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NAD+ precursors

Evidence grade: Human trials

Not peptides, but included because they are the most human-tested way to support the same mitochondrial pathway the peptides above target.

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Urolithin A

Evidence grade: Human trials

A gut-derived metabolite that triggers mitophagy — the clearance of damaged mitochondria — with completed human trials.

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1 cited source1 human studyReviewed 1 Jun 2026
1 cited sourceNo human data on fileReviewed 1 Jun 2026

At a glance

At a glance compared across NAD+ precursors, Urolithin A
AttributeNAD+ precursorsUrolithin A
Primary useMitochondria & energyMitochondria & energy
Evidence gradeHuman trialsHuman trials
Human datadiffersYes — see citationsNo human citations on file
Cited sourcesdiffers1 source · 1 human1 source · 0 human
In one sentenceNot peptides, but included because they are the most human-tested way to support the same mitochondrial pathway the peptides above target.A gut-derived metabolite that triggers mitophagy — the clearance of damaged mitochondria — with completed human trials.

Mechanism

Mechanism compared across NAD+ precursors, Urolithin A
AttributeNAD+ precursorsUrolithin A
How it is thought to workNAD+ is the electron carrier at the centre of energy metabolism and the required substrate for sirtuins and PARPs. Its levels decline substantially with age. Oral NR and NMN reliably raise blood NAD+ levels in humans — that part is settled. Whether raising the level produces a felt clinical benefit is the contested question.Urolithin A is produced when gut bacteria metabolise ellagitannins from pomegranate, walnuts and berries. Only around 40% of people carry the microbiome to make meaningful amounts. It induces mitophagy, the selective recycling of damaged mitochondria, which is a distinct mechanism from making mitochondria run better or making more of them.
What the research reports
  • Multiple human RCTs confirming increased blood NAD+ levels
  • Good safety profile across trials at commonly used doses
  • Some improvement in muscle mitochondrial markers in older adults
  • Randomised human trials showing improved muscle endurance in middle-aged and older adults
  • Confirmed induction of mitophagy biomarkers in humans
  • Well tolerated at trial doses
What it is NOT shown to do
  • Consistent improvement in energy, mood or cognition in healthy adults
  • Anti-ageing claims are not supported by human outcome data
  • Effect on depression is untested
  • No cognitive or mood endpoints tested in humans
  • Effect sizes on function are modest

Dosing & pharmacology

Dosing & pharmacology compared across NAD+ precursors, Urolithin A
AttributeNAD+ precursorsUrolithin A
Routes studieddiffersOral, SubcutaneousOral
Half-lifediffersOral dosing raises NAD+ over hours; tissue effects accumulate over weeksExtended by glucuronidation; steady state reached over days
Dose referenceHuman trials commonly use 250–1000 mg/day of NR or NMN orally.Human trials commonly use 500–1000 mg/day orally.
Typical study cyclediffersTrials run continuously for 8–12 weeks or longerTrials ran 4 months of continuous daily dosing

Chemistry & handling

Chemistry & handling compared across NAD+ precursors, Urolithin A
AttributeNAD+ precursorsUrolithin A
SequenceNot peptides — pyridine nucleotide precursors (NR, NMN)Not a peptide — 3,8-dihydroxy-urolithin, a gut-microbiome metabolite of ellagitannins
Molecular formuladiffersNR chloride C11H15ClN2O5 · NMN C11H15N2O8PC13H8O4
Molecular weightdiffersNR 290.7 g/mol · NMN 334.2 g/mol228.2 g/mol
CAS numberdiffersNR 23111-00-4 · NMN 1094-61-71143-70-0
Storage (reconstituted)differsPrepare fresh — aqueous solutions degrade quickly at room temperatureNot typically reconstituted; taken as an oral formulation

Risk

Risk compared across NAD+ precursors, Urolithin A
AttributeNAD+ precursorsUrolithin A
Reported side effects
  • Nausea
  • Flushing (more with high-dose niacin than with NR/NMN)
  • Mild GI upset
  • Generally well tolerated; occasional GI upset
Contraindications
  • Pregnancy and breastfeeding
  • Active cancer — NAD+ metabolism is relevant to tumour biology; discuss with an oncologist
  • Pregnancy and breastfeeding — not studied

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