How Does the Body Make NAD+?
Three starting points, one destination
The body builds NAD+ through three overlapping biosynthetic routes.[1][2] The de novo pathway starts from the amino acid tryptophan and runs through a multi-step process called the kynurenine pathway. The Preiss–Handler pathway starts from dietary niacin (nicotinic acid, a form of vitamin B3). The salvage pathway recycles nicotinamide — a byproduct generated whenever NAD+ is consumed by other enzymes — and can also convert precursor molecules like nicotinamide riboside (NR) and NMN into NAD+. In humans, the salvage pathway is generally considered the dominant route for maintaining day-to-day NAD+ levels, since it recycles material the body already has rather than building NAD+ entirely from scratch.[1][2]
The salvage pathway, in brief
Within the salvage pathway, an enzyme called NAMPT converts nicotinamide into NMN. NMN is then converted into NAD+ by a family of enzymes called NMNAT.[1][2] NAMPT is generally considered the rate-limiting step of this pathway, meaning its activity level has an outsized influence on how much NAD+ the salvage pathway can produce.[1][2] Dedicated pages on NAMPT, NMNAT, and the salvage pathway as a whole are planned for a later stage of this hub.
Where NMN fits
Because NMN is a direct intermediate partway through the salvage pathway, supplementing with it is intended to feed into this existing biochemical machinery rather than introduce a new mechanism.[1][2] This positioning is the biochemical basis for using NMN as a supplement ingredient — a separate question from what supplementing with it actually accomplishes in a given person, which is addressed with proper evidence grading elsewhere in this hub.
Tissue and species differences
Much of the detailed enzymology of NAD+ biosynthesis was first characterized in cell cultures and animal models before being studied in humans, and pathway activity is not uniform across tissues — liver, muscle, and blood, for example, do not necessarily behave identically. This is a normal and expected part of how biochemistry research develops, but it is also a reason to be cautious about assuming that findings from one tissue or one species automatically apply everywhere else in the human body.
- NAD+ is built through three overlapping pathways: de novo (from tryptophan), Preiss–Handler (from niacin), and salvage (recycling nicotinamide and precursors like NR and NMN).
- The salvage pathway is generally considered the main route the body uses to maintain NAD+ levels.
- NMN's role as a supplement ingredient is based on its position as a direct intermediate in this pathway — an established biochemical fact, separate from the question of what supplementing with it does in humans.
- Much of the underlying enzymology was first characterized in animal and cell models; activity also varies by tissue.
- Xie N, Zhang L, Gao W, et al. NAD(+) metabolism: pathophysiologic mechanisms and therapeutic potential. Signal Transduction and Targeted Therapy. 2020. doi:10.1038/s41392-020-00311-7. PMID: 33028824.
- Covarrubias AJ, Perrone R, Grozio A, Verdin E. NAD+ metabolism and its roles in cellular processes during ageing. Nature Reviews Molecular Cell Biology. 2021. doi:10.1038/s41580-020-00313-x. PMID: 33353981.