Also see:
Lactate Paradox: High Altitude and Exercise
Carbon Dioxide as an Antioxidant
Altitude Improves T3 Levels
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 Sickness: Therapeutic Effects of Acetazolamide and Carbon Dioxide
Quotes by Ray Peat, PhD:
“People who live at very high altitudes live significantly longer; they have a lower incidence of cancer (Weinberg, et al., 1987) and heart disease (Mortimer, et al., 1977), and other degenerative conditions, than people who live near sea level. As I have written earlier, I think the lower energy transfer from cosmic radiation is likely to be a factor in their longevity, but several kinds of evidence indicate that it is the lower oxygen pressure itself that makes the biggest contribution to their longevity.”
“K. P. Buteiko believed that increased carbon dioxide in the body fluids sometimes caused cancers to disappear. In many studies over the last 40 years (and the trend can also be seen in insurance statistics published in 1912), it is clear that cancer mortality is much lower at high altitude. Under all conditions studied, the characteristic lactic acid metabolism of stress and cancer is suppressed at high altitude, as respiration is made more efficient. The Haldane effect shows that carbon dioxide retention is increased at high altitude.
Studying athletes at sea level and at high altitude, it was seen that less lactic acid is produced by maximal exercise at high altitude than at sea level. Since oxygen deficiency in itself tends to cause the formation of lactic acid, this has been called the “lactate paradox”; the expectation was that more lactic acid would be formed, yet less was produced. Something was turning off the production of lactic acid. Normally, it is oxidative respiration that turns off glycolysis and lactic acid production, so that in exercise beyond the ability of the body to deliver oxygen, and in cancer with its respiratory defect, glycolysis produces lactic acid. So, something is happening at high altitude which turns off glycolysis.
The Haldane effect is a term for the fact that hemoglobin gives up oxygen in the presence of carbon dioxide, and releases carbon dioxide in the presence of oxygen. It is the increased retention of carbon dioxide that accounts for the “lactate paradox.” Carbon dioxide activates the Krebs cycle, but it also combines with ammonium, and in doing so, deactivates glycolysis because ammonium activates a regulatory enzyme. At high elevation, carbon dioxide is retained, and lactic acid formation is suppressed. (This is called the Pasteur effect, but altitude physiologists haven’t begun thinking in these directions.) Comparing very low altitude (Jordan valley, over 1000 feet below sea level) with moderate altitude (620 meters above sea level), ACTH was increased in runners after a race only at the low altitude, indicating that the stress reaction was prevented by a moderate increase of altitude. (el-Migdadi, et aI., 1996.)
The perspective we get on cancer, from the high altitude studies, allows us to go beyond the specific issue of cancer, to the more general issue of stress and regeneration. In outline, stress alters the physical nature of the cellular substance in a way that activates the cell, in which case it will either die from exhaustion, or grow into new cells. The replacement of injured cells means that mutations need not accumulate, and this renewal with elimination of mutant cells has been observed in sun-damaged skin. Among the many layers of form-generating and form-sustaining systems, the balance of electrical fields has a basic place.”
”The reasons for mountain sickness, and the reasons for the low incidence of heart disease, cancer, cataracts, etc., at high altitude, offer clues to the prevention of death and deterioration from many other causes.”
Radiat Res. 1987 Nov;112(2):381-90.
Altitude, radiation, and mortality from cancer and heart disease.
Weinberg CR, Brown KG, Hoel DG.
The variation in background radiation levels is an important source of information for estimating human risks associated with low-level exposure to ionizing radiation. Several studies conducted in the United States, correlating mortality rates for cancer with estimated background radiation levels, found an unexpected inverse relationship. Such results have been interpreted as suggesting that low levels of ionizing radiation may actually confer some benefit. An environmental factor strongly correlated with background radiation is altitude. Since there are important physiological adaptations associated with breathing thinner air, such changes may themselves influence risk. We therefore fit models that simultaneously incorporated altitude and background radiation as predictors of mortality. The negative correlations with background radiation seen for mortality from arteriosclerotic heart disease and cancers of the lung, the intestine, and the breast disappeared or became positive once altitude was included in the models. By contrast, the significant negative correlations with altitude persisted with adjustment for radiation. Interpretation of these results is problematic, but recent evidence implicating reactive forms of oxygen in carcinogenesis and atherosclerosis may be relevant. We conclude that the cancer correlational studies carried out in the United States using vital statistics data do not in themselves demonstrate a lack of carcinogenic effect of low radiation levels, and that reduced oxygen pressure of inspired air may be protective against certain causes of death.
N Engl J Med. 1977 Mar 17;296(11):581-5.
Reduction in mortality from coronary heart disease in men residing at high altitude.
Mortimer EA Jr, Monson RR, MacMahon B.
In New Mexico, where inhabited areas vary from 914 to over 2135 m above sea level, we compared age-adjusted mortality rates for arteriosclerotic heart disease for white men and women for the years 1957-1970 in five sets of counties, grouped by altitude in 305-m (1000-foot) increments. The results show a serial decline in mortality from the lowest to the highest altitude for males but not for females. Mortality rates for males residing in the county groups higher than 1220 m in order of ascending altitude were 98, 90, 86 and 72 per cent of that for the county group below 1220-m altitude (P less than 0.0001). The results do not appear to be explained by artifacts in ascertainment, variations in ethnicity or urbanization. A possible explanation of the trend is that adjustment to residence at high altitude is incomplete and daily activities therefore represent greater exercise than when undertaken at lower altitudes.
Circulation. 2009 Aug 11;120(6):495-501. Epub 2009 Jul 27.
Lower mortality from coronary heart disease and stroke at higher altitudes in Switzerland.
Faeh D, Gutzwiller F, Bopp M; Swiss National Cohort Study Group.
BACKGROUND:
Studies assessing the effect of altitude on cardiovascular disease have provided conflicting results. Most studies were limited because of the heterogeneity of the population, their ecological design, or both. In addition, effects of place of birth were rarely considered. Here, we examine mortality from coronary heart disease and stroke in relation to the altitude of the place of residence in 1990 and at birth.
METHODS AND RESULTS:
Mortality data from 1990 to 2000, sociodemographic information, and places of birth and residence in 1990 (men and women between 40 and 84 years of age living at altitudes of 259 to 1960 m) were obtained from the Swiss National Cohort, a longitudinal, census-based record linkage study. The 1.64 million German Swiss residents born in Switzerland provided 14.5 million person-years. Relative risks were calculated with multivariable Poisson regression. Mortality from coronary heart disease (-22% per 1000 m) and stroke (-12% per 1000 m) significantly decreased with increasing altitude. Being born at altitudes higher or lower than the place of residence was associated with lower or higher risk.
CONCLUSIONS:
The protective effect of living at higher altitude on coronary heart disease and stroke mortality was consistent and became stronger after adjustment for potential confounders. Being born at high altitude had an additional and independent beneficial effect on coronary heart disease mortality. The effect is unlikely to be due to classic cardiovascular disease risk factors and rather could be explained by factors related to climate.
Nephrol Dial Transplant. 2012 Jun;27(6):2411-7. Epub 2012 Jan 17.
Altitude and the risk of cardiovascular events in incident US dialysis patients.
Winkelmayer WC, Hurley MP, Liu J, Brookhart MA.
BACKGROUND:
Altitude is associated with all-cause mortality in US dialysis patients, but its association with cardiovascular outcomes has not been assessed. We hypothesized that higher altitude would be associated with lower rates of cardiovascular events due to an altered physiological response of dialysis patients to altitude induced hypoxia.
METHODS:
We studied 984,265 patients who initiated dialysis from 1995 to 2006. Patients were stratified by the mean elevation of their residential zip codes and were followed from the start of dialysis to the occurrence of several validated cardiovascular endpoints: myocardial infarction, stroke, cardiovascular death and a composite of these end points. Incidence rate ratios across altitude strata were estimated using proportional hazards regression.
RESULTS:
All outcomes occurred less frequently among patients living at higher altitude compared with patients living at or near sea level, and the association appeared monotonic for all outcomes except for stroke, which was most incident in the 250-1999 ft group. Compared with otherwise similar patients residing at or near sea level, patients living at ≥ 6000 ft had 31% [95% confidence interval (CI): 21-41%] lower rates of myocardial infarction, 27% (95% CI: 15-37%) lower rates of stroke and 19% (95% CI: 14-24%) lower rates of cardiovascular death. Additional adjustment for biometric information did not materially change these findings. Effect modification between race and altitude was only consistently significant for Native Americans. Altitude did not significantly alter the rates of non-cardiovascular death.
CONCLUSION:
We conclude that dialysis patients at higher altitude experience lower rates of cardiovascular events compared to otherwise similar patients at lower altitude.
Biull Eksp Biol Med. 1980 Apr;89(4):498-501.
[Morphologic characteristics of the hearts of argali continuously dwelling at high mountain altitudes].
[Article in Russian]
Zhaparov B, Kamitov SKh, Mirrakhimov MM.
The hearts of argali living at 3800-5000 m above the sea level were examined. Macroscopy showed complete absence of fatty tissue under the epicardium. Increased number of the capillaries surrounding cardiomyocytes, intercalated discs in many zones of the myocardium, sharp thickening giving pronounced cross lines of myofibrils were revealed on semithin and ultrathin sections. The data obtained demonstrate specificity of the heart structure of argali and are discussed from the standpoint of increased compensatory-adaptive changes in the test organ, these changes being associated with its enhanced function provoked by high altitude conditions.
Biull Eksp Biol Med. 1976 Jun;81(6):729-32.
[Myocardial cell ultrastructure of yaks dwelling at high altitudes].
[Article in Russian]
Zhaparov B, Mirrakhimov MM.
The ultrastructure of myocardial cells of the left, right ventricle, and the ventricular septum was studied in the Altai and Pamir Yaks permanently living at the altitude of 3000-3600 m. Electron microscopic studies of myocardial cells revealed, along with the normal mitochondria, the ones with a peculiar structure of the cristae; these had the appearance of polyhedral wavy membranes in some groups of the mitochondria, and of polyhedral netted structures – in the others. Considerable accumulations of glycogen granules were found beneath the sarcolemma, in the perinuclear cytoplasmic zone and between the myofibrils. The results suggest that by undulating and creating a certain structural regularity the mitochondrial cristae increased their active area ensuring the efficacy of the mitochondrial function. Considerable accumulation of glycogen granules in the majority of myocardial cells seems to maintain the energy potential of the myocardium preventing the development of hypoxia.
Biull Eksp Biol Med. 1977 Jul;84(7):109-12.
[Change in the ultrastructure of rat myocardium under the influence of 12-months’ adaptation to high altitude].
[Article in Russian]
Zhaparov B, Mirrakhimov MM.
The right and left ventricle myocardium of rats was studied in the course of a 12-month period of adaptation to high altitude (3200 m above the sea level). A long-term exposure of the animals to the high altitude led the development of ventricular hypertrophy mostly of the right, and partly of the left ventricle. Hyperplasia and hypertrophy of individual organellae, particularly mitochondria, were found in most cardiomyocytes of both ventricles. In animals adapted to the high altitude the mitochondrial succinic dehydrogenase activity was more pronounced than in control ones. The results obtained testified to the enhanced intracellular metabolism reflecting myocardial compensatory adaptive responses.
Arkh Patol. 1981;43(2):66-71.
[Ultrastructural bases of myocardial metabolic disorders under physical loads in alpine adaptation].
[Article in Russian]
Kononova VA.
Ultrastructural and metabolic manifestations of adaptation mechanisms of myocardium of white rats were studied in highlands (Tuya-Ashu pass, 3200 meter above sea level) upon treatment with dosed physical loading. The development of processes of myocardial adaptation to highland hypoxia was found to be step-wise and manifested by the development of destructive and compensatory-adaptative processes. Physical loads in the early period of adaptation resulted in destruction and loss of mitochondria and other intracellular organelles. Prolonged effect of physical loads and hypoxia was accompanied by mobilization of protein synthesis, activation of metabolic enzymes and new formation of mitochondria and myofibrills.
