Oral lactate slows gastric emptying and suppresses appetite in young males

Mette Glavind Bülow Pedersen,Esben Søndergaard,Camilla Bak Nielsen,Mogens Johannsen,Lars Christian Gormsen,Niels Møller,Niels Jessen,Nikolaj Rittig

doi:10.1016/j.clnu.2021.12.032

Mette Glavind Bülow Pedersen, Esben Søndergaard + Show 6 more

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https://doi.org/10.1016/j.clnu.2021.12.032

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Abstract

Lactate serves as an alternative energy fuel but is also an important signaling metabolite. We aimed to investigate whether oral lactate administration affects appetite-regulating hormones, slows gastric emptying rate, and dampens appetite. Ten healthy male volunteers were investigated on two separate occasions: 1) following oral ingestion of D/L-Na-lactate and 2) following oral ingestion of isotonic iso-voluminous NaCl and intravenous iso-lactemic D/L-Na-lactate infusions. Appetite was evaluated by questionnaires and ad libitum meal tests were performed at the end of each study day. Gastric emptying rate was evaluated using the acetaminophen test. Plasma concentrations of growth differential factor 15 (GDF15, primary outcome) increased following oral and iv administration of lactate (p<0.001) with no detectable difference between interventions (p=0.15). Oral lactate administration lowered plasma concentrations of acylated ghrelin (p=0.02) and elevated glucagon like peptide-1 (GLP-1, p=0.045), insulin (p<0.001), and glucagon (p<0.001) compared with iv administration. Oral lactate administration slowed gastric emptying (p<0.001), increased the feeling of being "full" (p=0.008) and lowered the "anticipated future food intake" (p=0.007) compared with iv administration. Food intake during the ad libitum meal test did not differ between the two study days. Oral lactate administration has a direct effect on the upper gastrointestinal tract, affecting gut hormone secretion, motility and appetite sensations which cannot be mediated through lactate in the systemic circulation alone. These data suggest that compounds rich in lactate may be useful in the treatment of metabolic disease. NCT0429981, https://clinicaltrials.gov/ct2/show/NCT04299815.

Highlights

Lactate is a key metabolite in the intermediary metabolism and serves as an alternative energy source in major organs including the heart and brain [1e4]
Lactate may interact with numerous receptors and potentially affect GI motility, appetite sensation, and secretion of gut hormones such as glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP)
Median plasma concentration of acylated ghrelin decreased during the hours following both oral and intravenous lactate administration (Fig. 2B) but more profoundly so after oral administration

Summary

Introduction

Lactate is a key metabolite in the intermediary metabolism and serves as an alternative energy source in major organs including the heart and brain [1e4] It is produced endogenously through nonoxidative glucose metabolism and through microbial fermentation of nutrients primarily in the lower gastrointestinal (GI) tract. Conclusion: Oral lactate administration has a direct effect on the upper gastrointestinal tract, affecting gut hormone secretion, motility and appetite sensations which cannot be mediated through lactate in the systemic circulation alone. These data suggest that compounds rich in lactate may be useful in the treatment of metabolic disease.

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