Sodium Bicarb Abstracts 1

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Correction of metabolic acidosis improves insulin resistance in chronic kidney disease.
            (Bellasi et al., 2016) Download
BACKGROUND:  Correction of metabolic acidosis (MA) with nutritional therapy or bicarbonate administration is widely used in chronic kidney disease (CKD) patients. However, it is unknown whether these interventions reduce insulin resistance (IR) in diabetic patients with CKD. We sought to evaluate the effect of MA correction on endogenous insulin action in diabetic type 2 (DM2) CKD patients. METHODS:  A total of 145 CKD subjects (83 men e 62 women) with DM2 treated with oral antidiabetic drugs were included in the study and followed up to 1 year. All patients were randomly assigned 1:1 to either open-label (A) oral bicarbonate to achieve serum bicarbonate levels of 24-28 mmol/L (treatment group) or (B) no treatment (control group). The Homeostatic model assessment (HOMA) index was used to evaluate IR at study inception and conclusion. Parametric and non-parametric tests as well as linear regression were used. RESULTS:  At baseline no differences in demographic and clinical characteristics between the two groups was observed. Average dose of bicarbonate in the treatment group was 0.7 ± 0.2 mmol/kg. Treated patients showed a better metabolic control as confirmed by lower insulin levels (13.4 ± 5.2 vs 19.9 ± 6.3; for treated and control subjects respectively; p < 0.001), Homa-IR (5.9[5.0-7.0] vs 6.3[5.3-8.2]; p = 0.01) and need for oral antidiabetic drugs. The serum bicarbonate and HOMA-IR relationship was non-linear and the largest HOMA-IR reduction was noted for serum bicarbonate levels between 24 and 28 mmol/l. Adjustment for confounders, suggests that serum bicarbonate rather than treatment drives the effect on HOMA-IR. CONCLUSIONS:  Serum bicarbonate is related to IR and the largest HOMA-IR reduction is noted for serum bicarbonate between 24 and 28 mmol/l. Treatment with bicarbonate influences IR. However, changes in serum bicarbonate explains the effect of treatment on HOMA index. Future efforts are required to validate these results in diabetic and non-diabetic CKD patients. TRIAL REGISTRATION:  The trial was registered at www.clinicaltrial.gov (Use of Bicarbonate in Chronic Renal Insufficiency (UBI) study - NCT01640119 ).


 

Sodium bicarbonate supplementation improves severe-intensity intermittent exercise under moderate acute hypoxic conditions.
            (Deb et al., 2018) Download
Acute moderate hypoxic exposure can substantially impair exercise performance, which occurs with a concurrent exacerbated rise in hydrogen cation (H+) production. The purpose of this study was therefore, to alleviate this acidic stress through sodium bicarbonate (NaHCO3) supplementation and determine the corresponding effects on severe-intensity intermittent exercise performance. Eleven recreationally active individuals participated in this randomised, double-blind, crossover study performed under acute normobaric hypoxic conditions (FiO2% = 14.5%). Pre-experimental trials involved the determination of time to attain peak bicarbonate anion concentrations ([HCO3-]) following NaHCO3 ingestion. The intermittent exercise tests involved repeated 60-s work in their severe-intensity domain and 30-s recovery at 20 W to exhaustion. Participants ingested either 0.3 g kg bm-1 of NaHCO3 or a matched placebo of 0.21 g kg bm-1 of sodium chloride prior to exercise. Exercise tolerance (+ 110.9 ± 100.6 s; 95% CI 43.3-178 s; g = 1.0) and work performed in the severe-intensity domain (+ 5.8 ± 6.6 kJ; 95% CI 1.3-9.9 kJ; g = 0.8) were enhanced with NaHCO3 supplementation. Furthermore, a larger post-exercise blood lactate concentration was reported in the experimental group (+ 4 ± 2.4 mmol l-1; 95% CI 2.2-5.9; g = 1.8), while blood [HCO3-] and pH remained elevated in the NaHCO3 condition throughout experimentation. In conclusion, this study reported a positive effect of NaHCO3 under acute moderate hypoxic conditions during intermittent exercise and therefore, may offer an ergogenic strategy to mitigate hypoxic induced declines in exercise performance.

Effect of sodium bicarbonate on prolonged running performance: A randomized, double-blind, cross-over study.
            (Freis et al., 2017) Download
BACKGROUND:  The ability to sustain intense exercise seems to be partially limited by the body's capability to counteract decreases in both intra- and extracellular pH. While the influence of an enhanced buffering capacity via sodium bicarbonate (BICA) on short-term, high-intensity exercise performance has been repeatedly investigated, studies on prolonged endurance performances are comparatively rare, especially for running. The aim of the following study was to assess the ergogenic effects of an oral BICA substitution upon exhaustive intensive endurance running performance. METHOD:  In a double-blind randomized cross-over study, 18 trained runners (VO2peak: 61.2 ± 6.4 ml•min-1•kg-1) performed two exhaustive graded exercise tests and two constant load tests (30 main at 95% individual anaerobic threshold (IAT) followed by 110% IAT until exhaustion) after ingestion of either sodium bicarbonate (BICA) (0.3 g/kg) or placebo (4 g NaCl) diluted in 700 ml of water. Time to exhaustion (TTE) in the constant load test was defined as the main outcome measure. Throughout each test respiratory gas exchange measurements were conducted as well as determinations of heart rate, blood gases and blood lactate concentration. RESULTS:  TTE in the constant load test did not differ significantly between BICA and placebo conditions (BICA: 39.6 ± 5.6 min, placebo: 39.3 ± 5.6 min; p = 0.78). While pH in the placebo test dropped to a slightly acidotic value two minutes after cessation of exercise (7.34 ± 0.05) the value in the BICA trial remained within the normal range (7.41 ± 0.06) (p < 0.001). In contrast, maximum running speed (Vmax) in the exhaustive graded exercise test was significantly higher with BICA (17.4 ± 1.0 km/h) compared to placebo (17.1 ± 1.0 km/h) (p = 0.009). The numerical difference in maximum oxygen consumption (VO2peak) failed to reach statistical significance (BICA: 61.2 ± 6.4 ml•min-1•kg-1, placebo: 59.8 ± 6.4 ml•min-1•kg-1; p = 0.31). Maximum blood lactate was significantly higher with BICA compared to the corresponding placebo test (BICA: 11.1 ± 2.3 mmol/l, placebo: 8.9 ± 3.0 mmol/l; p < 0.001). At the end of exercise, an acidotic pH value was found in both exhaustive graded exercise tests (p = 0.002). BICA caused gastrointestinal side effects in 15 patients. CONCLUSION:  Maximal performance was enhanced significantly after BICA administration. The ergogenic effect of BICA in the exhaustive graded exercise test can most likely be attributed to an increased anaerobic glycolysis that is reflected by an accumulation of lactate. However, TTE in prolonged high-intensity running was not improved. Even at the end of exercise no severe metabolic acidosis was found. Metabolic acidification as one of the dominant factors causing muscular fatigue should therefore be reconsidered. TRIAL REGISTRATION:  German Clinical Trials Register (DRKS) DRKS00011284.

Sodium bicarbonate improves 4 km time trial cycling performance when individualised to time to peak blood bicarbonate in trained male cyclists.
            (Gough et al., 2018) Download
The aim of this study was to investigate the effects of sodium bicarbonate (NaHCO3) on 4 km cycling time trial (TT) performance when individualised to a predetermined time to peak blood bicarbonate (HCO3-). Eleven male trained cyclists volunteered for this study (height 1.82 ± 0.80 m, body mass (BM) 86.4 ± 12.9 kg, age 32 ± 9 years, peak power output (PPO) 382 ± 22 W). Two trials were initially conducted to identify time to peak HCO3- following both 0.2 g.kg-1 BM (SBC2) and 0.3 g.kg-1 BM (SBC3) NaHCO3. Thereafter, on three separate occasions using a randomised, double-blind, crossover design, participants completed a 4 km TT following ingestion of either SBC2, SBC3, or a taste-matched placebo (PLA) containing 0.07 g.kg-1 BM sodium chloride (NaCl) at the predetermined individual time to peak HCO3-. Both SBC2 (-8.3 ± 3.5 s; p < 0.001, d = 0.64) and SBC3 (-8.6 ± 5.4 s; p = 0.003, d = 0.66) reduced the time to complete the 4 km TT, with no difference between SBC conditions (mean difference = 0.2 ± 0.2 s; p = 0.87, d = 0.02). These findings suggest trained cyclists may benefit from individualising NaHCO3 ingestion to time to peak HCO3- to enhance 4 km TT performance.


Bicarbonate therapy for prevention of chronic kidney disease progression.
            (Łoniewski and Wesson, 2014) Download
Kidney injury in chronic kidney disease (CKD) is likely multifactorial, but recent data support that a component is mediated by mechanisms used by the kidney to increase acidification in response to an acid challenge to systemic acid-base status. If so, systemic alkalization might attenuate this acid-induced component of kidney injury. An acid challenge to systemic acid-base status increases nephron acidification through increased production of endothelin, aldosterone, and angiotensin II, each of which can contribute to kidney inflammation and fibrosis that characterizes CKD. Systemic alkalization that ameliorates an acid challenge might attenuate the contributions of angiotensin II, endothelin, and aldosterone to kidney injury. Some small clinical studies support the efficacy of alkalization in attenuating kidney injury and slowing glomerular filtration rate decline in CKD. This review focuses on the potential that orally administered NaHCO₃ prevents CKD progression and additionally addresses its mechanism of action, side effects, possible complications, dosage, interaction, galenic form description, and contraindications. Current National Kidney Foundation guidelines recommend oral alkali, including NaHCO₃(-), in CKD patients with serum HCO₃(-) <22 mmol/l. Although oral alkali can be provided by other medications and by base-inducing dietary constituents, oral NaHCO₃ will be the focus of this review because of its relative safety and apparent efficacy, and its comparatively low cost.

The Effects of Novel Ingestion of Sodium Bicarbonate on Repeated Sprint Ability.
            (Miller et al., 2016) Download
This work examined the influence of an acute dose of sodium bicarbonate (NaHCO3) on buffering capacity and performance during a repeated sprint ability (RSA) protocol. Eleven (mean ± SD: age 24.6 ± 6.1 years; mass 74.9 ± 5.7 kg; height 177.2 ± 6.7 cm) participated in the study, undertaking 4 test sessions. On the first visit to the laboratory, each participant ingested 300 mg · kg(-1) of NaHCO3 (in 450 ml of flavored water) and blood samples were obtained at regular intervals to determine the individual times peak pH and HCO3. In subsequent visits, participants ingested 300 mg · kg(-1) of NaHCO3, 270 mg · kg(-1) body mass (BM) of NaCI, or no drink followed by a RSA cycling protocol (10 × 6 seconds sprints with 60 seconds recovery), which commenced at each individuals predetermined ingestion peak pH response time. Blood samples were obtained before exercise and after the first, fifth, and 10th sprint to determine the blood pH, HCO3, and lactate (La) responses. Total work completed during the repeated sprint protocol was higher (p ≤ 0.05) in the NaHCO3 condition (69.8 ± 11.7 kJ) compared with both the control (59.6 ± 12.2 kJ) and placebo (63.0 ± 8.3 kJ) conditions. Peak power output was similar (p > 0.05) between the 3 conditions. Relative to the control and placebo conditions, NaHCO3 ingestion induced higher (p ≤ 0.05) blood pH and HCO3 concentrations before exercise and during the bouts, and higher lactate concentrations (p ≤ 0.05) after the final sprint. Results suggest that NaHCO3 improves the total amount of work completed during RSA through enhanced buffering capacity.

Oral NaHCO3 Activates a Splenic Anti-Inflammatory Pathway: Evidence That Cholinergic Signals Are Transmitted via Mesothelial Cells.
            (Ray et al., 2018) Download
We tested the hypothesis that oral NaHCO3 intake stimulates splenic anti-inflammatory pathways. Following oral NaHCO3 loading, macrophage polarization was shifted from predominantly M1 (inflammatory) to M2 (regulatory) phenotypes, and FOXP3+CD4+ T-lymphocytes increased in the spleen, blood, and kidneys of rats. Similar anti-inflammatory changes in macrophage polarization were observed in the blood of human subjects following NaHCO3 ingestion. Surprisingly, we found that gentle manipulation to visualize the spleen at midline during surgical laparotomy (sham splenectomy) was sufficient to abolish the response in rats and resulted in hypertrophy/hyperplasia of the capsular mesothelial cells. Thin collagenous connections lined by mesothelial cells were found to connect to the capsular mesothelium. Mesothelial cells in these connections stained positive for the pan-neuronal marker PGP9.5 and acetylcholine esterase and contained many ultrastructural elements, which visually resembled neuronal structures. Both disruption of the fragile mesothelial connections or transection of the vagal nerves resulted in the loss of capsular mesothelial acetylcholine esterase staining and reduced splenic mass. Our data indicate that oral NaHCO3 activates a splenic anti-inflammatory pathway and provides evidence that the signals that mediate this response are transmitted to the spleen via a novel neuronal-like function of mesothelial cells.

The effect of sodium bicarbonate versus aluminum-magnesium hydroxide on postprandial gastric acid in duodenal ulcer patients.
            (Simmons et al., 1986) Download
When ingested 1 hour after a meal, conventional liquid antacids have a buffering effect of approximately 2 hours, while in the fasting state their effect is brief, lasting less than 1 hour. We tested the hypothesis that equal doses of antacid, one water soluble (sodium bicarbonate) and the other water insoluble (aluminum hydroxide plus magnesium hydroxide, MaaloxR), would have similar durations of postprandial buffering if the water soluble antacid regenerates the particulate protein buffer of the meal that leaves the stomach more slowly than liquids. Tests were conducted in random order on three separate days in 10 patients with duodenal ulcer. The effects of 30 ml of 2.39 M sodium bicarbonate (6.17 g, about 1 teaspoonful), the aluminum-magnesium antacid, each equivalent to 71.7 mmol of in vitro buffer, and water as a control on pH, hydrogen ion activity, and titratable acidity were compared. Thirty milliliters of each was swallowed 1 and 3 hours after ingestion of a standard solid plus liquid. Compared to the water control each dose of sodium bicarbonate significantly increased intragastric pH and decreased hydrogen ion activity and titratable acidity for only 1 hour. Each dose of the aluminum-magnesium antacid significantly buffered intragastric contents for 2 hours. These findings indicate that sodium bicarbonate transiently buffers postprandial intragastric contents. Therefore, sodium bicarbonate fails to reconstitute the protein buffer of the meal effectively, and the observations suggest that it leaves the stomach rapidly with the liquid phase of the meal. However, the water insoluble, aluminum-magnesium antacid has a longer duration of buffering, probably because it leaves the stomach more slowly, largely with the solid portion of the meal.

 


References

Bellasi, A, et al. (2016), ‘Correction of metabolic acidosis improves insulin resistance in chronic kidney disease.’, BMC Nephrol, 17 (1), 158. PubMed: 27770799
Deb, SK, et al. (2018), ‘Sodium bicarbonate supplementation improves severe-intensity intermittent exercise under moderate acute hypoxic conditions.’, Eur J Appl Physiol, 118 (3), 607-15. PubMed: 29344729
Freis, T, et al. (2017), ‘Effect of sodium bicarbonate on prolonged running performance: A randomized, double-blind, cross-over study.’, PLoS One, 12 (8), e0182158. PubMed: 28797049
Gough, LA, et al. (2018), ‘Sodium bicarbonate improves 4 km time trial cycling performance when individualised to time to peak blood bicarbonate in trained male cyclists.’, J Sports Sci, 36 (15), 1705-12. PubMed: 29183257
Łoniewski, I and DE Wesson (2014), ‘Bicarbonate therapy for prevention of chronic kidney disease progression.’, Kidney Int, 85 (3), 529-35. PubMed: 24107852
Miller, P, et al. (2016), ‘The Effects of Novel Ingestion of Sodium Bicarbonate on Repeated Sprint Ability.’, J Strength Cond Res, 30 (2), 561-68. PubMed: 26815179
Ray, SC, et al. (2018), ‘Oral NaHCO3 Activates a Splenic Anti-Inflammatory Pathway: Evidence That Cholinergic Signals Are Transmitted via Mesothelial Cells.’, J Immunol, PubMed: 29661827
Simmons, TC, et al. (1986), ‘The effect of sodium bicarbonate versus aluminum-magnesium hydroxide on postprandial gastric acid in duodenal ulcer patients.’, J Clin Gastroenterol, 8 (2), 146-49. PubMed: 3018068