Multiday acute sodium bicarbonate intake improves endurance capacity and reduces acidosis in men

Competitive sports performance is strongly dependent on optimal muscle function. During cycling exercise across the heavy and severe intensity domains [1], energy is provided more and more by anaerobic glycolysis. This leads to an increased rate of accumulation of metabolites, which have been linked with muscle fatigue (e.g. P_i, ADP, H⁺, and extracellular K⁺). Cycling exercise at the threshold between the heavy and severe domain, i.e. at ‘Critical Power’ (CP), can, in contrast to the theoretical concept [2], only be sustained for as long as 20 to 40 min [3] before task failure. Furthermore, it was shown that CP overestimates the highest possible metabolic steady state [4, 5] and, consequently, that exercise at or above CP is associated with a decline in muscle and blood pH [6, 7]. An activity-induced decrease in intracellular pH has been suggested to limit exercise because it inhibits glycogenolysis and glycolysis [8], increases muscular K⁺-release [9] and inhibits sarcoplasmatic Ca²⁺-release [10, 11]. Furthermore, it induces a metabolic acidosis that might impair muscle function [12] and compromise performance. To blunt the fall in intracellular pH and prolong time-to-exhaustion (T_lim), nutritional modulation might be a promising avenue. With respect to endurance exercise, to date especially sodium bicarbonate (NaHCO₃) has gained much attention. However, the mechanisms by which NaHCO₃ ingestion may enhance performance are not fully understood. It is believed that NaHCO₃ ingestion leads to an increase in blood bicarbonate concentration ([HCO₃^-]), which in turn increases extracellular buffer capacity. More precisely, it is proposed that the higher [HCO₃^-] gradient between blood and the intramyocellular compartment enhances H⁺-efflux out of the muscle cell, thereby delaying the fall in intracellular pH [13], which in turn may delay an impairment in optimal muscle function and performance [14, 15]. Therefore, NaHCO₃ supplementation would be expected to improve T_lim at CP if muscle pH is a limiting factor for exercise tolerance.

Basically, three types of NaHCO₃ supplementation protocols can be applied: acute (single dose), chronic (multiple dose) and multiday acute supplementation (one dose per day before competition for consecutive days of competition). During the acute delivery mode participants take one single dose (mostly 0.3 g∙ kg^-1 body mass NaHCO₃) 60 to 90 min before the start of competition. During the chronic delivery mode participants take a daily amount of NaHCO₃ (mostly 0.5 g∙ kg^-1 body mass), divided in 2 to 3 portions, for several days before competition takes place. On the day of competition, no NaHCO₃ is consumed [16, 17]. The multiday acute delivery mode comprises the ingestion of acute doses on consecutive days of competition. In contrast to the chronic loading protocol, acid–base balance is perturbed on every day during the multiday acute delivery mode. This fact leads to major differences regarding the acid–base status and accordingly the underlying mechanisms as well as the effectiveness of the different delivery modes. While the acute and chronic supplementation protocols are scientifically well described, data on the effects of multiday acute supplementation are lacking. There are several studies, which investigated NaHCO₃ ingestion during tournament-like sports, but only for single events. For example, it was shown that NaHCO₃ supplementation increases tennis performance [18] but does not affect prolonged intermittent cycling exercise performance [19]. However, up to date, no study investigated the effect of a consecutive multiday supplementation on consecutive multiday performance. Since consecutive, acute-load daily use of NaHCO₃ might represent an interesting option to increase performance during multiday competitions or tournaments that involve exercise in the heavy and severe intensity domains, further research is warranted. In particular, scientific knowledge is limited with respect to the recovery of the body’s acid–base balance after high-intensity exercise with NaHCO₃ supplementation and consequently, the initial positions on the following days remain elusive.

Thus, the purpose of this randomized, placebo-controlled, double-blind interventional crossover study was to investigate if multiday acute NaHCO₃ supplementation in well-trained endurance athletes leads to changes in T_lim at CP during constant-load cycle ergometer trials on a day-to-day basis with daily acute NaHCO₃vs. placebo supplementation for 5 days. Furthermore, we aimed to investigate if differences in T_lim can be explained by alterations in [HCO₃^-] and if the high amount of ingested Na⁺ influences plasma volume (PV) and thus [HCO₃^-]. Given that exercise at or above CP leads to muscle and blood acidification [6, 7], and that [HCO₃^-] increases extracellular buffer capacity [13], we hypothesized that consecutive, acute-load daily supplementation of NaHCO₃ increases T_lim relative to placebo. We assumed that an increase in [HCO₃^-] after the first intake is responsible for the rise in T_lim. Since during multiday NaHCO₃ intake, a high amount of Na⁺ is ingested and absorbed, detrimental effects on endurance performance are possible. In fact, a higher [Na⁺] leads to water retention and thereby results in PV expansion [20]. An increase in PV decreases blood ion concentrations, and as such results in a diminished [HCO₃^-], which in turn could counteract the benefits associated with NaHCO₃ intake. It is therefore questionable, whether [HCO₃^-] can be increased beyond the concentration reached after the first day of supplementation on all subsequent days of supplementation. Consequently, we hypothesized that PV expands following a high Na⁺ intake, limiting any further increase in [HCO₃^-], and consequently T_lim, beyond that observed after the first day of supplementation.

Several new findings have been observed in this randomized, placebo-controlled, double-blind interventional crossover investigation. First, multiday NaHCO₃ supplementation for 5 days increased T_lim at CP on each day relative to placebo in highly trained athletes. Second, there was no difference in the increased T_lim over the 5 days of supplementation with NaHCO₃ or NaCl. Third, the increase in T_lim was paralleled by increases in [HCO₃^-], pH and ABE. Fourth, [HCO₃^-] and [Na⁺] in the blood stabilized over time in the NaHCO₃ condition. Fifth, calculated PV increased during the NaHCO₃ more than in the placebo intervention.

We found that NaHCO₃ supplementation led to an increase in T_lim at CP and that the improvement in T_lim was paralleled by an increase in blood [HCO₃^-], pH and ABE, indicating that the alteration in T_lim appears to be linked to an elevated extracellular buffer capacity. In fact, it has been shown that an increased [HCO₃^-] gradient between the intra- and extramyocellular compartment leads to an amplified H⁺-efflux from the muscle cell and delays the fall in intramyocellular pH [8, 14]. We observed a trend for higher [La^-] during the constant-load tests following NaHCO₃ supplementation (P = 0.070, data not shown), supporting the notion that the increased H⁺-concentration resulted from a lactate-proton symport. A fall in intramyocellular [H⁺] is associated with muscle fatigue due to 1) an inhibition of glycogenolysis and glycolysis [8], 2) increased muscular K⁺ release, 3) lesser contractility of the heart muscle [9], 4) inhibition of the sarcoplasmatic calcium release [10] and 5) inhibition of the actin-myosin interactions [11]. Thus, delaying the fall in intramyocellular pH might postpone the fatigue process and prolong intact muscle function. Indeed, our results showed that the ingestion of NaHCO₃ induced metabolic alkalosis, which in turn enhanced T_lim at CP and thus improved high-intensity exercise in the range of 10 to 20 min duration.

As hypothesized, T_lim at CP could be increased with NaHCO₃ supplementation. This is in contrast to the theoretical model, which states that an intramyocellular metabolic steady state exists at exercise intensities up to CP. However, our results support the notion that CP overestimates the metabolic steady state [4, 5]. Furthermore, our result that NaHCO₃ increased T_lim at CP extends previous findings showing that NaHCO₃ supplementation increases exercise above CP relative to placebo [14, 29]. In the latter studies, short high-intensity tests, during which intramyocellular pH falls rapidly from the beginning of exercise, were completed. During these types of tests, the finite work capacity above CP (W ^′ ) is drawn on after the start of exercise and becomes reduced. In light of our findings, these results might be interpreted to mean that NaHCO₃ simply increases W’. However, Vanhatalo et al.[23] showed that NaHCO₃ does not increase W’ during a 3-min all-out test, and concluded that changes in intramyocellular pH might not influence W’ in this particular test setting, and that for short all-out exercise, [PCr] dynamics is more important in determining W’. In our constant-load trials at CP, W’ was supplied to a large extent by anaerobic glycolysis. Therefore, we assume that NaHCO₃ supplementation increases W’ in conditions where acidification occurs during exercise. Our result that the estimated V̇ O₂ slow component was not different between the two interventions lends further credence to this notion, although the influence of NaHCO₃ on the V̇ O₂ slow component remains ambiguous (reduction: [30]; no change: [31]). In our study, the identical V̇ O₂ slow component for both, the NaHCO₃ and placebo condition, indicated that V̇ O_2peak was attained at the same point in time. Based on the fact that the depletion of W’ coincides with the attainment of V̇ O_2peak[32], our results indicate that NaHCO₃ ingestion did not increase the rate of W’ utilization but rather W’ itself. Further support for our assumption comes from another study, where average power in a 60 min cycling time trial was found to be higher with NaHCO₃ as compared to placebo [33]. During a 60 min time trial, power output will fluctuate around CP with power peaks occurring e.g. at the start and during (final) sprints. In these occasions, i.e. when exercising above CP, W’ will be reduced. Consequently, a higher W’ can increase performance during tests of longer duration, especially if pacing strategies are implemented.

We also found that five bolus intakes on five consecutive days did not result in an increase of T_lim beyond the value observed after the first intake. Thus, multiday administration of NaHCO₃ did not lead to a cumulative effect on endurance capacity. Accordingly, [HCO₃^-], blood pH, and ABE after multiday NaHCO₃ administration also remained unchanged relative to the initial rise after the first bolus. The most obvious explanation would be that during each CP-trial a certain amount of NaHCO₃ was used, leading to lower values for [HCO₃^-], pH and ABE post vs. pre test. During the following 24 h of recovery, the body would then be expected to re-establish the resting values. On the following day, the participants then would start the CP trial at similar (complete recovery) or lower [HCO₃^-], blood pH, and ABE (incomplete recovery) relative to the first day, whereby an additional increase in performance would not be expected. Although we did not measure [HCO₃^-], pH and ABE before supplementation on the following days, these two described cases can be most likely excluded. The reason for this is that [Na⁺] also did not increase during the consecutive 5 days of NaHCO₃ supplementation despite the fact that Na⁺, unlike HCO₃^-, was not used as a buffer during the CP trials, and that the high amount of ingested Na⁺ could not be used completely through sweating. The predicted sweating rate during exercise of 1 dm³∙ h^-1 water, with a sweat [Na⁺] of 50 mEq∙ dm³[34] would have led to a Na⁺ loss of ~0.36 g. This calculated sweat-induced loss of Na⁺ corresponds to ~20% of the daily Na⁺ intake during the placebo intervention. Regarding the substantially higher Na⁺ intake during the NaHCO₃ intervention, the sweat-induced loss of Na⁺ was negligible during this intervention.

As shown in this study, the NaHCO₃ intervention led to an increase in [Na⁺] and plasma osmolality after the first bolus administration. This increase was counteracted by an expansion in PV. The increase in PV was to such an extent that pre-exercise blood [HCO₃^-], pH, and ABE remained constant during the 5 days of testing. This proposed mechanism of PV expansion has already been described by Máttar et al.[35], who showed that plasma [Na⁺] and plasma osmolality were increased after NaHCO₃ injections in acute cardiac resuscitation. Other mechanisms to counteract increases in [Na⁺] and plasma osmolality comprise a shift of fluid from the intra- to the extramyocellular compartment [36], a stimulation of arginine vasopressin secretion [37], which leads to an intensified water retention from the kidneys [38], and a stimulation of the thirst center whereby more fluid is consumed [37]. In accordance with our results, McNaughton et al.[29] found an increase in plasma [Na⁺] after the first of five doses of NaHCO₃ but no further increase of plasma [Na⁺] on the following days. The elevation of PV in the present study is mirrored by the measured increase in DXA whole-body lean mass. In the DXA two-component soft tissue model, lean mass comprises water, proteins, glycogen and non-bone minerals [27]. As increases in protein, glycogen and non-bone minerals can virtually be excluded (see below), the increase in whole-body lean mass must have resulted from an increase in whole body water, which led to an expansion in PV. Our findings are in accordance with the report of Lands et al.[39] who found a significantly higher value for DXA-derived whole-body lean mass after saline infusion given to healthy male participants. Finally, our finding that HR_CLT was reduced lends further credence to our result that PV increased as a consequence of NaHCO₃ supplementation, because PV expansion simultaneously increases stroke volume and reduces sympathetic nervous activity, leaving V̇ O_2,CLT unaffected [40].

In our study, DXA-derived leg lean mass did neither change between interventions nor over time (Table 2). As with each gram of glycogen stored in muscle tissue 3–4 g of water is bound [28], and body water is present within the lean soft tissue compartment [27], a decrease in leg lean mass in such a short time (2 days) would indicate a loss of glycogen. In turn, glycogen loss would implicate incomplete regeneration, which would manifest itself in a reduced anaerobic work capacity and, accordingly, decreased performance [41]. Since our participants displayed neither a reduction in leg lean mass nor performance, the provided regeneration drink and the participants’ daily nutritional intake were sufficient to restore glycogen from day to day, allowing them to perform maximally on each day.

Our results have at least two practical implications. First, since the [HCO₃^-] gradient between intramyocellular compartment and blood did not decrease over time, NaHCO₃ can be taken daily in multiday competitions or tournaments lasting ≤ 5 d without the risk of reducing performance. Second, the apparent PV expansion in response to the high ion intake (see above) blunted any further increase in [HCO₃^-]. If the same mechanism would be true for the chronic supplementation protocol, the effectiveness of this protocol should be questioned, as it seems that [HCO₃^-] cannot be increased limitlessly, i.e. that it probably reaches a ceiling. The observed ceiling effect was probably based on a metabolic compensation mechanism preventing a disproportionate increase in [HCO₃^-]. A respiratory compensation mechanism is unlikely to have occurred in our study because there were no differences between the NaHCO₃ and placebo intervention for V̇ CO₂ (P = 0.903, data not shown) and RER (P = 0.556, data not shown) during the resting measurements before the constant-load tests. Of further note is that the standard chronic protocol comprises a daily dose of 0.5 g NaHCO₃ kg^-1 body mass [42], which might accentuate the increase in PV and possible side effects. Thus, one adequate dose of NaHCO₃ administered before the competition should be effective in mediating all of the performance-enhancing effects without the need of a “loading phase”. In this context, our results expand the findings of McNaughton and Thompson [16] as well as Siegler et al.[17], who compared different acute and chronic protocols and found that there are no differences between these ingestion protocols with respect to exercise performance.

It may be argued that the present findings could be limited by 1) differences in performance ability throughout the study period and 2) decreasing motivation. Regarding the first point we have shown that CP was neither different between the first and second intervention period nor before the NaHCO₃ and placebo condition. An increase in CP from the first to the second intervention would have indicated a training effect, whereas a decrease in CP would have indicated incomplete recovery. Hence, we can assume that the participants had the same performance ability throughout the study, allowing a comparison of T_lim between the two conditions. Regarding the second point, decreasing motivation in a single participant would be evident from a decrease in T_lim within or between interventions. Considering the single variations in T_lim irrespective of condition, during which no distinct increases or decreases in T_lim over time (i.e. from the second to the fifth test day) were identified, a decreasing motivation can be excluded for all participants. In addition, V̇ O_2,CLT, V̇ CO_2,CLT and RER_CLT were not different between conditions and days of testing. This indicates that the participants’ effort was constant during the whole study period.

In conclusion, multiple acute, consecutive day NaHCO₃ supplementation led to an increase in T_lim at CP after the first bolus intake. However, while T_lim remained elevated in the NaHCO₃ condition, it was not further altered with prolonged NaHCO₃ supplementation. The increase in T_lim was accompanied by a higher [HCO₃^-] gradient between the blood and the intramyocellular compartment, which stabilized over time in the NaHCO₃ intervention. In contrast to the theoretical CP-model, where metabolites should reach a steady state during exercise at CP, and consequently, buffer substances should be ineffective in enhancing T_lim, we showed that in practice T_lim can be increased with NaHCO₃ supplementation. Furthermore, the high amount of ingested Na⁺ caused a sustained elevation in PV, which inhibited a further increase in [HCO₃^-], and consequently limited the performance-enhancing effect. Therefore, this study indicates that NaHCO₃ can be taken daily in multiday competitions or tournaments to maintain performance ability throughout the whole duration of the competition.