Abstract
Meat and nicotinamide acquisition was a defining force during the 2-million-year evolution of the big brains necessary for, anatomically modern, Homo sapiens to survive. Our next move was down the food chain during the Mesolithic 'broad spectrum', then horticultural, followed by the Neolithic agricultural revolutions and progressively lower average 'doses' of nicotinamide. We speculate that a fertility crisis and population bottleneck around 40 000 years ago, at the time of the Last Glacial Maximum, was overcome by Homo (but not the Neanderthals) by concerted dietary change plus profertility genes and intense sexual selection culminating in behaviourally modern Homo sapiens. Increased reliance on the 'de novo' synthesis of nicotinamide from tryptophan conditioned the immune system to welcome symbionts, such as TB (that excrete nicotinamide), and to increase tolerance of the foetus and thereby fertility. The trade-offs during the warmer Holocene were physical and mental stunting and more infectious diseases and population booms and busts. Higher nicotinamide exposure could be responsible for recent demographic and epidemiological transitions to lower fertility and higher longevity, but with more degenerative and auto-immune disease.