Longevity Articles

NMN for Peak Performance and Energy

NMN for Peak Performance and Energy

Peak performance means different things to everyone, and might even mean something different to you now than it did 20 years ago. We’re going to broadly define peak performance as having the physical and mental capacity to achieve what you set out to do, whether that’s a startup business proposal or a Spartan race. 

What determines your capacity? Your energy, and this means cellular energy in the form of NAD+, which both fuels your body and protects function, like strength and cognition. While you may not have thought about having the energy or strength to do something in your 30’s, by your 50’s a lot of your reserves have been depleted, leaving you feeling weaker, slower, and not as sharp…unless you’re addressing the root of your energy loss. 

When it comes to maintaining peak performance, even as your priorities shift, NAD+ is important not only for energy cycling, but also for regulating metabolic pathways which maintain cellular structure and viability. We’ll talk about the key molecular players and the pathways they interact with first, then get into a peak performance strategy in the second half of this article. 

NMN and NAD+ Metabolism 

NMN is a precursor to Nicotinamide Adenine Dinucleotide (NAD+), a coenzyme essential for redox reactions and a substrate for sirtuins and PARPs (Poly [ADP-ribose] polymerases), which are involved in DNA repair and genomic stability. By supporting NAD+ levels, NMN supplementation enhances the activity of sirtuins, particularly SIRT1, which regulates mitochondrial biogenesis, fatty acid oxidation, and oxidative stress resistance—key factors in sustaining energy production and muscle health. 

Sirtuins: SIRT1 and Mitochondrial Function 

SIRT1, activated by increased NAD+ levels, deacetylates (removes an acetyl- group from) various substrates involved in metabolic regulation, including PGC-1α (Peroxisome proliferator-activated receptor gamma coactivator 1-alpha), a master regulator of mitochondrial biogenesis. The activation of PGC-1α by SIRT1 promotes the formation of new mitochondria and enhances the capacity of muscle cells for oxidative phosphorylation, thereby supporting endurance and energy efficiency during prolonged physical activity. 

Sestrins and Metabolic Homeostasis 

Sestrins, stress-responsive proteins, contribute to metabolic homeostasis by activating AMPK and inhibiting mTORC1 signaling (which is exactly what we want for maintaining health and promoting longevity). Through the activation of AMPK, sestrins promote catabolic processes that generate ATP, such as glycolysis and fatty acid oxidation, responsible for energy production during exercise. Simultaneously, by inhibiting mTORC1, sestrins help modulate protein synthesis and cell growth, ensuring that energy resources are not excessively diverted to anabolic processes during periods of energy demand. 

Translation: sestrin activation inhibits muscle protein synthesis during exercise (when energy needs to be burned), and their downregulation during periods of rest allow resources to be diverted into building muscle, bone, and other tissues. 

AMPK: Energy Sensing and Metabolic Balance 

AMPK acts as a cellular energy sensor, activated under conditions of low energy (high AMP/ATP ratio) to restore energy balance. Activation of AMPK by sestrins or directly through metabolic stress stimulates glucose uptake and fatty acid oxidation, while inhibiting energy-consuming processes, including protein and lipid synthesis. AMPK's role in enhancing mitochondrial function and promoting glucose utilization directly supports muscle performance and endurance. 

Note: Everyone is familiar with ATP, adenosine triphosphate. AMP is it’s smallest sibling, adenosine monophosphate, which has a single phosphate group instead of being fully charged with three. 

mTORC: Growth and Protein Synthesis 

While mTORC1 is known for its role in stimulating anabolic processes, including protein synthesis and cell growth, keeping it regulated and balanced maintains muscle health and function. In the context of exercise and muscle stress, transient inhibition of mTORC1 by sestrins and AMPK can be beneficial, allowing cells to conserve energy and repair damage. However, post-exercise, the activation of mTORC1 is essential for muscle protein synthesis and hypertrophy, contributing to increased muscle strength and size over time. 

Integrative View for Peak Performance 

The synergistic and sometimes opposing actions of these pathways represent a finely tuned regulatory network that balances energy production, utilization, and recovery in muscle cells. NMN supplementation, by enhancing NAD+ and thereby modulating sirtuin activity, creates a downstream influence on AMPK and mTORC signaling, aligning metabolic and cellular responses with the energetic demands of physical performance. Sestrins ensure cellular resilience against stress and support metabolic adaptation to exercise. 


How NMN Enhances Muscle Protein Synthesis 

Muscle protein synthesis is the biological mechanism through which cells generate new proteins, a process essential for muscle repair, growth, and maintenance. This synthesis is influenced by factors such as nutrition, hormonal balance, and physical activity. NMN's influence on muscle protein synthesis can be attributed to its capacity to elevate NAD+ levels, thereby activating sirtuins (SIRT1), a family of NAD+-dependent deacetylases. SIRT1 activation enhances mitochondrial biogenesis and function. 

Moreover, NMN supplementation has been shown to improve insulin sensitivity, a factor that indirectly supports muscle protein synthesis. Enhanced insulin sensitivity facilitates the uptake of amino acids into muscle cells, a necessary step for the synthesis of new proteins. 

Differences in muscle protein synthesis between fast-twitch (Type II) and slow-twitch (Type I) muscle fibers are notable. Type I fibers, known for their endurance capabilities, primarily rely on oxidative phosphorylation for energy and are rich in mitochondria. Type II fibers, in contrast, are characterized by their rapid force generation and reliance on glycolytic pathways for energy. NMN's role in promoting mitochondrial biogenesis and enhancing oxidative metabolism suggests a potentially greater impact on the synthesis and maintenance of Type I fibers. However, by improving overall cellular energy availability and insulin sensitivity, NMN may also support the health and function of Type II fibers, albeit through mechanisms more related to energy supply than direct mitochondrial enhancement. 

The proportion of fast-twitch to slow-twitch muscle fibers in a person’s body can change over their lifetime due to normal aging or training specificity. Aging is associated with a decline in muscle mass and strength, with a more pronounced reduction in Type II fibers. This shift contributes to the decreased power and agility often observed in older adults. Conversely, specific types of training can induce changes in muscle fiber composition. Endurance training tends to enhance the oxidative capacity of both fiber types and can increase the proportion of Type I fibers, while strength training predominantly supports the size and strength of Type II fibers. 

The capacity to deliberately alter muscle fiber composition through NMN supplementation, in conjunction with training, opens up possibilities for mitigating age-related declines in muscle function and optimizing performance. While direct evidence of NMN's role in modifying muscle fiber type distribution is limited, its effects on enhancing mitochondrial function and energy metabolism suggest that NMN supplementation could support the maintenance and possibly the shift towards a more oxidative (Type I) muscle fiber profile, especially relevant for aging populations. 

Furthermore, NMN's potential to ameliorate age-related declines in NAD+ levels and enhance cellular energy status not only supports muscle protein synthesis but may also counteract the underlying mechanisms contributing to muscle loss. This includes combating the decrease in mitochondrial function, reducing oxidative stress, and improving the regenerative capacity of muscle cells. 

While deliberately training, or at least remaining active supports peak performance and strength, NMN can promote the maintenance of muscle tissue even in the absence of deliberate activity for those who find training impossible. 

NMN Supplementation: Amateur Runners Rejoyce 

A recent human trial conducted by Bagen Liao and his team at Guangzhou Sport University revealed that NMN supplementation could enhance the aerobic capacity of amateur runners. The study, published in the Journal of the International Society of Sports Nutrition, found that NMN supplementation improved the ability of skeletal muscles to utilize oxygen for more efficient energy production during endurance exercise. 

The participants of the study, consisting of 48 young and middle-aged runners, were given different doses of NMN (300 mg, 600 mg, and 1200 mg per day) for six weeks. The results showed a significant relationship between NMN supplements and specific measures of endurance capacity. These included improvements in oxygen uptake (VO2), percentages of maximum oxygen uptake (VO2max%), first ventilatory threshold (VT1), and power at the second ventilatory threshold (VT2). 

The results were dose-dependent, with the high NMN dosage group showing greater changes in VO2 and VO2max% than the medium dosage group. No adverse health effects were observed at any of the given doses, suggesting that NMN is safe for consumption even at doses exceeding what most people typically choose. 

Peak Performance Protocol 

  • NMN Supplementation: Start with a baseline NMN dose of 300 mg per day, gradually increasing to 500 mg after 2 weeks, assessing tolerance and effects. Consider pushing to 1000 mg if performance gains plateau and no adverse effects are experienced. If you are already taking 1000 mg daily, maintain this dose. 
  • Nutritional Support: Prioritize a high-protein diet to supply essential amino acids for muscle protein synthesis. While animal protein sources are typically more complete in terms of amino acid ratio, those on plant-based diets are cautioned to review their specific protein sources to ensure balance. Consider adding high-quality protein powders. Incorporate fresh foods rich in antioxidants to combat oxidative stress and support mitochondrial health. Hydrate with electrolyte-infused drinks to ensure nutrient delivery, energy production, and cellular waste removal. Consider adding creatine for a synergistic boost to muscle growth and performance. 
  • Training: Engage in strength training 4 days per week, focusing on compound movements that target multiple muscle groups simultaneously. Split sessions between upper body and lower body to allow for adequate recovery. Incorporate 2-3 cardio sessions weekly, on non-consecutive days to allow for muscle recovery and to avoid overtraining. If there is excessive fatigue preventing a full workout, consider supplementing with ATP 30 minutes before working out. 
  • Recovery and Sleep: Emphasize adequate recovery through rest days and ensure 7-9 hours of quality sleep nightly to facilitate muscle repair and growth. Magnesium is exceptionally helpful for sleep support and has the added benefit of soothing muscle soreness. 

What Have We Learned? 

The lifelong and steady decrease of NAD+ is one of the core issues at the root of age-related muscle and strength loss. By supporting NAD+ stores with supplemental NMN, you’re making a dramatic impact on your muscle protein synthesis and maintenance of strength. 

It can be difficult for older adults to stay strong and mobile, and a focus on peak performance can help slow or halt this decline. There are plenty of examples of people who have gotten fit in their 60’s, 70’s, and beyond, it just requires a targeted strategy for the unique needs of bodies who have experienced more life. 

NMN is the first and best place to start to support peak performance, followed by smart nutritional strategies and other supplemental formulas that enhance performance. Train hard and stay strong. It just might save your life. 


  1. Liao B, Zhao Y, Wang D, Zhang X, Hao X, Hu M. Nicotinamide mononucleotide supplementation enhances aerobic capacity in amateur runners: a randomized, double-blind study. Journal of the International Society of Sports Nutrition. 2021;18(1):54. doi:10.1186/s12970-021-00442-4 
  2. Yoshino J, Baur JA, Imai S ichiro. NAD+ intermediates: The biology and therapeutic potential of NMN and NR. Cell Metab. 2018;27(3):513-528. doi:10.1016/j.cmet.2017.11.002 
  3. Fang H, Shi X, Wan J, Zhong X. Role of sestrins in metabolic and aging-related diseases. Biogerontology. 2024;25(1):9-22. doi:10.1007/s10522-023-10053-y 
  4. Kazior Z, Willis SJ, Moberg M, et al. Endurance exercise enhances the effect of strength training on muscle fiber size and protein expression of akt and mtor. PLOS ONE. 2016;11(2):e0149082. doi:10.1371/journal.pone.0149082 
  5. Frederick DW, Loro E, Liu L, et al. Loss of NAD homeostasis leads to progressive and reversible degeneration of skeletal muscle. Cell Metab. 2016;24(2):269-282. doi:10.1016/j.cmet.2016.07.005 

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