Frequently used in complementary and alternative medicine and orthomolecular medicine, megavitamin therapists also may employ nutrients such as dietary minerals, enzymes, amino acids, essential fatty acids, natural antioxidants, fermentable dietary fiber or short chain fatty acids.
The use of large doses of vitamins is medically supported for several dozen specific medical conditions. Historically, some megadose treatments with non-orthomolecular vitamin forms used in conventional medicine have been known to cause harm. The broad claims of effectiveness of many other treatments made by advocates of alternative medicine are considered inadequately substantiated by mainstream medicine.
In 1954, Professor R. Altschul and Abram Hoffer, MD, PhD, applied large doses of the immediate release form of niacin (Vitamin B-3) to treat hypercholesterolemia (high cholesterol). High dose niacin was shown to be more effective than conventional treatments in the Canner study of the Coronary Drug Project, a large scale, prospective, randomized, controlled trial to reduce long term total mortality, showed 11% reduction in mortality at 15 years follow up with only 6 years of niacin treatment. The other conventional approaches (two estrogen regimens, dextrothyroxine and clofibrate) —treatments that are no longer standard of care—were ineffective.. Niacin is used to treat hypercholesterolemia because of its low cost and its unique ability to broadly improve lipid profiles for ApoB , LDL, small dense LDL, HDL, HDL2b (extremely good cholesterol), Lp(a), fibrinogen and trigycerides .
The 1956 publication of Roger J. Williams Biochemical Individuality introduced concepts for individualized megavitamins and nutrients. In the 1960s, biochemist Irwin Stone, author of The Healing Factor, observed that vitamin C's utility in the megadose treatments of human disease parallels the amounts of vitamin C physiologically produced in most animals and postulated humans' evolutionary loss of this capability. Megavitamin therapies were also publicly advocated by Linus Pauling in the late 1960s.
Several orthomolecular megavitamin protocols have been publicized. While formal medical recognition of niacin therapy for hypercholesterolemia followed confirmation by William Parsons of the Mayo Clinic (1956) and the Canner study (1986), the success of several popular books since the 1980s has made the public more aware of niacin's effective megavitamin therapy for dyslipidemias (abnormal lipid levels in the blood). Pauling's advocacy of megadoses of vitamin C for colds, beginning in the 1960s, and later for cancer, made millions aware of the concept of megavitamin treatment in disease. Pauling's vitamin C recommendations are lower than some modern recommendations.
Other treatments include orthomolecular oral dosing schedules for an early, "abortive" treatment of a cold at onset, and for bowel tolerance for more established colds, typically using 40 to 100+ grams per day in hourly doses as recommended as effective by orthomolecular practitioners.
The term "megavitamin therapy" itself was criticized by opponents of orthomolecular psychiatry in the early 1970s as misleading, because they believed the term falsely implied therapeutic benefit, because of still unresolved disputes over scientific rigor and efficacy for the early 1950s treatment of a carefully specified type of acute schizophrenia.
Some megadose vitamin uses, often older pharmaceutical ones such as neonatal use of synthetic menadione, "a synthetic lipid soluble product which was once called vitamin K3", can cause toxicity. In the specific case of synthetic K3, large doses may cause hemolytic anemia, which occurs when the red blood cells die more quickly than the body can reproduce. In addition, K3 speeds liver damage, producing jaundice, deafness, and severe neurological problems, including retardation in infants. There is no record that the other two, natural series of Vitamin K, have produced toxic levels. The pharmaceutical synthetic, K3, is now banned in most countries for neonatal or general human use. These were previously conventional medical therapeutics, not orthomolecular type megavitamin treatments.
The United States Department of Agriculture establishes a maximum intake level for most vitamins, at which no adverse effects should occur including many infrequent or minor effects. These are part of the Tolerable upper intake level (UL) recommendations. Extremely high dose vitamin A for previous conventional pediatrics and dermatology practices, beyond orthomolecular therapy ranges, have been deprecated by some medical organizations of minor political units as ineffective and potentially toxic Administration of very large doses of vitamin A, vitamin C, vitamin D, and pyridoxine (Vitamin B6) may have adverse side effects