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 Zürich’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.