Orthomolecular medicine

Orthomolecular medicine
Intervention
MeSH D009974
Biologically based alternative
and complementary therapy - edit
NCCAM classifications
  1. Alternative Medical Systems
  2. Mind-Body Intervention
  3. Biologically Based Therapy
  4. Manipulative Methods
  5. Energy Therapy
See also

Orthomolecular medicine[1][2] is a form of complementary and alternative medicine that seeks to maintain health and prevent or treat diseases by optimizing nutritional intake and/or prescribing supplements.[3][4][5] The approach is sometimes referred to as megavitamin therapy[1][2] as the practice evolved out of, and in some cases still uses, doses of vitamins and minerals many times higher than the recommended Dietary Reference Intake. Orthomolecular practitioners may also incorporate a variety of other treatment modalities into their approaches, including dietary restriction, megadoses of non-vitamin nutrients, and mainstream pharmaceutical drugs.[1][6] Proponents believe that non-optimal levels of certain substances can cause health issues beyond simple deficiency and see balancing them as an integral part of health.[7]

The term "orthomolecular" was coined by Linus Pauling to mean "the right molecules in the right amounts" (ortho is Greek for "right");[8] thus orthomolecular medicine focuses on using the right nutritional molecules in the right amounts for the individual. Proponents[9] state that treatments are based on patients' individual biochemistries.[10]

Critics have described some aspects of orthomolecular medicine as food faddism or quackery[11][12][13] and there is research suggesting that certain nutritional supplements are harmful[14][15][16] with several specific vitamin therapies linked to increased risk of cancer, heart disease, and death.[17][18][19]

Contents

History and development

In the early 20th century, some doctors hypothesised that vitamins could cure disease, and supplements were prescribed in megadoses by the 1930s.[20] Their effects on health were disappointing, though, and in the 1950s and 60s, nutrition was de-emphasised in standard medical curricula.[20] Orthomolecularists claim several figures from these early days of enthusiasm about nutrition as founders of their movement,[21] although the word "orthomolecular" was coined by Linus Pauling only in 1967.

Amongst the individuals claimed posthumously as orthomolecularists are Max Gerson, who developed a diet that he claimed could treat diseases, which the American Medical Association's 1949 Council on Pharmacy and Chemistry found ineffective;[22] and the Shute brothers, who attempted to treat heart disease with vitamin E.[23] Several concepts now claimed by orthomolecularists, including individual biochemical variation[10] and inborn errors of metabolism,[20][24][25] debuted in scientific papers early in the 20th century.

In 1948, William McCormick theorized that vitamin C deficiency played an important role in many diseases and began to use large doses in patients.[26] In the 1950s, Fred R. Klenner also used vitamin C megadosage as a therapy for a wide range of illnesses, including polio.[27] Irwin Stone claimed organisms that do not synthesise their own vitamin C due to a loss-of-function mutation have a disease he called "hypoascorbemia".[28] This term is not used by the medical community, and the idea of an organism-wide lack of a biosynthetic pathway as a disease was not endorsed by Stone's contemporaries.[29]

In the 1950s, some individuals believed that vitamin deficiencies caused mental illness.[20] Psychiatrists Humphry Osmond and Abram Hoffer gave people having acute schizophrenic episodes high doses of niacin,[30] while William Kaufman used niacinamide. While niacin has no known efficacy in psychiatric disease, the use of niacin in combination with statins and other medical therapies has become one of several medical treatments for cardiovascular disease.[31][32]

In the late 1960s, Linus Pauling introduced the expression "orthomolecular"[8] to express the idea of the right molecules in the right amounts.[8] Since the first claims of medical breakthroughs with vitamin C by Pauling and others, findings on the health effects of vitamin C have been controversial and contradictory.[33][34] Pauling has been criticised for making overbroad claims.[35]

Later research branched out into nutrients besides niacin and vitamin C, including essential fatty acids.[36]

Scope

According to Abram Hoffer, orthomolecular medicine does not purport to treat all diseases, nor is it "a replacement for standard treatment. A proportion of patients will require orthodox treatment, a proportion will do much better on orthomolecular treatment, and the rest will need a skillful blend of both."[37] Nevertheless, advocates have said that nutrients can prevent,[38] treat, and sometimes cure a wide range of medical conditions, including: acne,[39] alcoholism,[40] allergies, arthritis, autism, bee stings, bipolar disorder, burns, cancer,[41][42] the common cold, depression, drug addiction, drug overdose, epilepsy, heart diseases, heavy metal toxicity, acute hepatitis, herpes, hyperactivity, hypertension, hypoglycemia, influenza, learning disabilities, mental and metabolic disorders,[43] migraine, mononucleosis, mushroom poisoning, neuropathy & polyneuritis (including multiple sclerosis), osteoporosis,[44] polio, an hypothesised condition called "pyroluria", radiation sickness, Raynaud's disease, retardation, schizophrenia,[4] shock, skin problems, snakebite, spider bite, tetanus toxin and viral pneumonia.[45]

Orthomolecular psychiatry

Main article: Orthomolecular psychiatry

Hoffer believed that particular nutrients could cure mental illness. In the 1950s, he attempted to treat schizophrenia with niacin, although proponents of orthomolecular psychiatry say that the ideas behind their approach predate Hoffer.[46][47] Carl Pfeiffer of the Pfeiffer Treatment Center continued Hoffer’s approach, believing that for “every drug that benefits a patient, there is a natural substance that can achieve the same effect".[48] According to Hoffer and others who called themselves "orthomolecular psychiatrists", psychiatric syndromes result from biochemical deficiencies, allergies, toxicities or several hypothetical contributing conditions which they termed pyroluria, histadelia and histapenia. These purported causes were said to be found during an "individual biochemical workup" and treated with megavitamin therapy and dietary changes including fasting.[49] These diagnoses and treatments are not accepted by evidence-based medicine.[50]

Principles

According to Abram Hoffer, "primitive" peoples do not consume processed foods and do not have "degenerative" diseases.[51] In contrast, typical "Western" diets are said to be insufficient for long-term health, necessitating the use of megadose supplements of vitamins, dietary minerals, proteins, antioxidants, amino acids, ω-3 fatty acids, ω-6 fatty acids, medium chain triglycerides, dietary fiber, short and long chain fatty acids, lipotropes, systemic and digestive enzymes, other digestive factors, and prohormones to ward off hypothetical metabolism anomalies at an early stage, before they cause disease.[37]

Orthomolecularists say that they provide prescriptions for optimal amounts of micronutrients after individual diagnoses based on blood tests and personal histories.[3][9] Lifestyle and diet changes may also be recommended. The battery of tests ordered includes many that are not considered useful by medicine.[50]

Prevalence

Orthomolecular medicine is practiced by few medical practitioners,[52][53] but megavitamin treatments are increasingly found in over the counter retail products and naturopathic textbooks.

A survey released in May, 2004 by the National Center for Complementary and Alternative Medicine focused on who used complementary and alternative medicine (CAM), what was used, and why it was used in the United States by adults age 18 years and over during 2002. The survey reported uses in the previous twelve months that include orthomolecular related uses: Nonvitamin, nonmineral, natural products 18.9%, Diet-based therapies 3.5%, Megavitamin therapy 2.8%.[54]

Another recent CAM survey reported that 12% of liver disease patients used the antioxidant silymarin, more than 6% used vitamins, and that "in all, 74% of patients reported using CAM in addition to the medications prescribed by their physician, but 26% did not inform their physician of their CAM use."[55] 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.[56]

Medical and scientific reception

Methodology

Orthomolecular therapies have been criticized as lacking a sufficient evidence base for clinical use: their scientific foundations are too weak, the studies that have been performed are too few and too open to interpretation, and reported positive findings in observational studies are contradicted by the results of more rigorous clinical trials.[52][57] Accordingly, "there is no evidence that orthomolecular medicine is effective". Proponents of orthomolecular medicine strongly dispute this statement by citing studies demonstrating the effectiveness of treatments involving vitamins, though this ignores the belief that a normal diet will provide adequate nutrients to avoid deficiencies, and that orthomolecular treatments are not actually related to vitamin deficiency.[7] The lack of scientifically rigorous testing of orthomolecular medicine has led to its practices being classed with other forms of alternative medicine and regarded as unscientific.[58][59][60] It has been described as food faddism and quackery, with critics arguing that it is based upon an "exaggerated belief in the effects of nutrition upon health and disease."[11][12][13] Orthomolecular practitioners will often use dubious diagnostic methods to define what substances are "correct"; one example is hair analysis, which produces spurious results when used in this fashion.[7]

Proponents of orthomolecular medicine contend that, unlike some other forms of alternative medicine such as homeopathy, their ideas are at least biologically based, do not involve magical thinking,[61] and are capable of generating testable hypotheses.[62] Orthomolecular is not a standard medical term, and clinical use of specific nutrients is considered a form of chemoprevention (to prevent or delay development of disease) or chemotherapy (to treat an existing condition).[63]

Views on safety and efficacy

In general, the vitamin megadoses advocated by orthomolecular medicine are unsupported by scientific consensus.[31] Some vitamins are toxic in high doses,[64] including niacin (B3),[65] cholecalciferol (D)[66] and tocopherol (E).[67] Evidence does not support the efficacy of orthomolecular medicine in treating cancer or psychological health[68][69] and its claims have been criticized by most medical organizations, including the American Cancer Society, the American Psychiatric Association, the National Institute of Mental Health,[50] the American Academy of Pediatrics,[70] CHAMPUS, and the Canadian Paediatric Society. The American Medical Association describes as "myths" the ideas that adequate nutrition is not readily achievable with normal food, all food grown with pesticide is poisonous, all food additives are poisonous, vitamin and mineral deficiencies are common, that the cause of most disease is poor diet, which can be prevented by nutritional supplements. [71]

Similarly, the American Cancer Society comments that the current scientific evidence does not "support use of orthomolecular therapy for most of the conditions for which it is promoted." Some supplements have exhibited benefits for specific conditions, while a few have been confirmed to be harmful; the consumption of nutritious foods is the best recognized method to obtain vitamins, minerals, and nutrients crucial for good health.[31] Barrie Cassileth, an adviser on alternative medicine to the National Institutes of Health, stated that "scientific research has found no benefit from orthomolecular therapy for any disease,"[52] and medical textbooks also report that there is "no evidence that megavitamin or orthomolecular therapy is effective in treating any disease."[72]

A 1973 task force of the American Psychiatric Association unanimously concluded:

This review and critique has carefully examined the literature produced by megavitamin proponents and by those who have attempted to replicate their basic and clinical work. It concludes in this regard that the credibility of the megavitamin proponents is low. Their credibility is further diminished by a consistent refusal over the past decade to perform controlled experiments and to report their new results in a scientifically acceptable fashion. Under these circumstances this Task Force considers the massive publicity which they promulgate via radio, the lay press and popular books, using catch phrases which are really misnomers like "megavitamin therapy" and "orthomolecular treatment," to be deplorable.[73]

In response to claims that orthomolecular medicine could cure childhood psychoses and learning disorders, the American Academy of Pediatrics labelled orthomolecular medicine a "cult" in 1976.[74]

Proponents of orthomolecular medicine counter that some vitamins and nutrients are now used in medicine as treatments for specific diseases, such as megadose niacin and fish oil for dyslipidemias, and megavitamin therapies for a group of rare inborn errors of metabolism.[20] A review in the Annals of Internal Medicine concluded that while some therapies might be beneficial, others might be harmful or interfere with effective medical therapy.[75] A recent study of over 161,000 individuals provided, in the words of the authors, "convincing evidence that multivitamin use has little or no influence on the risk of common cancers, cardiovascular disease, or total mortality in postmenopausal women."[76] A recent meta-analysis in JAMA suggested that supplementation with combinations of antioxidant vitamins (beta-carotene, vitamin A, and vitamin E) may increase mortality, although with respect to beta-carotene this conclusion may be due to the known harmful effect in smokers.[77]

Safety

In the United States, pharmaceuticals must be proven safe and effective to the satisfaction of the FDA before they can be marketed, whereas dietary supplements must be proven unsafe before regulatory action can be taken.[78] A number of orthomolecular supplements are available in the US in pharmaceutical versions that are sometimes quite similar in strength and general content, or in other countries are regulated as pharmaceuticals. The US regulations also have provisions to recognize a general level of safety for established nutrients that can forgo new drug safety tests. Proponents of orthomolecular medicine argue that supplements are less likely to cause dangerous side-effects or harm, since they are normally present in the body.[5] Some vitamins are toxic in high doses[64] and nearly all will cause adverse effects given high levels of overdosing for prolonged periods as recommended by orthomolecular practitioners.[7] Forgoing medical care in favor of orthomolecular treatments can lead to adverse health outcomes.[68]

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. Potential risks[79] of inappropriate vitamin and supplement regimes include an increased risk of coronary heart disease,[80] hypertension, thrombophlebitis, peripheral neuropathy, ataxia, neurological effects, liver toxicity, congenital abnormalities, spontaneous abortion, gouty arthritis, jaundice, kidney stones, and diarrhea.[14][15][17][81][82][83][84] In their book Trick or Treatment, Edzard Ernst and Simon Singh conclude that "The concepts of orthomolecular medicine are not biologically plausible and not supported by the results of rigorous clinical trials. These problems are compounded by the fact that orthomolecular medicine can cause harm and is often very expensive."[7]

Example: vitamin E

Orthomolecular proponents claim that even large doses of vitamin E pose no risk to health and are useful for the treatment and prevention of a broad list of conditions, including heart and circulatory diseases, diabetes and nephritis.[85] Initial hopes for the usefulness of vitamin E in orthomolecular medicine were based on epidemiological studies suggesting that people who consumed more vitamin E had lower risks of chronic disease, such as coronary heart disease.[86] These observational studies could not distinguish between whether the higher levels of vitamin E improved health themselves, or whether confounding variables (such as other dietary factors or exercise) were responsible.[87][88] To distinguish between these possibilities, a number of randomized controlled trials were performed and meta-analysis of these controlled clinical trials have not shown any clear benefit from any form of vitamin E supplementation for preventing chronic disease.[89][90][91][92] Further clinical studies show no benefit of vitamin E supplements for cardiovascular disease.[93] The current position of the National Institutes of Health is that there is no convincing evidence that vitamin E supplements can prevent or treat any disease.[94]

Beyond the lack of apparent benefit, a series of three meta-analyses reported that vitamin E supplementation is associated with an increased risk of death; one of the meta-analyses performed by the Cochrane Collaboration also found significantly increased mortality for the antioxidant vitamins A and beta-carotene.[16] [95][96]

Use in AIDS

Several articles in the alternative-medicine literature have suggested that orthomolecular-related dietary supplementation might be helpful for patients with HIV/AIDS.[97][98] However, high-dose vitamin C treatments have been studied clinically to treat AIDS patients without any positive result.[99] An analysis of fifteen clinical trials of micronutrient therapies by the Cochrane Collaboration in 2005 found no evidence that such approaches either reduce symptoms or mortality in HIV-infected adults who are not malnourished, but found evidence, in one hospital, that giving vitamin A to infants with HIV may be beneficial.[100] Vitamin A deficiency is found in children with HIV infection who may or may not have symptoms of AIDS. Vitamin A supplementation reduces morbidity and mortality in AIDS symptomatic children, but has no effect on asymptomatic children. It does not prevent HIV infection, cannot treat the chronic HIV infection, and will not cure AIDS.[101][102]

Deaths resulting from illegal vitamin trials in South Africa

Main article: Matthias Rath

Matthias Rath has been extensively criticized for presenting his vitamin supplements as a treatment for AIDS and for testing them in illegal trials in South Africa.[103][104] A former associate of Linus Pauling, Rath now promotes vitamins as a treatment for HIV infection, describing treatment with effective antiretroviral drugs as toxic and part of a global conspiracy serving the financial interests of the pharmaceutical industry.[105] In a lawsuit that found against Rath, the South African Medical Association blamed his vitamin products for several deaths.[104][106][107] 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.”[108] The South African Centre for Social Science Research described the trials as "state sponsored pseudo-science".[109] Rath's trials, conducted with the aid of AIDS denialist David Rasnick, were declared unlawful by the Cape High Court; Rath, Rasnick and their foundation were barred from conducting further unauthorised clinical trials and from advertising their products.[110]

Conspiracy theories alleged by orthomolecular medicine advocates

Advocates of orthomolecular medicine, including Pauling, Hoffer and Ewan Cameron have claimed that their findings are actively suppressed by a conspiracy of the medical community and the pharmaceutical industry. 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".[111][112]

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

We had to create our own journals because it was impossible to obtain entry into the official journals of psychiatry and medicine. Before 1967 I had not found it difficult to publish reports in these journals, and by then I had about 150 articles and several books in the establishment press.[113]

The scientific and medical community regards such claims of a conspiracy as unsubstantiated.[114][115] A review in the Journal of Clinical Oncology described such conspiracy theories, which allege collusion amongst physicians against unconventional and unproven treatments, as a common theme in many forms of alternative medicine.[116] Despite claims of conspiracy, the Linus Pauling Institute's funding comes primarily from the National Institutes of Health,[117] and some orthomolecular therapies have been sanctioned in Japan.[118]

See also

Citations

  1. ^ a b c Saul AW; Hoffer A (2008). Orthomolecular Medicine For Everyone: Megavitamin Therapeutics for Families and Physicians. Laguna Beach, California: Basic Health Publications. ISBN 1-59120-226-4. OCLC 232131968. OL16944688M. 
  2. ^ a b McMichael AJ (January 1981). "Orthomolecular medicine and megavitamin therapy". Med. J. Aust. 1 (1): 6–8. PMID 7207301. 
  3. ^ a b Hoffer A, Walker M (2000). Smart Nutrients. Avery. ISBN 0895295628. 
  4. ^ a b Skinner Patricia (2004). "Gale encyclopedia of alternative medicine: holistic medicine". Thomson Gale. http://findarticles.com/p/articles/mi_g2603/is_0000/ai_2603000096. 
  5. ^ a b "Orthomolecular medicine". orthomed.org. http://www.orthomed.org/. Retrieved June 2006. 
  6. ^ Braverman Eric Dr. (1979). "Orthomolecular Medicine and Megavitamin Therapy: Future and Philosophy". Journal of Orthomolecular Medicine 8 (4): 265. http://www.orthomolecular.org/library/jom/1979/pdf/1979-v08n04-p265.pdf. 
  7. ^ a b c d e Singh, S; Ernst E (2008). Trick or Treatment: The Undeniable Facts About Alternative Medicine. Norton. pp. 320. ISBN 0393066616. 
  8. ^ a b c Pauling L (April 1968). "Orthomolecular psychiatry. Varying the concentrations of substances normally present in the human body may control mental disease". Science 160 (3825): 265–71. Bibcode 1968Sci...160..265P. doi:10.1126/science.160.3825.265. PMID 5641253. http://www.sciencemag.org/cgi/pmidlookup?view=long&pmid=5641253. 
  9. ^ a b Baumel Syd (August 2000). Dealing with depression naturally : complementary and alternative therapies for restoring emotional health (2nd ed.). Los Angeles: McGraw-Hill. ISBN 0658002910. OCLC 43641423. 
  10. ^ a b Williams RJ (1998). Biochemical individuality: the basis for the genetotrophic concept (2nd ed.). New Canaan, Connecticut: Keats. ISBN 0879838930. OCLC 38239195. 
  11. ^ a b Jarvis WT (1983). "Food faddism, cultism, and quackery". Annu Rev Nutr 3 (1): 35–52. doi:10.1146/annurev.nu.03.070183.000343. PMID 6315036. 
  12. ^ a b Jukes TH (1990). "Nutrition science from vitamins to molecular biology". Annual Review of Nutrition 10 (1): 1–20. doi:10.1146/annurev.nu.10.070190.000245. PMID 2200458.  A short summary is in the journal's preface.
  13. ^ a b Braganza SF; Ozuah PO (2005). "Fad therapies". Pediatrics in Review 26 (10): 371–376. doi:10.1542/pir.26-10-371. PMID 16199591. 
  14. ^ a b "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. 
  15. ^ a b 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. 
  16. ^ a b Bjelakovic G, Nikolova D, Gluud LL, Simonetti RG, Gluud C (2008). Bjelakovic, Goran. ed. "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. PMID 18425980. 
  17. ^ a b Satia JA, Littman A, Slatore CG, Galanko JA, White E (April 2009). "Long-term Use of β-Carotene, Retinol, Lycopene, and Lutein Supplements and Lung Cancer Risk: Results From the VITamins And Lifestyle (VITAL) Study". Am. J. Epidemiol. 169 (7): 815–28. doi:10.1093/aje/kwn409. PMC 2842198. PMID 19208726. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2842198. 
  18. ^ Brody, Jane (March 23, 2009). "Extra Vitamin E: No Benefit, Maybe Harm". New York Times. http://www.nytimes.com/2009/03/24/health/24brod.html. Retrieved March 24, 2009. 
  19. ^ "High dose vitamin E death warning". BBC. November 11, 2004. http://news.bbc.co.uk/1/hi/health/3998847.stm. Retrieved March 24, 2009. 
  20. ^ a b c d e Menolascino FJ, Donaldson JY, Gallagher TF, Golden CJ, Wilson JE (1988). "Orthomolecular therapy: its history and applicability to psychiatric disorders". Child Psychiatry Hum Dev 18 (3): 133–50. doi:10.1007/BF00709727. PMID 2898324. 
  21. ^ "History of Orthomolecular Medicine". http://www.orthomolecular.org/history/index.shtml. 
  22. ^ AMA Council on Pharmacy and Chemistry (January 8, 1949). "Report of the council: cancer and the need for facts". JAMA 139: 93–98. 
  23. ^ "Evan Shute & Wilfrid Shute". Hall of Fame. Orthomolecular.org. http://orthomolecular.org/hof/2004/ewshute.html. Retrieved 2009-03-13. 
  24. ^ Mason SF (1997). "The science and humanism of Linus Pauling (1901–1994)". Chemical Society Reviews 26 (1): 29. doi:10.1039/cs9972600029. http://oregonstate.edu/dept/spc/subpages/ahp/overview/entirearticle.htm. Retrieved 2009-02-16. 
  25. ^ Magner Lois N (2005). A history of medicine (Second ed.). Washington, DC: Taylor & Francis. ISBN 0824740742. OCLC 142979953. 
  26. ^ McCormick WJ (January 1951). "Vitamin C in the prophylaxis and therapy of infectious diseases". Arch Pediatr 68 (1): 1–9. PMID 14800557. 
  27. ^ Saul AW (2007). "Hidden in plain sight: the pioneering work of Frederick Robert Klenner, M.D". J Orthomolecular Med 22 (1): 31–38. http://www.doctoryourself.com/klennerbio.html. Retrieved 2009-02-16. 
  28. ^ Stone I (January 1967). "The genetic disease, Hypoascorbemia. A fresh approach to an ancient disease and some of its medical implications". Acta Genet Med Gemellol (Rome) 16 (1): 52–62. PMID 6063937. 
  29. ^ Chatterjee IB (December 1973). "Evolution and the Biosynthesis of Ascorbic Acid". Science 182 (4118): 1271–2. Bibcode 1973Sci...182.1271C. doi:10.1126/science.182.4118.1271. PMID 4752221. 
  30. ^ Hoffer A, Osmond H, Callbeck MJ, Kahan I (1957). "Treatment of schizophrenia with nicotinic acid and nicotinamide". J Clin Exp Psychopathol 18 (2): 131–58. PMID 13439009. 
  31. ^ a b c "Orthomolecular medicine". Making treatment decisions. American Cancer Society. 2007-06-19. http://www.cancer.org/docroot/ETO/content/ETO_5_3X_Orthomolecular_Medicine.asp?sitearea=ETO. Retrieved 2008-04-04. 
  32. ^ 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. 
  33. ^ 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 105 (32): 11105–11109. Bibcode 2008PNAS..10511105C. doi:10.1073/pnas.0804226105. PMC 2516281. PMID 18678913. http://www.pnas.org/content/105/32/11105.full. 
  34. ^ 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). 
  35. ^ Barrett, SJ (2001-05-05). "The dark side of Linus Pauling's legacy". Quackwatch. http://www.quackwatch.org/01QuackeryRelatedTopics/pauling.html. Retrieved 2008-04-04. 
  36. ^ Kidd PM (September 2007). "Omega-3 DHA and EPA for cognition, behavior, and mood: clinical findings and structural-functional synergies with cell membrane phospholipids" (PDF). Altern Med Rev 12 (3): 207–27. PMID 18072818. 
  37. ^ a b Huemer RP (August 1977). "A theory of diagnosis for orthomolecular medicine". J Theor Biol 67 (4): 625–35. doi:10.1016/0022-5193(77)90250-8. PMID 904336. http://linkinghub.elsevier.com/retrieve/pii/0022-5193(77)90250-8. 
  38. ^ Moyad Mark A (September 24, 2007). "Clinical data shows vitamin C may reduce risks of cancer, heart disease and variety of other health disorders". Genetic Engineering & Biotechnology News 3 (1): 25–35. http://www.genengnews.com/news/bnitem.aspx?name=23587988. Retrieved October 2007. 
  39. ^ Leung Lit-Hung (1997). "A stone that kills two birds: how pantothenic acid unveils the mysteries of acne vulgaris and obesity". J Orthomol Med 12 (2): 99–114. ISSN 0834-4825. OCLC 15726974. http://orthomolecular.org/library/jom/1997/articles/1997-v12n02-p099.shtml. 
  40. ^ Francis Hartigan (2000). Bill W. : a biography of Alcoholics Anonymous cofounder Bill Wilson. New York: Thomas Dunne Books. pp. 204–209. ISBN 0312200560. OCLC 42772358. 
  41. ^ Cameron Ewan, Pauling Linus (1976). "Supplemental ascorbate in the supportive treatment of cancer: Prolongation of survival times in terminal human cancer". Proceeding of the National Academy of Sciences 73 (10): 3685–9. Bibcode 1976PNAS...73.3685C. doi:10.1073/pnas.73.10.3685. PMC 431183. PMID 1068480. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=431183.  (self published)
  42. ^ Cameron Ewan, Pauling Linus (1979). Cancer and vitamin C : a discussion of the nature, causes, prevention, and treatment of cancer with special reference to the value of vitamin C. New York: Norton. ISBN 0393500004. OCLC 5788147. 
  43. ^ Princeton Brain Bio Center. Brochure, distributed to patients. Skillman, New Jersey, 1983, The Center.
  44. ^ Plaza, S. M.; Lamson, D. W. (2005). "Vitamin K2 in bone metabolism and osteoporosis". Alternative medicine review : a journal of clinical therapeutic 10 (1): 24–35. PMID 15771560.  edit
  45. ^ Klenner FR (1971). "Observations on the dose and administration of ascorbic acid when employed beyond the range of a vitamin in human pathology". J Appl Nutr 23: 61–88.  as reprinted with edits in Hoffer A, ed (1998). "Observations on the dose and administration of ascorbic acid when employed beyond the range of a vitamin in human pathology" (PDF). J Orthomol Med 13 (4): 198–210. ISSN 0834-4825. OCLC 15726974. http://orthomolecular.org/library/jom/1998/pdf/1998-v13n04-p198.pdf.  (self published)
  46. ^ Reiter, PJ (1927). "Behandlung von Dementia Praecox mit metallsalzen. Mangan. Z". Neur 108: 464–80.  as cited in Pfeiffer, C; LaMola, S (1983). "Zinc and Manganese in the Schizophrenias". Journal of Orthomolecular Psychiatry 12 (3). 
  47. ^ Kay Lily E (1993). The molecular vision of life: Caltech, the Rockefeller Foundation, and the rise of the new biology. Oxford: Oxford University Press. ISBN 0195111435. 
  48. ^ Barney, Paul (1998). Doctor's guide to natural medicine. Pleasant Grove, Utah: Woodland. ISBN 1885670842. 
  49. ^ Edelman Eva (2001). Natural healing for schizophrenia: and other common mental disorders. Borage. ISBN 0965097676. 
  50. ^ a b c Barrett, Stephen (2000-07-12). "Orthomolecular therapy". Quackwatch. http://www.quackwatch.org/01QuackeryRelatedTopics/ortho.html. Retrieved 2008-01-02. 
  51. ^ Weston Price (2008). [Nutrition and Physical Degeneration] (8th ed.). Price Pottenger Nutrition. ISBN 0916764206. 
  52. ^ a b c Cassileth Barrie R (1999). The alternative medicine handbook: the complete reference guide to alternative and complementary therapies. New York: W.W. Norton. pp. 67. ISBN 0393318168. OCLC 40880206. 
  53. ^ Wunderlich RC. "Orthomolecular Medicine Revisited" (PDF). Orthomolecular Medicine Online. http://www.orthomolecular.org/library/jom/1988/pdf/1988-v03n04-p159.pdf. Retrieved 2009-03-02. 
  54. ^ Barnes PM, Powell-Griner E, McFann K, Nahin RL (May 2004). "Complementary and alternative medicine use among adults: United States, 2002" (PDF). Adv Data (343): 1–19. PMID 15188733. http://www.cdc.gov/nchs/data/ad/ad343.pdf. 
  55. ^ Strader DB, Bacon BR, Lindsay KL, et al. (September 2002). "Use of complementary and alternative medicine in patients with liver disease". Am J Gastroenterol 97 (9): 2391–7. doi:10.1111/j.1572-0241.2002.05993.x. PMID 12358262. 
  56. ^ 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. 
  57. ^ "Vitamin C for SARS?". Canadian Statistical Assessment Service. June 12, 2003. Archived from the original on September 25, 2005. http://web.archive.org/web/20050925010741/http://www.canstats.org/readdetail.asp?id=542. 
  58. ^ Leibovici L (1999). "Alternative (complementary) medicine: a cuckoo in the nest of empiricist reed warblers". BMJ 319 (7225): 1629–32. PMC 1127092. PMID 10600974. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1127092. 
  59. ^ Sampson W, Atwood K (2005). "Propagation of the Absurd: demarcation of the Absurd revisited" (PDF). Med J Aust 183 (11–12): 580–1. PMID 16336135. https://www.mja.com.au/public/issues/183_11_051205/sam10986_fm.pdf. 
  60. ^ Task Force on Complementary and Alternative Medicine; Burch T et al. (2000). "Report on complementary and alternative medicine" (PDF). Frankfort, Kentucky: Legislative Research Commission. http://www.lrc.ky.gov/lrcpubs/Rm491.pdf. 
  61. ^ Lindeman M, Keskivaara P, Roschier M (April 1, 2000). "Assessment of magical beliefs about food and health". Journal of Health Psychology 5 (2): 195. doi:10.1177/135910530000500210. http://hpq.sagepub.com/cgi/content/abstract/5/2/195. 
  62. ^ Jonas WB (1999). "Magic and methodology: when paradigms clash". The Journal of Alternative and Complementary Medicine 5 (4): 319–21. doi:10.1089/acm.1999.5.319. PMID 10471010. http://www.liebertonline.com/doi/abs/10.1089/acm.1999.5.319. 
  63. ^ Martínez ME, Marshall JR, Giovannucci E (2008). "Diet and cancer prevention: the roles of observation and experimentation" (PDF). Nature Reviews: Cancer 8 (9): 694–703. doi:10.1038/nrc2441. PMID 19143054. http://www.nature.com/nrc/journal/v8/n9/pdf/nrc2441.pdf. 
  64. ^ a b Nutrition Committee, Canadian Paediatric Society (January 1, 1990). "Megavitamin and megamineral therapy in childhood. Nutrition Committee, Canadian Paediatric Society". CMAJ 143 (10): 1009–13. PMC 1452516. PMID 1699646. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1452516. 
  65. ^ National Library of Medicine (March 2009). "Niacin". MedlinePlus Encyclopedia. National Library of Medicine. http://www.nlm.nih.gov/medlineplus/ency/article/002409.htm. Retrieved 2010-04-28. "Large doses of niacin can cause liver damage, peptic ulcers, and skin rashes. Even normal doses can be associated with skin flushing. It can be prescribed as a treatment for elevated total cholesterol and other types of lipid disorders, but it should only be used with medical supervision due to its potential for severe side effects." 
  66. ^ National Library of Medicine (March 2009). "Vitamin D". MedlinePlus Encyclopedia. National Library of Medicine. http://www.nlm.nih.gov/medlineplus/ency/article/002405.htm. Retrieved 2010-04-28. "Vitamin D deficiency can lead to osteoporosis in adults or rickets in children. Too much vitamin D can make the intestines absorb too much calcium. This may cause high levels of calcium in the blood. High blood calcium can lead to calcium deposits in soft tissues such as the heart and lungs. This can reduce their ability to function. Kidney stones, vomiting, and muscle weakness may also occur in someone who has too much vitamin D." 
  67. ^ National Library of Medicine (March 2009). "Vitamin E". MedlinePlus Encyclopedia. National Library of Medicine. http://www.nlm.nih.gov/medlineplus/ency/article/002406.htm. Retrieved 2010-04-28. "In November, 2004, the American Heart Association stated that high amounts of vitamin E can be harmful. Taking 400 IU per day, or higher, may increase the risk of death. Taking smaller amounts, such as those found in a typical multivitamin, was not harmful." 
  68. ^ a b Aaronson S et al. (2003). "Cancer medicine". In Frei Emil, Kufe Donald W, Holland James F. Cancer medicine 6. Hamilton, Ontario: BC Decker. pp. 76. ISBN 1-55009-213-8. http://www.ncbi.nlm.nih.gov/books/bv.fcgi?call=bv.View..ShowTOC&rid=cmed6.TOC&depth=2. 
  69. ^ Miller M (1996). "Diet and psychological health". Altern Ther Health Med 2 (5): 40–8. PMID 8795935. 
  70. ^ Bennett, Forrest C. "Vitamin and mineral supplementation in Down's syndrome". http://pediatrics.aappublications.org/cgi/content/abstract/72/5/707. 
  71. ^ Council on Scientific Affairs (June 1997). "Report 12: Alternative medicine". American Medical Association. http://www.ama-assn.org/ama/no-index/about-ama/13638.shtml. Retrieved 2009-02-18. 
  72. ^ Frei Emil, Kufe Donald W, Holland James F (2003). "20.76. Complementary and alternative cancer therapies". Cancer medicine 6. Hamilton, Ontario: 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 2008-04-04. 
  73. ^ Lipton M, et al. (1973). Task force report on megavitamin and orthomolecular therapy in psychiatry. Washington DC: American Psychiatric Association. ; as cited in Barrett, Stephen (2000-07-12). "Orthomolecular Therapy". Quackwatch. http://www.quackwatch.org/01QuackeryRelatedTopics/ortho.html. Retrieved 2008-01-02. 
  74. ^ American Academy of Pediatrics Committee on Nutrition (1976). "Megavitamin therapy for childhood psychoses and learning disabilities". Pediatrics 58 (6): 910–2. PMID 995522. 
  75. ^ 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. 
  76. ^ Neuhouser ML, Wassertheil-Smoller S, Thomson C, et al. (February 2009). "Multivitamin use and risk of cancer and cardiovascular disease in the Women's Health Initiative cohorts". Arch Intern Med 169 (3): 294–304. doi:10.1001/archinternmed.2008.540. PMID 19204221. 
  77. ^ 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.
  78. ^ "Dietary Supplement Health and Education Act of 1994". Food and Drug Administration. 1994-10-25. http://www.fda.gov/opacom/laws/dshea.html. Retrieved 2008-04-04. 
  79. ^ Rosenbloom, M (2007-12-12). "Toxicity, vitamin". eMedicine. http://www.emedicine.com/emerg/topic638.htm. Retrieved 2008-04-04. 
  80. ^ 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. 
  81. ^ Arroyave G (1988). "[Abuse of megadoses of vitamins]" (in Spanish; Castilian). Arch Latinoam Nutr 38 (3): 589–98. PMID 3153129. 
  82. ^ Blair KA (1986). "Vitamin supplementation and megadoses". Nurse Pract 11 (7): 19–26, 31–6. doi:10.1097/00006205-198607000-00003. PMID 3737019. 
  83. ^ Roberts HJ; Roberts, H (1995). "Vitamin E". Lancet 345 (8951): 737. doi:10.1016/S0140-6736(95)90913-3. PMID 7885163. 
  84. ^ Bégin M, Kaegi E (1999). "Unconventional therapies and cancer" (PDF). CMAJ 161 (6): 686–7. PMC 1230613. PMID 10513271. http://www.cmaj.ca/cgi/reprint/161/6/686. 
  85. ^ "Vitamin E: Safe, Effective, and Heart-Healthy". Orthomolecular Medicine News Service. 2005-03-23. http://www.orthomolecular.org/resources/omns/v01n01.shtml. 
  86. ^ Traber MG (November 2006). "How much vitamin E? ... Just enough!". Am J Clin Nutr 84 (5): 959–60. PMID 17093143. 
  87. ^ Gaziano JM (December 2004). "Vitamin E and cardiovascular disease: observational studies". Ann N Y Acad Sci 1031 (1): 280–91. Bibcode 2004NYASA1031..280G. doi:10.1196/annals.1331.028. PMID 15753154. 
  88. ^ Hemilä H, Miller ER (July 1, 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. 
  89. ^ 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". The Lancet 361 (9374): 2017–23. doi:10.1016/S0140-6736(03)13637-9. PMID 12814711. 
  90. ^ Stocker R (2007). "Vitamin E". Novartis Found Symp. Novartis Foundation Symposia 282: 77–87; discussion 87–92, 212–8. doi:10.1002/9780470319444.ch6. ISBN 9780470319444. PMID 17913225. 
  91. ^ 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. 
  92. ^ 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. 
  93. ^ Sesso HD, Buring JE, Christen WG, et al. (November 2008). "Vitamins E and C in the Prevention of Cardiovascular Disease in Men: The Physicians' Health Study II Randomized Trial". J Am Med Assoc 300 (18): 2123–33. doi:10.1001/jama.2008.600. PMC 2586922. PMID 18997197. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2586922. 
  94. ^ "Vitamin E". National Institutes of Health. 2009. http://ods.od.nih.gov/factsheets/vitamine.asp. 
  95. ^ 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. 
  96. ^ 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". J Am Med Assoc 297 (8): 842–57. doi:10.1001/jama.297.8.842. PMID 17327526. http://jama.ama-assn.org/cgi/content/abstract/297/8/842. 
  97. ^ Patrick Lyn (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 2008-08-25. 
  98. ^ Lichtenstein BS (1995). "Nutrition and HIV". STEP Perspect 7 (1): 2–5. PMID 11362399. 
  99. ^ Batterham M, Gold J, Naidoo D, et al. (February 2001). "A preliminary open label dose comparison using an antioxidant regimen to determine the effect on viral load and oxidative stress in men with HIV/AIDS". Eur J Clin Nutr 55 (2): 107–14. doi:10.1038/sj.ejcn.1601124. PMID 11305623. 
  100. ^ Irlam JH, Visser ME, Rollins N, Siegfried N (2005). Irlam, James JH. ed. "Micronutrient supplementation in children and adults with HIV infection". Cochrane Database Syst Rev (4): CD003650. doi:10.1002/14651858.CD003650.pub2. PMID 16235333. 
  101. ^ 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. 
  102. ^ Mehta Saurabh, Fawzi Wafaie (2007). "Effects of vitamins, including vitamin A, on HIV/AIDS patients". Vitam Horm. Vitamins & Hormones 75: 355–83. doi:10.1016/S0083-6729(06)75013-0. ISBN 9780127098753. PMID 17368322. 
  103. ^ Kapp C (November 2006). "South Africans hope for a new era in HIV/AIDS policies". Lancet 368 (9549): 1759–60. doi:10.1016/S0140-6736(06)69717-1. PMID 17120343. 
  104. ^ a b Smith TC, Novella SP (August 2007). "HIV Denial in the Internet Era". PLoS Med 4 (8): e256. doi:10.1371/journal.pmed.0040256. PMC 1949841. PMID 17713982. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1949841. 
  105. ^ Boseley Sarah (May 14, 2005). "Discredited doctor's 'cure' for Aids ignites life-and-death struggle in South Africa". Manchester: The Guardian. http://www.guardian.co.uk/world/2005/may/14/southafrica.internationalaidanddevelopment. 
    *"Apartheid a pharmaceutical plot - Rath". Cape Town: Independent Online. May 10, 2007. http://www.int.iol.co.za/index.php?set_id=1&click_id=6&art_id=nw20070510150555640C886929. 
  106. ^ Watson J (January 2006). "Scientists, activists sue South Africa's AIDS 'denialists'". Nat Med 12 (1): 6. doi:10.1038/nm0106-6a. PMID 16397537. 
  107. ^ "TAC hails ruling on Rath". Cape Town: Independent Online. June 13, 2008. http://www.iol.co.za/index.php?set_id=1&click_id=15&art_id=nw20080613124210476C691501. 
  108. ^ Reed John (July 25, 2005). "HIV fight focuses on ads". Los Angeles Times. http://articles.latimes.com/2005/jul/25/business/ft-aids25. 
  109. ^ Geffen N (2005). "Echoes of Lysenko: State-sponsored pseudo-science in South Africa". Social Dynamics. http://www.tac.org.za/documents/wp149.pdf. 
  110. ^ "South African court bans AIDS vitamin trials". Reuters. June 13, 2008. http://www.reuters.com/article/latestCrisis/idUSL13834914. Retrieved June 20, 2008. 
  111. ^ Hoffer A (1987). "Is there a conspiracy?" (PDF). J Orthomol Med 2 (3): 158. http://www.orthomolecular.org/library/jom/1987/pdf/1987-v02n03-p158.pdf. 
  112. ^ Thomas Hager (1995). Force of nature: the life of Linus Pauling. New York: Simon & Schuster. ISBN 0684809095. 
  113. ^ Hoffer Abram. "History". J Orthomol Med. Archived from the original on 2007-11-01. http://web.archive.org/web/20071101114000/http://www.orthomed.org/jom/jomhist.htm.  (via archive.org) archived on November 1, 2007
  114. ^ Razzouk N, Seitz V (2003). "Marketing to the heart: a practical approach to dealing with health care quackery" (PDF). Clinical Research and Regulatory Affairs 20 (4): 469–478. doi:10.1081/CRP-120026128. http://www.informaworld.com/index/713622947.pdf. 
  115. ^ Weitzman S (1998). "Alternative nutritional cancer therapies". Int J Cancer Suppl 11: 69–72. doi:10.1002/(SICI)1097-0215(1998)78:11+<69::AID-IJC20>3.0.CO;2-7. PMID 9876483. 
  116. ^ 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. 
  117. ^ Frei, Balz (June 2006). "From the Director". LPI Research Newsletter (Linus Pauling Institute) (Spring 2006). http://lpi.oregonstate.edu/ss06/director.html. 
  118. ^ Kaitin KI, Brown JS (1995). "A drug lag update". Drug Information Journal 29 (2): 361–73. ISSN 0092-8615. http://cat.inist.fr/?aModele=afficheN&cpsidt=3529928. 

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