Beneficial Effects of Mild Acidosis and Mild Alkalosis Follow the Mirror‐J‐Nonlinearity Curve

Abstract

BackgroundPhysiological agents are strictly regulated within the reference range. Any deviation from that range is considered to be a disruption of homeostasis and a potentially harmful process. However, it has been reported that finite alterations of several physiological agents may behave according to a nonlinearity described as the mirror‐J‐shaped curve. Namely, small deviations from the reference range produce a positive (beneficial) effect, whereas larger deviations of the same physiological agents produce a negative (harmful) effect. Certain clinical trials and basic research data support such concept. These hormetic effects have been described for the physiological agents oscillations of glucose, oxygen, calcium, calories, osmolality, etc. It thus appeared as a more general physiological phenomenon.HypothesisMild acidosis and mild alkalosis may produce a beneficial physiological effect.MethodsResearch of published data that may support the concept of beneficial effects of mild acidosis and mild alkalosis.ResultsMild acidosis has beneficial effects in various experimental and clinical settings, whereas stronger acidosis is regularly toxic. On a cellular level mild acidosis has been proven to prolong human neutrophil lifespan by induction of phosphorylation of Akt, ERK, and p38MAPK, and therefore stabilizing mitochondrial transmembrane potential, delaying mitochondrial permeability transition and apoptosis. The same mechanism was found in ischemia/reperfusion injury models in which induced acidosis during reperfusion attenuated mitochondria‐dependent apoptosis and reduced reperfusion injury. The positive effect of a mild acidosis was also found in models of ventilator‐induced lung injury where permissive hypercapnia exerted positive effects. Mild alkalosis may be physiologically beneficial. The positive effects of mild alkalosis are mostly found in human exercise studies. It has been shown there to potentiate lactate efflux and by doing so improving cellular metabolism. Extracellular alkalosis during exercise contributed to the preservation of intracellular‐to‐extracellular K+ gradient and therefore the stability of the muscle membrane, and overall performance. Mild metabolic alkalosis was also found to increase muscle glycolytic flux and H+ efflux and increased total work done along with decreased exercise‐induced muscle fatigue in humans.ConclusionMild acidosis and alkalosis follow the principle of the mirror‐J‐physiology. This interpretation of counterintuitive studies results could be a step forward in our understanding of integral homeostasis and body adaptation. Expectedly, moderate and strong acidoses and alkaloses have been found harmful/toxic.