Report of a Randomized Placebo-Controlled Trial of the Effects of Oral NADH on Physical Endurance Levels

Background: Nicotinamide adenine dinucleotide hydride [NADH] is a vital coenzyme involved in cellular energy production and redox regulation. Oral NADH supplementation has shown promise in enhancing physical and mental performance; however, its direct effects on exercise endurance and related biochemical markers in healthy individuals remain understudied. Objective: This double-blind, placebo-controlled, randomized study aimed to evaluate the impact of oral NADH supplementation on physical endurance, aerobic capacity, and key metabolic markers (NADH, NAD+, ATP, and phospho-AMPKα1) in healthy, untrained young adults. Methods: Sixteen healthy male medical students aged 20–22 years were randomly assigned to receive either 40 mg/day of sublingual NADH or placebo for three weeks. Physical endurance was assessed using the PWC170 cycle ergometer test to estimate VO2max. Heart rate, blood pressure, and pulse pressure were monitored both before and after exercise. Blood samples were analyzed for NADH, NAD+, ATP, and phospho-AMPKα1 levels in leukocytes. Results: After three weeks, the NADH group demonstrated significant improvements in PWC170 [+25.6%] and VO2max (+23.9%) compared to both the baseline and placebo groups [p < 0.05]. Heart rate recovery post-exercise improved, and systolic blood pressure decreased, suggesting enhanced cardiovascular efficiency and reduced stress response. However, no significant changes were observed in the levels of NADH, NAD+, ATP, or phospho-AMPKα1 in leukocytes, possibly due to increased cellular utilization during physical exertion or tissue-specific effects. Conclusion: Oral NADH supplementation significantly enhances physical endurance, aerobic capacity, and cardiovascular recovery in healthy young adults under stress, without altering leukocyte metabolic markers. Further research is warranted to explore tissue-specific metabolic effects and the underlying molecular mechanisms.