Vitamin Megadoses May Help Treat Metabolic Diseases

In a review article in the April issue of the American Journal of Clinical Nutrition, UC Berkeley's Bruce N. Ames lists more than 50 genetic diseases successfully treated with high doses of vitamins, most of them rare inborn metabolic diseases due to defective enzymes.

Ames found a common thread in the effectiveness of these megavitamin therapies that suggests there may be many more diseases treatable with high-dose vitamins, in particular the eight B vitamins like niacin, thiamine and pyridoxine. And because aging involves similar biochemical deficiencies, megavitamins may help perk up an increasingly older population.

"I suspect that the big impact is going to be in aging," Ames said, though younger people, too, might benefit from supplementary B vitamins to "tune up" their metabolism. Ames is a professor of molecular and cell biology at UC Berkeley and a researcher at Children's Hospital Oakland Research Institute (CHORI).

Megadose vitamin therapy is the use of vitamins in amounts at least 10 times greater than the recommended daily allowance, or RDA. Ames noted that B vitamins are sold over the counter in dosages up to 100 times the RDA, and are generally considered safe at such levels.

In his paper, co-authored with recent UC Berkeley graduate Ilan Elson-Schwab and former CHORI technician Eli A. Silver, Ames argues that the key to the effectiveness of high-dose vitamin therapy lies in the role vitamins play in the body. Vitamins are converted to coenzymes, which team up with enzymes to perform some essential metabolic function.

As Elson-Schwab found in a computer sweep of the literature, about 50 diseases result from a genetic mutation that reduces the ability of an enzyme to bind to its coenzyme, thereby reducing the rate at which the enzyme catalyzes a molecular reaction. Saturating the body with high doses of the appropriate vitamin increases coenzyme levels to overcome the binding defect and boost the reaction rate towards normal.

"These 50 diseases are just the tip of the iceberg," Ames said. "Individual doctors have noticed this, but nobody put it all together. Now, doctors are going to try high-dose vitamin therapy the minute they know a coenzyme is involved in a disease or there is a problem with the substrate. It makes sense, since many of the vitamins are generally recognized as safe in large doses. I think this kind of thing will turn up all over once people start looking."

In the paper, Ames and Elson-Schwab estimate that up to one-third of all mutations in a gene may affect binding to a vitamin-derived coenzyme, which means that high-dose vitamin therapy might reverse the effects of these mutations.

The theory has far broader implications than just the treatment of genetic disease. The human genome is rife with genetic variation that probably affects enzyme-coenzyme interactions, and thus vitamin requirements. High-dose vitamins might tweak enzyme functioning enough to improve the health of many segments of society, Ames said. Eliminating vitamin and mineral deficiencies will restore what he calls "metabolic harmony."

"Zinc and iron deficiency, vitamin C, B-12 and B-6 deficiencies are very common," he said. "Yet, a multivitamin pill costs only a penny to make - you can buy a year's supply for ten dollars. Everybody in the world should take one as insurance and try to eat a good diet."

Flooding the body with an excess of some enzyme cofactors may perk up the aging body, too, since aging is accompanied by oxidati