Orthomolecular medicine

Orthomolecular medicine and optimum nutrition are controversial medical and health approaches 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.

Orthomolecular medicine is explicitly practiced by relatively few conventional medical practitioners. 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. 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.

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 nor hope. Orthomolecular megavitamin therapies, such as "megadose" usage of tocopherols and ascorbates, 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". "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."

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." 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. 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.

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.

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, run by the Journal of Orthomolecular Medicine, discusses differences between orthomolecular medicine and current mainstream medicine, which the website refers to as allopathic medicine.

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 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. 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" despite strong counterexamples such as megadose niacin for dyslipidemias (1955).

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  reduce the overall incidence of cancers


 * Studies finding that greater than RDA of "A, B6, C and E plus zinc", folic acid and selenium   reduce the incidence of specific cancers


 * Studies finding that supplementation of long-chain omega-3 essential fatty acids reduced the incidence of cardiac mortality in secondary prevention trials
 * Early studies finding that vitamin E alone and vitamin C & E together reduce coronary disease mortality


 * Studies finding that niacin, selenium , zinc , vitamin C 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 processes


 * The advocacy of daily multivitamins in cancer prevention by Bruce Ames and by others in a JAMA review article for "chronic disease prevention in adults"

Some of these findings have not been supported by subsequent studies. For example, a subsequent meta-analysis found a lack of benefit to 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 and rheumatic heart problems; modern orthomolecular medicine also has additional nutrient recommendations for CHF. 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. 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.

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. Based on investigational scientific studies, clinical experience, and anecdotal accounts, claims have been made that therapeutic nutrition can cure or treat "alcoholism, allergies, arthritis, autism, epilepsy, hypertension, hypoglycemia, migraine, clinical depression, learning disabilities, retardation, mental and metabolic disorders, skin problems, and hyperactivity."

Nutritional supplements, such as those used in orthomolecular medicine, are virtually unregulated in the United States and are not held to the same strict standards of proof of efficacy as pharmaceutical medications.

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. Orthomolecular proponents, such as Robert Cathcart who predicts that 120+grams per day intravenous vitamin C should cure SARS, have been criticised. 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.

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. Linus Pauling has been criticized for making overbroad claims for the efficacy of vitamin C but has received some support for modified claims in the last few years.

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

The accumulated evidence of randomized clinical trials with 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). 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. 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) . 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. 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 but synthetic "beta carotene... has previously been shown to be harmful" in smokers.  The preferred orthomolecular "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%-50% by weight of other R,R,R tocopherols.

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 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. Several orthomolecular related AIDS approaches such as multivitamins, selenium and amino acids 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 ; a minor 1994 in vitro laboratory study raised questions that sustained megadoses of vitamin C might inhibit some immune cells. 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. The Linus Pauling Institute's funding comes mostly from National Institutes of Health. Several orthomolecular therapies have been officially sanctioned within Japan .

Notable orthomolecular doctors

 * Robert Cathcart
 * Glen Dettman
 * Abram Hoffer
 * Ronald E. Hunnunghake
 * Archie Kalokerinos
 * Fred R. Klenner
 * Matthias Rath
 * Hugh D. Riordan
 * Julian Whitaker
 * Carl Pfeiffer

Orthomolecular scientists

 * Irwin Stone
 * Linus Pauling
 * Steve Hickey

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

Support

 * Orthomolecular Medicine
 * Orthomolecular Medicine Online
 * DoctorYourself.com - Personal site of Andrew Saul PhD, Contributing Editor for the Journal of Orthomolecular Medicine.
 * Analysis of Megavitamin Therapy
 * Linus Pauling Institute website

Criticism

 * "Vitamin Therapy, Megadose / Orthomolecular Therapy", British Columbia Provincial Health Services Authority 2000
 * Orthomolecular Therapy, a critical analysis of orthomolecular medicine by Stephen Barrett MD. 2000
 * Faddism and quackery in cancer nutrition, Nutr Cancer. 1984;6(3):196-206.
 * Should We "Thank God" for Julian Whitaker?, American Council on Science and Health, 1999
 * Recommendations of the NCAHF Task Force on Supplement Abuse (1987)

Reference links
Orthomolekulare Medizin Medicina Ortomolecular Médecine orthomoléculaire Orthomoleculaire therapie