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Why Nucleotides?


Exercise can be hard on your body.  However, the stress of exercise is also responsible for initiating many beneficial reactions.

Training involves subjecting your body to conditions it has not experienced before in order to provoke an adaptation. The greater the stress, the greater the adaptation. You get stronger in response to lifting heavier loads than you have previously. The limitation has always been the ability of your body to recover from this stress.

New research suggests that adding nucleotides to your diet mitigates some of the harm from that stress, boosting performance and allowing you to train harder.



Nucleotides are small molecules essential to nearly all biological processes. Nucleotides form the backbone of DNA and RNA, participate in coenzyme synthesis, cellular signaling, protein homeostasis and critically for athletes, the nucleotide adenosine is a constituent of ATP, the energy storage molecule.

Nucleotides have three components: a sugar (either ribose or deoxyribose), a phosphate group and an nitrogen-containing base (either adenine, cytosine, guanine, thymine or uracil).

The body constantly produces nucleotides, however, under certain conditions including stress and rapid growth, the body uses external sources of nucleotides from the diet to supplement its own production. These nucleotides, incorporated through salvage pathways, enable the body to maintain immune function, tissue growth, and cellular repair at levels higher than would otherwise be the case.



While nucleotides are critical to normal biological activity, they are also synthesized relatively easily within the body. Because there is no acute deficiency syndrome associated with the lack of nucleotides in your diet, their important nutritional role was overlooked for ages. However, research over the last twenty-five years has shown that under certain stressful conditions, dietary sources of nucleotides do indeed play a significant role and they are now considered conditionally essential nutrients.

An early clue to the importance of nucleotides in the diet came from the observation of transplant recipients, whose immune systems were suppressed to avoid rejection of the transplanted tissue. During the initial recovery period, patients received a nucleotide-free diet because they were consuming only parenteral (ie, intravenous) nutrition. As their recovery progressed and they were shifted to a normal diet, which included nucleotide sources, their immune systems surged.

Subsequent research in both humans and animals demonstrated that the effects of stress, such as malnutrition or injury, lead to limitations on the body’s own production of nucleotides, which could be remedied with the introduction of nucleotides into the diet. The availability of nucleotides (and their constituents via salvage pathways) facilitates a number of biologic processes including strengthening the immune system.

Since that time, nutritional products have been developed utilizing nucleotides designed to enhance the body’s immune system function. These so called immune-enhancing diets are recommended in numerous clinical settings where they are credited with reducing the rate of hospital-acquired infections among other benefits.



Another clue to the story of nucleotides’ dietary role came from the observation that breast milk is relatively high in nucleotides, while cow’s milk has much lower levels and milk substitutes (eg, soy “milk”) have virtually none.

Starting in the mid-1990s the producers of infant formula began research programs to investigate the question why this metabolically expensive molecule was present in breast milk. The answer, as confirmed over dozens of studies, was that nucleotides in the infant diet play a role in the maturation of the immune system, as well as contributing to a lower incidence of diarrhea.

To better mimic the composition of breast milk, the formula makers have all supplemented their products with nucleotides since the late 1990s.



The recognition that dietary nucleotides play a role in modulating the immune system suggested the possibility that they might have positive effects on the recovery of athletes. The immune system plays a central role in the process of rebuilding following the stress of exercise. 

Exercise is a stressful and damaging stimulus, significantly increasing demands on the immune system and temporarily attenuating immune cell function. Consequently, there has been a growing interest in the implications of dietary nucleotide supplementation on exercise-induced immune responses.

The first investigation of this question was done ten years ago by McNaughton using an endurance exercise model where the test subjects were on stationary bicycles for 90 minutes. As expected, athletes taking a nucleotide supplement had higher levels of immune system function and lower levels of stress response, (specifically higher levels of salivary immunoglobulin and lower levels of cortisol).

A follow up investigation by Ostojic shifted the exercise model to running, where subjects ran on an accelerating treadmill until exhaustion (usually less than 10 minutes)8,9. The results here confirmed the findings of McNaughton and also demonstrated a performance benefit, extending the run time to exhaustion for the athletes taking the nucleotide supplement.


Building upon this work, the Kraemer study modified the exercise model to include resistance exercise, where the athletes completed 60 heavily loaded barbell squats in a constrained time period. Those athletes taking a nucleotide supplement showed approximately one-third lower levels of stress and inflammatory response with significantly lower measurements of tissue degradation the following day (where stress was measured by cortisol, inflammation by myeloperoxidase and tissue damage by creatine kinase).


Athletes in this study also realized a major performance benefit. Those taking the nucleotide supplement showed 41% higher isometric force production immediately after exercise in comparison to the control group and it took three days for the control athletes to catch up in their recovery and match the performance of the athletes taking nucleotides.



While this is interesting, what steps can people take to benefit from these facts?

The best natural sources of nucleotides in the diet are nutritionally dense foods such as organ meats and whole fish. Those who are familiar with the diets recommended for gout will recognize these foods as those that have high levels of purines (nucleotides are classed as either purines or pyrimidines, depending on the nitrogenous base they contain).

These foods have become less common in the average American diet over the course of time. In the 19th century when most people lived on farms, organ meats were a regular part of every cuisine; liver, kidneys, tripe and brains were normal fare. Liver and onions was a menu staple in the mid-20th century. Since that time, changing tastes and changing availability have resulted in the almost complete disappearance of these foodstuffs, except for certain ethnic specialties.

Much like infants have been found to benefit from the addition of nucleotides to formula, there is an emerging case that athletes could similarly benefit. There are some striking parallels between infants and athletes: both are growing rapidly and both are under great stress.  Athletes subject their bodies to the stress of training in order to produce adaptations, such as strengthened muscles and vascular systems. Infants, with their immature immune systems, are in a race to gain weight and strengthen their physical frames.

The alternatives available are to increase the consumption of foods rich in nucleotides or add a nucleotide supplement to your diet. nuBound is the first commercially available, nucleotide supplement designed to meet the needs of athletes.



1)    Sterczala, AJ, DuPont, WH, Comstock, BA, Flanagan, SD, Szivak, TK, Hooper, DR, Kupchak, BR, Lee, EC, Volek, JS, Maresh, CM and Kraemer, WJ. Physiological effects of nucleotide supplementation on resistance exercise stress in men and women. J Strength Cond Res 30: 569-578, 2016.

2)    Carver, JD and Walker, WA. The role of nucleotides in human nutrition. Nutr Biochem 2: 58-72, 1995.

3)    Kulkarni, AD, Rudolph, FB and Van Buren, CT. The role of dietary nucleotides in immune function: a review. Jour Nutr 124: 1442S-1446S, 1994.

4)    Hess, JR and Greenberg, NA. The role of nucleotides in the immune and gastrointestinal systems: potential clinical applications. Nutr Clin Practice 27:2 281-294, 2012.

5)    Schaller, JP, Kuchan, MJ, Thomas, DL, Cordle, CT, Winship, TR, Buck, RH, Baggs, GE, and Wheeler, JG. Effect of ribonucleotides on infant immune status, part 1: humoral responses and part 2: immune cell development. Pediatric Res 56:6 883-900, 2004.

6)    McNaughton, L, Bentley, D and Koeppel, P, The effects of a nucleotide supplement on the immune and metabolic response to short term, high intensity exercise performance in trained male subjects. J Sports Med Phys Fitness 46: 112-118, 2007.

7)    McNaughton, L, Bentley, D and Koeppel, P, The effects of a nucleotide supplement on salivary IgA and cortisol after moderate endurance exercise. J Sports Med Phys Fitness 46: 84-89, 2006.

8)    Ostojic, SM, Idrizovic, K and Stojanovic, MD. Sublingual nucleotides prolong run time to exhaustion in young physically active men. Nutrients 5: 4776-4785, 2013.

9)    Ostojic, SM and Obrenovic, M. Sublingual nucleotides and immune response to exercise. J Int Soc Sports Nutr 9: 31, 2012.