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Orthomolecular medicine, or megavitamin therapy is a form of complementary and alternative medicine that purports to prevent or treat diseases with nutrients prescribed as dietary supplements or derived from diets.

The term "orthomolecular" was coined by Nobel laureate Linus Pauling to mean "the right molecules in the right amounts" (ortho is Greek for "right"). Pauling theorized that "substances that are normally present in the human body" are necessarily good and can be used at high doses to treat disease. The term is not used in medicine, where 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).

Proponents state that nutrient treatments are based on patients' personal biochemistries. Supplements are prescribed at high levels or "megadoses" beyond the Dietary Reference Intake. A 2002 survey found that approximately one in twenty-five US adults uses megadose therapy, a practice particularly common among cancer patients.

Nutrients may be useful in preventing and treating some illnesses, but the conclusions of medical research are that the broad claims by advocates of megavitamin therapy are unsubstantiated by the available evidence. Critics have described some aspects of orthomolecular medicine as food faddism or quackery. Research on nutrient supplementation in general suggests that some nutritional supplements might be harmful; several specific nutritional therapies are associated with an increased likelihood of the condition they are meant to prevent. A recent study analyzing over 161,000 post-menopausal women provided "convincing evidence that multivitamin use has little or no influence on the risk of common cancers, cardiovascular disease, or total mortality".

History and development

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. Orthomolecularists claim several figures from these early days of enthusiasm about nutrition as founders of their movement, although the word "orthomolecular" was coined by Linus Pauling only in 1967.

Amongst the individuals claimed posthumously as orthomolecularists are Max Gerson, who developed a diet that he claimed could treat diseases, but which is now thought to be ineffective and dangerous; and the Shute brothers, who attempted to treat heart disease with vitamin E. Several concepts now claimed by orthomolecularists, including individual biochemical variation, inborn error 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, Frederick Klenner also used vitamin C megadosage as a therapy for a wide range of illnesses, including polio. Irwin Stone claimed 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 acute schizophrenics high doses of niacin, while William Kaufman used niacinamide. Unlike other megavitamin therapies, 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 has been criticised for making overbroad claims.

Later research branched out into nutrients besides niacin and vitamin C, including essential fatty acids.

Scope

According to Abram Hoffer, orthomolecular medicine does not purport to treat all diseases, nor is it "a replacement for standard treatment. A proportion of patients will require orthodox treatment, a proportion will do much better on orthomolecular treatment, and the rest will need a skillful blend of both." Nevertheless, unsubstantiated claims have been made that nutrients can prevent, treat, and sometimes cure a wide range of medical conditions, including: acne, alcoholism, allergies, arthritis, autism, bee stings, bipolar disorder, burns, cancer, the common cold, depression,drug addiction, drug overdose, epilepsy, heart diseases, heavy metal toxicity, acute hepatitis, herpes, hyperactivity, hypertension, hypoglycemia, influenza, learning disabilities, mental and metabolic disorders, migraine, mononucleosis, mushroom poisoning, neuropathy & polyneuritis (including multiple sclerosis), osteoporosis, polio, an hypothesised condition called "pyroluria", radiation sickness, Raynaud's disease, retardation, schizophrenia, shock, skin problems, snakebite, spider bite, tetanus toxin and viral pneumonia.

Hoffer believed in particular that 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. Carl Pfeiffer of the Pfeiffer Treatment Center, continued Hoffer’s approach, believing that for “every drug that benefits a patient, there is a natural substance that can achieve the same effect". 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 are 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.

  • Pyroluria

Pyroluria (or malvaria from the term mauve factor) involves hypothetical excessive levels of pyrroles in the body resulting from improper hemoglobin synthesis. According to Carl Pfeiffer, pyroluria is a form of schizophrenic porphyria, similar to acute intermittent porphyria where both pyrroles and porphyrins are excreted in the human urine to an excessive degree. These pyrroles are then said to bind to vitamin B6 and zinc, leading to elimination through urine and causing deficiencies; large-dose supplementation is said to return health. Pyroluria is variously claimed to affect people diagnosed with ADHD, alcoholism, autism, depression, down syndrome, manic-depression, schizophrenia, coeliac disease, epilepsy, or psychosis. Pyroluria is sometimes claimed to have a genetic origin and to be activated by stress. Pfeiffer's methods have not been rigorously tested, and pyrroles are not considered related to schizophrenia. Studies have either failed to detect hemopyrrole and kryptopyrrole in the urine of normal controls and schizophrenics, or found no correlation between these chemicals and mental illness. Few, if any, medical experts regard the condition as genuine, and few or no articles on pyroluria are found in modern medical literature; the approach is described as "snake oil" by pediatrician and author Julian Haber.

  • Histadelia

Histadelia is a condition hypothesised by Carl Pfeiffer to involve elevated serum levels of histamine and basophils, which he says can be treated with methionine and vitamin B6 megadoses. Pfeiffer claims that "histadelia" can cause depression with or without psychosis, but no published clinical trials have tested the effectiveness of this therapy.

  • Histapenia

Histapenia is described as high serum copper with low histamine.

Hoffer writes that actress Margot Kidder credits his approach with helping her overcome bipolar disorder. Mark Vonnegut attributed his recovery from schizophrenia to orthomolecular psychiatry and advocated its adoption by mainstream medicine, but he later disavowed his statements.

Principles

According to Abram Hoffer, "primitive" peoples do not consume processed foods and do not have "degenerative" diseases. In contrast, typical "Western" diets are said to be insufficient for long-term health, necessitating the use of megadose supplements of vitamins, dietary minerals, proteins, antioxidants, amino acids, ω-3 fatty acids, ω-6 fatty acids, medium chain triglycerides, dietary fiber, short and long chain fatty acids, lipotropes, systemic and digestive enzymes, other digestive factors, and prohormones to ward off hypothetical metabolism anomalies at an early stage, before they cause disease.

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.

Prevalence

Orthomolecular medicine is practiced by few medical practitioners, but megavitamin treatments are increasingly found in over the counter retail products and naturopathic textbooks.

A survey released in May, 2004 by the National Center for Complementary and Alternative Medicine focused on who used complementary and alternative medicine (CAM), what was used, and why it was used in the United States by adults age 18 years and over during 2002. The survey reported uses in the previous twelve months that include orthomolecular related uses: Nonvitamin, nonmineral, natural products 18.9%, Diet-based therapies 3.5%, Megavitamin therapy 2.8%.

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." The use of high doses of vitamins is also common in people who have been diagnosed with cancer, although usage depends of the type of cancer and ranges from 26% to 35% among prostate cancer survivors up to 75% to 87% in breast cancer survivors.

Treatments

Criticism

Methodology

Critics state that orthomolecular therapies have insufficient evidence 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 contradict the results of more rigorous clinical trials.. Evidence-based medicine is critical to clinical decisions, particularly to rigorous double-blind randomized controlled trials that test if a treatment is genuinely effective and exclude the placebo effect.

The perceived 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". Defenders respond that, unlike some other forms of alternative medicine, such as homeopathy, its ideas are at least biologically-based do not involve magical thinking, and it can generate testable hypotheses.

Views on safety and efficacy

Since its inception, orthomolecular medicine has been rejected by mainstream medicine. Critics note that the claims advanced by its proponents are unsubstantiated or false. These critics include the American Cancer Society, the American Psychiatric Association, the National Institute of Mental Health, the American Academy of Pediatrics, CHAMPUS, and the Canadian Paediatric Society. The American Medical Association describes as "myths" the ideas that vitamin and mineral deficiencies are widespread, that the causes of most diseases are poor diets, or that most diseases can be prevented by nutritional supplements. 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". They stated some supplements have exhibited benefits for certain conditions, while a few have been confirmed to be harmful, and that the consumption of nutritious foods is the best recognized method to obtain vitamins, minerals, and nutrients crucial for good health. In another example, 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 a recent medical textbook also states 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.

The American Academy of Pediatrics labelled orthomolecular medicine a "cult" in 1976, in response to claims that orthomolecular medicine could cure childhood psychoses and learning disorders.

Proponents of orthomolecular medicine counter that vitamins and nutrients are now used in medicine as treatments for disease, such as megadose niacin and fish oil for dyslipidemias, and megavitamin therapies for over a dozen amino acid metabolism disorders. A recent review in the Annals of Internal Medicine concluded that while some therapies might be beneficial, others might be harmful or interfere with conventional 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".

Dietary supplements are less regulated than pharmaceuticals in the United States. Furthermore, a recent meta-analysis in JAMA suggested that supplementation with combinations of 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. An essential regulatory difference is that pharmaceuticals must be proven safe and effective to the satisfaction of the FDA before they can be marketed, whereas supplements must be proven unsafe before regulatory action can be taken. A number of orthomolecular US supplements are available in pharmaceutical versions that are sometimes quite similar in strength and general content, or in other countries are 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 nutritional supplement use have argued that the lower level of regulation results in cost savings for American consumers, pointing to higher supplement prices in Europe, where some supplements are more tightly regulated or even unavailable. They also argue that supplements are less likely to cause dangerous side-effects or harm, since they are normally present in the body.

Health professionals see orthomolecular medicine as encouraging individuals to dose themselves with large amounts of vitamins and other nutrients without conventional supervision, which they worry might be damaging to health. Rare risks of non-orthomolecular "mega" dosages of vitamin relatives, which frequently involved pharmaceutical analogues such as synthetic menadione, unsupervised misuse, deliberate abuse and earlier medical treatments, may include increased risk of coronary heart disease, hypertension, thrombophlebitis, peripheral neuropathy, ataxia, neurological effects, liver toxicity, congenital abnormalities, spontaneous abortion, gouty arthritis, jaundice, kidney stones, and diarrhea.

Vitamin E

In the 1940s, Vogelsang and the Shute brothers promoted the use of vitamin E in the high-dose range of 200-600 mg/day as a therapy for heart disease and other health problems, and established a center called the Shute Institute. They published uncontrolled positive studies of it as a treatment for heart disease, but high-dose vitamin E was called as "valueless" even in 1948, and the first negative double-blind controlled trial occured in 1950. In 1972 a double-blind randomized controlled trial of 3200 IU/day of vitamin E found no effect in 50 adults. A 2005 meta-analysis found that more than 400 units of alpha tocopherol per day was associated with an increase in all-cause mortality. A significant relationship was also seen between dose and all-cause mortality, with the risk of death increasing with higher dose. An increase in mortality was confirmed in a 2007 meta-analysis, which was later repeated and extended by the same authors in the Cochrane Collaboration.

As a lower-dose dietary supplement for deficiency rather than a high-dose treatment regime, initial consideration of vitamin E supplementation for preventing disease was based on epidemiological studies which suggested 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, many randomized controlled trials were performed. Meta-analysis of these controlled clinical trials have not shown any clear benefit from any form of vitamin E supplementation for preventing chronic disease.

Time and therapeutic priority

Conventional physicians express concern that megavitamin and orthomolecular therapies used solely as alternative treatments by other practitioners, if not successful, may create dangerous delays in obtaining conventional treatments, such as radiation and chemotherapy for cancer. For example, in a highly publicized Canadian controversy, the chemotherapy of a 13-year-old cancer patient, Tyrell Dueck, encountered a delay from legal actions, due to his parents' religious beliefs and interest in alternative treatments such as diet, herbs and vitamins. Orthomolecular medical practitioners and orthomolecular oriented naturopaths have long expressed similar concerns about conventional medicine, particularly with gut related and chronic diseases as well as viral diseases. It is usually possible, however, to combine orthomolecular and conventional treatments.

Use in AIDS

Several orthomolecular related AIDS approaches such as multivitamins, selenium and amino acids are used with reported improvements in patients. High dose vitamin C treatments have long been used clinically to treat AIDS patients without any positive result. Use of this orthomolecular treatment rather than current medical treatments such as antiretroviral drugs has been subject to criticism.

An analysis of fifteen clinical trials of micronutrient therapies by the Cochrane Collaboration in 2005 found no evidence that such micronutrient 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. The protective effect of vitamin A in children was also seen in a further trial. Interestingly, no protection from vitamin A against infection was seen in healthy children.

Deaths from illegal vitamin trials in South Africa

Vitamin salesman Matthias Rath has been roundly criticised for presenting his supplements as a treatment for AIDS and testing them in illegal trials in South Africa. A former associate of Linus Pauling, Rath now promotes 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.” Rath's trials, conducted with the aid of AIDS denialist David Rasnick, were declared unlawful; Rath, Rasnick and their foundation were barred from conducting further unauthorised clinical trials and from advertising their products.

Conspiracy theories

Orthomolecularists, including Pauling, Hoffer and Ewan Cameron have alleged that their findings are actively suppressed by a conspiracy of mainstream medicine and the pharmaceutical industry. Hoffer wrote that "there is no conspiracy led and directed by a single person or by a single organization ... owever, 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".

The Journal of Orthomolecular Medicine, founded in 1967 as the Journal of Schizophrenia, is the main publication of those involved in Orthomolecular Medicine. It was founded, as Abram Hoffer wrote, because of the alleged conspiracy: "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."

Mainstream medicine regards such claims of a conspiracy as unsubstantiated, with a review in Journal of Clinical Oncology stating that the idea there is a conspiracy amongst physicians against unconventional and unproven treatments is a common theme in forms of alternative medicine such as megavitamin therapy. Despite claims of conspiracy, most of the Linus Pauling Institute's funding comes from the National Institutes of Health, and several orthomolecular therapies have been officially sanctioned within Europe and Japan.

Additional supporters of orthomolecular medicine

This article is in list format but may read better as prose. You can help by converting this article, if appropriate. Editing help is available. (March 2009)
David Horrobin
Archie Kalokerinos
Carl Pfeiffer
John Hans Stroh
Julian Whitaker
Roger J. Williams

See also

Citations

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Further reading

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Criticism

  • Barrett Stephen (1980). The Health Robbers (Second ed ed.). Stickley. p. 52. {{cite book}}: |edition= has extra text (help)
  • Cassileth Barrie R (1998). Alternative medicine handbook: the complete reference guide to alternative and complementary therapies. New York: W.W. Norton. ISBN 0-393-04566-8.
  • Bender David A (2003). Nutritional Biochemistry of the Vitamins (Second ed ed.). Cambridge University Press. p. 230. ISBN 0521803888. {{cite book}}: |edition= has extra text (help)
  • Gratzer Walter (2005). Terrors of the table. Oxford University Press. p. 210. ISBN 0192806610.

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