NAD+

The NAD+ evidence base cited here is 6 sources — 2 clinical, 4 review. Its strongest evidence is human — 2 clinical studies, most recently 2022 ("Human Whole Blood NAD+ Contents Decrease with Age"). Regulatory status: Not FDA-approved (injectable).

• NAD+ is NOT a peptide — it's a coenzyme (a dinucleotide, ~663 Da) present in every cell, essential for energy production (ATP), DNA repair, and sirtuin activation. Cellular levels decline with age.
• Injectable/IV NAD+ is marketed for energy, cognition, and longevity to bypass poor oral bioavailability, but it is sold as a supplement/research compound — not FDA-approved as a therapeutic.
• ⚠️ Evidence caveat: the literature mixes injectable NAD+, intranasal NAD+, and ORAL NAD+ PRECURSORS (nicotinamide riboside / NMN) — these are NOT interchangeable, and much of the best human data is actually on the oral precursors, not injectable NAD+.

NAD+ (nicotinamide adenine dinucleotide) is a central metabolic coenzyme — it shuttles electrons in energy metabolism and is the substrate for the sirtuins and PARPs involved in aging and DNA repair. Because NAD+ falls with age, raising it is a popular longevity strategy, and IV/injectable NAD+ is marketed to deliver it directly.

It is not a peptide and not an FDA-approved therapeutic. Everything below is research context, not medical guidance — and the route-of-administration distinction below matters a lot.

NAD+ is a dinucleotide (~663 Da) — two nucleotides (an adenine and a nicotinamide) joined through ribose-phosphate groups. It cycles between an oxidized form (NAD+) and a reduced form (NADH) as it carries electrons through metabolism; that redox cycling is the basis of its role in ATP production.

It is raised in the body either directly (IV/injectable NAD+) or via precursors the body converts to NAD+ — nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN), which are taken orally. This matters for reading the evidence (below).

NAD+ is required for the electron-transport reactions that generate ATP, serves as the fuel the sirtuins consume to regulate metabolism and stress responses, and is a substrate for DNA-repair enzymes (PARPs). The longevity rationale is that restoring age-depleted NAD+ supports mitochondrial function, DNA repair, and sirtuin activity. Injectable delivery is used to bypass the poor oral bioavailability of NAD+ itself.

• Reported (injectable/infusion) peak ~30 minutes, half-life ~45 minutes, cleared within a few hours
• Attribution for these figures is vague in circulating sources ('various NAD+ infusion studies') — verify against primary literature

NAD+ is rapidly metabolized, which is why protocols use repeated dosing or slow infusions rather than single boluses.

No FDA-approved dosing exists. Figures below are from research/clinic protocols, included for context only.

• General wellness: ~100–250 mg, 1–2× weekly, IV or IM
• Anti-aging: ~250–500 mg, 2–3× weekly, IV
• Cognitive: ~500–1,000 mg, 1–2× weekly, IV
• IV infusions are given SLOWLY — a rapid push causes intense flushing and chest discomfort

• Reconstitute with bacteriostatic water (e.g. ~2–3 mL per 500 mg vial); swirl gently, never shake — full dissolution may take 2–3 minutes.
• Heat degrades NAD+ rapidly — refrigerate strictly at 2–8°C and never store at room temperature; use within ~28 days.
• Discard if cloudy or discolored.

The signature issue is the acute IV-infusion reaction: rapid administration causes flushing, chest tightness/pressure, lightheadedness, and nausea — uncomfortable but transient, and the reason infusions are slowed down. IV use should be medically supervised. Otherwise it's generally considered well-tolerated; monitor injection sites, avoid alcohol (which consumes NAD+), and keep dosing consistent. Long-term injectable-NAD+ safety data in humans is limited.

This is the key nuance: published NAD+ research spans three non-interchangeable routes, and the strongest human data is often on the oral precursors, not injectable NAD+.

• Age-associated NAD+ decline (Massudi et al., 2012, human tissue): ~10–50% decline with age — the rationale for repletion.
• Nicotinamide riboside safety/metabolism (2019, human, oral NR 100–1,000 mg, 8 wk): safe and raised NAD+ metabolites — but this tests an ORAL PRECURSOR (NR), not injectable NAD+.
• Intranasal NAD+ for TBI (2012, rats): hippocampal neuroprotection — animal, and a different route again.

When citing NAD+ benefits, specify the route — injectable, intranasal, or oral precursor (NR/NMN). They are studied separately and should not be treated as one body of evidence.

NAD+ is sold as a supplement/research compound, not an FDA-approved therapeutic. IV NAD+ is administered in clinics; injectable forms outside that setting are unregulated.

All citations link to the original source (PubMed, journal site, or regulatory filing). Independent research database — no vendor influence on what's cited.