Lactate: metabolic fuel or poison

Dr Robergs has written an interesting commentary in response to my recent Viewpoint espousing lactate as a metabolic fuel (Lindinger, 2011). While the title of the Viewpoint was designed to attract attention, criticism was levelled at the fact that I did not discuss the ‘benefits’ of lactate accumulate on muscle function, and that I did not make remarks about the stoichiometry between lactate efflux and apparent H+ efflux from contracting muscle fibres. These topics do not freely arise from the paper by Kitaoka et al. (2011) and, given the word constraints on Viewpoints, did not warrant comment at the time. Robergs refers to biochemical reactions represented by published biochemical equations as a proof of how metabolic pathways in contracting skeletal muscle actually work (Robergs, 2011; Robergs et al. 2005). These equations and reaction schemes are constructs that represent the current understanding of some, but not all, people who are interested in skeletal muscle function. The reality may be quite different from these contructs. One example is provided by the proposed functioning of the monocarboxylate transporter, which is purportedly a lactate−–H+ symport. There is no physical evidence that a proton is actually transported. There is also no evidence that a proton can physically be transported by the sarcolemma by any means. Physical studies reveal that it is hydronium (H3O+) that is ‘sensed’ by electrodes and in turn interpreted by us as a proton. Furthermore, a given molecule of hydronium (or proton) is in fleeting physical existence, about 10−6 s (see Lindinger et al. 2005 for recent discussion of this topic). Thus, this ion (H3O+ or H+) is not amenable to any transmembrane transport process. One might therefore ask why some researchers evoke proton transport mechanisms. The main reason is that charge balance for transport across membranes is usually maintained (except in the case of the Na+,K+-ATPase) and that there is a measurable change in the pH of the extracellular solution in which the cellular studies are performed. One should then question why the pH of the extracellular, or intracellular, solution changes. There is agreement that a decrease in pH is associated with an increase in the concentrations of H+ and/or hydronium. There is no agreement that such a change in pH must occur by the physical transport of a ‘proton’ from one side of the membrane to the other. Physical and chemical studies can be performed (for example, see classical texts by Edsall & Wyman, 1958; Harned & Owen, 1958) to show that physically transporting lactate− from one side of a semi-permeable membrane to the other will raise the pH on the side where lactate− concentration is decreased and lower the pH on the side where lactate− concentration is increased. It can also be demonstrated physically and chemically that the pH change on either side of the membrane is due to changes in the association of hydronium with H+ and water and of H+ with HO− (Edsall & Wymann, 1958; Harned & Owen, 1958). Unfortunately, physiologists and many biochemists are not familiar with the physical characteristics of physiological solutions, and this has led to some unreasonable interpretations of physiological phenomena. Robergs also appears to refute the concept that intracellular acidosis is a contributor to skeletal muscle fatigue and urges us to take an ‘evidence-based view of the benefits of lactate production’‘rather than a traditional blame of fatigue and acidosis’. This is a strange comment given the evidence-based research supporting both the benefits, as well as the detriments, of intracellular lactate− accumulation on muscle fatigue/function, and of intracellular acidification on muscle fatigue/function (see Bangsbo & Juel, 2006 and related commentary). It is contrived to assert that lactate− does not have to have a ‘direct negative role’ in order to be implicated in skeletal muscle fatigue. Lactate−, by virtue of its physical and chemical properties in physiological solutions, affects solution acid–base chemistry and this, in turn, has effects on many cellular functions. While accumulation of muscle lactate is not evil, there is evidence-based research that it is a contributor to intracellular acidosis and to skeletal muscle fatigue using in vivo and in situ research models (Fitts, 1994; Bangsbo & Juel, 2006; Cairns, 2006; Messonnier et al. 2007; Cairns & Lindinger, 2008; Juel, 2008). Where is the in vivo and in situ evidence-based research showing that intracellular and extracellular lactate accumulation and acidification have beneficial effects on exercise performance?

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