Lactose and sucrose each stimulate hepatic de novo lipogenesis: A randomized crossover trial

BACKGROUND: Fructose-containing sugars can exaggerate postprandial lipemia and stimulate hepatic de novo lipogenesis (DNL) relative to glucose-based carbohydrates. Despite being consumed by most of the global population, the effects of galactose-containing sugars on hepatic DNL are currently unknown. OBJECTIVES: To assess the effects of lactose ingestion on lipemia and DNL. METHODS: Twenty-four adults without obesity (12 male and 12 female) completed 3 laboratory visits in a randomized, crossover design [33 ± 14 d washout; mean ± SD]. During laboratory visits, participants consumed beverages containing 50-g fat with 100 g of carbohydrate. The control carbohydrate was a glucose polymer (maltodextrin), the experimental carbohydrate was a galactose-containing carbohydrate (lactose), and the active comparator was a fructose-containing carbohydrate (sucrose). Hepatic DNL was assessed using the ²H₂O method, and [U-¹³C]-palmitate was added to the test drink to trace the fate of the ingested fat. Blood and breath samples were taken to determine plasma metabolite and hormone concentrations, in addition to plasma and breath ²H and ¹³C enrichments. Summary statistics were analyzed by 1-way analysis of variance (ANOVA), and time series data by 2-way (time × treatment) ANOVA or linear mixed models when data were missing. RESULTS: The plasma triacylglycerol incremental area under the curve (iAUC) (mean ± SD) in response to maltodextrin was 0.85 ± 1.13 mmol·L‒1·360 min and peak hepatic DNL was 11% ± 3%. Following lactose ingestion, plasma triacylglycerol iAUC increased to 1.63 ± 1.47 mmol·L‒1·360 min (P < 0.001 compared with maltodextrin), and hepatic DNL increased to 22% ± 4% (P < 0.001 compared with maltodextrin), to a degree statistically indistinguishable from following sucrose ingestion [1.50 ± 1.58 mmol·L‒1·360 min (P = 0.41 compared with lactose); and 23% ± 4% (P = 0.54 compared with lactose)]. Contributions of dietary fat to very low-density lipoprotein- and chylomicron-triacylglycerol-palmitate were both higher after ingestion of lactose compared with maltodextrin (both P < 0.05) and were statistically indistinguishable after lactose ingestion compared with sucrose (both P > 0.05). CONCLUSIONS: Lactose ingestion stimulates hepatic DNL by a magnitude that is not significantly different from that of fructose. This challenges the prevailing view that galactose-containing sugars are metabolically equivalent to glucose-based carbohydrates. This trial was registered at clinicaltrials.gov as NCT04924530.