Nucleotides and their role in maintaining health

Nucleotides are the building blocks of every cell in the body. It is easy to see, therefore, that proper human development, the functioning of the immune and nervous systems (e.g., the creation of neurotransmitters), hormonal balance, and tissue regeneration all depend on their presence and availability in sufficient quantities. However, the role of nucleotides is not limited to being mere building blocks. They do much more—nucleotides improve tissue insulin sensitivity and participate in DNA repair processes, which is essential for preventing cancer and neurodegenerative diseases, as well as slowing down the aging process (which, in turn, promotes longevity).

What are nucleotides made of?

A nucleotide consists of a sugar – a pentose (deoxyribose in DNA and ribose in RNA), a phosphate group (at least one), and a nitrogenous base. Nitrogenous bases include adenine, guanine, cytosine, thymine (in the case of DNA), and uracil (in the case of RNA). Depending on which pentose is part of the nucleotide, we can distinguish between deoxyribonucleotides (when the sugar is deoxyribose) and ribonucleotides (when the sugar is ribose).

For example, adenosine triphosphate (ATP), the "energy currency" of cells, is a nucleotide consisting of three phosphate groups attached to ribose and adenine. Ribose and adenine alone form a compound called adenosine, and such a combination (a pentose with a nitrogenous base, without a phosphate group) is called a nucleoside.

What are the sources of nucleotides?

To a large extent, nucleotides are produced by the body itself, but they can be provided through diet or supplementation. In terms of food sources, the highest amounts of nucleotides are found in meat, fish, seafood, and legumes. Good sources also include mushrooms (e.g., oyster mushrooms which contain uridine, essential for building cell membranes in the nervous system and thus supporting brain function). To a lesser extent, you can obtain nucleotides by eating vegetables (e.g., lettuce, cabbage), grain products, eggs, or fruits (e.g., avocado). So, if you want to meet your body's demand for nucleotides, make sure to eat a varied and nutritious diet. Malnutrition (resulting from insufficient food intake or a poorly balanced diet, such as the typical "Western diet") will lead to a nucleotide deficiency and the associated consequences, such as susceptibility to infections.

However, there are situations where nucleotides must be supplied in larger quantities, and in such cases you should consider supplementing these compounds.

This occurs during:

• periods of rapid growth (e.g., infants, children);
• tissue regeneration (e.g., intestinal mucosa, post-surgery);
• infections, when the body requires building blocks for the intensive production of immune system cells.

Chronic stress or intense physical exercise also increase the body's demand for nucleotides, as these compounds are involved in energy metabolism (e.g., ATP, NAD+).

When should you supplement with nucleotides?

Supporting growth and immune system function

Infants and children have a particularly high demand for nucleotides due to their rapid growth and the maturation of their immune and digestive systems. Numerous studies have shown that nucleotides found in breast milk or infant formula influence the immune system by, among other things, increasing the population of B and T lymphocytes, antibodies (e.g., secretory IgA, IgG, IgM), and NK (Natural Killer) cells. In adults as well, particularly those who are ill, recovering from injuries, or experiencing chronic gastrointestinal issues, nucleotide supplementation improves health outcomes and the course of the disease.

The efficiency of the immune system depends not only on the availability of nutrients (malnutrition increases the risk of infection and worsens the course of disease) but also on the integrity of the intestinal barrier. It is well known that the intestines play a crucial role in the functioning of the immune system, partly due to the presence of cells associated with both acquired and innate immunity, as well as a diverse gut microbiota. Nucleotides can modulate the populations of microorganisms inhabiting our gut. In turn, the aforementioned regeneration of the intestinal epithelium is essential for maintaining immunity because, firstly, it acts as a defensive barrier against potentially harmful substances, and secondly, as the epithelium is shed, the body gets rid of potential pathogens that have managed to "attach" themselves to the intestinal walls.

Nucleotides and longevity

As science advances, we are learning more and more about how the body ages and how to slow down this process. Adulthood is associated with many characteristic diseases; for example, the risk of neurodegenerative conditions (such as Alzheimer's disease) and cancer increases. A healthy lifestyle and smart supplementation are allies in their prevention, helping to maintain both physical and mental fitness for as long as possible. We then speak of so-called healthspan, which means living a long life in good health, even in old age.

It turns out that in addition to a healthy lifestyle (i.e., one based on physical activity, not overeating, and a varied diet consisting mainly of plant-based products with the addition of fish), longevity is also influenced by increasing the amount of nicotinamide adenine dinucleotide in the body (NAD+, Nicotinamide adenine dinucleotide). NAD+ is involved in energy metabolism, detoxification and DNA repair processes, the neutralization of free radicals, and the efficiency of the immune system. Furthermore, the activity of sirtuins, which are proteins associated with longevity, depends to a large extent on NAD+ levels.

Given that NAD+ stores in the body decrease with age and during the course of numerous diseases (e.g., cancer, but also viral infections, such as COVID-19), it is necessary to provide this compound through supplementation or by changing harmful habits. Current scientific reports suggest that increasing NAD+ levels has a neuroprotective effect and may prevent age-related neurodegenerative processes, primarily due to its antioxidant potential. NAD+ regeneration is possible through methods such as caloric restriction or physical activity, which further emphasizes the role of lifestyle in building longevity and maintaining health even at an advanced age. Currently, scientists emphasize that in the context of longevity, supplementation with NAD+ precursors, such as nicotinamide mononucleotide (NMN, nicotinamide mononucleotide).

• Do you train? Consider nucleotide supplementation

Physical activity, much like caloric restriction, enhances NAD+ regeneration. Intense physical exertion (e.g., amateur or, especially, professional sports) increases the body's demand for energy and bioactive compounds. These compounds are needed not only to meet training demands but also to support tissue repair and antioxidant defense. The primary site of energy production is the mitochondria, which produce ATP, the so-called "cellular energy currency." For these organelles to function properly, they require NAD+, which not only participates in ATP production but also in antioxidant defense, i.e., neutralizing excess free radicals (a "side effect" of energy production). An excess of free radicals negatively affects mitochondrial function and, consequently, the entire cell, which can ultimately lead to reduced physical performance.

A study published in the journal Journal of the International Society of Sports Nutrition analyzed the effect of supplementation with an NAD+ precursor (NMN) on the physical performance of amateur runners. The participants were randomly divided into 4 groups; each received a different dose of NMN or a placebo. After 6 weeks of supplementation, it was observed that the group of runners receiving the medium and highest doses of NMN (600-1200 mg/day) significantly improved their aerobic capacity, which may be due to the positive effect of NAD+ on mitochondrial function.

Nucleotides and insulin resistance

Nucleotide supplementation can also be used to support the treatment of insulin resistance, as evidenced by the results of a study published in the journal Science. The study involved postmenopausal women struggling with overweight or obesity and prediabetes. For 10 weeks, they took 250 mg of NMN or a placebo daily. Supplementation with the NMN precursor significantly improved tissue insulin sensitivity to a degree comparable to that observed after a 10% reduction in body weight. Of course, supplementation alone does not mean we can ignore diet and physical activity in the treatment of insulin resistance, but it can undoubtedly be a valuable support in this regard.

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