Megavitamin therapies were also publicly advocated by Linus Pauling in the late 1960s. Williams introduced concepts for individualized megavitamins and nutrients. In a 1956 publication entitled Biochemical Individuality, Roger J. Rudolf Altschul and Abram Hoffer applied large doses of the immediate release form of niacin (Vitamin B 3) to treat hypercholesterolemia. William Kaufman published articles in the 1940s that detailed his treatment of arthritis with frequent, high doses of niacinamide. Jungeblut with larger doses of vitamin C led to Frederick Klenner's development of megadose intravenous vitamin C treatments for polio and other viruses in the 1940s. Tentative experiments in the 1930s by Claus W.

Beginning in the 1930s in Canada, a megadose vitamin E therapy for cardiovascular and circulatory complaints was developed by Evan Shute and colleagues, named the 'Shute protocol'. In the 1930s and 1940s, some scientific and clinical evidence suggested that there might be beneficial uses of vitamins C, E, and niacin in large doses. A study of 161,000 individuals (post-menopausal women) provided, in the words of the authors, 'convincing evidence that multivitamin use has little or no influence on the risk of common cancers, cardiovascular disease, or total mortality in postmenopausal women'. Megavitamin doses are far higher than the levels of vitamins ordinarily available through western diets. Megavitamin therapy must be distinguished from the usual 'vitamin supplementation' approach of traditional multivitamin pills. Research on nutrient supplementation in general suggests that some nutritional supplements might be beneficial, and that others might be harmful several specific nutritional therapies are associated with an increased likelihood of the condition they are meant to prevent. Critics have described some aspects of orthomolecular medicine as food faddism or even quackery.

It is generally accepted that doses of any vitamin greatly in excess of nutritional requirements will result either in toxicity (vitamins A and D) or in the excess simply being metabolised thus evidence in favour of vitamin supplementation supports only doses in the normal range. Vitamins are useful in preventing and treating illnesses specifically associated with dietary vitamin shortfalls, but the conclusions of medical research are that the broad claims of disease treatment by advocates of megavitamin therapy are unsubstantiated by the available evidence. Megavitamin therapy is typically used in alternative medicine by practitioners who call their approach orthomolecular medicine. Megavitamin therapy is the use of large doses of vitamins, often many times greater than the recommended dietary allowance (RDA) in the attempt to prevent or treat diseases.

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