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 (Delta Rd(glu)) were evaluated using [9,10-H-3]palmitate and [3-H-3]glucose tracers. In addition, whole body- and forearm protein metabolism was assessed using [N-15]phenylalanine, [H-2(4)]tyrosine, [N-15]tyrosine, and [C-13]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 <mu>mol/min vs. 120 +/- 35 mu mol/min, P = 0.003). During the HEC, palmitate flux was suppressed similarly during both interventions (P = 0.7). EGP, Delta Rd(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 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.