Vitamin B3 variant reverses effects of fetal alcohol syndrome in mice

A form of vitamin B3 called nicotinamide can reverse the molecular, cellular, and behavioral effects of fetal alcohol syndrome (FAS) in mice, according to a study by physician-scientists at Weill Medical College of Cornell University.

The study, published in today's journal PLoS Medicine, suggests that nicotinamide may hold promise as a preventative therapy in the treatment of FAS in humans.

The findings may also have implications for children born with other neurological diseases such as cerebral palsy.

"Despite attempts to increase awareness of FAS, consumption of alcohol during pregnancy, especially binge drinking, has increased in recent years and currently there are no effective treatments to prevent or revert the devastating effects of FAS. Our findings offer hope that nicotinamide may fill this need," says Dr. Daniel Herrera, assistant professor of psychiatry at Weill Medical College of Cornell University and assistant attending psychiatrist at Payne Whitney Manhattan at NewYork-Presbyterian Hospital/Weill Cornell Medical Center.

Ethanol and nicotinamide were administered to seven-day-old postnatal mice, an age at which the brain development of mice is comparable to the human third trimester.

The study found that most damage occurred in brain regions that are particularly sensitive to ethanol during development, namely the anterior cingulate cortex (involved in cognition), the hippocampus (needed for learning and memory) and the thalamus (relays sensory information to other brain regions); nicotinamide treatment reduced this damage. Several days following ethanol exposure, the study found reduced numbers of neurons (compared with control brains) in similar brain regions; again, nicotinamide reduced ethanol's effects. Finally, the researchers used three standard behavioral tests to determine whether the reduction in ethanol-induced neuronal death produced by nicotinamide affected the behavior of adult mice. They report that nicotinamide reversed the increase in hyperactivity and the decrease in fear caused by ethanol exposure, and prevented the impairment in learning and memory induced by ethanol.

While the beneficial effects observed were most pronounced when nicotinamide was given at the same time or shortly after alcohol exposure, the study suggests that there is a window of a few hours during which treatment with nicotinamide might be effective.

FAS is estimated to be the most common, preventable cause of mental retardation in the western world. About one in 1,000 U.S. children is born with FAS. Children with FAS typically have abnormal facial features and reduced growth. They also have central nervous system abnormalities that lead to impaired learning and memory skills, hyperactivity and other behavioral problems. These neurological disabilities arise because ethanol disrupts the formation and survival of neurons in the developing brain, particularly in the last trimester of pregnancy and the first few years of postnatal life when brain development is particularly active.

There is no cure for FAS, but it is 100 percent preventable. Public health officials recommend that sexually active women who do not use effective birth control and women planning pregnancy avoid alcohol -- there is no safe dose of alcohol or safe time to drink it during pregnancy. Sadly, this advice is often ignored. In the U.S., 1 in 12 pregnant women admit to drinking alcohol and 1 in 30 report binge drinking (five or more drinks at one time).

Nicotinamide and other forms of vitamin B3 have been used for many years as dietary supplements to treat and prevent pellagra, a vitamin deficiency disease. Large oral doses of nicotinamide have also been used in clinical trials to treat type I diabetes and bullous pemphigoid (a chronic, autoimmune skin-blistering disease). In addition, recent animal data indicate that nicotinamide is also neuroprotective. Nicotinamide has little or no side effects and results in no birth defects.

The study was co-authored with Dr. Alessandro Ieraci, a postdoctoral fellow at Weill Cornell.

PLoS Medicine is an open-access, peer-reviewed medical journal published monthly, online and in print, by the Public Library of Science.

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