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A subsequent meta-analysis published in 2005 found that "high dose" alpha tocopheryl esters (>=400 units/day) was associated with an all-cause mortality risk difference of 39 per 10,000 persons)<ref name="miller">{{cite journal | author = Miller E, Pastor-Barriuso R, Dalal D, Riemersma R, Appel L, Guallar E | title = Meta-analysis: high-dosage vitamin E supplementation may increase all-cause mortality. | journal = ''Ann Intern Med'' | volume = 142 | pages = 37-46 | year = 2005 | id = PMID 15537682}}</ref>. Furthermore, a significant relationship was seen 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.<ref>[http://www.annals.org/cgi/reprint/143/2/155-a.pdf High-Dosage Vitamin E Supplementation and All-Cause Mortality (pdf download)]</ref> 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. This supplement and exposure combination once had some academic support<ref>PMID 16027469</ref> but synthetic "beta carotene...
A subsequent meta-analysis published in 2005 found that "high dose" alpha tocopheryl esters (>=400 units/day) was associated with an all-cause mortality risk difference of 39 per 10,000 persons)<ref name="miller">{{cite journal | author = Miller E, Pastor-Barriuso R, Dalal D, Riemersma R, Appel L, Guallar E | title = Meta-analysis: high-dosage vitamin E supplementation may increase all-cause mortality. | journal = ''Ann Intern Med'' | volume = 142 | pages = 37-46 | year = 2005 | id = PMID 15537682}}</ref>. Furthermore, a significant relationship was seen 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.<ref>[http://www.annals.org/cgi/reprint/143/2/155-a.pdf High-Dosage Vitamin E Supplementation and All-Cause Mortality (pdf download)]</ref> 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. This supplement and exposure combination once had some academic support<ref>PMID 16027469</ref> but synthetic "beta carotene...
has previously been shown to be harmful"<ref>PMID 12600900</ref> in smokers, a subpopulation with high oxidative stress. Long commercialized megavitamin formulas, "[[ACES (nutritional supplement) | ACES]]", that also include vitamin C and selenium to recycle the first two antioxidants and aid liver peroxide detoxification, were not tested or measured.{{cn}}
has previously been shown to be harmful"<ref>PMID 12600900</ref> in smokers, a subpopulation with high oxidative stress. Long commercialized megavitamin formulas, "[[ACES (nutritional supplement) | ACES]]", that also include vitamin C and selenium<ref>Hercberg S, Galan P, et al, [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15557412&dopt=Abstract 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.</ref> to recycle the first two antioxidants and aid liver peroxide detoxification, were not tested or measured.{{cn}}


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, D<SUB>3<SUB>, K<SUB>1<SUB>, K<SUB>2<SUB>, selenium, co-enzyme Q10, etc.) in the common orthomolecular range, 600 - 3200 IU alpha tocopherol <i>plus<i> 25%-200% by weight of other R,R,R tocopherols. However, with the exception of controlling for standard comorbidities such as heart disease, controlling for pancreatic function, various vitamin cofactors has not been felt to be clinically relevant.{{cn}}
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, D<SUB>3<SUB>, K<SUB>1<SUB>, K<SUB>2<SUB>, selenium, co-enzyme Q10, etc.) in the common orthomolecular range, 600 - 3200 IU alpha tocopherol <i>plus<i> 25%-200% by weight of other R,R,R tocopherols. However, with the exception of controlling for standard comorbidities such as heart disease, controlling for pancreatic function, various vitamin cofactors has not been felt to be clinically relevant.{{cn}}

Revision as of 03:54, 26 October 2006

Orthomolecular medicine and optimum nutrition are controversial medical and health approaches[1] that posit that many diseases and abnormalities result from various chemical imbalances or deficiencies and can be prevented, treated, or sometimes cured by achieving optimal levels of naturally occurring chemical substances, such as vitamins, dietary minerals, enzymes, antioxidants, amino acids, lipotropes, essential fatty acids, prohormones, dietary fiber and intestinal short chain fatty acids.[2] [3] [4]

Orthomolecular medicine is explicitly practiced by relatively few conventional medical practitioners.[5][6][7][8] Orthomolecular treatments are also utilized in complementary and alternative medicine fields. 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 combined with the clinical experience of a number of physicians and physician scientists. It remains controversial among mainstream medical organizations and physicians without the authoritative validation of efficacy and reservations about safety. Orthomolecular proponents argue that many mainstream nutritional studies, both recent and historical, provide investigational and clinical support for their theories.[9] They also argue that orthomolecular therapies are intrinsically less likely to cause dangerous side-effects or harm, since they utilize only molecules which are normally present in the body through healthy diet or normal metabolism.[3][4][10]

History and development

Orthomolecular type treatments typically have been experimentally or empirically introduced by physicians with advanced scientific or research backgrounds when conventional medical treatments offered neither solution[11][12] nor hope.[13][14] Orthomolecular megavitamin therapies, such as "megadose" usage of tocopherols[15] and ascorbates,[16] date back to the 1930s.

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".[17] "Orthomolecular medicine" was subsequently defined 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."[18]

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, states: "In 1968, the Nobel-prize-winning scientist Linus Pauling coined the term "orthomolecular" to describe the treatment of disease with large quantities of nutrients."[5] 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. However, such definitions of orthomolecular therapy are not synonymous with Pauling's ideas.

Method

Orthomolecular medicine argues that some diseases reflect biochemical anomalies and that it is advantageous to recognize and to correct these anomalies at an early stage, before they result in recognizable diseases. Orthomolecular medicine posits that many typical diets are insufficient for long term health; thus, orthomolecular medical diagnoses and treatment often focus on use of natural substances found in a normal diet such as vitamins, dietary minerals, enzymes, antioxidants, amino acids, essential fatty acids, dietary fiber and short and long chain fatty acids.

Orthomolecular therapy consists in attempting to provide optimal amounts of substances normal to the body, most commonly by oral administration. Most often, "optimal" has been a matter of the clinical judgment of the orthomolecular practitioner, who gave nutrients in accord with the clinical symptoms of the patient and his or her judgement of what is appropriate. 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 as valid for diagnostic use.

In the early days of orthomolecular medicine, supplementation usually meant high-dose, single-agent nutrient therapy.[7] Most often today, the orthomolecular practitioner uses many substances: amino acids, enzymes, non-essential nutrients, hormones, vitamins, minerals, or derivate substances in a therapeutic effort to restore optimum levels for healthy young persons.[19]

Often, supplementation with relatively large doses of vitamins is given, and the name megavitamin therapy has become popularly associated with the field. Megavitamin therapy is the administration of large amounts of vitamins, many times greater than the recommended dietary allowance (RDA). The necessary ratio of dose to RDA to qualify for the term "megavitamin therapy" has been a matter of some debate, and is not resolved as of 2006.

Administration of short-chain fatty acids in orthomolecular practice is usually accomplished by fiber supplementation. The fatty acids are produced by fermentation of dietary fiber in the colon, then absorbed and utilized. This process is often aided by a combination of probiotics, prebiotics and "glyconutrients" added to the diet. Administration of long chain fatty acids, such as the omega-3 fatty acids alpha-linolenic acid (ALA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) may be accomplished by dietary means, or by supplementation with the appropriate fats or fatty acid esters in capsule form.

Nutritional substances may also be administered by changing the diet to emphasize certain foods high in nutrients, by dietary supplementation with oral preparations such as tablets or capsules, or by intravenous injection of nutrient solutions.

Popularity

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. According to this recent survey, megavitamin therapy was the twelfth most commonly used CAM therapy (2.8%) in the United States during 2002, though the study did not distinguish between orthodox orthomolecular medicine and lay use of publicized Vitamin C megadose supplements.[20]

Relation to mainstream medicine

Orthomolecular medicine claims an evolving nutritional pharmacology that overlaps between natural medicine and mainstream medicine. The International Society for Orthomolecular Medicine has some conventionally-trained doctors among its members and authors. However, the leading orthomolecular medicine website, Orthomolecular Medicine Online,[21] run by the Journal of Orthomolecular Medicine, discusses differences between orthomolecular medicine and current mainstream medicine,[19] which the website refers to as allopathic medicine.[8]

Amongst the differences, mainstream medicine attaches great importance to rigorous double-blind randomized controlled trials to prove a treatment is effective and to exclude the placebo effect. Orthomolecular medicine proponents, on the other hand, believe that such studies overemphasize [22] presupposed minimization of uncertainty in measurement and have instead led to false-negative results from otherwise poorly designed and executed studies that resulted in misrepresented "authoritative" disparagement of nutritional treatments.[23][24][25] Mainstream medicine avoids use of new, unproven xenobiotic molecules whose effects are unknown, instead favoring extensively tested, clinically proven drugs. Orthomolecular medicine holds that natural equivalent molecules, as non-toxic nutritional therapies, are often useful in the interim, before extremely expensive, time-consuming authoritative tests are available.

Individual mainstream medical proponents are sometimes dismissive of orthomolecular medicine: "Scientific research has found no benefit from orthomolecular therapy for any disease"[5][6] despite strong counterexamples such as megadose niacin for dyslipidemias (1955).[26]

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:

  • Studies finding that greater than RDA of selenium[27][28][29] reduce the overall incidence of cancers
  • Studies finding that supplementation of long-chain omega-3 essential fatty acids reduced the incidence of cardiac mortality in secondary prevention trials[32][33][34]
  • The advocacy of daily multivitamins in cancer prevention by Bruce Ames[43][44] and by others in a JAMA review article for "chronic disease prevention in adults"[45][46]

Some of these findings have not been supported by subsequent studies. For example, a subsequent meta-analysis found a lack of benefit to single isomeric alpha tocopheryl ester forms of vitamin E supplementation.[47] Indeed, alpha tocopheryl ester supplementation might increase the risk for congestive heart failure.[48] The Shutes decades earlier did specifically caution about tocopherol dosage and slow buildup rates for CHF patients and those with pre-exisiting rheumatic heart problems; modern orthomolecular medicine also has additional specific nutrient recommendations for CHF patients.[49] 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 desireable.[50] 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.[43][44]

The skepticism about orthomolecular medicine comes in part because some of its proponents make claims more broad than those supported by double-blind controlled studies.[5][6][7][51][52] Based on investigational scientific studies, clinical experience, and anecdotal accounts, claims have been made that therapeutic nutrition can treat, or sometimes cure, "alcoholism, allergies, arthritis, autism, epilepsy, hypertension, hypoglycemia, migraine, clinical depression, learning disabilities, retardation, mental and metabolic disorders, skin problems, and hyperactivity."[53][7]

Nutritional supplements, such as those used in orthomolecular medicine, are less regulated, as food supplements, in the United States and are not held to the same strict standards of proof of efficacy as pharmaceutical medications.[54]

Criticism and controversy

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.[6] Orthomolecular proponents, such as Robert Cathcart who predicts that 120+grams per day intravenous vitamin C should cure SARS,[55] have been criticised.[56] Proponents of orthomolecular medicine also argue that many mainstream doctors are unfamiliar with the concepts and clinical background of orthomolecular medicine. They dispute the results of mainstream studies, arguing that those studies are "strawmen", using much lower doses, frequencies, duration or assimilable forms than they recommend or suffered from other special conditions, contamination, populations or statistical treatment often not clearly published in the documentation.[citation needed]

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.[7][6][5][57][58] Linus Pauling has been criticized for making overbroad claims[59] for the efficacy of vitamin C but has received some support for modified claims in the last few years.[60][61]

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.[19] 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.[62] 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.[6] Rare risks[63] of megadose vitamins, which frequently involved pharmaceutical analogues such as synthetic menadione and isotretinoin, unsupervised misuse, deliberate abuse and earlier medical treatments, may include increased risk of coronary heart disease[64], hypertension, thrombophlebitis, peripheral neuropathy, ataxia, neurological effects, liver toxicity, congenital abnormalities, spontaneous abortion, gouty arthritis, jaundice, kidney stones, and diarrhea.[6][65] [66][67][68][69] Megavitamin proponents point[70] 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.[71]

The accumulated evidence of randomized clinical trials with conventional, chemically-modified alpha tocopheryl esters, containing only one kind of natural vitamin E (of eight) in the stabilized (chemically inactivated) ester form (usually acetate) have been controverted. Initial hopes for alpha tocopheryl esters (usually acetate) were based on theoretical and epidemiological grounds that often involved the natural, full spectrum dietary forms of vitamin E (mixed R,R,R tocopherols - alpha- beta- gamma-, delta- isomers).[72][73] 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.[74] Orthomolecular recommendations for the full vitamin E complex typically include an additional 20% to 200% w/w of beta-, gamma-, and delta-tocopherols.[75] 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."[76]

A subsequent meta-analysis published in 2005 found that "high dose" alpha tocopheryl esters (>=400 units/day) was associated with an all-cause mortality risk difference of 39 per 10,000 persons)[77]. Furthermore, a significant relationship was seen 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.[78] 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. This supplement and exposure combination once had some academic support[79] but synthetic "beta carotene... has previously been shown to be harmful"[80] in smokers, a subpopulation with high oxidative stress. Long commercialized megavitamin formulas, " ACES", that also include vitamin C and selenium[81] to recycle the first two antioxidants and aid liver peroxide detoxification, were not tested or measured.[citation needed]

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, 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. However, with the exception of controlling for standard comorbidities such as heart disease, controlling for pancreatic function, various vitamin cofactors has not been felt to be clinically relevant.[citation needed]

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.[6] For example, in a highly publicized Canadian case, the chemotherapy treatment of a 13-year-old cancer patient, Tyrell Dueck, was delayed, possibly fatally, due to his parents' religous beliefs, interest in alternative treatments, and lengthy legal battles. [82] Several orthomolecular related AIDS approaches such as multivitamins[83], selenium and amino acids[84] are used with claimed improvements in patients. High dose vitamin C treatments have long been used clinically by some orthomolecular practitioners to treat AIDS patients[85]; a minor 1994 in vitro laboratory study raised questions that sustained megadoses of vitamin C might inhibit some immune cells.[86] In these situations, mainstream medical criticism arises because orthomolecular approaches are advocated as substitutes for, rather than complements to, current medical treatments.

Some orthomolecular proponents claim partisan politics, pharmaceutical industry influence, and competitive considerations to be significant factors. However, some prominent orthomolecular proponents sell lines of orthomolecular products and acceptance for some tests questioned about their benefit vary by medical affiliation such as hair analysis.[87][88][89] The Linus Pauling Institute's funding comes mostly from National Institutes of Health[90]. Several orthomolecular therapies have been officially sanctioned within Japan[91] [92][93].

Notable orthomolecular doctors

Column-generating template families

The templates listed here are not interchangeable. For example, using {{col-float}} with {{col-end}} instead of {{col-float-end}} would leave a <div>...</div> open, potentially harming any subsequent formatting.

Column templates
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Handles wiki
table code?†
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mobile suited 		Start template Column divider End template
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"columns-start" Yes Yes {{columns-start}} {{column}} {{columns-end}}
Columns "div col" Yes Yes {{div col}} – {{div col end}}
"columns-list" No Yes {{columns-list}} (wraps div col) – –
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† Can template handle the basic wiki markup {| | || |- |} used to create tables? If not, special templates that produce these elements (such as {{(!}}, {{!}}, {{!!}}, {{!-}}, {{!)}})—or HTML tags (<table>...</table>, <tr>...</tr>, etc.)—need to be used instead. Abram Hoffer
Fred R. Klenner
Robert Cathcart

Glen Dettman
Archie Kalokerinos
Matthias Rath
Hugh D. Riordan
Carl Pfeiffer
Julian Whitaker
Ronald E. Hunnunghake

Orthomolecular scientists

Bibliography

Advocates

  • 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
  • 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
  • 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

See also

Support

Criticism

  1. ^ The War Against Vitamin Therapy doctoryourself.com , Andrew Saul, PhD - Accessed, August 2006
  2. ^ The American Heritage Stedman's Medical Dictionary, 2nd Edition, 2004.
  3. ^ a b Definition of Orthomolecular medicine at www.orthomed.org Accessed June 2006
  4. ^ a b What is Orthomolecular Medicine?, Linus Pauling Inst. Oregon State University , Accessed August 2006
  5. ^ a b c d e Cassileth BR. Alternative medicine handbook: the complete reference guide to alternative and complementary therapies. New York: W.W.Norton & Co., 1998:67.
  6. ^ a b c d e f g h "Vitamin Therapy, Megadose / Orthomolecular Therapy" British Columbia Provincial Health Services Authority 2000
  7. ^ a b c d e http://www.quackwatch.org/01QuackeryRelatedTopics/ortho.html
  8. ^ a b http://orthomed.org/wund.html
  9. ^ Orthomolecular Medicine News Service (OMNS) Listing or research and news items favourable to the Orthomolecular point of view
  10. ^ How safe are vitamins? Orthomolecular Medicine News Service, November 9, 2005 - Accessed August 2006
  11. ^ Observations On the Dose and Administration of Ascorbic Acid When Employed Beyond the Range of a Vitamin in Human Pathology
  12. ^ Alpha-Lipoic Acid (Thioctic Acid): My Experience
  13. ^ Reduction of Cholesterol and Lp(A) in Regression of Coronary Artery Disease: A Case Study
  14. ^ Coenzyme Q10: A Novel Cardiac Antioxidant (1997)
  15. ^ New/Old Findings on Unique Vitamin E
  16. ^ AscorbateWeb: Timeline from 1935 to 1939
  17. ^ Orthomolecular psychiatry. Varying the concentrations of substances normally present in the human body may control mental disease,Science 1968 Apr 19;160(825):265-71.(PMID 5641253) [1]
  18. ^ Definition of Orthomolecular medicine at www.orthomed.org Accessed June 2006 and What is Orthomolecular Medicine?, Linus Pauling Inst.
  19. ^ a b c http://orthomed.org/kunin.html Principles That Identify Orthormolecular Medicine: A Unique Medical Specialty by Richard A. Kunin Cite error: The named reference "kunin" was defined multiple times with different content (see the help page).
  20. ^ NCCAM.NIH table 1 on page 8
  21. ^ http://orthomed.org Orthomolecular Medicine Online
  22. ^ DJ Hess, Complementary or Alternative? Stronger vs Weaker Integration Policies Am J Public Health. 2002 October; 92(10): 1579–1581.
  23. ^ The Acid Test For Schizophrenia, essay, 2005, accessed September 10, 2006
  24. ^ Hoffer's Home Page -The Schizophrenias, accessed September 10, 2006
  25. ^ P. Scott, E. Richards, B. Martin, Captives of Controversy: The Myth of the Neutral Social Researcher in Contemporary Scientific Controversies, Science, Technology, & Human Values, Vol. 15, No. 4, Fall 1990, pp. 474-494, accessed September 10, 2006
  26. ^ http://www.doctoryourself.com/hoffer_cardio.html
  27. ^ a b c Effects 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
  28. ^ a b 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
  29. ^ a b 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
  30. ^ 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"
  31. ^ Multivitamin 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.
  32. ^ http://www.ajcn.org/cgi/content/full/77/2/279?ijkey=9ab8b23f0bdf45f83af656d8623815f69608ad01&keytype2=tf_ipsecsha
  33. ^ GISSI-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.[PMID 10465168]
  34. ^ Orthomolecular Research
  35. ^ a b c d 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
  36. ^ Fifteen 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.
  37. ^ Associations 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)."
  38. ^ 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
  39. ^ Bruce N Ames, Ilan Elson-Schwab and Eli A Silver (2002). "High-dose vitamin therapy stimulates variant enzymes with decreased coenzyme binding affinity (increased Km): relevance to genetic disease and polymorphisms". American Society for Clinical Nutrition. 75: 616–658. Retrieved 2006-08-12.
  40. ^ Age-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)
  41. ^ 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)
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