NAD+

NAD+ acts as a critical coenzyme in redox reactions, accepting or donating electrons in metabolic pathways such as glycolysis, fatty acid oxidation, and the citric acid cycle. It is a substrate for sirtuins, NAD+-dependent deacetylases that remove acetyl groups from proteins and regulate gene expression. Sirtuins are involved in DNA repair, stress resistance, inflammation, and metabolic homeostasis.

NAD+ is also consumed by poly(ADP-ribose) polymerases (PARPs) in response to DNA damage. PARPs help repair DNA but can deplete NAD+ levels if overactivated. CD38, an enzyme that generates cyclic ADP-ribose, also consumes NAD+.

NAD+ can be synthesized de novo from the amino acid tryptophan or through salvage pathways using precursors like nicotinic acid, nicotinamide, and nicotinamide riboside. Supplementing with these precursors can boost NAD+ levels.

Research suggests that maintaining optimal NAD+ levels may provide the following benefits:

• Longevity: Studies in yeast, worms, and mice have shown that boosting NAD+ levels can extend lifespan. Sirtuins, which are NAD+-dependent, are linked to increased longevity in various organisms.

• Metabolic health: NAD+ is crucial for energy metabolism. Increasing NAD+ levels can improve mitochondrial function, glucose metabolism, and insulin sensitivity. It may help protect against obesity, type 2 diabetes, and metabolic syndrome.

• Cardiovascular health: NAD+ precursors have shown potential benefits for cardiovascular health, such as improving blood pressure, reducing inflammation, and protecting against oxidative stress.

• Neurological health: NAD+ is important for neuronal function and energy metabolism in the brain. Boosting NAD+ levels may help protect against age-related cognitive decline, Alzheimer's disease, and Parkinson's disease.

• DNA repair: NAD+ is a substrate for PARPs, which are involved in repairing DNA damage. Maintaining adequate NAD+ levels may support DNA repair mechanisms and genomic stability.

• Inflammation: Sirtuins, which are NAD+-dependent, have anti-inflammatory effects. Increasing NAD+ levels may help regulate inflammation and protect against chronic inflammatory diseases.

NAD+ precursors like nicotinic acid, nicotinamide, and nicotinamide riboside are generally well-tolerated. However, high doses of nicotinic acid can cause flushing, itching, and gastrointestinal discomfort. Nicotinamide at high doses may also cause gastrointestinal side effects and liver toxicity.

NAD+ is a vital coenzyme involved in energy metabolism, DNA repair, cell signaling, and aging. Maintaining optimal NAD+ levels through supplementation with precursors or other means may provide benefits for longevity, metabolic health, cardiovascular health, neurological function, DNA repair, and inflammation. While NAD+ precursors are generally safe, it is important to use them under medical supervision and be aware of potential side effects at high doses.

1. Rajman L, Chwalek K, Sinclair DA. Therapeutic Potential of NAD-Boosting Molecules: The In Vivo Evidence. Cell Metab. 2018 Mar 6;27(3):529-547. doi: 10.1016/j.cmet.2018.02.011. PMID: 29514064; PMCID: PMC6342515.

2. Fang EF, Lautrup S, Hou Y, Demarest TG, Croteau DL, Mattson MP, Bohr VA. NAD+ in Aging: Molecular Mechanisms and Translational Implications. Trends Mol Med. 2017 Oct;23(10):899-916. doi: 10.1016/j.molmed.2017.08.001. Epub 2017 Sep 9. PMID: 28899755; PMCID: PMC7494058.

3. Yoshino J, Mills KF, Yoon MJ, Imai S. Nicotinamide mononucleotide, a key NAD(+) intermediate, treats the pathophysiology of diet- and age-induced diabetes in mice. Cell Metab. 2011 Oct 5;14(4):528-36. doi: 10.1016/j.cmet.2011.08.014. PMID: 21982712; PMCID: PMC3204926.

4. Trammell SA, Schmidt MS, Weidemann BJ, Redpath P, Jaksch F, Dellinger RW, Li Z, Abel ED, Migaud ME, Brenner C. Nicotinamide riboside is uniquely and orally bioavailable in mice and humans. Nat Commun. 2016 Oct 10;7:12948. doi: 10.1038/ncomms12948. PMID: 27721479; PMCID: PMC5062546.