The Oxygen Mirror-J-Curve: Mild Hyperoxia and Mild Hypoxia Induce Beneficial Adaptations

Background Mirror‐J‐response, named based on the shape of dose response curve, claims that physiological agents of living organism (including humans) when they deviate mildly from the reference range produce beneficial effects (e.g. glucose, calcium and osmolality, etc). A higher degree of deviations of those same agents produces harmful effects. Hypothesis Both mild hyperoxia and mild hypoxia may induce a positive adaptive response. Could the mirror‐J be substantiated for oxygen? Methods Objective of this study was to search for a support of hypothesis in the published data. Results Beneficial effects of mild hypoxia have been shown both on cells and whole organisms. Cellular response to hypoxia consists of gene transcription modification and metabolic adaptations. These effects translate to adaptations of whole organisms. Animal studies show improved outcomes in both healthy subjects and disease models when challenged with hypoxia. Studies on healthy human subjects were mainly focused on physical activity performance, but have also shown decrease in inflammatory cytokines and glucose resistance. Studies on patients mostly focused on cardiovascular and neurologic diseases and show improvement in cardiorespiratory fitness similar to physical exercise. Mild hyperoxia animal studies demonstrated that ischemia improved tolerance following hyperoxia in myocardium, brain and kidney. Human studies focus primarily on exercise performance in healthy subjects and cardiovascular and neurological pathology, same as hypoxia research. Mild hyperoxia during exercise promoted fat oxidation, reduced sugar oxidation, and delayed time to exhaustion. Hyperoxia preconditioning reduced risk of heart surgery. Also, following traumatic brain injury, periods of hyperoxia can normalize oxidative metabolism markers in brain long after return to normoxia. Conclusion/Discussion Hypoxia and hyperoxia are in antithesis, but their effects are surprisingly similar. Both were shown to precondition various tissues to ischemia and to improve cardiorespiratory fitness. These similarities invoke a usage of a similar mechanism of action, as suggested for disarrangements in calcium, glucose and osmolality. Indeed, it was shown that both, mild hypoxia and mild hyperoxia induce production of reactive oxygen species which induce cellular adaptive response. Furthermore, studies have shown that both hypoxia and hyperoxia activate hypoxia inducible factor and promote erythropoietin production. Taken together, this data supports single unified cellular response to tipping oxygen balance. Those responses follow the mirror‐J nonlinearity. These adaptive responses appear to function on cellular level and level of organism as a whole and may improve functioning in normoxia.