Endocrine Cephalic Phase Responses to Food Cues: A Systematic Review

Abstract

Cephalic phase responses (CPRs) are conditioned anticipatory physiological responses to food cues. They occur before nutrient absorption and are hypothesized to be important for satiation and glucose homeostasis. Cephalic phase insulin responses (CPIRs) and pancreatic polypeptide responses (CPPPRs) are found consistently in animals, but human literature is inconclusive. We performed a systematic review of human studies to determine the magnitude and onset time of these CPRs. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were used to develop a search strategy. The terms included in the search strategy were cephalic or hormone response or endocrine response combined with insulin and pancreatic polypeptide (PP). The following databases were searched: Scopus (Elsevier), Science Direct, PubMed, Google Scholar, and The Cochrane Library. Initially, 582 original research articles were found, 50 were included for analysis. An insulin increase (≥1μIU/mL) was observed in 41% of the treatments (total n = 119). In 22% of all treatments the increase was significant from baseline. The median (IQR) insulin increase was 2.5 (1.6–4.5) μIU/mL, 30% above baseline at 5± 3 min after food cue onset (based on study treatments that induced ≥1 μIU/mL insulin increase). A PP increase (>10 pg/mL) was found in 48% of the treatments (total n = 42). In 21% of the treatments, the increase was significant from baseline. The median (IQR) PP increase was 99 (26–156) pg/mL, 68% above baseline at 9± 4 min after food cue onset (based on study treatments that induced ≥1 μIU/mL insulin increase). In conclusion, CPIRs are small compared with spontaneous fluctuations. Although CPPPRs are of a larger magnitude, both show substantial variation in magnitude and onset time. We found little evidence for CPIR or CPPPR affecting functional outcomes, that is, satiation and glucose homeostasis. Therefore, CPRs do not seem to be biologically meaningful in daily life.

Effects of Oro-Sensory Exposure on Satiation and Underlying Neurophysiological Mechanisms—What Do We Know So Far?

“…CPRs are anticipatory and conditioned responses to food cues [ 5 , 6 ]. They occur within minutes after food consumption and are, therefore, not related to nutrient sensing further down in the digestive tract [ 4 , 5 ]. Cephalic responses include increased production of saliva, gastric juice, secretion of bile by the gallbladder, increased gut motility, and gastric and pancreatic hormone secretion [ 79 , 80 , 81 , 82 ].…”

“…Cephalic responses include increased production of saliva, gastric juice, secretion of bile by the gallbladder, increased gut motility, and gastric and pancreatic hormone secretion [ 79 , 80 , 81 , 82 ]. Examples of cephalic hormones are insulin, pancreatic polypeptide, and ghrelin [ 4 , 5 , 83 ]. The supposed function of CPRs is to “prepare” the body for incoming nutrients to optimize digestion [ 6 , 84 ].…”

“…Additionally, only two studies found an effect of a reduced CPRs on subjective appetite ratings [ 83 , 90 ]. Accordingly, it should be questioned whether these CPRs affect satiation and are biologically meaningful in daily life [ 4 ]. If cephalic phase responses play an important role in satiation, it is likely to be caused by cephalic phase responses other than insulin and pancreatic polypeptide response, such as early production of saliva and gastric juice [ 69 ].…”

“…This allows for the start of carbohydrate digestion in the mouth and makes the bolus safe to swallow [ 3 ]. During this mastication process, food is perceived in the mouth by the senses (mostly taste and retro-nasal smell) and multiple physiological processes are initiated (for reviews see [ 4 , 5 ]). Eating food is potentially a threat to the body’s homeostasis, therefore, oral exposure serves as an alarm such that the body can anticipate and prepare incoming nutrients for optimal digestion [ 6 , 7 ].…”

Expectation for sweet taste changes peripheral glucose metabolism via basolateral amygdala

“…These neuronal pathways may control peripheral glucose metabolism. However, the importance of CPIR on the regulation of blood glucose levels is still in debate ( 35 ). Thus, we focused on blood glucose level itself instead of CPIR.…”