When it comes to nutrition, it’s often assumed that the physiological effects of a food item are directly attributable to the properties of the food itself. What’s often overlooked is “mindset” — the expectations and attitudes of the person consuming the food.
In 2003, Christine Feinle-Bisset, a German-born scientist, at that time working in Switzerland, now at the University of Adelaide, in Australia (1) found individuals with functional dyspepsia (FD) could have their symptoms manipulated merely by reading a label. People with the disorder FD report gastrointestinal (GI) symptoms like fullness, nausea, bloating, and decrease in appetite after a perfectly normal meal. As a result, they tend to avoid fatty and heavy foods. The researchers in this experiment decided to test the extent to which the symptoms were driven by the food itself, as compared with subjects’ expectations about the food.
In the study, people with FD consumed either a low-fat or a high-fat yogurt — labeled appropriately — on different occasions. Then, on two different occasions, they consumed the same two yogurts with the labels switched: the high-fat product was labeled low-fat, and vice versa. In all cases, the researchers measured GI symptoms as well as levels of plasma CCK (a gastrointestinal hormone released as satiety increases) and gastric volume (as a measure of stomach emptying: normally delayed with dyspeptic symptoms).
While CCK levels and gastric volume affected by the actual fat content of the yogurts, all of the yogurt products (including the ones with the wrong labels) produced approximately the same GI symptoms. Thus, a mismatch occurred between objective measures of gut function and reported symptoms (2); and of the two, the symptoms were more salient to the subjects.
“Mindset” was the name given to this phenomenon around ten years later, as the work was extended to healthy individuals and not only those who suffered from FD. Alia J. Crum, a psychologist at Yale University, led a series of experiments that originated from work in placebo/nocebo research (4).
How did the neurocognitive beliefs of the volunteer influence physiological responses? In one study (3), this group tested the effects of different 380-kcal milkshakes in healthy volunteers. The identical shake was labeled as being either “indulgent,” containing 650 kcal, or “sensible,” containing 140 kcal. The researchers asked volunteers to drink and rate their shakes, and give blood samples to track levels of ghrelin (another satiety regulating hormone, which is normally suppressed with food intake).
The volunteers who thought they were consuming the “indulgent” shake produced a much steeper decline in ghrelin after consuming it; those who had in mind that the shake was sensible produced a flatter ghrelin response. So the participants’ satiety was based on what they believed they were consuming rather than what they were actually consuming.
The phenomenon even extended to people drinking pure spring water, as the authors found out in a subsequent experiment (5). In this one, volunteers consumed pure spring water falsely labelled as containing 200 mg caffeine, under one of three conditions: (1) with no one else present, (2) with a confederate who denied the effect of the product, or (3) with a confederate who endorsed the effect of the product (i.e., a “confirming social influence” condition). This time, the experimenters measured not only mood and subjective alertness but also blood pressure—an objective measure. Participants experienced more subjective, physiological, and functional alertness from the imaginary caffeine when they consumed the water in the confirming social influence condition than when they consumed the product in other two conditions. This showed that in addition to what someone believes, what they learn from others can shape their experience; in accordance with this, researchers have already established social learning of placebo and nocebo effects (6).
What mechanisms could account for this? In-seon Lee, a Ph.D. student in Paul Enck’s laboratory in Tübingen, Germany, explored this in a recent experiment with individuals with FD and healthy control subjects who had consumed a standard breakfast (7). She measured autonomic responses (skin conductance and heart rate variability), emotional responses (via facial electromyography), and visual attention (through eye movement) when the subjects were presented with food and non-food images.
Compared with healthy controls, those with FD ate less food, had more dyspeptic symptoms, and reported lower pleasantness when rating the food images (particularly the high-fat ones). In terms of their physiological responses, they showed a higher vagal tone and suppressed processing time of the food images, but no differences in skin conductance or facial electromyography. So for these individuals with FD, higher-level cognitive functions, rather than autonomic and emotional mechanisms, appeared to function differently.
Lee decided to investigate brain activity through functional magnetic resonance imaging (fMRI) in a second experiment (8) based on the yogurt test by Feinle-Bisset (above). She asked and measured those with FD and healthy controls to ingest high-fat (10% fat) and low-fat (0.1%) yogurt, with either correct or incorrect labels, so each volunteer ate yogurt four times in randomized order.
Subjects with FD again showed more symptoms than healthy controls, and the symptoms were heightened after consuming the yogurt with the high-fat label rather than the one with the low-fat label (regardless of the actual fat content).
What of their brain activation? Before and after eating the yogurt, people with FD showed greater activity than healthy controls in occipital brain areas, regardless of fat content and label. They also showed more activity in the middle frontal gyrus before ingestion—a finding that indicated higher attention toward food. Interestingly, the high-fat yogurt resulted in stronger functional connectivity between the insula and the occipital cortex, while low-fat ingestion decreased this connectivity; and since this brain network activity was significantly associated with nausea, it seemed to reflect “true” symptom load.
On the other hand, the low-fat label influenced connectivity between the insula and the precuneus—which was associated with food craving, symptom intensity, and depression. These results show the disparate influences on the brain of the food itself and the expectations of the food. The experiment cemented the importance of cognitive components in the perception of food, food craving, intestinal symptoms, depression, and brain functions in the pathophysiological mechanisms of FD.
This fascinating line of research indicates that mindset can influence responses to food — both in healthy individuals and in those with functional dyspepsia. The gut and the brain are in constant conversation. And complex neurocognitive perceptions are clearly a factor in nutrition and health.
This is part 1 of a series covering “placebo” provided by Paul Enck from the Tübingen University Hospital and science writer Kristina Campbell. Continuous updates on placebo research can be found at www.jips.online.
- Feinle-Bisset C, Meier B, Fried M. Role of cognitive factors in symptom induction following high and low fat meals in patients with functional dyspepsia. Gut. 2003;52:1414–1418
- Enck P, Azpiroz F, Boeckxstaens G, Elsenbruch S, Feinle-Bisset C, Holtmann G, et al. Functional dyspepsia. Nat Rev Dis Primers. 2017;3:17081.
- Crum AJ, Corbin WR, Brownell KD, Salovey P. Mind over milkshakes: Mindsets, not just nutrients, determine ghrelin response. Health Psychology. 2011; 30:424–429
- Elsenbruch S, Enck P. Placebo effects and their determinants in gastrointestinal disorders. Nat Rev Gastroenterol Hepatol. 2015;12:472-485.
- Crum AJ, Phillips DJ, Goyer JP, Akinola M, Higgins ET. Transforming water: Social influence moderates psychological, physiological, and functional response to a placebo product. PLoS ONE. 2016; 11: e0167121.
- Colloca L, Benedetti F. Placebo analgesia induced by social observational learning. Pain. 2009;144:28-34.
- Lee IS, Preissl H, Giel K, Schag K, Enck P. Attentional and physiological processing of food images in functional dyspepsia patients: A pilot study. Sci Rep. 8;2018:1388
- Lee IS, Kullmann S, Scheffler K, Preissl H, Enck P. Fat label versus fat content: Gastrointestinal symptoms and brain activity in functional dyspepsia patients and healthy controls. Am J Clin Nutr. 2018 (in press)