Dietary niacin and brain function

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Clinical niacin deficiency remains a problem in developing countries while subclinical deficiency persists in affluent countries. Niacin deficiency is observed with alcohol abuse and can lead to serious cognitive problems that enhance the impact of the disease. The risk of niacin toxicity is also a current issue as many adults consume gram quantities of nicotinic acid to lower blood cholesterol and some children at risk of developing IDDM are consuming similar quantities of nicotinamide. Pellagra, the disease in humans caused by severe niacin deficiency, is characterized, in part, by a striking dementia. This dementia may range from depression through hallucinations to behavior similar to schizophrenia. The neurological symptoms are dramatically relieved within hours after niacin supplementation, showing that niacin is involved in the biochemistry of nervous transmission. Niacin is required for the synthesis of nicotinic acid adenine dinucleotide phosphate (NAADP) and cyclic ADP-ribose, calcium signaling molecules known to regulate synaptic efficiency between neurons in the brain. Our hypothesis is that niacin deficiency and pharmacological supplementation will affect neuron function, leading to changes in learning and memory, social interactions and other behaviors. We have shown that mice lacking one of the enzymes that makes cyclic ADP-ribose display hyperactive behavior.  We have also shown that niacin deficiency and megadosing cause decreased and increased cyclic ADP-ribose levels, respectively, in rat brain, and that the ability of rats to solve spatial learning tasks responds to niacin status.  We are currently developing a model of niacin deficiency in more mature rats to look at a greater range of behaviors, and to examine the role of tryptophan metabolites in these disturbances. Given the lack of knowledge in the area of niacin status and brain function, these basic experiments are essential to develop effective animal models which will allow us to determine safe intakes ranges for different forms of niacin, and to explore the roles that niacin plays in brain function. In the long term, learning now niacin deficiency causes dementia may provide clues in the treatment of conditions like schizophrenia.