To the best of our knowledge, this is the first study to examine the effect of BS supplementation during maximal incremental test in individuals with T2DM. The hypothesis of this research was to observe improvement in physical performance and biochemical and cardiovascular parameters after supplementation. A significant increase in test duration was observed in the BS condition. Additionally, both conditions showed significant reductions in blood glucose levels after interventions, indicating comparable efficacy of isolated and/or combined physical exercise with BS in glucose metabolism regulation, but without differences in cardiovascular parameters. These results suggest that while both interventions seem effective in glucose regulation, active BS supplementation may confer an additional benefit to participants' exercise capacity, warranting further investigation in future studies.
PHYSICAL PERFORMANCE ANALYSIS
Acid-base balance is achieved by the action of physicochemical buffers, which can be improved through supplementation with SB. Studies that evaluated pH during exercise have observed a delay in the onset of intramuscular acidosis and, consequently, better exercise performance [18]. SB supplementation is often associated with the context of physical training, especially in athletes, due to its potential benefits in sports performance [30]. In this sense, it is not commonly studied in groups that have some health condition, such as individuals with T2DM. Therefore, our results are relevant in suggesting that supplementation may have beneficial effects on cardiovascular and physical performance parameters in this population.
While we did not conduct a comprehensive analysis through laboratory tests to assess the biochemical changes resulting from supplementation, previous studies offer relevant results. The research conducted by Stephens et al. (2002) [31] observed a significant increase in plasma bicarbonate concentration after ingesting 0.3 g.kg-1 of SB in a maximal incremental test on a cycle ergometer. Kumstat et al. (2018) [32] research demonstrated that blood pH, bicarbonate concentration, and base excess (BE) increased significantly after supplementation with 0.3 g.kg-1 of SB (p < 0.05) in professional swimmers (20.7 ± 2.1 years old). Similarly, the systematic review and meta-analysis conducted by Miranda et al. (2022) [33] highlighted a significant effect on increasing blood lactate levels (p = 0.006) in combat athletes undergoing a SB supplementation protocol. This may be attributed to the fact that SB promotes an increase in the efflux of H+ ions from muscle cells to the blood, where they are neutralized. This process results in the reduction of intramuscular acidosis, which, in turn, allows for prolonged operation of the glycolytic pathway [18, 30].
Additionally, Gurton et al. (2023) [34] suggested that administering SB in solution form may be more effective than encapsulated supplementation, demonstrating a 2% increase in repeated sprint and Yo-Yo IR2 test performance in the solution supplementation group. They observed that the decline in serum bicarbonate during maximal exercise was more pronounced for SB administered in solution compared to capsules (2.7 ± 2.1 mmol.L kg-1, p = 0.001), which was the method used in our research. The biochemical changes observed in previous studies may have influenced the results obtained in our research, providing a valuable context for interpreting the findings.
The active intervention condition had a mean test time of 481 ± 116.97 seconds, while the placebo condition had a mean time of 439 ± 99.92 seconds, representing an average increase of approximately 9.57% in test time. Carr et al. (2011) [35] literature review included 38 studies that evaluated performance effects with SB supplementation, which observed a moderate performance improvement of 1.7% (± 2.0%) with a standard dose of 0.3g.kg-1 in a 1-minute sprint test in male athletes, notable but with a lesser effect when compared to our research. Additionally, a moderate correlation (r = 0.33; 90% CI -0.10, 0.65) was observed between test performance and pre-exercise serum bicarbonate values after SB supplementation. Acute and chronic SB intake can lead to diverse outcomes. Durkalec-Michalski et al. (2020) [36] investigated the effects of acute (0.2 g.kg-1) and chronic (8 days with a 25% dosage increase every 2 days, from 0.5 g.kg-1 on days 1 and 2 to 0.2 g.kg-1 on days 7 and 8) SB on the physical performance of hockey athletes. Acute supplementation showed significant improvements in the time of a specific discipline test and in the anaerobic capacity of the Wingate test (939 ± 26 vs. 914 ± 22 s, p = 0.006), while chronic supplementation did not result in substantial improvements. However, Lopes-Silva et al. (2019) [37] meta-analysis indicated that chronic SB intake (0.5 g.kg-1 for 5 days) promoted significant improvements in peak and mean power in the Wingate test. These results highlight the importance of the present research in the practical evaluation of different supplementation protocols.
HIGH-INTENSITY PHYSICAL EXERCISE
Our results demonstrated an improvement in physical performance and, consequently, an increase in tolerance to high-intensity activities in subjects with T2DM after SB supplementation. Hwang et al. (2019) [20] aimed to evaluate high-intensity interval training (HIIT) compared to moderate-intensity continuous training (MICT) in 58 elderly individuals with T2DM (63 ± 1 years old) over 8 weeks of supervised training. Improvements in aerobic fitness were observed, with a 10% increase in peak VO2 for the HIIT group and 8% for the MICT group. Additionally, there was an increase in maximum exercise tolerance, with additions of 1.8 and 1.3 minutes (p ≤ 0.002 in both groups; p ≥ 0.90 for the comparison between HIIT and MICT). Støa et al. (2017) [19] investigated the effects of HIIT (85% and 95% of maximum HR) and MICT (70% and 75% of maximum HR) in 38 individuals with T2DM over 12 weeks of supervised training. The results demonstrated a significant 21% increase in maximum VO2 (from 25.6 to 30.9 ml.kg-1, p < 0.001) in the HIIT group, accompanied by a -0.58% reduction in HbA1c levels (from 7.78 to 7.20%, p < 0.001). Additionally, there was a 1.9% reduction in body weight (p < 0.01) and BMI. These improvements were statistically significant compared to the group undergoing MICT, with no differences in lactate threshold and blood pressure. Moderate correlations were identified between the change in maximum VO2 and HbA1c when combined (r = -0.52, p < 0.01). In summary, the results obtained in this investigation corroborate the feasibility, safety, and effectiveness of high-intensity training in individuals with T2DM. These findings are relevant in the context of exercise prescription for this population, as the training methods in question provide comparable benefits, with the additional advantage of a lower time demand associated with HIIT protocols.
BLOOD GLUCOSE
A significant reduction in glucose levels was observed in both conditions. In the SB condition, there was a reduction of 15.5% (151.31 ± 60.33 to 127.85 ± 57.37 mg/dL; p = 0.002), and in the placebo condition, the reduction was 15.85% (155.85 ± 76.97 to 131.15 ± 79.78 mg/dL; p = 0.004). These results highlight the role of exercise as a strategy in glycemic control and the promotion of metabolic health. Furthermore, the dose-response relationship suggests that higher-intensity activities offer additional benefits for metabolic control [38]. Physical exercise has acute and chronic impacts on the regulation of glucose uptake and inflammatory processes, resulting in a reduction in blood glucose for up to 48 hours, and increasing glucose uptake by up to 50 times through insulin-dependent and independent mechanisms [7, 38]. Hiyane et al. (2008) [40] study with 10 participants (56.9 ± 11.2 years old) demonstrated a significant reduction in blood glucose up to 90 minutes after two sessions of constant load exercise performed at 90% and 110% of the anaerobic threshold. Furthermore, Munan et al. (2020) [41] meta-analysis of 23 studies of acute exercise showed a significant decrease in mean glucose concentrations after 24 hours by 9.01 mg/dL (p < 0.001). In Zhang et al. (2020) [42] research, the HIIT group showed substantial differences in fasting, pre-exercise, and 11-hour post-exercise glucose levels compared to the control (p < 0.05). These results are consistent with our findings, where we identified a significant reduction in blood glucose levels immediately after the test, suggesting that this reduction may be maintained in the short and long term.
CHRONOTROPIC INCOMPETENCE
CI, assessed through CR, is characterized by the inability of the HR to increase proportionally to the increase in activity or metabolic demand, and plays a significant role in exercise tolerance. Recent studies have shown that CI is associated with cardiovascular dysfunctions in people with T2DM, and these conditions can lead to an increased risk of acute myocardial infarction, stroke, and sudden cardiac death [3, 4]. Regarding our results, an average of 86.45 ± 20.47% was observed in CR in the SB condition and 82.93 ± 17.63% in the placebo condition. Although there was no statistically significant difference between these values (p = 0.126), it was observed that 38.46% (n = 5) of the subjects in the SB condition and 46.15% (n = 6) in the placebo condition had values below 85% of CR, which is considered indicative of CI, which can negatively influence performance during exercise.
In a study conducted by Hansen et al. (2014) [43], which investigated the maximum chronotropic response index (CRI) in individuals with T2DM and healthy individuals, a significant difference in maximum CRI was demonstrated between the groups (0.85 ± 0.17 for patients with T2DM and 1.02 ± 0.17 for healthy individuals, p < 0.01). Similar to our study, they identified the presence of CI in 42% of patients with T2DM, while only 6% of healthy individuals had this condition. Furthermore, CI showed an association with other factors, such as obesity, glycemic control, insulin resistance, and level of physical fitness. Therefore, CI can be considered a risk marker in this population, but it is important to note that the origin of this condition is multifactorial and not fully understood [3, 4].
Physical exercise not only proves to be effective in the treatment of CI, but also plays a crucial role in the prevention and improvement of associated risk factors. A study conducted by Jin et al. (2017) [44] investigated the effects of a 12-week aerobic training program in 30 individuals with T2DM with CI, revealing a significant increase in maximum HR by 13% (129.23 ± 16.32 vs. 140.50 ± 13.41 bpm, p < 0.01), a 24% increase in test time (703 ± 196 vs. 873 ± 177 seconds, p < 0.01), and a 26% increase in peak VO2 (16.99 ± 3.96 vs. 21.40 ± 4.94 ml.kg.min-1, p < 0.01).
HEART RATE RECOVERY
Heart rate recovery refers to the decrease in maximum/peak heart rate in the period following exercise. This process reflects the dynamic interaction between the parasympathetic and sympathetic systems and is widely recognized as a non-invasive measure to assess autonomic function, providing information on how the cardiovascular system responds to effort [45]. Regarding heart rate recovery in the first 30 seconds after the test, the values were 140 ± 19.39 in the SB condition and 134.77 ± 17.02 in the placebo condition, showing no significant difference (p = 0.472). The variations in heart rates between exercise peak and 60 seconds after were 24.85 bpm in the SB and 30.15 bpm in the placebo. Both values exceeded the 18 bpm threshold, an important indicator of altered chronotropic response [29]. Additionally, no participant had a baseline heart rate above 100 bpm, which, along with a reduction in chronotropic response, is an independent predictor of cardiovascular and all-cause mortality in individuals with T2DM [4], indicating a lower-risk profile in our sample.
Qiu et al. (2017) [45], meta-analysis including 9,113 participants with an average follow-up period of 8.1 years, revealed a significant association between slower heart rate recovery and a substantial increase in the risk of developing T2DM (HR 1.66, 95% CI 1.16–2.38). Furthermore, Jae et al. (2016) [46] investigated the relationship between delayed heart rate recovery and the development of T2DM in 2,231 men, over an average follow-up of 5 years. During this period, 90 men (4.0%) developed the disease. The relative risks were significantly higher in the lowest quartiles of heart rate reserve (HR 2.71, 95% CI 1.20–6.11) and heart rate recovery (HR 2.81, 95% CI 1.36–5.78) compared to the highest quartiles. Each 1 bpm increase in heart rate reserve and recovery was associated with a 2–3% reduction in the incidence of T2DM.
Delayed heart rate recovery after exercise is directly related to an increased risk of adverse cardiac events, including sudden cardiac death (SCD). Several studies have shown this association between SCD and changes in heart rate recovery. A study by Kurl et al. (2021) [47] examined 1,967 men (aged 42 to 61 years) over a 25-year period, finding a significant increase in the incidence of SCD among those with a lower heart rate reserve (HR 3.86, 95% CI 2.56–5.80) and slower heart rate recovery (HR 2.86, 95% CI 1.95–4.20). Each 1 bpm increase in heart rate recovery reduced the incidence of SCD by 1–2%. Additionally, Vivekananthan et al. (2003) [48] emphasized that heart rate recovery can be a prognostic indicator of mortality in six years for patients with coronary artery disease, regardless of the severity of the condition. These results indicate that such programs not only improve participants' quality of life but are also associated with a reduction in hospitalizations related to cardiac conditions and highlight the importance of this analysis as a valuable prognostic indicator in assessing cardiovascular risk.
LIMITATIONS
This study has some limitations to be considered. Firstly, the diversity in the clinical condition of participants, including hormonal conditions, especially in female subjects, differences in disease duration, the presence and degree of cardiac autonomic neuropathy, and variations in cardiorespiratory fitness. Additionally, the intervention was performed on different days, which could introduce some daily variability in the results, although we took measures to minimize this impact. These limitations should be taken into account when interpreting the results of this study and suggest the need for more comprehensive and controlled future investigations.