To the Editor Lazarus and collegues,1 both in the title and in the introduction of their article published in a recent issue of JAMA Internal Medicine, used the term lactic acidosis, which endorses the concept that lactic acidosis is a state of acidosis determined by an elevated plasma lactate concentration. This term, based on the old lactate paradigm,2 does not consider that, since the 1980s, this paradigm has radically shifted, and lactate is not considered responsible for acidosis. The same lactic acidosis is deemed a misnomer and should be replaced by the term lactate anion acidosis.3 Indeed, the intermediate acids—another misleading definition4—of glycolysis (including lactic acid) have a low pKa; therefore, at body pH levels, they all exist in their base form, and in their production process, no molecules are ever in an acid form and do not function as sources of protons. The acidosis associated with hypoxia is induced by the increased H+ production from the cytosolic adenosine triphosphate hydrolysis. As a matter of fact, the production of lactate also consumes 2 protons and, by definition, retards acidosis. Although blood lactate accumulation is a good proxy of increased proton release, and the potential for decreased cellular and blood pH, such relationships should not be interpreted as cause and effect, but rather “guilt by association.”5 More explicitly, high levels of lactate are only a marker for the acidosis. As physiologist Robert A. Robergs put it, “The lactic acidosis explanation of metabolic acidosis is not supported by fundamental biochemistry, has no research base of support, and remains a negative trait of all clinical, basic, and applied science fields and professions that still accept this construct.”6(pR502)
Gulli G. Lactic Acidosis, Metformin Use, and Dose-Response Association. JAMA Intern Med. 2018;178(10):1428. doi:10.1001/jamainternmed.2018.4433
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