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Mind Over Milkshakes: Mindsets, Not Just Nutrients, Determine Ghrelin Response – Research Review

Mind over milkshakes: Mindsets, not just nutrients, determine ghrelin response.  Crum AJ et. al.  Health Psychol. 2011 May 16. [Epub ahead of print]

Objective: To test whether physiological satiation as measured by the gut peptide ghrelin may vary depending on the mindset in which one approaches consumption of food. Methods: On 2 separate occasions, participants (n = 46) consumed a 380-calorie milkshake under the pretense that it was either a 620-calorie “indulgent” shake or a 140-calorie “sensible” shake. Ghrelin was measured via intravenous blood samples at 3 time points: baseline (20 min), anticipatory (60 min), and postconsumption (90 min). During the first interval (between 20 and 60 min) participants were asked to view and rate the (misleading) label of the shake. During the second interval (between 60 and 90 min) participants were asked to drink and rate the milkshake. Results: The mindset of indulgence produced a dramatically steeper decline in ghrelin after consuming the shake, whereas the mindset of sensibility produced a relatively flat ghrelin response. Participants’ satiety was consistent with what they believed they were consuming rather than the actual nutritional value of what they consumed. Conclusions: The effect of food consumption on ghrelin may be psychologically mediated, and mindset meaningfully affects physiological responses to food. (PsycINFO Database Record (c) 2011 APA, all rights reserved).



Ok, in addition to having possibly the coolest title of any paper I’ve reviewed on the site, this is also one of the weirdest papers I’ve looked at.  But I’ve seen it getting a lot of press and, of course, have to put in my own two cents, if for no other reason than I suspect many people will take the findings far out of context.  First, some necessary background; this will probably take more space than discussing the actual paper itself.

In recent years, the number of factors in the body controlling hunger has multiplied by leaps and bounds.  Leptin was discovered in 1994 or so and since then numerous other compounds have been identified that play some role in hunger, appetite, body weight regulation or even body composition.  One of those is ghrelin, which I also talked about in more detail in the Bodyweight Regulation Series.

In brief, ghrelin is a compound released from the gut in response to a whole host of physiological factors.  Among other things, ghrelin binds to a receptor in the brain and stimulates growth hormone release (useless trivia for the day: ghrelin was a compound where the brain receptor was discovered before the hormone itself was discovered; it was actually the presence of the receptor that drove researchers to go look for what was supposed to bind to it).

More relevant to today’s article, increases in ghrelin stimulate hunger (and alter fuel utilization and calorie partitioning, at least in animal models) and acute injections of ghrelin reliably increase hunger.  As well, ghrelin antagonists reliably blunt hunger.  Please note that ghrelin is one of those hormones where, in a sense, high levels are ‘bad’ and low levels are ‘good’, at least from the standpoint of things like hunger and appetite.  As is to be expected, as leptin levels fall on a diet, ghrelin typically goes up.

One of the oddities of ghrelin was that levels appeared to change in anticipation of meal time.  That is, through some mechanism (that so far as I could tell was never determined), ghrelin levels would go up just prior to normal meal times.  So if you habitually ate lunch at 12pm, ghrelin would go up right before then, lowering blood sugar and making you hungry.   Scientists call this entrainment and ghrelin levels would entrain to normal meal times through some mechanism or another.

Tangentially, this probably explains why changing meal frequency is at least initially difficult: ghrelin levels are changing in accord with your normal meal times and get out of synch with the new one.  So if you’re trying to increase meal frequency, you initially find that you’re simply not hungry when you’re supposed to eat.

And if you’re trying to decrease meal frequency, for a few days at least, you’re ravenous at the times you used to normally eat, at least initially.  However, over a few days time, ghrelin entrains to the new meal frequency and you stop being hungry when you used to eat, only getting hungry when you’re habitually eating.

Most of the early studies on ghrelin looked at how food intake, calorie intake and macronutrient intake and such were impacting on ghrelin levels.  Carbs seemed to have a greater impact than fat, protein was unclear (at least the last time I looked at the research); mind you ghrelin is not the only hormone of relevance.  I look at a bunch of the others in Bodyweight Regulation Wrap-Up: Other Hormones.

The total caloric value of the meal seemed to play a determining role; more calories dropped ghrelin more than fewer calories.   I seem to recall one odd study where sham feeding (I think they gave them noncaloric fiber or something) reduced ghrelin which is the first indication that something weird was going on: how could thinking you were eating something lower ghrelin?  Ok, that’s the first half of the background on this paper.

The bottom line is that the above is all good and well and interesting and relevant.  And would be the final word in all of this if humans were nothing more than a gut and a nervous system. That is, if we just responded in a lovely deterministic way to changes in hormones, this would all be a lot simpler.  Sadly, that’s not the case.

Big brained humans have this thing called self-awareness, sometimes we even use it for our own benefits.  We can think, reason, etc. and this impacts on many things including hunger, appetite, food choices, etc.  So while most animals will pretty much eat when hungry and not when full, it’s not nearly so clear cut in the case of humans.

Humans will eat out of boredom, depression, because they are at a party.  Most eat more on the weekends and there is a reliable relationship between the number of people at a meal and how much people eat: more people and folks eat more food.  My point is that you can’t just look at the physiology of what’s going on and ignore the psychology or other aspects.

A simple example is that of anorexia, or even dieting in a more general sense: in the case of full blown anorexia there is a situation where despite presumably massive drive to eat, the individual consciously chooses not to do so (I’d note here a brand new study, that I am still trying to get ahold of where researchers are suggesting a metabolic ‘brokenness’ contributing to anorexia and driving the psychology; I suspect it’s a complex loop where one is driving the other).

Even dieters, in the face of hunger, make conscious choices whether or not to ‘obey’ the signals being sent by hormones.  Basically, humans do not represent some deterministic system where you just look at the hormones and go ‘This is what’s going to happen’.  And if that didn’t complicate things enough, it’s clear that people differ in their psychological approach to things like eating.

Researchers often talk about things like restrained and unrestrained eaters, rigid versus flexible dieters (a topic I looked at in my own A Guide to Flexible Dieting), disinhibited eaters and others and there are clearly different psychologies when it comes to how people approach eating, food restriction, overeating.

And it won’t be surprising to find that all of the above psychological  (along with physiological) stuff differs to at least some degree for lean versus obese individuals.  We already know that there can be an insensitivity to leptin in the brains of the obese (whether this is a cause or effect of obesity is still up to debate) and there is evidence of differing sensitivity to other hormones such as ghrelin, GLP-1, PPY and the rest of the mix.

Basically, human hunger and appetite and real-world food intake is very complicated and something the strangest things impact on food intake in a way that you might not necessarily predict ahead of time (i.e. who would have thought that having more people present at a meal would lead to higher food intakes).  One of those is related to belief or how people can often rationalize certain food choices because of the situation or what else they are eating.

Here’s a classic example that will finally segue into today’s paper: back during the low-fat craze someone did a study more or less along the following lines.  Folks were given a food (I think it was frozen yogurt) and then ‘told’ that it was either low-fat or full/high-fat yogurt.  Note that the yogurt was identical in both cases, they were simply told that they were being given different types.  Subjects who thought they were eating the low-fat yogurt ate more.  Presumably they rationalized that since it had less calories/fat, they could eat more of it and this, among many other factors, has been held up as one reason that the whole low-fat movement failed.

You might also look at this as the Oreo/skim milk or double cheeseburger/diet coke effect whereby people rationalize eating something crappy because they are ‘balancing’ it out with something healthy or whatever.  This is often given as a reason that things like diet sodas fail to impact on bodyweight; some people simply justify eating more of the other stuff because they aren’t getting calories from the diet soda.  Yes, there’s more to it than that but this introduction is already way too long.

My point is this: human appetite and hunger is clearly an interaction between physiology and psychology, not that you can ever really separate the two (as I discussed in Dieting Psychology vs. Physiology before I lost the plot of what I was trying to talk about).  Because physiology impacts on psychological function.  And, as today’s study shows, psychological function impacts on the physiology of eating behavior. Ok, on to the paper.


The Paper

46 participants, between the ages of 18-35, within a normal to overweight BMI were recruited to take part in two separate sessions for the study.  Of those 46 people, 65% of the subjects were women, 56% were white, 12% African American, 11% Asian American, 10% Hispanic/Latino and 11% other.  Subjects were told that the Yale nutritional center was working on two different milkshake with differing nutrient contents that they would sample and that the goal of the study was to evaluate whether or not the shakes tasted different and to examine the body’s reaction to the different shakes.

Basically, they were lied to; the milkshakes were identical in composition, but were presented with two different labels, which I’ve shown below.


Decadence you Deserve
Decadence You Deserve
Guilt Free Satisfaction
Guilt Free Satisfaction











So the indulgent shake was presented as a high fat, high calorie shake and the sensible shake was touted as being low fat and low calorie.  Again, the shakes were actually identical in terms of their nutrient and caloric content, all that differed was the labelling.   Each day lasted 2.5 hours divided into two time intervals.  In the first interval, after 20 minute rest period, blood was drawn at 60 and 90 minutes and the subjects were asked to rate the label of the shake in terms of hunger ratings.

In the second interval, subjects drank the shake within 10 minutes and were asked again to rate hunger along with taste (including smell and taste along with enjoyment and healthiness).  If you’re wondering how hunger is rated, it’s done subjectively through something called a Visual Analog Scale (VAS), a little graphic doodad that ranks things from 0-100; it’s subjective as hell but used commonly.

Measurements of ghrelin were made from the blood draws and subjects also filled out a questionnaire to determine their degree of dietary restraint and this was used to see if there was any effect of dietary restraint on the other variables measured.

So what about the results.  Not shockingly, subjects rated the sensible shake as 7 times healthier than the indulgent shake and the degree of restraint had no impact on this.  Basically, they firmly believed that the sensible shake was healthier.  No differences were seen in the ratings of tastiness between shake conditions.

Ok, let’s look at ghrelin first since this seems to be where most of the Internet punditry is focusing.  The indulgent group showed a much higher rise in ghrelin prior to consumption of the shake followed by an equally significant drop after consumption.  In contrast, the sensible shake situation found a fairly flat ghrelin change: there was a small increase with little change downwards.  I’ve shown the actual changes in ghrelin in the graph below and you can see the clear difference in ghrelin response pattern for the two conditions.


Changes in Ghrelin
Changes in Ghrelin



Looking solely at this physiological response, the researchers state:

When drinking the shake in an indulgent mindset, participants’ levels of ghrelin reflected a moderate level of physiological craving followed by a significant level of physiological satiety…when drinking the shake in a sensible mindset, suggesting that, despite consuming the same nutrient contents, they were not physiologically satisfied.

So good intersting stuff, mindset affects physiology and the folks who thought they were indulging had a significantly different ghrelin response, suggesting of differences in both craving and satiety, than those who thought they were eating the sensible shake.  Clearly how you approach your diet meals or whatever can impact your physiology and all you have to do is adjust your mindset to sail along in your diet.  Right?

But, now, you’re wondering, what’s the catch in all of this because we all know I wouldn’t be discussing this paper if there wasn’t something more going on?  Be patient, I know this is long but bear with me.


My Comments

Today’s paper is certainly interesting, if nothing else it indicates that an individual’s mindset going into eating something can affect at least one marker of physiology, in this case ghrelin.  Specifically, the ghrelin response to the shake intake was based on the person’s expectancies of the shake rather than it’s actual caloric content.  And that’s what the researchers talked about in the abstract: how mindset affected this one singular physiological response.

That’s most of what I’ve seen people focusing on in their commentary about this study on the Internets (one title was “It’s All About the Hormones”).  It’s also why I spent so much time in the introduction trying to point out that humans aren’t just physiological automatons responding to changing hormones in this fashion.  Because it’s not just about the hormones in humans.  There’s way more going on.

Before moving on the researchers point out something that most seem intent on ignoring: this was a single meal study.  As the researchers state:

Although the effects of such psychologically mediated differences in subsequent consumption or long-term alterations in weight were not measured in this particular study, future research on the impact of this phenomenon on metabolic maintenance is warranted.

I don’t disagree and in the real-world the above matters since what is seen acutely often doesn’t translate at all to the long-term; you often see compensation at the next meal or the next day or whatever and it all balances out in the wash.  Simply, few conclusions can be drawn from this one study in terms of food intake across a day, a week, a month.

Don’t misread me: I’m not saying it won’t or couldn’t have an impact.  It might or it might not.  But it might also all balance out given that there are other systems regulating things as well.  There is also the fact that, as I discussed in Homeostatic and Non-Homeostatic Pathways Involved in the Control of Food Intake and Energy Balance the physiological systems present in humans can clearly and easily be overwhelmed by non-physiological factors (such as how many people you are eating with).

Looking at their results, the researchers get into a whole speculative discussion about how some of the mindset of dieter’s about their food might be contributing negatively to overall results.  For example, based on data that increased ghrelin tends to drive hunger and lower metabolic rate (at least in animal models), they speculate that:

The relatively flat ghrelin profiles in response to consuming the shake in a sensible mindset may be placing participants in a psychologically challenging state marked by increased appetite and decreased metabolism.

Two problems with this.  One they didn’t measure metabolic rate and speculating from what is mostly animal data is a mistake. But that’s not the bigger issue here, it’s time to focus on their claim of increased appetite (or perhaps less blunting of hunger).

Did you notice something missing in my discussion of the study above?  Like how I mentioned that they measured hunger using a Visual Analog Scale early on but then didn’t say anything more about it?  It’s because I was saving it for now. In a single throwaway sentence hidden at the end of the results section that nobody who has just read the abstract will actually see, the researchers state what I think is the truly important finding that everyone seems to be ignoring:

For the measure of hunger, these analyses produces no significant main or interaction effects as a function of shake, time or restrained eating.

Translated into English that means this: despite the changes in ghrelin as a physiological marker of craving and satiety there was no difference in hunger between the indulgent and sensible condition and dietary restraint had no impact on this.   So the differential ghrelin  response, while interesting, didn’t amount to anything in the real-world in terms of actual hunger ratings differences between the two mindsets.  Please read that sentence again until it sinks in.

Hell, the researchers didn’t even bother to provide the VAS hunger data for the different conditions anywhere in the paper.  They just went through this whole involved discussion on ghrelin and everything else and then, as an afterthought mentioned “Oh yeah, there was no difference in actual hunger.”  And they didn’t mention it in the abstract.

So while the physiological response they measured is nifty as hell and certainly worthy of more research, the simple fact is that it didn’t amount to any real world difference in actual hunger.   Which is important because people are already taking this paper completely out of context, going from the hormonal response (which was different based on mindset) and extrapolating that to differences in hunger (which was not different based on mindset).

A question might be why there was no difference in hunger and the best the researchers could do was to say:

This study did not find any significant differences with respect to subjective hunger regardless of mindset after participants consumed the milkshake.  This result may have been a function of the measuring timing (hunger levels were assessed 10 min prior to ghrelin changes as opposed to simultaneously or subsequently), or the manner in which hunger was measured (visual analog scale).

Basically they are crapping on their own measurement methodology to try to dismiss their non-result.   Don’t get me wrong, maybe they would have seen a difference in hunger had they measured things differently.  At least they used the word ‘may’ above.

I’d note that the VAS is used extensively to measure hunger and has been for years now; so far as I know, it’s pretty accurate and able to discriminate different levels of hunger.  So saying ‘The measurement method we choose might have sucked’ is kind of weak given that VAS is a commonly used measure.  And, of course there are other potential reasons that their nifty physiological response didn’t generate a real world change in hunger.

Maybe those small changes in ghrelin were irrelevant to overall hunger drive (the graph looks pretty impressive but the absolute difference in ghrelin wasn’t huge).  Maybe that kind of small change just isn’t enough to have an impact.  Maybe you need to factor in the myriad other hormones such as leptin, GLP-1, PPY and the rest when you look at this; there are too many overlapping systems here to just focus on a small difference in ghrelin response and then extrapolate to the entire system. Or maybe it was something else going on. We don’t really know until more research is done and speculating is kind of pointless at the end of the day.

What we do know is this: psychological mindset impacted on the response of a singular hormone that is important in terms of hunger drive and satiety.  But despite a measured physiological change in that hormone that differed between groups, there was no difference in real world hunger based on psychological mindset.  The hormonal response simply didn’t amount to anything in the real world.

And that last paragraph above is really my main point, and yes I took a long time to get to it.  Everywhere I’m seeing folks prattle about ‘thinking themselves thin’ hoping that thinking that what they are eating is more indulgent than it is while dieting will lower ghrelin and make them be less hungry.  But that’s absolutely not what the paper found as there was no difference in actual hunger ratings based on mindset.

As well, I think you could just as easily parse this paper to suggest that the indulgent group would be more likely to overconsume calories due to the early increase in ghrelin.  That is, if increasing ghrelin drives hunger, who’s to say that folks won’t eat more of a food if they put themself in an indulgent mindset? Especially if they aren’t in the artificial situation where regardless of hormonal response, they are being given a fixed calorie shake to drink.

Mind you, the study didn’t find this either since, beating the dead horse, hunger ratings didn’t differ at any time point for either group.  But it would be just as accurate an interpretation of the physiological response as assuming that the drop in ghrelin will decrease hunger (which it didn’t).

So here we have a fascinating paper, clearly things are more complex than we even thought up until this point, and this study shows that psychological mindset can impact on at least one measure of the physiology of hunger regulation (the mechanism wasn’t even guessed at).  Hopefully more work on this will determine not only if there is an impact but what the mechanism of it all is.

But at the end of the day, it didn’t amount to any actual change in real world hunger which is what matters.  More research is needed but drawing unwarranted conclusions from this paper is a mistake even if that’s what the Internet is doing right now.  So the physiological response while interesting as all hell simply had no real-world impact on actual hunger.  That’s the bottom line.


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