Prosol has been reported on Nutrition Insight about the use of dietary nucleotides for sports nutrition.

“The sports nutrition market is persevering despite the effects of COVID-19, with ingredient producer Prosol highlighting the role of dietary nucleotides in fighting fatigue, which can weaken the immune system.

Prosol notes that due to the accelerating pace of life and fierce social competition, fatigue has become a commonly occurring condition. However, fatigue is a suboptimal health status and may be associated with various illnesses. The Italy-based company details that repetitive and sustained physical labor results in fatigue, provoking systemic alterations, including endocrine, immune and metabolic dysfunctions.

Prosol also notes that several studies have found salivary immunoglobulin A (IgA) – an antibody that plays a role in mucosal immunity – to decrease following a bout of endurance exercise, such as cycling, cross country skiing, running and swimming, and also after shorter intense exercise.

However, Prosol states that dietary nucleotides, which are low-molecular-weight intracellular compounds, can help address many of these issues in sports nutrition by increasing salivary IgA and leading to faster recovery after performances. Additionally, the nucleotides can limit the inflammation process by lowering cortisol levels, neutrophils activation and muscle damage. An anti-fatigue effect can also be seen, with dietary nucleotides inhibiting oxidative stress and improving mitochondrial function in skeletal muscles.

Nucleotides participate in various biochemical processes and 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.

According to Prosol, some cells with a high turn-over rate – such as those related to the brain, gut and immunity – are not able to produce enough nucleotides to cover their needs. Therefore, dietary nucleotides may be able to aid intestinal morphology and function, composition of intestinal microbiota, immune response, nervous system, as well as having the aforementioned anti-fatigue effect.”

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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.

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.

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 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.

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

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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.
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   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