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Research Newsletter-Spring/Summer 2008


This year marks the 40th anniversary of Linus Pauling's seminal paper "Orthomolecular Psychiatry," in which Pauling introduced the term orthomolecular medicine and provided its scientific basis. Published in the highly regarded scientific journal Science in April 1968, the paper argued for the application of vitamins to treat mental illness. Pauling had worked on problems in mental illness since the mid-1950s, believing that abnormalities in enzyme function may help explain schizophrenia and other mental illnesses because the brain is exquisitely sensitive to its constituent chemicals. For example, chronic deficiencies of niacin or vitamin B12, resulting in pellagra or pernicious (or megaloblastic) anemia, respectively, are accompanied by mental impairment like psychosis and dementia, as well as physical symptoms. When vitamin B12 deficiency was more common in the early 20th century, affected individuals often exhibited "megalobastic madness." Indeed, Pauling's mother Belle suffered from this and succumbed in 1926 to the disease. Chronic deficiency of another B vitamin, biotin, can also cause neurological symptoms like depression and hallucinations. Even a chronic deficiency of vitamin C can result in depression.

Pauling suggested that supplying certain vitamins in amounts much larger than those required to prevent the associated deficiency diseases may help normalize brain biochemistry, resulting in attenuation of mental illness. In his paper Pauling discussed how large amounts of vitamins may enhance biological activity and cited work by Beadle and Tatum showing that the growth rate of vitaminrequiring mutant strains of Neurospora, a genus of fungi, actually surpassed that of the normal, vitamin-synthesizing parental strain when the vitamin was supplied in the culture medium in large amounts. Pauling also noted that the rates of enzyme-catalyzed reactions, which may be impaired in mental illness because of defective enzymes, may be normalized by supplying large amounts of the substrate, such as vitamins. For example, in a 2002 paper in the American Journal of Clinical Nutrition, Dr. Bruce Ames, recipient of the 2001 LPI Prize for Health Research, discussed the vitamin remediation of about 50 genetic diseases caused by poor affinity of a mutant enzyme for its coenzyme. Additionally, genetic polymorphisms (slight differences in genes among people) affect enzyme-coenzyme reactivity.

In his book How to Live Longer and Feel Better (20th anniversary edition from the Oregon State University Press, 2006), Pauling provided a succinct definition of orthomolecular medicine: "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." An abbreviated definition might be "the right molecules in the right amounts," since ortho is a prefix meaning right or correct. Clearly, Pauling had vitamins and nutritionally essential minerals in mind, but his definition also encompasses phytochemicals (chemicals from plants that may affect health) and other constituents of the diet. These concepts form the basis of the research mission of the Linus Pauling Institute, which is to:

  • Determine the function and role of vitamins and essential minerals (micronutrients) and chemicals from plants (phytochemicals) in promoting optimum health and preventing and treating disease,
  • Determine the role of oxidative and nitrative stress and antioxidants in human health and disease,
and, continuing the humanitarian interest and spirit of Linus Pauling, to:
  • Help people everywhere achieve a healthy and productive life, full of vitality, with minimal suffering, and free of cancer and other debilitating diseases.

For more information on orthomolecular medicine, please see "What is Orthomolecular Medicine" by Stephen Lawson in the Fall/Winter 1999 LPI Research Report, archived online.

Last updated June 2008