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.
