Effects of acute and multi-day low-dose sodium bicarbonate intake on high-intensity endurance exercise performance in male recreational cyclists.

PURPOSE: This study aimed to compare the effects of acute and multi-day low-dose sodium bicarbonate (SB) intake on high-intensity endurance exercise performance. METHODS: In a randomized, double-blind, cross-over design, twelve recreational male cyclists (age: 31.17 ± 4.91 years; V ˙ O2peak: 47.98 ± 7.68 ml·kg-1·min-1) completed three endurance performance tests following acute SB (ASB, 0.2 g·kg-1 SB), multi-day SB (MSB, 0.2 g·kg-1·day-1 SB for four days), and placebo (PLA) intake. The high-intensity endurance performance was assessed with a cycling exercise test, wherein participants cycled on a bicycle ergometer at 95% of the predetermined anaerobic threshold for 30 min, followed by a time-to-exhaustion test at 110% of the anaerobic threshold. Data were analyzed using one-way and two-way repeated-measures ANOVA. RESULTS: Significant main effects of supplementation protocol were evident in pre-exercise bicarbonate concentrations (F = 27.93; p < 0.01; partial eta squared (η2) = 0.72; false discovery rate (FDR)-adjusted p value = 0.001). Prior to performance test, blood bicarbonate concentrations were significantly higher in MSB (25.78 ± 1.63 mmol·L-1 [95% CI 26.55-28.44] (p < 0.001; FDR-adjusted p value = 0.001)) and ASB (27.49 ± 1.49 mmol·L-1 [95% CI 24.75-26.81] (p < 0.001; FDR-adjusted p value = 0.007)) compared to PLA (23.75 ± 1.40 mmol·L-1 [95% CI 22.86 to 24.64]). Time-to-exhaustion increased in MSB (54.27 ± 9.20 min [95% CI 48.43-60.12]) compared to PLA (49.75 ± 10.80 min [95% CI 42.89-56.62]) (p = 0.048); however, this increase in MSB did not reach the significance threshold of 1% FDR (FDR-adjusted p value = 0.040). No significant difference was noted in exhaustion times between ASB (51.15 ± 8.39 min [95% CI 45.82-56.48]) and PLA (p > 0.05). CONCLUSION: Both acute and multi-day administration of low-dose SB improves buffering system in cyclists; nevertheless, neither intervention demonstrates sufficient efficacy in enhancing high-intensity endurance performance.

Increasing Tumor Extracellular pH by an Oral Alkalinizing Agent Improves Antitumor Responses of Anti-PD-1 Antibody: Implication of Relationships between Serum Bicarbonate Concentrations, Urinary pH, and Therapeutic Outcomes.

Acidic extracellular pH (pHe) is characteristic of the tumor microenvironment. Several reports suggest that increasing pHe improves the response of immune checkpoint inhibitors in murine models. To increase pHe, either sodium bicarbonate (NaHCO3) or citric acid/potassium-sodium citrate (KNa-cit) was chronically administered to mice. It is hypothesized that bicarbonate ions (HCO3-), produced from these alkalinizing agents in vivo, increased pHe in the tumor, and excess HCO3- eliminated into urine increased urinary pH values. However, there is little published information on the effect of changing serum HCO3- concentrations, urinary HCO3- concentrations and urinary pH values on the therapeutic outcomes of immunotherapy. In this study, we report that oral administration of either NaHCO3 or KNa-cit increased responses to anti-programmed cell death-1 (PD-1) antibody, an immune checkpoint inhibitor, in a murine B16 melanoma model. In addition, we report that daily oral administration of an alkalinizing agent increased blood HCO3- concentrations, corresponding to increasing the tumor pHe. Serum HCO3- concentrations also correlated with urinary HCO3- concentrations and urinary pH values. There was a clear relationship between urinary pH values and the antitumor effects of immunotherapy with anti-PD-1 antibody. Our results imply that blood HCO3- concentrations, corresponding to tumor pHe and urinary pH values, may be important factors that predict the clinical outcomes of an immunotherapeutic agent, when combined with alkalinizing agents such as NaHCO3 and KNa-cit.

Alkali Therapy for Respiratory Acidosis: A Medical Controversy.

Alkali therapy for certain organic acidoses remains a topic of ongoing controversy, but little attention has been given to a related medical controversy, namely the prescription of alkali for respiratory acidosis. We first describe the determinants of carbon dioxide retention in the 2 types of respiratory failure; hypercapnic respiratory failure and hypoxemic respiratory failure with coexisting hypercapnia. We then highlight the deleterious consequences of severe acidemia for several organ systems, particularly the cardiovascular and central nervous systems. We argue that alkali therapy is not indicated for respiratory acidosis as a simple acid-base disturbance. Notwithstanding, we recommend prescription of alkali for severe acidemia caused by mixed acidosis (ie, combined respiratory and metabolic acidosis) or permissive hypercapnia. We examine the utility of alkali therapy in various clinical scenarios incorporating respiratory acidosis. We conclude that controlled studies will be required to test the impact of alkali therapy on clinical outcomes of these clinical settings. Such studies should also examine the optimal mode of administering alkali (amount, rate, and tonicity) and the blood pH to be targeted. The development of new buffers should be explored, especially systems that do not generate carbon dioxide or even consume it.

Nutrient density and bioaccessibility, and the antioxidant, satiety, glycemic, and alkalinizing potentials of fruit-based foods according to the degree of processing: a narrative review.

Epidemiological studies suggest that the protective effects of fruits against chronic diseases may vary according to their extent of processing. We therefore reviewed what the scientific literature states about the potential mechanisms underlying this "processing" effect by focusing on the most significant nutritional properties, namely, the nutritional density of bioactive compounds, the digestive bio-accessibility of nutrients, and the antioxidant, satietogenic, alkalizing and glycemic potentials. When possible, we have ranked fruits according to the international NOVA classification as un-/minimally processed, processed (mainly with added sugars), and ultra-processed fruits. Our literature review confirms that the more fruits are processed, the lower are their alkalizing, antioxidant and satietogenic potentials. For the glycemic index, the results are more difficult to interpret because fruits are a significant source of fructose with a very low glycemic index that "distorts" the "processing" effect. However, fruits in sirup tend to have a higher glycemic index, probably because of the highly bioavailable added sugars. Overall, the destructuration of the fruit fibrous matrix by thermal and mechanical treatments, combined with the addition of simple sugars, constitute the treatments that most degrade the fruit nutritive quality by diluting the nutritional density and attenuating the "matrix" effect. The new technological processes described as "nonthermal" (e.g., pulsed electric fields, high pressures, supercritical CO2, radiation, etc.) seem promising as they limit vitamin C and antioxidant phytonutrient losses in fruit while allowing satisfactory storage time. To preserve fruit longer, drying appears to be an interesting alternative to maintain the health potential of fruit, although it causes antioxidant losses. Finally, although "5 fruits and vegetables a day" is a well-known nutritional recommendation, in view of the results reviewed here, it would be relevant to be precise and include "preferably minimally processed".

NIR-Emitting Hemicyanines with Large Stokes' Shifts for Live Cell Imaging: from Lysosome to Mitochondria Selectivity by Substituent Effect.

Lysosome imaging without perturbing intracellular activity remains challenging, as the current commercial lysosome probes contain weakly basic amino groups that could perturb lysosome pH. Herein, we illustrate NIR-emitting dyes 2 and 3 (λem ≈ 700 nm) with very large Stokes' shifts (Δλ = 231-246 nm), attributing to the presence of a 2-hydroxyphenyl(benzo[d]oxazol) (HBO) unit that undergoes excited-state intramolecular proton transfer (ESIPT). The structures of 2 and 3 also contain a hemicyanine unit with benzothiazolium and indolium as a terminal group, respectively. Although the fluorescent probe 2 (Φfl ≈ 0.28-0.35 in CH2Cl2) does not contain any basic amino functional group, it exhibits excellent selectivity for staining intracellular lysosomes, showing the potential for long-term in vivo lysosome imaging without "alkalinizing effect." However, probe 3 (Φfl ≈ 0.27, in CH2Cl2) exhibits excellent selectivity toward mitochondria. The observation showed that the terminal group in the hemicyanine unit played an essential role in guiding the intracellular selectivity to different organelles. In addition, the probes also displayed a transparent optical window between 520 and 590 nm, which is useful to achieve multicolor co-staining study, without fluorescence crosstalk that is a common problem on fluorescence microscopes.

Approach to the Treatment of Chronic Metabolic Acidosis in CKD.

Chronic metabolic acidosis is not uncommon in patients with chronic kidney disease (CKD). Clinical practice guidelines suggest that clinicians administer alkali to maintain serum bicarbonate level at a minimum of 22 mEq/L to prevent the effects of acidosis on bone demineralization and protein catabolism. Small interventional studies support the notion that correcting acidosis slows CKD progression as well. Furthermore, alkaline therapy in persons with CKD and normal bicarbonate levels may also preserve kidney function. Observational studies suggest that targeting a serum bicarbonate level near 28 mEq/L may improve clinical outcomes above and beyond targeting a value ≥ 22 mEq/L, yet values > 26 mEq/L have been reported to be associated with incident heart failure and mortality in the CRIC (Chronic Renal Insufficiency Cohort) Study. Furthermore, correcting acidosis may provoke vascular calcification. This teaching case discusses several uncertainties regarding the management of acidosis in CKD, such as when to initiate alkali treatment, potential side effects of alkali, and the optimum serum bicarbonate level based on current evidence in CKD. Suggestions regarding the maximum sodium bicarbonate dose to administer to patients with CKD to achieve the target serum bicarbonate concentration are offered.

Efeito da solução de Ringer com lactato sobre os equilíbrios hidroeletrolítico e acidobase de equinos, ovelhas e bezerros sadios / Effect of lactated Ringer’s solution on fluid, electrolyte and acid-base balances of healthy horses, ewes and calves

O objetivo deste trabalho foi investigar os efeitos da solução de Ringer com lactato (SRL) sobre os equilíbrios hidroeletrolítico e acidobase de equinos, ovelhas e bezerros hígidos. Equinos adultos (n=6), ovelhas adultas (n=6) e bezerros (n=5) receberam a SRL em volume correspondente a 10% do peso corporal, administrada por infusão contínua intravenosa durante quatro (ovelhas e bezerros) ou seis (equinos) horas. Amostras de sangue venoso e de urina foram colhidas antes do início da infusão, na metade do volume infundido, ao término da infusão e duas (ovelhas e bezerros) ou três (equinos) horas após. Foram determinados valores de pH sanguíneo e urinário, de pCO2, HCO3- e BE no sangue, de Na+, K+, Cl- e SID no soro, de AG, PPT, Atot e lactato L no plasma e das excreções fracionadas urinárias de Na+, K+, Cl- e lactato L. A SRL provocou hemodiluição e não afetou os equilíbrios eletrolítico e acidobase nas três espécies estudadas, não sendo capaz de promover aumento da reserva alcalina. Por outro lado, deve ser considerada segura para a terapia de manutenção com infusão de grandes volumes porque não provoca desequilíbrios eletrolíticos.

The effects of lactated Ringer's solution (LRS) on fluid, electrolyte and acid-base balances were investigated in healthy horses, ewes and calves. LRS was intravenously infused in six adult horses, six adult ewes and five calves in a volume corresponding to 10% of body weight, continously during four (ewes and calves) or six (horses) hours. Venous blood and urine samples were taken before the beginning, in the middle, at the end of the infusion and two (ewes and calves) or three (horses) hours after. Blood and urine pH, blood pCO2, HCO3- and BE, serum Na+, K+ and Cl-, and plasma TP and L lactate were measured. Na+, K+, Cl- and L lactate fractional clearance and plasma SID, AG, and Atot were calculated. In all species LRS caused hemodilution but didn't change electrolyte and acid-base balances. It was not able to increase alkali reserve. On the other hand, LRS must be considered safe for maintenance therapy with large volume infusions because it doesn't induce electrolyte imbalances.

Estudo da capacidade alcalinizante de tampões metabolizáveis em bovinos sadios / The alkalinizing effects of different metabolizable buffers in healthy steers

Seis novilhos mestiços, com cerca de 250kg e um ano de idade, foram infundidos, no decorrer de quatro horas, com cinco litros de diferentes soluções isotônicas de sais sódicos, com 150mM/l de bicarbonato, acetato, propionato, lactato L, lactato racêmico e cloreto (controle), em delineamento em quadrado latino (6x6). Análises hemogasométricas e do pH urinário foram determinadas no decorrer da infusão - zero, primeira e quatro horas - e após o seu término, na oitava hora. O pH do sangue foi maior nos animais infundidos com os tampões que nos infundidos com cloreto; teores mais elevados de bicarbonato e de excesso de ácido-base sanguíneos foram obtidos na quarta e oitava hora nos infundidos com bicarbonato e lactato; o mesmo ocorreu com a pressão de CO2 na oitava hora. Os resultados indicam que os tratamentos com Bicarbonato e lactato proporcionam acúmulo de tampões no sangue e geram discreta alcalose metabólica, compensada organicamente por leve retenção de CO2. a infusão com bicarbonato de sódio causa elevação do pH urinário

Six healthy crossbred yearling 250kg steers were infused intravenously, during four hours, with five liters of each of the six different isotonic solutions of sodium salts containing 150 mMol/l of the bicarbonate, acetate, propionate, L-lactate, D and L-lactate and chloride in a 6 x 6 latin square experimental design. Blood was collected from the jugular vein, anaerobically, for blood gas analysis, samples were obtained at different times throughout the infusion (zero, 1st, 4th and 8th h ). Urine was collect for determining the pH at the same schedule. Higher blood pH was found in cattle infused with all buffers than the chloride infused animals; higher level of blood bicarbonate and base excess were obtained at 4th and 8th h with bicarbonate and L-lactate, as well as with pCO2 at the 8th h. These results show that treatments with B and L lead to a slight accumulation of buffers in the blood, and generate a discrete metabolic alkalosis compensated organically by a small retention of CO2. Best alkalinizing effects are obtained by bicarbonate and L-lactato infusions. Bicarbonate infusions causes a high urinary pH