Carbogen, Oxygen and CO2 Contributions for Cancer Tumors

Is there any experimental evidence indicating usefulness of CO2 for malignant tumors?

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 arterial blood: 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 freely 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 tumors, are 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. 

Clinical References

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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