2018
Rosemary A Fricker, Emma L Green, Stuart I Jenkins, and Síle M Griffin

 

Abstract

Nicotinamide, the amide form of vitamin B3 (niacin), has long been associated with neuronal development, survival, and function in the central nervous system (CNS), being implicated in both neuronal death and neuroprotection. Here, we summarise a body of research investigating the role of nicotinamide in neuronal health within the CNS, with a focus on studies that have shown a neuroprotective effect. Nicotinamide appears to play a role in protecting neurons from traumatic injury, ischaemia, and stroke, as well as being implicated in 3 key neurodegenerative conditions: Alzheimer’s, Parkinson’s, and Huntington’s diseases.

A key factor is the bioavailability of nicotinamide, with low concentrations leading to neurological deficits and dementia and high levels potentially causing neurotoxicity.

Finally, nicotinamide’s potential mechanisms of action are discussed, including the general maintenance of cellular energy levels and the more specific inhibition of molecules such as the nicotinamide adenine dinucleotide-dependent deacetylase, sirtuin 1 (SIRT1).

 

Summary

There is a growing body of evidence that nicotinamide is implicated in neuronal differentiation and health, neuronal injury, and neurodegeneration in the CNS. Changes in nicotinamide levels have been linked with AD, PD, and HD, and nicotinamide treatment in animal models has shown amelioration of neurodegeneration and associated behavioural recovery. Equally, there is evidence of nicotinamide being used as a restorative agent in animal models of neuronal injury and ischaemia.

The plethora of intracellular systems influenced by nicotinamide levels makes it difficult to determine precise mechanisms of action by this dietary metabolite. However, it is becoming clear that nicotinamide should be titrated to balanced levels in the CNS to avoid neural sequelae caused by either too little or too much nicotinamide within mature neurons.

With this in mind, supporting neuronal health through good dietary supplementation and management of small bioactive molecules such as nicotinamide appears an exciting and achievable prospect.