Orthomolecular medicine

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Orthomolecular medicine aims to restore the optimum environment of the body by correcting imbalances or deficiencies based on individual biochemistry using substances natural to the body such as vitamins, dietary minerals, proteins, antioxidants, amino acids, ω-3 fatty acids, ω-6 fatty acids, lipotropes, prohormones, dietary fiber and short and long chain fatty acids. It holds that such imbalances or deficiencies can be prevented, treated, or sometimes cured by achieving optimum bodily levels of these substances, either through diet or metabolism. Definition of Orthomolecular medicine at www.orthomed.org Accessed June 2006


Orthomolecular medicine is practiced by few conventional medical practitioners. Cassileth BR. Alternative medicine handbook: the complete reference guide to alternative and complementary therapies. New York: W.W.Norton & Co., 1998:67.Orthomolecular Medicine Revisited, Wunderlich RC, Orthomolecular Medicine Online, accessed 6 Nov 2006 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.OMACOR®(omega-3-acid ethyl esters), Reliant Pharmaceuticals, Inc.Mason M. "An Old Cholesterol Remedy Niacin Is New Again". NY Times, January 23, 2007 The controversial field of orthomolecular psychiatry deals with the use of orthomolecular medicine to treat psychiatric problems.The orthomolecular field is based on research in biochemistry, nutrition, medicine, and pharmaceuticals, which is interpreted in the light of the clinical experience of its practitioners. Orthomolecular medicine and optimum nutrition are based on the idea of individual variation in humans, with individual nutrient requirements varying widely with health, genetic and environmental influences.Roger J. Williams (1998) Biochemical Individuality: The Basis for the Genetotrophic Concept. 2nd ed. Keats Publishing. ISBN 0-87983-893-0 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. Orthomolecular Medicine News Service (OMNS) Listing or research and news items favourable to the Orthomolecular point of view 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. 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

History and development

Orthomolecular treatments typically have been experimentally or empirically introduced by physicians or researchers when conventional medical treatments offered neither solutionObservations On the Dose and Administration of Ascorbic Acid When Employed Beyond the Range of a Vitamin in Human PathologyAlpha-Lipoic Acid (Thioctic Acid): My Experience nor hope.Reduction of Cholesterol and Lp(A) in Regression of Coronary Artery Disease: A Case StudyCoenzyme Q10: A Novel Cardiac Antioxidant (1997) Orthomolecular psychiatry began to be developed in the early 1950s by a group of biochemists and psychiatrists who identified a number of biochemical abnormalities that they thought were associated with mental illness and treated a number of mental disorders using high dosages of certain vitamins. Orthomolecular megavitamin therapies, such as with tocopherolsNew/Old Findings on Unique Vitamin E and ascorbates,AscorbateWeb: Timeline from 1935 to 1939 date back to the 1930s.Frederick Klenner, (1907 – 1984) was an American medical researcher and doctor in general practice in Reidsville, North Carolina. From the 1940s on he experimented with the use of vitamin C megadosage as a therapy for a wide range of illnesses, most notably polio. He authored 28 research papers during his career. He is considered one of the originators of orthomolecular medicine, but his work remains largely unacknowledged by established medicine.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[http://www.seanet.com/~alexs/ascorbate/198x/smith-lh-clinical_guide_1988.htm 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.In the late 1950’s, Irwin Stone stated published his belief that scurvy was not a dietary disturbance, but a potentially fatal problem that had been misunderstood by nutritionists. Ascorbate was not a trace vitamin but was required in humans in large daily amounts. He produced four papers, between 1965 and 1967, describing the human requirement for ascorbate as genetic defect which he named hypoascorbemia.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. The term "orthomolecular" was first used by Linus Pauling in 1968 to express the "idea of the right molecules in the right amounts" within the context of psychiatry". 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) [http://www.roccomanzi.it/imp-vitaminerali/SCIENZIATI/scienziati-docu/pauling/orthomed-pauling2-mental-con_file/orthomed-pauling2-mental-con.htm] 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." Definition of Orthomolecular medicine at www.orthomed.org Accessed June 2006 and What is Orthomolecular Medicine?, Linus Pauling Inst.Since 1968 the orthomolecular field has diversified, but the term is still often closely associated with Pauling's advocacy of multi-gram doses of vitamin C for optimal health. Partly for this reason, detractors of orthomolecular ideas have described them entirely in terms of megadose nutrient therapy. Cassileth, a widely quoted critic of Pauling's ideas, asserts: "In 1968, the Nobel-prize-winning scientist Linus Pauling coined the term "orthomolecular" to describe the treatment of disease with large quantities of nutrients." 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.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" However, such definitions of orthomolecular therapy are not synonymous with Pauling's definition.Based on investigational scientific studies, single blinded and double blinded randomized controlled trials, clinical experience, and case histories, claims have been made that therapeutic nutrition can prevent,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 treat, or sometimes cure, acne,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 bee sting, burns, cancer, common cold, drug addiction, drug overdose, heart diseases, acute hepatitis, herpes, influenza, mononucleosis, mushroom poisoning, neuropathy & polyneuritis (including Multiple sclerosis), osteoporosis,Plaza SW, Lamson DW. Vitamin K2 in Bone Metabolism and Osteoporosis. Alt Medicine Review, Vol 10, No 1. polio, "alcoholism,Hoffer A, et al. Treatment Protocol for Alcoholism. Orthomolecular Medicine News Service, 1 Jul 2005 allergies, arthritis, autism, epilepsy, hypertension, hypoglycemia, migraine, clinical depression, learning disabilities, retardation, mental and metabolic disorders, skin problems, and hyperactivity,"Princeton Brain Bio Center. Brochure, distributed to patients. Skillman, N.J., 1983, The Center. Raynaud's disease, heavy metal toxicity, radiation sickness,
  • Pyroluria, schizophrenia,Skinner P, "Orthomolecular Medicine", Gale Encyclopedia of Alternative Medicine: Holistic medicine, Thomson Gale, 2004. shock, snakebite, spider bite, tetanus toxin and viral pneumonia.Klenner FR, Observations On the Dose and Administration of Ascorbic Acid When Employed Beyond the Range of A Vitamin In Human Pathology, J Applied Nutrition, Winter 1971, Vol. 23, No. 3 & 4, pp. 61-88
  • Method

    Orthomolecular medicine argues 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 use of nutrients such as vitamins, dietary minerals, proteins, antioxidants, amino acids, ω-3 fatty acids, ω-6 fatty acids, lipotropes, prohormones, dietary fiber and short and long chain fatty acids. Orthomolecular therapy attempts to provide what are seen as optimal amounts of these nutrients. Most often, "optimal" has been a matter of the clinical judgment of the orthomolecular practitioner, who gives nutrients in accord with the clinical symptoms of the patient and their judgement of what is appropriate, rather than the published dietary reference intakes of these nutrients. The modern orthomolecular practitioner also uses a wide range of laboratory analyses, including those for amino acids, organic acids, vitamins and minerals, functional vitamin status, hormones, immunology, microbiology, and gastrointestinal function. However, many of these tests have not been accepted by mainstream medicine for common diagnostic use.In the early days of orthomolecular medicine, supplementation usually meant high-dose, single-agent nutrient therapy.Richard P. Huemer MD, Orthomolecular Medicine, Encyclopedia of Complementary Health Practice, Springer Publishing Company, September 18, 1997. available online Most often today, the orthomolecular practitioner uses many substances: amino acids, enzymes, hormones, vitamins, minerals, or derivate substances in an effort to supply what they see as optimum levels of these substances.http://orthomed.org/kunin.html Principles That Identify Orthormolecular Medicine: A Unique Medical Specialty by Richard A. KuninFrequently 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.http://Monica & Gene Spiller (2005) [books.google.com/books?id=SPeQLCwz9ncC&pg=PA34&lpg=PA34 What's with Fiber?], Ch 3, pp 22-29. Basic Health Publications. ISBN: 159120111XGene A. Spiller (2001) CRC Handbook of Dietary Fiber in Human Nutrition, Third Edition. CRC Press. ISBN: 0849323878 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 probiotics, prebiotics and "glyconutrients". 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.


    A survey released in May 2004 by the National Center for Complementary and Alternative Medicine focused on who used (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 12 months that include orthomolecular related uses: Nonvitamin, nonmineral, natural products 18.9%, Diet-based therapies 3.5%, Megavitamin therapy 2.8%.NCCAM.NIH table 1 on page 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 12% of liver disease patients using the antioxidant silymarin, more than 6% used megavitamins among others, and "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."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 claims an evolving nutritional pharmacology that overlaps between natural medicine and mainstream medicine. The International Society for Orthomolecular Medicine has conventionally-trained doctors among its members and authors. However, the leading orthomolecular medicine website, Orthomolecular Medicine Online,http://orthomed.org Orthomolecular Medicine Online run by the Journal of Orthomolecular Medicine, discusses differences between orthomolecular medicine and mainstream medicine, Principles That Identify Orthormolecular Medicine: A Unique Medical Specialty which the website refers to as allopathic medicine.http://orthomed.org/wund.html 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 effective and exclude the placebo effect. Orthomolecular medicine proponents, on the other hand, believe that such studies overemphasize certainty and underemphasise patient choice and health freedom.DJ Hess, Complementary or Alternative? Stronger vs Weaker Integration Policies Am J Public Health. 2002 October; 92(10): 1579–1581. Mainstream medicine also avoids the use of new treatments whose effects are unknown, instead favoring extensively tested, clinically proven drugs. They point out that, even with extensive testing, 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.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. Orthomolecular medicine holds that their approach may be useful in treating new or incurable diseases, before conventional medical treatments are available.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 contradict clinical trials http://www.canstats.org/readdetail.asp?id=542 and instead consider 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.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

    Views on Safety and Efficacy

    The conventional view amongst 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. Some mainstream medical practitioners dismiss orthomolecular medicine. For example, an adviser on alternative medicine to the National Institutes of Health, once stated that "Scientific research has found no benefit from orthomolecular therapy for any disease" Cassileth BR. Alternative medicine handbook: the complete reference guide to alternative and complementary therapies. New York: W.W.Norton & Co., 1998, p.67. Proponents of orthomolecular medicine counter that vitamins are used in conventional medicine as treatments for a few diseases, such niacin for dyslipidemias (1955).Berra K. Clinical update on the use of niacin for the treatment of dyslipidemia. J Am Acad Nurse Pract. 2004 Dec;16(12):526-34.][http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=ShowDetailView&TermToSearch=15100082&ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVAbstractPlus 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.] Harvard Heart Letter. 2004 Apr;14(8):4-5.]Nutritional supplements, such as those used in orthomolecular medicine, are less regulated than pharmaceuticals in the United States. Furthermore, a recent meta-analysis in JAMA has suggested that supplementation with combinations of beta carotene, vitamin A, and vitamin E may increase mortality, and this risk may be particularly high in smokers.Mortality in randomized trials of antioxidant supplements for primary and secondary prevention: systematic review and meta-analysis. Bjelakovic G, Nikolova D, Gluud LL, Simonetti RG, Gluud C. The Cochrane Hepato-Biliary Group, Copenhagen Trial Unit, Center for Clinical Intervention Research, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark. goranb@junis.ni.ac.yu. JAMA. 2007 Feb 28;297(8):842-57. 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. Text of the Dietary Supplement Health and Education Act of 1994, legislating that vitamin supplements are regulated as foods rather than as medications. Accessed 21 Sept 2006. 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.Falloon W. What Do “Regulated” Supplements Cost. LE Magazine (online archives), July 2005, p 1

    Relation to mainstream medicine

    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:
  • Greater than the RDA of seleniumEffects of selenium supplementation for cancer prevention in patients with carcinoma of the skin. A randomized controlled trial. Nutritional Prevention of Cancer Study Group. Clark LC, Combs GF Jr, Turnbull BW, Slate EH, Chalker DK, Chow J, Davis LS, Glover RA, Graham GF, Gross EG, Krongrad A, Lesher JL Jr, Park HK, Sanders BB Jr, Smith CL, Taylor JR. JAMA 1996 ;276:1957-63 PMID 8971064 200ug/d of selenium for 4.5 years resulted in a 17% reduction of totality mortality by over 11 years (in total), due to a 50% reduction of (all) cancer mortality, 37% reduction in (all) cancer occurrence Reduction of cancer mortality and incidence by selenium supplementation. Combs GF Jr, Clark LC, Turnbull BW in Med Klin 1997 ;92 Suppl 3:42-5. PMID 9342915Reduction of cancer risk with an oral supplement of selenium. Combs GF Jr, Clark LC, Turnbull BW in Biomed Environ Sci 1997;10:227-34 PMID 9315315 may reduce the overall incidence of cancers; this effect is strongest in people who had low selenium levels before treatment.
  • Greater than the RDA of vitamin D may reduce the risk of cancer in post-menopausal women. It may also increase the immune response to a wide range of viruses, fungi and bacteria.
  • Greater than the RDA of "A, B6, C and E plus zinc",J Urol. 1994 Jan;151(1):21-6.
  • Megadose vitamins in bladder cancer: a double-blind clinical trial.Lamm DL, Riggs DR, Shriver JS, vanGilder PF, Rach JF, DeHaven JI. PMID 8254816 "The 5-year estimates of tumor recurrence are 91% in the RDA arm and 41% in the megadose arm"
    folic acidMultivitamin use, folate, and colon cancer in women in the Nurses Health Study. Giovannucci E, Stampfer MJ, Colditz GA, Hunter DJ, Fuchs C, Rosner BA, Speizer FE, Willett WC; Ann Intern Med" 1998 Oct 1;129(7):517-24 PMID 9758570 Long-term use (>15 years) of folate-containing multivitamin supplements produced an almost 5-fold reduction in the incidence of colon cancer. and seleniumEffects of selenium supplementation for cancer prevention in patients with carcinoma of the skin. A randomized controlled trial. Nutritional Prevention of Cancer Study Group. Clark LC, Combs GF Jr, Turnbull BW, Slate EH, Chalker DK, Chow J, Davis LS, Glover RA, Graham GF, Gross EG, Krongrad A, Lesher JL Jr, Park HK, Sanders BB Jr, Smith CL, Taylor JR. JAMA 1996 ;276:1957-63 PMID 8971064 200ug/d of selenium for 4.5 years resulted in a 17% reduction of totality mortality by over 11 years (in total), due to a 50% reduction of (all) cancer mortality, 37% reduction in (all) cancer occurrence
    Reduction of cancer mortality and incidence by selenium supplementation. Combs GF Jr, Clark LC, Turnbull BW in Med Klin 1997 ;92 Suppl 3:42-5. PMID 9342915
    Reduction of cancer risk with an oral supplement of selenium. Combs GF Jr, Clark LC, Turnbull BW in Biomed Environ Sci 1997;10:227-34 '' PMID 9315315 reduce the incidence of specific cancers
  • Studies finding that supplementation of long-chain omega-3 essential fatty acidsRidker PM; Ballantyne CM. MD)[http://www.lipidsonline.org/slides/slide01.cfm?q=omacor&dpg=1
  • Effects of n-3 Fatty Acid Therapy on Lipids and sCAMs], slide, Lipids Online, Baylor College of Medicine, 3 Oct 2001, accessed 10 Nov 2006 reduced the incidence of cardiac mortality in secondary prevention trialshttp://www.ajcn.org/cgi/content/full/77/2/279?ijkey=9ab8b23f0bdf45f83af656d8623815f69608ad01&keytype2=tf_ipsecshaGISSI-Prevenzione Investigators. Dietary supplementation with n-3 polyunsaturated fatty acids and vitamin E in 11,324 patients with myocardial infarction: results of the GISSI-Prevenzione trial. Lancet 1999;354:447–55.10465168Orthomolecular Research
  • Early studies finding that vitamin E alone Vitamin E and vitamin C supplement use and risk of all-cause and coronary heart disease mortality in older persons: the Established Populations for Epidemiologic Studies of the Elderly. Losonczy KG, Harris TB, Havlik RJ in Am J Clin Nutr 1996 Aug;64(2):190-6 PMID: 8694019 over 9 years of vitamin E found a 34% reduction in total mortality along with a 47% reduction coronary disease mortality; over 9 years from vitamin C & E use found a 42% reduction in total mortality with a 53% reduction in coronary disease mortality and vitamin C & E together reduce coronary disease mortality
  • Studies finding that niacinFifteen year mortality in Coronary Drug Project patients: long-term benefit with niacin. Canner PL, Berge KG, Wenger NK, Stamler J, Friedman L, Prineas RJ, Friedewald W in J Am Coll Cardiol 1986 Dec;8(6):1245-55 PMID: 3782631 "With a mean follow-up of 15 years, nearly 9 years after termination of the trial, mortality from all causes in each of the drug groups, except for niacin, was similar to that in the placebo group. Mortality in the niacin group was 11% lower than in the placebo group (52.0 versus 58.2%; p = 0.0004)." Dose used = 2g 3g/day for 6 years. The drop in mortality was only evident after 6-8 years., selenium, zincAssociations of Mortality With Ocular Disorders and an Intervention of High-Dose Antioxidants and Zinc in the Age-Related Eye Disease Study: AREDS Report No. 13. AREDS Research Group (Authors: Traci E. Clemons, PhD; Natalie Kurinij, PhD; Robert D. Sperduto, MD.) in Arch Ophthalmol. 2004 May;122(5):716-26. PMID: 15136320 "Participants randomly assigned to receive zinc 80mg/d had lower mortality than those not taking zinc (RR, 0.73; 95% CI, 0.61-0.89).", vitamin C Vitamin C intake and mortality among a sample of the United States population. Enstrom JE, Kanim LE, Klein MA in Epidemiology 1992 May;3(3):194-202 (PMID 1591317) 35% reduction in mortality over 10 years from vitamin C use alone and vitamin E alone and vitamin C & E together reduce overall mortality rates
  • Bruce Ames's studies on the effects of vitamins on genetic diseases and biochemical aging processesAge-associated mitochondrial oxidative decay: improvement of carnitine acetyltransferase substrate-binding affinity and activity in brain by feeding old rats acetyl-L- carnitine and/or R-alpha -lipoic acid. Liu J, Killilea DW, Ames BN in Proc Natl Acad Sci U S A 2002 Feb 19;99(4):1876-81 (PMID 11854488)Memory loss in old rats is associated with brain mitochondrial decay and RNA/DNA oxidation: partial reversal by feeding acetyl-L-carnitine and/or R-alpha -lipoic acid. Liu J, Head E, Gharib AM, Yuan W, Ingersoll RT, Hagen TM, Cotman CW, Ames BN in Proc Natl Acad Sci U S A. 2002 Feb 19;99(4):2356-61. (PMID 11854529) Feeding acetyl-L-carnitine and lipoic acid to old rats significantly improves metabolic function while decreasing oxidative stress. Hagen TM, Liu J, Lykkesfeldt J, Wehr CM, Ingersoll RT, Vinarsky V, Bartholomew JC, Ames BN in Proc Natl Acad Sci U S A. 2002 Feb 19;99(4):1870-5. (PMID 11854487)
  • The advocacy of daily multivitamins in cancer prevention by Professor Bruce Ameshttp://www.juvenon.com/pdfs/june05_ames-prescrip.pdfhttp://reason.com/amesint.shtml, by a JAMA review article for "chronic disease prevention in adults"Vitamins for chronic disease prevention in adults: clinical applications. Fletcher RH, Fairfield KM in JAMA 2002 Jun 19;287(23):3127-9 (PMID 12069676) “Most people do not consume an optimal amount of all vitamins by diet alone. Pending strong evidence of effectiveness from randomized trials, it appears prudent for all adults to take vitamin supplements.…. We recommend that all adults take one multivitamin daily.….. It is reasonable to consider a dose of 2 ordinary RDA levels multivitamins daily in the elderly” Vitamins for chronic disease prevention in adults: scientific review. Fairfield KM, Fletcher RH in ''JAMA 2002 Jun 19;287(23):3116-26 (PMID: 12069675) “Although the clinical syndromes of vitamin deficiencies are unusual in Western societies, suboptimal vitamin status is not unusual”, and by an NEJM Editorial. Eat Right and Take a Multivitamin NEJM, Volume 338:1060-1061, April 9, 1998, Number 15. Published 9 April 1998. Accessed 27 Dec 2007.
  • Some of these findings have been reported as not consistent with other studies. For example, (see Vitamin E controversy below), a subsequent meta-analysis failed to find benefit to single isomeric alpha tocopheryl ester forms of vitamin E supplementation. Indeed, alpha tocopheryl ester supplementation might increase the risk for congestive heart failure. The Shutes decades earlier did specifically caution about tocopherol dosage and slow buildup rates for CHF patients and those with pre-existing rheumatic heart problems; modern orthomolecular medicine has different specific nutrient recommendations for CHF patients.[http://www.doctoryourself.com/congestive.html] Reconciling and confirming the conclusions of individual nutritional studies is a subject of ongoing research. These studies all come from mainstream medical sources 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.Spencer JW, Jacobs JJ. Complementary/alternative medicine: an evidence based approach. Toronto: Mosley, 1999:134,137; The selenium shocker. University of California at Berkeley Wellness Letter 1997;13:8-9; http://www.news.cornell.edu/releases/Jan97/selenium.ssl.html Ames supports daily USRDA multivitamin supplements as a public-policy solution to the lack of vegetables in United States diets, but has not endorsed global use of megavitamin therapy propounded by orthomolecular medicine. Orthomolecular proponents, such as Robert Cathcart, who predicts that 120+ grams per day intravenous vitamin C should cure SARSThe Ascorbate Effect in Infectious and Autoimmune Diseases Fourth World Conference on Nutritional Medicine, San Francisco, June 2004. and has used up to 250 grams IV vitamin C per day, have been criticised for not having any conventional medical trials of such intravenous vitamin C treatments.Hasslberger S. Vitamin C could be effective against SARS. New Media Explorer. 6 June 2003 includes republication of article: Mawhinney J. "Vitamin C touted to fight virus." Toronto Star, 30 May 2003.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.American Cancer Society 2006 "Orthomolecular Medicine has not been definitively or authoritatively proven to help many of the conditions for which it recommends treatments. However, vitamins, minerals, and other supplements have been and continue to be studied to see if they can help or prevent many types of illness." [http://www.cancer.org/docroot/ETO/content/ETO_5_3X_Orthomolecular_Medicine.asp?sitearea=ETO] Nutrition Committee, Canadian Paediatric Society. Megavitamin and megamineral therapy in childhood. Canadian Medical Association Journal 143:1009-13, 1990, reaffirmed April 2000. Based on testing with dosages well below orthomolecular recommendations, Linus Pauling has been criticized for making overbroad claimsStephen Barrett MD, The Dark Side of Linus Paulings Legacy, Quackwatch.available online 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.Padayatty SL et al., Vitamin C Pharmacokinetics: Implications for Oral and Intravenous Use Ann Intern Med 2004;140:533-7.The relationship of mainstream medicine to orthomolecular proponents has often been adversarial; orthomolecular proponents 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.Committee on Nutrition, American Academy of Pediatrics. Megavitamin therapy for childhood psychoses and learning disabilities. Pediatrics 58:910­912, 1976. PMID 995522 Conventional health professionals see orthomolecular medicine as encouraging individuals to dose themselves with large amounts of vitamins and other nutritients without conventional supervision, which they worry might be damaging to health. Rare risksemedicine - Toxicity statistics, 2003 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 diseaseRapola JM, et al. Randomized trial of alpha-tocopherol and beta-carotene supplements on incidence of major coronary events in men with previous myocardial infarction. Lancet 1997;349;1715-20., hypertension, thrombophlebitis, peripheral neuropathy, ataxia, neurological effects, liver toxicity, congenital abnormalities, spontaneous abortion, gouty arthritis, jaundice, kidney stones, and diarrhea.PMID 3153129 PMID 3737019 Roberts HJ. Vitamin E letter. Lancet 1995 Mar 18;345:737 Kaegi E, on behalf of the Task Force on Alternative Therapies of the Canadian Breast Cancer Research Initiative. Unconventional therapies to cancer: 5. Vitamins A, C, and E. Canadian Medical Association 1998; 158:1483-88. Megavitamin proponents pointhttp://www.doctoryourself.com/testimony.htm TESTIMONY by Andrew W. Saul before the Government of Canada, House of Commons Standing Committee on Health, regarding natural health product safety (Ottawa, May 12, 2005). 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.http://www.emedicine.com/EMERG/topic638.htm

    Vitamin E controversy

    The accumulated evidence of randomized clinical trials with conventional, chemically-modified alpha tocopheryl esters, containing only one kind of natural vitamin E (of eight vitamers) in the stabilized (chemically inactivated) ester formHorwitt MK, et al, Serum concentrations of a-tocopherol after ingestion of various vitamin E preparations, Am J Clin Nutr 1984;40: 240-245. ''The rat-fetal-resorption test currently is used to assess the biological activity of vitamin E compounds. Previous studies in humans, however, suggest that rat assays underestimate the potency of free tocopherol relative to the acetate ester form and of RRR-a-tocopheryl acetate relative to all-rac-a-tocopheryl acetate. Therefore, we studied...20 adult human subjects. Measurements...of 800 IU of the various preparations...at 24 h...mean increase in concentration of a-tocopherols (mg/g lipid) in 24 h was 71.2% after RRR-a-tocopherol, 63.3% after RRR-a-tocopheryl acetate plus apple pectin, 60.9% after RRR-a-tocopheryl acetate, 31.6% after all-rac-a-tocopheryl acetate, and 41.2% after RRR-a-tocopheryl succinate. Animal assay data do not correlate with data from studies of absorption and retention in serum of a-tocopherols ingested by humans. (usually acetate) have been controverted. Initial hopes for alpha tocopheryl esters (usually acetate) were based on suppositional grounds and epidemiological data that often involved the natural, full spectrum dietary forms of vitamin E (mixed R, R,R tocopherols - alpha- beta- gamma-, delta- isomers).Jiang Q et al.Gamma tocopherol, the major form of vitamin E in the US diet, deserves more attention. Am J Clin Nutr 2001; 74: 714-22.JM Gaziano, Vitamin E and Cardiovascular Disease: Observational Studies, Ann. N.Y. Acad. Sci. 1031: 280–291 (2004) " Meta analysis of several randomized clinical trials of manufactured antioxidants, including alpha tocopheryl esters (acetate, succinate) not in an antioxidant form, have not shown any benefit to alpha tocopheryl ester supplementation for preventing coronary heart disease. Orthomolecular recommendations for the full vitamin E complex typically include an additional 25% to 200% w/w of beta-, gamma-, and delta-tocopherol''s.M Walker, New/Old Findings on Unique Vitamin E, Townsend Letter for Doctors and Patients, No. 111, 1992, p. 826 Recent scientific and medical research shows gamma-tocopherol, the most common vitamer of natural vitamin E, has unique beneficial functions and "gamma tocopherol is considered an integral component of the nutrient-based recommendations in many EU member countries."L MacWilliam,What Makes Gamma Tocopherol Superior to Alpha Tocopherol, LE Magazine, Report, April 2006A controversial meta-analysisM. Houston, “Meta-Analysis, Metaphysics and Mythology” JANA Vol. 8 No. 1, 2005 original published in 2005 claimed that "high dose" alpha tocopheryl esters (>=400 units/day) were associated with an all-cause mortality risk difference of 39 per 10,000 persons. Furthermore, a significant relationship was claimed between dose and all-cause mortality, with increased risk with doses exceeding 150 I.U. per day. This meta-analysis, however, was criticized on a number of grounds.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 One of several criticisms which the authors did not rebut was that the mortality effect was a confounder resulting entirely from excess mortality in a few studies of combined alpha-tocopheryl ester and synthetic beta carotene in heavy smokers. Known for decades,Dam HCP. Influence of antioxidants and redox substances on signs of vitamn E defciency. Pharmacol Rev 1957 9: 1-16. that "the antagonisms that exist between...carotene and vitamin E are complicated",Hoskins FH. (1980) Antinutrients, Kirk-Othmer Encyclopedia of Chemical Technology, 3rd Edition, John Wiley & Sons, New York, pp 213-214 this supplement and smoking exposure combination once had some academic supportPMID 16027469 but synthetic "beta carotene...has previously been shown to be harmful"Jialal I, Devaraj S. Antioxidants and atherosclerosis: don't throw out the baby with the bath water. Circulation. 2003 Feb 25;107(7):926-8. (Comment on: Circulation. 2003 Feb 25;107(7):947-53.) PMID 12600900 in smokers, a subpopulation with high oxidative stress.Schectman G, Byrd JC, Gruchow HW. The influence of smoking on vitamin C status in adults. Am J Public Health. 1989 February; 79(2): 158–162. Long commercialized, multiple antioxidant megavitamin combinations, such as "ACES", that also include antioxidants vitamin C Stone I. Smoker’s Scurvy: Orthomolecular Preventive Medicine in Cigarette Smoking. Orthomolecular Psychiatry, 1976, Vol 5, No 1, pp. 35-42 and seleniumHercberg S, Galan P, et al, The SU.VI.MAX Study: a randomized, placebo-controlled trial of the health effects of antioxidant vitamins and minerals. Arch Intern Med. 2005 Feb 14;165(3):286. to recycle the first two antioxidants and aid liver peroxide detoxification, were not tested or measured.The orthomolecularly-preferred "vitamin E", mixed (natural) R, R,R tocopherols, available for two-thirds of a century, remain to be authoritatively evaluated in tests controlled for bile, pancreatic function, certain specific heart problems and risk factors, blood levels and cofactors (vitamins C, D3, K1, K2, JM Geleijnse, C Vermeer, DE Grobbee, LJ Schurgers, MHJ Knapen, IM van der Meer, A Hofman, JCM Witteman, Dietary Intake of Menaquinone Is Associated with a Reduced Risk of Coronary Heart Disease: The Rotterdam Study J. Nutr. 134:3100-3105, November 2004 selenium, co-enzyme Q10, etc.) in the common orthomolecular range, 600 - 3200 IU alpha tocopherol plus 25%-200% by weight of other R, R,R tocopherols. With the exception of controlling for standard comorbidities such as heart disease, controlling for pancreatic function, various vitamin cofactors, etc. has not been felt by conventional medicine to be clinically relevant nor routinely done in clinical trials. However, naturopathic medicine texts Pizzorno JE, Murray MT (November 2005) Textbook of Natural Medicine, 3rd edition, Churchill Livingstone, ISBN 0-443-07300-7, Chapters 12, 14, 24, 59, 181 and naturopathic physicians routinely recommend such laboratory testsEducational Documents, CDSA 2.0 Universal Kit Guide, Digestive Analysis Solution Center, Genova Diagnostics, accessed 2 Nov 2006 of biliary and pancreatic functions in their orthomolecular-related modalities.

    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 case, the chemotherapy and orthomolecular treatments of a 13-year-old cancer patient, Tyrell Dueck, were delayed, possibly fatally, due to his parents' religious beliefs, interest in alternative treatments, and lengthy legal battles. http://www.healthwatcher.net/Quackerywatch/Cancer/Dueck/index.html 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.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: The use of conventional medical treatments, if not successful, may create dangerous delays in people obtaining orthomolecular treatments. It is usually possible, however, to combine orthomolecular and conventional treatments.

    Other benefits

    Several orthomolecular related AIDS approaches such as multivitamins Multivitamin found to slow pace of HIV, Study examined Tanzanian women, The Boston Globe, July 1, 2004, selenium and amino acids[http://www.doctoryourself.com/aids.html] HD Foster Treating AIDS with Nutrition. are used with reported improvements in patients. High dose vitamin C treatments have long been used clinically by some orthomolecular practitioners to treat AIDS patientshttp://www.doctoryourself.com/aids_cathcart.html RF Cathcart, Vitamin C in the Treatment of Acquired Immune Deficiency Syndrome (AIDS), Medical Hypotheses 14:423-433, 1984 ; a minor 1994 in vitro laboratory study raised questions that sustained megadoses of vitamin C might inhibit some immune cells.Eylar E, et al. Sustained levels of ascorbic acid are toxic and immunosuppressive for human T cells. Puerto Rico Health Sciences Journal 1996;15:21-6 In these situations, mainstream medical criticism arises when orthomolecular approaches are advocated as substitutes for, rather than complements to, current medical treatments.

    Economic interests and politics

    Some orthomolecular proponents claim partisan politics, pharmaceutical industry influence, and competitive considerations to be significant factors. Some prominent orthomolecular proponents sell lines of orthomolecular products and accept some tests questioned about their benefit that vary by medical affiliation. The Linus Pauling Institute's funding comes mostly from National Institutes of Health[http://lpi.oregonstate.edu/ss06/director.html] Director's newsletter, Linus Pauling Institute, Spring 2006. Several orthomolecular therapies have been officially sanctioned within EuropeOMACOR deal signed with new Euro partners, HYDRO, 11 Dec 2001 and Japan fibrinolytic activity of nattokinase, Miyazaki Medical College, Japan Coenzyme Q10, prescribed for CHF in Japan since 1974, AAFPKaitin, KI, Brown, J. 1995. A Drug Lag Update. Drug Information Journal 29:361–73.

    Orthomolecular doctors

  • Glen Dettman
  • Abram Hoffer
  • David Horrobin
  • Archie Kalokerinos
  • Carl Pfeiffer
  • Matthias Rath
  • Julian Whitaker
  • Orthomolecular scientists

  • Abram Hoffer
  • Linus Pauling
  • Irwin Stone
  • Albert Szent-Gyorgyi
  • Orthomolecular Journals

    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."[http://www.orthomed.org/jom/jomhist.htm] History of the Journal of Orthomolecular Medicine by Abram Hoffer.



  • Abram Hoffer (1998) Putting It All Together: The New Orthomolecular Nutrition, McGraw-Hill, ISBN 0-87983-633-4
  • Abram Hoffer, M.D. with Linus Pauling (2004) Healing Cancer: Complementary Vitamin & Drug Treatments, CCNM Press, ISBN 1-897025-11-4
  • David Moss (2000) Ph.D, Antioxidants Against Cancer, Equinox Press , ISBN 1881025284
  • Pauling, Linus (1986) How to Live Longer and Feel Better, W. H. Freeman and Company, ISBN 0-380-70289-4
  • Roger J. Williams, Dwight K. Kalita (1979) Physician's Handbook on Orthomolecular Medicine, Keats Publishing, ISBN 0-87983-199-5
  • J. Alexander (2001) LABORATORY EVALUATIONS IN MOLECULAR MEDICINE: Nutrients, Toxicants and Cell Regulators. Inst. for Advances in Mol. Med., ISBN 0967394910
  • Melvyn R. Werbach, Jeffrey Moss (1999) Textbook of Nutritional Medicine, Third Line Press, ISBN 0-9618550-9-6
  • Joseph E. Pizzorno, Jr., Michael T. Murray (November 2005) Textbook of Natural Medicine, 3rd edition, Churchill Livingstone, ISBN 0-443-07300-7 · 2368pp
  • Critics

  • Barrie R. Cassileth (1998) Alternative medicine handbook: the complete reference guide to alternative and complementary therapies. New York: W.W.Norton & Co., ISBN 0-393-04566-8

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