In my previous post, I looked at two hormones released during the cephalic phase (gastric secretion that occurs before food is eaten), ghrelin and obestatin, and how they may contribute to runaway eating behavior. Today I’m going to be looking at insulin release during chew and spit (CHSP), a fairly common symptom in eating disorders where the food is tasted, chewed and spit out. Insulin is a small peptide hormone that acts as a key regulator of metabolism; deregulation of insulin signalling plays a role in illnesses such as diabetes and metabolic syndrome. Some people have theorized that CHSP behavior may influence insulin regulation. In fact, there are a number of individuals stating on internet forums that chronic CHSP could lead to insulin resistance, potentially promoting diabetes. As interesting as these theories are, recent data have shown that they are probably not true.
INSULIN RELEASE DURING THE CEPHALIC RESPONSE
The taste of food activates the vagus nerve, a part of the peripheral nervous system that sends signals to the pancreas. In response, the pancreas releases insulin (as well as other hormones) in preparation for food ingestion. This is called the cephalic phase insulin release (CPIR). The magnitude of CPIR has been shown to positively correlate with food palatability, as well as reflect one’s motivation to eat.
The size and duration of CPIR depends on multiple factors. Sweet tasting foods seem to elicit the largest response, on the other hand, multiple studies have shown that sweet tasting solutions or artificial sweeteners fail to stimulate CPIR (although this is controversial). Fatty foods, in combination with sugar, elicits an even larger CPIR. The phase of digestion also matters. In overnight-fasted individuals, CPIR peaks roughly 4min after sensory stimulation and returns to baseline within 10min. After eating (postprandial state), CPIR is much larger and can last up to an hour. Conversely, individual preference towards different food types does not seem to play a role in regulating CPIR magnitude.
Of note is that CPIR is NOT always measured in healthy individuals following presentation and tasting of food. This may be due to the concurrent activation of sympathetic nervous system, which inhibits insulin secretion. Hence individual differences should be taken into consideration when looking at CPIR.
WHAT IS THE PHYSIOLOGICAL ROLE OF CPIR?
Although the magnitude of CPIR is only 1% of total insulin release AFTER a meal, it may play a significant role in metabolism, especially in individuals with metabolic disorders.
After healthy individuals engage in CHSP, CPIR-induced decrease in blood sugar can act as a preemptive measure to prevent a rapid rise in glucose if food is ingested. CPIR also inhibits gluconeogenesis (the generation of glucose from other sources, such as protein), reducing liver glucose production, and inhibits fat-burning in fatty tissue, thereby reducing free fatty acids in the blood.
Remember, CPIR occurs during chewing, but before food is actually swallowed. All of these actions can provide the body with a buffer system for subsequent incoming glucose and fat, and thus help the body maintain metabolic balance (homeostasis). Indeed, CPIR deregulation may be one factor promoting chronic high blood sugar, ultimately leading to Type II diabetes.
CPIR can also indirectly regulate hunger by regulating blood glucose. A decrease in blood sugar in response to CPIR right before food ingestion enhances the state of nutrient deficiency, which promotes greater hunger sensations and increased short-term food intake. (Though, not all studies have found changes in blood glucose levels in response to CPIR.)
CPIR IN PATIENTS WITH ANOREXIA NERVOSA
A study by Teff and Engleman (1996) using the CHSP paradigm demonstrated that in healthy women, attitude towards food influences the magnitude of CPIR, with dietary constraint positively correlating with increased CPIR.
Unfortunately, CPIR is far less studied in patients with anorexia nervosa (AN). In an older study by Brogberg and Bernstein (1989), four AN patients and four age-matched lean controls were presented with an appetizing cinnamon bun (time 0min) after an overnight fast. Blood samples were collected before and after presentation of the food. The subjects were asked to rate the bun’s palatability, and to complete several questionnaires assessing restrained eating behavior. They were then instructed to eat the bun (time 6min).
As you can see, while control subjects did not elicit a significant CPIR, patients with AN showed a 31% increase in insulin levels at 5min compared to 0min, BEFORE food is ingested (in fact one AN subject refused to eat the roll).
Hence, AN patients elicited greater CPIR compared to controls. All subjects rated the bun as equally palatable. Behaviorally, AN subjects scored significantly higher in the item ”cognitive restraint over eating,” and rated lower hunger levels than controls. This psychological self-evaluation directly contradicts the physiological response, which predicts higher levels of hunger. These results support the study by Teff (2001) that attitude towards food and restrictive eating may be the dominating factors towards insulin release during the cephalic phase.
A common notion seen in CHSP forums is that continuous CHSP may lead to diabetes. Based on the above studies this does not seem to be the case. An increased CPIR in AN patients may result in lower blood sugar levels in response to chewing and spitting out food. While this may lead to persistent feelings of hunger, there is no evidence increased CPIR can lead to insulin resistance. However, constant CHSP may cause chronic pulses of insulin release with unknown consequences to the body. Furthermore, the limited number of subjects and studies caution against generalization of the results.
CPIR IN PATIENTS WITH BULIMIA NERVOSA
As CPIR might be related to hunger and overeating, it is conceivable that bulimia nervosa patients, who often show endocrine abnormalities, may have an altered CPIR that, in turn, might be related to the precipitation and maintenance of binges. Moyer et al (1993) conducted one of the few studies examining this hypothesis. They sought to answer 3 questions:
- “Does the profile of CPIR in bulimic women differ from that of non-eating disordered controls?”
- “Does ingestion of food alter subsequent CPIR in bulimics compared with controls?”
- “Are mood state and desire to binge related to CPIR?”
The authors recruited 11 women with BN and 11 age-matched controls. Following an overnight fast, they were instructed to look at, smell, and taste chocolate chip cookies (Trial 1). Although subjects eventually swallowed the food, the authors proposed a 12-minute window before any absorption occurs. Hence insulin changes within 12 minutes can still be viewed as the cephalic “chew” phase. The women were then fed a 350 calorie breakfast, and 40 minutes later (in the postprandial phase) repeated the cookie trial (Trial 2). Recall that in healthy individuals, CPIR is enhanced in magnitude and length of time in the postprandial phase compared to a fasting state.
Under basal conditions, BN subjects had less blood insulin than controls. After the cookie challenge, neither BN nor control group showed an increase in insulin in Trial 1 during the window of the cephalic phase. However, insulin levels for both groups were increased in Trial 2. The authors did not report whether there was a group difference. There was no difference in blood sugar levels in either group in both trials, nor any difference in stress hormone levels. Finally, BN subjects rated higher in the Binge Scale, which correlated with higher scores on depression and anger. However, CPIR was not correlated with mood in either group.
These results strongly suggest that CPIR is elicited in patients with BN, although the magnitude was not compared to healthy controls. Overall, BN and control subjects showed a similar CPIR profiles, both fasting and postprandial. While it’s possible that greater deregulation only occurs during bingeing and purging episodes in BN, there is no clinical data to support this idea.
Hence, although impaired CPIR was hypothesized to contribute to bingeing and purging episodes, these data do not support that notion. In fact, despite reports of neuroendocrine abnormalities, BN patients have normal baseline insulin levels, and show a normal insulin response when ingesting glucose. Hence, it is possible that dysphoric states or stress leads to binge eating, rather than hunger brought on by impaired CPIR.
THE TAKE HOME MESSAGE
Given insulin’s central role in metabolism and its deregulation in metabolic diseases, I had assumed that insulin released during CHSP would have profound effects on the body in both healthy individuals and patients with eating disorders. However, these data do not seem to support this.
In healthy individuals, CHSP results in a rapid rise and fall in insulin secretion, concurrent with a similar change in blood glucose levels. In patients with AN, CPIR is exaggerated, but we don’t know if this corresponds to a drop in blood glucose. One idea is decreased blood sugar may induce physical hunger in patients with eating disorders which eventually overrides any psychological control of eating, leading to more CHSP or food consumption. However there are no studies directly supporting this hypothesis.
In patients with BN, CPIR does not differ significantly from healthy individuals, both under fasting and postprandial conditions. The extent of CPIR seems to correlate with an individual’s attitude towards food, with calorie restriction inducing higher insulin release. While this is proposed to stimulate hunger and feeding, there is no direct evidence to support the hypothesis. Finally, insulin release during CHSP is most likely not directly associated with insulin resistance and diabetes.
However, it’s CRITICAL to keep in mind that studies on this matter are few and far between. The studies I’ve touched on have very few subjects, inadequate controls, and limited measurements of physiological factors. Unfortunately this is an extremely understudied area. A search for “cephalic response” and “anorexia” or “bulimia” on clinicaltrails.gov turned up only 1 result, starting 2007 with no updates since (http://clinicaltrials.gov/show/NCT00493519). Hopefully with increased outreach more health professionals will take interest.
Broberg DJ, & Bernstein IL (1989). Cephalic insulin release in anorexic women. Physiology & behavior, 45 (5), 871-4 PMID: 2675143
Moyer A, Rodin J, & Cummings N (1993). Cephalic phase insulin release in bulimia. The International journal of eating disorders, 14 (3), 331-9 PMID: 8275069
Teff KL, & Engelman K (1996). Palatability and dietary restraint: effect on cephalic phase insulin release in women. Physiology & behavior, 60 (2), 567-73 PMID: 8840920
Teff KL (2011). How neural mediation of anticipatory and compensatory insulin release helps us tolerate food. Physiology & behavior, 103 (1), 44-50 PMID: 21256146