NAD+ (Nicotinamide Adenine Dinucleotide)
The coenzyme of life that declines with age and is key to longevity
Definition
NAD+ is a coenzyme present in all living cells, fundamental to over 500 biochemical reactions. Its primary functions are: electron transport in the mitochondria for ATP (cellular energy) production, substrate for sirtuins (longevity-regulating enzymes), activation of PARP-1 (DNA repair), and regulation of the circadian rhythm. NAD+ levels decline by up to 50% between ages 40 and 60, a process directly associated with energy and cognitive decline and the acceleration of ageing.
Detailed explanation
David Sinclair (Harvard) and Johan Auwerx (EPFL) have published findings showing that restoring NAD+ levels in animal models reverses ageing markers equivalent to decades. The mechanisms are multiple: NAD+ activates all 7 sirtuins (SIRT1–7), which regulate gene expression, repair DNA, reduce inflammation (SIRT1 inhibits NF-κB), and maintain the epigenome.
Routes of administration have vastly different bioavailabilities: oral (NMN or NR as precursors, limited conversion of 10–30%), sublingual (greater absorption, 40–60%), and intravenous (100%, plasma levels 6–10× higher than oral). For individuals over 50 with severely depleted NAD+, IV is the only route that achieves clinically significant restoration.
Infusion duration ranges from 1.5 to 4 hours (doses of 250–1,000 mg), with possible side effects of nausea and a sensation of warmth that are managed by adjusting the drip rate.
Scientific sources
- PubMed — NAD+ metabolism and the control of energy homeostasis (Cantó, Auwerx)
- PubMed — NAD+ in aging: molecular mechanisms and translational implications
- PubMed — Chronic nicotinamide riboside supplementation increases NAD+ (Martens)
- PubMed — Nicotinamide mononucleotide and insulin sensitivity (Yoshino)
Related terms
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