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The effect of body acid–base state and manipulations on body glucose regulation in human

Abstract

Long-term exposure to high dietary acid load has been associated with insulin resistance and type 2 diabetes in epidemiological studies. However, it remains unclear whether the acid load of the diet translates to mild metabolic acidosis and whether it is responsible for the impairment in glucose regulation in humans. Previously, in a cross-sectional study we have reported that dietary acid load was not different between healthy individuals with normal weight and those with overweight/obesity, irrespective of insulin sensitivity. However, 4-week high acid load diet increased plasma lactate (a small component of the anion gap) and increased insulin resistance in healthy participants. The change in plasma lactate correlated significantly with the change in insulin resistance. Because cause-and-effect could not be evaluated in these settings, we sought to directly test the effect of an alkalizing treatment preload on postprandial glucose regulation. In a randomized placebo-controlled study with a crossover design, we administered sodium bicarbonate (NaHCO3, 1.68 g) prior to high acid load meal to healthy individuals. We found that while the bicarbonate preload attenuated the post meal decrease in pH observed with placebo, no effect on postprandial glucose regulation (glucose, insulin, and C-peptide) was observed. Following 3-month treatment of nondiabetic individuals with bicarbonate, others have reported no change in insulin resistance markers, consistent with our findings. Together, studies in human suggest that insulin resistance associated with longstanding obesogenic diet may be mediated by mild metabolic acidosis. However, buffering the Western diet with bicarbonate and increasing body pH does not change glucose homeostasis in nondiabetic individuals. Further studies are required to shed light on the role of body acid–base balance and glucose homeostasis in health and disease.

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Fig. 1: Mechanisms proposed to mediate the influence of dietary acid load on type 2 diabetes risk.
Fig. 2: Difference in the degree of insulin resistance and plasma lactate concentrations between lean, overweight/obese insulin-sensitive and insulin-resistant individuals.
Fig. 3: The effect of overfeeding on peripheral insulin resistance and plasma lactate in healthy individuals.
Fig. 4: The effect of sodium bicarbonate versus placebo administered with a high acid load meal on venous blood pH.
Fig. 5: Postprandial glucose regulation following 1.68 g of NaHCO3 or placebo administered with a high acid load meal in healthy individuals.

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Acknowledgements

We thank our study participants and the members of the Clinical Insulin Resistance group at the Garvan Institute of Medical Research.

Funding

The clinical studies performed in Samocha-Bonet’s laboratory were funded by Diabetes Australia Research Program and the Garvan Research Foundation, Sydney, Australia. This article is published as part of a supplement sponsored by NuOmix-Research k.s. The conference was financially supported by Protina Pharmazeutische GmbH, Germany and Sirius Pharma, Germany, and organized by NuOmix-Research k.s. Neither company had any role in writing of the paper.

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DS-B conceived some of the clinical studies reported in the review, presented the findings at the 3rd International Acid–Base Symposium, and wrote the report. EC contributed to writing and reviewed the report.

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Correspondence to Dorit Samocha-Bonet.

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Chalmers, E., Samocha-Bonet, D. The effect of body acid–base state and manipulations on body glucose regulation in human. Eur J Clin Nutr 74, 20–26 (2020). https://doi.org/10.1038/s41430-020-0692-6

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