Carbogen, Oxygen and CO2 Contributions for Cancer Tumors
Is there any experimental evidence indicating usefulness of CO2 for
During the last decade, there has been a steady progress in clinical investigations
and applications of CO2-O2 gas mixtures called "carbogen". The mixture
contains somewhere from 2 to 5% of carbon dioxide and the remaining portion is
oxygen (from about 95 to 98%). Carbogen breathing is usually applied for several hours during administration of
certain anti-cancer medications (i.e., cancer patients breathe carbogen for some
hours). Why carbogen? The logic is simple: increased CO2 will help to dilate
blood vessels (due to vasodilatory properties of
CO2) and release more oxygen in tissues and tumors (due to enhanced
Bohr effect), while increased O2 will improve
oxygenation of the arterial blood. Hence, there are triple benefits, as many medical
professionals have been reasoning, for using carbogen.
Let us review some results in this area and the
reasons for carbogen application.
Several studies from England and the USA found that breathing various
carbogen mixtures significantly improves oxygenation of tumors. The general
opinion of these researchers is that
"Perfusion insufficiency and the
resultant hypoxia are recognized as important mechanisms of resistance to
anticancer therapy. ..."(Powell et al, 1997).
A large group of British scientists from the Paul Strickland Scanner Centre
revealed that when 14 cancer patients breathed various carbogen mixtures (with
2%, 3.5% and 5% CO2 content, the rest was O2) "arterial oxygen tension
increased at least three-fold from basal values" (Baddeley et al, 2000).
They also found that
"...The results suggest that 2% CO2 in O2 enhances
arterial O2 levels to a similar extent as 3.5% and 5% CO2 and that it is
well tolerated" (Baddeley et al, 2000).
Another group of British researchers directly measured oxygen pressure in
cancer cells and concluded,
"This study confirms that breathing 2% CO2 and
98% oxygen is well tolerated and effective in increasing tumor oxygenation"
(Powell et al, 1999).
These results generate the following question. Which gas, CO2 or O2 is the
main contributor to increased oxygenation of cells and by how much? The amounts of both
gases in mixtures were much higher than the amounts of O2 and CO2 in normal air.
Let us, first, consider the influence of O2. There are two O2 states in the
O2 that is combined with hemoglobin or red blood cells and O2 that is dissolved
in blood plasma. Which component produces the main increase
in oxygenation of the arterial blood? As we considered in Chapter 1, the saturation
of hemoglobin with O2 under normal conditions (or when breathing normal air) is
about 98%. Increased O2 pressure can raise this value to almost 100%. This would
cause about a 2% increase in the arterial blood in comparison with the initial
value. In addition, when patients breathe carbogen mixtures more O2 can be
dissolved in blood plasma (this O2 is not bound to red blood cells). In
normal conditions the contribution of dissolved O2 is about 1.5% of the total
blood O2 as the remaining 98.5% O2 is combined with hemoglobin. Increasing O2
content in the inspired air (almost five times) can increase freely dissolved
oxygen to about 6-7% in relation to
the initial value (1.5%).
Hence, increasing the O2 component in the inspired air (from about normal 20% up to almost 100%)
can cause about 8-9% increase in total O2 content in the arterial blood (with 2%
increase for combined oxygen and 6-7% for freely dissolved oxygen).
British professionals decided “to assess the relative
contributions of carbon dioxide and oxygen to this response and the tumor
oxygenation state, the response of GH3 prolactinomas to 5% CO2/95% air, carbogen
and 100% O2” (Baddeley et al, 2000). That was done using magnetic resonance
imaging and PO2 histography. They found that,
“A 10-30% image intensity increase was observed during 5% CO2/95% air
breathing, consistent with an increase in tumor blood flow, as a result of
CO2-induced vasodilation... A small 5-10% increase
was observed in response to 100% oxygen, highlighting the dominance of CO2-induced
vasodilation in the carbogen response” (Baddeley et al, 2000).
It is not oxygen, but carbon dioxide that is the main substance responsible for
the main improvement in oxygenation of tumors, while high O2 concentrations,
while providing additional improvement in oxygenation of the arterial blood and
toxic for lungs alveoli due to high reactivity of oxygen and resulting oxidative damage
to tissues and formation of free radicals. Hence, it is logical to expect that
if the same patients use 100% O2 for many days, not just hours, the oxidative
damage can produce more harm for the whole body than the benefits of pure oxygen
for tumor reduction. Higher CO2, on the other hand, will cause sustained
improvements in tumor oxygenation without any negative effects. (In fact, there
are many more positive effects due to various uses of CO2
in the human body.)
Indeed, more detailed analysis or dynamic of improved oxygenation was
investigated by German scientists (the abstract is one paragraph below; Thews et
al, 2002). They found that positive effects of pure oxygen are very short in
duration, while CO2 produces lasting improvement.
But a cancer patient can safely increase own CO2 content in the body and
oxygenation of the tumors naturally by learning how to breathe
less (Section "Learn here"), while preserving normal arterial blood oxygenation (about 98%
for O2 hemoglobin saturation) and avoiding oxidative damage, expensive
therapies and equipment, hours and hours of labor done by medical professionals.
Baddeley H1, Brodrick PM, Taylor NJ, Abdelatti MO, Jordan LC, Vasudevan AS, Phillips H, Saunders MI, Hoskin PJ, Gas exchange parameters in radiotherapy patients during breathing of 2%, 3.5% and 5% carbogen gas mixtures., Br J Radiol. 2000 Oct;73(874):1100-4.
Powell ME, Hill SA, Saunders MI, Hoskin PJ, Chaplin DJ, Human tumour blood flow is enhanced by nicotinamide and carbogen breathing, Cancer Res 1997 Dec 1; 57(23): p. 5261-5264.
Powell ME, Collingridge DR, Saunders MI, Hoskin PJ, Hill SA, Chaplin DJ, Improvement in human tumour oxygenation with carbogen of varying carbon dioxide concentrations, Radiother Oncol 1999 Feb; 50(2): p. 167-171.
Thews O, Kelleher DK, Vaupel P, Dynamics of tumor oxygenation and red blood cell flux in response to inspiratory hyperoxia combined with different levels of inspiratory hypercapnia, Radiother Oncol. 2002 Jan; 62(1): p. 77-85.
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