Also see:
Protect the Mitochondria
Carbon Dioxide Basics
Comparison: Carbon Dioxide v. Lactic Acid
Comparison: Oxidative Metabolism v. Glycolytic Metabolic
Promoters of Efficient v. Inefficient Metabolism
Altitude Sickness: Therapeutic Effects of Acetazolamide and Carbon Dioxide
Low CO2 in Hypothyroidism
Protective Altitude
Lactate Paradox: High Altitude and Exercise
Protective Carbon Dioxide, Exercise, and Performance
Synergistic Effect of Creatine and Baking Soda on Performance
Ray Peat, PhD on Carbon Dioxide, Longevity, and Regeneration
Altitude Improves T3 Levels
Mitochondria & Mortality
Altitude and Mortality
Lactate vs. CO2 in wounds, sickness, and aging; the other approach to cancer
Quotes by Ray Peat, PhD:
“The suppression of mitochondrial respiration increases the production of toxic free radicals, and the decreased carbon dioxide makes the proteins more susceptible to attack by free radicals.”
“The presence of carbon dioxide is an indicator of proper mitochondrial respiratory functioning.”
“In every type of tissue, it is the failure to oxidize glucose that produces oxidative stress and cellular damage.”
Physiol Res. 2002;51(4):335-9.
The role of carbon dioxide in free radical reactions of the organism.
Veselá A, Wilhelm J.
Carbon dioxide interacts both with reactive nitrogen species and reactive oxygen species. In the presence of superoxide, NO reacts to form peroxynitrite that reacts with CO2 to give nitrosoperoxycarbonate. This compound rearranges to nitrocarbonate which is prone to further reactions. In an aqueous environment, the most probable reaction is hydrolysis producing carbonate and nitrate. Thus the net effect of CO2 is scavenging of peroxynitrite and prevention of nitration and oxidative damage. However, in a nonpolar environment of membranes, nitrocarbonate undergoes other reactions leading to nitration of proteins and oxidative damage. When NO reacts with oxygen in the absence of superoxide, a nitrating species N2O3 is formed. CO2 interacts with N2O3 to produce a nitrosyl compound that, under physiological pH, is hydrolyzed to nitrous and carbonic acid. In this way, CO2 also prevents nitration reactions. CO2 protects superoxide dismutase against oxidative damage induced by hydrogen peroxide. However, in this reaction carbonate radicals are formed which can propagate the oxidative damage. It was found that hypercapnia in vivo protects against the damaging effects of ischemia or hypoxia. Several mechanisms have been suggested to explain the protective role of CO2 in vivo. The most significant appears to be stabilization of the iron-transferrin complex which prevents the involvement of iron ions in the initiation of free radical reactions.
Fiziol Zh Im I M Sechenova. 1995 Feb;81(2):47-52.
[The unknown physiological role of carbon dioxide].
[Article in Russian]
Baev VI, Vasil’eva IV, L’vov SN, Shugaleĭ IV.
In rats adapted to hypoxia, in gradual increase of CO and decrease in monosialogangliosides, were shown as well as insufficient accumulation of the lipid peroxidation products. The data suggests that carbon dioxide is a natural element of the organism antioxidant defence system.
Vopr Med Khim. 1996 Jul-Sep;42(3):193-202.
[Ability of carbon dioxide to inhibit generation of superoxide anion radical in cells and its biomedical role].
[Article in Russian]
Kogan AKh, Grachev SV, Eliseeva SV, Bolevich S.
The study was carried out on blood phagocytes and alveolar macrophages of 96 persons, cells of inner organs and tissue phagocytes (liver, brain, myocardium, lungs, kidneys, stomach, skeletal muscles), as well as on mitochondria of the liver of 186 non-linear white mice. Generation of active oxygen forms (AOF) was evaluated by various methods with CO2 directly affecting the cells and bioptates and indirectly the whole organism. The results show that CO2 with tension close to that of the blood (37.0 mm Hg) and at higher tensions (60 and 146 mm Hg) is a powerful inhibitor of AOF generation by human and animal cells, as well as by liver mitochondria of mice. The data obtained allow to explain, in terms of AOF role, a number of physiological and pathophysiological (medical) CO2 effects.
Izv Akad Nauk Ser Biol. 1997 Mar-Apr;(2):204-17.
[Carbon dioxide–a universal inhibitor of the generation of active oxygen forms by cells (deciphering one enigma of evolution)].
[Article in Russian]
Kogan AKh, Grachev SV, Eliseeva SV, Bolevich S.
Studies were carried out on blood phagocytes and alveolar macrophages of 96 humans, on the cells of the viscera and tissue phagocytes (liver, brain, myocardium, lungs, kidneys, stomach, and skeletal muscle), and liver mitochondria of 186 random bred white mice. Generation of the active oxygen forms was determined using different methods after direct effect of CO2 on the cells and biopsies and indirect effect of CO2 on the integral organism. The results obtained suggest that CO2 at a tension close to that observed in the blood (37.0 mm Hg) and high tensions (60 or 146 mm Hg) is a potent inhibitor of generation of the active oxygen forms by the cells and mitochondria of the human and tissues. The mechanism of CO2 effect appears to be realized, partially, through inhibition of the NADPH-oxidase activity. The results are important for deciphering of a paradox of evolution, life preservation upon appearance of oxygen in the atmosphere and succession of anaerobiosis by aerobiosis, and elucidation of some other problems of biology and medicine, as well as analysis of the global bioecological problem, such as ever increasing CO2 content in the atmosphere.
Patol Fiziol Eksp Ter. 1995 Jul-Sep;(3):34-40.
[Comparative study of the effect of carbon dioxide on the generation of active forms of oxygen by leukocytes in health and in bronchial asthma].
[Article in Russian]
Kogan AKh, Bolevich S, Daniliak IG.
The study was conducted by using leukocytes isolated from 74 apparently healthy donors and 60 patients with bronchial asthma. The generation of active oxygen forms was determined by luminolo- and lucigenin-dependent chemiluminescence techniques and NTC-reaction. The findings suggest that at the tension close to the blood tension of 37.5 mm Hg and the high tension of 146 mm Hg is a powerful natural inhibitor of leukocytic generation of active oxygen forms. At an exacerbation, the inhibitory effect of carbon dioxide on the leukocytic generation of active oxygen forms decreased in most (70%) patients with bronchial asthma, which potentiates the free radical mechanism of development of bronchial asthma. It may be held that the literature-described use of carbon dioxide for the treatment of bronchial asthma is justifiable only in a lower proportion of patients who have preserved a high sensitivity to the inhibitory effect of carbon dioxide on the generation of active oxygen forms.
Vojnosanit Pregl. 1996 Jul-Aug;53(4):261-74.
[Carbon dioxide inhibits the generation of active forms of oxygen in human and animal cells and the significance of the phenomenon in biology and medicine].
[Article in Serbian]
Boljevic S, Kogan AH, Gracev SV, Jelisejeva SV, Daniljak IG.
Carbon dioxide (CO2) influence in generation of active oxygen forms (AOF) in human mononuclear cells (blood phagocytes and alveolar macrophages) and animal cells (tissue phagocytes, parenchymal and interstitial cells of liver, kidney, lung, brain and stomach) was investigated. The AOF generation was examined by the methods of chemiluminiscence (CL) using luminol, lucigenin and NBT (nitro blue tetrazolium) reaction. It was established that CO2 in concentrations similar to those in blood (5.1%, pCO2 37.5 mmHg) and at high concentrations (8.2%, pCO2 60 mmHg; 20%, pCO2 146 mmHg) showed pronounced inhibitory effect on the AOF generation in all the studied cells (usually reducing it 2 to 4 times). Those results were obtained not only after the direct contact of isolated cells with CO2, but also after the whole body exposure to CO2. Besides, it was established that venous blood gas mixture (CO2 – 45 mmHg, +O2 – 39 mmHg, + N2 – 646 mmHg) inhibited the AOF generation in cited cells more than the arterial blood gas mixture (CO2 – 40 mmHg, + O2 – 95 mmHg, + N2 – 595 mmHg). Carbon dioxide action mechanism was developed partially through the inhibition of the OAF generation in mitochondria and through deceleration of NADPH oxidative activity. Finally, it was established that CO2 led to the better coordination of oxidation and phosphorylation and increased the phosphorylation velocity in liver mitochondria. The results clearly confirmed the general property of CO2 to inhibit significantly the AOF generation in all the cell types. This favors the new explanation of the well-known evolutionary paradox: the Earth life and organisms preservation when the oxygen, that shows toxic effects on the cells through the AOF, occurs in the atmosphere. The results can also be used to explain in a new way the vasodilating effect of CO2 and the favorable hypercapnotherapy influence on the course of some bronchial asthma forms. The results are probably significant for the analysis of important bio-ecological problem, such as the increase of CO2 concentration in the atmosphere and its effect on the humans and animals.
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Implications in health vs. diseease:
J Pharmacol Exp Ther. 2012 Sep;342(3):608-18. doi: 10.1124/jpet.112.192120. Epub 2012 Jun 13.
Oxidative shielding or oxidative stress?
Naviaux RK.
In this review I report evidence that the mainstream field of oxidative damage biology has been running fast in the wrong direction for more than 50 years. Reactive oxygen species (ROS) and chronic oxidative changes in membrane lipids and proteins found in many chronic diseases are not the result of accidental damage. Instead, these changes are the result of a highly evolved, stereotyped, and protein-catalyzed “oxidative shielding” response that all eukaryotes adopt when placed in a chemically or microbially hostile environment. The machinery of oxidative shielding evolved from pathways of innate immunity designed to protect the cell from attack and limit the spread of infection. Both oxidative and reductive stress trigger oxidative shielding. In the cases in which it has been studied explicitly, functional and metabolic defects occur in the cell before the increase in ROS and oxidative changes. ROS are the response to disease, not the cause. Therefore, it is not the oxidative changes that should be targeted for therapy, but rather the metabolic conditions that create them. This fresh perspective is relevant to diseases that range from autism, type 1 diabetes, type 2 diabetes, cancer, heart disease, schizophrenia, Parkinson’s disease, and Alzheimer disease. Research efforts need to be redirected. Oxidative shielding is protective and is a misguided target for therapy. Identification of the causal chemistry and environmental factors that trigger innate immunity and metabolic memory that initiate and sustain oxidative shielding is paramount for human health.
