Thursday, 26 October 2017

Cancer and cell selectivity - by Dr Peter Damian Koeppel

Today's blog is written by Dr Peter Damian Koeppel who Robin interviewed on the on UK Health Radio, along with Rachel Hoyle and Rob Verkerk, a while back. You can listen to this here. He writes about how nucleotides can support people with cancer. 

Dr Koeppel has a PhD in Biochemistry and Immunology and was trained in Biochemistry (with a special interest in clinical immunology) at the University of Z├╝rich’s Institute of Virology.

Nucleotides are the basic molecules of the DNA and RNA. The DNA of each cell contains the whole information of the body and must be correctly doubled before the cell is able to proliferate. This DNA multiplication and therefore also the cell proliferation is fully dependent on the availability of sufficient nucleotides. The normal cells of the body are capable to produce the needed amount of nucleotides by de novo synthesis. Additionally the normal body cells also absorb nucleotides from the blood circulation by the salvage pathway.

The cells of the immune system, like bone marrow cells, lymphocytes, macrophages as well as NK-cells are not able to produce nucleotides by themselves and are fully dependant on an outside supply of nucleotides either by the liver or by the food. Any external supply of nucleotides will therefore support a strong immune response.
Nucleotides are present in higher amounts in human breast milk, and their uptake enhances a number of immunological as well non immunological functions in young children. It is clear that nature supplies these nucleotides in breast milk for positive development of the body. This would not be the case should nucleotides have a negative effect on the body.

Nucleotide Nutrition Ltd is the supplier of the Swiss Pro Bio AG pioneering line of nutritional additives based on purified RNA and nucleotides, Nutri-tide®. These nucleotides can be used by the body for an increased cell multiplication. The additives are mainly designed to support the immune system and a good development of the gastro-intestinal tract.

People would think that potentially carcinogenic cells could also profit from the additional supply of nucleotides for their faster development. But, the body is equipped with some mechanisms to avoid this from happening.

1.             The rate of uptake of nucleotides is dependent on the state of differentiation of the cancer cells, e.g. Caco-2 cells, and the uptake by undifferentiated cells is less efficient than that by differentiated cells. (Ian R. Sanderson and Youping He; The journal of nutrition, Vol.124, January 1994)
Therefore the supply of nucleotides gives more support to an optimal function of the immune system than to the growth of cancer cells.

2.             The capacity for de novo and salvage pathway synthesis of nucleic acids in cancer cells is increased with a concurrent decrease in the activity of key enzymes in nucleotide degradation, suggesting that nucleobases are re-used more efficiently than in non-neoplastic cells. (R.W. Holley; Proc. Natl. Acad. Sci. U.S.A. 69: 2840-2841; G. Weber; Cancer Res. 43: 3466-3492)
This means that cancer cells are able to cover their needs by their own production and re-utilisation of nucleotides, whereas immune cells are fully dependent on external supply.

3.             Because they have smaller nucleotide pools, non-malignant (normal) cells would be more dependent on an external supply of nucleotides. Normal enterocytes are less able to expand their pools in the face of nucleotide supplementation and the pools themselves contain metabolites that are more catabolized than those in the pools of malignant cells. (Ian R. Sanderson and Youping He; The journal of nutrition, Vol.124, January 1994)
This means that the cancer cells are in the position to make better use of their nucleotide pools and therefore are less dependent on an external supply.

4.              When glutamine and non-essential amino acids were present, adding nucleotides had no significant effect on the proliferation of Caco-2 cells (malignant cells). However, nucleotide supplementation increased the proliferation of IEC–6 cells (normal body cells). (Ian R. Sanderson and Youping He; The journal of nutrition, Vol.124, January 1994)
Therefore mostly normal body cells profit from an oral supplementation of nucleotides in combination with a normal uptake of food.

5.             Nucleotides stimulate the Natural Killer Cell Activity and have a positive effect of the Macrophage activation. NK cells are one of the main populations involved in the immune response against transformed cells (J.D. Carver et al; J. Parenter Enteral Nutr 14: 18-22, 1990)
By stimulating the NK cell activity the body is able to fight against carcinogenic cell formation.

6.             DNA and also RNA can suppress the spontaneous growth of transformed cells like, Caco-2 cells. (E. Holen et al ;Nutrition Research 24 :197 – 207, 2004)
By adding RNA in the normal nutrition the development of cancer can even be lowered.

7.        Experiments show that the de novo biosynthesis of nucleotides is sufficient to support the proliferation of neoplastic cell lines but not that of normal cell lines. Nucleotide supplementation may therefore increase the growth and maturation of normal cells. (Ian R. Sanderson and Youping He; The journal of nutrition, Vol.124, January 1994)
Therefore the biosynthesis process is capable of producing sufficient nucleotides for the proliferation of neoplastic cells. Carcinogenic cells are therefore not dependent on an external supply of nucleotides for their fast multiplication.
But oral supplementation of nucleotides increases the proliferation rate of normal body cells. The inability of the cells of the immune systems to produce nucleotides indicates that supplementation orally is paramount to the improved functioning of the immune system increasing its ability to eliminate neoplastic cells from the body.

8.             Researchers showed that the basis for genome instability induced by oncogenes activating the Rb-E2F pathway is uncoordinated S phase entry, leading to insufficient factors required for normal DNA replication. We revealed that cells are forced to proliferate with an insufficient pool of nucleotides to support normal DNA replication. Under these conditions, the replication machinery fails to achieve regular rate and processivity, resulting in DNA damage and genome instability. (A. Bester et al, Cell 145, 435–446, April 29, 2011)
This means that a lack of nucleotides can lead to DNA damage and finally to cancer. Supplementation of nucleotides helps to lower the formation of cancer cell. 

9.             Normal human cells have 46 chromosomes, each of which is a long string of DNA. But in certain bowel cancers, this number can change over time - a process called chromosomal instability. This makes the cells in a tumour incredibly diverse, and helps it become resistant to treatment. Researchers at Cancer Research UK’s London Research Institute and the UCL Cancer Institute found that loss of any one of three particular genes on chromosome 18q interfered with the normal copying process. They were able to dramatically reduce this chromosomal instability in bowel cancer cells lacking the three genes. They did this by adding the basic building blocks of DNA to the cells – called nucleosides - preventing further copying errors from occurring, and the chromosomes from being shuffled.
(R. Burrell et al, Nature 494, 492-496, February 28, 2013)
This means that a lack of nucleotides can lead to DNA damage and finally to cancer. Supplementation of nucleotides helps to lower the formation of cancer cell.

10.          A trial performed at the Department of Experimental Pathology, St Bartholomew`s and Royal London School of Medicine and Dentistry, Charterhouse Square in London showed that there was no statistical evidence that tumour growth was enhanced by the supplement NuCell®, which contains the Nutri-tide®IM nucleotide formula.

11.          Over many years of use of the various nucleotide formulations of Pro Bio Ltd no reported increase in cancer incidence in humans or animals has ever been recorded.

Use indications

Supplementary nucleotides should not be taken during Chemotherapy as they potentially interact with the specific treatment. 
They can be taken:
a)      before chemotherapy treatment to help optimise the functioning of the various body systems e.g. immune system or gut, and this helps to minimize the side effects of the cancer treatment,
b)      and/or after finishing the chemotherapy treatment to restore the damaged immune system and the gut structure.

Supplementary nucleotides can be taken before, during and after radiation treatment to help repair damage body cells.

Based on the above information it can be assumed that nucleotide based products do not lead or support a higher incidence of neoplastic cell development.