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Schwartz L. J Cancer Treat & Diagnosis. (2017); 1(1): 6-10
Journal of Cancer Treatment and Diagnosis
Mini review Open Access
Page 6 of 10
Chlorine dioxide as a possible adjunct to metabolic treatment
Laurent Schwartz
Assistance Publique des Hôpitaux de Paris, Avenue Victoria 75003 Paris, France
Article Info
Article Notes
Received: October 02, 2017
Accepted: October 30, 2017
*Correspondence:
Dr. Laurent Schwartz, M.D.
Assistance Publique des Hôpitaux de Paris, Avenue Victoria
75003 Paris, E-mail: dr.laurentschwatz@gmail.com
© 2017 Schwartz L. This article is distributed under the terms of
the Creative Commons Attribution 4.0 International License.
ABSTRACT
A rst paent with metastac adenocarcinoma of the pancreas has
decided, on his own, to refuse chemotherapy but to treat himself with lipoïc
acid, hydroxycitrate combined with oral ingeson of chlorine dioxide. His blood
tests and radiological examinaons have almost normalized and the disease
is stable at 18 months. Another paent with hormone resistant metastac
prostate cancer has experienced a sharp drop in PSA level as well as improved
medical condion. From extensive literature review, the mechanism of acon
of chlorine dioxide is unknown. It is our hypothesis (albeit unproven) that
chlorine dioxide results in tumor cell acidicaon of the alkaline pH of cancer
cells.
Introduction: Cancer is a fermentation process
In the early 1920’s Otto Warburg demonstrated a unique feature
of cancer cells, namely an increased uptake of glucose and secretion
of lactic acid by cancer cells, even in the presence of oxygen (e.g.
the aerobic glycolytic phenotype)1,2. This aerobic fermentation is the
signature of cancer3. Warburg also noticed a concomitant decreased
number of mitochondria (grana)4. In normal, differentiated cells, the
yield of a molecule of glucose is 34 ATP. ATP is derived mostly from
oxidative phosphorylation which takes place in the mitochondria5,6.
In the absence of mitochondria the energy yield drops to two
molecules of ATP per molecule of glucose5,6. As stated by Warburg
mitochondria resulting in lesser yield. Despite increased glucose
uptake, there is a 50% drop in ATP level in human colon cancer
cells compared to adjacent benign cells7. This decrease in ATP is a
consequence of impairment of the oxidative phosphorylation6–9.
To compensate for the decreased energy yield, the cell increases
its glucose uptake7,10. The decreased activity of the mitochondria has
many consequences, one of which is an increased secretion of lactic
acid and another one is the activation of the pentose phosphate
pathway (PPP). Another consequence is the activation of the
glutaminolysis which is necessary for nucleic acid synthesis6–9.
The activation of the Pentose Phosphate Pathway results
from an increase in glucose uptake with a concomitant obstacle
downstream of the pentose phosphate shunt, most probably at the
level of pyruvate dehydrogenase and/or of pyruvate kinase2,6,11. The
A shift toward anabolism due to increased synthesis of NADPH
that plays a crucial role in NADPH/NADP+ ratio that determines
Schwartz L. J Cancer Treat & Diagnosis. (2017); 1(1): 6-10 Journal of Cancer Treatment and Diagnosis
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the redox state of the cell via removal of reactive oxygen
species (ROS) and so prevents cellular death and controls
cellular fate7,11.
The shift toward the pentose pathway also results in
the production of ribose-5-phosphate, required for the
synthesis of nucleic acids5.
One other crucial consequences of the mitochondrial
defect is intracellular alkalosis7. Tumors show a ‘reversed’
pH gradient with a constitutively increased intracellular
pH that is higher than the extracellular pH. This gradient
enables cancer progression by promoting proliferation, the
evasion of apoptosis, metabolic adaptation, migration, and
invasion12–15.
There is evidence that an acidic extracellular pH
promotes invasiveness and metastatic behaviour in several
tumor models14,16, proteolytic enzyme activation and
matrix destruction17–19.
In normal cells, the intracellular pH (pHi) oscillates
during the cell cycle between 6.8 and 7.37. The oscillation
of the pH during the cell cycle matches the value of the
decompaction of the histones, RNA polymerase activation,
DNA polymerase activation and DNA compaction before
mitosis7,11.
The intracellular pH of the cancer cells has been less
studied. During the cell cycle, it oscillates between 7.2
and 7.5. Intracellular alkalosis is probably a consequence
of the decreased oxidative phosphorylation resulting
in decreased secretion of carbon dioxide (CO2) and
the CO2 reacts with water to create carbonic acid. Cell
transformation or enhanced cancer cell division and
resistance to chemotherapy are all associated with a more
alkaline pHi20–23.
The Warburg effect may be a direct consequence of the
activation of oncogenes6. Infection by an oncogenic virus
or exposure to a carcinogen inhibits the mitochondrial
function and causes the Warburg’s effect24–29.
Reversing the Warburg inhibits tumor growth
The introduction of normal mitochondria into cancer
cells restores mitochondrial function, inhibits cancer cell
growth and reverses chemoresistance30-35. Also the fusion of
cancer cells with normal mitochondria results in increased
ATP synthesis, oxygen consumption and respiratory chain
activities together with marked decreases in cancer growth,
resistance to anti-cancer drugs, invasion, colony formation
in soft agar, and « in vivo » tumor growth in nude mice31.
As the Warburg aerobic glycolytic phenotype and
its effects on metabolism are key to cancer, the obvious
question is whether drugs can be designed to target it. To
alleviate the Warburg effect, pyruvate should be converted
into Acetyl-CoA, which would decrease the bottleneck that
results in the activation of both the Pentose Phosphate
Pathway and the glutaminolysis. The mitochondrial yield
should be increased to stimulate the synthesis of CO2 and
the increased secretion of CO2 would result in a decreased
intracellular alkalosis.
36–39
has been reported to slow cancer growth, in murine
xenografts. This inhibition appears to be independent
of the primary tumor site and has been reproduced in
different laboratories40,41.
its reduction of tumor growth is the inhibition of pyruvate
dehydrogenase kinase (the same target of Dichloroacetic
acid (DCA)). This enzyme inhibits the activity of pyruvate
dehydrogenase and is known to be up-regulated in cancer
cells expressing the Warburg aerobic glycolytic phenotype.
Pyruvate dehydrogenase catalyses the conversion of
of glucose to carbon dioxide and water in the TCA cycle,
with the concomitant production of ATP. Therefore, it is
reasonable to suggest that blocking the activity of pyruvate
dehydrogenase kinase will at least partially restore the
activity of pyruvate dehydrogenase, thereby increasing the
while simultaneously reducing the production of lactic acid
pathway shunt9.
There are several reports of metabolic treatment
together with conventional cancer therapy. Starting
hydroxycitrate with low doses of chemotherapy plus
Naltrexone) was offered to patients sent home after
the failure of conventional cytotoxic chemotherapy for
metastatic cancer (irrespective of the primary site) but with
cancer patients’ general well-being and activities of daily
life)42–46
were alive and reasonably well 30 months after the start of
treatment43-45.
In the update of a subsequent study, patients with
multiple brain metastasis (n=4) or glioblastoma (n=6)
were treated with a combination of conventional and
as ketogenic diet. Five out of six patients with glioblastoma
were alive and stable after two years, while two of the four
patients with multiple brain metastases are alive and well
three years later46,47.
Cases reports
Patient number 1
Schwartz L. J Cancer Treat & Diagnosis. (2017); 1(1): 6-10 Journal of Cancer Treatment and Diagnosis
Page 8 of 10
with biopsy-proven unresectable well differentiated
adenocarcinoma of the pancreas in June 2016 . The
cholestasis was treated by a derivation in December 2016
which was effective in alleviating the obstruction. The
tumor markers (CA 19-9 and CEA) were uninformative. The
patient subsequently refused chemotherapy and decided
by himself to start a treatment involving
1) Ketogenic diet
2)
500mg three times a day
3) Chlorine dioxide up to 32 drops per day. Chlorine
dioxide was produced by the activation of NaCLO2
by 4% HCl. The activation time takes 3mn and a
drop contains around 86 micromoles of CLO2 if the
activation is total.
As of 9/2017, the patient was living normally, the blood
tests were normal, the tumour mass such as seen on CT
scan had grown from 3 to 5 cm. No side effects were noted.
There was ne concomitant chemotherapy or radiation
therapy.
Patient number 2
started a similar treatment. He is a 67-year-old man. He
was diagnosed in 8/16 with Gleason 8 adenocarcinoma
of the prostate responsible of a cord compression that
was successfully treated by laminectomy and post op
radiationtherapy. At the start of disease PSA was 1320.
Degarelix was started in 8/16 with concomitant ketogenic
diet. Because of partial responds chemotherapy with
Docetaxel (150mg IV) was started in December 2016.
Chemotherapy was discontinued after two cycles because
of poor tolerance. Simultaneously, starting In mid
hydroxycitrate. He performs weekly assessment of his PSA.
End of march, the PSA had dropped to 27 and stayed at
this value up to beginning of June, but started increasing,
increased and was responsible of Karnovsky of 70. At that
stage the patient started to take chloride dioxide. The PSA
dropped linearly for eight weeks to 26. The patient took
eight times a day, 344 micromoles of chlorine dioxide. After
these eight weeks of decrease, the PSA started to increase
in three weeks from 26 to 39. At that stage, metastatic pain,
which has almost completely disappeared, was responsible
of insomnia. He started to take chlorine dioxide drops not
only during the daytime but also every 90 minutes at night.
Nightly metastatic pain decreased drastically from day one,
and the second part of the night was practically pain free.
The PSA decreased again linearly from 39 to 24.
Discussion and conclusion
Chlorine dioxide is a poorly studied chemical entity. The
mechanism of action of ClO2 is poorly understood. It is our
hypothesis that chlorine dioxide decreased the intracellular
be an alternative or an adjunct to a metabolic treatment
as there is extensive literature that many effective cancer
treatments decrease the intracellular pH (pHi)2,23,47
literature on increased survival support for the combined
use of antacids (which prevent proton extrusion from the
tumour cells) with standard chemotherapy15,48–50.
Today, cancer is thought to be a set of very complex
diseases with thousands of different mutations. That
apparent complexity has led to personalized medicine.
of the Warburg aerobic glycolytic phenotype. Furthermore,
hydroxycitrate slows down cancer growth in every tumor
model studied to date suggests that at least some targets
are the same in a large spectrum of tumors.
It is possible that the addition of chlorine dioxide
increases the response to metabolic treatment.
Acknowledgement
We want to thank Professor Francis Taulelle for his help
in understanding the chemistry and probable mechanism
of action of chlorine.
Conict of interest
None
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