A Comparison of Sodium Citrate and Sodium Bicarbonate Ingestion: Blood Alkalosis and Gastrointestinal Symptoms

in International Journal of Sport Nutrition and Exercise Metabolism

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Charles S. UrwinCentre for Sport Research, School of Exercise and Nutrition Sciences, Faculty of Health, Deakin University, Geelong, VIC, Australia

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Rodney J. SnowInstitute for Physical Activity and Nutrition, School of Exercise and Nutrition Sciences, Faculty of Health, Deakin University, Geelong, VIC, Australia

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Dominique CondoCentre for Sport Research, School of Exercise and Nutrition Sciences, Faculty of Health, Deakin University, Geelong, VIC, Australia
Institute for Physical Activity and Nutrition, School of Exercise and Nutrition Sciences, Faculty of Health, Deakin University, Geelong, VIC, Australia

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Rhiannon M.J. SnipeCentre for Sport Research, School of Exercise and Nutrition Sciences, Faculty of Health, Deakin University, Geelong, VIC, Australia

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Glenn D. WadleyInstitute for Physical Activity and Nutrition, School of Exercise and Nutrition Sciences, Faculty of Health, Deakin University, Geelong, VIC, Australia

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Lilia ConvitCentre for Sport Research, School of Exercise and Nutrition Sciences, Faculty of Health, Deakin University, Geelong, VIC, Australia

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Amelia J. CarrCentre for Sport Research, School of Exercise and Nutrition Sciences, Faculty of Health, Deakin University, Geelong, VIC, Australia

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This study compared the recommended dose of sodium citrate (SC, 500 mg/kg body mass) and sodium bicarbonate (SB, 300 mg/kg body mass) for blood alkalosis (blood [HCO3]) and gastrointestinal symptoms (GIS; number and severity). Sixteen healthy individuals ingested the supplements in a randomized, crossover design. Gelatin capsules were ingested over 15 min alongside a carbohydrate-rich meal, after which participants remained seated for forearm venous blood sample collection and completion of GIS questionnaires every 30 min for 300 min. Time-course and session value (i.e., peak and time to peak) comparisons of SC and SB supplementation were performed using linear mixed models. Peak blood [HCO3] was similar for SC (mean 34.2, 95% confidence intervals [33.4, 35.0] mmol/L) and SB (mean 33.6, 95% confidence intervals [32.8, 34.5] mmol/L, p = .308), as was delta blood [HCO3] (SC = 7.9 mmol/L; SB = 7.3 mmol/L, p = .478). Blood [HCO3] was ≥6 mmol/L above baseline from 180 to 240 min postingestion for SC, significantly later than for SB (120–180 min; p < .001). GIS were mostly minor, and peaked 80–90 min postingestion for SC, and 35–50 min postingestion for SB. There were no significant differences for the number or severity of GIS reported (p > .05 for all parameters). In summary, the recommended doses of SC and SB induce similar blood alkalosis and GIS, but with a different time course.

Performance of short-duration and high-intensity exercise can be limited by the deleterious effect of acidosis which has been noted to occur during this type of exercise (decreased blood pH and blood bicarbonate concentration [HCO3]; Fitts, 2016). Accordingly, athletes competing in events such as 4,000 m cycling, 1,500 m running, and 2,000 m rowing can aim to minimize the inhibitory effect of acidosis by inducing blood alkalosis (increased blood pH and [HCO3]) prior to their event (Maughan et al., 2018). Blood alkalosis can be induced by sodium citrate (SC) or sodium bicarbonate (SB) ingestion (Carr et al., 2011), both legal and commercially available dietary supplements. Supplementation with SB has been investigated for over 90 years, while supplementation with SC has been investigated for over 60 years (Dennig et al., 1930; Johnson & Black, 1953). However, the supplements have been compared in the same investigation on only a few occasions, returning equivocal findings regarding exercise performance and blood alkalosis (Kumstát et al., 2018; Potteiger et al., 1996; Van Montfoort et al., 2004). Further investigation is also warranted to identify differences between the supplements with regard to the number and severity of associated gastrointestinal symptoms (GIS), which may influence their efficacy for athletes.

Prior investigations of SB or SC supplementation have identified that both induce blood alkalosis compared with baseline or placebo (Hilton et al., 2019; Urwin et al., 2016). It has been suggested that a 6 mmol/L or greater increase in blood [HCO3] may improve the likelihood of an ergogenic benefit being obtained (Boegman et al., 2020), although further investigation is needed to confirm this potential threshold because similar outcomes were reported when this increase was 4–6 mmol/L (de Oliveira et al., 2021). Ingestion of the recommended dose of either SC (500 mg/kg body mass [BM]) or SB (300 mg/kg BM) typically elicits an increase in blood [HCO3] of between 5 and 8 mmol/L (Boegman et al., 2020; Hilton, Leach, Hilton, et al., 2020; Russell et al., 2014; Urwin et al., 2019; Vaher et al., 2014). The only previous investigation to have administered the recommended dose of both supplements reported no difference between SC (500 mg/kg BM) and SB (300 mg/kg BM) for the magnitude of blood alkalosis (Potteiger et al., 1996). These doses, as well as the use of capsules rather than solution as the delivery mode, are recommended because they are associated with a possible ceiling of exercise performance benefit and/or induced blood alkalosis (i.e., greater doses produce no further ergogenic benefit or alkalosis; McNaughton, 1990, 1991; Urwin et al., 2016, 2019). It therefore appears that SC and SB supplementation in capsules can induce blood alkalosis to an extent that may improve performance, but more experimental data are needed to support the sole prior study that implemented the currently recommended dose of each supplement.

Separate investigations have reported that peak blood alkalosis occurs ∼180–240 min postingestion for SC (Urwin et al., 2016, 2019, 2021) and ∼30–180 min postingestion for SB (Boegman et al., 2020; Gough et al., 2018; Jones et al., 2016), suggesting that peak alkalosis may occur later with SC supplementation. Indeed, a recent study which directly compared the two supplements using the same dose (i.e., 300 mg/kg BM) reported a significantly later peak for blood [HCO3] with SC when compared with SB (Peacock et al., 2021). Interestingly, when the recommended doses for each supplement were compared (Potteiger et al., 1996), there also appeared to be a delayed blood [HCO3] peak with SC (120 vs. 100 min); however, it was unclear from the report whether this time difference was statistically significant. Therefore, it is currently unclear whether time to peak alkalosis is in fact delayed with SC compared with SB ingestion with recommended doses. Additionally, past research has not assessed blood alkalosis beyond 180 min postingestion, so a more prolonged comparison with respect to the time course of blood alkalosis is warranted.

Participants have reported GIS following ingestion of SC or SB in several studies (Cerullo et al., 2020; Requena et al., 2005; Urwin et al., 2020), possibly limiting exercise performance (de Oliveira et al., 2014; Hoffman & Fogard, 2011). In studies investigating ingestion of SC or SB, different proportions of participants have reported GIS across studies, likely due to differing supplementation protocols and GIS assessment tools (i.e., questionnaires and scales). The International Olympic Committee identified SC as an alternative to SB, on the basis that SC may elicit less GIS (Maughan et al., 2018). However, no prior studies have statistically compared GIS between SC and SB using the recommended dose of both supplements (SC = 500 mg/kg BM; SB = 300 mg/kg BM). Only one investigation has conducted statistical comparisons of GIS following ingestion of SC and SB (Peacock et al., 2021), where 300 mg/kg BM SB elicited a greater number and severity of GIS when compared with 300 mg/kg BM SC. Therefore, there is currently limited evidence on which to make recommendations on the comparative suitability of SC and SB with regard to GIS when the recommended doses of each supplement are consumed.

The primary aim of this investigation was therefore to compare the effect of ingestion of 500 mg/kg BM SC to ingestion of 300 mg/kg BM SB on GIS (number and severity), and the secondary aim was to compare for induced blood alkalosis (peak and time to peak blood pH and blood [HCO3]).

Materials and Methods

Participants

Healthy and recreationally active (McKay et al., 2022) participants (n = 16; eight males and eight females; mean ± SD for age, 27 ± 4 years; BM, 72.81 ± 10.65 kg; height, 1.75 ± 0.11 m) were recruited, with eligibility and inclusion determined via health questionnaire. Individuals were excluded from participation if they reported a history of kidney disease or use of medication that alters blood acidity. Participants were informed of the nature of the investigation, including potential risks and benefits, and signed a written informed consent statement. The Deakin University Human Research Ethics Committee (2021–2023) approved all protocols. No participant dropout occurred, and therefore, all 16 participants completed all protocols.

Study Design Overview

Each participant completed three sessions; the first comprised the assessment of eligibility, and measurements of height and BM. Two experimental sessions were completed using a double-blinded, crossover design. The order of supplementation for each participant was randomized by computer-generated sequence (Urbaniak & Plous, 2013). On the day before each experimental testing session, participants recorded all food and fluid ingested, and the duration, intensity, and type of exercise undertaken (Easy Diet Diary [EDD]; Xyris). Due to an absence of evidence to suggest that diet in the day(s) prior to SC or SB supplementation impacts postingestion responses, and the absence of an exercise test within this study, dietary standardization was not performed >60 min prior to the commencement of each session. Within-session dietary standardization is described below. Participants were instructed to avoid alcohol and caffeine on the day of each session, checked verbally and via EDD upon arrival. Participants arrived ∼07:30 a.m. having fasted overnight from 10:00 p.m. the night before and voided their bladder immediately before commencing the ingestion protocol. The washout period (mean ± SD days) between experimental sessions was 24 ± 31 days. BM and subsequent supplementation composition were reassessed for participants with a washout period exceeding 14 days (n = 4), which was an unintended consequence of COVID-19-related restrictions.

Experimental Testing Sessions

According to the findings of recent ingestion protocol studies (Urwin et al., 2019, 2021), participants ingested the relevant supplement over a 15-min period, in size 0 gelatin capsules (Melbourne Food Ingredient Depot). The number of capsules (mean ± SD) ingested was 39 ± 6 and 23 ± 3 in the SC and SB treatments, respectively. Capsules were provided in opaque bags to minimize the potential impact that the necessary different numbers of capsules may have had on subsequent participant responses. Participants co-ingested a standardized carbohydrate-rich meal (1.75 g/kg BM; Thomas et al., 2016), consisting of an average per participant of: 750 ml Powerade, 1.5 slices bread, 21 g of jam, one muesli bar, and one banana (Woolworths).

For standardization across participants and sessions, capsules, drinks, and meals were consumed in three equal portions (0, 7.5, and 15 min). For the 300-min postingestion period, participants remained seated and consumed a similar volume of water across sessions (ad libitum in the first session, matched in the second; mean ± SD water intake was 967 ± 484 ml for sodium citrate, 870 ± 334 ml for sodium bicarbonate; p = .705 estimated via linear mixed models described in the statistical analyses section below).

Blood Collection and Analysis

Forearm venous blood samples (1 ml) were obtained at baseline (preingestion), immediately after ingestion, and every 30 min for 300 min after ingestion, via a cannula inserted in the antecubital vein prior to supplementation and kept patent via saline infusion postsampling. Blood samples were drawn via safePICO syringe (Radiometer) and were immediately analyzed for blood pH and blood [HCO3] using a blood-gas analyzer (Radiometer ABL800).

GIS Questionnaire

Participants completed a questionnaire to assess GIS (number and severity; Gaskell et al., 2019) at the same time points as described for blood sampling. Participants rated how they were experiencing “overall gut distress” and 16 specific GIS (seven upper, six lower, and three other GIS) on an 11-point Likert scale. Any GIS rated as ≥5 out of 10 was classified as “severe,” as this represented midway between “no symptoms” and “extremely bad symptoms” (Gaskell et al., 2019).

Statistical Analyses

Data normality was assessed using Shapiro–Wilk tests. Longitudinal blood pH, blood [HCO3], and change in blood [HCO3] above baseline (gDelta [HCO3]) data were assessed using linear mixed models (LMM). The parameters of these LMM were defined by the study design and data collection methodology, and included participant as a random effect, and treatment, time (12 levels; baseline and 0 to 300 min postingestion every 30 min), the interaction treatment by time, and order as fixed effects. For each treatment, estimates from these LMM were used to obtain the peak (gPeak, the maximum mean value identified from group data); the time to gPeak (in minutes, the time from completion of ingestion to gPeak); and the time interval where blood pH or blood [HCO3] was significantly greater than baseline, but not significantly below gPeak. Recent research has proposed buffering agents may improve performance to a greater extent when blood [HCO3] is elevated above baseline by either ≥4 mmol/L or ≥6 mmol/L (Boegman et al., 2020; de Oliveira et al., 2021; Heibel et al., 2018; Jones et al., 2016). Accordingly, time intervals where the lower limit of the 95% confidence intervals for delta blood [HCO3] exceeded these thresholds were estimated.

Separately, the blood pH and blood [HCO3] data from each session were smoothed using a cubic spline function with B-spline bases and one knot (Friedman et al., 2001), obtaining the following outcomes: peak (iPeak; the maximum value in each session); change from baseline to iPeak (iDelta); and time to iPeak (time from completion of ingestion to iPeak). Area under the curve was calculated for each session using the trapezoidal method using the raw data. Effect sizes (Hedges g, for investigations with a sample size <20; Lakens, 2013) were calculated to compare treatments.

For the number and the severity of GIS, the following were assessed (means and 95% confidence intervals): baseline, peak, time to peak, and total session GIS (sum of all time points). Due to nonnormal distribution of data, differences between treatments for GIS were assessed using Mann–Whitney U tests and associated effect sizes. Longitudinal GIS data were summarized as the sum of the number and severity of all symptoms at each time point (mean and range reported). All statistical analyses were conducted in Stata (version 15, StataCorp). Results were considered statistically significant when p < .05.

Results

Induced Blood Alkalosis

For blood pH and blood [HCO3], the main effects for time, treatment, and the treatment-by-time interaction were all statistically significant (p < .05, Figure 1a–1c). No differences were detected between SC and SB for baseline blood pH or blood [HCO3] (Table 1). When comparing on an individual participant/session level for the magnitude of induced blood alkalosis, no differences were detected for iPeak, iDelta, or area under the curve for either blood pH or blood [HCO3] (Table 1). Peak blood pH and peak blood [HCO3] occurred significantly earlier following SB ingestion (150–171 min postingestion) when compared with SC (216–233 min postingestion), with a large effect size detected for each variable (Table 1).

Figure 1
Figure 1

Blood pH and blood bicarbonate concentration ([HCO3]) following ingestion of 500 mg/kg body mass (BM) sodium citrate or 300 mg/kg BM sodium bicarbonate. Blood [HCO3] (in millimoles per liter) (a), delta blood [HCO3] (in millimoles per liter) (b), and blood pH (c) following ingestion of 500 mg/kg BM sodium citrate or 300 mg/kg BM sodium bicarbonate. All n = 16 participants per treatment. Values are mean and 95% confidence intervals. Zero (0) value on the x-axis corresponds to the completion of ingestion. Light gray (shaded) area in (b) indicates 4–6 mmol/L above baseline, and dark gray indicates ≥ 6 mmol/L above baseline. Time interval where blood [HCO3] (a), delta blood [HCO3] (b), or blood pH (c) values are significantly above baseline and not significantly below peak for asodium citrate and for bsodium bicarbonate. Sodium citrate #significantly greater or *significantly lower when compared with sodium bicarbonate (p < .05). Time, treatment, and interaction (treatment by time) effects were estimated using linear mixed model. N = 16 participants per treatment.

Citation: International Journal of Sport Nutrition and Exercise Metabolism 2022; 10.1123/ijsnem.2022-0083

Table 1

Estimates of Curve Characteristics for Blood pH and Blood [HCO3] Following Ingestion of 500 mg/kg BM Sodium Citrate or 300 mg/kg BM Sodium Bicarbonate

Curve characteristics
Sodium citrateSodium bicarbonatepEffect size (g)
Blood pH
 Baselinea7.326 [7.308, 7.343]7.338 [7.321, 7.355].158−0.3 [−1.0, 0.4]
 iPeaka,b7.431 [7.418, 7.444]7.433 [7.420, 7.446].729−0.2 [−0.9, 0.4]
 iDeltaa,b0.102 [0.086, 0.118]0.098 [0.082, 0.114].6540.1 [−0.6, 0.8]
 Time to iPeak (min)a,b233 [206, 259]171 [144, 197]<.0011.0 [0.3, 1.8]
 Area under the curvea2,218 [2,200, 2,237]2,209 [2,190, 2,228].4940.2 [−0.5, 0.9]
 gPeakc7.420 [7.405, 7.435]7.429 [7.414, 7.444]
 Time to gPeakc270150
Blood [HCO3]
 Baseline (mmol/L)a26.3 [25.3, 27.4]26.3 [25.2, 27.4].9120.0 [−0.7, 0.7]
 iPeak (mmol/L)a,b34.2 [33.4, 35.0]33.6 [32.8, 34.5].3080.3 [−0.4, 0.9]
 iDelta (mmol/L)a,b7.9 [6.8, 8.9]7.3 [6.3, 8.4].4780.2 [−0.4, 0.9]
 Time to iPeak (min)a,b216 [199, 232]150 [134, 166]<.0011.8 [1.0, 2.6]
 Area under the curveb9,575 [9,309, 9,841]9,405 [9,139, 9,671].3540.2 [−0.4, 0.9]
 gPeak (mmol/L)c34.0 [32.8, 35.1]33.4 (32.2, 34.5)
 Time to gPeak (min)c240120
 Peak gDelta [HCO3] (mmol/L)c7.6 [6.6, 8.7]7.1 [6.0, 8.1]
 Time to gDelta [HCO3] peak (min)c240120

Note. Bolded values represent a significant difference (p < .05) and a moderate or greater effect (g > 0.6) between sodium citrate and sodium bicarbonate. N = 16 participants per treatment. [HCO3] = bicarbonate concentration; LMM = linear mixed model; BM = body mass; iPeak = the maximum value from each individual session; iDelta = change from baseline to iPeak; time to iPeak = from completion of ingestion to iPeak.

aMean (95% confidence interval), estimated under a LMM including treatment as fixed effect and participant as random effect. bCalculated from a smoothed curve for each participant during each individual session. cMargin (95% confidence interval), estimated under a LMM including participant as a random effect, and treatment, time, interaction (treatment by time) and order as fixed effects, with outputs (gPeak, time to gPeak, and gDelta variables) calculated from group data rather than from each individual session.

Blood [HCO3] exceeded an increase of at least 4 mmol/L above baseline from 120 to 300 min postingestion for SC and from 90 to 210 min postingestion for SB (Figure 1b). Blood [HCO3] exceeded an increase of at least 6 mmol/L above baseline from 180 to 240 min postingestion for SC and from 120 to 180 min postingestion for SB (Figure 1b).

Gastrointestinal Symptoms

Time-course analysis indicated mostly minor GIS across the entire postingestion period for both SC and SB (Figure 2a and 2b). No differences were detected for baseline or iPeak number or severity of GIS, or total session number or severity of GIS (Figure 2c and 2d). The iPeak number of GIS occurred significantly later for SC when compared with SB, but no difference was detected for time to iPeak severity of GIS (Table 2). SC and SB did not differ for the number of severe GIS reported (symptoms rated ≥5, Table 2), and similar proportions of participants and symptoms were reported as severe for each treatment (Table 2). The maximum possible number of reports for any one symptom was 192 (12 times per session for 16 participants). Though most symptoms were irregularly reported, the most frequently reported GIS for both treatments were bloating (76 reports for SC, 45 for SB), belching (55 reports for SC, 33 for SB), flatulence (51 reports for SC, 29 for SB), and nausea (42 reports for SC, 29 for SB).

Figure 2
Figure 2

Gastrointestinal symptoms (GIS; number and severity) reported for 300 min (at specific times and as aggregate for the session) after 500 mg/kg body mass (BM) sodium citrate or 300 mg/kg BM sodium bicarbonate ingestion. The time-specific number (a), time-specific severity (b), total session number (c), and total session severity (d) of GIS reported over 5 hr following ingestion 500 mg/kg BM sodium citrate or 300 mg/kg BM sodium bicarbonate. Values in (a) and (b) are mean and range (due to nonnormal distribution). Zero (0) value on the x-axis corresponds to the completion of ingestion. Maximum possible number of GIS at each time (a) was 16; maximum possible severity of GIS at each time (b) was 160 (16 symptoms, each with a maximum possible rating of 10). Values in (c) and (d) are the sum of all GIS ratings reported by participants in the relevant treatment, irrespective of time. Group value in (c) and (d) (bolded square symbols) is the mean total session value of all participants; individual values (circular symbol) are those reported by each individual participant. Maximum possible number of GIS (c) was 192 (12 times, each with a maximum number of 16 symptoms); maximum possible severity of GIS (d) was 1,920 (16 symptoms, each with a maximum possible rating of 10, each recorded at 12 times). All n = 16 participants per treatment. N = 16 participants per treatment.

Citation: International Journal of Sport Nutrition and Exercise Metabolism 2022; 10.1123/ijsnem.2022-0083

Table 2

Estimates of Curve Characteristics for Number and Severity of Gastrointestinal Symptoms (Rating) Following Ingestion of 500 mg/kg BM Sodium Citrate or 300 mg/kg BM Sodium Bicarbonate

Sodium citrateSodium bicarbonatepEffect size (g)
Number of gastrointestinal symptoms reported
 Baseline0.8 [0.2, 1.3]0.4 [−0.1, 1.0].9050.2 [−0.4, 0.9]
 iPeak4.2 [3.0, 5.3]3.3 [2.2, 4.5].2100.4 [−0.3, 1.1]
 Time to iPeak (min)81 [49, 113]36 [6, 67].0280.6 [0.2, 1.3]
 Total session (number of symptoms)21.8 [14.8, 28.9]14.5 [7.4, 21.5].1800.5 [−0.2, 1.2]
 Number of severe symptoms (rating ≥5)2.0 [0.5, 3.5]1.5 [0.0, 3.0].8510.1 [−0.5, 0.8]
 Proportion of symptoms that were severe9%10%
 Proportion of participants reporting severe symptoms37%31%
Severity of reported gastrointestinal symptoms
 Baseline1.3 [0.3, 2.3]0.7 [−0.3, 1.7].9050.3 [−0.4, 1.0]
 iPeak12.9 [6.6, 19.2]11.5 [5.2, 17.8].4490.2 [−0.5, 0.9]
 Time to iPeak (min)88 [49, 126]47 [10, 85].2740.5 [−0.3, 1.2]
 Total session (severity of symptoms)51.8 [31.4, 72.3]34.8 [14.3, 55.3].3260.5 [−0.2, 1.1]

Note. All values are reported as mean (95% confidence interval), estimated under a linear mixed model including treatment as fixed effect and participant as random effect. Total session values are the sum of the reported gastrointestinal symptoms at all times from the relevant session. For number of severe symptoms, baseline and iPeak number of symptoms, the maximum possible value is 16 (number of symptoms on the questionnaire); for severity of symptoms, the maximum possible value is 160 (16 symptoms, each with a maximum rating of 10). For total session number of symptoms, the maximum possible value is 192 (16 symptoms, reported at 12 times); for severity of symptoms, the maximum possible value is 1,920 (16 symptoms, reported at 12 times, each with a maximum rating of 10). Percentage of symptoms that were severe was calculated as: (number of severe symptoms/total session number of symptoms) × 100. Participants reporting severe symptoms were calculated as: (number of participants who rated at least one symptom as ≥5/sample size of 16) × 100. Bolded values represent a significant difference (p < .05) and a moderate or greater effect (g > 0.6) between sodium citrate and sodium bicarbonate. N = 16 participants per treatment. BM = body mass; iPeak = the maximum value from each individual session; Time to iPeak = from completion of ingestion to iPeak.

Discussion

The aim of this study was to compare the recommended SC and SB supplementation doses for their effect on blood alkalosis and GIS. A key finding was that 500 mg/kg BM SC and 300 mg/kg BM SB induced a similar magnitude of blood alkalosis, but alkalosis peaked later for SC (216–233 min postingestion) than for SB (150–171 min postingestion). Both supplements elicited similarly minor GIS, with peak symptoms occurring later for SC (80–90 min postingestion) than for SB (35–50 min postingestion).

Magnitude and Timing of Induced Blood Alkalosis

In the current study, SC induced a greater mean session blood [HCO3] and a lower mean session blood pH (i.e., main effects for treatment) than SB. While statistically significant, these differences (∼0.02 for blood pH; ∼0.4 mmol/L for blood [HCO3]) may represent little practical implication, given that both are small relative to confidence intervals of each supplement. Further, the supplements did not differ for peak or delta blood pH or blood [HCO3]. Accordingly, it can be summarized that 500 mg/kg BM SC and 300 mg/kg BM SB induced similar maximum responses for blood alkalosis. The similar peak alkalosis observed here is in accordance with the sole prior investigation to compare these supplements using the same doses as the current study (Potteiger et al., 1996). Ingestion of equal SC and SB doses (300 mg/kg BM) has previously returned equivocal blood alkalosis comparisons (Kumstát et al., 2018; Parry-Billings & MacLaren, 1986; Peacock et al., 2021; Tiryaki & Atterbom, 1995). One of these studies reported that SB elicited greater alkalosis compared with SC (Peacock et al., 2021), and earlier investigations reported no difference between the supplements for indicators of magnitude of blood alkalosis (Kumstát et al., 2018; Parry-Billings & MacLaren, 1986; Tiryaki & Atterbom, 1995). It remains unclear why there is this inconsistency; however, a possible explanation may include variations in the timing and duration of the postingestion blood sampling across previous investigations, and may also be contributed to by differing sampling sites (i.e., venous, arterial, and capillary) and presampling procedures (e.g., arterialization) across studies.

Based on the findings of this study and consistent with others (Peacock et al., 2021; Potteiger et al., 1996), it appears that a greater dose of SC (500 mg/kg BM) than SB (300 mg/kg BM) is required to induce a similar peak blood alkalosis. Both of these supplements likely induce blood alkalosis via a homeostatic response to a disturbance in strong ion difference that occurs after their respective constituent ions (sodium and citrate for SC; sodium and bicarbonate for SB) enter the circulation (Siegler et al., 2016). Citrate and bicarbonate ions are absorbed via different cotransporters and subsequent anion exchange responses (Hopfer & Liedtke, 1987; Wolffram et al., 1994). There is likely to be a difference in the rate at which these anions are absorbed across the intestinal wall, and therefore, the rate of entry into the circulation may differ between SC and SB. For SB, the pathway to disturbing strong ion difference may be simpler than for SC, if part of the strong ion difference disturbance comes from a direct increase in circulating bicarbonate from the supplement itself. Furthermore, given that the rates of entry and removal from circulation of citrate and bicarbonate also likely differ, fewer bicarbonate than citrate ions may be needed to elicit an equal change in strong ion difference. A more direct pathway for SB than for SC may also explain the significantly earlier occurrence of peak blood alkalosis in the current study, though this requires further investigation.

Both SC and SB supplementation induced blood alkalosis that remained above baseline for 5 hr. However, blood alkalosis peaked ∼60 min later for SC (233 min for blood pH; 216 min for blood [HCO3]) than for SB (171 min for blood pH; 150 min for blood [HCO3]). Further, blood [HCO3] (absolute and delta) were lower for SC than for SB 120 min postingestion, but higher for SC than for SB by 210 min postingestion, illustrating different time-course responses between the supplements. Comparing these findings to previous studies is difficult, given that many monitored alkalosis for shorter periods, at fewer time points (i.e., preingestion, preexercise, postexercise; Kumstát et al., 2018; Parry-Billings & MacLaren, 1986), or after use of different ingestion protocols (i.e., doses, mode of delivery and ingestion period) to the current study (Peacock et al., 2021). Potteiger et al. (1996) assessed blood alkalosis for 120 min using the same doses as the current study, and despite a relatively short postingestion observation period, they reported similar times to peak blood alkalosis for SC and SB, although no statistical analysis was reported to support this finding. Previously, similar statistical findings as the current study have been reported, whereby peak blood alkalosis occurred significantly later for SC than for SB (both 300 mg/kg BM; Peacock et al., 2021). However, for both SC and SB, peak blood alkalosis occurred earlier in the Potteiger and Peacock studies (Peacock et al., 2021; Potteiger et al., 1996) (both ∼120 min postingestion for SB and 120–145 min for SC) when compared with the current study. Why this may have occurred is unclear, but may be due to methodological differences such as the site of blood collection (i.e., antecubital vein in the current study, arterialized dorsal hand vein in the Potteiger study, and fingertip capillary in the Peacock study), or the absence of a co-ingested meal in the prior investigations increasing the rate of supplement digestion and absorption. These findings are of importance in determining practical supplementation recommendations, given that it has previously been suggested that SB supplementation be completed 60–150 min prior to exercise (Maughan et al., 2018).

Proposed Thresholds of Induced Blood Alkalosis

An increased blood [HCO3] exceeding 6 mmol/L above baseline has been suggested to increase the likelihood of a performance improvement (Boegman et al., 2020; Heibel et al., 2018). For both SC and SB in the current investigation, mean delta blood [HCO3] was at least 7.3 mmol/L, aligning with prior investigations (de Oliveira et al., 2021; Urwin et al., 2020). Blood [HCO3] exceeded the 6 mmol/L threshold from 180 to 240 min postingestion for SC, and from 120 to 180 min postingestion for SB. A recent review of buffering agent supplementation reported statistically similar exercise performance responses (i.e., small effect size) when blood [HCO3] increase was >6 mmol/L above baseline compared with when blood [HCO3] increase was between 4 and 6 mmol/L (de Oliveira et al., 2021). In the current study, the interval where blood [HCO3] was ≥4 mmol/L above baseline was 180–300 min postingestion for SC, and 120–180 min postingestion for SB. Extending the duration of the time interval where exercise performance may be benefited by buffering agent supplementation allows more flexibility in athlete preparation, whereby supplementation could be completed earlier before exercise with similar efficacy. However, it must be acknowledged that these thresholds have not been examined in experimental research; they have been derived from distinct studies (Boegman et al., 2020; Carr et al., 2011; Heibel et al., 2018; Jones et al., 2016), each implementing different supplementation (i.e., dose and mode of ingestion) and exercise protocols.

Number and Severity of GIS

Both SC and SB ingestion elicited minor GIS, in terms of peak and total session values for number and severity of reported symptoms. Eight participants reported a greater total session severity of GIS for SC, and eight participants did so for SB (Figure 2d), illustrating the absence of a clear difference between the supplements. Severe GIS (rated ≥5) were relatively infrequent following ingestion of either supplement; 9%–10% of all GIS were severe, and 31%–37% of all participants reported one or more severe symptoms. The first investigation to statistically compare GIS following ingestion of SC and SB (both 300 mg/kg BM) reported a greater occurrence of GIS following SB supplementation (Peacock et al., 2021). However, the sole prior investigation to compare the currently recommended dose of both supplements did not quantify GIS (Potteiger et al., 1996). Based on the results from the present study, it appears that 500 mg/kg BM SC and 300 mg/kg BM SB induces a similar number and severity of GIS. Previously, SC has been listed as an alternative to SB in the International Olympic Committee consensus statement on dietary supplements, on the basis that SC may minimize the GIS associated with SB (Maughan et al., 2018), but based on current findings this may not be the case.

Previously, it has been proposed that the greater molecular mass of SC (258.07 g/Mol) may result in a slower rate of digestion compared with SB (84.007 g/Mol) (Peacock et al., 2021). If this was the case, we may expect most GIS to be related to digestion within the upper gastrointestinal tract following SC ingestion (e.g., belching and regurgitation). However, upper and lower (e.g., flatulence and urge to defecate) GIS after SC or SB supplementation have been reported to a similar extent in the current and a previous study (Peacock et al., 2021). Accordingly, it is unclear why a similar number and severity of GIS were reported in each treatment of the current study despite the different dosage used. Pathways that warrant investigation include: (a) the effect these supplements have on the function of digestive and/or absorptive enzymes, (b) the retention of water with accordant changes in gastric osmolality within the gastrointestinal tract (Cerullo et al., 2020; Requena et al., 2005), and (c) the rate and amount of carbon dioxide released from any metabolism of HCO3 and citrate formed when the respective supplement molecules dissociate into their constituent ions in the gastrointestinal tract (Turnberg et al., 1970).

For SC and SB, the most frequently reported symptoms were belching, bloating, flatulence, and nausea. This indicates that buffering agents may induce upper (belching and bloating), lower (flatulence), and other (nausea) GIS. Peacock et al. (2021) reported primarily lower GIS (flatulence, bowel urgency, and diarrhea) after ingestion of either supplement, possibly due to their use of delayed-release capsules (Hilton et al., 2019). Despite using different GIS assessment tools, previous investigations identified bloating and nausea as commonly reported GIS after SC supplementation alongside a similar meal to the current study (Urwin et al., 2019, 2021), and bloating and belching as commonly reported after SB supplementation with no meal (Gough et al., 2018; Hilton et al., 2019; Hilton, Leach, Craig, et al., 2020). These collective findings illustrate the variation of specific GIS occurring after ingestion SC or SB, promoting the need for athletes to trial the use of these supplements prior to implementation for competition to observe their individual GIS responses.

Timing of GIS

Peak GIS occurred 80–90 min postingestion for SC and 35–50 min postingestion for SB. One investigation reported the time at which the most severe symptom occurred after ingestion of SC and SB (both 300 mg/kg BM) on an individual participant basis, with a similar range (30–100 min postingestion) apparent for both supplements (Peacock et al., 2021). Alternately, separate investigations of either one of these supplements have reported the occurrence of peak symptoms 60–90 min postingestion for SC (Urwin et al., 2016) and approximately 40 min postingestion for SB (Hilton et al., 2019). However, these studies each used different methods to assess GIS, and none have compared the time course of GIS following supplementation of SC and SB.

In the current study, both the number and severity of GIS began to decline 180 min and 120 min postingestion, for SC and SB, respectively, when blood alkalosis was near the peak. Traditional time-course statistical analyses, such as LMM, are typically not appropriate for GIS data due to skewing caused by a large proportion of participant responses being a rating of 0. Therefore, for practical relevance, it may be prudent to consider the timing of GIS in relation to peak blood alkalosis. Therefore, it is encouraging that GIS were not substantially elevated at the time when blood alkalosis may be of most ergogenic benefit. Variability in the timing of peak GIS should also be considered prior to implementation. In the current investigation, individual participants reported peak GIS anywhere from 0 to 270 min postingestion for SC and from 0 to 240 min postingestion for SB. Accordingly, athletes and coaches should trial SC or SB supplementation in a controlled training environment, to identify the occurrence and timing of any associated GIS in relation to the timing of peak blood alkalosis.

Limitations

No placebo treatment was administered in the current study, given the primary aim was to conduct a novel comparison of SC and SB. The inclusion of a placebo condition in the current study may have allowed a more thorough examination of the etiology of associated GIS when ingesting either SC or SB, alongside the comparison between SC and SB. Future studies should include a placebo treatment if aiming to establish etiology for GIS or when investigating novel ingestion strategies. A true peak for blood pH may not have been determined in the current study, despite the 300-min postingestion period exceeding all similar previous studies. This period was informed by a prior investigation from our laboratory, where blood pH peaked and returned toward baseline within 270 min after SC ingestion (Urwin et al., 2021). Surprisingly, blood pH remained significantly elevated above baseline at the conclusion of the current study’s SC intervention (Figure 1c), indicating that there is some variability in the postingestion blood pH recovery curve across sample populations. Therefore, future studies should also assess postingestion blood alkalosis responses in highly trained individuals/athletes to confirm transferability to this population. To meet the recommended dose of SC (500 mg/kg BM) and SB (300 mg/kg BM), participants were required to ingest a different number of capsules, which we acknowledge is a minor impediment to participant blinding. Providing the supplements in opaque bags, with a washout period >7 days aimed to minimize this risk of bias.

Practical Application Statement

Based on the results of the current study, 500 mg/kg BM SC and 300 mg/kg BM SB supplementation in gelatin capsules elicits similar levels of induced blood alkalosis and GIS. For SC, blood alkalosis peaks and GIS subside 180–240 min postingestion. For SB, the same occurs 120–180 min postingestion. Accordingly, these findings suggest that to maximize alkalosis and minimize GIS, SB should be ingested 2–3 hr preexercise, and SC 3–4 hr preexercise.

Novelty Statement

This is the first study to compare postingestion blood alkalosis responses to the currently recommended dose of SC (500 mg/kg BM) and SB (300 mg/kg BM) for a period exceeding 120 min. No prior investigation had quantified GIS following supplementation at these recommended doses for any time period. These observations facilitate a more complete understanding of how these supplements may be incorporated into athlete preparation prior to an event or training bout.

Acknowledgments

The School of Exercise and Nutrition Sciences at Deakin University provided all funding for this investigation. Author Contributions: All authors designed the investigation; Urwin and Convit collected and analyzed data. All authors undertook data interpretation and manuscript preparation. All authors approved the final version of the paper.

References

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    Figure 1

    Blood pH and blood bicarbonate concentration ([HCO3]) following ingestion of 500 mg/kg body mass (BM) sodium citrate or 300 mg/kg BM sodium bicarbonate. Blood [HCO3] (in millimoles per liter) (a), delta blood [HCO3] (in millimoles per liter) (b), and blood pH (c) following ingestion of 500 mg/kg BM sodium citrate or 300 mg/kg BM sodium bicarbonate. All n = 16 participants per treatment. Values are mean and 95% confidence intervals. Zero (0) value on the x-axis corresponds to the completion of ingestion. Light gray (shaded) area in (b) indicates 4–6 mmol/L above baseline, and dark gray indicates ≥ 6 mmol/L above baseline. Time interval where blood [HCO3] (a), delta blood [HCO3] (b), or blood pH (c) values are significantly above baseline and not significantly below peak for asodium citrate and for bsodium bicarbonate. Sodium citrate #significantly greater or *significantly lower when compared with sodium bicarbonate (p < .05). Time, treatment, and interaction (treatment by time) effects were estimated using linear mixed model. N = 16 participants per treatment.

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    Figure 2

    Gastrointestinal symptoms (GIS; number and severity) reported for 300 min (at specific times and as aggregate for the session) after 500 mg/kg body mass (BM) sodium citrate or 300 mg/kg BM sodium bicarbonate ingestion. The time-specific number (a), time-specific severity (b), total session number (c), and total session severity (d) of GIS reported over 5 hr following ingestion 500 mg/kg BM sodium citrate or 300 mg/kg BM sodium bicarbonate. Values in (a) and (b) are mean and range (due to nonnormal distribution). Zero (0) value on the x-axis corresponds to the completion of ingestion. Maximum possible number of GIS at each time (a) was 16; maximum possible severity of GIS at each time (b) was 160 (16 symptoms, each with a maximum possible rating of 10). Values in (c) and (d) are the sum of all GIS ratings reported by participants in the relevant treatment, irrespective of time. Group value in (c) and (d) (bolded square symbols) is the mean total session value of all participants; individual values (circular symbol) are those reported by each individual participant. Maximum possible number of GIS (c) was 192 (12 times, each with a maximum number of 16 symptoms); maximum possible severity of GIS (d) was 1,920 (16 symptoms, each with a maximum possible rating of 10, each recorded at 12 times). All n = 16 participants per treatment. N = 16 participants per treatment.

  • Boegman, S., Stellingwerff, T., Shaw, G., Clarke, N., Graham, K., Cross, R., & Siegler, J.C. (2020). The impact of individualizing sodium bicarbonate supplementation strategies on world-class rowing performance. Frontiers in Nutrition, 7, 138. https://doi.org/10.3389/fnut.2020.00138

    • Crossref
    • Search Google Scholar
    • Export Citation
  • Carr, A., Hopkins, W., & Gore, J. (2011). Effects of acute alkalosis and acidosis on performance: A meta analysis. Sports Medicine, 41(10), 801814. https://doi.org/10.2165/11591440-000000000-00000

    • Crossref
    • Search Google Scholar
    • Export Citation
  • Cerullo, G., Parimbelli, M., Perna, S., Pecoraro, M., Liguori, G., Negro, M., & D’Antona, G. (2020). Sodium citrate supplementation: An updated revision and practical recommendations on exercise performance, hydration status and potential risks. Translational Sports Medicine, 3(6), 518525. https://doi.org/10.1002/tsm2.174

    • Crossref
    • Search Google Scholar
    • Export Citation
  • de Oliveira, E., Burini, R., & Jeukendrup, A. (2014). Gastrointestinal complaints during exercise: Prevalence, etiology, and nutritional recommendations. Sports Medicine, 44(Suppl. 1), 7985. https://doi.org/10.1007/s40279-014-0153-2

    • Crossref
    • Search Google Scholar
    • Export Citation
  • de Oliveira, L.F., Dolan, E., Swinton, P.A., Durkalec-Michalski, K., Artioli, G.G., McNaughton, L.R., & Saunders, B. (2021). Extracellular buffering supplements to improve exercise capacity and performance: A comprehensive systematic review and meta-analysis. Sports Medicine, 52(1), 122. https://doi.org/10.1007/s40279-021-01575-x

    • Search Google Scholar
    • Export Citation
  • Dennig, H., Talbott, J., Edwards, H., & Dill, D. (1930). Effect of acidosis and alkalosis upon capacity for work. The Journal of Clinical Investigation, 9(4), 601613. https://doi.org/10.1172/JCI100324

    • Crossref
    • Search Google Scholar
    • Export Citation
  • Fitts, R. (2016). The role of acidosis in fatigue: Pro perspective. Medicine & Science in Sports & Exercise, 48(11), 23352338. https://doi.org/10.1249/MSS.0000000000001043

    • Crossref
    • Search Google Scholar
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