Background
Sodium bicarbonate (NaHCO
3) is a well-established nutritional ergogenic aid. Supplementation can improve short-duration (~ 1–10 min), high-intensity exercise performance [
1], with various meta-analyses confirming its efficacy [
2‐
4]. As an extracellular buffering agent, NaHCO
3 enhances endogenous bicarbonate buffering capacity by inducing significant, albeit transient, elevations in extracellular bicarbonate. Consequently, this enhances efflux of hydrogen cations (H
+) from skeletal muscle, therefore delaying muscle fatigue and positively affecting numerous performance variables, such as power output [
5] and time to exhaustion [
6]. While it remains unclear whether minimal increases are required to achieve these benefits, substantial changes (~ 6 mmol∙L
−1) in blood bicarbonate may improve the likelihood of performance-enhancing effects [
2,
7]. Given that bicarbonate is lost in the neutralisation of gastric acid [
8], large oral doses (200–300 mg kg
−1 body mass) are required to induce meaningful elevations in the blood.
Acute gastrointestinal (GI) distress is a known side-effect of ingesting large amounts of NaHCO
3 [
9], particularly when administered as an aqueous solution [
10]. Ergogenic effects have still been observed in those reporting GI distress [
1,
11]; however, there is evidence to suggest that GI distress may be ergolytic for some individuals [
1,
12‐
14]. Furthermore, some authors have suggested that GI distress may deter individuals from using NaHCO
3 regardless of its potential ergogenic benefits [
7]. Although the impact of GI distress on performance remains ambiguous, symptoms such as vomiting and diarrhoea may present a major practical limitation for athletes and coaches.
Polymeric-coated compounds can resist gastric degradation and reduce GI symptoms provoked by acid sensitive compounds, such as NaHCO
3 [
15]. Hydroxypropyl methylcellulose, contained in delayed-release capsules, can resist degradation in acidic environments (pH ~ 1–2 arbitrary units (AU)), and therefore, provides gastro-resistant properties. Instead, degradation occurs in the duodenum where the pH is far more alkaline (pH ~ 6–7 AU) and absorption can take place rapidly. Since GI distress is partly attributable to degradation in the stomach [
8], it has been suggested that gastro-resistant capsules may alleviate symptoms that are typical with NaHCO
3 ingestion [
16]. Given that less bicarbonate is lost in the stomach, it has also been suggested that smaller doses may produce comparable acid-base changes to larger doses [
16]. In contrast, as gut transit time is reduced with gastro-resistant formulations [
15], this may reduce bicarbonate bioavailability when administered in this form. No study to date has examined the use of delayed-release NaHCO
3 on markers of GI distress, nor on bicarbonate bioavailability and subsequent blood acid-base responses. Reducing GI distress following NaHCO
3 ingestion may enhance use by athletes, particularly among those who are deterred by potential side-effects.
Therefore, the aim of this study was to investigate whether delayed-release NaHCO3 could mitigate GI distress compared with an aqueous solution, as well as to compare the pharmacokinetic and acid-base responses. It was hypothesised that delayed-release NaHCO3 would reduce GI symptoms and display at least bioequivalence when compared to an aqueous solution.
Discussion
This is the first study to investigate the effects of gastro-resistant capsules on GI distress, bicarbonate bioavailability and subsequent acid-base responses following NaHCO
3 ingestion. The main finding was that delayed-release NaHCO
3 mitigated GI distress, as hypothesised. Fewer GI symptoms (~ 45.1%) were reported with the delayed-release capsules, and the overall severity was reduced (~ 47.1%) when compared to the aqueous solution. Interestingly, reductions in GI symptoms were due to gastric but not intestinal symptoms, a finding that has been suggested in the relevant literature [
15]. Gastrointestinal symptoms were negated with the delayed-release capsules, with a reduction in the most severe symptom experienced up to 3 h following supplementation (Table
1). Given that GI symptoms may be ergolytic [
13,
14,
26], delayed-release NaHCO
3 may be more ergogenic in those who experience severe GI distress with the aqueous solution. Furthermore, since GI distress may deter some individuals from using NaHCO
3 as an ergogenic aid [
7,
10], delayed-release NaHCO
3 would appear to be a more favourable option for athletes and coaches.
While necessary to achieve erogenicity [
27], large boluses (~ 200–300 mg kg
−1 body mass) of NaHCO
3 can induce significant GI symptoms. In the current study, there was a high incidence of GI distress with the aqueous solution, which is in agreement with some authors [
13] but not others [
10,
28]. Symptoms are considered to have both gastric and intestinal causes [
8], a finding that is supported by the current study. On entering the stomach, NaHCO
3 dissociates to sodium and bicarbonate ions, the latter of which produces carbon dioxide during the neutralisation of gastric acid [
8]. Consequently, carbon dioxide tension increases exponentially with exposure and is associated with gastric symptoms, such as belching, nausea and stomach ache. Intestinal symptoms, though partly induced from elevated carbon dioxide tension in the intestinal lumen, originate from excess sodium that aggravates the intestinal mucosa and creates osmotic fluctuations leading to bowel urgency and diarrhoea [
13]. Delayed-release capsules, partly formulated with a polymeric barrier, have gastro-resistant properties and can minimise disintegration in the stomach. Mitigating gastric symptoms may indeed have implications for performance. Previous research indicates that symptoms can inhibit high-intensity cycling performance [
14], while others have reported improvements irrespectively [
26]. Since numerous participants have withdrawn from studies due to GI distress [
29], previous research may have underestimated the ergolytic effect of such symptoms. Studies that have attempted to mitigate GI symptoms following NaHCO
3 ingestion have done so using alternative dosing strategies. Gelatine capsules co-ingested with a small high-carbohydrate (1.5 g kg
−1 body mass) meal are currently regarded as the formulation least likely to induce GI symptoms following NaHCO
3 ingestion [
10]. In the current study, delayed-release capsules were ingested after an overnight fast, largely to minimise potential confounding effects of food on acid-base changes. Nevertheless, co-ingestion with a small high-carbohydrate meal may have further reduced GI symptoms and warrants further investigation. Furthermore, while comparison with an aqueous solution was chosen based on its frequency of use within the literature, this may not be the case in the practice and is thus a limitation to the study. Future work should look to assess the pharmacokinetics of NaHCO
3 administered based on capsule composition only, so that the mechanism underpinning bioavailability and reductions in GI distress may be better understood.
In relation to bioavailability, both ingestion forms provided adequate sources of bicarbonate and displayed similar pharmacokinetic properties. Increases in bicarbonate were comparable, with both forms exceeding the 6 mmol L
−1 threshold suggested to enhance ergogenicity [
2]. Interestingly, some (
N = 3) participants displayed enhanced bicarbonate availability (≥ 1 mmol L
−1) with delayed-release capsules (Fig.
4), while only one participant was found to have enhanced bicarbonate availability of this magnitude with the aqueous solution. Similarly, more participants achieved a 5 mmol L
−1 (SOL
N = 10, CAP
N = 11) and 6 mmol L
−1 (SOL:
N = 8; CAP:
N = 9) increase in bicarbonate with the delayed-release capsules than with the aqueous solution. These results would be explained by the gastric bypass model proposed by Oliveira et al. [
16], which includes the effect of gastric transit time, and bicarbonate loss associated with neutralisation. As suggested by these authors, reducing bicarbonate neutralisation in the stomach increases bioavailability when NaHCO
3 is administered orally. Since changes of ~ 1 mmol L
−1 in bicarbonate concentration can positively affect performance [
26], delayed-release NaHCO
3 may elicit superior ergogenicity. In contrast to the aqueous solution, bicarbonate absorption did not commence immediately following capsule ingestion, suggesting that the delayed-release capsules were effective [
15,
30]. This result indicates that the capsules achieved disintegration in the intestine, which had the effect of lengthening (+ 48.3 min) the time to reach peak bicarbonate concentration. Bicarbonate peaked at ~ 120 min post-ingestion with the delayed-release capsules, which is later than previously reported with an aqueous solution in some studies [
20] but not all [
21]. Similar to previous studies [
31‐
33], there was a high degree of individual variability in the time to reach peak bicarbonate concentration, although this was greater with the capsules. The current findings for bicarbonate indicate that for most individuals, delayed-release NaHCO
3 may increase the likelihood of inducing a performance-enhancing effect; however, as this was not consistent for all individuals, decisions around ingestion form should be based upon individual concentration-time profiles.
Metabolic alkalosis was induced earlier with the aqueous solution (~ 40 min) than with delayed-release capsules (~ 60 min), although this state was maintained for longer (+ 30 min) when ingested in the delayed-release form. Homeostatic regulation, through respiratory compensation [
34], may have been stimulated to a lesser extent with slower bicarbonate absorption, rather than the abrupt elevation observed with an aqueous solution. Exercise performance timed with peak alkalosis may enhance the ergogenicity of NaHCO
3 [
7,
29]; therefore, it is reasonable to consider that delayed-release may provide a larger ergogenic window. In a competitive setting, this may be more favourable since performance may not commence parallel with peak alkalosis due to variable factors, such as sports fixtures. In the current study, time to reach peak alkalosis was much later with delayed-release NaHCO
3 (~ 125 min) than with the aqueous solution (~ 72 min), with one participant peaking at 180 min post-ingestion. In a practical setting, delayed-release NaHCO
3 would have to be ingested sooner than an aqueous solution to elicit similar acid-base changes. This may be favourable in terms of ergogenicity since GI symptoms were negligible at later time points. In contrast, given that bicarbonate concentrations were significantly lower with delayed-release NaHCO
3 up to 60 min post-ingestion, this form may be less ergogenic when ingested less than 60 min prior to exercise.