Nicotinamide Mononucleotide Supplementation for Exercise Tolerance Improvement in Healthy Older Adults

This randomized, double-blind, placebo-controlled, two-arm crossover trial will compare the effects of two NAD⁺-modulating interventions-EGA® and conventional nicotinamide mononucleotide (NMN) supplementation-on exercise tolerance and metabolic biomarkers in healthy older adults. EGA® is a proprietary formulation composed of three endogenously occurring metabolomic compounds (including NMN) and has been used in prior non-FDA-regulated studies involving human participants. The EGA® arm will involve a twice-daily oral dose of EGA® containing 1000 mg of NMN, while the comparison arm will involve twice-daily oral dose of 1000 mg of conventional NMN per day. Doses will be self-administered each morning and evening with water.

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 EGA® compared to conventional NMN under tightly controlled exercise testing and training conditions. Data from this study will be used to inform the therapeutic potential of EGA® in improving physical performance in healthy older adults (60-80 years). Future directions may include further clinical evaluation or regulatory submissions, depending on outcomes from this pilot investigation.

Inclusion criteria

• 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
• Normal or near-normal cardiovascular function to safely engage in moderate to vigorous exercise, demonstrated by either: stress echocardiogram or coronary CT angiogram within the past 12 months showing normal left ventricular function, no significant valvular heart disease, no ischemic changes, and no other clinically significant abnormalities, plus confirmation that no new cardiovascular symptoms (e.g., chest pain, dyspnea, syncope) or changes in health status have occurred since testing
• 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
• Successful completion of a graded exercise test (e.g., stationary bike) without significant adverse events or contraindications
• Ability to attend at least four in-person laboratory visits in Beverly Hills, California
• Non-smoker for at least 12 months
• Able to provide informed consent and comply with study procedures
• Willing to refrain from initiating new exercise, dietary supplement, or medication regimens during the study

Exclusion criteria

• Severe cardiovascular disease (e.g., recent myocardial infarction <6 months, unstable angina, uncontrolled hypertension >160/100 mmHg)
• Severe respiratory conditions (e.g., advanced COPD or other conditions preventing exercise participation)
• Significant neurological impairments that hinder comprehension of instructions or participation in exercise
• Terminal illness or conditions limiting life expectancy or ability to complete the study
• Severe cognitive impairment preventing informed consent, protocol adherence, or comprehension of interventions
• Significant orthopedic limitations or injuries that prevent safe exercise participation
• Use of NMN, NR, or other NAD+-altering supplements within the past 14 weeks
• Anticipated or current alcohol consumption >2 drinks per week, or unwillingness to abstain from alcohol during the study
• Current substance abuse affecting study participation or adherence
• Other acute or chronic health conditions judged by the investigators to pose risk or interfere with study objectives
• Non-compliance with study requirements, withdrawal of informed consent, or unforeseen circumstances compromising completion
• Any condition which, in the opinion of the investigator, would interfere with study participation or interpretation of results