Effects of Sucralose vs. Sucrose on Hypothalamic Blood Flow, Glucose Signaling, and Appetite

Sucralose is a non-nutritive sweetener (NNS) commonly consumed to provide sweet taste without calories. Yet, some studies suggest NNS stimulate appetite, potentially by altering post-ingestive metabolic signals that communicate with the hypothalamus to reduce hunger. We tested the hypothesis that sucralose vs sucrose would elicit different metabolic, hypothalamic blood flow (BF) and appetite responses, and that post-ingestive increases in metabolic signals would be associated with reductions in hypothalamic BF and hunger. In a randomized cross-over trial, hypothalamic BF (measured by perfusion MRI), appetite ratings, and glucose/hormone responses were obtained before, 15 and 30 min after ingestion of drinks containing sucrose (75g) or sucralose (sweetness matched). Paired t-tests were used to compare sucralose vs sucrose on metabolic responses, hypothalamic BF, and appetite. Linear regression was used to examine associations between peripheral glucose, insulin, GLP-1 and hypothalamic BF and hunger. 76 adults (43F; 23.3±3.9 yrs; BMI 27.2±5) completed the study. Subjects reported increased hunger at 15 (p<.04) and 30min (p<.003) after sucralose vs sucrose. Peripheral glucose, insulin, and GLP-1 were lower after sucralose vs sucrose (all p<.0001). Glycemic response (whole hypothalamus (β=-.002, p=.05), medial subfield (β=−.005, p<.006)), but not insulin or GLP-1, was associated with the hypothalamic response to sucrose at 30 min, controlling for age, sex, BMI. These associations were not observed after sucralose (β=.008 p=.2). The medial hypothalamic response predicted hunger response after both drinks (β=1.79, p<.02). Sucralose vs sucrose elicited disparate metabolic, hypothalamic, and hunger responses. Sucrose-induced increases in glycemia were associated with reductions in medial hypothalamic BF, which was linked to reduced hunger. Compared to sucrose, post-ingestive signaling responses were altered after sucralose, which may affect appetite. Disclosure S.P.Chakravartti: None. K.A.Page: None. S.Kullmann: None. R.Veit: None. A.G.Yunker: None. B.C.Angelo: None. K.Jann: None. S.H.Luo: None. A.Xiang: None. J.R.Monterosso: None. Funding National Institute of Diabetes and Digestive and Kidney Diseases (R01DK102794)