Dr. Ron’s Research Review – July 26, 2017

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This week’s research review focuses on meat and niacinamide.

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. The authors 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. (Williams and Dunbar, 2014)

Meat and vitamin B3 - nicotinamide - intake was high during hunter-gatherer times. Intake then fell and variances increased during and after the Neolithic agricultural revolution. Health, height, and IQ deteriorated. Vitamin B3 deficiency may now be common among the poor billions on a low-meat diet. An optimal dosage of vitamin B3 could lead to better health, but some people may require personalized doses. (Hill and Williams, 2017)

Hunting for meat was a critical step in all animal and human evolution. A key brain-trophic element in meat is vitamin B3 / nicotinamide. The supply of meat and nicotinamide steadily increased from the Cambrian origin of animal predators ratcheting ever larger brains. This culminated in the 3-million-year evolution of Homo sapiens and our overall demographic success. A biochemical and immunological switch is highlighted that affects fertility in the 'de novo' tryptophan-to-kynurenine-nicotinamide 'immune tolerance' pathway. High meat intake correlates with moderate fertility, high intelligence, good health, and longevity with consequent population stability, whereas low meat/high cereal intake (short of starvation) correlates with high fertility, disease, and population booms and busts. Too high a meat intake and fertility falls below replacement levels. (Williams and Hill, 2017)

 

Dr. Ron


 

Articles

Meat Intake and the Dose of Vitamin B3 - Nicotinamide: Cause of the Causes of Disease Transitions, Health Divides, and Health Futures
            (Hill and Williams, 2017) Download
Meat and vitamin B3 - nicotinamide - intake was high during hunter-gatherer times. Intake then fell and variances increased during and after the Neolithic agricultural revolution. Health, height, and IQ deteriorated. Low dietary doses are buffered by 'welcoming' gut symbionts and tuberculosis that can supply nicotinamide, but this co-evolved homeostatic metagenomic strategy risks dysbioses and impaired resistance to pathogens. Vitamin B3 deficiency may now be common among the poor billions on a low-meat diet. Disease transitions to non-communicable inflammatory disorders (but longer lives) may be driven by positive 'meat transitions'. High doses of nicotinamide lead to reduced regulatory T cells and immune intolerance. Loss of no longer needed symbiotic 'old friends' compounds immunological over-reactivity to cause allergic and auto-immune diseases. Inhibition of nicotinamide adenine dinucleotide consumers and loss of methyl groups or production of toxins may cause cancers, metabolic toxicity, or neurodegeneration. An optimal dosage of vitamin B3 could lead to better health, but such a preventive approach needs more equitable meat distribution. Some people may require personalised doses depending on genetic make-up or, temporarily, when under stress.

Big brains, meat, tuberculosis and the nicotinamide switches: co-evolutionary relationships with modern repercussions on longevity and disease
            (Williams and Dunbar, 2014) Download
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.

Meat and Nicotinamide: A Causal Role in Human Evolution, History, and Demographics.
            (Williams and Hill, 2017) Download
Hunting for meat was a critical step in all animal and human evolution. A key brain-trophic element in meat is vitamin B3 / nicotinamide. The supply of meat and nicotinamide steadily increased from the Cambrian origin of animal predators ratcheting ever larger brains. This culminated in the 3-million-year evolution of Homo sapiens and our overall demographic success. We view human evolution, recent history, and agricultural and demographic transitions in the light of meat and nicotinamide intake. A biochemical and immunological switch is highlighted that affects fertility in the 'de novo' tryptophan-to-kynurenine-nicotinamide 'immune tolerance' pathway. Longevity relates to nicotinamide adenine dinucleotide consumer pathways. High meat intake correlates with moderate fertility, high intelligence, good health, and longevity with consequent population stability, whereas low meat/high cereal intake (short of starvation) correlates with high fertility, disease, and population booms and busts. Too high a meat intake and fertility falls below replacement levels. Reducing variances in meat consumption might help stabilise population growth and improve human capital.

 

References

Hill, LJ and AC Williams (2017), ‘Meat Intake and the Dose of Vitamin B3 - Nicotinamide: Cause of the Causes of Disease Transitions, Health Divides, and Health Futures’, Int J Tryptophan Res, 10 1178646917704662. PubMed: 28579801
Williams, AC and RI Dunbar (2014), ‘Big brains, meat, tuberculosis and the nicotinamide switches: co-evolutionary relationships with modern repercussions on longevity and disease’, Med Hypotheses, 83 (1), 79-87. PubMed: 24767939
Williams, AC and LJ Hill (2017), ‘Meat and Nicotinamide: A Causal Role in Human Evolution, History, and Demographics.’, Int J Tryptophan Res, 10 1178646917704661. PubMed: 28579800