Nicotinamide Mononucleotide Supplementation for Exercise Tolerance Improvement in Healthy Older Adults

What Was Tested

This registered not phased trial tested NAD+.

This is a randomized, double-blind, placebo-controlled, two-arm crossover clinical trial evaluating the effects of nicotinamide mononucleotide (NMN) combined with trimethylglycine (TMG) supplementation, compared to NMN alone.

The primary outcome is cycle ergometry constant work rate (CWR) exercise tolerance, measured as time to fatigue.

It had four arms (groups): Arm 1 - NMN with TMG -> Placebo (experimental), Arm 2 - Placebo -> NMN with TMG (experimental), Arm 3 - NMN -> Placebo (experimental) and Arm 4 - Placebo -> NMN (experimental).

Participants receive NMN with TMG during Period 1, followed by Placebo during Period 2 after a washout. Assigned Interventions: NMN with TMG; Placebo.

Participants receive Placebo during Period 1, followed by NMN with TMG during Period 2 after a washout. Assigned Interventions: Placebo; NMN with TMG.

Participants receive Nicotinamide Mononucleotide (NMN) during Period 1, followed by Placebo during Period 2 after a washout. Assigned Interventions: NMN; Placebo.

The registry classes the interventions as dietary supplement.

More on the Plan

This randomized, double-blind, placebo-controlled, two-arm crossover trial will compare the effects of two NAD⁺-modulating interventions-nicotinamide mononucleotide (NMN) with trimethylglycine (TMG) and conventional NMN supplementation-on exercise tolerance and metabolic biomarkers in healthy older adults.

The primary endpoint is time to fatigue during constant work rate cycle ergometry (CWR-Tlim), a validated surrogate for submaximal exercise tolerance.

Secondary endpoints include peak oxygen uptake (VO₂peak), lactate threshold, anaerobic work capacity, and critical power, in addition to circulating NAD⁺ and its related metabolites.

The trial is designed to evaluate the short-term physiological effects and biological activity of NMN with TMG compared to NMN alone under tightly controlled exercise testing and training conditions.

Who Took Part

The registry lists 40 planned participants were the target.

It was open to people of any sex aged from 60 years up to 80 years.

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

Examples of who could join: Adults aged 60 to 80 years, of any sex. Written clearance from primary care physician confirming medical fitness to participate in an exercise-based clinical study. Montreal Cognitive Assessment (MoCA) score of 26 or higher. Free from acute or uncontrolled chronic medical conditions that would pose a risk or interfere with study participation. Physically capable of engaging in structured exercise involving moderate to vigorous intensity stationary cycling.

The full record lists 11 inclusion and 12 exclusion criteria; among the exclusions: severe cardiovascular disease (e.g., recent myocardial infarction \<6 months, unstable angina, uncontrolled hypertension \>160/100 mmhg); terminal illness or conditions limiting life expectancy or ability to complete the study; use of nmn, nr, or other nad+-altering supplements within the past 14 weeks.

How the Study Was Run

The set-up was randomized, crossover and quadruple-blind.

Random assignment meant chance, not the researchers, decided who got NAD+ and who got the comparison, which limits bias.

Each person switched between NAD+ and the comparison at some point, usually with a gap in between.

Blinding on both sides kept the participants and researchers unaware of who received NAD+.

Those kept unaware of assignments: participant, care provider, investigator and outcomes assessor.

It started in 2026-02-21 with completion listed for 2026-12-30.

It ran at 1 site in United States.

Its stated primary purpose is basic science.

What Was Measured

Primary outcome: Time to Fatigue During Constant Work Rate Cycle Ergometry (tLIM) (time frame: Measured at the beginning and end of each 4-week intervention period).

It also tracked 5 secondary outcomes, for example Peak Oxygen Uptake (VO2max), Lactate Threshold, Anaerobic Work Capacity, Critical Power and Circulating NAD+ and Related Metabolites.

What This Means in Plain Language

Put simply, this is a not phased, randomized trial of NAD+ in 40 people.

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.