Importance of NAD for Muscle Function: Supplementation Implications for the Performance Cyclist

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Andy Shao

NAD could be a key to unlocking a considerable performance boost for competitive cyclists.

What is N-A-D?

N-A-D stands for nicotinamide adenine dinucleotide, an essential coenzyme present in every cell in the body. Sound familiar?

 

Well, it might, that is, IF you’ve ever taken an introductory biology class. Remember learning about aerobic respiration? Then you will recall how cells turn glucose into energy (or specifically ATP – adenosine triphosphate – the energy “currency” of every cell).  

 

In your bio textbook, you may also recall reading about the TCA cycle (a.k.a. Kreb’s cycle). The Krebs cycle relies on NAD to work correctly. It turns out that what you learned in basic biology about NAD plays an essential role in skeletal muscle (and indeed many other organs) health and function.  

 

It might also be a key to unlocking a considerable performance boost for competitive cyclists. Are you interested in learning more? Read on.

cartoon image of science textbooks

NAD is Critical for Converting Nutrients from Food into Energy

I already reminded you how NAD (and its counterparts – NADH, NADP, NADPH) act as a critical coenzyme when cells convert carbs, fat, and protein (macronutrients) into energy. Working primarily in your cells’ mitochondria (the thousands of tiny little “organelles” that serve as the engine of each cell), NAD helps turn the food you eat into the energy – ATP – you need to function.  

 

Without ATP, cells can’t function or survive. That in itself is a reason for athletes, including cyclists, to pay close attention to NAD since skeletal muscle is such an energy-demanding organ. Any disruption in this process could compromise performance. It is the case with some conditions, like sarcopenia, characterized by a rapid loss in skeletal muscle mass and function, commonly observed in older adults.

woman smiling

NAD is Crucial to Muscle Defense and Repair

But there is another critical role for NAD as a coenzyme in skeletal muscle cells that you should take note of – cell defense and repair. When stress damages cells, repair enzymes kick in to restore damaged DNA and proteins so cells can continue to function.  

 

The enzymes involved in the cell stress and repair response to damage “consume” NAD to perform their function. During “bouts” of metabolic stress (see the table for examples), the level and activity of these repair enzymes increase drastically, depleting cells’ NAD, potentially compromising energy metabolism, and leaving cells vulnerable to subsequent damage.

Examples of metabolic stress that deplete cells’ NAD:

NAD Depletion is Linked to Disease

Accumulation of damage over time from exposure to repeated “bouts” of metabolic stress compromises performance and accelerates aging. Metabolic stress and NAD depletion are linked to many age-related diseases and dysfunction, e.g., Alzheimer’s disease, heart failure, sarcopenia, fatty liver, etc.

 

Your skeletal muscle is a highly metabolically active tissue rich in mitochondria and heavily ATP-dependent. Like with other cells, damage activates NAD-dependent enzymes, and in the case of skeletal muscle cells, it controls inflammation and helps repair exercise-induced damage.  

 

So you might ask, “Can NAD depletion compromise skeletal muscle function?” Well, I already raised the extreme example of sarcopenia, but what about elite athletes? Elite cyclists?

rusted bike wheels hanging on a wall

Can Boosting NAD Enhance Performance?

Probably the more relevant question for this audience is, “Can a boost in NAD enhance the performance of elite cyclists?” Given NAD’s role in mitochondria and muscle function, it suggests that boosting NAD in conjunction with exercise training might improve the body’s response to exercise, which may lead to a performance benefit.

 

When it comes to demonstrating the impact of NAD boosting on athletic performance, the state of the science is still early on and emerging. Data from preclinical studies are fascinating, and results from early human clinical studies show promise, but results have been inconsistent thus far.

NAD Boosting Strategies:

Boosting the body’s NAD levels can be achieved with different approaches, including lifestyle modifications like moderate resistance exercise or intermittent fasting (a form of calorie restriction).

 

Some pharmaceuticals block the activity of NAD-consuming enzymes, but this also stops the repair mechanisms.  We can enhance NAD production through supplementation with NAD precursors.  

 

The precursors are found in the diet (or dietary supplements) as various forms of vitamin B3.  They include niacin (or nicotinic acid), nicotinamide (or niacinamide), nicotinamide riboside, nicotinamide mononucleotide, and even the amino acid tryptophan can serve as a NAD precursor.  

 

Most of us get enough of these in our diet to prevent B3 deficiency (known as pellagra). Still, to achieve the NAD boost needed to affect the conditions mentioned above or obtain a performance benefit, one needs to supplement with quantities that far exceed that typically received in the diet⁶.

The Studies are Promising But the Results Mixed

Studies in mice have shown a performance benefit from combining NAD boosting with exercise. However thusfar, most studies have examined the impact in older mice to answer questions about age-related performance decline.

 

For example, the combination of nicotinamide riboside (NR) supplementation + aerobic training improved muscle mitochondria function and aerobic capacity vs. training alone in mice¹. Another study demonstrated that NR supplementation improved endurance and activity level and reduced the decline in grip strength in older mice vs. placebo².

 

Results from published human clinical studies are mixed. NR supplementation improved cycling performance in older but not younger adults³. Acute (one week) NR supplementation did not improve the performance in a single cycling test compared to placebo in trained athletes⁴. Another study showed that nicotinamide mononucleotide (NMN) supplementation improved aerobic capacity vs. placebo in a small group of runners⁵.

NAD biosynthesis diagram

Conclusion—Boosting NAD is an Intriguing Possibility

So there you have it. It seems like an intriguing possibility that boosting NAD through supplementation with precursors might have a performance-enhancing effect. However, the jury is still out. At this point, whether there is a specific benefit for the elite cyclist is also unclear.  

 

We DO know that overtraining (repeated bouts of training without sufficient recovery in between, leading to performance decline) is a real problem for many athletes, including cyclists, and this, in turn, depletes muscle NAD. So stay tuned for more exciting findings!

image of periodic table of elements

Your Thoughts?

The jury may be out, but what is your initial impression of boosting NAD with forms of vitamin B3 supplementation and the potential performance benefits?  Comment below.  Your fellow virtual cyclists want to know.

References

1. Crisol, B. M. et al. NAD+ precursor increases aerobic performance in mice.  Eur J Nutr 59, 2427–2437 (2020).

2. Seldeen, K. L. et al. Short-term nicotinamide riboside treatment improves muscle quality and function in mice and increases cellular energetics and differentiating capacity of myogenic progenitors.  Nutrition 87, 111189 (2021).

3. Dolopikou, C. F. et al. Acute nicotinamide riboside supplementation improves redox homeostasis and exercise performance in old individuals: a double-blind cross-over study.  Eur J Nutr 59, 505–515 (2020).

4. Stocks, B. et al. Nicotinamide Riboside supplementation does not alter whole-body or skeletal muscle metabolic responses to a single bout of endurance exercise.  Biorxiv 2020.06.23.143446 (2020) doi:10.1101/2020.06.23.143446.

5. Liao, B. et al. Nicotinamide mononucleotide supplementation enhances aerobic capacity in amateur runners: a randomized, double-blind study.  J Int Soc Sport Nutr 18, 54 (2021).

6. Conze, D., Brenner, C. & Kruger, C. L. Safety and Metabolism of Long-term Administration of NIAGEN (Nicotinamide Riboside Chloride) in a Randomized, Double-Blind, Placebo-controlled Clinical Trial of Healthy Overweight Adults.  Sci Rep-uk 9, 9772 (2019).

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About the Author

Andrew Shao, Ph.D.

ChromaDex, Inc.

Sr VP, Global Regulatory & Scientific Affairs

https://www.linkedin.com/in/andrew-shao-phd/ 

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