Physiological responses to chew & spit - ghrelin and obestatin

This is my second guest post for Science of Eating Disorders blog. Tetyana has a lovely piece up looking at Deep Brain Stimulation as a potential therapy for intractable AN. If you haven't seen it yet, please go check it out and join the discussion!

Your body responds to food long before it reaches your stomach. The taste, smell, even the mere sight of food all act to trigger a physiological response, “priming” the gut by stimulating various enzymes required for proper digestion and absorption of nutrients. This is called the “cephalic response”, and it is mediated by a part of the nervous system that’s generally not under conscious control (the autonomous nervous system). Keep in mind, the actual consumption of food is NOT necessary to trigger this reflex.

As you may have already guessed, the act of chewing and spitting out food activates this response, increasing the secretion of stomach acid, digestive enzymes and insulin as well as changing one’s metabolic rate. Which leads me to wonder – what are the changes that occur in the body during the cephalic response? Are these responses altered in patients with eating disorders who also chew and spit? If so, how? And are there any long-term consequences for engaging in chew and spit?

These are obviously very broad questions. To narrow it down, in this post I’d like to look specifically at two hormones involved in appetite control: ghrelin and obestatin. A little background first. Ghrelin and obestatin are both gut-brain hormones that are secreted (mainly) from the stomach and act on the brain. While ghrelin has many neurological functions (such as buffering against stress-induced depression), it was first identified as a hunger-promoting hormone. Ghrelin is secreted during the cephalic phase, and can promote feeding in multiple ways.

First, ghrelin travels through the bloodstream to areas of the brain involved in appetite regulation.  There it acts directly on specific receptors designed to trigger hunger and drive food-seeking behaviors. In fact, injecting humans with synthetic ghrelin was enough to produce feelings of intense hunger. Ghrelin can also make food seem more desirable. It does this by activating the reward system, causing dopamine release at the sight, taste and smell of yummy foods.  Hence, it may play a central role in conveying the pleasure and reinforcing aspects of high-calorie “rewarding” foods. Finally, ghrelin can directly act on the GI tract, blunting the stomach’s “fullness” signal and promoting overeating.

There is much less research on the recently discovered obestatin. However, it seems to directly oppose ghrelin’s effect on food intake, acting as a “brake” for the desire to feed (note, this is a MASSIVE oversimplification).

In the current paper, researchers wanted to know if patients with anorexia nervosa (AN) secret ghrelin and/or obestatin differently than control subjects when allowed to chew, taste and spit out food. To test this, they recruited 8 women with AN (both binge-purging and restrictiving) and 8 age-matched healthy female subjects. Following an overnight fast and a standardized breakfast, researchers served the women a lunch made up of 67% carbohydrates, 13%protein and 20%fat. To chew and spit in a controlled setting (in this case, called “modified sham feeding”), the women were allowed to see and smell the food for 5 minutes before chewing and spitting each bite into a napkin. Blood samples were taken before and after feeding (or chew and spit) for analysis, and the subjects were asked to fill out the Three Factor Eating Questionnare (TFEQ) to assess their eating behavior.

Here’s what they found:

1)   Patients with AN had higher levels of ghrelin before and after chew and spit compared to controls. Both groups showed a spike in ghrelin secretion within 30 minutes of chew and spit, but AN women showed a much higher peak than controls.

2)   AN women had higher obestatin levels compared to control women, and showed a much sharper DECREASE in blood obestatin levels 30 minutes after chew and spit.

3)   Blood sugar levels didn’t significantly change after chew and spit – there was also no difference in blood sugar levels between AN and control women both before and after chew and spit.

4)   Ghrelin levels after chew and spit correlated with TFEQ factor 2 in all women, and TFEQ factor 3 in women with AN.

So what does this mean?

In healthy women, chew and spit can cause an increase in ghrelin and a simultaneous decrease in obestatin. As mentioned above, ghrelin promotes hunger and food seeking, while obestatin may counteract its effect. Together, these hormonal changes may represent the body’s normal response to the presence of palatable food, promoting the initiation of food intake. To support this idea, increased ghrelin levels correlated with TFEQ factor 2, which measures the tendency to lose control over eating.

In AN patients, base levels of both ghrelin and obestatin were increased, and the hormonal responses to chew and spit were significantly enhanced. This amplification of ghrelin increase and obestatin drop might result in an amplified signal of hunger for at least 30 minutes after chew and spit. This is supported by the eating behavior data in AN patients that shows a correlation between enhanced ghrelin levels with TFERQ factor 3, which measures hunger. Hence, it is conceivable that chew and spit may increase hunger levels in AN patients, leading to feelings of a lack of control over eating. This may counteract the patients’ rigid control over food intake and promote more chewing and spitting (or binge eating), resulting in a downward spiral.

While this is an interesting study, there are some problems with it. First, subjects may have swallowed food unconsciously- a nurse monitored their chew and spit session, but a more subjective measure would be to look at cholecystokinin levels (released by the small intestine), which increases during feeding but stays stable during chew and spit. Second, the number of subjects is quite small, hence I’m not sure how generalizable it is to a greater population. And finally, note that this study looks at AN patients undergoing chew and spit in a controlled setting – they did not ask whether these patients engaged in chew and spit outside the experiment. It is conceivable that chronic chew and spit may alter the body’s response somewhat.

Nevertheless, this study shows that AN patients have enhanced ghrelin and obestatin responses after chew and spit, and this may be a strong factor in promoting hunger and loss of control over eating, ultimately leading to more chew and spit sessions and/or binging behavior.

Monteleone P, Serritella C, Martiadis V, & Maj M (2008). Deranged secretion of ghrelin and obestatin in the cephalic phase of vagal stimulation in women with anorexia nervosa. Biological psychiatry, 64 (11), 1005-8 PMID: 18474361

Méquinion, M., Langlet, F., Zgheib, S., Dickson, S., Dehouck, B., Chauveau, C., & Viltart, O. (2013). Ghrelin: Central and Peripheral Implications in Anorexia Nervosa Frontiers in Endocrinology, 4 DOI: 10.3389/fendo.2013.00015 This is a recent review on ghrelin in AN in general, and a good read for those interested in exploring the subject further. Note the authors argue that AN can be viewed as an addictive disorder - I'm not fully on board.