Recent studies in rodents suggest that exercise training combined with supplementation of nicotinamide adenine dinucleotide (NAD+) precursors has synergistic effects. However, there are currently no human clinical trials examining this combination. This study aims to investigate the effects of exercise training combined with supplementation of nicotinamide mononucleotide (NMN), an immediate precursor of NAD+, on cardiovascular fitness in amateur runners.
The study involved a randomized, double-blind, placebo-controlled, four-arm clinical trial with 48 recreationally trained runners. Participants were divided into four groups: low dosage group (300 mg/day NMN), medium dosage group (600 mg/day NMN), high dosage group (1200 mg/day NMN), and control group (placebo). Training sessions were 40-60 minutes, 5-6 times per week, for a duration of six weeks. Cardiopulmonary exercise testing was conducted at baseline and after the intervention to assess aerobic capacity.
Analysis showed that the medium and high dosage groups had greater improvements in oxygen uptake, percentages of maximum oxygen uptake, power at first ventilatory threshold, and power at second ventilatory threshold compared to the control group. However, there were no significant differences in other measurements such as VO2max, O2-pulse, VO2 related to work rate, and peak power between the groups. The conclusion is that NMN supplementation increases aerobic capacity during exercise training, potentially due to enhanced oxygen utilization in skeletal muscle.
The Importance of NAD+ and NAD+ Precursors
Nicotinamide adenine dinucleotide (NAD+) is important for physiological processes and activation of NAD+-consuming enzymes. NAD+ participates in more than 50% of all physiological processes. Low NAD+ levels are associated with age-associated physical disability and diseases. The NAD+ salvage pathway using NAD+ precursors is important for maintaining cellular NAD+ levels. Nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN) are two NAD+ precursors that have been studied extensively and shown to increase NAD+ levels. Replenishing depleted NAD+ pools with NR or NMN alleviates pathologic states in rodent models. Clinical studies have shown limited effects of NR on skeletal muscle, cardiovascular function, and physical function.
Previous Findings on NMN and Exercise
Regular exercise increases NAMPT expression and NAD+ levels, and is related to improvements in physical function. NMN has stronger effects than exercise on hepatic fat metabolism. Deletion or inhibition of CD38 or PARP-1 improves mitochondrial function and endurance performance. Combination of exercise and NMN or NR supplementation increases endurance performance in mice. However, the effect of exercise and NMN supplementation on cardiovascular fitness in healthy humans has not been reported.
The study was performed at the Key Laboratory of Exercise and Health Promotion of Guangzhou Sport University and approved by the ethics committee. Forty-eight healthy recreationally trained runners (40 males and 8 females) were recruited from the Guangzhou Pearl River running team. Participants were randomly assigned to one of four groups with allocation concealed. Supplementation with NMN or placebo lasted for 6 weeks. All participants were instructed to not change their habitual diet and daily living routines and refrain from caffeine during the study. Training consisted of 6 weeks of aerobic exercise with specific intensity targets based on heart rate measurements. Participants underwent cardiopulmonary endurance performance evaluations before and after the intervention period using a ramp exercise test. Anthropometric data were assessed.
The combination of exercise and NMN supplementation did not result in changes in body mass or body composition. Baseline characteristics of the participants in the four groups were similar. There were no significant differences in body mass, BMI, or body fat percentage between the treatment groups and control group after 6 weeks of NMN supplementation. There were no significant changes in various measurements related to cardiovascular fitness between the control group and any of the NMN treatment groups. However, NMN supplementation resulted in significant increases in specific measurements such as VO2@VT1, %VO2max@VT1, HR@VT1, power@VT1, and power@VT2 compared with baseline. The positive effect of NMN supplementation on cardiopulmonary function was dose-dependent. No adverse events were reported during the intervention period, and there were no abnormalities shown on the ECG during exercise.
Safety and Conclusion
NMN supplementation in rodents has been shown to increase cellular NAD+ content and is safe in dosage ranges. In humans, a single dose of NMN increased circulatory NAD+ and was safe. In a study involving amateur runners, NMN supplementation during exercise improved first ventilatory threshold and power at the second ventilatory threshold in a dose-dependent manner. NMN supplementation combined with exercise did not change body composition. The findings suggest that NMN supplementation as an adjunct treatment could potentially improve performance during exercise training. NMN supplementation has been shown to be safe and free from obvious side effects in both rodents and humans. Further research is needed to investigate gender differences and effects on vascular endothelium function, capillary density, blood flow, and mitochondrial function.
Key Findings and Implications
- The combination of NMN supplementation and exercise has been found to enhance the ventilatory threshold in amateur runners.
- This improvement is dependent on the dosage of NMN, with larger doses producing better effects.
- The benefits of NMN supplementation and exercise on ventilatory threshold are muscle-related, rather than cardiac-related.
- The findings suggest that NMN supplementation as an adjunct treatment could potentially improve performance during exercise training.
- Additionally, the combination of exercise training and NMN supplementation could be a novel and practical strategy to enhance endurance performance in athletes.
The supplementary information provided in the study includes baseline cardiopulmonary function parameters of the participants, changes in cardiopulmonary function after the intervention, baseline results of the physical function test, change in the physical function test results after the intervention, and effect sizes between the groups after the intervention.
Title of paper: Nicotinamide mononucleotide supplementation enhances aerobic capacity in amateur runners: a randomized, double-blind study
Author(s): Liao B, Zhao Y, Wang D, Zhang X, Hao X, Hu M.
Year published: 2021
Published in: J Int Soc Sports Nutr
Original article can be found here.