medicine concluded that while some therapies might be beneficial, others might be harmful or interfere with effective medical therapy. A recent study of over 161,000 individuals provided, in the words of the authors, "convincing evidence that multivitamin use has little or no influence on the risk of common cancers, cardiovascular disease, or total mortality in postmenopausal women." A recent meta-analysis in JAMA suggested that supplementation with combinations of antioxidant vitamins (beta-carotene, vitamin A, and vitamin E) may increase mortality, although with respect to beta-carotene this conclusion may be due to the known harmful effect in smokers.
In the United States, pharmaceuticals must be proven safe and effective to the satisfaction of the FDA before they can be marketed, whereas dietary supplements must be proven unsafe before regulatory action can be taken. A number of orthomolecular supplements are available in the US in pharmaceutical versions that are sometimes quite similar in strength and general content, or in other countries are regulated as pharmaceuticals. The US regulations also have provisions to recognize a general level of safety for established nutrients that can forgo new drug safety tests. Proponents of orthomolecular medicine argue that supplements are less likely to cause dangerous side-effects or harm, since they are normally present in the body. Some vitamins are toxic in high doses and nearly all (with the possible exception of Vitamin C) will cause adverse effects given high levels of overdosing for prolonged periods as recommended by orthomolecular practitioners. Forgoing medical care in favor of orthomolecular treatments can lead to adverse health outcomes.
Orthomolecular proponents claim that even large doses of vitamin E pose no risk to health and are useful for the treatment and prevention of a broad list of conditions, including heart and circulatory diseases, diabetes and nephritis. Initial hopes for the usefulness of vitamin E in orthomolecular medicine were based on epidemiological studies suggesting that people who consumed more vitamin E had lower risks of chronic disease, such as coronary heart disease. These observational studies could not distinguish between whether the higher levels of vitamin E improved health themselves, or whether confounding variables (such as other dietary factors or exercise) were responsible. To distinguish between these possibilities, a number of randomized controlled trials were performed and meta-analysis of these controlled clinical trials have not shown any clear benefit from any form of vitamin E supplementation for preventing chronic disease. Further clinical studies show no benefit of vitamin E supplements for cardiovascular disease. The current position of the National Institutes of Health is that there is no convincing evidence that vitamin E supplements can prevent or treat any disease.
Beyond the lack of apparent benefit, a series of three meta-analyses reported that vitamin E supplementation is associated with an increased risk of death; one of the meta-analyses performed by the Cochrane Collaboration also found significantly increased mortality for the antioxidant vitamins A and beta-carotene. A subsequent meta-analysis found no mortality benefit from vitamin E, but also no increase in mortality either.
Use in AIDS
Several articles in the alternative-medicine literature have suggested that orthomolecular-related dietary supplementation might be helpful for patients with HIV/AIDS. However, high-dose vitamin C treatments have been studied clinically to treat AIDS patients without any positive result. An analysis of fifteen clinical trials of micronutrient therapies by the Cochrane Collaboration in 2005 found no evidence that such approaches either reduce symptoms or mortality in HIV-infected adults who are not malnourished, but found evidence, in one hospital, that giving vitamin A to infants with HIV may be beneficial. Vitamin A deficiency is found in children with HIV infection who may or may not have symptoms of AIDS. Vitamin A supplementation reduces morbidity and mortality in AIDS symptomatic children, but has no effect on asymptomatic children. It does not prevent HIV infection, cannot treat the chronic HIV infection, and will not cure AIDS.
Deaths resulting from illegal vitamin trials in South Africa
Matthias Rath has been extensively criticized for presenting his vitamin supplements as a treatment for AIDS and for testing them in illegal trials in South Africa. A former associate of Linus Pauling, Rath has promoted vitamins as a treatment for HIV infection, describing treatment with effective antiretroviral drugs as toxic and part of a global conspiracy serving the financial interests of the pharmaceutical industry. In a lawsuit that found against Rath, the South African Medical Association blamed his vitamin products for several deaths. The World Health Organization and two health agencies of the United Nations also described Rath’s advertisements as “wrong and misleading” and “an irresponsible attack on ARV (antiretroviral) therapy.” The South African Centre for Social Science Research described the trials as "state sponsored pseudo-science". Rath's trials, conducted with the aid of AIDS denialistDavid Rasnick, were declared unlawful by the Cape High Court; Rath, Rasnick and their foundation were barred from conducting further unauthorised clinical trials and from advertising their products.
Alleged institutional bias
Advocates of orthomolecular medicine, including Pauling, Hoffer and Ewan Cameron have claimed that their findings are actively suppressed by the medical and pharmaceutical industry. Hoffer wrote "There is no conspiracy led and directed by a single person or by a single organization. There is no Mafia in psychiatry. However, there is a conspiracy led and directed by a large number of professionals and their associations who have a common aim to protect their hard-earned orthodoxy, no matter what the cost to their opponent colleagues or to their patients.".
We had to create our own journals because it was impossible to obtain entry into the official journals of psychiatry and medicine. Before 1967 I had not found it difficult to publish reports in these journals, and by then I had about 150 articles and several books in the establishment press.
^ abcdAaronson S et al. (2003). "Cancer medicine". In Frei Emil, Kufe Donald W, Holland James F. Cancer medicine 6. Hamilton, Ontario: BC Decker. p. 76. ISBN1-55009-213-8. "There is no evidence that megavitamin or orthomolecular therapy is effective in treating any disease."
^ ab"NIH state-of-the-science conference statement on multivitamin/mineral supplements and chronic disease prevention". NIH Consens State Sci Statements23 (2): 1–30. 2006. PMID17332802.
^Lipton M, et al. (1973). Task Force Report on Megavitamin and Orthomolecular Therapy in Psychiatry. American Psychiatric Association.
^ abBaumel Syd (August 2000). Dealing with depression naturally : complementary and alternative therapies for restoring emotional health (2nd ed.). Los Angeles: McGraw-Hill. ISBN0-658-00291-0. OCLC43641423.
^Duff, Roberta Larson: American Dietetic Association Complete Food and Nutrition Guide, ISBN 0470912073
^ abcdeMenolascino FJ, Donaldson JY, Gallagher TF, Golden CJ, Wilson JE (1988). "Orthomolecular therapy: its history and applicability to psychiatric disorders". Child Psychiatry Hum Dev18 (3): 133–50. doi:10.1007/BF00709727. PMID2898324.
^Kidd PM (September 2007). "Omega-3 DHA and EPA for cognition, behavior, and mood: clinical findings and structural-functional synergies with cell membrane phospholipids". Alternative Medicine Review (PDF|format= requires |url= (help)) 12 (3): 207–27. PMID18072818.
^Cameron Ewan, Pauling Linus (1979). Cancer and vitamin C : a discussion of the nature, causes, prevention, and treatment of cancer with special reference to the value of vitamin C. New York: Norton. ISBN0-393-50000-4. OCLC5788147.
^Princeton Brain Bio Center. Brochure, distributed to patients. Skillman, New Jersey, 1983, The Center.
^Plaza, S. M.; Lamson, D. W. (2005). "Vitamin K2 in bone metabolism and osteoporosis". Alternative medicine review : a journal of clinical therapeutic10 (1): 24–35. PMID15771560. edit
^Reiter, PJ (1927). "Behandlung von Dementia Praecox mit metallsalzen. Mangan. Z". Neur108: 464–80. doi:10.1007/bf02863975. as cited in Pfeiffer, C; LaMola, S (1983). "Zinc and Manganese in the Schizophrenias". Journal of Orthomolecular Psychiatry12 (3).
^Kay Lily E (1993). The molecular vision of life: Caltech, the Rockefeller Foundation, and the rise of the new biology. Oxford: Oxford University Press. ISBN0-19-511143-5.
^Edelman Eva (2001). Natural healing for schizophrenia: and other common mental disorders. Borage. ISBN0-9650976-7-6.
^ abcCassileth Barrie R (1999). The alternative medicine handbook: the complete reference guide to alternative and complementary therapies. New York: W.W. Norton. p. 67. ISBN0-393-31816-8. OCLC40880206.
^Ohno, S; Ohno, Y; Suzuki, N; Soma, G; Inoue, M (2009). "High-dose vitamin C (ascorbic acid) therapy in the treatment of patients with advanced cancer". Anticancer research29 (3): 809–15. PMID19414313. edit
^Levine, M.; Padayatty, S. J.; Espey, M. G. (2011). "Vitamin C: A Concentration-Function Approach Yields Pharmacology and Therapeutic Discoveries". Advances in Nutrition: An International Review Journal2 (2): 78–88. doi:10.3945/an.110.000109. ISSN2156-5376.
^National Library of Medicine (March 2009). "Niacin". MedlinePlus Encyclopedia. National Library of Medicine. Retrieved 2010-04-28. "Large doses of niacin can cause liver damage, peptic ulcers, and skin rashes. Even normal doses can be associated with skin flushing. It can be prescribed as a treatment for elevated total cholesterol and other types of lipid disorders, but it should only be used with medical supervision due to its potential for severe side effects."
^National Library of Medicine (March 2009). "Vitamin D". MedlinePlus Encyclopedia. National Library of Medicine. Retrieved 2010-04-28. "Vitamin D deficiency can lead to osteoporosis in adults or rickets in children. Too much vitamin D can make the intestines absorb too much calcium. This may cause high levels of calcium in the blood. High blood calcium can lead to calcium deposits in soft tissues such as the heart and lungs. This can reduce their ability to function. Kidney stones, vomiting, and muscle weakness may also occur in someone who has too much vitamin D."
^National Library of Medicine (March 2009). "Vitamin E". MedlinePlus Encyclopedia. National Library of Medicine. Retrieved 2010-04-28. "In November, 2004, the American Heart Association stated that high amounts of vitamin E can be harmful. Taking 400 IU per day, or higher, may increase the risk of death. Taking smaller amounts, such as those found in a typical multivitamin, was not harmful."
^Bjelakovic, G; Nikolova, D; Simonetti, RG; Gluud, C (2004). "Antioxidant supplements for preventing gastrointestinal cancers". In Bjelakovic, Goran. The Cochrane database of systematic reviews (4): CD004183. doi:10.1002/14651858.CD004183.pub2. PMID15495084.
^Miller M (1996). "Diet and psychological health". Altern Ther Health Med2 (5): 40–8. PMID8795935.
^Neuhouser ML, Wassertheil-Smoller S, Thomson C, et al. (February 2009). "Multivitamin use and risk of cancer and cardiovascular disease in the Women's Health Initiative cohorts". Arch Intern Med169 (3): 294–304. doi:10.1001/archinternmed.2008.540. PMID19204221.
^Bjelakovic G, Nikolova D, Gluud LL, Simonetti RG, Gluud C (2007). "Mortality in randomized trials of antioxidant supplements for primary and secondary prevention: systematic review and meta-analysis". JAMA297 (8): 842–57. doi:10.1001/jama.297.8.842. PMID17327526. See also the letter to JAMA by Philip Taylor and Sanford Dawsey and the reply by the authors of the original paper.
^Rapola JM, Virtamo J, Ripatti S, et al. (1997). "Randomised trial of alpha-tocopherol and beta-carotene supplements on incidence of major coronary events in men with previous myocardial infarction". Lancet349 (9067): 1715–20. doi:10.1016/S0140-6736(97)01234-8. PMID9193380.
^Bjelakovic G, Nikolova D, Gluud LL, Simonetti RG, Gluud C (2012). "Antioxidant supplements for prevention of mortality in healthy participants and patients with various diseases". Cochrane Database Syst Rev3: CD007176. doi:10.1002/14651858.CD007176.pub2. PMID22419320.
^Abner, E. L.; Schmitt, F. A.; Mendiondo, M. S.; Marcum, J. L.; Kryscio, R. J. (2011). "Vitamin E and all-cause mortality: A meta-analysis". Current aging science4 (2): 158–170. doi:10.2174/1874609811104020158. PMID21235492. edit
^Batterham M, Gold J, Naidoo D, et al. (February 2001). "A preliminary open label dose comparison using an antioxidant regimen to determine the effect on viral load and oxidative stress in men with HIV/AIDS". Eur J Clin Nutr55 (2): 107–14. doi:10.1038/sj.ejcn.1601124. PMID11305623.
^Irlam JH, Visser ME, Rollins N, Siegfried N (2005). "Micronutrient supplementation in children and adults with HIV infection". In Irlam, James JH. Cochrane Database Syst Rev (4): CD003650. doi:10.1002/14651858.CD003650.pub2. PMID16235333.
^Grotto I, Mimouni M, Gdalevich M, Mimouni D (March 2003). "Vitamin A supplementation and childhood morbidity from diarrhea and respiratory infections: a meta-analysis". J Pediatr142 (3): 297–304. doi:10.1067/mpd.2003.116. PMID12640379.
Huemer Richard P, ed. (1986). The Roots of molecular medicine : a tribute to Linus Pauling. W. H. Freeman. pp. 290pp. ISBN0-7167-1761-1. OCLC13009998. "Based on a collection of papers presented at a symposium of the Orthomolecular Medical Society in San Francisco, May 7–8, 1983, with revisions and additional papers."