Scientific Consensus: The "Longevity" Verdict on NAD+ Precursors (NMN, NR, etc.)

#1

Scientific Consensus: The “Longevity” Verdict

Does the broader literature support it?
No, not for lifespan extension in healthy humans.
The current scientific consensus (as of late 2025) is that while NAD+ precursors reliably restore NAD+ levels in human tissues, there is no robust clinical evidence that this translates to extended lifespan or reversed aging in healthy adults. The “longevity” benefits (lifespan extension, DNA repair) are well-documented in rodents, but human trials have largely shown benefits limited to metabolic markers (e.g., insulin sensitivity, lipid profiles) rather than systemic rejuvenation.

For a healthy person, you are essentially paying for a metabolic therapeutic that might slow specific cellular decay pathways, not a verified fountain of youth.

Comparative Analysis: Cost & Efficacy

The following table compares the molecule costs based on Q4 2025 market prices.

Molecule Est. Cost per 100mg Annual Cost (at 1g/day) Verdict
Niacin (Nicotinic Acid) $0.003 (0.3¢) ~$11 The Rational Choice. Unbeatable price/efficacy ratio if you tolerate the flush.
Nicotinamide (NAM) $0.003 (0.3¢) ~$11 The Risky Bet. Cheap, but potentially inhibits sirtuins (the “longevity genes”).
NMN (Bulk Powder) $0.10 - $0.15 ~$365 - $550 The Middle Ground. Good balance of theory/bioavailability, but quality varies wildy.
NR (Brand Capsules) $0.45 - $0.60 ~$1,600+ The “Taxed” Option. Most expensive due to patents/marketing. High safety data.

Detailed Pros, Cons & Critical Analysis

1. Niacin (Nicotinic Acid)

  • Pros:
    • Gold Standard Efficacy: Raises NAD+ levels in human muscle and blood as effectively as novel precursors in many contexts.
    • Lipid Benefits: Uniquely improves cardiovascular markers (raises HDL, lowers LDL/triglycerides).
    • Price: It is virtually free compared to NMN/NR.
  • Cons:
    • The Flush: Causes intense cutaneous vasodilation (redness, itching, heat) lasting 30-60 mins. This is harmless but uncomfortable.
    • Insulin Resistance: High doses (>1g) can temporarily reduce insulin sensitivity in some users.
  • Key Research:

2. Nicotinamide (NAM)

  • Pros:
    • Cheap and flush-free.
    • The primary precursor used by the body’s salvage pathway naturally.
  • Cons:
    • Sirtuin Inhibition: Excess Nicotinamide acts as a feedback inhibitor to sirtuins. By flooding the system with the breakdown product of the reaction you are trying to encourage, you may inadvertently jam the mechanism. This makes it a poor candidate for “longevity” purposes despite raising NAD+.
  • Key Research:

3. Nicotinamide Mononucleotide (NMN)

  • Pros:
    • FDA Status (2025 Update): After a tumultuous regulatory battle, the FDA acknowledged NMN as lawful for use in supplements as of Sep 2025, stabilizing the supply chain.
    • Direct Pathway: Requires one fewer step than NR to become NAD+ (intracellularly), though it likely converts to NR to enter the cell first.
  • Cons:
    • Storage Instability: NMN degrades into Nicotinamide if exposed to heat/moisture. Buying bulk powder requires strict cold storage.
    • Bioavailability Debate: There is conflicting evidence on whether the NMN transporter (Slc12a8) is active enough in humans to matter.
  • Key Research:

4. Nicotinamide Riboside (NR)

  • Pros:
    • Human Safety Data: Has the most robust safety trials for doses up to 2g/day.
    • Cell Entry: Clearly enters cells via the ENT nucleoside transporters.
  • Cons:
    • Cost: You are paying for the patent (ChromaDex).
    • Stability: NR is unstable as a standalone powder and must be bound as a chloride salt (NR-Cl), limiting bulk generic availability.
  • Key Research:

Methylation Warning (Crucial for All)

Taking any NAD+ precursor at high doses (approx. >500mg) forces your liver to excrete the excess degraded nicotinamide via methylation. This drains your body’s “methyl pool” (TMG/Betaine), potentially raising Homocysteine levels (a cardiovascular risk factor).

  • Actionable Insight: If you take >500mg of NMN/NR/Niacin, co-supplement with Trimethylglycine (TMG) at a 1:1 ratio.

Updated Recommendation

  1. For pure cost-efficiency: Take Niacin (50-500mg) with breakfast.
  2. For longevity theory: Take NMN Bulk Powder (500mg - 1g), dissolved in water, stored in the fridge.
  3. For safety/convenience: Take NR Capsules.
#2

New video release from Dr Brad

He said old data showed NMN/NR don’t extend life and the new data shows it did not help long covid. Having said this, pre rapa when I did take NMN, I did feel a boost… placebo or not :slight_smile:

  • Discovery of SIR2 and NAD in Longevity (1930s-1990s): Calorie restriction extended rat lifespans, leading MIT researchers to identify SIR2 protein activation via NAD in yeast as key to longevity benefits.​
  • NAD Decline with Age: Human skin samples showed NAD levels drop with age, correlating with increased DNA damage and impaired repair, suggesting NAD decline drives aging processes.​
  • NR Supplementation in Mice (2016): Nicotinamide riboside (NR), an NAD precursor, boosted NAD levels, restored muscle stem cell function, and extended mouse lifespans, sparking human supplement hype.​
  • David Sinclair’s Advocacy: Sinclair promoted NMN (another NAD precursor) on Joe Rogan in 2019, claiming it restores youthful NAD levels based on animal data, despite no human trials at the time.​
  • Reproducibility Issues and ITP Findings: Interventions Testing Program (ITP) tested NR across three labs; it raised blood NAD but failed to extend mouse lifespan or improve function, questioning NMN/NR efficacy.​
  • Challenging NAD Decline Theory: Muscle biopsies from exercising older adults showed NAD levels similar to younger adults, undermining the age-related decline hypothesis.​
  • Long COVID Trial Disappointment: NR supplementation in long COVID patients (with strained NAD metabolism) raised NAD sharply over 20 weeks but produced no symptom improvements vs. placebo.​
  • Anecdotal Benefits Explained: Perceived NMN/NR gains may stem from co-supplemented TMG (betaine), which meta-analyses show enhances strength, jumping, and testosterone with exercise—not NAD boosting.​
  • Key Takeaway: No robust human evidence supports NMN/NR for anti-aging or disease benefits; blood NAD rises, but functional outcomes fail across trials.
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#3

i have been taking NR and NMN for a decade, i am probbaly one of the earliest, after reading david sinclair’s book.

but because i have been taking it so long, i have forgotten the effects. but i recall when i first tried it, it was great, improvements in memory, clarity, physical abilities, etc.

it definitely works for me. i used to take 1g like david but i realised it was too high for me so mostly 300mg thereabouts these days, which roughly doubles my nad+ level to probably 60ish, similar to a teen.

i take it mostly for cognition and physical benefits these days.

also they activate the sirtuins and make them work better mostly. nmn is basically like vitamin b3, it is a deriavative basically.

i dont think it extends lifespan for me, but david and his colleagues did a study and shows it extends median lifespan by 8% in female mice but not male mice (Preiss-Handler pathway metabolism):

there have been studies showing it works as well:

Japan:

professor she has a very good website with lots of good info on nmn:

great nmn site:

creatinine is a supplement you can try if you are keen on nmn, they both work synergistically.

creatinine basically helps in recycling atp while nad+ boosts atp. they are both really just powering the mitochondria more which is the engine of our cells.

there have been many many human studies on it showing it boosts cognition, muscle, bla bla.

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