Abstract

Nicotinamide is neuroprotective in the laboratory to many external and genetic insults and is implicated in the reduction of age-related disease seen with caloric restriction. We have overlooked an important clinical clue to current ageing disease and should revisit Pellagra. Pellagra is the only ageing and neurodegenerative disease to have been cured. Pellagra still exists in poor corn eating communities such as in Africa though the diagnosis is usually missed. Nicotinamide as the precursor to NAD(H) when deficient impairs cellular energetics and the SIRT and PARP functions necessary for optimal ageing and DNA repair. Nicotinamide itself inhibits suggesting an optimal dose range, relevant as rich communities are exposed to high doses. A review of the clinical literature from the last epidemic of Pellagra in the SE states of the USA 100 years ago shows that Pellagra caused Dementias of all types alongside Parkinson's and ALS mimics. Festinant gaits and fasciculating tongues were first noted in pellagrins. Children had delayed development and premature ageing. Gut and skin manifestations were due to chronic infections including tuberculosis. Cancer rates were high. Familial cases were common. Amyloidosis and lipofuscinosis alongside vascular and inflammatory lesions were seen and pathologists likened it to premature ageing.