Independent · non-commercial · publishes on a quarterly cycle|Current cycle 2026 Q3
Compound Evidence InstituteEvidence synthesis · established 2023Graded assessments of compounds, trials, methods and supply
Document set current to 30 July 2026
Compound monograph · §4

NAD+ (nicotinamide adenine dinucleotide) — safety

Adverse events as reported, contraindications, warnings, and an explicit statement of what the safety evidence does not establish.

Document identifier
CEI-MN-045/4
Series
Compound monograph
Version
2.1
Published
23 Aug 2026
Last reviewed
23 Aug 2026
Next review
23 Aug 2028
Identifier
10.71829/cei.mono.45
Certainty
Very low
Cycle
2026 Q3

§4Safety

§4.1Adverse events reported in controlled trials

Table 4. Adverse events for NAD+ (nicotinamide adenine dinucleotide) as reported in the trial safety tables the Institute holds. Percentages are of randomised participants in the stated trial and arm.

EventActive, %Comparator, %Difference, ppSource
Infusion-related chest tightness, nausea and crampingConsistently reported with rapid intravenous infusion and the reason infusions are given slowly over hours
FlushingReported
Injection-site painReported with subcutaneous administration
Sterility and endotoxin riskCompounded intravenous preparations of a non-pharmacopoeial substance carry the sterility, endotoxin and particulate risks of any unlicensed parenteral
A difference column is computed by the Institute from the two reported percentages and is not itself a published figure. Confidence intervals for adverse-event differences are not reported in the contributing trials and are not constructed here.

§4.2Contraindications

  • Not established — no marketing authorisation as a parenteral medicine

§4.3Warnings and precautions

  • Intact NAD+ does not enter cells; the mechanistic premise of administration is questionable
  • Compounded parenteral preparations carry sterility, endotoxin and particulate risks
  • Evidence for oral precursors should not be transferred to parenteral NAD+

§4.4What this section does not establish

Related assessments: tolerability of incretin receptor agonists · acute pancreatitis · the rodent thyroid C-cell signal.[1,2]

References cited on this page

References are numbered in order of first citation in this document. Each superscript in the text links to its entry below.

  1. Lee C, Zeng J, Drew BG, Sallam T, Martin-Montalvo A, Wan J, Kim SJ, Mehta H, Hevener AL, de Cabo R, Cohen P. The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance. Cell Metabolism 2015;21(3):443–454. doi:10.1016/j.cmet.2015.02.009 · PMID 25738459
  2. Szeto HH. First-in-class cardiolipin-protective compound as a therapeutic agent to restore mitochondrial bioenergetics. British Journal of Pharmacology 2014;171(8):2029–2050. doi:10.1111/bph.12461 · PMID 24117165

Identifiers are reproduced only where the Institute holds them. Where a digital object identifier or PubMed identifier is not shown, the Institute has recorded the journal and year and has not constructed an identifier.

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