Dietary Nucleotides in Sport Nutrition

Nutrition is becoming more and more important for everybody, this is especially true when we are considering professional sportsmen, but also normal people. They take care of their diet to improve performances or just increase their wellbeing.

Furthermore, with an accelerating pace of life and fierce social competition, fatigue has become a commonly occurring condition. It is wise looking for new nutritional solutions to limit physical exercise consequences and to struggle against fatigue. Actually, fatigue is a suboptimal health status and may be associated with various illnesses.

Physiological issues in athletes 

Repetitive and sustained physical labor results in fatigue, provoking systemic alterations, including endocrine, immune, and metabolic dysfunctions:

Immunity has been shown to be compromised in athletes, making them more susceptible to Upper Respiratory Tract Infections. Several studies have found salivary IgA to be decreased following bout of endurance exercise such as cycling, cross country skiing, running and swimming and also after shorter intense exercise (1, 2).

– Slight ischemia in the gut can damage mucosa and disrupt the mucosal barrier, resulting in increased permeability, and the resultant passage of pathogens, such as lipopolysaccharide, into the circulation (3,4).

Cortisol level increases and it stimulates hepatic glucose release. Key signal for cortisol secretion is blood glucose decrease. Cortisol is also triggering an inflammation process through aspecific immune system as, for example, neutrophils degranulation.

– The innate immune system can also induce secondary muscle damage via the generation of reactive oxygen species (ROS), further attenuating athletic performance (5, 6).

Excess of lactic acid is generated and accumulated in skeletal muscles, leading to muscle fatigue.

Dietary Nucleotides Benefits

Upper Respiratory Tract Infections

A study, published in 2007, showed a positive effect of dietary supplements including RNA nucleotides on some immune system parameters post strenuous, high-intensity exercise. Dietary nucleotides significantly increased post supplementation period Salivary IgA, that is the major effector for defence against micro-organism causing Upper Respiratory Tract Infection and salivary cortisol, that is triggering an inflammation process through aspecific immune system (7).

Muscle Damages & Faster Recovery

The effect on cortisol is confirmed also in another trial performed in US, where a dietary supplement with nucleotides, was tested on resistance exercise stress and recovery, involving 20 people. Blood samples analysis collected after 15 and 30 minutes of an Acute Heavy Resistance Exercise Protocol (AHREP) showed a lower cortisol level against the control. The authors speculate that this effect may be due to the ability of dietary nucleotides to increase hepatic glucose output. Acting in this way the signal for the cortisol release disappears or it is reduced with all the related side effects. Another outstanding output was related to a marker of the muscles tissue damage: Creatine Kinase (CK) was significantly lower 24 hours after AHREP.
A lower CK value in nucleotide group means that muscle tissue damage was at a lower rate. Evidence, of what above mentioned, was that nucleotide group showed a faster recovery managing to finish AHREP already 24 hours after the first session, while control group managed to carry out all the physical protocol only after 48 hours (8).

Time to Exhaustion

A double-blind, placebo-controlled, randomized trial was conducted to assess the effect of sublingual dietary nucleotides as compared to placebo, both administered for 14 days in 30 healthy young male participants. Time to exhaustion, as well as serum immunoglobulin A and Natural Killer Cells cytotoxic activity, were significantly higher at day 14 (p < 0.05) in participants supplemented with nucleotides compared with those who consumed placebo. Once again dietary nucleotides improved some immunological and exercise performance indices (9).

Oxidative Stress Biomakers

In a study, mice fed with dietary nucleotides, after 30 days of treatment, increased the forced swimming time, enhance Lactate DeHydrogenase activity and hepatic glycogen levels, as well as delay in the accumulation of Blood Urea Nitrogen and Blood Lactic Acid in mice. Nucleotides also markedly improved fatigue-induced alterations in oxidative stress biomarkers and antioxidant enzymes. The results suggested that nucleotides exert anti-fatigue effects, which may be attributed to the inhibition of oxidative stress and the improvement of mitochondrial function in skeletal muscles. (10)


In conclusion, dietary nucleotides exert these effects when used in sport nutrition:

–          Increasing Salivary IgA

–          Limiting the inflammation process:

o          Lower cortisol level

o          Lower Neutrophils activation

o          Lower Muscles damages

–          Faster recovery after performances

–          Ergogenic substances – Increase in time to exhaustion during running test

–          Anti-fatigue effect – Inhibition of oxidative stress and the improvement of mitochondrial             function in skeletal muscles (↑ ATP for energy supplementation)


Nucleotides are low-molecular-weight intracellular compounds that participate in numerous biochemical processes. They are composed of a nitrogenous base (pyrimidine or purine) linked to a pentose (ribose or deoxyribose) sugar to which one, two or three phosphate groups are attached.

De-novo synthesis does not satisfy the Nucleotides requirements of many tissues and particular life physiological phases, making necessary a reinforcement by dietary source. Particularly, some cells at high turn-over rate, such as gut, immune system and cerebral ones (lymphocytes, erythrocytes, bone marrow cells, glial cells) are not able to produce enough Nucleotides to cover their needs.

Functional Role of Nucleotides 

There is increasing evidence that dietary nucleotides may affect different aspects of body function and health in single-stomached animals, including:

  • Intestinal morphology and function
  • Immune response
  • Composition of the intestinal microbiota
  • Nervous system
  • Anti-fatigue effect


  1. Douglas DJ, Hanson PG. Upper respiratory infections in the conditioned athlete. Med Sci Sports Exerc 1978;10:55-60.
  2. Mackinon LT, Chick TW et al. Decreases secretory immunoglobulins following intense endurance exercise. Sports Training Med Rehabil 1989; 1:209-18
  3. Bosenberg AT, Brock-Utne JG et al. Strenuous exercise causes systemic endotoxemia. Journal of applied physiology 65: 106-108, 1988
  4. Lamprecht M and Frauwallner A. Exercise, intestinal barrier dysfunction a probiotic supplementation. Medicine and sport science 59: 47-56, 2012.
  5. Aoi W, Naito Y, et al. Oxidative stress and delayed-onset muscle damage after exercise. Free radical biology & medicine 37: 480-487, 2004
  6. Close GL, Ashton T, et al. The emerging role of free radicals in delayed onset muscle soreness and contraction-induced muscle injury. Comparative biochemistry and physiology Part A, Molecular & integrative physiology 142: 257-266, 2005
  7. Mc Naughton L, Bentley D et al. The effect 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 2007;47:112-8.
  8. Sterzcala AJ, DuPont WH et al. The Physiological Effects of Nucleotide Supplementation on Resistance
    Exercise Stress in Men and Women J of Strenght and Conditioning Research 2016;
  9. Ostojic SM, Idrizovic K et al. Sublingual Nucleotides Prolong Run Time to Exhaustion in Young Physically Active Men 2013; 5 4776-4785.
  10. Xu M, Liang R et al. Anti-fatigue effects of dietary nucleotides in mice. Food & Nutrition Research 2017 Vol 61

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