Effects of exogenous lactate on lipid, protein, and glucose metabolism - a randomized cross-over trial in healthy males

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Background: Lactate may inhibit lipolysis and thus enhance insulin sensitivity, but there is a lack of metabolic human studies. This study aimed to determine how hyperlactatemia affects lipolysis, glucose- and protein metabolism, and insulin sensitivity in healthy men. Methods: In a single-blind, randomized, cross-over design, eight healthy men were studied after an overnight fast on two occasions: 1) during a sodium-lactate infusion (LAC) and 2) during a sodium-matched NaCl infusion (CTR). Both days consisted of a 3-hour postabsorptive period followed by a 3-hour hyperinsulinemic-euglycemic clamp (HEC). Lipolysis rate, endogenous glucose production (EGP), and delta glucose rate of disappearance (ΔRd glu) were evaluated using [9,10- 3H]palmitate and [3- 3H]glucose tracers. In addition, whole-body- and forearm protein metabolism was assessed using [ 15N]phenylalanine, [ 2H 4]tyrosine, [ 15N]tyrosine, and [ 13C]urea tracers. Results: In the postabsorptive period, plasma lactate increased to 2.7±0.5 mmol/L during LAC vs. 0.6±0.3 mmol/L during CTR (p<0.001). In the postabsorptive period, palmitate flux was 30% lower during LAC compared to CTR (84±32 mmol/min vs. 120±35 mmol/min, p=0.003). During the HEC, palmitate flux was suppressed similarly during both interventions (p=0.7). EGP, ΔRd glu, and M-value were similar during LAC and CTR. During HEC, LAC increased whole-body phenylalanine flux (p=0.02) and protein synthesis (p=0.03) compared with CTR; LAC did not affect forearm protein metabolism compared to CTR. Conclusion: Lactate infusion inhibited lipolysis by 30% under postabsorptive conditions but did not affect glucose metabolism or improve insulin sensitivity. In addition, whole-body phenylalanine flux was increased. Clinical trial registrations: NCT04710875.

Original languageEnglish
JournalAmerican Journal of Physiology: Endocrinology and Metabolism
Pages (from-to)E443-E453
Number of pages11
Publication statusPublished - Apr 2024


  • Blood Glucose/metabolism
  • Cross-Over Studies
  • Glucose Clamp Technique
  • Glucose/pharmacology
  • Humans
  • Hyperlactatemia
  • Insulin
  • Insulin Resistance
  • Lactic Acid/pharmacology
  • Male
  • Palmitates
  • Phenylalanine
  • Proteins
  • Single-Blind Method
  • Sodium
  • Tyrosine


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