Nucleotides can be described as the “building blocks” of human cells. It’s therefore easy to conclude that their presence (and adequate supply according to requirements) will have an important role in promoting normal human development, proper function of the immune, nervous (e.g. release of neurotransmitters) and hormonal systems or regular tissue regeneration. However, nucleotides are more than just simple “building blocks”. Their role is much wider: nucleotides improve insulin sensitivity in tissues and are involved in DNA repair mechanisms, which is important in preventing cancer or neurodegenerative diseases and slowing down the ageing processes (which contributes to a longer lifespan).
What is the structure of nucleotides?
Nucleotides consist of a sugar molecule – a pentose (either ribose in RNA or deoxyribose in DNA), a phosphate group (at least one) and a nitrogenous base. Nitrogenous bases (nucleobases) include adenine, guanine, cytosine and thymine (in DNA), and uracil (in RNA). Nucleotides can also be distinguished into two classes according to the type of pentose sugar: deoxyribonucleotides (contain deoxyribose) or ribonucleotides (contain ribose).
To give an example, adenosine triphosphate (ATP), often referred to as the “energy currency” of cells, is a nucleotide composed of three phosphate groups bound to ribose and adenine. These two molecules, ribose and adenine, make up adenosine and such a combination (a pentose plus a nitrogenous base, without a phosphate group) is called a nucleoside.
What are sources of nucleotides?
Nucleotides are mostly generated by the human body, but they can also be sourced from food or an additional intake of food supplements. The main food sources of nucleotides include meat, fish, seafood and legume seeds. Mushrooms are also known to be a good source of nucleotides (e.g. oyster mushroom contains uridine, which is essential to the structure of cell membranes in the nervous system, thus supporting brain functions). Other food products such as vegetables (e.g. lettuce, cabbage), cereal products, eggs or fruit (e.g. avocado) are less abundant in nucleotides. As a result, if you want to supply the required amount of nucleotides, make sure that you eat a varied and healthy diet. Malnutrition (due to insufficient food intake or a poorly balanced diet, e.g. a typical “Western diet”) leads to nucleotide deficiencies and their consequences, e.g. vulnerability to infections.
In some situations, however, nucleotides need to be supplied in greater amounts through supplementation.
These situations include:
- intense body growth (e.g. in infants, children);
- tissue regeneration (e.g. intestinal mucosal epithelium, following surgery);
- infections, when the human body needs building material to intensify the production of immune system cells.
Long-term stress or intense physical activity also stimulate the demand for nucleotides due to their participation in energy metabolism (e.g. ATP, NAD+).
When should you supplement nucleotides?
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Promoting growth and immune response
A greater demand for nucleotides is especially important in infants and children due to their rapid body growth and development of the immune and gastrointestinal systems. A number of research studies have shown that nucleotides contained in human breast milk or infant formulas support the immune system, e.g. by increasing the population of B and T cells, antibodies (e.g. secretory IgA, IgG, IgM) and natural killer (NK) cells. The supplementation of nucleotides also helps to improve health and reduce disease severity in adults, especially patients suffering from a disease, an injury or chronic gastrointestinal disorders.
The efficient function of the immune system requires not only the adequate supply of nutrients (malnutrition increases the risk of infections and worsens disease symptoms) but also a healthy intestinal barrier. It is well known that the human gut has a crucial role in the proper functioning of the immune system, which relies e.g. on the presence of cells associated both with acquired and innate immune response, as well as a diverse gut microbiota. Nucleotides can modulate the population of microorganisms residing in the human gut. On the other hand, the regeneration of the intestinal epithelium we mentioned earlier promotes optimum immune response because, first of all, epithelial cells provide a protective barrier against potentially harmful substances, and second of all, the removal of epithelial cells from the body helps to get rid of potential disease-causing pathogens which attach themselves to the intestinal wall.
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Nucleotides and longevity
As science progresses, we gain more knowledge about body ageing processes as well as remedies and solutions we might use to slow them down. An advanced age is associated with a number of characteristic diseases, e.g. there is a greater risk of neurodegenerative disorders (such as Alzheimer’s disease) or cancer diseases. A healthy lifestyle and reasonable supplementation are great allies in the prevention of these conditions, helping to keep both good physical fitness and mental health as long as possible. This is referred to as health span – a long healthy life, be it at a young or old age.
It seems that apart from a healthy lifestyle (which refers to a combination of physical activity, not eating to excess and following a varied diet of mostly fruit and vegetables plus fish), you also need to increase the supply of nicotinamide adenine dinucleotide (NAD+) to extend your lifespan and live longer. NAD+ is involved in energy metabolism, detoxification processes and DNA repair mechanisms, neutralization of free radicals and promoting the efficient function of the immune system. Additionally, the activity of sirtuins – proteins related to longevity – depends to a large extent on NAD+ levels.
The levels of NAD+ in the body decrease with age and in the course of many diseases (e.g. cancer or viral diseases such as COVID-19), and therefore it is necessary to compensate the reduced supply of NAD+ by means of supplementation or by breaking bad habits. The currently available scientific data suggest that improving the supply of NAD+ provides neuroprotective benefits and helps to prevent age-related neurodegenerative processes, mostly as a result of antioxidative potential. The regeneration of NAD+ is potentiated through e.g. calorie restriction or physical activity, which adds to the importance of a healthy lifestyle in the promotion of a longer lifespan and good health even at an advance age. Currently, scientists highlight that the supplementation of NAD+ precursors, e.g. nicotinamide mononucleotide (NMN), can also be relevant in terms of longevity.
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Do you work out? You may want to think about supplementing nucleotides!
Physical activity, similarly to calorie restriction, promotes NAD+ regeneration. Intense physical effort (e.g. practicing amateur or professional sports) increases the body’s requirements for energy and active biological ingredients which are required not only to meet workout needs, but also to boost tissue regeneration or stimulate antioxidative protection. Energy is produced mainly in the mitochondria. They produce ATP – the “energy currency of cells”. These organelles require NAD+ to function properly. NAD+ is involved both in the production of ATP and antioxidative protection – the neutralization of excess free radicals (which are a side effect to the production of energy). The excess of free radicals produces an adverse impact on mitochondrial functions and, as a result, on the entire cell, which in the end can undermine physical performance and fitness.
A study published in the Journal of the International Society of Sports Nutrition analyzed the effects of supplementation with NAD+ precursor (NMN) on the physical performance of amateur runners. The study participants were divided at random into 4 groups and each group received a different dose of NMN or placebo. Following 6 weeks of supplementation, it was found that the runners receiving a medium and high dose of NMN (600-1200 mg/day) showed significant improvement in their aerobic performance, which can be attributed to positive effects of NAD+ on mitochondrial function.
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Nucleotides and insulin resistance
Supplementation with nucleotides can also be used to support the treatment of insulin resistance, as evidenced by the results of a study published in Science. The study group included postmenopausal women affected by overweight or obesity and pre-diabetes. During a period of 10 weeks they were taking either a daily dose of 250 mg of NMN or placebo. The supplementation of NMN helped to improve significantly insulin sensitivity in tissues to the extent observed following a 10% reduction in body weight. Naturally, you should always keep in mind that even with supplementation, you must not give up a healthy diet and physical activity in the treatment of insulin resistance. However, supplementation can be considered a valuable add-on in this respect.
Bibliography:
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- Covarrubias AJ, Perrone R, Grozio A, Verdin E. NAD+ metabolism and its roles in cellular processes during ageing. Nat Rev Mol Cell Biol. 2021 Feb;22(2):119-141. doi: 10.1038/s41580-020-00313-x.
- Yoshino J, Baur JA, Imai SI. NAD+Intermediates: The Biology and Therapeutic Potential of NMN and NR. Cell Metab. 2018 Mar 6;27(3):513-528. doi: 10.1016/j.cmet.2017.11.002.
- Yadav SK, Ir R, Jeewon R, Doble M, Hyde KD, Kaliappan I, Jeyaraman R, Reddi RN, Krishnan J, Li M, Durairajan SSK. A Mechanistic Review on Medicinal Mushrooms-Derived Bioactive Compounds: Potential Mycotherapy Candidates for Alleviating Neurological Disorders. Planta Med. 2020 Nov;86(16):1161-1175. doi: 10.1055/a-1177-4834.
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