Bendich: Niacinamide is the molecule commonly used in multivitamin supplements and is safe. Niacinamide does not lower cholesterol levels. Nicotinic acid has been shown to be a very effective agent in lowering cholesterol when given at high doses. Nicotinic acid, as is true for all cholesterol-lowering agents, increases liver enzyme levels and can cause liver toxicity. High doses of nicotinic acid should be taken only under a physician's supervision, which should include the monitoring of liver enzymes. There have been reports that the use of time-release nicotinic acid has resulted in liver damage severe enough to require liver transplant.

Passwater: Yes, there is such a big difference in nicotinic acid and niacinamide, some may wonder how such two different compounds can be the same vitamin. They both prevent pellagra (the "black tongue" disease that produces skin eruptions, gastric disturbances and nervous disorders including insanity), and they both can form nicotinamide nucleotide coenzymes (NAD+, NADP+ and NADH). One -- nicotinic acid -- can cause a temporary skin "flushing" and lower blood cholesterol levels, while the other -- niacinamide -- does neither.

Since the mid-1980's, there has been increasing concern over possible adverse effects of vitamin B-6. Do any of the pyridoxine vitamers cause nerve damage? Bendich: Vitamin B-6 has been used in pharmacologic doses to treat conditions such as premenstrual syndrome, carpal tunnel syndrome, homocystinuria, galactorrhea and kidney stones. These treatments have generally not been associated with severe adverse effects. However, since 1983, reports have appeared in the literature suggesting that high-dose, long-term administration of pyridoxine produces sensory neuropathy (symptoms such as tingling sensation, loss of feeling, or weakness due to damage or disease of a nerve) in some patients.

Dr. Marvin Cohen and I evaluated the published scientific literature and reported our results in Toxicology Letters in 1986. That study found that the human data on the safety of pyridoxine suggest that oral administration of doses greater than 500 milligrams per day for a prolonged period of time can result in the development of sensory neuropathy. Doses less than 500 milligrams per day appear to be safe on the basis of reports where pyridoxine was administered for periods ranging from six months to six years.

The survey did not reveal any consistent trends for any other adverse effects.

In 1990, we updated our review and examined closely the dose-duration relationship. [12] We concluded that vitamin B-6 intakes of less than 500 milligrams per day for up to two years were safe. However, daily doses above one gram (1,000 milligrams) or total lifetime intakes above 1,000 grams (1,000,000 milligrams) were consistently associated with neuropathy.

As a precaution, I would not recommend the use of vitamin B-6 supplements at levels greater than 200 milligrams per day. Higher doses, if needed, should be used under the supervision of a physician who monitors neurological function.

Passwater: You mentioned that folic acid (folate or folacin) reduces the risk of neural tube birth defects. Yet some hesitate to recommend folate supplements because of a fear of masking B-12 deficiency. Would a supplement containing vitamin B-12 in addition to the folic acid, eliminate this worry? Isn't the risk of birth defects greater in young women than the risk of a hidden vitamin B-12 deficiency?