Orthomolecular Medicine

Pauling's 1968 paper

The International Society for Orthomolecular Medicine credits the chemist Linus Pauling with coining the term orthomolecular, and lists his 1968 Science article, 'Orthomolecular psychiatry', as further reading. The abstract of that paper proposes that brain function is affected by the molecular concentrations of substances normally present in the brain, that the optimum concentrations for a person may differ from those supplied by the normal diet and genetic machinery, and that orthomolecular therapy may be the preferred treatment for many mentally ill patients.

The abstract also suggests that the postulated gene for schizophrenia might itself be a gene leading to a localized cerebral deficiency in one or more vital substances. The abstract presents this as a suggestion by the author. It describes a hypothesis, not a tested finding.

From psychiatry to general medicine

The Linus Pauling Institute at Oregon State University says Pauling later broadened the idea into orthomolecular medicine, an approach to preventing and treating disease with nutrients such as vitamins, minerals and amino acids, and glosses the term as the right molecules in the right concentration. The Institute says he saw it as a complement to standard medical care rather than a replacement. Its biography also describes research with Abram Hoffer on vitamins in cancer and says Pauling became convinced that vitamin C helped with cancer, influenza and other conditions.

A Cochrane review of vitamin B6 and magnesium in autism states that mega-vitamin intervention began in the 1950s with the treatment of people with schizophrenia, and that vitamin B6 was later tried in children described as having autism after speech and language improvement was observed in some of them. The review reports this as background and does not itself test the 1950s work.

Later organizations and news service

The International Society for Orthomolecular Medicine and the Orthomolecular Medicine News Service now carry the term. The news service describes itself as a wire-service style news feed for press, radio and television, published by an editorial board of physicians and scientists. A 2005 release lists Abram Hoffer as one of four editors. These are advocacy and information bodies of the movement, so their pages are used here to show how the movement describes itself and not as independent evidence.

The term and its definitions

The Orthomolecular Medicine News Service attributes to Pauling the definition of orthomolecular medicine as the treatment of disease by the provision of the optimum molecular environment, specifying optimum concentrations of substances normally found in the body. The International Society for Orthomolecular Medicine describes it as using natural substances such as vitamins, minerals and amino acids to prevent and treat disease, supplying the right molecules in the right amounts.

Related names and neighboring Machipedia pages

Sources use several names for related ideas. Pauling's paper uses orthomolecular psychiatry and orthomolecular therapy, a 1984 case report is titled with the phrase megavitamin therapy, and the Cochrane review above uses mega-vitamin intervention. PubMed indexes the area under the heading Orthomolecular Therapy. These terms overlap but are not identical in scope, and the sources reviewed do not define a single agreed boundary.

Orthomolecular medicine is one framework for using supplements. The Machipedia page Dietary Supplements covers supplements as a product category and this page does not repeat it. Other related pages include Multivitamin Supplements, Nutritional Psychiatry, Nutritional Therapy, High-Dose Intravenous Vitamin C and Naturopathy. Findings on any of those pages should not be assumed to apply here, and the reverse also holds.

What the movement says it involves

The International Society for Orthomolecular Medicine describes a practice that considers nutrients first in diagnosis and treatment, treats each person according to individual biochemistry, looks for root causes rather than only symptoms, and allows nutrient amounts above standard daily intake recommendations when therapeutic. It also says the approach assesses toxicity risk, uses the lowest effective drug dose when drugs are needed, and respects patient choice and informed consent. These are the society's own statements and have not been independently tested as a package. This page gives no doses or protocols.

Who delivers it

The sources reviewed do not describe a register, protected title, curriculum or training standard for orthomolecular practitioners, and the society page opened does not list one. A 1984 case report notes that ingesting large doses of vitamins was increasing in a considerable segment of the population, which suggests that self-directed use occurs alongside practitioner-led use. The sources do not say how common either is.

Psychiatric conditions

Pauling's paper proposed orthomolecular therapy for many mentally ill patients and gave schizophrenia particular attention. The Cochrane review of vitamin B6 and magnesium notes that high-dose vitamin approaches were applied to schizophrenia from the 1950s and later to autism. These claims originated within the movement and are separate from the trial results summarized below.

Cancer, infection and general disease

The Linus Pauling Institute biography says Pauling came to hold that vitamin C helped with cancer and influenza. The movement's news service also publishes releases with strongly positive titles for individual nutrients, such as a 2005 release headed 'Vitamin E: Safe, Effective, and Heart-Healthy'. Such headings state the movement's position. They are not findings from the reviews summarized on this page, which reached different conclusions for some nutrients.

Vitamin C in advanced cancer

Two randomized, double-blind trials from the Mayo Clinic group tested high-dose oral vitamin C against placebo. The 1979 trial in 150 patients with advanced cancer (60 evaluable on vitamin C, 63 on placebo) found no appreciable difference in symptoms, performance status, appetite, weight or survival, with median survival of about seven weeks. The 1985 trial in 100 patients with advanced colorectal cancer and no prior chemotherapy found no advantage over placebo for time to progression or survival, and the authors concluded that high-dose vitamin C was not effective against advanced malignant disease.

The National Cancer Institute summary notes that these were oral trials and that intravenous administration reaches much higher blood levels than oral dosing. It describes laboratory findings, mixed phase II results and limitations in trial rigor for the intravenous work. It says intravenous use is generally well tolerated in trials but is not established. That intravenous literature is treated on the Machipedia page High-Dose Intravenous Vitamin C, and the oral trial results should not be carried across to it, or the reverse.

Antioxidant supplements and mortality

A 2012 Cochrane review of 78 randomized trials with 296,707 participants assessed antioxidant supplements (beta-carotene, vitamin A, vitamin C, vitamin E and selenium) for preventing mortality. The authors found no evidence to support antioxidant supplements for primary or secondary prevention, and concluded that beta-carotene and vitamin E seem to increase mortality, as may higher doses of vitamin A. Vitamin C and selenium showed no significant effect on mortality in low-bias trials. A 2007 JAMA meta-analysis of 68 trials reached a similar conclusion for beta-carotene, vitamin A and vitamin E. These trials tested oral antioxidant supplements and were not trials of orthomolecular programs as a whole.

Psychiatric and developmental conditions

A 2017 systematic review and meta-analysis of 18 randomized trials (832 patients) of vitamin and mineral supplements in schizophrenia found that vitamin B supplementation reduced psychiatric symptoms more than control conditions, with a wide confidence interval and substantial heterogeneity, and no effects on positive or negative symptom domains. It found no overall effect from antioxidant vitamins, inositol or dietary minerals. The authors describe the evidence as preliminary, and the trials used supplements as an adjunct to antipsychotic medication. Only the abstract was read.

For autism, a Cochrane review of combined vitamin B6 and magnesium included three small trials with 33 participants in total and advanced no recommendation because of the small number, quality and size of the studies. A later overview of 17 Cochrane reviews of autism interventions reported that no benefit was found for vitamin B6 with magnesium, among other treatments.

Gaps in the sources reviewed

No free-access copy of the 1970s professional task force reports on megavitamin and orthomolecular therapy in psychiatry could be opened and verified, so their findings are not reported here. Searches of PubMed for megavitamin therapy in ADHD and autism, for the Hoffer and Osmond niacin work, and for a Cochrane review of vitamin therapy in schizophrenia returned no record that could be verified for this page. The sources reviewed also include no professional-body position statement on orthomolecular medicine.

Why findings do not transfer

The reviews summarized here tested specific nutrients, routes and conditions. Results for oral vitamin C in advanced cancer, antioxidant prevention trials and adjunctive B vitamins in schizophrenia do not establish or refute the broader orthomolecular framework, in which individual biochemistry guides choices. Authors of the safety literature make a related point: a 1984 case report states that many claims of benefit for megavitamin therapy have been made but few have been demonstrated in controlled trials, and the 2012 Cochrane authors say antioxidant supplements should be treated as medicinal products and evaluated sufficiently before marketing.

Niacin and vitamin B6

The NIH Office of Dietary Supplements reports that supplemental nicotinic acid commonly causes skin flushing with burning, tingling and itching. At pharmacologic intakes it can cause more serious effects, including impaired glucose tolerance, gastrointestinal effects, blurred vision with macular edema, raised liver enzymes, hepatitis and liver failure. It says liver toxicity is more likely with extended-release nicotinic acid, and that signs of liver toxicity can also occur with very high nicotinamide intakes.

The same office reports that chronic high oral intake of vitamin B6 can cause severe and progressive sensory neuropathy, including ataxia. It notes that the Food and Nutrition Board cited neuropathy reports at lower intakes in some cases while other studies found none, and that the board set its upper intake level with that uncertainty in mind.

Vitamin A, vitamin C and combined intakes

A 1984 case report describes a man with pancytopenia, severe sensory neuropathy and portal hypertension after six years of excessive vitamin intake, with a liver biopsy showing hypervitaminosis A. A 1988 case report describes benign intracranial hypertension from excess vitamin A in a child with juvenile chronic arthritis, who recovered after it was withdrawn. These are single-patient reports and do not show how often such harm occurs. MedlinePlus notes that fat-soluble vitamins, including vitamin A, can accumulate in the body.

MedlinePlus says very high vitamin C intakes can cause stomach upset and diarrhea and, rarely, kidney stones. The National Cancer Institute reports renal failure in people with preexisting kidney disorders given intravenous vitamin C, hemolysis risk in people with G6PD deficiency, and interference with some blood tests and glucose meters. The Cochrane reviews above also link higher vitamin A doses and beta-carotene or vitamin E with higher mortality in prevention trials. The sources reviewed do not cover iron overload.

Care boundaries

The Linus Pauling Institute describes Pauling as viewing the approach as a complement to standard medical care. Nothing in the sources reviewed supports using high-intake supplements in place of established treatment for cancer, psychiatric illness or other conditions. Anyone with a medical condition, who is pregnant, takes prescribed medicines or has kidney or liver disease should discuss supplements with a qualified clinician, and necessary care should not be delayed or replaced.