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Orthomolecular medicine, or megavitamin therapy, is a form of complementary and alternative medicine whose practitioners claim to prevent and treat a wide range of diseases with nutrients. According to advocates of the concept, nutrients are prescribed as dietary supplements or are derived from diets designed to eliminate what proponents consider deleterious substances, such as allergens, refined foods, sugar and transfats.

The term "orthomolecular" was coined by Nobel Prize winner Linus Pauling to mean "the right molecules in the right amounts" (ortho is Greek for "right"). Pauling supposed 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 the conventional medical community, where 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 of orthomolecular medicine state that nutrient treatments are based on patients' personal biochemistries. Supplements, especially of vitamin C, are prescribed at high levels or "megadoses" beyond the Dietary Reference Intake. A 2002 survey underscored the popularity of megavitamin therapies, finding that approximately one in twenty-five US adults uses high doses of vitamins as a form of therapy, a practice particularly common in people diagnosed with cancer.

Nutrients may be useful in preventing and treating some illnesses, but the conclusions of medical research are that the broad claims of disease treatment by advocates of megavitamin therapy are unsubstantiated by the available evidence. Critics have described some aspects of orthomolecular medicine as food faddism or even quackery. Research on nutrient supplementation in general suggests that some nutritional supplements might be beneficial, and that others 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 individuals (post-menopausal women) 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".

History and development

In the early 20th century, some doctors hypothesised that vitamins could cure many ailments, and supplements became widely available. Their affects on health were disappointing, though, and in the 1950s and 60s, nutrition was de-emphasised in standard medical curricula. Orthomolecular medicine proponents 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.

In the early 1900s, Max Gerson developed Gerson therapy, a diet that he claimed could treat many diseases, but which is now thought to be ineffective and dangerous. Wilfred and Evan Shute used vitamin E in attempts to treat heart disease. Several concepts now claimed by orthomolecularists, including individual biochemical variation, inborn error of metabolism, and exogenous supply of essential substances in therapy debuted in scientific and medical papers early in the 20th century. Orthomolecular megavitamin therapies, such as with tocopherols and ascorbates, also date back to the 1930s.

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, American doctor Frederick Klenner also experimented with the use of vitamin C megadosage as a therapy for a wide range of illnesses, including polio. Irwin Stone, who received the first patent for the commercial use of vitamin C, 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.

Individuals who believed that vitamin deficiencies were associated with mental illness began to develop orthomolecular psychiatry in the early 1950s. Psychiatrists Humphry Osmond and Abram Hoffer treated acute schizophrenics with high doses of niacin, while William Kaufman used niacinamide. In 1955, Rudolf Altschul and Abram Hoffer discovered that nicotinic acid (a form of niacin) reduced cholesterol. Unlike other megavitamin therapies, the use of niacin for this purpose has become a standard medical treatment.

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 himself has been criticised for making overbroad claims.

Research since the 1960s has branched out into nutrients besides niacin and vitamin C, including essential fatty acids. Patrick Kidd calls the omega-3 fatty acids docosahexanoic acid (DHA) and eicosapantenoic acid (EPA) truly "orthomolecular" in a 2007 review of their benefits.

Scope

According to orthomolecular practitioner 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." Hoffer admits that in his experience, acute and not chronic schizophrenia responds to niacin.

Nevertheless, 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, Pyroluria, radiation sickness, Raynaud's disease, retardation, schizophrenia, shock, skin problems, snakebite, spider bite, tetanus toxin and viral pneumonia.

Some advocates of orthomolecular medicine, for example, Linus Pauling and his collaborator Ewan Cameron, allege that there is a conspiracy by proponents of traditional medicine to denigrate and cover up the results of their research.

Principles

Orthomolecular medicine is predicated on the premise that it is preferable to recognize and correct any possible anomalies in metabolism at an early stage, before they cause disease. Orthomolecular medicine posits that many typical diets are insufficient for long term health; thus, orthomolecular medical diagnoses and treatment often focus on the use of nutrients such as vitamins, dietary minerals, proteins, antioxidants, amino acids, ω-3 fatty acids, ω-6 fatty acids, medium chain triglycerides, dietary fiber, and short and long chain fatty acids, although a wide range of other substances are used, such as lipotropes, systemic and digestive enzymes, other digestive factors, and prohormones. Abram Hoffer wrote a foreword to one edition of Weston Price's 1930 description of his travels and observations of the health and diet among "primitive" peoples who did not consume processed foods, and were spared the ravages of "degenerative" diseases.

Orthomolecular nutrition and therapy attempts to provide optimal amounts of micronutrients. This is done after a diagnoses of the individual, which may involve a blood test, and a detailed personal history. Based on any deficiencies evident in the blood, an understanding of the patient's diet for the last six months or more, and the practitioners understanding of the symptoms exhibited, a prescription of nutrients, including megadoses of certain of them, will be given. Lifestyle changes, and diet changes, if these are indicated, will also be recommended. Modern orthomolecular practitioners also use a wide range of laboratory analyses, including those for amino acids, organic acids, vitamins and minerals, functional vitamin status, hormones, immunology, microbiology, digestive and gastrointestinal function. However, many of these tests are not employed by mainstream medicine for common diagnostic use.

In the early years of orthomolecular medicine, supplementation usually meant high-dose, single-agent nutrient therapy. Today, orthomolecular practitioners use many substances: amino acids, enzymes, hormones, digestive factors, vitamins, minerals, or derivate substances in an effort to supply what they see as optimum dosages of these substances.

Frequently supplementation with relatively large doses of vitamins is given, and the name megavitamin therapy is popularly associated with the area. Megavitamin therapy is the administration of large amounts of vitamins, often many times greater than the recommended dietary allowance (RDA). The nominal ratio of dose to RDA to qualify for the term 'megavitamin therapy' has been a matter of minor semantic debate.

Prevalence

Orthomolecular medicine is practiced by few conventional medical practitioners. Orthomolecular treatments are instead more common in complementary and alternative medicine fields, increasingly being integrated into over the counter retail products, naturopathic medical textbooks and mainstream pharmaceuticals.

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%. The survey did not include other popular related categories such as juicing, supplemental antioxidants, essential fatty acids, amino acids, enzymes and others.

Another recent CAM survey reported that 12% of liver disease patients used the antioxidant silymarin, more than 6% used megavitamins among others, 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.

Criticism

Methodology

Orthomolecular medicine advocates claim that their methods overlap those of natural medicine and mainstream medicine, stating that the International Society for Orthomolecular Medicine (ISOM) has conventionally-trained doctors among its members, and that the notable founders of orthomolecular medicine all had professional degrees. The leading orthomolecular medicine website, Orthomolecular Medicine Online, run by the ISOM's Journal of Orthomolecular Medicine, discusses differences between orthomolecular medicine and mainstream medicine.

Current medical consensus is that most orthomolecular therapies are insufficiently proven for clinical use: their scientific foundations are too weak, the studies that have been performed are too few and too open to interpretation, and reportedly positive findings in observational studies contradict the results of more rigorous clinical trials.. Mainstream medicine attaches great importance to evidence-based medicine, particularly to rigorous double-blind randomized controlled trials that test if a treatment is genuinely effective and exclude the placebo effect. Orthomolecular medicine proponents, on the other hand, believe that such studies overemphasize uniformity, under-emphasize variability between patients, and reduce choice and health freedom.

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. This form of alternative medicine has therefore been described as food faddism and even quackery, with critics arguing that it is based upon an "exaggerated belief in the effects of nutrition upon health and disease". However, orthomolecular medicine is different from some other forms of alternative medicine, such as homeopathy, in that its ideas are at least biologically-based and apparently consistent with scientific laws, it does not involve magical thinking, and it can generate testable hypotheses.

Views on safety and efficacy

Most influential medical organizations dismiss orthomolecular medicine. These 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."

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 conventional medicine as treatments for disease, such as megadose niacin and fish oil for dyslipidemias, 6000-25,000 iu vitamin E per day for the lipid disorder, abetalipoproteinemia, and megavitamin therapies for over a dozen amino acid metabolism disorders. Current medical research on alternative medicine attempts to assess the evidence either for or against the variety of nutritional therapies currently offered, with a recent review in the Annals of Internal Medicine concluding that while some might be beneficial, others might be harmful or interfere with conventional therapy. A recent study analyzing over 161,000 individuals (post-menopausal women) 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, such as those used in orthomolecular medicine, 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.

Conventional 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.

Example: use of vitamin E in orthomolecular medicine

Vitamin E comprises eight related chemicals, which are classed as either tocopherols or tocotrienols. These chemicals also exist as several stereoisomers. Vitamin E supplements contain stabilized ester forms, which are converted into the active form in the intestines. Research has focussed on alpha-tocopherol, since this is the form preferentially taken up by the body and the most abundant form in tissues. Alpha-tocopherol is also regarded in orthomolecular medicine as the form with greatest nutritional significance. In supplements this is either a mixture of stereoisomers (all-rac-alpha-tocopherol), or the biological stereoisomer RRR-alpha-tocopherol.

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. However, these observational studies could not distinguish between whether the higher levels of vitamin E improved health themselves, or whether confounding variables were responsible - such as whether or not such people ate a more healthy diet or took more exercise. 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 alpha-tocopherol supplementation for preventing chronic disease.

Not only are no benefits apparent, meta-analyses also report that vitamin E supplementation is associated with increased death rates. A meta-analysis published in 2005 found that more than 400 units of alpha tocopherol per day was associated with an increase in all-cause mortality. Furthermore, a significant relationship was seen between dose and all-cause mortality, with the risk of death increasing in line with the dose. A similar increase in mortality was seen in a 2007 meta-analysis This meta-analysis was later repeated and extended by the same authors, with the new analysis published by the Cochrane Collaboration; this also concluded that some vitamin E supplements could be harmful.

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 by some orthomolecular practitioners to treat AIDS patients. However, in these situations, medical criticism arises when orthomolecular approaches are advocated as substitutes for, rather than complements to, current medical treatments such as antiretroviral drugs.

An analysis of fifteen clinical trials of micronutrient therapies by the Cochrane Collaboration in 2005 found no conclusive evidence that such micronutrient approaches either reduce symptoms or mortality in HIV-infected adults who are not malnourished, but found evidence that giving vitamin A to infants with HIV is beneficial. The protective effect of vitamin A in children was also seen in a further trial, and it has been hypothesized that this effect might be due to vitamin A modulating the gut immune system. 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

Beginning with Linus Pauling, orthomolecular proponents have claimed that their findings are actively suppressed by a conspiracy of mainstream medicine and the pharmaceutical industry. Abram 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

See also

• Health freedom movement
• Life extension
• List of life extension related topics
• Histadelia

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Further reading

Support

• Williams Roger J, Kalita Dwight K (1979). Physician's Handbook on Orthomolecular Medicine. Keats Publishing. ISBN 0-87983-199-5.
• Huemer Richard P (ed) (1986). The Roots of Molecular Medicine: A Tribute to Linus Pauling. W. H. Freeman. pp. 290pp. ISBN 0-7167-1761-1. {{cite book}}: |author= has generic name (help)
• Pauling Linus (1986). How to Live Longer and Feel Better. W. H. Freeman. ISBN 0-380-70289-4.
• Hoffer Abram (1998). Putting It All Together: The New Orthomolecular Nutrition. McGraw-Hill. ISBN 0-87983-633-4.
• Werbach Melvyn R, Moss Jeffrey (1999). Textbook of Nutritional Medicine. Third Line Press. ISBN 0-9618550-9-6.
• Hoffer Abram, with Pauling Linus (2004). Healing Cancer: Complementary Vitamin & Drug Treatments. CCNM Press. ISBN 1-897025-11-4.
• Moss David (2000). Antioxidants Against Cancer. Equinox Press. ISBN 1-88102528-4.
• Alexander J (2001). Laboratory evaluations in molecular medicine (First ed.). Norcross, Georgia: Institute for Advances in Molecular Medicine. ISBN 0-96739491-0. (self-published)
• Pizzorno Joseph E Jr, Murray Michael T (2005). Textbook of Natural Medicine (Third ed ed.). Churchill Livingstone. p. 2368. ISBN 0-443-07300-7. {{cite book}}: |edition= has extra text (help); Unknown parameter |month= ignored (help)

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.

External links

Support

• Journal of Orthomolecular Medicine
• orthomolecular.org
• Orthomolecular Medicine Online
• Official website for the International Society of Orthomolecular Medicine
• Linus Pauling Institute website
• Orthomolecular Vitamin Information Centre
• Index orthomolecular research pages, Orthomolecular Education Foundation SOE (Netherlands)

Criticism

• Biologically Based Practices: An Overview, National Institute of Health National Center for Complementary and Alternative Medicine
• Food, Health and Well-Being in British Columbia. BC Provincial Health Officer’s Annual Report 2005.
• Should We "Thank God" for Julian Whitaker?, American Council on Science and Health, 1999
• Recommendations of the NCAHF Task Force on Supplement Abuse (1987)

• Orthomolecular medicine
• Biologically based therapies