Investigational / not FDA-approved

NAD+

Endogenous cofactor NAD+ — biochemistry ≠ IV NAD+/NADH ≠ oral NR/NMN precursors.

Editorial review:

What evidence says

Evidence snapshot

This drawer marks papers. It is not a plan, a dose, or a source. A paper is a bounded report. It is not a protocol. Grades name the object. They are not a safety rating.

Identity lock. NAD+ is an endogenous pyridine nucleotide cofactor (oxidized nicotinamide adenine dinucleotide), not a synthetic therapeutic peptide. PubChem CID 5892 (title often “Nadide”); formula C21H27N7O14P2 / MW 663.4; CAS 53-84-9. Distinguish three objects every time: (1) cellular biochemistry / aging biology of NAD+; (2) intravenous or parenteral NAD+ / NADH clinical reports (often small, open, or metabolome-pilot); (3) oral precursor trials — nicotinamide riboside (NR), nicotinamide mononucleotide (NMN), etc. — which raise NAD+ metabolome markers but are not identical to IV NAD+. Do not treat endogenous cofactor biology as a drug label. Unsourced wellness-clinic claims are not grades. This drawer marks papers. It is not use advice.

Bottom line

NAD+ is foundational biochemistry. Human evidence for IV NAD+ is thin (pilot metabolome infusion; older small Parkinson NADH series with mixed/weak controlled signals). Broader “NAD augmentation” literature is dominated by NR/NMN precursor RCTs and systematic reviews that still leave many clinical unknowns. Do not equate precursor oral trials with IV NAD+ clinic narratives, and do not invent anti-aging approval from cofactor biology. Refuse “IV NAD clinic = proven anti-aging” inflation.

Papers

IV / parenteral NAD+ or NADH (human, limited)

PMID 31572171 — Grant 2019

Tested: pilot study of plasma and urine NAD+ metabolome changes during a multi-hour intravenous NAD infusion in humans.

Does not show: disease-modifying clinical efficacy, anti-aging outcomes, or equivalence to oral NR/NMN trials.

PMID 7887134 — Dizdar 1995

Tested: small double-blind study of parenteral NADH in moderate Parkinson’s disease (disability scores; very small n).

Does not show: modern Phase 3 Parkinson efficacy, or that NADH equals NAD+ IV clinic protocols.

PMID 9013405 — Kuhn 1997

Tested: open prospective study of parenteral NADH on Parkinsonian symptoms and levodopa bioavailability framing.

Does not show: confirmatory blinded efficacy; authors note improvement may partly reflect endogenous levodopa biosynthesis stimulation.

Systematic reviews / aging-biology framing (NAD as cofactor)

PMID 37971292 — Gindri 2024

Tested: systematic review of safety and effectiveness of NAD (NAD+/NADH) as a supplement across clinical conditions.

Does not show: a single definitive indication; synthesis quality depends on sparse primary trials.

PMID 37364580 — Bhasin 2023

Tested: Endocrine Reviews synthesis of NAD in aging biology — potential applications and many unknowns.

Does not show: that unknowns are resolved into approved anti-aging therapy.

PMID 41655607 — Gallagher 2026

Tested: PRISMA-guided systematic review of NAD+ supplementation for anti-aging and wellness (preclinical and clinical evidence).

Does not show: an approved wellness indication; treats the literature’s limits as part of the map.

Different object — oral NAD precursors (NR / NMN) as metabolome context

PMID 29599478 — Martens 2018

Tested: chronic nicotinamide riboside supplementation elevating NAD+ in healthy middle-aged and older adults (tolerability / metabolome).

Does not show: IV NAD+ efficacy, or disease-outcome approval.

PMID 31412242 — Elhassan 2019

Tested: nicotinamide riboside effects on aged human skeletal-muscle NAD+ metabolome and transcriptomic / anti-inflammatory signatures.

Does not show: IV NAD+ clinic outcomes, or functional performance as a labeled claim.

PMID 35235774 — Brakedal 2022

Tested: NADPARK — randomized Phase I trial of nicotinamide riboside in Parkinson’s disease.

Does not show: IV NAD+ equivalence, or a completed Phase 3 Parkinson approval for NR.

PMID 33888596 — Yoshino 2021

Tested: nicotinamide mononucleotide effects on muscle insulin sensitivity in prediabetic women.

Does not show: IV NAD+ results, or NMN as identical to NAD+ infusion.

PMID 36482258 — Yi 2023

Tested: randomized multicenter trial of β-NMN supplementation safety/efficacy framing in healthy middle-aged adults.

Does not show: IV NAD+ proof or an anti-aging drug label.

What is not established

That endogenous cofactor biology equals a drug-approved anti-aging therapy. That IV NAD+ clinic marketing is backed by large modern RCTs (it is not, in this pack). That NR/NMN oral trial results prove IV NAD+ outcomes (different objects/routes). Parkinson disease modification from 1990s NADH series. Product identity and purity for compounded infusions versus research-trial material. This drawer does not provide use advice, schedules, or sourcing.

Selected sources

31572171 7887134 9013405 37971292 37364580 41655607 29599478 31412242 35235774 33888596 36482258

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