Lower numbers = closer to natural. Higher numbers = more enhanced.
Why this rating?
NAD+ is a naturally occurring coenzyme present in all living cells, essential for cellular energy production and DNA repair. Supplementation aims to restore declining age-related NAD+ levels. Does not affect hormones, muscle building, or athletic performance directly. Available as a supplement or medical treatment. Rated 1 as it is a cellular health supplement with no performance-enhancing effects.
Overview
A coenzyme essential for cellular energy and DNA repair. NAD+ levels decline with age, and supplementation may support cellular health and energy production.
Purpose & Use Cases
Cellular Energy
Supports mitochondrial function and ATP production.
Anti-Aging
May slow aspects of cellular aging through sirtuin activation.
DNA Repair
Supports DNA repair mechanisms.
Benefits
- Enhanced cellular energy
- Improved mental clarity
- Potential anti-aging effects
- DNA repair support
- Mitochondrial health
Good to Know
NAD+ declines with age and fuels sirtuins + DNA repair
NAD+ is a coenzyme every cell needs for energy metabolism, sirtuin (longevity enzyme) activity, and DNA repair. Levels fall with age, which is the whole rationale for boosting it. This is health/longevity territory, not performance.
"Direct" NAD+ is mostly broken down to precursors anyway
IV/subq NAD+ bypasses first-pass metabolism, but the intact molecule is too large to enter cells well. It is largely degraded outside the cell into NMN/NR/nicotinamide, which are then taken up. So even injectable NAD+ acts partly as a precursor delivery system.
Niacin flushes and burdens methylation; NR/NMN do not
Among oral precursors, niacin (nicotinic acid) raises NAD but causes flushing and the highest methylation demand; NR and NMN raise NAD without flushing. TMG is reasonable methyl-donor insurance but is only clearly needed for high-dose niacin, not NR/NMN at normal doses.
Dosage Guidelines
| Route | Typical Dose | Frequency | Cycle |
|---|---|---|---|
| IV infusion | 500 – 750 mg/week | Typically once per week as a single IV infusion or subcutaneous session (250-1000mg; IV is dripped over 1-4+ hours to avoid nausea/chest tightness, subq is given as one or several smaller shots). This weekly figure is maintenance dosing, some protocols (e.g. detox/addiction clinics) instead front-load with a short daily "loading" course of roughly 250-750mg/day IV for 3-10 days before tapering to a weekly maintenance dose. | 4 – 12 wk |
| Subcutaneous Injection | 200 – 450 mg/week | 2-3x per week is the most-cited cadence (some sources say 1-3x/week); a minority of community protocols instead use daily dosing during an initial 1-2 week 'ramp' before dropping to 2-3x/week maintenance. | 4 – 12 wk |
| Oral / Sublingual | 250 – 600 mg/day | Once daily or split into 2-3 doses; either swallowed as a capsule/tablet or held sublingually as a troche/lozenge/powder for a few minutes. | 4 – 12 wk |
| Transdermal Patch | 50-200 mg patch (~5-15% absorbed) | One patch applied daily, worn approximately 8-12 hours before being replaced. | 4 – 12 wk |
Dosing depends on how it's administered. Pick your route in the calculator to score the one you use.
These are practitioner/clinic- and community-derived dosing conventions, not an official prescribing guideline. NAD+ is not FDA-approved for these uses. The one dose with actual published human safety data is 750mg infused IV over 6 hours, which produced no adverse events (Grant et al. 2019); most clinics sell a similar 250-1000mg per-session menu, but the higher end is clinic convention rather than trial-verified. IV/subq bypasses first-pass metabolism, but even "direct" NAD+ is largely broken down extracellularly (by the ectoenzymes CD38/CD73/ENPP1) into precursors (NMN/NR/nicotinamide) before cells take it up, see the NMN and NR pages for the oral-precursor route. Among the precursors, niacin (nicotinic acid) raises NAD but flushes (via GPR109A) and carries the highest methylation burden; NR and NMN raise NAD without flushing and have the strongest human data. The TMG/methyl-donor consideration tracks total nicotinamide flux, not the route. It applies to oral and injectable alike, and is most relevant with high-dose niacin.
Positioned by peptide vendors/clinics as a practical, cheaper alternative to IV that skips the multi-hour infusion. Injection-site stinging is commonly reported (see sideEffects). Bioavailability is claimed by vendors to approach IV (~90-95%) since it also bypasses first-pass metabolism, but this figure - like nearly all the numbers in this route - comes from peptide-vendor and community-clinic blogs (thepeptidecatalog.com, peptidewiki.co, peptidedosingprotocols.com, peptidesinsider.com, peptidedeck.com, purepeptideclinic.com) rather than controlled trials, so confidence is lower than for the IV route's one.
Bioavailability of intact oral/sublingual NAD+ is low and poorly characterized in controlled human studies - vendor sources cite roughly 20-40% oral bioavailability vs. 90-95% claimed for injectable routes, but these figures are marketing-derived, not from a dedicated human PK trial of oral NAD+ itself. Mechanistically this is expected: NAD+ is largely broken down (by CD38/CD73/ENPP1 and gut/liver metabolism) into nicotinamide and other precursors before absorption, which is why standalone NMN and NR precursor supplements exist as a purpose-built oral alternative (see those compound pages) rather than dosing.
One patch (50-200mg NAD+ content) applied daily, worn 8-12 hours. Lowest-confidence route in this list. The mg figure printed on a patch is the loaded content, not what is actually absorbed - estimated transdermal bioavailability is only ~5-15% (some newer patches add iontophoresis to improve this), versus 90-95% claimed for subq/IV. No independent pharmacokinetic data was found for NAD+ patches; all figures trace back to vendor blogs (bestmedshub.com, ivconcierge.com, ionlayer.com).
No formal PK half-life has been calculated for infused/injected NAD+, plasma levels remain elevated at least ~2h post-infusion. Intracellular NAD+ turnover (a different measure) is separately estimated at ~1-4h depending on compartment (cytoplasmic ~2h, mitochondrial ~4-6h).
Side Effects
Flushing
commonTemporary warmth/flushing sensation, especially with IV administration.
Normal and transient; slow the infusion rate if bothersome.
Nausea
uncommonMild nausea with IV infusion.
Slow infusion rate; stay hydrated.
Chest Tightness / Abdominal Cramping (Rapid Infusion)
uncommonWidely reported in clinical/community experience when NAD+ is infused too quickly, a wave of chest or gut tightness, cramping, or an anxiety-like sensation that resolves once the drip is slowed or paused. This is why protocols run NAD+ over hours rather than as a quick push (the one published safety study used a 6-hour infusion for a 750mg dose).
Infuse slowly (hours, not minutes); pause or slow the drip if symptoms appear.
Injection Site Pain / Stinging (Subcutaneous)
commonSubcutaneous NAD+ injections are commonly reported as more stinging/uncomfortable than typical peptide injections.
Inject slowly, dilute if possible, rotate sites, and consider icing the area beforehand.
General Mitigation Strategies
Side effects are generally mild and transient at the doses studied, the one published safety study found no adverse events at 750mg over a 6-hour IV infusion. Most reported discomfort (flushing, nausea, chest/abdominal tightness) tracks with infusion speed, so a slow drip (hours, not a quick push) is the main mitigation. Subcutaneous injections commonly sting more than other peptide injections; injecting slowly and rotating sites helps.
Support Supplements
Ancillary supplements commonly run alongside NAD+ to manage side effects, support the target tissue, or fill nutrient demands it creates.
TMG (Trimethylglycine / Betaine)
Methyl-donor "insurance." NAD turnover produces nicotinamide, which the enzyme NNMT clears by methylation using SAM, spending methyl groups and generating homocysteine. TMG remethylates homocysteine back to methionine (regenerating SAM), buffering that drain.
- Dose
- 500-1,000mg/day (some use up to 2.5g)
- Timing
- Daily, with the NAD precursor or a meal: consistency matters more than clock time
- When
- Honest evidence: the mechanism is textbook, but the methyl-depletion concern is dose- and form-dependent. Real and well-supported for high-dose nicotinic acid (niacin), which reliably raises homocysteine. Largely theoretical for NR/NMN at normal supplement doses, a 1g/day NR RCT showed no change in homocysteine or methylation. TMG is cheap, low-risk and independently lowers homocysteine, so it is reasonable insurance, just not biochemically mandatory for NMN/NR.
Post Cycle Therapy (PCT)
Not hormonal. No PCT required.
How It Works
NAD+ is a critical coenzyme in cellular metabolism, involved in energy production (ATP synthesis) and DNA repair. It activates sirtuins, proteins involved in longevity and cellular stress response.
Fundamentals
Reference on the practices relevant to NAD+: how they are done and where they go wrong. Not a recommendation to use it.
Legal Status
Oral/sublingual NAD+ is sold as an OTC dietary supplement (USA). IV and subcutaneous NAD+ are typically prepared by a compounding pharmacy and administered at a clinic/med-spa under a practitioner. It is not an FDA-approved drug for anti-aging, addiction, or cognitive indications. Not licensed for medical use in the UK.
Legal status varies by country and changes over time. This is a general summary, not legal advice.
WADA Status
NAD+ is not listed on the WADA Prohibited List. It is a naturally occurring cellular coenzyme available as a supplement.
References
- Grant et al. (2019): Human NAD+ metabolome during a 6h IV infusion of 750mg NAD+; no adverse events (PMC6751327)
- Gaare et al. (2023): NR supplementation not associated with altered methylation homeostasis, NADPARK trial sub-study (PMC10014306)
- Roberti et al. (2021), NNMT & one-carbon metabolism review (PMC7868988)
- Gasparrini et al. (2021): Enzymology of extracellular NAD metabolism (PMC8038981)