There are many health benefits to taking a nucleotide supplement, but the boost to the immune system is probably the best-documented effect. The scientific community now agrees that nucleotides are necessary for a healthy immune system and that they support normal T-cell development, specifically the development of helper T cells.

Nucleotides are organic molecules consisting of a nucleic base bound to a five-carbon sugar, and one to three phosphate groups. Nucleotides are the building blocks of nucleic acids, like DNA and RNA. DNA is a long polymer of nucleotides with deoxyribose sugar rings. It stores all the genetic information, the specific sequence of the nucleotides codes for the sequence of amino acids in all the proteins in the body. The DNA molecules are extremely long, each chromosome in a cell’s nucleus contains one long DNA molecule. RNA generally contains shorter chains of nucleotides, and they contain ribose sugar rather than deoxyribose. Different forms of RNA play a vital role in transferring the genetic information from the nucleus to the cytoplasm and in protein synthesis. In fact ribosomes, the organelles where protein synthesis takes place are in part of ribosomal RNA.

Because of their roles in storing genetic information and in protein synthesis, nucleotides are essential to support proliferation of tissues with a high turnover rate. Every time a cell divides, all the DNA contained in its nucleus must be replicated to pass the genetic information to daughter cells. Because of this it is not surprising that nucleotides boost the immune system, which depends on being able to expand its population of cells rapidly when it is challenged by pathogenic microbes. In addition nucleotides have other roles. Adenosine triphosphate gives rise to cyclic adenosine monophosphate (cAMP) a second messenger which plays an essential part in relaying the signals of extracellular signaling molecules, such as hormones, to the inside of the cell and even the nucleus.

The human immune system depends on a complex interplay of many cells and signaling pathways. To work well it must be able to respond quickly to invading pathogens, while at the same time recognizing the body’s own tissues and not attacking them. Roughly it can be divided into two types. Innate immunity consists of cells such as macrophages, monocytes, and killer T cells which attack micro-organisms directly. On the other hand, acquired immunity depends on immune cells such as lymphocytes, which become sensitized against a particular disease and produce antibodies to fight it. The lymphocyte system has a ‘memory’, once it encounters a challenge, it remembers it and is prepared to fight it when it encounters it again. Acquired immunity is the reason we only suffer from diseases such as measles once, and why inoculations work.

The evidence is very strong that taking nucleotide supplements strengthens the acquired immune system. Many studies show that dietary nucleotides lead to higher levels of antibodies. For example in one study on athletes, the volunteers were divided into two groups, one group was given a nucleotide supplement for 14 days. At the end of the trial the group taking supplementary nucleotides showed significantly higher levels of immune system markers such as higher serum immunoglobulin A (IgA) levels, higher natural killer cell counts, and bacteria toxic activities. The volunteers taking dietary nucleotides also had higher levels of secretory IgA in their saliva. These results were confirmed by other studies. For example in a trial conducted by a team from Hull University, fourteen male volunteers were divided into two groups, one given supplementary nucleotides while the second one was given a placebo. The trial lasted sixty days and studied how the effect of endurance exercise on the immune response is modulated. At the end of the study period both groups undertook a session of endurance cycling, and the level of secretory immunoglobulin A antibodies (sIgA) in their saliva were tested. Although exercise naturally dampens the immune response, the levels of secretory IgA in the saliva of volunteers taking supplementary nucleotides was significantly higher than in the placebo group.

These, and other studies, show that dietary nucleotides are necessary for optimal levels of antibodies, both in the serum and in saliva, and in the blood serum. Nucleotides also appear to be necessary for natural killer T cells and for their cytotoxic activities. Animal studies show that when diet lack nucleotides the animals show much lower proliferation of lymphocytes in response to T cell specific mitogens such as photohaemglutinnin. However, they show normal responses to B cell specific mitogens such as lipopolysaccharides. Scientists have therefore concluded that nucleotides are necessary for the proliferation and function of T lymphocytes. The nucleotide-deprived animals also showed a lack of increase in the markers of helper T cells when their immune system was challenged, leading scientists to conclude that dietary nucleotides are necessary to support normal T cell manufacture. It is interesting to note that the effects can be reversed when adding uracil to the diet, suggesting that it is pyrimidines that are particularly important for this function.

Helper T cells are a type of lymphocyte, the main type of immune cells found in lymph. Unlike B cells they do not produce antibodies, and unlike natural killer cells, the third type of lymphocyte, they don’t directly kill pathogens. Instead helper T cells control the other immune cells by secreting powerful chemicals known as cytokines. Cytokines, such as interleukin 2, activate other cells causing them to proliferate, and secrete antibodies in the case of B lymphocytes. The cytokines also stimulate cytotoxic action of natural killer cells. To understand how important T lymphocytes are for the immune response, just consider that the HIV virus specifically infects these cells. All the symptoms of AIDs are down to the lack of helper T cell activity.

T cells develop in the thymus gland (which is where they get their name from). Mature cells leave the gland and travel throughout the body, many of them ending up in the lymph nodes. Helper T cells can be distinguished because they express the CD4 glycoprotein marker in their membranes. The cells become activated by specialized antigen presenting cells (APCs). APC cells engulf bacteria, viruses, or other foreign particles by endocytosis, process them, and then travel to the lymph nodes and present peptides from these microbes in their membranes. If an APC encounters a helper T cell that is sensitized to that particular antigen, two independent signaling cascades are set off which turn the cell into a memory T cell. The lymphocyte ‘remembers’ the foreign antigen it encountered, and If it encounters it again, it will secrete chemical signals that activate other parts of the immune system against the infection. Once it is activated the helper T cell releases interleukin 2, a growth factor which will act on it to cause it to proliferate. Studies show that dietary nucleotides are essential for the production of interleukin-2, and therefore essential for helper T cell proliferation.

Supplementary nucleotides will also, of course, support the rapid proliferation of T cells. To divide a cell must first copy all the DNA in its chromosomes. The DNA contained in each nucleus of a human cell consists of three billion nucleotides, and this is the amount of nucleotide molecules that are used up in each cell division just to ensure that the daughter cells receive their full genetic information.

After many rounds of cell division the cells will stop dividing and they will start differentiating. Helper T cells give rise to three different types of mature lymphocytes, effector Th cells, memory Th cells and regulatory Th cells. The effector cells are responsible for secreting signals that stimulate other parts of the immune system. They cause other lymphocytes, macrophages and monocytes to proliferate and carry out their actions. Memory cells ‘remember the exposure to the antigen’, they remain in the circulation, and start the whole process again if re-infection happens. Because they are already present, the immune system can respond much faster to a repeat infection, and can kill of the pathogens before any symptoms develop. This is why it is possible to experience diseases only once. Regulatory cells have a dampening effect on the immune response, they limit the scope of the response and protect against autoimmune disease.

Nucleotides supplements play a crucial role in boosting your ability to resist diseases. They work by enhancing the proliferation and activity of the cells that control the other aspects of the immune system, since they support the normal helper T cell manufacture. Helper T cells in their turn enhance antibody production by B lymphocytes, and the actions of the cells of the innate immune system such as macrophages. All this adds up to an enhanced resistance to cold and flu infections as well as a better ability to resist more serious microbes.

Further Reading:

A review of the role of nucleotides in the immune system:

The effect of nucleotides on cellular immunity and antibody production:

Image Attribution:

The chemical structure of purine and pyrimidine nucleotides is by Boris and is in the public domain.

The basic structure of an immunoglobulin molecule is by Y-Tambe’s and is used here under the Creative Commons Attribution-Share Alike 3.0 (CC-BY-SA-3.0) licence.

The scanning electron micrograph of a human T lymphocyte is by NIAID and is in the public domain.