Orthomolecular medicine is a form of complementary and alternative medicine which aims to prevent and treat disease with substances which are natural to the body. Prescriptions typically focus on providing nutrients, either through dietary supplements or modified diets which provide proper nutrition and eliminate deleterious substances such as allergens, refined foods, sugar and transfats.
The term "orthomolecular" was first coined in a 1967 letter by Nobel Prize winner Linus Pauling and later elaborated on in a 1968 paper on micronutrients and psychiatry to express the idea of "the right molecules in the right amounts" (ortho is Greek for right). 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. Proponents state that orthomolecular treatments are based on patients' personal biochemistries and employ naturally-occurring or bioequivalent biomolecules, particularly nutrients such as vitamins, dietary minerals, proteins, antioxidants, amino acids, lipotropes, prohormones, dietary fiber, fatty acids and other similar substances, as well as various digestive factors.
Some megavitamin therapies can be classified as components of orthomolecular medicine. Orthomolecular practitioners often recommend levels beyond the Recommended Daily Allowance, especially in the prescription of vitamin C megadosage. 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, with this being 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 orthomolecular medicine are unsubstantiated by the available evidence. 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". 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.
 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, although 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 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 ailments, and nutrition was incorporated into the medical curriculum. Supplements became widely available. 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 being founded. Orthomolecular medicine highlights some figures from these early years as their founders.
In the 1930s Max Gerson (1881 - 1959) developed Gerson therapy, a specific diet which he claimed could treat many diseases. In 1933, Wilfred and Evan Shute began to use vitamin E in attempts to treat heart disease. Some of the concepts frequently utilized in orthomolecular medicine, such as individual biochemical variation, inborn error of metabolism, and exogeneous 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, 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, most notably polio, and authored 28 research papers during his career. McCormick and Klenner influenced biochemist 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. 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. This contrasts with the current Dietary Reference Intake, which maintains that 90 mg is adequate, and increases that to 120 mg if pregnant. 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. In 1966 Stone met Linus Pauling and sparked Pauling's interest in vitamin C.
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. In particular, psychiatrists Humphry Osmond and Abram Hoffer began to treat a subset of schizophrenics ("acute") with high doses of niacin, continuing work done by William Kaufman, who used niacinamide. Incidental to this effort, Hoffer contributed to the discovery that niacin could treat dyslipidemia in 1954-5.
In 1967, Linus Pauling introduced the expression orthomolecular medicine to describe one aspect of medicine, and the term "orthomolecular therapy", as published in Science in 1968, to express the idea of the right molecules in the right amounts. 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."
Orthomolecular medicine has diversified since its beginnings in1968, but the term orthomolecular is still associated with Pauling's advocacy of vitamin C megadosage for optimal health. Partly for this reason, detractors of orthomolecular medicine have described the practice entirely in terms of megadose nutrient therapy. Barrie R. 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." 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.  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. 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. In 2007, the researchers demonstrated how vitamin C in vivo could possibly kill cancer cells. 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 significant treatment" for these patients was vitamin C. However, this is far from conclusive, and studies are currently planned at the McGill University.
In 2008 researchers gave vitamin C intravenously to mice with human derived cancers and observed slower tumor growth and may less metastasis. The authors suggested that the ascorbate was 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. However, other researchers studying the effects of vitamin C in cancers in mice saw no effect on tumor growth, and found that vitamin C interfered with many standard anti-cancer drugs. 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.
Research since the 1960s has branched out further into nutrients besides niacin and vitamin C. David Horrobin did important work with essential fatty acids, which have played an increasingly important part in orthomolecular medicine. Patrick Kidd calls the omega-3 fatty acids docosahexanoic acid (DHA) and eicosapantenoic acid (EPA) truly "orthomolecular" in a 2007 review of their benefits.
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, and even reverse, cancer. As time went on Pauling came to believe that there was a deliberate and concerted effort to denigrate, distort and dissemble his efforts. Ewan Cameron the Scottish oncologist, who collaborated with Pauling, reluctantly came to agree as he believed to perceive mounting evidence to support Pauling's allegations of bad faith.
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 treat, and sometimes cure acne, 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, polio, alcoholism, allergies, arthritis, autism, epilepsy, hypertension, hypoglycemia, migraine, clinical depression, learning disabilities, retardation, mental and metabolic disorders, skin problems, and hyperactivity," Raynaud's disease, heavy metal toxicity, radiation sickness, * Pyroluria, schizophrenia, shock, snakebite, spider bite, tetanus toxin and viral pneumonia.
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." For example, Hoffer admits that in his experience, acute and not chronic schizophrenia responds to niacin.
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.
Administration of short-chain fatty acids in orthomolecular practice is usually done by increasing the level of dietary fiber. The fatty acids are produced by fermentation of the fiber in the colon, then absorbed into the body. Attempts are also made to aid this process by a combination of prebiotics and mucopolysaccharides. 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.
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.
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, run by the Journal of Orthomolecular Medicine, discusses differences between orthomolecular medicine and mainstream medicine,
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. The 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. 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 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, and it can generate testable hypotheses.
Amongst the differences, 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.
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.
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, 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.
 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. 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."
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.
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. 
 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. 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. 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.
Orthomolecular proponents, such as Robert Cathcart, who predicts that 120+ grams per day intravenous vitamin C should cure severe acute respiratory syndrome 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.
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. Based on testing with dosages well below orthomolecular recommendations, Linus Pauling has been criticized for making overbroad claims 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.
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. 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.
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. Megavitamin proponents point 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.
 Use of vitamin E in orthomolecular medicine
Vitamin E contains eight related chemicals, which are classed as either tocopherols or tocotrienols. These chemicals also exist as several stereoisomers. In supplements these are usually present in 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. 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. 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.
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. 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. A similar increase in mortality was seen in a 2007 meta-analysis 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, these results may not apply to the general population. 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.
Orthomolecular recommendations for vitamin E supplementation typically are based on a mixture of tocopheols and tocotrienols. Forms of "vitamin E", which contain mixed R,R,R tocopherols and are also recommended by some orthomolecular practitioners. 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 alone.
 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.
 Economic interests and politics
Some orthomolecular proponents claim that their findings are actively suppressed by 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 ... [h]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". 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.
The actions of Matthias Rath in South Africa have come under particular scrutiny. Rath worked with Linus Pauling and served as Director of Cardiovascular Research at the Linus Pauling Institute until 1992. He has published several papers on orthomolecular medicine, most notably a review co-authored with Pauling, with Abram Hoffer listing Rath as a notable contributor to the Journal of Orthomolecular Medicine. However, the relationship between Rath and Pauling later broke down over a lawsuit on intellectual property rights. Rath now promotes vitamins as a treatment for HIV infection, describing treatment with antiretroviral drugs as part of a global conspiracy serving the financial interests of the pharmaceutical industry. In a lawsuit that found against Rath, the South African Medical Association blamed his vitamin products for several deaths, the World Health Organization and two health agencies of the United Nations also described Rath's advertisements as "wrong and misleading" and "an irresponsible attack on ARV (antiretroviral) therapy."
The Linus Pauling Institute's funding comes mostly from National Institutes of Health. Several orthomolecular therapies have been officially sanctioned within Europe and Japan. 
 Notable supporters of orthomolecular medicine
 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."
 See also
- Alternative medicine
- Health freedom movement
- Life extension
- List of life extension related topics
- Megavitamin therapy
- Nutritional genomics
- Orthomolecular psychiatry
- ^ A Hoffer, M Walker (2000) Smart Nutrients, Avery, ISBN 0895295628
- ^ Orthomolecular medicine Encyclopedia of Alternative Medicine by Patricia Skinner
- ^ a b Definition of Orthomolecular medicine at www.orthomed.org Accessed June 2006
- ^ a b 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.
- ^ a b 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) 
- ^ ISOM. About OM
- ^ 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
- ^ a b Roger J. Williams (1998) Biochemical Individuality: The Basis for the Genetotrophic Concept. 2nd ed. Keats Publishing. ISBN 0-87983-893-0
- ^ Alpha-Lipoic Acid (Thioctic Acid): My Experience
- ^ Reduction of Cholesterol and Lp(A) in Regression of Coronary Artery Disease: A Case Study
- ^ Coenzyme Q10: A Novel Cardiac Antioxidant (1997)
- ^ RC Atkins (1998) Dr. Atkins' Vita-Nutrient Solution: Nature's Answer to Drugs, Simon & Schuster, ISBN 0684844885
- ^ JV Wright, L Lenard (2001) Why Stomach Acid Is Good for You, M. Evans and Company, Inc. ISBN 0871319314
- ^ a b NCCAM.NIH table 1 on page 8
- ^ a b 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. http://www.jco.org/cgi/pmidlookup?view=long&pmid=18235127.
- ^ a b c d "ACS : Orthomolecular Medicine". American Cancer Society (2007-06-19). Retrieved on 2008-04-04.
- ^ Lakhan SE, Vieira KF (2008) Nutritional therapies for mental disorders. Nutr J 7: 2. doi:10.1186/1475-2891-7-2 PMID 18208598
- ^ Stuart Aaronson et al. "Cancer Medicine", 2003, BC Decker Inc ISBN 1–55009–213–8, Section 20, p76
- ^ Nutrition Committee, Canadian Paediatric Society (1990). "Megavitamin and megamineral therapy in childhood". CMAJ 143 (10): 1009–1013. PMID 1699646. http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1452516. Retrieved on 4 April 2008.
- ^ a b Report 12 of the Council on Scientific Affairs: Alternative medicine American Medical Association June 1997, Accessed 21 March 2008
- ^ a b Jarvis WT (1983). "Food faddism, cultism, and quackery". Annu. Rev. Nutr. 3: 35–52. doi:10.1146/annurev.nu.03.070183.000343. PMID 6315036.
- ^ a b 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.
- ^ a b Braganza, S.F.; Ozuah, P.O. (2005). "Fad Therapies". Pediatrics in Review 26 (10): 371–376. doi:10.1542/pir.26-10-371. PMID 16199591.
- ^ "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. http://consensus.nih.gov/2006/2006MultivitaminMineralSOS028main.htm.
- ^ Huang HY, Caballero B, Chang S, et al (September 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. http://www.annals.org/cgi/pmidlookup?view=reprint&pmid=16880453.
- ^ a b Bjelakovic G, Nikolova D, Gluud LL, Simonetti RG, Gluud C (2008). "Antioxidant supplements for prevention of mortality in healthy participants and patients with various diseases". Cochrane Database of Systematic Reviews (2): CD007176. doi:10.1002/14651858.CD007176.
- ^ History of Orthomolecular Medicine
- ^ a b c d 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
- ^ Wilfred and Evan Shute
- ^ 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) "
- ^ Lois N. Magner A History of Medicine, Informa Healthcare; 2nd edition (June 23, 2005) ISBN 0824740742
- ^ Beard J. The action of 'trypsin' upon living cells of the Jensen sarcoma. Brit Med J 1906;1:140-141 (Jan. 20, 1906).
- ^ AscorbateWeb: Timeline from 1935 to 1939
- ^ MEGADOSES OF VITAMIN C AND DR. WILLIAM J. McCORMICK, McCormick HoF
- ^ 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
- ^ 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.
- ^ The Natural History of Ascorbic Acid in the Evolution of Mammals and Primates, Irwin Stone, 1972
- ^ Observations On the Dose and Administration of Ascorbic Acid When Employed Beyond the Range of a Vitamin in Human Pathology
- ^ Council for Responsible Nutrition. Vitamin and Mineral Recommendations
- ^ STONE. I.: Studies of a Mammalian Enzyme System for Producing Evolutionary Evidence on Man. Amer. J. Phys. Anthrop. 15, 83-85, 1965.
- ^ STONE. I.: On the Genetic Etiology of Scurvy. Acts Genet. Med. Gemellol. 15, 345-350,1966.
- ^ STONE, I.: Hypoascorbemia, the Genetic Disease Causing the Human Requirement for Exogenous Ascorbic Acid, Perspectives Bio. Med. 10, 133-134, 1966.
- ^ STONE, I.: The Genetic Disease, Hyposacorbemia: A Fresh Approach to an Ancient Disease and Some of its Medical Implications, Acta Genet Med. Gemellol. 16, 52-62. 1967.
- ^ In Memoriam Irwin Stone
- ^ ISOM. ISOM History of OM
- ^ Humphry Osmond HoF
- ^ Walter Kaufman HoF, Kaufman's bibliography
- ^ Guyton JR (2007). "Niacin in cardiovascular prevention: mechanisms, efficacy, and safety". Curr. Opin. Lipidol. 18 (4): 415–20. doi:10.1097/MOL.0b013e3282364add. PMID 17620858.
- ^ Definition of Orthomolecular medicine at www.orthomed.org Accessed June 2006 and What is Orthomolecular Medicine?, Linus Pauling Inst.
- ^ a b c d e Cassileth BR. Alternative medicine handbook: the complete reference guide to alternative and complementary therapies. New York: W.W.Norton & Co., 1998:67.
- ^ Meyer TC, Angus J. "The effect of large doses of 'Synkavit' in the newborn". Arch Dis Child 1956; vol 31, p. 212-5.
- ^ Laurance B. "Danger of vitamin K analogues to newborn." Lancet 1955; vol 1, p 819.
- ^ Sutor AH. New Aspects of Vitamin K Prophylaxis. Semin Thromb Hemost 2003; vol 29, p 373-376 "The problem was solved when synkavit [editor's note: no longer on the market] was replaced by low-dose (1 mg) [vitamin K1 phytomenadion"
- ^ Annals of Internal Medicine. [Vitamin C Pharmacokinetics: Implications for Oral and Intravenous Use http://www.annals.org/cgi/content/full/140/7/533]
- ^ PNAS. Pharmacologic ascorbic acid concentrations selectively kill cancer cells
- ^ Ascorbate in pharmacologic concentrations selectively generates ascorbate radical and hydrogen peroxide in extracellular fluid in vivo
- ^ Padayatty SJ, Riordan HD, Hewitt SM, Katz A, Hoffer LJ, Levine M (March 2006). "Intravenously administered vitamin C as cancer therapy: three cases". CMAJ 174 (7): 937–42. doi:10.1503/cmaj.050346. PMID 16567755. http://www.cmaj.ca/cgi/pmidlookup?view=long&pmid=16567755.
- ^ Assouline S, Miller WH (March 2006). "High-dose vitamin C therapy: renewed hope or false promise?". CMAJ 174 (7): 956–7. doi:10.1503/cmaj.060228. PMID 16567756. http://www.cmaj.ca/cgi/pmidlookup?view=long&pmid=16567756.
- ^ Research backs theory that vitamin C shrinks tumours. The Independent, 28 March 2006
- ^ Chen Q, Espey MG, Sun AY, et al (August 2008). "Pharmacologic doses of ascorbate act as a prooxidant and decrease growth of aggressive tumor xenografts in mice". Proc. Natl. Acad. Sci. U.S.A. 105 (32): 11105–11109. doi:10.1073/pnas.0804226105. PMID 18678913. http://www.pnas.org/content/105/32/11105.full.
- ^ Heaney ML, Gardner JR, Karasavvas N, et al (October 2008). "Vitamin C antagonizes the cytotoxic effects of antineoplastic drugs". Cancer Res. 68 (19): 8031–8. doi:10.1158/0008-5472.CAN-08-1490. PMID 18829561. Lay summary – New York Times (2008-10-01).
- ^ Vitamin C jabs may combat cancer New Scientist news service 04 August 2008. Accessed August 2008.
- ^ Kidd PM (September 2007). "Omega-3 DHA and EPA for cognition, behavior, and mood: clinical findings and structural-functional synergies with cell membrane phospholipids". Altern Med Rev 12 (3): 207–27. PMID 18072818. http://www.thorne.com/altmedrev/.fulltext/12/3/207.pdf.
- ^ Cameron E, Pauling L (1976). "Supplemental ascorbate in the supportive treatment of cancer: prolongation of survival times in terminal human cancer" (pdf). Proceeding of the National Academy of Sciences 73: 3685–3689. doi:10.1073/pnas.73.10.3685. PMID 1068480. http://yost.com/health/klenner/klenner-1971.pdf. Retrieved on 31 May 2008.
- ^ Ewan Cameron, Linus Pauling (1979). Cancer and vitamin C : a discussion of the nature, causes, prevention, and treatment of cancer with special reference to the value of vitamin C. New York: Norton. ISBN 0-393-50000-4.
- ^ Thomas Hager (1995). Force of Nature: The Life of Linus Pauling. New York: Simon & Schuster. ISBN 0684809095.
- ^ Clinical Data Shows Vitamin C May Reduce Risks of Cancer, Heart Disease and Variety of Other Health Disorders Genetic Engineering & Biotechnology News , September 24 2007 reporting on Seminars in Preventive and Alternative Medicine (vol. 3, iss. 1, pp. 25-35) Mark A. Moyad, MD, MPH of University of Michigan. accessed October 2007
- ^ Leung LH, A Stone that Kills two Birds: How Pantothenic Acid Unveils the Mysteries of Acne Vulgaris and Obesity, J. Orthomolecular Med., Vol. 12, 2nd Qtr 1997, Accessed 9 July 2007
- ^ Plaza SW, Lamson DW. Vitamin K2 in Bone Metabolism and Osteoporosis. Alt Medicine Review, Vol 10, No 1.
- ^ Hoffer A, et al. Treatment Protocol for Alcoholism. Orthomolecular Medicine News Service, 1 Jul 2005
- ^ Princeton Brain Bio Center. Brochure, distributed to patients. Skillman, N.J., 1983, The Center.
- ^ Skinner P, "Orthomolecular Medicine", Gale Encyclopedia of Alternative Medicine: Holistic medicine, Thomson Gale, 2004.
- ^ Klenner, F.R. (1971). "Observations on the dose and administration of ascorbic acid when employed beyond the range of a vitamin in human pathology" (pdf). J Appl Nutr 23: 61–88. http://yost.com/health/klenner/klenner-1971.pdf. Retrieved on 21 March 2008.
- ^ a b Richard P. Huemer MD, Orthomolecular Medicine, Encyclopedia of Complementary Health Practice, Springer Publishing Company, September 18, 1997. available online
- ^ Hoffer, A. Letter - Megavitamin and megamineral therapy in childhood
- ^ Huemer RP. A theory of diagnosis for orthomolecular medicine. J Theor Biol 1977 67:625-635. Reprinted in Advances 1984 1(3):53-59.
- ^ Weston Price (2008) [Nutrition and Physical Degeneration],Price Pottenger Nutrition; Eight Edition edition . ISBN-10: 0916764206
- ^ a b c http://orthomed.org/kunin.html Principles That Identify Orthormolecular Medicine: A Unique Medical Specialty by Richard A. Kunin
- ^ Monica & Gene Spiller (2005) What's with Fiber?, Ch 3, pp 22-29. Basic Health Publications. ISBN 159120111X
- ^ Gene A. Spiller (2001) CRC Handbook of Dietary Fiber in Human Nutrition, Third Edition. CRC Press. ISBN 0849323878
- ^ Escudero Alvarez E, González Sánchez P (2006). "Dietary fibre". Nutr Hosp 21 Suppl 2: 60–71, 61–72. PMID 16771074.
- ^ Lester M Morrison, OA Schjeide (1974) Coronary heart disease and the mucopolysaccharides (glycosaminoglycans), Charles C Thomas, Springfield, IL,, ISBN 0398029032
- ^ a b Orthomolecular Medicine Revisited, Wunderlich RC, Orthomolecular Medicine Online, accessed 6 Nov 2006
- ^ OMACOR®(omega-3-acid ethyl esters), Reliant Pharmaceuticals, Inc.
- ^ Mason M. "An Old Cholesterol Remedy [Niacin Is New Again"]. NY Times, January 23, 2007
- ^ Strader DB, Bacon BR, Lindsay KL, La Brecque DR, Morgan T, Wright EC, Allen J, Khokar MF, Hoofnagle JH, Seeff LB. Use of complementary and alternative medicine in patients with liver disease. Am J Gastroenterol. 2002 Sep;97(9):2391-7.
- ^ Orthomolecular Medicine Online
- ^ Leibovici L (1999). "Alternative (complementary) medicine: a cuckoo in the nest of empiricist reed warblers". BMJ 319 (7225): 1629–32. PMID 10600974. PMC: 1127092. http://bmj.com/cgi/pmidlookup?view=long&pmid=10600974.
- ^ Sampson, W.; Atwood Iv, K. (2005). "Propagation of the Absurd: demarcation of the Absurd revisited". Med. J Aust 183 (11-12): 580–581. https://www.mja.com.au/public/issues/183_11_051205/sam10986_fm.pdf.
- ^ Task Force on Complementary and Alternative Medicine (2000), Report on Complementary and Alternative Medicine, http://www.lrc.ky.gov/lrcpubs/Rm491.pdf
- ^ Lindeman, M.; Keskivaara, P.; Roschier, M. (2000). "Assessment of Magical Beliefs about Food and Health". Journal of Health Psychology 5 (2): 195. http://hpq.sagepub.com/cgi/content/abstract/5/2/195.
- ^ Jonas, W. B. (1999), "Magic and Methodology: when Paradigms Clash", The Journal of Alternative and Complementary Medicine 5 (4): 319–321, doi:10.1089/acm.1999.5.319, http://www.liebertonline.com/doi/abs/10.1089/acm.1999.5.319
- ^ Akobeng AK (2005). "Principles of evidence based medicine". Arch. Dis. Child. 90 (8): 837–40. doi:10.1136/adc.2005.071761. PMID 16040884. http://adc.bmj.com/cgi/content/full/90/8/837.
- ^ Weihrauch TR, Gauler TC (1999). "Placebo--efficacy and adverse effects in controlled clinical trials". Arzneimittelforschung 49 (5): 385–93. PMID 10367099.
- ^ DJ Hess, Complementary or Alternative? Stronger vs Weaker Integration Policies Am J Public Health. 2002 October; 92(10): 1579–1581.
- ^ Lasser KE, Allen PD, Woolhandler SJ, Himmelstein DU, Wolfe SM, Bor DH. Timing of New Black Box Warnings and Withdrawals for Prescription Medications. JAMA. 2002;287:2215-2220.
- ^ http://www.canstats.org/readdetail.asp?id=542
- ^ Marcia Angell, (August 24, 2004) The Truth About the Drug Companies: How They Deceive Us and What to Do About It, Random House, 1st ed, ISBN 0-375-50846-5
- ^ Frei, Emil; Kufe, Donald W.; Holland, James F. (2003). Cancer medicine 6. Hamilton, Ont: BC Decker. pp. 76. ISBN 1550092138. http://www.ncbi.nlm.nih.gov/books/bv.fcgi?highlight=orthomolecular&rid=cmed6.section.18479&WebEnv=0MnZPX94hO0XD2ugCELLkbhpkV5QLNBinRc8fAJ1IwDvCVoCzamY2zTpsFeeRiEdbTVTXzrZpQLqXt%40263F77C978AD3D40_0136SID&WebEnvRq=1#18482. Retrieved on 4 April 2008.
- ^ Braverman ER, Weissberg E, "Fish Oil As One Therapy in Cardiovascular Risk Factor Reduction," J Orthomolecular Medicine, 3(1), 1987
- ^ Berra K (2004). "Clinical update on the use of niacin for the treatment of dyslipidemia". J Am Acad Nurse Pract 16 (12): 526–34. PMID 15645997.
- ^ "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". Harv Heart Lett 14 (8): 4–5. 2004. PMID 15100082.
- ^ 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)"
- ^ Granot E, Kohen R. Oxidative stress in abetalipoproteinemia patients receiving long-term vitamin E and vitamin A supplementation, AJCN, Vol. 79, No. 2, 226-230, February 2004
- ^ Eisenberg DM, Cohen MH, Hrbek A, Grayzel J, Van Rompay MI, Cooper RA (December 2002). "Credentialing complementary and alternative medical providers". Ann. Intern. Med. 137 (12): 965–73. PMID 12484712. http://www.annals.org/cgi/pmidlookup?view=long&pmid=12484712.
- ^ 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. See also the letter to JAMA by Philip Taylor and Sanford Dawsey and the reply by the authors of the original paper.
- ^ "Dietary Supplement Health and Education Act of 1994". Food and Drug Administration (1994-10-25). Retrieved on 2008-04-04.
- ^ Falloon, W (2005-07-01). "What Do "Regulated" Supplements Cost". Life Extension Magazine. Retrieved on 2008-04-04.
- ^ Dodge T, Kaufman A (July 2007). "What makes consumers think dietary supplements are safe and effective? The role of disclaimers and FDA approval". Health Psychol. 26 (4): 513–7. doi:10.1037/0278-618.104.22.1683. PMID 17605572.
- ^ Orthomolecular Medicine News Service (OMNS) Listing or research and news items favourable to the Orthomolecular point of view
- ^ What is Orthomolecular Medicine?, Linus Pauling Institute. Accessed online, 1 Nov 2007
- ^ How safe are vitamins? Orthomolecular Medicine News Service, November 9, 2005 - Accessed August 2006
- ^ Jacobs, Joseph; Spencer, John A. D. (2003). Complementary and alternative medicine: an evidence-based approach. St. Louis: Mosby. ISBN 0323020283.
- ^ Cathcart, RF. "The Ascorbate Effect in Infectious and Autoimmune Diseases". Retrieved on 2008-04-04.
- ^ Hasslberger, S (2003-06-06). "Vitamin C could be effective against SARS". New Media Explorer. Retrieved on 2008-04-04.
- ^ Barrett, SJ (2001-05-05). "The Dark Side of Linus Pauling's Legacy". Quackwatch. Retrieved on 2008-04-04.
- ^ Padayatty SJ, Sun H, Wang Y, et al (2004). "Vitamin C pharmacokinetics: implications for oral and intravenous use" (pdf). Ann. Intern. Med. 140 (7): 533–7. PMID 15068981. http://www.annals.org/cgi/reprint/140/7/533.pdf.
- ^ "American Academy of Pediatrics Committee on Nutrition: megavitamin therapy for childhood psychoses and learning disabilities". Pediatrics 58 (6): 910–2. 1976. PMID 995522.
- ^ Rosenbloom, M (2007-12-12). "emedicine Toxicity, vitamin". eMedicine. Retrieved on 2008-04-04.
- ^ Rapola JM, Virtamo J, Ripatti S, et al (1997). "Randomised trial of alpha-tocopherol and beta-carotene supplements on incidence of major coronary events in men with previous myocardial infarction". Lancet 349 (9067): 1715–20. doi:10.1016/S0140-6736(97)01234-8. PMID 9193380.
- ^ Arroyave G (1988). "[Abuse of megadoses of vitamins]" (in Spanish; Castilian). Arch Latinoam Nutr 38 (3): 589–98. PMID 3153129.
- ^ Blair KA (1986). "Vitamin supplementation and megadoses". Nurse Pract 11 (7): 19–26, 31–6. PMID 3737019.
- ^ Roberts HJ (1995). "Vitamin E". Lancet 345 (8951): 737. PMID 7885163.
- ^ Bégin M, Kaegi E (1999). "Unconventional therapies and cancer" (pdf). CMAJ 161 (6): 686–7. PMID 10513271. http://www.cmaj.ca/cgi/reprint/161/6/686.
- ^ Saul, AW (2005-05-12). "Testimony by Andrew W. Saul before the Government of Canada, House of Commons Standing Committee on Health, regarding natural health product safety". Retrieved on 2008-04-04.
- ^ a b c Kline K, Lawson KA, Yu W, Sanders BG (2007). "Vitamin E and cancer". Vitam. Horm. 76: 435–61. doi:10.1016/S0083-6729(07)76017-X. PMID 17628185.
- ^ Cheeseman KH, Holley AE, Kelly FJ, Wasil M, Hughes L, Burton G (November 1995). "Biokinetics in humans of RRR-alpha-tocopherol: the free phenol, acetate ester, and succinate ester forms of vitamin E". Free Radic. Biol. Med. 19 (5): 591–8. doi:10.1016/0891-5849(95)00083-A. PMID 8529918.
- ^ Rigotti A (2007). "Absorption, transport, and tissue delivery of vitamin E". Mol. Aspects Med. 28 (5-6): 423–36. doi:10.1016/j.mam.2007.01.002. PMID 17320165.
- ^ a b Vitamin E Micronutrient Information Center, Linus Pauling Institute, Accessed31 May 2008
- ^ Traber MG (November 2006). "How much vitamin E? ... Just enough!". Am. J. Clin. Nutr. 84 (5): 959–60. PMID 17093143. http://www.ajcn.org/cgi/pmidlookup?view=long&pmid=17093143.
- ^ Gaziano JM (December 2004). "Vitamin E and cardiovascular disease: observational studies". Ann. N. Y. Acad. Sci. 1031: 280–91. doi:10.1196/annals.1331.028. PMID 15753154. http://www.annalsnyas.org/cgi/pmidlookup?view=long&pmid=15753154.
- ^ Hemilä H, Miller ER (July 2007). "Evidence-based medicine and vitamin E supplementation". Am. J. Clin. Nutr. 86 (1): 261–2; author reply 262–4. PMID 17616790. http://www.ajcn.org/cgi/pmidlookup?view=long&pmid=17616790.
- ^ Vivekananthan DP, Penn MS, Sapp SK, Hsu A, Topol EJ (2003). "Use of antioxidant vitamins for the prevention of cardiovascular disease: meta-analysis of randomised trials". Lancet 361 (9374): 2017–23. doi:10.1016/S0140-6736(03)13637-9. PMID 12814711.
- ^ Stocker R (2007). "Vitamin E". Novartis Found. Symp. 282: 77–87; discussion 87–92, 212–8. doi:10.1002/9780470319444.ch6. PMID 17913225.
- ^ Cherubini A, Vigna GB, Zuliani G, Ruggiero C, Senin U, Fellin R (2005). "Role of antioxidants in atherosclerosis: epidemiological and clinical update". Curr. Pharm. Des. 11 (16): 2017–32. doi:10.2174/1381612054065783. PMID 15974956.
- ^ Miller ER, Pastor-Barriuso R, Dalal D, Riemersma RA, Appel LJ, Guallar E (2005). "Meta-analysis: high-dosage vitamin E supplementation may increase all-cause mortality". Ann. Intern. Med. 142 (1): 37–46. PMID 15537682. http://www.annals.org/cgi/reprint/142/1/37.
- ^ Carter, T. Responses and Comments: High-Dosage Vitamin E Supplementation and All-Cause Mortality, Ann Intern Med. 2005 Jul 19;143(2):155; responses 150-160
- ^ Bjelakovic G, Nikolova D, Gluud L, Simonetti R, 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. http://jama.ama-assn.org/cgi/content/abstract/297/8/842.
- ^ Study Citing Antioxidant Vitamin Risks Based On Flawed Methodology, Experts Argue News release from Oregon State University published on ScienceDaily, Accessed 19 April 2007
- ^ M Walker, New/Old Findings on Unique Vitamin E, Townsend Letter for Doctors and Patients, No. 111, 1992, p. 826
- ^ Hoffer, A. The Finnish Antioxidant and Lung Cancer Study
- ^ Jiang Q, Christen S, Shigenaga MK, Ames BN (2001). "gamma-tocopherol, the major form of vitamin E in the US diet, deserves more attention". Am. J. Clin. Nutr. 74 (6): 714–22. PMID 11722951. http://www.ajcn.org/cgi/reprint/74/6/714.
- ^ Helzlsouer KJ, Huang HY, Alberg AJ, Hoffman S, Burke A, Norkus EP, Morris JS, Comstock GW. (2000). "Association between alpha-tocopherol, gamma-tocopherol, selenium, and subsequent prostate cancer.". J Natl Cancer Inst. 92 (24): 2018–23. PMID 11121464. http://www.ncbi.nlm.nih.gov/pubmed/11121464.
- ^ MA Somerville (2004) The Ethical Canary: Science, Society and the Human Spirit, pp 175-179, McGill-Queen's University Press; 1 ed, ISBN 0773527842
- ^ Sask. court rules boy with cancer can't pick treatment CBC, Friday, November 10, 2000, Accessed 07 April 2008
- ^ Hoffer A, "The Politics of Medical Research" J Orthomol Med, vol 8, no 1, 1993
- ^ Klenner, FR. Observations On the Dose and Administration of Ascorbic Acid When Employed Beyond the Range Of A Vitamin. Human Pathology Journal of Applied Nutrition Vol. 23, No's 3 & 4, Winter 1971.
- ^ Klenner FR. Virus Pneumonia and Its Treatment With Vitamin C. Southern Med Surg, v110, no 2, p36, 1948.
- ^ Klenner FR. The Treatment of Poliomyelitis and Other Virus Diseases with Vitamin C, Southern Med Surg, v111, no 7, p209, 1949.
- ^ Klenner FR. The Use of Vitamin C as an Antibiotic. J Appl Nutr, vol 6, p274, 1953
- ^ Abrams B, Duncan D, Hertz-Picciotto I (August 1993). "A prospective study of dietary intake and acquired immune deficiency syndrome in HIV-seropositive homosexual men". J. Acquir. Immune Defic. Syndr. 6 (8): 949–58. PMID 8100273.
- ^ Patrick L (December 1999). "Nutrients and HIV: part one -- beta carotene and selenium" (PDF). Altern Med Rev 4 (6): 403–13. PMID 10608913. http://www.thorne.com/altmedrev/.fulltext/4/6/403.pdf. Retrieved on 25 August 2008.
- ^ Lichtenstein BS (1995). "Nutrition and HIV". STEP Perspect 7 (1): 2–5. PMID 11362399.
- ^ RF Cathcart, Vitamin C in the Treatment of Acquired Immune Deficiency Syndrome (AIDS), Medical Hypotheses 14:423-433, 1984
- ^ Priestly JC. Highly Beneficial Results in the Treatment of AIDS, J Orthomolecular Med, 1991, Vol. 6, No.3 & 4, p174
- ^ a b Sarah Boseley Discredited doctor's 'cure' for Aids ignites life-and-death struggle in South Africa The Guardian May 14 2005
*Smith TC, Novella SP (August 2007). "HIV denial in the Internet era". PLoS Med. 4 (8): e256. doi:10.1371/journal.pmed.0040256. PMID 17713982. PMC: 1949841. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1949841.
*Apartheid a pharmaceutical plot - Rath Independent Online May 10 2007
- ^ Irlam JH, Visser ME, Rollins N, Siegfried N (2005). "Micronutrient supplementation in children and adults with HIV infection". Cochrane Database Syst Rev (4): CD003650. doi:10.1002/14651858.CD003650.pub2. PMID 16235333.
- ^ Semba RD, Ndugwa C, Perry RT, et al (January 2005). "Effect of periodic vitamin A supplementation on mortality and morbidity of human immunodeficiency virus-infected children in Uganda: A controlled clinical trial". Nutrition 21 (1): 25–31. doi:10.1016/j.nut.2004.10.004. PMID 15661475.
- ^ Mora JR, Iwata M, von Andrian UH (September 2008). "Vitamin effects on the immune system: vitamins A and D take centre stage". Nat. Rev. Immunol. 8: 685-698. doi:10.1038/nri2378. PMID 18690246.
- ^ Grotto I, Mimouni M, Gdalevich M, Mimouni D (March 2003). "Vitamin A supplementation and childhood morbidity from diarrhea and respiratory infections: a meta-analysis". J. Pediatr. 142 (3): 297–304. doi:10.1067/mpd.2003.116. PMID 12640379. http://linkinghub.elsevier.com/retrieve/pii/S0022347602403666.
- ^ Hoffer A. (1987) Is There a Conspiracy? Journal of Orthomolecular Medicine Volume 2 - 3rd Quarter p158
- ^ Razzouk, N.; Seitz, V. (2003), "Marketing to the Heart: a Practical Approach to Dealing with Health Care Quackery", Clinical Research and Regulatory Affairs 20 (4): 469–478, doi:10.1081/CRP-120026128, http://www.informaworld.com/index/713622947.pdf
- ^ Weitzman S (1998). "Alternative nutritional cancer therapies". Int. J. Cancer Suppl. 11: 69–72. PMID 9876483.
- ^ Gertz MA, Bauer BA (May 2003). "Caring (really) for patients who use alternative therapies for cancer". J. Clin. Oncol. 21 (9 Suppl): 125s–128s. doi:10.1200/JCO.2003.01.195. PMID 12743218.
- ^ Linus Pauling and Matthias Rath An Orthomolecular Theory of Human Health and Disease Journal of Orthomolecular Medicine Volume 6, p135
- ^ Abram Hoffer The Journal of Orthomolecular Medicine: history The Journal of Orthomolecular medicine, Accessed 25 August 2008
- ^ A. Hoffer Linus Pauling 1901 - 1994 Journal of Orthomolecular Medicine Vol. 9, No.3, 1994
- ^ Watson J (January 2006). "Scientists, activists sue South Africa's AIDS 'denialists'". Nat. Med. 12 (1): 6. doi:10.1038/nm0106-6a. PMID 16397537.
- ^ TAC hails ruling on Rath Independent Online June 13 2008
- ^ John Reed HIV Fight Focuses on Ads Los Angeles Times July 25, 2005
- ^ Frei, Balz, LPI Research Newsletter - Spring 2006, Linus Pauling Institute, June ,2006. available online
- ^ OMACOR deal signed with new Euro partners, HYDRO, 11 Dec 2001
- ^ fibrinolytic activity of nattokinase, Miyazaki Medical College, Japan
- ^ Coenzyme Q10, prescribed for CHF in Japan since 1974, AAFP
- ^ Kaitin, KI, Brown, J. 1995. A Drug Lag Update. Drug Information Journal 29:361–73
- ^ Hoffer, Abram, History, Journal of Orthomolecular Medicine. available online
 Further reading
- 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.
- 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 (November 2005). Textbook of Natural Medicine (Third ed ed.). Churchill Livingstone. pp. 2368. ISBN 0-443-07300-7.
- Barrett Stephen (1980). The Health Robbers (Second ed ed.). Stickley. pp. 52.
- 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. pp. 230. ISBN 0521803888.
- Gratzer Walter (2005). Terrors of the table. Oxford University Press. pp. 210. ISBN 0192806610.
 External links
- Journal of Orthomolecular Medicine
- 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)
- 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)
AHANAOA A. C.
Lic. Nut. Miguel Leopoldo Alvarado