Williams Adrian C, Dunbar Robin I M
Institute for Cognitive and Evolutionary Anthropology, University of Oxford, 64 Banbury Road, Oxford OX2 6PN, UK.
Department of Experimental Psychology, University of Oxford, South Parks Rd, Oxford OX1 3UD, UK.
Med Hypotheses. 2014 Jul;83(1):79-87. doi: 10.1016/j.mehy.2014.04.003. Epub 2014 Apr 13.
Meat eating has been an important trigger for human evolution however the responsible component in meat has not been clearly identified. Here we propose that the limiting factors for expanding brains and increasing longevity were the micronutrient nicotinamide (vitamin B3) and the metabolically related essential amino-acid, tryptophan. Meat offers significant sourcing challenges and lack causes a deficiency of nicotinamide and tryptophan and consequently the energy carrier nicotinamide adenine dinucleotide (NAD) that gets consumed in regulatory circuits important for survival, resulting in premature ageing, poor cognition and brain atrophy. If a trophic supply of dietary nicotinamide/tryptophan is so essential for building brains, constraining their size and connectivity, we hypothesise that back-up mechanisms to ensure the supply evolved. One strategy may be increasing the reliance on gut symbionts to break down celluloses that produces NADH and only nicotinamide indirectly, and may cause diarrhoea. We suggest that a direct supplier was the chronic mycobacterial infection tuberculosis (TB) that is a surprise candidate but it co-evolved early, does not inevitably cause disease (90-95% of those infected are healthy), and secretes (and is inhibited by) nicotinamide. We hypothesise that TB evolved first as a symbiont that enabled humans to cope with short-lived shortages of meat and only later behaved as a pathogen when the supply deteriorated chronically, for those in poverty. (TB immunology and epidemiology is riddled with paradoxes for a conventional pathogen). We test this in pilot data showing that sharp declines in TB (and diarrhoea) - `environmental enteropathy' strongly correlate with increasing meat consumption and therefore nicotinamide exposure, unlike later onset cancers and Parkinson's disease that increased in incidence, perhaps - as we propose a hypothetical hypervitaminosis B3 (to include obesity and the metabolic syndrome) - as the trade-off for increased brain power and longevity, a recently evolved human characteristic.
肉食一直是人类进化的重要触发因素，然而肉类中起作用的成分尚未明确。在此我们提出，大脑扩张和寿命延长的限制因素是微量营养素烟酰胺（维生素B3）以及代谢相关的必需氨基酸色氨酸。获取肉类存在重大挑战，缺乏肉类会导致烟酰胺和色氨酸缺乏，进而导致能量载体烟酰胺腺嘌呤二核苷酸（NAD）缺乏，而NAD在对生存至关重要的调节回路中被消耗，从而导致早衰、认知能力差和脑萎缩。如果膳食烟酰胺/色氨酸的营养供应对于大脑发育、限制大脑大小和连接性如此重要，我们推测确保供应的备用机制已经进化。一种策略可能是增加对肠道共生菌的依赖，以分解纤维素，纤维素间接产生NADH和仅烟酰胺，并且可能导致腹泻。我们认为直接的供应者是慢性分枝杆菌感染——结核病（TB），这是一个出人意料的候选者，但它很早就共同进化了，不一定会导致疾病（90 - 95%的感染者是健康的），并且会分泌（并被）烟酰胺抑制。我们推测结核病最初作为一种共生菌进化而来，使人类能够应对肉类的短期短缺，只是后来在供应长期恶化时，对于贫困人口而言，才表现为病原体。（结核病的免疫学和流行病学充满了传统病原体所没有的悖论）。我们在试点数据中对此进行了测试，结果表明结核病（和腹泻）——“环境肠病”的急剧下降与肉类消费增加以及因此烟酰胺暴露增加密切相关，这与后来发病率增加的癌症和帕金森病不同，也许——正如我们提出的假设性维生素B3过多症（包括肥胖和代谢综合征）——作为大脑能力增强和寿命延长的代价，这是人类最近进化出的特征。
