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Template:Biologically based therapy Orthomolecular medicine is a form of complementary and alternative medicine with the goal of preventing and treating disease with optimal amounts of substances which are natural to the body. These often take the form of nutrients in modified diets with additional dietary supplements, eliminating deleterious substances and food artifacts^[1] such as allergens, refined foods, sugar and transfats.^[2]^[3]

The term "orthomolecular" was first coined in a 1967 letter^[4] by Nobel Prize winner Linus Pauling and later elaborated on in a 1968 paper^[5] on micronutrients and psychiatry to express the idea of "the right molecules in the right amounts" (ortho is Greek for right^[6]). In this paper, Pauling indicated that the right molecules are "substances that are normally present in the human body."

Orthomolecular medicine began with a particular focus upon mental illness, and orthomolecular psychiatry remains a major subdiscipline.^[7] Proponents state that orthomolecular treatments are based on patients' personal biochemistries^[8] and employ naturally-occurring or bioequivalent biomolecules, particularly nutrients such as vitamins, dietary minerals, proteins, antioxidants,^[9] amino acids, lipotropes,^[10] prohormones, dietary fiber, fatty acids and other similar substances,^[11] as well as various digestive factors.^[12]^[13]

Some megavitamin therapies can be classified as components of orthomolecular medicine. Orthomolecular practitioners often recommend levels beyond the Recommended Daily Allowance, especially for vitamin C, and prescribe the removal of unhealthy foods from the diet. Megavitamin therapies have become relatively popular, with a survey in 2002 finding that approximately one in twenty-five US adults use high doses of vitamins as a form of therapy,^[14] with this being particularly common in people diagnosed with cancer.^[15]

Nutrients are useful in preventing and treating some illnesses^[16]^[17], but the mainstream medical consensus is that the broad claims of disease treatment by advocates of orthomolecular medicine are unsubstantiated by the available evidence.^[18]^[19]^[16] The American Medical Association stated in 1997 that "much of the dietary intervention stressed by alternative healers is prudent and reasonable", but described as a "myth" the idea that "most diseases are caused by faulty diets and can be prevented by nutritional interventions".^[20] Critics have described some aspects of orthomolecular medicine as food faddism or quackery.^[21]^[22]^[23] Research on nutrient supplementation in general suggests that some nutritional supplements might be beneficial, and that others might be harmful.^[24]^[25]

History and development

As a discipline focused upon using nutrients to treat illness, orthomolecular medicine practitioners trace the origin of the field back to the discovery of vitamins in the early 20th century.^[26] However, the word "orthomolecular" was coined by Linus Pauling in 1967. Thus orthomolecular practitioners lay claim to figures who preceded later controversies and labels, and perhaps would have rejected the controversial treatments which were later called orthomolecular medicine. Practitioners claim these figures were orthomolecular because of their emphasis on the role of nutrition in treating disease. In a paper on the history of orthomolecular medicine, Menolascino^[27] notes that there were several eras in the use of nutrition to treat disease. After the discovery of nutrients at the dawn of the 20th century, some doctors began to think that vitamins could cure many things, and nutrition was incorporated into the medical curriculum. Supplements became ubiquitous. As spectacular results were not forthcoming, in the 1950s and 1960s medical science slowly became disillusioned with nutrition and cut it from the standard curriculum, just as orthomolecular medicine was heating up. Orthomolecular medicine highlights some figures from these early years as their founders.

In the 1930s Dr. Max Gerson (1881 - 1959) developed Gerson therapy, a strict diet which he claimed could treat many diseases. In 1933, Drs. Wilfred and Evan Shute began to use vitamin E to treat heart disease.^[28] Some of the concepts frequently utilized in orthomolecular medicine, such as individual biochemical variation,^[8] inborn error of metabolism,^[29]^[27]^[30] and exogeneous supply of essential substances in therapy ^[31] debuted in scientific and medical papers early in the 20 th century. Orthomolecular megavitamin therapies, such as with tocopherols and ascorbates,^[32] date back to the 1930s.

In 1948, Dr. William McCormick theorized that vitamin C deficiency played an important role in many diseases, and began to use large doses in patients.^[33] 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, most notably polio, and authored 28 research papers during his career.^[34]^[35] McCormick and Klenner influenced biochemist Dr. Irwin Stone, who extensively researched vitamin C and received the first patent for its commercial use. Stone found that all living beings have vitamin C. Further, nearly all vertebrates produce vitamin C, and produce much more when stressed. Some primates, including humans, do not produce vitamin C, and Stone claimed that this was due to a genetic defect which he called hypoascorbemia.^[36] Based on a rat's production of vitamin C, a 70 kg human would produce between 1.8 and 4 grams of vitamin C, and a stressed human up to 15.2 grams.^[37] This contrasts with the current Dietary Reference Intake, which maintains that 90 mg is adequate, and increases that to 120 mg if pregnant.^[38] Based on the levels of vitamin C in other vertebrates, Stone believed that ascorbate was not a trace vitamin but was required in humans in large daily amounts. He produced four papers between 1965 and 1967 to back up this assertion.^[39]^[40]^[41]^[42] In 1966 Stone met Linus Pauling and sparked Pauling's interest in vitamin C.^[43]

Concurrent with vitamin C developments, orthomolecular psychiatry began to be developed in the early 1950s by a group of biochemists and psychiatrists who believed that certain vitamin deficiencies were associated with mental illness.^[44] In particular, psychiatrists Drs. Humphry Osmond and Abram Hoffer began to treat schizophrenia with high doses of niacin,^[45] continuing work done by Dr. William Kaufman, who used niacinamide.^[46] Incidental to this effort, Hoffer contributed to the discovery that niacin could treat dyslipidemia in 1954-5.^[47]

In 1967, Linus Pauling introduced the expression orthomolecular medicine to describe one aspect of medicine,^[4] and the term "orthomolecular therapy", as published in Science in 1968, to express the idea of the right molecules in the right amounts.^[5] Pauling subsequently defined "orthomolecular medicine" as "the treatment of disease by the provision of the optimum molecular environment, especially the optimum concentrations of substances normally present in the human body" or as "the preservation of good health and the treatment of disease by varying the concentrations in the human body of substances that are normally present in the body and are required for health."^[48]

Orthomolecular medicine has diversified since its beginnings in1968, but the term orthomolecular is still associated with Pauling's advocacy of multi-gram doses of vitamin C for optimal health. Partly for this reason, detractors of orthomolecular medicine have described the practice entirely in terms of megadose nutrient therapy. Cassileth, a widely quoted critic of Pauling's ideas, asserts: "In 1968, the Nobel-prize-winning scientist Linus Pauling coined the term "orthomolecular" to describe the treatment of disease with large quantities of nutrients."^[49] In this way, criticism of orthomolecular medicine has, to a large extent, been confused with much older medical traditions of high-dose vitamin therapies, such as earlier "megadose" usages of retinol and ergocalciferol or synthetic pharmaceutical analogues, such as menadione.^[50] ^[51]^[52] However, such definitions of orthomolecular therapy are not synonymous with Pauling's definition. Interest in vitamin C has been renewed, beginning with the discovery that intravenous vitamin C can achieve plasma concentrations up to 70-fold higher than oral vitamin C.^[53] A 2005 paper in the Proceedings for the National Academy of Sciences noted that vitamin C selectively killed cancer cells in vitro. This paper noted that, although the original observational studies of vitamin C were based on intravenous administration, the subsequent double-blind placebo-controlled studies used oral ascorbate.^[54] In 2007, the researchers demonstrated how vitamin C in vivo could possibly kill cancer cells.^[55] A recent historical study of the past ten years has found three patients whose tumors shrank after receiving intravenous vitamin C along with other alternative and conventional treatments. The authors of the study claimed that the case studies "only signficant treatment" for these patients was vitamin C.^[56]^[57] However, this is far from conclusive, and studies are currently planned at the McGill University.^[58]

In 2008 researchers at the National Institute of Diabetes and Digestive and Kidney Diseases in Bethesda, Maryland, gave vitamin C intravenously to mice with human derived cancers and found that it slowed tumor growth by 41–53% and may suppress metastasis.^[59] The authors suggest that the ascorbate is acting as a pro-oxidant and generating hydrogen peroxide in tumors. By injecting into the bloodstream it is possible to get much larger amounts of the vitamin to a tumor than is possible with oral supplements. The Cancer Treatment Centers of America (CTCA) in Zion, Illinois, is currently (2008) testing the safety of intravenous vitamin C in late-stage cancer patients for whom there is no other treatment option. ^[60]

Research since the 1960s has branched out further into nutrients besides niacin and vitamin C. Dr. David Horrobin did important work with essential fatty acids, which have played an increasingly important part in orthomolecular medicine.

Scope

Although orthomolecular medicine is based on the idea that nutritional imbalances should be corrected before illness occurs, and consequently is not easily integrated into any single branch of medicine, its claims are particularly associated with psychiatry, in the field of orthomolecular psychiatry, and oncology, where Linus Pauling reported that Vitamin C could slow the progression of,^[61] and even reverse,^[62] cancer. As time went on Pauling came to believe that there was a deliberte and concerted effort to denigrate, distort and dissemble about his efforts, Ewan Cameron the Scottish oncologist, who collaborated with Pauling, very reluctantly came to agree as he believed to perceive mounting evidence to support the Pauling's allegations of bad fath.^[63]

Proponents of orthomolecular medicine claim that scientists associated with orthomolecular medicine had identified specific biochemical anomalies that account for many cases of bipolar disorder, schizophrenia, and some similar manifestations, such as, in one case, an previously undescribed copper toxicity disorder.

Based on investigational scientific studies, single-blind and double-blind randomized controlled trials, clinical experience, and case histories, claims have been made that therapeutic nutrition can prevent^[64] treat, and sometimes cure acne,^[65] bee stings, burns, cancer, the common cold, drug addiction, drug overdose, heart diseases, acute hepatitis, herpes, influenza, mononucleosis, mushroom poisoning, neuropathy & polyneuritis (including multiple sclerosis), osteoporosis,^[66] polio, alcoholism,^[67] allergies, arthritis, autism, epilepsy, hypertension, hypoglycemia, migraine, clinical depression, learning disabilities, retardation, mental and metabolic disorders, skin problems, and hyperactivity,"^[68] Raynaud's disease, heavy metal toxicity, radiation sickness, * Pyroluria, schizophrenia,^[69] shock, snakebite, spider bite, tetanus toxin and viral pneumonia.^[70]

However, most orthomolecular practitioners do not claim to be able to treat all diseases. As Abram Hoffer wrote in 1989: "Nor is orthomolecular treatment 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."^[71] For example, Hoffer admits that in his experience, acute and not chronic schizophrenia responds to niacin.^[72]

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.^[73] 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.^[74]

Orthomolecular nutrition and therapy attempts to provide optimal amounts of micronutrients. Most often, 'optimal' has been a matter of the clinical judgment of the orthomolecular practitioner, who gives these compounds in accord with the clinical symptoms of the patient and the practioner's judgment of what is appropriate, rather than the published dietary reference intakes of these nutrients. 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.^[71] 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.^[75]

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.

Administration of short-chain fatty acids in orthomolecular practice is usually done by increasing the level of dietary fiber.^[76]^[77] The fatty acids are produced by fermentation of the fiber in the colon, then absorbed into the body.^[78] Attempts are also made to aid this process by a combination of prebiotics and mucopolysaccharides.^[79] Long chain fatty acids, such as the omega-3 fatty acids alpha-linolenic acid (ALA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA), may also be given directly, in food or in capsules.

Prevalence

Orthomolecular medicine is practiced by few conventional medical practitioners.^[49]^[80] 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.^[81]^[82]

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%.^[14] 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."^[83] 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.^[15]

Criticism

Methodology

Orthomolecular medicine advocates claim that the methods of orthomolecular medicine overlap with those of both natural medicine and mainstream medicine. The International Society for Orthomolecular Medicine has conventionally-trained doctors among its members and authors, and the notable founders of orthomolecular medicine have all had professional degrees. The leading orthomolecular medicine website, Orthomolecular Medicine Online,^[84] run by the Journal of Orthomolecular Medicine, discusses differences between orthomolecular medicine and mainstream medicine,^[75]^[80]

On the other hand, the conventional view among mainstream medical physicians is that most orthomolecular therapies are insufficiently proven for clinical use, that the scientific foundations are weak, and that the studies that have been performed are too few and too open to disputed interpretation. This lack of serious testing of orthomolecular medicine has led to its practices being classed with other less plausible forms of alternative medicine and regarded as unscientific.^[85] 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".^[21]^[22]^[23] However, orthomolecular medicine is distinct from many other forms of alternative medicine, such as homeopathy, since its ideas are biologically-based and consistent with scientific laws, it does not involve magical thinking,^[86] and it can generate testable hypotheses.^[87]

Amongst the differences, mainstream medicine attaches great importance to evidence-based medicine,^[88] particularly to rigorous double-blind randomized controlled trials that test if a treatment is genuinely effective and exclude the placebo effect.^[89] Orthomolecular medicine proponents, on the other hand, believe that such studies overemphasize uniformity, under-emphasize variability between patients, and reduce choice and health freedom.^[90]

Mainstream medicine also avoids the use of new treatments whose effects are unknown, instead favoring 'clinically proven' drugs tested using mainstream medical standards. Even with this standard of caution, it has been estimated that up to 20% of drugs may subsequently have unrecognized, serious adverse reactions, requiring the later addition of the "black box warning", or withdrawal from market.^[91]

The skepticism about orthomolecular medicine comes in part because some of its proponents make claims more broad than those supported by scientific research, particularly claims that may contradict the results of clinical trials,^[49]^[92] and rely instead on less reliable observational studies, clinical and anecdotal experience, single blinded controlled tests, and case histories. Proponents of orthomolecular medicine argue that, despite the extensive testing of pharmaceuticals, some medications are withdrawn after approval, due to serious adverse events, and the FDA regulatory methodology and relationship with the pharmaceutical industry has been criticized.^[93]

Views on safety and efficacy

Many mainstream medical institutions dismiss orthomolecular medicine entirely. 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.^[20] 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.^[16] 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"^[49] and a recent medical textbook also states that there is "no evidence that megavitamin or orthomolecular therapy is effective in treating any disease."^[94] 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,^[95]^[96]^[97] 6000-25,000 iu vitamin E per day^[98]^[99] for the lipid disorder, abetalipoproteinemia, and megavitamin therapies for over a dozen amino acid metabolism disorders.^[27]

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.^[100] 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.^[101] 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.^[102]

Relation to mainstream medicine

Aspects of orthomolecular therapy remain controversial among mainstream medical organizations and physicians, who consider many aspects to be lacking sufficient RCT-based evidence. In contrast, orthomolecular proponents argue that many mainstream nutritional studies, both recent and historical, provide investigational and clinical support for their treatments and recommendations.^[103] They also argue that orthomolecular therapies are intrinsically less likely to cause dangerous side-effects or harm, since they utilize only chemicals that are normally present in the body.^[3]^[104]^[105] Supporters claim that some aspects of orthomolecular medicine, and in particular the optimal nutrition subset, have support in mainstream scientific research in a variety of areas that do not claim to support orthomolecular doctrine, and in at least some cases, explicitly reject claims of orthomolecular proponents that nutritional supplements are desirable.^[106]

Orthomolecular proponents, such as Robert Cathcart, who predicts that 120+ grams per day intravenous vitamin C should cure severe acute respiratory syndrome^[107] and has used up to 250 grams IV vitamin C per day, have been criticized for not having any conventional medical trials of such intravenous vitamin C treatments.^[108]

The orthomolecular field remains controversial among mainstream medical organizations, including 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. A number of individuals and organizations contest the claims, benefits, degree of evidence and toxicity.^[49]^[16] Based on testing with dosages well below orthomolecular recommendations, Linus Pauling has been criticized for making overbroad claims^[109] for the efficacy of vitamin C but Paulings' claims have received some support from tests closer to the orthomolecular recommendations during the last few years.^[110]

The relationship of mainstream medicine to orthomolecular proponents has often been adversarial; orthomolecular proponents, including Dr. Richard Kunin, argue that mainstream medical claimants confuse orthomolecular medicine with other, less science based modalities.^[75] 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.^[111]

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^[112] 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,^[113] hypertension, thrombophlebitis, peripheral neuropathy, ataxia, neurological effects, liver toxicity, congenital abnormalities, spontaneous abortion, gouty arthritis, jaundice, kidney stones, and diarrhea.^[114]^[115]^[116]^[117] Megavitamin proponents point^[118] to an almost zero level of deaths caused by vitamins, even with large overdoses, compared to the significant numbers from pharmaceuticals, including a number of over-the-counter items.

Vitamin E controversy

Vitamin E contains eight related chemicals, which are classed as either tocopherols or tocotrienols. These chemicals also exist as several stereoisomers.^[119] In supplements these are usually present in stabilized ester forms, which are converted into the active form in the intestines.^[120] Research has focussed on alpha-tocopherol, since this is the form preferentially taken up by the body and the most abundant form in tissues.^[121] Alpha-tocopherol is also regarded in orthomolecular medicine as the form with greatest nutritional significance.^[122] In supplements this is either a mixture of stereoisomers (all-rac-alpha-tocopherol), or the biological stereoisomer RRR-alpha-tocopherol.^[119]

Initial hopes for vitamin E were based on epidemiological studies. These suggested that people who consumed more vitamin E had lower risks of chronic disease, such as coronary heart disease, and led to the idea that vitamin E supplementation could be beneficial.^[123] However, these observational studies could not distinguish between if the higher levels of vitamin E improved heath themselves, or if confounding variables were responsible - such as if these people eat a more healthy diet or took more exercise.^[124]^[125] 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.^[126]^[127]^[128]^[119]

A meta-analysis published in 2005 found that more than 400 units alpha tocopherol per day was associated with an increase in all-cause mortality.^[129] Furthermore, a significant relationship was seen between dose and all-cause mortality, with the risk of death increasing in line with the dose. This meta-analysis was criticized on a number of grounds, including that this increase in mortality could have been caused by alpha-tocopherol and beta carotene increasing the risk of lung cancer in heavy smokers.^[130] A similar increase in mortality was seen in a 2007 meta-analysis^[131] Here, no health risk was seen when all the randomized controlled studies were examined together, but an increase in mortality was detected when the high-quality and low-bias risk trials were examined separately. However, as the majority of these low-bias trials dealt with either elderly people, or people already suffering disease, so these results may not apply to the general population.^[132] 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.^[133]

Orthomolecular recommendations for vitamin E supplementation typically are based on a mixture of tocopheols and tocotrienols.^[134] Forms of "vitamin E", which contain mixed R,R,R tocopherols and are also recommended by some orthomolecular practitioners.^[135] These other forms of vitamin E have not been examined in as much detail as alpha-tocopherol and may have effects on health that are not produced by the alpha-tocopherol form.^[136]^[122]

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.^[137]^[138] Orthomolecular medical practitioners and orthomolecular oriented naturopaths have long expressed similar concerns about conventional medicine,^[139] particularly with gut related and chronic diseases as well as viral diseases.^[140]^[141]^[142]^[143] It is usually possible, however, to combine orthomolecular and conventional treatments.

Use in AIDS

Several orthomolecular related AIDS approaches such as multivitamins,^[144] selenium and amino acids^[145] 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.^[146]^[147] However, a meta-analysis of fifteen clinical trials of vitamin therapy by the Cochrane Collaboration in 2005 found no conclusive evidence that such approaches either reduce symptoms or mortality in HIV-infected adults who are not malnourished, but found some evidence that giving vitamin A to infants with HIV is beneficial.^[148] In these situations, mainstream medical criticism arises when orthomolecular approaches are advocated as substitutes for, rather than complements to, current medical treatments such as antiretroviral drugs.^{[citation needed]}

Economic interests and politics

Some orthomolecular proponents claim partisan politics, pharmaceutical industry influence, and competitive considerations to be significant factors. The Linus Pauling Institute's funding comes mostly from National Institutes of Health.^[149] Several orthomolecular therapies have been officially sanctioned within Europe^[150] and Japan.^[151] ^[152]^[153]

Notable supporters of orthomolecular medicine

Abram Hoffer
David Horrobin
Archie Kalokerinos
Otto Warburg

Linus Pauling
Carl Pfeiffer
Matthias Rath

Irwin Stone
Albert Szent-Györgyi
Julian Whitaker
Roger J. Williams

Journal of Orthomolecular Medicine

The Journal of Orthomolecular Medicine, founded in 1967 as the Journal of Schizophrenia, is the main publication of those involved in Orthomolecular Medicine. Abram Hoffer has written that "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."^[154]

Citations

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^ ^a ^b ^c Menolascino FJ, et al. "Orthomolecular Therapy: Its History and Applicability to Psychiatric Disorders", Child Psychiatry and Human Development, Vol.18(3), Spring 1988, pp 140-1
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^ 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". JAMA. 297 (8): 842–57. doi:10.1001/jama.297.8.842. PMID 17327526.{{cite journal}}: CS1 maint: multiple names: authors list (link) See also the letter to JAMA by Philip Taylor and Sanford Dawsey and the reply by the authors of the original paper.
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^ ^a ^b Vitamin E Micronutrient Information Center, Linus Pauling Institute, Accessed31 May 2008
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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
DoctorYourself.com - Personal site of Andrew Saul PhD, Contributing Editor for the Journal of Orthomolecular Medicine.
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)

[1] A Hoffer, M Walker (2000) Smart Nutrients, Avery, ISBN 0895295628

[2] Orthomolecular medicine Encyclopedia of Alternative Medicine by Patricia Skinner

[orthomed-3] Definition of Orthomolecular medicine at www.orthomed.org Accessed June 2006

[pauling1967-4] Pauling L. Orthomolecular Somatic and Psychiatric Medicine “, Communication: Luxembourg and Trier on 18-24 September 1967; Pauling L. 1968b: Orthomolecular Somatic and Psychiatric Medicine J Vital Substances and Diseases of Civilization’’, 14; 1-3.

[pauling1968-5] Orthomolecular psychiatry. Varying the concentrations of substances normally present in the human body may control mental disease,Science 1968 Apr 19;160(825):265-71. (PMID 5641253) [1]

[6] ISOM. About OM

[7] Syd Baumel (Aug 2000) "Chapter 5, The Orthomolecular Medical Approach to Depression", "Chapter 6, Vitamin Power", Dealing with Depression Naturally: Complementary and Alternative Therapies, 2nd ed, McGraw-Hill; ISBN 0658002910

[autogenerated1-8] Roger J. Williams (1998) Biochemical Individuality: The Basis for the Genetotrophic Concept. 2nd ed. Keats Publishing. ISBN 0-87983-893-0

[9] Alpha-Lipoic Acid (Thioctic Acid): My Experience

[10] Reduction of Cholesterol and Lp(A) in Regression of Coronary Artery Disease: A Case Study

[11] Coenzyme Q10: A Novel Cardiac Antioxidant (1997)

[12] RC Atkins (1998) Dr. Atkins' Vita-Nutrient Solution: Nature's Answer to Drugs, Simon & Schuster, ISBN 0684844885

[13] JV Wright, L Lenard (2001) Why Stomach Acid Is Good for You, M. Evans and Company, Inc. ISBN 0871319314

[NCCAMsurvey-14] NCCAM.NIH table 1 on page 8

[Velicer-15] Velicer CM, Ulrich CM (2008). "Vitamin and mineral supplement use among US adults after cancer diagnosis: a systematic review". J. Clin. Oncol. 26 (4): 665–73. doi:10.1200/JCO.2007.13.5905. PMID 18235127.

[ACS-16] "ACS : Orthomolecular Medicine". American Cancer Society. 2007-06-19. Retrieved 2008-04-04.

[17] Lakhan SE, Vieira KF (2008) Nutritional therapies for mental disorders. Nutr J 7: 2. doi:10.1186/1475-2891-7-2 PMID 18208598

[18] Stuart Aaronson et. al. "Cancer Medicine", 2003, BC Decker Inc ISBN 1–55009–213–8, Section 20, p76

[References1990-19] Nutrition Committee, Canadian Paediatric Society (1990). "Megavitamin and megamineral therapy in childhood". CMAJ. 143 (10): 1009–1013. PMID 1699646. Retrieved 2008-04-04.

[AMA-20] Report 12 of the Council on Scientific Affairs: Alternative medicine American Medical Association June 1997, Accessed 21 March 2008

[autogenerated3-21] Jarvis WT (1983). "Food faddism, cultism, and quackery". Annu. Rev. Nutr. 3: 35–52. doi:10.1146/annurev.nu.03.070183.000343. PMID 6315036.

[Jukes1990-22] Jukes, T.H. (1990). "Nutrition Science from Vitamins to Molecular Biology". Annual Review of Nutrition. 10 (1): 1–20. doi:10.1146/annurev.nu.10.070190.000245. A short summary is in the journal's preface. Cite error: The named reference "Jukes1990" was defined multiple times with different content (see the help page).

[autogenerated2-23] Braganza, S.F. (2005). "Fad Therapies". Pediatrics in Review. 26 (10): 371–376. doi:10.1542/pir.26-10-371. PMID 16199591. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)

[24] "NIH State-of-the-Science Conference Statement on Multivitamin/Mineral Supplements and Chronic Disease Prevention". NIH Consens State Sci Statements. 23 (2): 1–30. 2006. PMID 17332802.

[25] Huang HY, Caballero B, Chang S; et al. (2006). "The efficacy and safety of multivitamin and mineral supplement use to prevent cancer and chronic disease in adults: a systematic review for a National Institutes of Health state-of-the-science conference". Ann. Intern. Med. 145 (5): 372–85. doi:10.1001/archinte.145.2.372. PMID 16880453. {{cite journal}}: Explicit use of et al. in: |author= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)

[OMHistory-26] History of Orthomolecular Medicine

[Menolascino-27] Menolascino FJ, et al. "Orthomolecular Therapy: Its History and Applicability to Psychiatric Disorders", Child Psychiatry and Human Development, Vol.18(3), Spring 1988, pp 140-1

[Shute-28] Wilfred and Evan Shute

[29] Stephen F. Mason. THE SCIENCE AND HUMANISM OF LINUS PAULING (1901-1994). Chemical Society Reviews, 26, no. 1 (February 1997). Section 5, Molecular Medicine: “...Garrod in his book, Inborn Error of Metabolism (1909, 1923)”

[30] Lois N. Magner A History of Medicine, Informa Healthcare; 2nd edition (June 23, 2005) ISBN 0824740742

[31] Beard J. The action of 'trypsin' upon living cells of the Jensen sarcoma. Brit Med J 1906;1:140-141 (Jan. 20, 1906).

[32] AscorbateWeb: Timeline from 1935 to 1939

[McCormick-33] MEGADOSES OF VITAMIN C AND DR. WILLIAM J. McCORMICK, McCormick HoF

[34] Hidden in Plain Sight: The Pioneering Work of Frederick Robert Klenner, M.D. Andrew W. Saul, online reprint from J Orthomolecular Med, 2007. Vol 22, No 1, p 31-38, Accessed October 2007

[35] A posthumous summary of Frederick Klenner's 28 papers. Lendon H. Smith, M.D., Clinical Guide to the Use of Vitamin C - The Clinical Experiences of Frederick R. Klenner, M.D. . Accessed October 2007.

[36] The Natural History of Ascorbic Acid in the Evolution of Mammals and Primates, Irwin Stone, 1972

[ascorbic-37] Observations On the Dose and Administration of Ascorbic Acid When Employed Beyond the Range of a Vitamin in Human Pathology

[38] Council for Responsible Nutrition. Vitamin and Mineral Recommendations

[39] STONE. I.: Studies of a Mammalian Enzyme System for Producing Evolutionary Evidence on Man. Amer. J. Phys. Anthrop. 15, 83-85, 1965.

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@@ Line 71: / Line 71: @@
 ===Methodology===
 Orthomolecular medicine advocates claim that the methods of orthomolecular medicine overlap with those of both natural medicine and mainstream medicine. The International Society for Orthomolecular Medicine has conventionally-trained doctors among its members and authors, and the notable founders of orthomolecular medicine have all had professional degrees. The leading orthomolecular medicine website, Orthomolecular Medicine Online,<ref>[http://orthomed.org Orthomolecular Medicine Online]</ref> run by the [[Journal of Orthomolecular Medicine]], discusses differences between orthomolecular medicine and mainstream medicine,<ref name="kunin">[http://www.orthomed.org/kunin.html Principles That Identify Orthormolecular Medicine: A Unique Medical Specialty]</ref><ref name="wund">[http://orthomed.org/wund.html Wunderlich]</ref>
+On the other hand, the conventional view among mainstream medical [[physician]]s is that most orthomolecular therapies are insufficiently proven for clinical use, that the scientific foundations are weak, and that the studies that have been performed are too few and too open to disputed interpretation. This lack of serious testing of orthomolecular medicine has led to its practices being classed with other less plausible forms of alternative medicine and regarded as unscientific.<ref>{{cite journal |author=Leibovici L |title=Alternative (complementary) medicine: a cuckoo in the nest of empiricist reed warblers |journal=BMJ |volume=319 |issue=7225 |pages=1629–32 |year=1999 |pmid=10600974 |pmc=1127092 |url=http://bmj.com/cgi/pmidlookup?view=long&pmid=10600974}}</ref> 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".<ref name="autogenerated3" /><ref name=Jukes1990>{{cite journal | author = Jukes, T.H. | year = 1990 | title = Nutrition Science from Vitamins to Molecular Biology | journal = Annual Review of Nutrition | volume = 10 | issue = 1 | pages = 1–20 | doi = 10.1146/annurev.nu.10.070190.000245}}  A short summary is in [http://arjournals.annualreviews.org/doi/full/10.1146/annurev.nu.10.072106.100001 the journal's preface].</ref><ref name="autogenerated2" /> However, orthomolecular medicine is distinct from many other forms of alternative medicine, such as [[homeopathy]], since its ideas are biologically-based and consistent with [[scientific law]]s, it does not involve [[magical thinking]],<ref name=Lindeman2000>{{cite journal | author = Lindeman, M.; Keskivaara, P.; Roschier, M. | title=Assessment of Magical Beliefs about Food and Health |year = 2000 | journal = Journal of Health Psychology | volume = 5 | issue = 2 | pages = 195 | url = http://hpq.sagepub.com/cgi/content/abstract/5/2/195}}</ref> and it can generate testable hypotheses.<ref name=Jonas1999>{{citation
+ | author = Jonas, W. B. | year = 1999 | title = Magic and Methodology: when Paradigms Clash | journal = The Journal of Alternative and Complementary Medicine | volume = 5 | issue = 4 | pages = 319–321 | doi = 10.1089/acm.1999.5.319 | url = http://www.liebertonline.com/doi/abs/10.1089/acm.1999.5.319}}</ref>
 Amongst the differences, mainstream medicine attaches great importance to [[evidence-based medicine]],<ref>{{cite journal |author=Akobeng AK |title=Principles of evidence based medicine |journal=Arch. Dis. Child. |volume=90 |issue=8 |pages=837–40 |year=2005 |pmid=16040884 |url=http://adc.bmj.com/cgi/content/full/90/8/837 |doi=10.1136/adc.2005.071761}}</ref> particularly to rigorous [[double-blind]] [[randomized controlled trial]]s that test if a treatment is genuinely effective and exclude the [[placebo effect]].<ref>{{cite journal |author=Weihrauch TR, Gauler TC |title=Placebo--efficacy and adverse effects in controlled clinical trials |journal=Arzneimittelforschung |volume=49 |issue=5 |pages=385–93 |year=1999 |pmid=10367099}}</ref> Orthomolecular medicine proponents, on the other hand, believe that such studies overemphasize uniformity, under-emphasize variability between patients, and reduce choice and [[health freedom]].<REF>DJ Hess, [http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1447283#top Complementary or Alternative? Stronger vs Weaker Integration Policies] Am J Public Health. 2002 October; 92(10): 1579–1581.</REF>
@@ Line 79: / Line 82: @@
 ===Views on safety and efficacy===
-The conventional view among mainstream medical [[physician]]s is that most orthomolecular therapies are insufficiently proven for clinical use, that the scientific foundations are weak, and that the studies that have been performed are too few and too open to disputed interpretation. 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".<ref name="autogenerated3" /><ref name=Jukes1990>{{cite journal | author = Jukes, T.H. | year = 1990 | title = Nutrition Science from Vitamins to Molecular Biology | journal = Annual Review of Nutrition | volume = 10 | issue = 1 | pages = 1–20 | doi = 10.1146/annurev.nu.10.070190.000245}}  A short summary is in [http://arjournals.annualreviews.org/doi/full/10.1146/annurev.nu.10.072106.100001 the journal's preface].</ref><ref name="autogenerated2" /> However, orthomolecular medicine is distinct from many other forms of alternative medicine, such as [[homeopathy]], since its ideas do not contravene any [[scientific law]]s, it does not involve [[magical thinking]],<ref name=Lindeman2000>{{cite journal | author = Lindeman, M.; Keskivaara, P.; Roschier, M. | title=Assessment of Magical Beliefs about Food and Health |year = 2000 | journal = Journal of Health Psychology | volume = 5 | issue = 2 | pages = 195 | url = http://hpq.sagepub.com/cgi/content/abstract/5/2/195}}</ref> and it can generate testable hypotheses.<ref name=Jonas1999>{{citation
- | author = Jonas, W. B. | year = 1999 | title = Magic and Methodology: when Paradigms Clash | journal = The Journal of Alternative and Complementary Medicine | volume = 5 | issue = 4 | pages = 319–321 | doi = 10.1089/acm.1999.5.319 | url = http://www.liebertonline.com/doi/abs/10.1089/acm.1999.5.319}}</ref>
 Many mainstream medical institutions dismiss orthomolecular medicine entirely. 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.<ref name=AMA/> 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.<ref name = ACS>{{cite web | url = http://www.cancer.org/docroot/ETO/content/ETO_5_3X_Orthomolecular_Medicine.asp?sitearea=ETO  | title = ACS : Orthomolecular Medicine | accessdate = 2008-04-04 | format = | work = | publisher = [[American Cancer Society]] | date = 2007-06-19}}</ref> 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"<ref name="cassileth">{{cite book |author=Cassileth, Barrie R. |title=The alternative medicine handbook: the complete reference guide to alternative and complementary therapies |publisher=W.W. Norton |location=New York |year=1998 |pages=67 |isbn=0-393-04566-8 |oclc= |doi=}}</ref> and a recent medical textbook also states that there is "no evidence that megavitamin or orthomolecular therapy is effective in treating any disease."<ref>{{cite book |author=Frei, Emil; Kufe, Donald W.; Holland, James F. |title=Cancer medicine 6 |publisher=BC Decker |location=Hamilton, Ont |year=2003 |pages= |isbn=1550092138 |oclc= |doi=| url = http://www.ncbi.nlm.nih.gov/books/bv.fcgi?highlight=orthomolecular&rid=cmed6.section.18479&WebEnv=0MnZPX94hO0XD2ugCELLkbhpkV5QLNBinRc8fAJ1IwDvCVoCzamY2zTpsFeeRiEdbTVTXzrZpQLqXt%40263F77C978AD3D40_0136SID&WebEnvRq=1#18482 | pages = 76 | accessdate = 2008-04-04}}</ref>   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 [[dyslipidemia]]s,<ref>Braverman ER, Weissberg E, [http://www.orthomolecular.org/library/jom/1988/pdf/1988-v03n01-p006.pdf  "Fish Oil As One Therapy in Cardiovascular Risk Factor Reduction,"] ''J Orthomolecular Medicine'', 3(1), 1987</ref><ref>{{cite journal |author=Berra K |title=Clinical update on the use of niacin for the treatment of dyslipidemia |journal=J Am Acad Nurse Pract |volume=16 |issue=12 |pages=526–34 |year=2004 |pmid=15645997 |doi=}}</ref><ref>{{cite journal |author= |title=Don't overlook niacin for treating cholesterol problems. If you can conquer or cope with the "niacin flush," this B vitamin can do wonders for cholesterol |journal=Harv Heart Lett |volume=14 |issue=8 |pages=4–5 |year=2004 |pmid=15100082 |doi=}}</ref> 6000-25,000 iu vitamin E per day<ref>M Traber, Linus Pauling Institute, A Kamal-Eldin; "Oxidative stress and vitamin E in anemia", p. 164, Ch 11 in ''Nutritional Anemia '', 2007, SIGHT AND LIFE, Basel, Switzerland  "   " both hypobetalipoproteinemic or abetalipoproteinemic subjects become vitamin E deficient and develop a characteristic neurologic if they are not given large vitamin E supplements (approximately 10 g per day)"</ref><ref>Granot E, Kohen R. [http://www.ajcn.org/cgi/content/full/79/2/226 ''Oxidative stress in abetalipoproteinemia patients receiving long-term vitamin E and vitamin A supplementation''], ''AJCN'', Vol. 79, No. 2, 226-230, February 2004</ref> for the lipid disorder, [[abetalipoproteinemia]], and megavitamin therapies for over a dozen amino acid metabolism disorders.<ref name="Menolascino"/>