Effects of exogenous lactate on lipid, protein, and glucose metabolism—a randomized crossover trial in healthy males

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. In a single-blind, randomized, crossover 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-h postabsorptive period followed by a 3-h hyperinsulinemic-euglycemic clamp (HEC). Lipolysis rate, endogenous glucose production (EGP), and delta glucose rate of disappearance (DRd 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. 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 with CTR (84 ± 32 lmol/min vs. 120 ± 35 lmol/min, P ¼ 0.003). During the HEC, palmitate flux was suppressed similarly during both interventions (P ¼ 0.7). EGP, DRd glu, and M value were similar during LAC and CTR. During HEC, LAC increased whole body phenylalanine flux (P ¼ 0.02) and protein synthesis (P ¼ 0.03) compared with CTR; LAC did not affect forearm protein metabolism compared with CTR. 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. NEW & NOTEWORTHY Lactate is a decisive intermediary metabolite, serving as an energy substrate and a signaling molecule. The present study examines the effects of lactate on substrate metabolism and insulin sensitivity in healthy males. Hyperlactatemia reduces lipolysis by 30% without affecting insulin sensitivity and glucose metabolism. In addition, hyperlactatemia increases whole body amino acid turnover rate.