In the present study, we evaluated the effects of chronic NaHCO3 ingestion during 7 days of exposure to moderate and high altitudes on anaerobic performance parameters and laboratory blood and urine parameters. The primary finding of the study was that chronic NaHCO3 ingestion had a considerable impact on acid-base balance, which resulted in a higher alkalotic state; however, chronic NaHCO3 ingestion did not significantly influence PTSR-related performance outputs and associated physiological responses. A higher alkalotic acid-base balance prior to exercise under hypoxic conditions has been reported to be related to higher performance output and higher maximum blood lactate values after high-intensity exercise [11, 16, 19]. The suggested mechanism underlying the increased [H+] buffering from intramuscular to extramuscular compartments may lead to improved protection of intramuscular pH and increased anaerobic energy provision and glycogen utilization [16, 50]. However, although some outliers showed the expected increases in anaerobic performance outputs and the associated lactate response, the current study revealed no significant overall effect of chronic NaHCO3 ingestion on anaerobic performance outputs (indicated by ∆MF, ∆PF, and ∆FI) or on the related parameter ∆Lamax. This apparent discrepancy may be attributable to several factors.
Several recent studies reported increased or constant anaerobic exercise performance during acute altitude exposure in hypoxic chambers following supplementation with alkalizing agents prior to exercise [11, 16, 19, 22,23,24]. All these studies analyzed the effects of bicarbonate supplementation on different aspects of exercise performance under acute hypoxic conditions (between 15 min and 4 h of altitude exposure). In contrast, the present study assessed long-term altitude exposure over 7 days. We suggest that experimental acute hypoxia may not reflect the physiological acid-base responses to hypoxic conditions sufficiently, because the proposed lower [HCO3−] concentrations under hypoxic conditions  and the subsequently reduced [HCO3−] buffering capacity and anaerobic exercise performance [16, 17] should also take into account the time course of renal compensation of hypoxia-induced respiratory alkalosis, which is generally considered to be a slow-adapting mechanism affecting [HCO3−] concentrations after several hours or days. More specifically, renal [HCO3−] compensation has been shown to occur after 6 h and to be complete after 24 h of exposure to low to moderate altitudes, but to still be incomplete after 24 h of exposure to high altitudes . In the present study, the enhanced renal [HCO3−] compensation was most obvious in the first 3 days of hypoxic exposure based on early morning urinary pH values. This finding complements the results of Ge et al. , who reported the renal [HCO3−] compensation based on early morning urinary pH values at simulated moderate altitudes of 1780, 2085, 2455 and 2800 m. They demonstrated that renal compensation was completed by 24 h at 1780, 2085 and 2455 m, but not at 2800 m. The time course of urinary pH values in our control group suggested that the renal [HCO3−] compensation at higher altitudes (between 2500 and 3500 m) seemed to be completed by 48 h. However, these results should be interpreted with caution because there was no significant increase of early morning urinary pH in the control group. This may be because of the high variability in pre-test urine and blood pH values. Urine and blood pH are influenced by several external factors such as nutrition, intake of dietary supplements, and high-intensity exercise . Although subjects in the present study were asked to cease any special diets, supplements, and high-intensity exercise at least 2 days before the pre-testing, their nutrition was not controlled. Remer  showed a high impact of alkalizing-food intake on urine and blood pH values within 3 days, suggesting that nutrition should be standardized and controlled at least 3 days before anaerobic exercise testing in future investigations to reduce variability in urinary pH. In summary, we suggest that NaHCO3 ingestion during an altitude sojourn might be most effective when renal compensation of respiratory alkalosis is in progress or completed. However, to the best of our knowledge, the exact time course of renal compensation of hypoxia-induced respiratory alkalosis is unknown, and should be investigated in a controlled setting with at least 6 h of hypoxic exposure.
Notably, hypoxia-induced respiratory alkalosis is usually described as a desirable and important process that contributes to altitude adaption . Chronic NaHCO3 ingestion thus contrasts with recommendations regarding the use of acetazolamide for the prevention of AMS when ascending to moderate and high altitudes . Acetazolamide is a potent carbonic anhydrase inhibitor that increases minute ventilation and oxygenation and causes diuresis and renal [HCO3−] loss by enhancing central chemoreceptor output . Via this mechanism, acetazolamide has been shown to provide prophylaxis for the symptoms of AMS in individuals ascending to high altitudes [55, 57]. Because NaHCO3 ingestion aims to compensate for the [HCO3−] loss rather than supporting hypoxia-induced diuresis and the associated renal [HCO3−] loss, we measured the AMS score every morning using the LLS in the present study, to control a potential higher risk of AMS due to NaHCO3 ingestion. However, chronic NaHCO3 ingestion had no significant effect on LLS values during the 7-day altitude sojourn, suggesting that it did not increase the risk of developing AMS symptoms. In addition, information on the effect of acetazolamide on exercise performance is still insufficient. Although acetazolamide was shown to impair submaximal and maximal exercise performances at sea level, its influences on submaximal and maximal exercise at altitude remain controversial . We therefore conclude that NaHCO3 supplementation as an alkalotic buffer remains an interesting approach to alleviating acidic stress during exercise above the lactate threshold under hypoxic conditions, with no increase in the risk of AMS development.
The current dosage strategy may have been another possible reason for the lack of anaerobic performance enhancement by chronic NaHCO3 ingestion, which was contrary to our original hypothesis. We administered NaHCO3 according to a chronic schedule due to a lack of studies using chronic dosing schedules ; moreover, a chronic alkalotic state may meet the requirements of mountain sport disciplines better than single-dose NaHCO3, resulting in short-term performance enhancement. However, the effects of chronic NaHCO3 ingestion on anaerobic exercise performance improvements may have been hindered by the relatively long mountaineering exercise with altitude exposure, as well as the associated altitude adaption processes. Furthermore, most studies investigating the influence of NaHCO3 supplementation on anaerobic exercise performance under acute normobaric hypoxic conditions determined the individual time to peak [HCO3−] after NaHCO3 ingestion, and administered NaHCO3 in test trials at the participant’s pre-determined time to peak [HCO3−] to achieve the optimal performance changes [11, 16, 19]. The time course to peak blood [HCO3−] using liquid supplementation has previously been shown to range from 40 to 90 min . Unfortunately, we were unable to assess the pre-determined time to peak [HCO3−] in the present study and we therefore decided to administer the daily NaHCO3 dose in 1 l of water 60 min before exercise testing. Although we assumed that this time frame met the requirements for maximizing the ergogenic effect of NaHCO3, it is possible that individualized supplementation strategies may be superior for the optimization of the performance-enhancing properties of NaHCO3.
It is also possible that the results might have differed if anaerobic performance tests had been performed at higher altitudes or for longer altitude exposures and associated daily NaHCO3 ingestion periods. We therefore intended to assess anaerobic performance after 7 days of NaHCO3 ingestion (HYP6) at 4554 m, but were unable to report the associated performance data due to computer crashes caused by high-altitude barometric pressure changes. Follow-ups to the current pilot study should thus focus on anaerobic performance tests at higher altitudes and after longer NaHCO3 ingestion periods, bearing in mind the potential computer-related problems caused by high altitude barometric pressure changes. Additionally, it has been proposed that performance of single sprints of short duration (up to 45 s) can be maintained in acute hypoxic conditions because of a shift toward anaerobic metabolism, whereas power output for tests with continuous or repeated high-intensity exercise longer than 45 s (such as the 3-min all-out critical power test and repeated sprints [11, 59, 60]), is often reduced in acute hypoxia [61, 62]. Therefore, we assumed that a 60-s continuous test protocol would be sufficient to assess changes in anaerobic exercise performance under hypoxic conditions. However, we presume that follow-up studies may involve the use of different test protocols, including assessments of all-out running for longer durations up to 3 min or repeated-sprint performance, to further investigate the results of impaired anaerobic exercise performance in hypoxia.
A further potential limitation of the present study and possible explanation for the lack of any significant effect of chronic NaHCO3 ingestion on ∆MF, ∆PF, ∆FI, and ∆Lamax may be the low test-power of the comparisons between the bicarbonate and control groups. An a priori power calculation indicated that a sample size of three participants per group would allow the detection of differences between the groups, based on an earlier study that reported significantly improved force in a 60-s anaerobic performance cycling test under normoxic conditions after chronic NaHCO3 ingestion, with a statistical power of 57% . However, we acknowledge that the use of data from the abovementioned investigation resulted in a surprisingly low calculated sample size for detection of possible changes. Indeed, smaller effect sizes were found within the current investigation and a sample size of 10 participants resulted in a test power of 10% (6–14%) for the effect of NaHCO3 ingestion on PTSR-related parameters. In contrast, power calculations for the metabolic parameters measured in this study were associated with higher power values (11–99.8%). This indicates sufficient test power to analyze the effect of NaHCO3 supplementation, but an underpowered trial in terms of determining the effect of anaerobic exercise at altitude, making the detection of significant difference in ∆MF, ∆PF, ∆FI, and ∆Lamax between the bicarbonate and control groups highly unlikely. These small effects meant that we would probably not be able to detect differences in these parameters with the current sample size of 10 participants, and could therefore not exclude a type 2 error within our interpretation.
Furthermore, the high individual variations represented by individual trajectories in Fig. 2 in response to anaerobic exercise at altitude may have contributed to the lack of power for the effect of anaerobic exercise at altitude. Individual variations in this context may represent a previously suggested responder vs. non-responder phenomenon to intervention with NaHCO3 supplementation [64, 65] or exercise performance changes under hypoxic conditions [66, 67]. Another explanation for variations in the response to anaerobic exercise at altitude may be an unfamiliar exercise pattern, such that the participants were unable to properly implement the test instructions. It has already been shown that tethered sprinting reduces maximal velocity, flight time, and stride length, and increases contact time, compared with free sprinting [68, 69]. Therefore, it is possible that the PTSR test pattern may have prevented our participants from sprinting to their full potential, meaning that the maximal performance measurement may not reflect the participants’ true maxima. In addition, the inclusion of a single female participant in each group may have contributed to variability in the effect of anaerobic exercise at altitude; a general sex-related difference may have introduced additional heterogeneity. We therefore also performed statistical analyses on PTSR-related performance parameters in male participants alone, but found no significant differences in the outcomes from the results of analyzing the complete groups. Therefore, we decided to report the data from both groups, including the female participants, to achieve higher study power.
Nevertheless, we assumed that the possible undetected differences in PTSR-related performance parameters were likely to be too small to contribute to an anaerobic performance enhancement, and influences of other factors may have negatively affected the ergogenic effects of NaHCO3 ingestion. This assumption was supported by the higher [HCO3−] and BE values pre- and post-PTSR in the bicarbonate group compared with the control group, but the lack of any significant difference in exercise-induced difference between pre- and post-PTSR values. Recent studies reported an increased glycolytic energy contribution to exercise and improved anaerobic exercise performance following NaHCO3 ingestion under normoxic  and acute hypoxic conditions . It has also been suggested that changes in blood pH and [HCO3−] are greater during exercise with NaHCO3 ingestion and the associated elevation of pre-exercise [HCO3−] and BE values, which is supposed to explain the increased anaerobic exercise performance in acute hypoxic conditions following NaHCO3 ingestion . However, our data do not support these assumptions because despite higher [HCO3−] and BE values pre- and post-PTSR following NaHCO3 ingestion, only the exercise-induced difference between pre- and post-PTSR values for ∆pHb differed between conditions, indicating similar glycolytic energy contributions and exercise performance outputs irrespective of NaHCO3 ingestion, but a possible difference in respiratory contributions resulting in less-pronounced acidosis following NaHCO3 ingestion.
Participant acclimatization may also have had a negative influence of the ergogenic effect of NaHCO3 ingestion by negating the additional acidic load apparent in unacclimatized individuals. Although the results for saO2, [HCO3−], and BE do not suggest that our participants were already fully acclimatized at HYP3 when they performed the PTSR test at altitude, further studies are needed to prove the assumptions raised in the present pilot study. Furthermore, the unexpected lack of an ergogenic effect of NaHCO3 could be explained by the theory of strong ion difference (SID) . The present findings refer to the Henderson-Hasselbach approach, which assumes that blood pH is determined by changes in [H+] and [HCO3−]. In contrast, the SID approach refers to the intra- and extracellular ions (e.g. chloride, potassium, sodium) and describes the difference between the concentrations of strong cations and strong anions. The SID is also suggested to have an independent effect on blood pH, and thus impair muscle performance by altering intra- or extra-cellular pH . The SID approach may therefore explain the exercise-induced difference between pre- and post-PTSR values for ∆pHb between the bicarbonate and control groups with simultaneously similar developments of changes in PTSR-related parameters, [HCO3−], and BE. However, this conclusion should be interpreted with caution because we did not calculate the SID values in the present study, and future studies are needed to examine the influence of changes in the SID on anaerobic exercise performance at altitude.
PTSR performance parameters in this study might also have been influenced by gastro-intestinal (GI) disturbances. Negative GI symptoms caused by bicarbonate ingestion have been reported in the literature [21, 72, 73] and GI discomfort is suggested to have ergolytic effects on anaerobic performance [15, 19]. Unfortunately, we did not carry out any structured monitoring of GI discomfort in the current participants, which represents a limitation of this study. However, we asked the subjects—in daily individual unstructured interviews—about any GI disturbances after consuming the NaHCO3 solution; most participants in the bicarbonate group reported GI complaints after NaHCO3 ingestion. We mainly attributed these GI disturbances to the dose of NaHCO3 (0.3 g/kg). Although this dose has been recommended for NaHCO3 supplementation under normoxic and hypoxic conditions [15, 16, 39,40,41,42], smaller doses have been suggested for participants who display severe GI symptoms after NaHCO3 ingestion . Given that GI discomfort seems to increase with increasing NaHCO3 dose , we decided to reduce the dose to 0.15 g/kg body mass on day five of supplementation, after which the subjects’ reported GI symptoms decreased. However, in retrospect, we would potentially recommend a reduction to the common dose of 0.20 g/kg body mass, rather than the pronounced reduction (by 50%) to 0.15 g/kg body mass. Finally, within the present study, the PTSR test under hypoxic conditions was performed at a dose of 0.3 g/kg, and the performance outputs may have been inhibited due to GI discomfort. In addition, it must be noted that GI problems are common at high altitude and are often reported, regardless of NaHCO3 ingestion [74, 75]. The reported GI discomfort in the present study may thus have been due to both NaHCO3 ingestion and altitude exposure. Further investigations under hypobaric hypoxic conditions should thus be performed using NaHCO3 at a lower dose or in a different dosage form; these should include controls for and monitoring of GI upset using structured daily self-reports . Different dosage forms and strategies that have been reported to reduce GI side effects include the use of tablets or capsules (instead of liquid supplementation), serial loading , and co-ingestion of NaHCO3 with water and a high-carbohydrate meal . Future studies should include the use of a placebo supplement for the control group; this aspect was not implemented in the present study and therefore constitutes a limitation of the study.
Finally, another limitation of the study is that it was not double-blinded. Although the study was originally designed with this in mind, the serious gastrointestinal problems reported by the participants forced us to inform the study investigators and participants regarding group affiliations, prior to reducing the NaHCO3 dose. Therefore, the present study provides the first results in this field, but further research is needed to confirm the findings of this investigation with regard to the effects of chronic NaHCO3 ingestion on anaerobic exercise performance under hypobaric, hypoxic conditions.
Although mountaineering is mainly associated with aerobic performance , the results of the current study will be applicable to other mountain sports disciplines performed at moderate to high altitudes. Previous studies demonstrated the need for a high level of anaerobic power during steep climbs and sprints in cross-country ski races , and cross-country sprint disciplines with maximal-effort durations of 2.5–3 min are also expected to have a significant anaerobic contribution . Moreover, alpine ski races last for 45 s to 2 min, and anaerobic fitness has been identified as being of primary importance in alpine skiing [32, 33]. To the best of our knowledge, no studies have examined ski mountaineering, though the findings for alpine skiing may be transferable to ski touring and ski mountaineering. Additionally, anaerobic power has been suggested to be an important determinant of performance in cross-country and downhill mountain biking and transalpine challenges [34, 35, 77]. Unfortunately, no studies have examined the physiological requirements of disciplines such as multi-pitch rock, mixed, or ice climbing, and recent studies have focused on the physiology of difficult rock or indoor climbing. Performance in single-pitch climbing disciplines is mainly determined by anaerobic power and muscular strength [36, 37]; it might be necessary to consider whether multi-pitch climbing requires greater anaerobic power due to longer exercise duration. However, further studies are required to support these assumptions. The above-mentioned sport disciplines are thus affected by hypoxia-induced reduced exercise performance at altitude and may therefore benefit from a dietary strategy involving NaHCO3 ingestion to improve anaerobic exercise performance.