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When it was recognized that pellagra, a condition marked by diarrhea, dermatitis, dementia, and mortality, could be treated with foods containing NAD+ precursors, particularly vitamin B3, the clinical significance of maintaining NAD+ levels was established in the early 1900s (9). Notably, the skin does not flush with NAD+ injection, in contrast to vitamin B3 (niacin) intake, which also causes this negative effect (10). Low NAD+ levels have recently been associated with a variety of age-related ailments and diseases linked to increased oxidative/free radical damage, including diabetes, heart disease, vascular dysfunction, ischemic brain injury, Alzheimers disease, and vision loss (8, 11-17)

Moreover, this condition leads to a low level of intrinsic factor, a protein that prevents vitamin B12 deficiency

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Conservative dosing also reduces risk of excessive energy deficit and the metabolic stress markers (low T3, menstrual irregularity) that emerge when both compounds are pushed to upper dose ranges simultaneously.