Oral lactate slows gastric emptying and suppresses appetite in young males

Clin Nutr. 2022 Feb;41(2):517-525. doi: 10.1016/j.clnu.2021.12.032. Epub 2021 Dec 24.

Abstract

Background: 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.

Methods: 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.

Results: 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.

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.

Clinical trial registry number: NCT0429981, https://clinicaltrials.gov/ct2/show/NCT04299815.

Keywords: GDF-15; GIP; GLP-1; Ghrelin.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Intravenous
  • Administration, Oral
  • Adult
  • Appetite / drug effects*
  • Appetite Depressants / administration & dosage*
  • Eating / physiology
  • Gastric Emptying / drug effects*
  • Gastrointestinal Hormones / blood
  • Ghrelin / blood
  • Glucagon / blood
  • Glucagon-Like Peptide 1 / blood
  • Growth Differentiation Factor 15 / blood
  • Healthy Volunteers
  • Humans
  • Insulin / blood
  • Lactic Acid / administration & dosage*
  • Male
  • Young Adult

Substances

  • Appetite Depressants
  • GDF15 protein, human
  • GHRL protein, human
  • Gastrointestinal Hormones
  • Ghrelin
  • Growth Differentiation Factor 15
  • Insulin
  • Lactic Acid
  • Glucagon-Like Peptide 1
  • Glucagon

Associated data

  • ClinicalTrials.gov/NCT04299815