Tracing the Metabolic Flux of Orally Administered NAD+ Precursors

What Was Tested

In this phase 1 trial, researchers set out to test NAD+.

The researchers are doing this research to learn how healthy younger and older adults use two forms of vitamin B3-called nicotinamide mononucleotide (NMN) and nicotinamide (NAM)-to make NAD+.

NAD+ is a natural substance that cells need for energy and other important processes.

Their goal is to find out how these NAD precursors are absorbed and metabolized and how they raise NAD+ in different tissues.

It had two arms (groups): NMN- Nicotinamide Mononucleotide (active comparator) and NAM- Nicotinamide (active comparator).

This arm will include 16 participants (8 young and 8 older adults) who will receive NMN once daily for 14 consecutive days.

This arm will include 16 participants (8 young and 8 older adults) who will receive NAM once daily for 14 consecutive days.

The registry classes the interventions as drug.

More on the Plan

Beyond its vital role in redox reactions and ATP generation, NAD+ also serves as a co-substrate for several signaling enzymes such as sirtuins, PARPs, and CD38.

There is a need to clarify how they are absorbed and how exactly they elevate NAD+ in different tissues.

Using stable isotope-labeled NMN and NAM will help map the flux from oral precursors into blood, muscle, urine, and stool, and will also reveal how aging influences NAD+ turnover. 2\.

Aims and Objectives Aim 1: Use stable isotope tracers and mass spectrometry in healthy young adults to track how orally administered NMN or NAM are metabolized, how they enter NAD+ pools, and how much is excreted or converted to other metabolites.

Who Took Part

The registry lists 32 planned participants were the target.

It was open to people of any sex aged from 18 years with no upper age limit.

Healthy volunteers could join, not only people with the condition.

Examples of who could join: A healthy, community-living, man or a woman between 18 and 40 years, inclusive or 65 years or older. Has a body mass index (BMI) between 19 and 35 kg/m2, inclusive. Is capable of providing written informed consent. Is willing and able to provide authorization for the use and disclosure of personal health information in accordance with Health Insurance Portability and Accountability Act.

The full record lists 5 inclusion and 13 exclusion criteria; among the exclusions: has ast or alt \> 2 times the upper limit of normal; prohibited medications and substances: use of anabolic steroids, rhgh, dhea, androstenedione, or any performance enhancing drug; current use of opiates, amphetamine, cannabinoids and cocaine; for women only: pregnant or planning to get pregnant over the next 6 months, or lactating.

How the Study Was Run

Design: randomized, parallel-group and open-label.

The participants were allocated by chance, so the NAD+ group and the comparison group should start out alike.

Groups ran in parallel: each of the participants stayed in one arm throughout.

Everyone knew when NAD+ was being given (open label), which is simpler to run but leaves more room for expectations to affect what is reported.

It started in 2025-04-28 with completion listed for 2026-12.

It ran at 1 site in United States.

Its stated primary purpose is basic science.

What Was Measured

The main thing measured (primary outcome): Labelled NAD+ in Peripheral Blood (time frame: During the Study Intervention Period Day 1 through Day 14).

It also tracked 13 secondary outcomes, for example Labelled NAD+ in Muscle, 1-Methyl nicotinamide (MeNAM) in Plasma, 1-Methyl nicotinamide (MeNAM) in Muscle, 1-Methyl nicotinamide (MeNAM) in Urine, 1-Methyl nicotinamide (MeNAM) in Stool and N-methyl-2-pyridone-5-carboxamide (2PY) in Plasma.

What This Means in Plain Language

Put simply, this is a phase 1, randomized trial of NAD+ in 32 people.

Its size is small, so on its own it can only give an early look.

It is still recruiting; no results are posted to the registry yet, so nothing here describes outcomes.

More context: the NAD+ compound page, all human trials.