Nicotinamide mononucleotide – a fail as a longevity supplement

Pyruvate dehydrogenase and the 2-oxoglutarate dehydrogenase are rate limiting enzymes of the pyruvate dehydrogenase complex and the 2-oxoglutarate complex respectively.  NADH activates pyruvate dehydrogenase kinase which inhibits pyruvate dehydrogenase and inhibits 2-oxoglutarate dehydrogenase. Increasing levels of NAD+ via supplemental  nicotinamide mononucleotide, which is marketed as an anti-aging and longevity supplement,  would increase levels of NADH which would inhibit pyruvate dehydrogenase and 2-oxoglutarate dehydrogenase which would decrease activity of the pyruvate dehydrogenase complex and the 2-oxoglutarate complex which could be a large misstep in terms of increased longevity. Decreased activity of the pyruvate dehydrogenase complex and the 2-oxoglutarate complex enzymes are present in brains of individuals who had Alzheimer’s disease. Supplementing with nicotinamide mononucleotide must be avoided.

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