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Current Gerontology and Geriatrics Research
Volume 2012, Article ID 302875, 24 pages
Review Article

Nicotinamide, NAD(P)(H), and Methyl-Group Homeostasis Evolved and Became a Determinant of Ageing Diseases: Hypotheses and Lessons from Pellagra

1Neuropharmacology and Neurobiology, School of Clinical and Experimental Medicine, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK
2Institute for Cognitive and Evolutionary Anthropology, University of Oxford, 64 Banbury Road, Oxford OX2 6PN, UK

Received 10 October 2011; Accepted 19 December 2011

Academic Editor: Fabio Coppedè

Copyright © 2012 Adrian C. Williams et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Compartmentalized redox faults are common to ageing diseases. Dietary constituents are catabolized to NAD(H) donating electrons producing proton-based bioenergy in coevolved, cross-species and cross-organ networks. Nicotinamide and NAD deficiency from poor diet or high expenditure causes pellagra, an ageing and dementing disorder with lost robustness to infection and stress. Nicotinamide and stress induce Nicotinamide-N-methyltransferase (NNMT) improving choline retention but consume methyl groups. High NNMT activity is linked to Parkinson’s, cancers, and diseases of affluence. Optimising nicotinamide and choline/methyl group availability is important for brain development and increased during our evolution raising metabolic and methylome ceilings through dietary/metabolic symbiotic means but strict energy constraints remain and life-history tradeoffs are the rule. An optimal energy, NAD and methyl group supply, avoiding hypo and hyper-vitaminoses nicotinamide and choline, is important to healthy ageing and avoids utilising double-edged symbionts or uncontrolled autophagy or reversions to fermentation reactions in inflammatory and cancerous tissue that all redistribute NAD(P)(H), but incur high allostatic costs.