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August, 2021

A unique source of nucleotides

We found a product with an unique source of the four semi-essential nucleotides Adenine, Cytosine, Guanine and Uracil. ImmuCell is a safe and natural product derived from Saccharomyces Cerevisiae yeast. The product has a high degree of purity, namely 60% nucleotides. Nucleotides have been used for years to strengthen the immune system and intestinal function. Nucleotides are the building blocks of DNA.

The construction of DNA

DNA (deoxyribonucleic acid) is the building block of all life. Simple bacteria have a limited genetic code and a limited number of genes. More complex organisms have many thousands of genes and a large genetic code. The genetic code of humans and every other organism is encoded in the structure of the DNA. Man has about 20,000 hereditary characteristics. We distinguish between eukaryotes and prokaryotes. The biggest difference between eukaryotes and prokaryotes is having a cell nucleus. Prokaryotes have a cell construction in which the DNA is not enclosed by a nuclear membrane, but lies freely in the cytoplasm. Other cell organelles are also lacking here. Eukaryotes are all organisms of which each cell contains a nucleus. In addition to a nucleus in which the DNA is located, most eukaryotic cells also have other organelles. These are the mitochondria and a golgi apparatus. In addition, prokaryotes often have fewer organelles than eukaryotes and are less complicated.

Nucleotides are the building blocks from which DNA and RNA are constructed

DNA and RNA are built up from these building blocks, and these are the nucleotides. The hereditary information is contained in the nucleotide sequence. Since there are an incredible number of possible combinations, each combination provides unique hereditary information. A nucleotide consists of a nitrogen base, a sugar group and one or more phosphate groups. There are five nitrogen bases that can occur in DNA and RNA. These are Adenine (A), Cytosine (C), Guanine (G), Thymine (T) and Uracil (U). In the DNA, however, only Adenine, Cytosine, Guanine and Thymine are present. The RNA does not contain the nitrogen base Thymine, but does contain the Uracil. The nitrogen bases are connected to a carbon atom of a sugar group (BiNaS71A). In DNA the sugar group present is Deoxyribose and in RNA the sugar group is Ribose. Both sugar groups are formed from four carbon atoms and one oxygen atom.

The difference between Deoxyribose and Ribose is that the Ribose molecule has an OH-group attached to the second carbon atom. Deoxyribose only has an H-atom attached to the second carbon atom (BiNaS 67H). The phosphate group is attached to the fifth carbon atom of the sugar group. This then binds to the third carbon atom of the sugar group of the previous nucleotide. Thus the chain is built that is the backbone of the DNA.

DNA and RNA form a strand with an opposite strand of nucleotides

The DNA and RNA form a strand with an opposite strand of nucleotides. This occurs through hydrogen bonds formed between the nitrogen bases. Cytosine (C), and Guanine always bind with each other in the DNA and RNA. Whereas in DNA, the hydrogen bonds are formed between Adenine (A) and Thymine (T). In the RNA, however, Adenine (A) binds with Uracil (U).

A DNA molecule consists of a double helix formed by two long strands of nucleotides

A DNA molecule consists of a double helix formed from two long strands of nucleotides. These nucleotides bind to each other via hydrogen bonds. The construction of DNA is much more extensive, but we will limit ourselves to this part in this article. With the final remark that DNA (the whole genome) is in every cell of our body. Research shows that we can consider nucleotides to be essential nutrients. This is because rapidly growing tissues, such as the intestinal epithelium and lymphoid cells, do not have a significant capacity for the Novo synthesis of nucleotides. These tissues require exogenous sources of purine and pyrimidine bases.

Nucleotides are important for normal development, cell renewal, maturation and repair of cells of the gastrointestinal tract and immunity, among others. Each time a cell divides, billions of nucleotides are needed to reproduce the DNA. We also consume nucleotides when our bodies produce proteins. Therefore, nucleotides in the diet or from supplements are essential. The unique product provides all the nucleotides needed for DNA reproduction, cell proliferation and tissue renewal. To keep the immunity and the gastrointestinal system healthy, nucleotides are needed. A well-functioning immune system keeps you healthy and prevents infections and diseases. While a healthy gut and its microbiome is extremely important for a perfectly functioning immune system.

To keep the immunity and the gastrointestinal tract healthy, nucleotides are also needed. Our immunity is an ingenious but also very complicated system. It recognizes bacteria, viruses, toxic substances, cancer cells and danger and then eliminates them. Scientific researchers have still not penetrated to the core of how our immune system works exactly. Much research is still going on, especially regarding certain diseases that are caused by an improperly functioning immune system. What is now clear is that our immune system and gastrointestinal system must be absolutely healthy. And Immucell helps with that like no other.

Many diseases and complaints caused by a failing immune system

Many diseases and complaints are caused by an overburdened and/or failing immune system. This may be due to genetic transfer, which has led to chronic deficiencies in the main and sub-classes of the immune cells. But also because the many different types of cells involved in the defensive action of the immune system can no longer develop or regenerate properly. The cause lies mainly in wrong nutrition, excessive stress, too much physical training, medicine use and an unhealthy lifestyle. These demanding conditions, the cell renewal of the immune system and the gastrointestinal system requires nucleotides. But nucleotides an also be used in cases of cognitive problems. As stated earlier, the unique product Immucell supplies the nucleotides that are necessary for, among other things, cell regeneration. Supplementation with nucleotides is a fast and safe way to meet this increased need for nucleotides.

The immune system plays an important role in the communication between the barrier and immune cells

The immune system plays an important role in the communication between the barriers of the intestinal mucosa and the immune cells of both the adaptive system and the innate system. The intestinal mucosa is the first barrier of the immune system. Keeping the immunity and the first barrier of the immune system intact is therefore of great importance.

The immune system has three systems, namely:

  • First-line immune system: Primarily counteracts the penetration of bacteria, viruses and fungi. The skin, the mucous membranes of the airways and intestines, as well as all bodily orifices such as the mouth, play a major role in this. Approximately 80% of the immune system's defence takes place in the mucous membranes. That is why a healthy mucous membrane barrier is of great importance. ImmuCell is ideally suited to this.
  • Second-line or innate immune system: This system is acquired immediately after birth and its function is determined by DNA. It focuses on general defence and on all pathogens present in the body. It consists mainly of white blood cells, but has no memory. ImmuCell also supports the innate immune system.
  • Adaptive immune system: Is the acquired system that we develop in the course of our lives. It does this by coming into contact with various pathogens, so that antibodies are formed against them in the body. Therefore, too much hygiene for a child is not always advisable. Let children play in the mud or sand! This is particularly good for the development of a good adaptive immune system. A good adaptive immune system targets specific pathogens and therefore has a memory. Through experienced infections, the immunity will be trained against the same pathogen and will immediately have the right defence.

Stress and the immune system

The immune system will be activated by the sympathetic nervous system during acute stress. So that it is prepared for possible injuries and infections that may occur during a (physical) fight or flight situation. Acute stress mainly activates the innate immune system, which is responsible for the acute phase inflammatory response. The consequence of constant stress is therefore that the immune system is constantly "on". An immunity that is constantly "on" hardly has time for cell renewal. That is why support with nucleotides is so important! Children often grow up with "Early Life Stress", too much stress in their young lives. Research has shown that "Early Life Stress" develops diseases and complaints later on. These are mainly due to an overloaded, derailed immune system and an unhealthy gut microbiome. Stress reduction is therefore an important part of improving the immune system. It is advisable to support stress reduction with nucleotide supplements. So that the cells of the intestinal wall and the immunity can renew themselves. Also, supplementation of nucleotides improved the immune response markers in response to strenuous exercise in cold conditions.

Breast milk is the best source of nucleotides

Dietary nucleotides are mainly ingested as nucleoproteins. Nucleoproteins are compounds of nucleic acid (DNA or RNA) with proteins. Nucleoproteins include chromatin, consisting of DNA and RNA, histones and acidic proteins; ribosomes, consisting of RNA and some proteins. Mushrooms, yeast extract and organ meats also contain nucleotides. However, mother's milk is the best source of nucleotides. That is why it is so important for young infants to be breastfed for a long time. Research also shows that when the baby is not breastfed, it is best to enrich the formula with nucleotides. This is because cow's milk contains far too few nucleotides. The enrichment of formula and imitation of breast milk has the advantage of providing substrates for maximum intestinal development and repair (J. Nutr. 124:1436S - 1441S, 1994).

The digestion of nucleoproteins

The digestion of nucleoproteins is initiated by proteases. Nucleic acids undergo partial hydrolysis in the stomach. They are then subjected to pancreatic nucleases and phospho-esterase to obtain nucleotides and produce nucleosides. Most DNA and RNA are fully hydrolysed to nucleotides in the gut. Alkaline phosphatases in the enterocyte cleave the phosphate groups in nucleotides to form nucleosides. Nucleosidases will release the sugar moiety, releasing the free N-bases (Lehninger1982, Quan et al 1990, Uauy 1989). Figure 1 illustrates the digestion of nucleoproteins and the absorption of nucleotides. The evidence suggests that a mixture of nucleosides and N-bases are presented to the enterocyte for absorption.

Figure 1: Digestion of nucleoprotein and absorption of nucleotides

A transport study using evolved intestinal sacs and isolated perfused loops have demonstrated a highly efficient Na+ dependent active transport system for nucleosides. More than 90% of ingested nucleotides are absorbed. Only 5% is absorbed in the form of intestinal nucleic acids and a relatively small amount is found in liver cells. (Jarvis 1989, Saviano and Clifford 1978). Most of the absorbed purines are broken down into uric acid in the intestine. The intestine not only harbours considerable quantities of N-bases and nucleosides, but also oxidises the excess purines to form uric acid. (mcGilvery 1983) This research indicates that nucleotide supplementation is very effective and that nucleotides are indeed absorbed.

Scientific research on nucleotide supplementation

Diets supplemented with nucleotides Adenine, Cytosine, Guanine and Uracil, have been shown to increase the concentration of immunoglobulin (Navarro et al., 1996). Dietary supplementation of purified nucleotides to milk replacers feeding newborn bull calves exposed to lipopolysaccharide (LPS) led to higher mean IGG levels in the supplemented calves compared to the calves without supplementation (Oliver et al., 2003). Nucleotide supplementation also increased lymphocyte stimulation of phytohaemagglutinin and concanavalin-A in weanling piglets by 50% and 30%, respectively (Zomborsky-Kovacs et al., 1998). Similar results have been observed for challenges by keyhole limpet haemocyanin (KLH). But also for non-specific T-cell mitogens in piglets fed with yeast RNA (Cameron et al., 2001).

Pigs with pathogenic E. coli infection were fed a diet supplemented with Nupro TM, a yeast extract, as a source of nucleotides. The pigs had less diarrhoea and improved weight gain and feed conversion. This compared to pigs fed the control diet without Nupro TM. (Maribo, 2003). It has also been shown that piglets fed a nucleotide enriched diet favourably affect the healing of Ulcerative Ileitis and the associated small ulcers in the intestine. The results of these studies imply that dietary sources of nucleotides play a role in the development, maintenance and improvement of the immune and gastrointestinal systems.

Dietary nucleotides enhance intestinal absorption of iron

Dietary nucleotides improve the intestinal absorption of iron, influence the metabolism of lipoproteins and polyunsaturated fatty acids, have trophic effects on the intestinal mucosa and liver and reduce the incidence of diarrhoea (Cosgrove, 1998; Schlimme et al., 2000). The faecal flora of infants fed a commercial milk formula containing nucleotides had a predominance of bifidobacteria (Tanaka and Mutai, 1980). In the control group, enterobacteria predominated in the faecal flora of infants fed a commercial diet without nucleotide supplementation (Uauy, 1994). Nucleotides modify the type and growth of the intestinal microflora. In vitro experiments have shown that addition of nucleotides to a minimal culture of bifidobacteria promotes their growth (Tanaka and Mutai 1980). These studies suggest that nucleotide supplementation may positively influence the microflora in the gastrointestinal tract, leading to a lowering of the gastric pH and inhibiting the proliferation of pathogenic bacterial species, as indicated by a lower rate of diarrhoea (Yu, 1998).

Nucleotide supplementation increased bacterial resistance

Nucleotide supplementation increased the bacterial resistance of mice inoculated with Candida albicans (Fanslow et al., 1988) and Staphylococcus aureus (Kulkarni et al., 1986; Carver, 1994). Intraperitoneal administration of nucleotides and nucleosides reduced bacterial translocation, the number of colony-forming units, and increased survival of mice against methicillin-resistant S. aureus (Yamamoto et al., 1997). Therefore, nucleotides are capable of increasing resistance to a wide range of potentially pathogenic bacteria. Dietary nucleotides from yeast extract, added to calf milk replacers, improved gut health. This is evidenced by better faecal scores compared to the non-supplemented control group (Oliver et al., 2002).

In piglets, nucleotides at concentrations comparable to those in human milk have a protective effect in the intestinal lumen against an inflammatory response to ischaemia-reperfusion (Bustamante et al., 1994). In a study with weanling rats fed either a purified diet without nucleotides or the same diet supplemented isocalorically with 0.8% nucleotides for a period of two weeks. The villus (height), crypt (depth), total protein and DNA content of the proximal intestine was higher in young animals fed the nucleotide supplemented diet compared to young animals fed the nucleotide free purified diet. The maltase-specific activity in the mucosa of the entire intestine was also higher in the supplemented animals, but the lactase and sucrase activities were minimally affected (Uauy et al. 1990).

Figure 2: Healthy Villi and Crypts and affected Villi and Crypts

The effects were more pronounced in the duodenum and proximal jejunum. Similar studies with electron microscopy show increased villus density and deeper crypts, during nucleotide supplementation. This has a good influence on the restoration of Tight-Junctions in the gut.

Conclusion

Scientific research proves that the addition of nucleotides has a beneficial effect on our immunity, the gastrointestinal system and its microbiome. Therefore, nucleotides can be used in Leaky-gut syndrome, Celiac disease, Crohn's disease, Colitis Ulcerosa, diverticulosis/diverticulitis, malabsorption and post-operative recovery. Nucleotide supplementation is very beneficial during radiotherapy and/or chemotherapy, as these treatments destroy the microbiome. Nucleotide supplementation may also have a beneficial effect during cancer development or prevention because nucleotide deficiency increases the number of genome mutations in early developmental stages of cancer. Chromosomal instability, caused by stress on DNA replication, may also be seen in the same early stages. In addition, nucleotides can not only alleviate replication stress, but also DNA damage and the transformation dramatically reduced by cancer. We therefore emphasise again what nucleotide supplementation can do for us and how important the prevention of stress is.

For infants not receiving breast milk, nucleotide supplementation in formula is recommended

For infants who are not fed breast milk, it is advisable to add nucleotides to the formula to allow the intestines and the microbiome to develop optimally. The addition of nucleotides can therefore be considered for many diseases and physical complaints. In addition to the above-mentioned physical complaints, one can think of autoimmune diseases, CFS, MS, Alzheimer's and dementia. But also obesity, diabetes, eczema, psoriasis, leukopenia, ADHD/ADD, autistic spectrum and many psychological disorders. However, the applications are much broader.

Wherever a leaky gut and a failing immune system cause any illness or complaint, it has been scientifically proven that nucleotide supplementation thus optimises health. Nucleotide supplementation also has a beneficial effect in preventing and remedying damage caused by the use of painkillers such as NSAIDs, aspirin and ibuprofen. All of the above diseases and complaints are characterised by memory deficiencies, focus problems and a feeling of cotton wool in the head. Therefore, supplementation with nucleotides will also have a favourable effect on this. It has also been known for years that supplementation with nucleotides helps athletes and people who do strength training, among other things, to improve their performance.

Supplementation on the basis of laboratory tests

Laboratory tests can clarify when Nucleotides should be taken:

  • Abnormal (increased or decreased) sIgA values (secretory immunoglobulin A) in faeces;
  • Increased zonulin levels in faeces (indicates leaky gut, degraded function of the tight junctions);
  • Elevated calprotectin levels in faeces;
  • Elevated alpha-1-antitrypsin values;
  • Low leukocyte count in blood;
  • Increased anti-transglutaminase and anti-gliadin antibodies in faeces and/or blood.

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