NAD+

NAD+ is an essential cellular cofactor in redox metabolism and enzyme signaling. Direct IV evidence is limited to an 11-man metabolism pilot, while current randomized registrations focus on biomarkers, pain, and tolerability rather than wellness outcomes.

oxidized dinucleotide cofactor

Oxidized nicotinamide adenine dinucleotide
Not a peptide
Distinct from NADH, NR, and NMN
No FDA-approved IV anti-aging indication

What exactly is NAD+?

NAD+ is the oxidized form of nicotinamide adenine dinucleotide, an endogenous cofactor used in redox reactions and enzyme signaling. NADH is its reduced form; NR and NMN are precursors. Data from one cannot automatically be assigned to another.

IV pilot · metabolism, not clinical benefit

Human pharmacokinetic pilot

Grant R et al. Frontiers in Aging Neuroscience, 2019.

Eleven healthy men received NAD+ at 3 micromoles per minute for six hours, totaling about 750 mg. During the first two hours, infused NAD+ was removed from plasma faster than it accumulated; later blood and urine metabolites changed. No anti-aging, cognitive, addiction, or functional efficacy endpoint was tested.

Participants / model: 11 healthy male volunteers
Treatment: Continuous intravenous NAD+ at 3 micromoles per minute for 6 hours
Follow-up: One 6-hour infusion with blood and urine sampling
Study design: Uncontrolled pharmacokinetic and metabolomic pilot

This study describes handling of one infusion, not clinical efficacy.

Read the original source

NMN RCT · narrow metabolic outcome

Randomized placebo-controlled trial of a precursor

Yoshino M et al. Science, 2021.

In postmenopausal women with prediabetes, ten weeks of oral NMN increased muscle insulin signaling and insulin-stimulated glucose disposal. It did not improve several other measured metabolic outcomes and did not test intravenous NAD+.

Participants / model: Postmenopausal women with prediabetes
Treatment: Oral NMN or placebo
Follow-up: 10 weeks
Study design: Randomized double-blind placebo-controlled trial

NMN is a precursor and cannot validate a direct NAD+ infusion.

Read the original source

What does intravenous NAD+ do in people?

The direct published pilot measured short-term plasma and urine handling in 11 healthy men and did not test clinical benefit. Two newer randomized trial records focus mainly on biomarkers, pain, and tolerability and have no posted results.

IV pilot · metabolism, not clinical benefit

Human pharmacokinetic pilot

Grant R et al. Frontiers in Aging Neuroscience, 2019.

Eleven healthy men received NAD+ at 3 micromoles per minute for six hours, totaling about 750 mg. During the first two hours, infused NAD+ was removed from plasma faster than it accumulated; later blood and urine metabolites changed. No anti-aging, cognitive, addiction, or functional efficacy endpoint was tested.

Participants / model: 11 healthy male volunteers
Treatment: Continuous intravenous NAD+ at 3 micromoles per minute for 6 hours
Follow-up: One 6-hour infusion with blood and urine sampling
Study design: Uncontrolled pharmacokinetic and metabolomic pilot

This study describes handling of one infusion, not clinical efficacy.

Read the original source

NCT06382688 · 53 people, no results posted

Trial registry record

ClinicalTrials.gov.

The sponsor reports actual enrollment of 53 adults in a randomized comparison of IV nicotinamide riboside, IV NAD+, oral nicotinamide riboside, and saline. The listed endpoints are NAD biomarkers and infusion tolerability; the registry lists unknown status and no posted results.

Participants / model: 53 adults aged 40 years or older
Treatment: IV NAD+, IV nicotinamide riboside, oral nicotinamide riboside, or saline
Study design: Randomized double-masked biomarker and tolerability study

The registration does not provide an efficacy result and does not test broad healthspan.

Read the original source

NCT06919328 · IM, SC, and IV-push study

Trial registry record

ClinicalTrials.gov.

The registered study compares 100 mg NAD+ and nicotinamide riboside by intramuscular, subcutaneous, and IV-push routes with route-matched placebo. Primary endpoints concern injection pain and discomfort; biomarker and short questionnaire endpoints are secondary or exploratory. The registry posts no results.

Treatment: NAD+, nicotinamide riboside, or placebo by three injection routes
Study design: Randomized quadruple-masked route and tolerability study

No results were posted, and the registered primary endpoints concern injection pain and discomfort rather than anti-aging efficacy.

Read the original source

Does NAD biology prove an anti-aging effect?

NAD+ is biologically essential, but the cited age study only measured a cross-sectional plasma association. It did not test whether an infusion improves healthspan or any functional outcome.

Cross-sectional study · plasma assay only

Cross-sectional biomarker study

Clement J et al. Rejuvenation Research, 2019.

The study measured plasma NAD+ in adults aged 20 to 87 and reported an age association. A cross-sectional plasma measure does not establish a universal whole-body decline, its cause, or benefit from replacement.

Participants / model: Adults aged 20 to 87
Treatment: No intervention
Study design: Cross-sectional plasma biomarker study

Read the original source

IV pilot · metabolism, not clinical benefit

Human pharmacokinetic pilot

Grant R et al. Frontiers in Aging Neuroscience, 2019.

Eleven healthy men received NAD+ at 3 micromoles per minute for six hours, totaling about 750 mg. During the first two hours, infused NAD+ was removed from plasma faster than it accumulated; later blood and urine metabolites changed. No anti-aging, cognitive, addiction, or functional efficacy endpoint was tested.

Participants / model: 11 healthy male volunteers
Treatment: Continuous intravenous NAD+ at 3 micromoles per minute for 6 hours
Follow-up: One 6-hour infusion with blood and urine sampling
Study design: Uncontrolled pharmacokinetic and metabolomic pilot

This study describes handling of one infusion, not clinical efficacy.

Read the original source

Do NR or NMN trials validate IV NAD+?

No. Oral NMN and NR use different molecules, absorption, metabolism, and exposure. Some trials move NAD-related biomarkers and a few narrow outcomes, but that does not establish efficacy for intravenous NAD+.

NMN RCT · narrow metabolic outcome

Randomized placebo-controlled trial of a precursor

Yoshino M et al. Science, 2021.

In postmenopausal women with prediabetes, ten weeks of oral NMN increased muscle insulin signaling and insulin-stimulated glucose disposal. It did not improve several other measured metabolic outcomes and did not test intravenous NAD+.

Participants / model: Postmenopausal women with prediabetes
Treatment: Oral NMN or placebo
Follow-up: 10 weeks
Study design: Randomized double-blind placebo-controlled trial

NMN is a precursor and cannot validate a direct NAD+ infusion.

Read the original source

NCT06382688 · 53 people, no results posted

Trial registry record

ClinicalTrials.gov.

The sponsor reports actual enrollment of 53 adults in a randomized comparison of IV nicotinamide riboside, IV NAD+, oral nicotinamide riboside, and saline. The listed endpoints are NAD biomarkers and infusion tolerability; the registry lists unknown status and no posted results.

Participants / model: 53 adults aged 40 years or older
Treatment: IV NAD+, IV nicotinamide riboside, oral nicotinamide riboside, or saline
Study design: Randomized double-masked biomarker and tolerability study

The registration does not provide an efficacy result and does not test broad healthspan.

Read the original source

What are the main risks and unknowns?

Direct human safety data are small, and injections add line, formulation, sterility, endotoxin, and rapid-exposure risks. FDA has documented severe reactions from contaminated compounded NAD+ products, including a three-patient cluster tied to a lot with very high endotoxin.

FDA tied the three-patient cluster to one compounded lot that measured 3,360 EU/mL of bacterial endotoxin. The episode does not provide an intrinsic adverse-event rate for chemically pure NAD+, but it documents serious harm from sterile-manufacturing failure.

FDA · adverse events after compounded NAD+

FDA safety communication

US Food and Drug Administration.

FDA describes reports of severe chills, shaking, vomiting, and fatigue after compounded NAD+ injections made with material unsuitable for sterile compounding. The pattern was consistent with endotoxin exposure and illustrates a manufacturing hazard separate from the molecule’s intended pharmacology.

Study design: Agency compounding safety communication

Read the original source

FDA 2026 · 3 patients and 3,360 EU/mL endotoxin

FDA warning letter

US Food and Drug Administration, 20 January 2026.

Three patients developed hypotension, uncontrollable shaking, shivers, and body aches during or shortly after a compounded NAD+ product from one vial and were sent to an emergency department. An unopened vial from the same lot measured 3,360 EU/mL bacterial endotoxin. FDA also said NAD+ was not eligible for the facility’s claimed 503B exemptions because it was not on the 503B bulks or shortage lists.

Participants / model: Three reported recipients from one implicated vial and lot
Treatment: Compounded NAD+ product
Study design: Regulatory inspection and complaint investigation

This documents a contaminated product episode, not an intrinsic adverse-event rate for chemically pure NAD+.

Read the original source

IV pilot · metabolism, not clinical benefit

Human pharmacokinetic pilot

Grant R et al. Frontiers in Aging Neuroscience, 2019.

Eleven healthy men received NAD+ at 3 micromoles per minute for six hours, totaling about 750 mg. During the first two hours, infused NAD+ was removed from plasma faster than it accumulated; later blood and urine metabolites changed. No anti-aging, cognitive, addiction, or functional efficacy endpoint was tested.

Participants / model: 11 healthy male volunteers
Treatment: Continuous intravenous NAD+ at 3 micromoles per minute for 6 hours
Follow-up: One 6-hour infusion with blood and urine sampling
Study design: Uncontrolled pharmacokinetic and metabolomic pilot

This study describes handling of one infusion, not clinical efficacy.

Read the original source

Is IV NAD+ an approved anti-aging treatment?

The cited FDA records list no approved IV NAD+ anti-aging or wellness indication. FDA's Category 1 nomination status under 503A means the substance is still under evaluation, and the 2026 warning letter separately found NAD+ ineligible for that outsourcing facility's 503B exemptions.

FDA 503A · NAD under evaluation

FDA regulatory document

US Food and Drug Administration, updated 14 May 2026.

NAD and NADH appear in Category 1 as nominated bulk substances under evaluation for 503A compounding. Category 1 is not approval, an approved indication, or a favorable efficacy determination.

Study design: Current compounding-nomination status document

Read the original source

FDA 2026 · 3 patients and 3,360 EU/mL endotoxin

FDA warning letter

US Food and Drug Administration, 20 January 2026.

Three patients developed hypotension, uncontrollable shaking, shivers, and body aches during or shortly after a compounded NAD+ product from one vial and were sent to an emergency department. An unopened vial from the same lot measured 3,360 EU/mL bacterial endotoxin. FDA also said NAD+ was not eligible for the facility’s claimed 503B exemptions because it was not on the 503B bulks or shortage lists.

Participants / model: Three reported recipients from one implicated vial and lot
Treatment: Compounded NAD+ product
Study design: Regulatory inspection and complaint investigation

This documents a contaminated product episode, not an intrinsic adverse-event rate for chemically pure NAD+.

Read the original source

Studies and sources

IV pilot · metabolism, not clinical benefit

Human pharmacokinetic pilot

Grant R et al. Frontiers in Aging Neuroscience, 2019.

Eleven healthy men received NAD+ at 3 micromoles per minute for six hours, totaling about 750 mg. During the first two hours, infused NAD+ was removed from plasma faster than it accumulated; later blood and urine metabolites changed. No anti-aging, cognitive, addiction, or functional efficacy endpoint was tested.

Participants / model: 11 healthy male volunteers
Treatment: Continuous intravenous NAD+ at 3 micromoles per minute for 6 hours
Follow-up: One 6-hour infusion with blood and urine sampling
Study design: Uncontrolled pharmacokinetic and metabolomic pilot

This study describes handling of one infusion, not clinical efficacy.

Read the original source

NCT06382688 · 53 people, no results posted

Trial registry record

ClinicalTrials.gov.

The sponsor reports actual enrollment of 53 adults in a randomized comparison of IV nicotinamide riboside, IV NAD+, oral nicotinamide riboside, and saline. The listed endpoints are NAD biomarkers and infusion tolerability; the registry lists unknown status and no posted results.

Participants / model: 53 adults aged 40 years or older
Treatment: IV NAD+, IV nicotinamide riboside, oral nicotinamide riboside, or saline
Study design: Randomized double-masked biomarker and tolerability study

The registration does not provide an efficacy result and does not test broad healthspan.

Read the original source

NCT06919328 · IM, SC, and IV-push study

Trial registry record

ClinicalTrials.gov.

The registered study compares 100 mg NAD+ and nicotinamide riboside by intramuscular, subcutaneous, and IV-push routes with route-matched placebo. Primary endpoints concern injection pain and discomfort; biomarker and short questionnaire endpoints are secondary or exploratory. The registry posts no results.

Treatment: NAD+, nicotinamide riboside, or placebo by three injection routes
Study design: Randomized quadruple-masked route and tolerability study

No results were posted, and the registered primary endpoints concern injection pain and discomfort rather than anti-aging efficacy.

Read the original source

NMN RCT · narrow metabolic outcome

Randomized placebo-controlled trial of a precursor

Yoshino M et al. Science, 2021.

In postmenopausal women with prediabetes, ten weeks of oral NMN increased muscle insulin signaling and insulin-stimulated glucose disposal. It did not improve several other measured metabolic outcomes and did not test intravenous NAD+.

Participants / model: Postmenopausal women with prediabetes
Treatment: Oral NMN or placebo
Follow-up: 10 weeks
Study design: Randomized double-blind placebo-controlled trial

NMN is a precursor and cannot validate a direct NAD+ infusion.

Read the original source

Cross-sectional study · plasma assay only

Cross-sectional biomarker study

Clement J et al. Rejuvenation Research, 2019.

The study measured plasma NAD+ in adults aged 20 to 87 and reported an age association. A cross-sectional plasma measure does not establish a universal whole-body decline, its cause, or benefit from replacement.

Participants / model: Adults aged 20 to 87
Treatment: No intervention
Study design: Cross-sectional plasma biomarker study

Read the original source

FDA · adverse events after compounded NAD+

FDA safety communication

US Food and Drug Administration.

FDA describes reports of severe chills, shaking, vomiting, and fatigue after compounded NAD+ injections made with material unsuitable for sterile compounding. The pattern was consistent with endotoxin exposure and illustrates a manufacturing hazard separate from the molecule’s intended pharmacology.

Study design: Agency compounding safety communication

Read the original source

FDA 2026 · 3 patients and 3,360 EU/mL endotoxin

FDA warning letter

US Food and Drug Administration, 20 January 2026.

Three patients developed hypotension, uncontrollable shaking, shivers, and body aches during or shortly after a compounded NAD+ product from one vial and were sent to an emergency department. An unopened vial from the same lot measured 3,360 EU/mL bacterial endotoxin. FDA also said NAD+ was not eligible for the facility’s claimed 503B exemptions because it was not on the 503B bulks or shortage lists.

Participants / model: Three reported recipients from one implicated vial and lot
Treatment: Compounded NAD+ product
Study design: Regulatory inspection and complaint investigation

This documents a contaminated product episode, not an intrinsic adverse-event rate for chemically pure NAD+.

Read the original source

FDA 503A · NAD under evaluation

FDA regulatory document

US Food and Drug Administration, updated 14 May 2026.

NAD and NADH appear in Category 1 as nominated bulk substances under evaluation for 503A compounding. Category 1 is not approval, an approved indication, or a favorable efficacy determination.

Study design: Current compounding-nomination status document

Read the original source

Why is NAD+ in B tier?

B reflects established NAD+ biology and a growing human precursor literature. The direct IV pilot measured short-term metabolism in 11 healthy men, not aging, cognition, fatigue, addiction, or athletic performance.