NAD+ Precursor
NANiacin
The Preiss-Handler route — the flushing cousin of Nam.
Niacin (nicotinic acid) raises NAD+ via the Preiss-Handler pathway, a distinct route from the salvage pathway used by NR, NMN, and Nam. Pharmacologic doses cause cutaneous flushing via GPR109A receptor activation but are well-studied for lipid management and NAD+ elevation.
What are the pharmacokinetics of NA?
- Half-life
- ~1 hour (IR), ~4 hours (ER)
- Time to peak (Tmax)
- 30-60 min (IR)
- Clearance
- Hepatic conjugation and urinary excretion
Flush dose threshold typically 50-100 mg in naive users; tolerance develops within a few weeks of daily use.
What doses of NA have been studied?
Typical use
250-1,000 mg/day (ER formulations to blunt flush)
Clinically studied
Up to 2,000 mg/day for lipid management
Safety ceiling
Hepatotoxicity risk above 3,000 mg/day ER
How can NA be delivered?
Which mechanisms does NA affect?
What does the research on NA show?
Cell Metabolism · 2020 · PMID 32386567
Niacin restores NAD+ in mitochondrial disease patients and improves muscle performance
Pirinen E, et al.
10-month niacin supplementation restored NAD+ and improved muscle strength in patients with adult-onset mitochondrial myopathy.
Read summary
Frequently asked questions
- Is NR or NMN better for raising NAD+?
- Both reliably raise blood NAD+ at studied doses. NMN has a dedicated intestinal transporter (Slc12a8) and higher sublingual bioavailability, while NR has the longer human safety record and the most published placebo-controlled trials. Neither has been shown superior in head-to-head human data.
- How does NAD+ decline with age?
- Tissue NAD+ concentrations drop by roughly 50% between age 20 and 70 in measured human tissues. The decline is driven primarily by rising CD38 activity (an NAD+-hydrolyzing enzyme), reduced NAMPT expression, and increased PARP activation from accumulated DNA damage.
- What is the optimal NMN or NR dosage?
- Published human trials use 250-1,000 mg/day for both NMN and NR. The dose-response for NAD+ elevation plateaus around 500-600 mg/day in most studies — higher doses raise blood NAD+ further but with diminishing tissue-level returns. There is no established clinical dose for longevity outcomes.
- Is long-term NAD+ supplementation safe?
- Short-term (up to 12 weeks) NMN and NR supplementation at studied doses shows a favorable safety profile with no serious adverse events in published trials. Long-term (multi-year) human safety data does not yet exist. Known considerations include methyl donor depletion, potential sirtuin inhibition at very high nicotinamide doses, and unclear interactions with some chemotherapies.
- What is NAD+ and why does it matter?
- NAD+ (nicotinamide adenine dinucleotide) is a coenzyme found in every living cell. It shuttles electrons in metabolic reactions (the NAD+/NADH redox pair), and it fuels three critical enzyme families: sirtuins (deacylases governing longevity), PARPs (DNA damage sensors), and CD38 (immune signaling).