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Pellagra, a disease linked to poverty, offers lessons on dietary nicotinamide and NAD homeostasis. High nicotinamide intake can disrupt NAD levels, potentially causing a new form of hypervitaminosis-B3.

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Area of Science:

  • Nutritional Science
  • Biochemistry
  • Public Health

Background:

  • Pellagra, a disease historically linked to poverty, is often overlooked.
  • Lessons from pellagra are relevant to understanding dietary nicotinamide and nicotinamide adenine dinucleotide (NAD) homeostasis.
  • NAD homeostasis can be disrupted by poor diet or increased NAD consumption due to genotoxic and other stresses.

Purpose of the Study:

  • To re-examine the lessons from pellagra regarding nutritional deficiencies and their broader health implications.
  • To explore the mechanisms of NAD disruption beyond simple dietary deficiency.
  • To investigate the potential for adverse effects from high-dose nicotinamide supplementation.

Main Methods:

  • Review of historical and current literature on pellagra and vitamin B3 metabolism.
  • Analysis of biochemical pathways involving nicotinamide, NAD, and related enzymes.
  • Examination of the impact of genotoxic and other stresses on NAD levels.

Main Results:

  • High doses of nicotinamide can inhibit NAD-consuming enzymes.
  • Excessive induction of nicotinamide-n-methyl transferase (NNMT) is observed with high nicotinamide intake.
  • These disruptions provide a potential mechanism for a novel form of hypervitaminosis-B3.

Conclusions:

  • Pellagra's lessons extend to understanding the complex interplay of diet, stress, and NAD metabolism.
  • High nicotinamide intake can lead to adverse health effects, including disruption of the methylome.
  • Further research is needed to understand the full implications of hypervitaminosis-B3.