IV NAD+ Vs Oral NMN NR Absorption Debate

Does injecting NAD+ make sense if it just breaks down to NMN/NR/NAM anyway

Thread summary

I've done both. (shared by @mito_mike)
From the pharmacy side, NAD+ itself is also just not a stable molecule once reconstituted, it degrades with light, heat and freeze thaw cycles faster than NR does as a finished... (shared by @PharmD_Nadia)
This is a classic case of people chasing the exotic delivery method instead of fixing sleep and protein first. (shared by @CoachTerrell)
IV NAD+ wrecked me for the first hour, chest tightness and nausea, but I slept like a rock that night. (shared by @NightShiftNurse)

Top answer from @mito_mike. Jump to reply

posted by LabRatLouis OP 5d ago

Genuine mechanistic question, not trying to start a fight. NAD+ is a big charged molecule, it doesn't cross the plasma membrane intact in any meaningful amount. Whether you push it IV or sub-q, the working model is that it gets broken down extracellularly into NAM (and some NR) by CD38 and other ectoenzymes before cells can actually take up the pieces and resynthesize NAD+ inside. NMN and NR are already those breakdown products, and both have oral bioavailability data in humans, NR especially has decent pharmacokinetic work behind it. So what is the actual argument for paying a premium for the precursor's precursor and infusing it, versus just taking NR or NMN orally and letting the salvage pathway do the same job for less money and less hassle. Not saying NAD+ IV doesn't make people feel something acutely, I just don't see the biochemical case that the intact molecule route gets you anywhere oral precursors don't.

Preclinical is not a promise.

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mito_mike Top answerBoulder, CO11 points5d ago

I've done both. Oral NR for 8 weeks, no real signal I could point to. Did a few NAD+ IVs this spring and felt noticeably sharper for about 2 days after each one, but I can't rule out placebo or just being well hydrated from the drip itself.

Watts do not lie. Neither do lactate strips.

NightShiftNurseSacramento, CA10 points5d ago

IV NAD+ wrecked me for the first hour, chest tightness and nausea, but I slept like a rock that night. No idea what that means mechanistically.

Recovery happens at 3am, if it happens.

PharmD_NadiaPhoenix, AZ6 points5d ago

From the pharmacy side, NAD+ itself is also just not a stable molecule once reconstituted, it degrades with light, heat and freeze thaw cycles faster than NR does as a finished oral product. So even setting the breakdown-before-uptake question aside, you're paying for something with a shorter usable shelf life. I won't weigh in on whether that tradeoff is worth it for anyone's goals, that's a dosing and strategy question, not a pharmacy one.

If the vial looks cloudy, the answer is no.

CoachTerrellAtlanta, GA3 points5d ago

This is a classic case of people chasing the exotic delivery method instead of fixing sleep and protein first. I've got athletes who got more out of consistent NR and actually sleeping 7 hours than anyone I've seen running IV drips.

You cannot inject your way out of a bad program.