The cephalic phase insulin response to nutritive and low-calorie sweeteners in solid and beverage form

Physiol Behav. 2017 Nov 1;181:100-109. doi: 10.1016/j.physbeh.2017.09.009. Epub 2017 Sep 9.


The purpose of the study was to examine the role of the cephalic phase insulin response (CPIR) following exposure to nutritive and low-calorie sweeteners in solid and beverage form in overweight and obese adults. In addition, the role of learning on the CPIR to nutritive and low-calorie sweetener exposure was tested. Sixty-four overweight and obese adults (age: 18-50years, BMI: 24-37kg/m2, body fat percentage>25% for men and >32% for women) were sham-fed (at 2-minute intervals for 14min) a randomly assigned test load comprised of a nutritive (sucrose) or low-calorie sweetener (sucralose) in beverage or solid form in phase 1 of the study. A 2-3ml blood sample was collected before and 2, 6, 10, 14, 61, 91 and 121min after oral exposure for serum insulin and glucose analysis. During phase 2, participants underwent a 2-week training period to facilitate associative learning between the sensory properties of test loads and their post-ingestive effects. In phase 3, participants were retested for their cephalic phase responses as in phase 1. Participants were classified as responders if they demonstrated a positive insulin response (rise of serum insulin above baseline i.e. Δ insulin) 2min post-stimulus in phase 1. Among responders exposed to the same sweetener in Phases 1 and 3, the proportion of participants that displayed a rise of insulin with oral exposure to sucralose was significantly greater when the stimulus was in the solid form compared to the beverage form. Sucralose and sucrose exposure elicited similarly significant increases in serum insulin 2min after exposure and significant decreases after 2min in responders in both food forms. The solid food form elicited greater CPIR over 2, 6 and 10min than the beverage form. There was no effect of learning on insulin responses after training. The results indicate the presence of a significant CPIR in a subset of individuals with overweight or obesity after oral exposure to sucralose, especially when present in solid food form. Future studies must confirm the reliability of this response.

Keywords: Cephalic phase; Food form; Insulin response; Learning; Low-calorie sweeteners; Obesity.

MeSH terms

  • Adolescent
  • Adult
  • Association Learning
  • Beverages*
  • Blood Glucose / drug effects*
  • Female
  • Humans
  • Insulin / blood*
  • Male
  • Middle Aged
  • Obesity / blood
  • Obesity / physiopathology
  • Obesity / psychology
  • Overweight / blood
  • Overweight / physiopathology
  • Overweight / psychology
  • Powders / pharmacology
  • Sucrose / analogs & derivatives*
  • Sucrose / pharmacology*
  • Sweetening Agents / pharmacology*
  • Young Adult


  • Blood Glucose
  • Insulin
  • Powders
  • Sweetening Agents
  • Sucrose
  • trichlorosucrose