Poverty and Pellagra’s Penumbras

Pellagra has largely been forgotten. This is unfortunate as important lessons are to be learnt about the diseases and social and economic consequences of poverty – and for the root cause of poverty (and of affluence) – that involve dietary nicotinamide and nicotinamide adenine dinucleotide (NAD) homeostasis. NAD disruption can occur not only from poor diet but from increased consumption from genotoxic, infectious and metabolic stresses. NAD deficiency is closely linked to poor physical and intellectual development, premature ageing and diseases of ageing. Acute infections, many with NAD-consuming toxins, that may differentially affect the NAD-depleted, now include COVID-19. Some Covid manifestations, such as myoclonic encephalopathy and “Long Covid,” resemble pellagra clinically and biochemically as both have disturbed nicotinic and tryptophan metabolism. Symbionts that supply nicotinic acid, such as TB and some gut micro-organisms, can become dysbiotic if the diet is very deficient in milk and meat, as it is for 1–2 billion or more. High doses of nicotinamide lead to inhibition of NAD-consuming enzymes and excessive induction of nicotinamide-n-methyl transferase (NNMT) with consequent effects on the methylome: this gives a mechanism for an unrecognised hypervitaminosis-B3 with adverse effects of nicotinamide overload for consumers on a high meat diet with “fortified” foods and “high energy” drinks. Methods of measuring NAD metabolism routinely for screening the populations at risk of deficiency and in metabolically ill or infectious disease patients should be developed urgently. Successful intervention should improve human capital and prevent many aspects of poverty, reduce discrimination and even the drive to emigrate.