COUNTERPOINT: THE LACTATE PARADOX DOES NOT OCCUR DURING EXERCISE AT HIGH ALTITUDE
2007; American Physiological Society; Volume: 102; Issue: 6 Linguagem: Inglês
10.1152/japplphysiol.00039a.2007
ISSN8750-7587
Autores Tópico(s)Adipose Tissue and Metabolism
ResumoPOINT-COUNTERPOINTCOUNTERPOINT: THE LACTATE PARADOX DOES NOT OCCUR DURING EXERCISE AT HIGH ALTITUDEGerrit van HallGerrit van HallPublished Online:01 Jun 2007https://doi.org/10.1152/japplphysiol.00039a.2007MoreSectionsPDF (51 KB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations Some 75 years of research has been undertaken studying lactate metabolism at acute and chronic exposure to altitude. Despite these endeavors there are no data providing either an explanation or convincing evidence for a change in muscle lactate production and accumulation in the blood during exercise at chronic exposure to altitude. The simple reason is that the lactate paradox does not exist. Hochachka (11) tried to explain the phenomenon. He suggested a reduced glycolytic potential and tighter coupling between ATP production and use, based on observation that Quechuas (altitude natives in the Andes) accumulated less lactate in blood than lowlanders and that they had a lower muscle lactate dehydrogenase activity (12, 13). However, these observations have been questioned as the subjects were anemic and the metabolic adaptation observed was due to anemia rather than to genetic or developmental hypoxia-induced adaptations (7). Indeed, we did not find any differences in muscle lactate dehydrogenase activity or isoform or other proteins involved in acid/base balance or lactate transport in Aymaras compared to lowlanders (15). Moreover, maximal lactate levels were similar, pointing at a similar glycolytic potential in altitude natives. Since Aymaras and Quechuas are closely related, it seems highly unlikely for genetic differences to explain the discrepancy in lactate dehydrogenase and blood lactate responses. In our study at Chacaltaya (Bolivia, 5,260 m), the lactate concentration and leg net lactate release were higher at submaximal but similar at maximal workloads compared to sea level after 9 wk of acclimatization. We wondered whether the altitude above that of permanent habitation or longer duration of acclimatization compared to most studies might have caused the lactate response to be similar as acute hypoxia after initially reduced levels. Our data were similar when the studies were performed after 2–8 wk at El Alto (Bolivia, 4,100 m), meaning that the lactate paradox does not exist (20, 25). In addition, the lactate concentration and net leg lactate release during continuous submaximal exercise were high after 4 wk of acclimatization (21) and confirmed the finding of Klausen et al. (18, 19). Additional support for the normal glycolytic potential after acclimatization is the observation that when incremental exercise until exhaustion was performed with a small muscle mass, one legged knee-extensor exercise, the submaximal and maximal net leg lactate release was the same (25). These studies and others (5, 6, 7, 17–19) provide further evidence that there is no change in glycolytical potential with chronic exposure to hypoxia. Furthermore, the relationship between relative workload and either plasma lactate accumulation or net leg lactate release was maintained with acclimatization in lowlanders (25). This was already shown previously by Dill (6) in 1931. The study of Dill was used by Reeves et al. (23) as the first report of the lactate paradox, “blood lactate during exercise initially rose higher in one subject (THE, Edwards), than at sea level, but after several months residence, the concentrations were similar to those at sea level.” However, two other subjects, Talbot and Dill, did not show a change in submaximal and peak lactate blood accumulation with acclimatization similar to our observations (20, 25). Second, and more importantly, Edwards' maximal lactate was actually unaffected with acclimatization, and the reason for his submaximal lactate levels nearing sea level values with duration of acclimatization was simply due to a shift of the lactate curves to the right caused by training. This meant that he was able to do similar work after 8 wk of acclimatization compared with sea level, which is actually discussed in the paper. Therefore, the Leadville expedition provides good support for the nonexistence of the lactate paradox, and it showed that at altitude the normal lactate to relative workload relationship is maintained, including that of Edwards.Maximal lactate levels are difficult to determine since that last 30–60 s of an incremental max test will make a big difference in lactate concentration due to the exponential nature of blood lactate accumulation. Therefore, the two studies of Brooks and coworkers published in a series of papers (1–4, 22) are the most convincing support for the lactate paradox, as they showed reduced arterial lactate levels during 40 min of continuous exercise at 50% V̇o2 max after 3 wk at Pikes Peak (4,100 m) compared with acute hypoxia. Unfortunately, the first report (1, 2, 4) has serious methodological problems. The two-legged glucose uptake and lactate release exceeded up to above 200% of the systemic glucose disappearance and lactate appearance. In addition, to determine lactate oxidation rates, an inappropriate tracer was used and the required tracer bicarbonate prime was omitted. Therefore, the conclusions from these papers should be ignored. Of note is also that in both studies from Brooks and coworkers, no difference in leg net lactate release was found between acute hypoxia and 3 wk of acclimatization, thus there were no differences in muscle lactate production similar to our findings (20, 25). This may suggest that in their study the rate of lactate clearance from the circulation was increased, causing the reduced arterial lactate accumulation.Another area with conflicting results is the activity in the sympathetic nerve system. It has been suggested that sympathoadrenal activity is reduced with acclimatization (22), but this was dismissed by direct muscle nerve activity determination (9). Consistent with these findings we have observed much higher blood levels of epinephrine and norepinephrine levels with acclimatization (20, 25). Despite the controversy on sympathetic activity it does not seem to be related to blood lactate levels, implying that it does not play a major role in muscle lactate production during exercise (20, 22, 25).If we are so certain that the lactate paradox does not exist, why does an important review on the topic (23) and in Handbook of Physiology (8) show a graph with data suggesting the existence of the lactate paradox? The graph is assembled from two studies that were designed to investigate pulmonary gas exchange with simulated altitude, not lactate accumulation. Nevertheless, Reeves et al. (23) used the lactate concentration of acute hypoxia data from Wagner et al. (27) and the chronic hypoxia data from the study of Sutton et al. (24). For the following reasons, the acute and chronic hypoxia data cannot be compared: 1) different and inappropriate discontinuous exercise protocols to study the lactate paradox phenomenon; 2) different simulated altitudes (429 Torr and 347 Torr) for acute and chronic hypoxia, respectively; 3) different subjects; 4) chronic hypoxia was not prolonged exposure to a certain level of hypoxia since altitude was increased continuously (14).In conclusion, we feel that there is more than reasonable doubt for the lactate paradox to exist and that no special adaptation occurs in the regulation of glycolysis to chronic hypoxic exposure. The studies that report a lactate paradox phenomenon might suffer more from confounders related to field studies in remote areas or hypobaric chambers, which cause lactate to be decreased with acclimatization not related to prolonged exposure to hypoxia per se. One could wonder whether the words of the Nobel Prize laureate A. V. 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J Appl Physiol 61: 260–270, 1986.Link | ISI | Google Scholar Download PDF Previous Back to Top Next FiguresReferencesRelatedInformation Cited ByDelayed parasympathetic reactivation and sympathetic withdrawal following maximal cardiopulmonary exercise testing (CPET) in hypoxia26 July 2018 | European Journal of Applied Physiology, Vol. 118, No. 10Regulation of human metabolism by hypoxia-inducible factor28 June 2010 | Proceedings of the National Academy of Sciences, Vol. 107, No. 28Variation in human performance in the hypoxic mountain environment9 February 2010 | Experimental Physiology, Vol. 95, No. 3The lactate paradox: a review18 June 2010 | Comparative Exercise Physiology, Vol. 7, No. 01The lactate paradox revisited in lowlanders during acclimatization to 4100 m and in high-altitude natives27 February 2009 | The Journal of Physiology, Vol. 587, No. 5Evidence that reduced skeletal muscle recruitment explains the lactate paradox during exercise at high altitudeT. D. 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