Monday, February 4, 2013

Why Do We Eat? A Neurobiological Perspective. Part VII

Welcome back to the series, after a bit of a hiatus!  In previous posts, we covered the fact that humans eat because we're motivated to eat, and many things can motivate us to eat.  These include factors related to energy need (homeostatic factors), such as hunger, and factors that have little to do with energy need or hunger (non-homeostatic factors).  These many factors are all processed in specialized brain 'modules' that ultimately converge on a central action selection system (part of the reward system); this is the part of you that decides whether or not to initiate eating behaviors.

This will be somewhat of a catch-all post in which I discuss cognitive, emotional, and habit influences on food intake.  Since these factors are not my specialty, I'll keep it brief, but I don't mean to suggest they aren't important.

Food 'Cost'


One of the primary factors in deciding when and what to eat is determining how much you have to give up to obtain the food in question.  We can call this the 'cost' of food, but in this context a food's 'cost' refers to effort cost in addition to monetary cost.  If you like hamburgers, and there's a hamburger on your desk, you may eat it even when you aren't hungry and your general motivation to eat is relatively low.  If the same hamburger is across the street, you'll need to be at least a little bit hungry (or motivated by something else, for example boredom or a great love of hamburgers) to have enough motivation to get it.  If you had to walk three miles and climb a tree to get your hamburger, you'd have to be quite hungry!  But this was precisely the situation for our non-industrial ancestors-- food was not at arm's reach at all times of day.  The 'cost' of food was higher because it took effort to obtain and prepare, and therefore it required a higher level of motivation (hunger) to drive food seeking behavior.

The effort cost of food is a major determinant of food intake.  Even small increases in effort cost can have a significant impact on food and beverage intake (1, 2).  For example, placing a snack bowl 140 cm (4'7") away from a person leads to less snack intake than placing the same bowl 20 cm (8") away (3).  Getting up simply requires a bit more motivation than reaching out your arm.  Having food in your immediate vicinity, and particularly within arm's reach, is generally a bad idea if you're concerned about your weight.  The monetary cost of food also influences intake and selection.

This concept is the domain of a research discipline called 'behavioral economics'.  It's not my field, but I do find it interesting.  I'll explore this a bit further in the next post in the series.

Cognitive Restraint and Goals

Our behavior is strongly influenced by unconscious factors, but clearly we have some degree of conscious control over when and what we eat.  Our 'higher' cognitive functions, many of which are seated primarily in the cerebral cortex, serve to guide our behavior in a manner that supports our long-term goals.  Your reward system may want you to eat a donut, but your cortex can inhibit that behavior because you know eating the donut is inconsistent with your long-term goal of health and leanness.  The technical term for this is 'cognitive restraint', the common-sense term for it is willpower, and it is perceived as a conflict between unconsciously driven desires and conscious goals.

Negative Emotions

Emotions such as stress and sadness can drive food intake in susceptible people, and they may do so at least in part by increasing reward-seeking behavior in an effort to combat negative emotions.  The American Psychological Association reported in 2007 that 43 percent of Americans overeat when stressed, while 36 percent skip a meal (4).  Clearly the response to stress is highly individual.  However, among those who overeat, the foods consumed tend to be calorie-dense and highly palatable, such as candy, chocolate, ice cream, potato chips, cookies, cake, fast food, pizza, etc.

Social Environment

Who you eat with has a large impact on food intake.  For example, a person eating with 6 or more other people will eat on average nearly twice as many calories as a person eating by herself (5).  Eating is part of socializing, and the alcohol consumed in such social situations also disinhibits eating behavior.  People often wrongly believe they are unaffected by these factors.

Habit

To begin to illustrate the importance of habit in food intake behaviors, all we need is a common-sense example: how many times have you eaten lunch not because you're hungry, but simply because it's lunchtime?      The power of time cues is evident in a very interesting experiment that was conducted in amnesic patients in 1998 (6).  Researchers brought the patients a meal, told them it was lunchtime, and they ate a full meal completely.  15 minutes later, after the patients had forgotten they had eaten, researchers brought in a second full meal and told them it was lunchtime again.  They ate the second meal completely.  15 minutes later, researchers brought in a third meal, told them it was lunchtime again, and some of the patients ate part of the meal.  Satiety eventually kicked in and prevented further food intake, but not before these people had consumed more than twice their usual calorie intake simply due to their habit-driven response to a mealtime cue.

Habits serve a very important role in our everyday lives: they allow us to outsource information processing tasks from our conscious mind to our unconscious mind, freeing our conscious mind for other tasks.  If you had to consciously focus on brushing your teeth, how to move each finger on a keyboard to type a sentence, how to  hold a fork, and how to react when your phone rings, you would be a much less effective person.  When these behaviors are repeated enough times, they're 'outsourced' from conscious areas including the cortex, to unconscious structures such as the basal ganglia (7).

The influence of habits on our lives runs deep.  The large majority of our behaviors, including food selection, are driven by habit.  Therefore, habits to a large extent determine our weight and health over time.

The Complete Model

We've finally arrived at the complete version of my simplified model of food intake behavior.  Each colored shape represents a functional and (sort of) anatomical brain module, while the words that surround them represent the external and internal factors they respond to.  One thing I want to note here is that the right-most module, "Cognition and Emotions", is a catch-all category that represents a variety of processes that are regulated by a number of different brain areas.
As you can see, even my highly simplified model is quite complex-- this reflects the complexity of human biology and culture.

46 comments:

Gretchen said...

The study of the social environment and eating illustrates one flaw in formal research on eating: It contradicts other evidence, and scientists have to accept the formal studies and reject the "annecdotal evidence."

One reason I put on weight in middle age was that I lived alone, with no one observing me when I had seconds, or thirds, of some palatable food.

When I was in school, I had a roommate who hid pies and cakes under her bed and ate them when no one was around. At meals with other people, she ate sparingly, less than other people.

Some people will do what other people are doing, and others won't.

I agree that this is a complex problem with no simple solution.

Stephan Guyenet said...

Hi Gretchen,

The research I cited was conducted in free-living people going about their daily lives, not a laboratory environment. That being said, it is certainly true that not everyone reacts like the "average" person. I think this is a big limitation of most biomedical research-- we can get a lot of information about the average, but most studies may miss important individual variability.

Marty said...

Is that the series over? You forgot arguably the single biggest factor in why we overeat: carbs. They cause an insulin spike that makes our body 'crave' more food.

Dr Guyenet I suggest you read a book called Good Calories, Bad Calories. It explains this effect in great detail.

Gretchen said...

Stephan, I agree with you that not everyone reacts like the average, bell curve and all that. The problem in my view is when questionable results are presented as facts.

You said, "For example, a person eating with 6 or more other people will eat on average nearly twice as many calories as a person eating by herself." Now, you did say "on average," but it sounded like a well-established fact. You didn't say they "may" do that.

I wouldn't have been bothered if someone said, "A study of free-living adults (with some indication of what kind of adults, as insecure students might be more susceptible to peer pressure than a gathering of a freethinkers' club) showed that ..." or "Many studies have shown that . . ."

That would clarify how reliable the data were as well as whether the study was only done with a specific population, like college students.



Crown of Snarls said...

LOL @ Marty

Stephan Guyenet said...

Hi Marty,

Not sure if you're joking or not, but if you aren't I suggest having a look at studies that investigated the effect of insulin on hunger and food intake:

www.ncbi.nlm.nih.gov/pubmed/9530223
www.ncbi.nlm.nih.gov/pubmed/9500570
www.ncbi.nlm.nih.gov/pubmed/6388352
www.ncbi.nlm.nih.gov/pubmed/3897769

Of the four, only the last one suggested that insulin increases hunger and/or food intake in humans in the absence of hypoglycemia, and that study also happens to be the least well controlled of the four. The evidence overall suggests that insulin has no effect on meal-to-meal food intake in humans unless it causes frank hypoglycemia (which is rare in non-diabetics, even among people who think they suffer from hypoglycemia without having confirmed it using a glucose meter). The myth that insulin increases hunger persists despite rather clear evidence to the contrary.

Since some people report anecdotally that eating carbohydrate increases their hunger, I won't dismiss the phenomenon completely, but this doesn't seem to be a general phenomenon, and there is currently no evidence that it is related to insulin.

Hi Gretchen,

Still not sure why you find the study "questionable", particularly since you appear not to have read it. The study reported that the number of people at a meal correlates positively with food intake on average. That is a fact, which is why I presented it as a fact. If you have a problem with the study's findings, you're welcome to take it up with the authors.

Gretchen said...

Stephan, Questionable because it's just one study and the Abstract (which I had read) provides very little information. No finding in science is trustworthy without confirmation by other groups.

In fact, it's not really an Abstract but an Introduction. Their conclusion is, "Hence, real-world research teaches valuable lessons, and much more is needed to complement laboratory studies."

This doesn't impress me, and I'm not about to pay $31 to read the whole article.

Maybe it's excellent and cites supporting studies. Maybe not.

Marty said...

Thanks for your response Stephen. I'm not sure what makes you think I might have been joking, it is very clear from the book I cited that this is no laughing matter.

Your pubmed studies about insulin are interesting, but scientists can prove anything with facts. The real question is why would carbs NOT make you fat when we all know that they do?

Dave said...

@Marty

In case you aren't joking/trolling, read this post.

http://wholehealthsource.blogspot.com/2011/08/carbohydrate-hypothesis-of-obesity.html

Dave said...

"Since some people report anecdotally that eating carbohydrate increases their hunger, I won't dismiss the phenomenon completely, but this doesn't seem to be a general phenomenon, and there is currently no evidence that it is related to insulin"

My hypothesis is that its mere coincidence that the type of foods that lead to overeating are typically high in carbohydrates.

Examples:

cake - high in both sugar and fat
ice cream - high in both sugar and fat
soda - high in sugar
fruit juice - high in sugar
pizza - high in both carbs and fat
cookies - high in sugar, flour, and fat

As you can see, the types of foods that people attribute to obesity because of their lack of satiety usually are 1) heavily processed, 2) contain little micronutrients, 3) high in refined carbs, 4) high in processed oils

But when we start looking at foods like baked potatoes that are high in carbs and not all that palatable, they don't have the same effect. Probably because insulin isn't the reason that people overeat these other foods.

Joshua Bennett said...

Stephan, as far as I can tell, the full text of the article you cited on people eating more in social situations is not freely available. Is there a good place to find it without having to have a subscription to a journal?

I'm curious if the researchers accounted for the fact that eating with that many people suggests they're at a party. Perhaps the increased calorie intake is more related to the type of foods consumed in those situations versus, say, a family dinner?

Diana said...

Are any of you aware of the research done demonstrating the carbs alone do not make human beings fat?

Deirdre said...

Hi Stephen,

Thank you for this overview, and I appreciate you going outside your comfort zone (or I think you said "specialty") to present an important piece of the puzzle.

I appreciate this because I'm not a neuroscientist, but a researcher and consumer educator. I learn a lot from you, and am grateful for the time you spend educating all of "us" on what is undoubtedly an incredibly complex system of systems - much of which is still unknown.

I will say, however, that I've noticed a tone shift from some of the regular contributors on your blog. And to them, I would like to say this: If you are here to merely critique, criticize or argue for the sake of intellectual chest thumping, then please start your own blog. Your energy is beginning to cloud what has always been a platform for interesting and lively debates. Just sayin'.

Stephan Guyenet said...

Hi Dave,

That could well be.

Hi Josh,

You make a good point-- the same thought about parties etc. also occurred to me. I don't know the answer to your question. The paper I cited in my post is a review paper by John de Castro that summarizes a variety of his findings, but below I've pasted the primary citations for these data from his research group as well as a second group. At least two of these papers are free access.

http://www.ncbi.nlm.nih.gov/pubmed/1741437
http://www.ncbi.nlm.nih.gov/pubmed/2756911
http://www.ncbi.nlm.nih.gov/pubmed/7972393
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2276563/

Hi Deirdre,

Thanks for the support. The comments are about to get a lot cleaner because comment moderation is coming.

Gretchen said...

Stephan, Thanks for the references. Those were interesting, especially full text.

What I found interesting was that one cliche explanation for the relative lack of obesity (at least in the past) among the French was that their main meal was a family affair that included conversation as well as food, whereas Americans often grabbed something and ran out the door to some evening event.

This research would suggest the opposite, although obviously grabbing junk food would be different from eating a full meal alone.

aruhea said...

A major drawback in your model is that it assumes we eat only once (it is a static model). In fact though these variables are dynamically interrelated - there is a lot of feedback going on. Moreover what matters is the integral of net food intake over time. Since some of these variables are also going to affect metabolism and propensity to expend calories, the whole equation becomes a lot more complicated. It is not clear to me that, given these drawbacks, your model is even useful. In econometric terms it seems woefully misspecified. Any thoughts on that?

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I love the healthy debates happening about device specific vs responsive design approaches. It allows for parties to see the light and dark side of each techniques.

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Chip Spitter said...

Peter,

Your links are intriguing. My LDL-C is somewhere in the region of 350. When I wake up tomorrow I shall embark on a journey of vegan-enlightenment.

Nah...I'll make a bet with you instead; if I drop dead in the sixth months I shall visit you from the afterlife and shout you dinner at the restaurant of your choice.

Not really - I don't believe in the afterlife. Which is why I'm making the most of this one.

Cheers for the comic relief.

Thomas said...

Yet another good post Stephan!

I have been lurking on this blog for a long while and the post preceding this one, in particular the comment thread of it, provided such an interesting reading. I am certain plenty of studies could be conducted with that sole post (plus comments) as resource object. Especially in regards to the Information Era and all of it's attributes, possibilities and shortcomings.

Anyway, the previous post also triggered me to step out of the dark to high five you on your work so far and the high quality of this blog. While I understand some of the negative...reactions...I consider your stuff very trustworthy. Especially, but not only, considering the cesspool standards in the entire field of health, nutrition, training etc.

Anyway, I just wanted to contribute that along the info you provide regarding habit in this post, could be added the issue of habit also being part of the so called cycle of CURH. Put differently "negative" issues in regards to what you define as cognitive behaviour, and perhaps primarily lack thereof, as well as negative emotions will in that context connect with habits.

To differentiate from the type of "everyday habit" you exemplify with, the habit in the CURH-cycle is more of a (destructive) feedback factor. E.g. not only do we engage in physical activities with that attractive work colleague and/or much down that bag of donuts...but we make it a habit of diversion on a pursuit of the sensations of pleasure or "numbing down".

Keep up the good work Stephan!

Gretchen said...

Another possible factor in amounts eaten: gender.

http://www.sciencedirect.com/science/article/pii/S019566630900587X

I haven't read full text because of paywall.

Interestingly, the two exceptions to the rule I cited are female.

Maybe we have the solution to female obesity: Eat whatever you want as long as there are at least 7 men at the table with you.

Now I'll shut up on this somewhat peripheral topic. Stephan, thanks for this series. It's useful.

LeonRover said...

Peter's on the (s)troll again.

My prediction: 3 strikes & yr out!

Dapko said...

Finally, comment moderation comes to WHS. For all those naughty boys and girls who even think of using insulin and carbs in the same sentence, you have been warned!

Diana said...

@Gretchen,

I don't think that social aspects of eating are off topic at all. Eating among human beings is a supremely social act. Otherwise why else would entire populations show such different levels of obesity? The Japanese eat differently than Americans, they have lower obesity levels.

I used to binge alone. Never in public. No fat person is ever going to admit to a researcher that they binge eat.

Gob said...

"Peter's on the (s)troll again."

Well what do you expect now that his other troll account (Bog) is banned from posting comments here.

Just proves what we all already knew -- veganism causes mental instability, which in turn causes a guy like Peter (who's probably relatively normal in-person) to troll the blogs of those with whom he disagrees in order to get his anger out. Nothing surprising there. :-)

Stephan Guyenet said...

Peter is (once again) a goner.

So tired of the trolls. Comment moderation is coming soon.

donny said...

Dave said;

But when we start looking at foods like baked potatoes that are high in carbs and not all that palatable, they don't have the same effect. Probably because insulin isn't the reason that people overeat these other foods.
----------------------------
If insulin caused increase in appetite due to its effects on blood glucose, you'd expect plain potato to satisfy this with less calories than potato chips, though, wouldn't you?

Sara said...

Is it ok to link to a blog post I wrote on this (environmental influences on eating)?

Moderate me if you don't like self blog pimping.

http://www.fittoblog.org/2012/05/world-wants-you-to-eat-it.html

That was all based on a couple of journal articles I read by Prof. Wansink.

As regards carbs making you 'hungrier', I've experienced this, but I wouldn't say it was true, stomach growling hunger (except if the carby meal was really insubstantial). What I get is my brain remembering how yummy carbs are and then demanding more of them. Now that I expect that, I can control it. It's not real hunger, it's just 'wanting more of that'.

Alex said...

I do experience an increase in hunger with starchy carbs; in sufficient quantity, the hunger is voracious and gnawing. I eat ad libitum, and in general, starch eaten on a regular basis increases my appetite and drives me to overeat. Fortunately for me, the fruit I eat doesn't have that effect.

At the opposite end of the spectrum, protein and fat provide amazing satiety. E.g., the other day I had an 8oz grass-fed ribeye and half an onion sauteed in a little butter for breakfast before driving out of town. I ate nothing while I was out and didn't get home until 7 hours later. At that point, I was hungry, but the hunger impulses were very mild.

Jane said...

@Sara
Liked your article.

@Alex
Could I ask you please, do you ever eat refined carbs? If you don't, how long is it since you gave them up, and how do you manage when you get invited out and refined carbs are on the menu?

I ask because the hunger you get from eating starch may be because your pancreas is not working properly and cannot keep your blood sugar stable. A lifetime of eating refined carbs means in theory, nutritional deficiencies and possibly, a poorly functioning pancreas, not bad enough to be diabetic but enough to cause problems eating starch.

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Dave said...

"If insulin caused increase in appetite due to its effects on blood glucose, you'd expect plain potato to satisfy this with less calories than potato chips, though, wouldn't you?"

Not sure I follow you. The alleged reason that insulin increases appetite is because it supposedly locks away fat, causing internal cellular starvation. This would only work if hyperinsulinemia occurred without insulin resistance, which seldom seems to be the case. Usually they both happen at the same time, so when someone is obese and insulin resistant, they are having trouble keeping fat locked away.

So in the context of common obesity, it makes no sense that insulin would cause increased hunger because of fat being locked away.

My own anecdotes show that the only carb that causes me to overeat is sugar, and I think its because sugary foods are the only ones I can eat while my stomach is literally stuffed. I believe my desire to eat sugar is in the brain, not due to insulin's effect on fat tissue.

Alex said...

@Jane
Almost every day I eat a big bowl of fresh berries with a little container of full fat fruit yogurt, and the yogurt does contain honey, dried sugar cane juice, and maple syrup. And, occasionally I treat myself to some ice cream. I only eat out about once a month, and I'll have a burger or a wrap and skip dessert. I'm less rigid about my diet when I go out or visit family.

I've had glucose control issues since I was a kid. But, moving to Fairfield Iowa and getting involved with Transcendental Meditation at age 21 set me up to believe all sorts of vegetarian dogma about whole grains and beans as ideal human nutrition. My young adult body could sort of handle that diet, but starting in my late 30s, the descent into middle age was not pretty, and by age 42, I had 30 pounds of subcutaneous fat hanging off an otherwise scrawny body. If I lay on my side in bed, my stomach would literally flow out onto the mattress.

In September 2003, I cut out all the starch except for two slices per day of sprouted whole grain toast, with the rest of the diet being fruit, veggies, and meat. In 5 months, I lost 30 pounds with no effort because there was no hunger telling me to eat more. For me, that satiety is the beauty of low-carb, and in my case, it never required eating truly low carb. A few years after my initial weight loss, I ditched the last little bit of grain left in my diet. I was never into the whole caveman emulation thing, but my diet is easily recognizable as Sisson style, moderate carb "Primal".

donny said...

"The alleged reason that insulin increases appetite is because it supposedly locks away fat, causing internal cellular starvation."



I don't believe this is a full picture of how insulin might increase appetite and be a cause of obesity. Insulin doesn't just tell the fat cells to store fat; it also tells other cells (muscle, liver etc.) to switch over to a glucose metabolism, lower fat metabolism. But that's not really a can of worms I have time to get into this afternoon.

I was referring specifically to hunger, not obesity in my post about potatoes vs potato chips. A very common idea among low carber is that hypoglycemia after eating a high-carbohydrate food, caused by an excess insulin secretion, causes an increase in hunger. Whether this would lead to obesity is another question. I don't think obesity is an inevitable consequence of insulin, just a possible one.

Suppose somebody eats seventy five grams of glucose as potato, and in response, they have hypoglycemia. So they eat more potato. What's helping them recover from the hypoglycemia? The glucose. Now suppose they eat the same amount of potato, but as potato chips with 60 percent calories as fat. Of course the fat will slow down absorption--let's ignore that for now. Suppose the same hypoglycemic reaction. Maybe if you chose the right fat, this could even be the case.

You've got the same 75 grams of glucose, but you've eaten much more. And then you need to eat still more, just to offset the hypoglycemia.



Stephan Guyenet said...

Hi Donny,

I think more research needs to be done in the area of blood glucose and food intake (despite the fact that a huge amount of research has been done already), but I can say with confidence that post-meal hypoglycemia (or "reactive hypoglycemia") is rare in the non-diabetic general population, including among obese/overweight people. Blood glucose will frequently dip below the typical fasting level after a carbohydrate meal, but not enough to qualify as hypoglycemia.

There was a lot of interest in this a few decades back, and so researchers studied non-diabetic people who claimed to have "hypoglycemia" based on subjective symptoms. It turned out that almost none of them were hypoglycemic during the times that they were experiencing symptoms they attributed to hypoglycemia (hunger, brain fog, the shakes, low energy, etc).

It is clear that true hypoglycemia increases food intake, and post-meal glucose spikes contribute to satiety, but in between those extremes there's really very little evidence that circulating glucose is related to appetite.

I still think it's possible that there may be something to it-- perhaps in a subset of people rapid changes in blood glucose within the normal range could contribute to hunger-- but it remains speculation at this time.

Dave said...

Donny,

What Stephan said about hypoglycemia. The insulin hypothesis seems to change, depending on what evidence one presents to the believer they are debating at the time.

Back in the day low-carbers used to preach that the problem with carbs is that they are converted to fat. This is how they made the case for low-fat diets promoted by the USDA causing the obesity epidemic. But of course it turns out de novo lipogenesis has an insignificant effect on fat stores in the human body.

Sanjeev said...

> post-meal hypoglycemia (or "reactive hypoglycemia") is rare in the non-diabetic general population
____________
Every time I have this "debate" I mentally prepare for the other to come back with the small subset of studies that correlated low blood glucose to some (varying list of) symptoms.

Gretchen said...

See https://www.ncbi.nlm.nih.gov/pubmed/23169787

What is interesting is that the mice gained weight *despite not eating any more.* We all know that mouse studies don't always translate into humans, but it's interesting.

Gretchen said...

> There was a lot of interest in this a few decades back, and so researchers
> studied non-diabetic people who claimed to have "hypoglycemia" based on
> subjective symptoms. It turned out that almost none of them were
> hypoglycemic during the times that they were experiencing symptoms they
> attributed to hypoglycemia (hunger, brain fog, the shakes, low energy,
> etc).

Symptoms of hypoglycemia depend not only on the absolute blood glucose level
but on how high the person has been before and the speed of the BG decrease.
Thus, a person who has been going around with BGs in the 300s and then gets
diagnosed with diabetes will have symptoms of low blood sugar at what would
normally be consider high BG.

So these people may not have had absolute hypoglycemia, but they probably
had relative hypoglycemia.

A healthy person with a healthy pancreas would not have problems eating a
lot of carbohydrate. But having such problems usually means they have a
predisposition to diabetes, and they often develop it in middle age or
later. Of course, people with a predisposition to diabetes also often have
weight problems.

> I still think it's possible that there may be something to it-- perhaps in
> a subset of people rapid changes in blood glucose within the normal range
> could contribute to hunger-- but it remains speculation at this time.

It sure does in me.

Jane said...

I have neuroscientist friend who has an epileptic son. I lent him a book on hypoglycemia which suggested epileptics have seizures when their blood sugar is low. He had his son take a 6-hour glucose tolerance test, and found to his astonishment that the young man has severe reactive hypoglycemia, like many other epileptics.

It seems the standard 2-hour GTT does not find it because blood glucose doesn't fall below fasting level until about 3 hours.

My friend is wondering whether the damage in his son's brain extends to the hypothalamus. If a damaged hypothalamus is common in obese people, perhaps reactive hypoglycemia is too, and we don't know about it because the standard GTT is too short?

@Alex
Thanks, that's very helpful.

Stephan Guyenet said...

Hi Gretchen,

Yes, the hypoglycemia paper is interesting. Intermittent hypoglycemia (once a week) caused body fat accumulation despite no change in fasting insulin, glucose, or glucose tolerance. Food intake was higher early in the intervention period, as expected, but normalized later. This is also expected because the counter-regulatory response to hypoglycemia becomes desensitized with repeated hypos.

The thing I find most interesting about the paper is it proposes a novel explanation for why insulin-treated diabetics sometimes gain fat. It may be intermittent hypoglycemia rather than an increase in circulating insulin itself that causes changes in brain circuits regulating energy balance over time, resulting in fat accumulation.

In the paper, they saw a decrease in UCP1, indicating reduced sympathetic stimulation of brown fat, probably accounting for at least part of the reduced energy expenditure they observed. This suggests alterations in brain energy balance circuits in response to repeated hypoglycemia, since these are the circuits that control sympathetic activation of brown fat.

Gretchen said...

I agree that UCPs are important and may explain things like "metabolic advantage." Ketogenic diets increase UCP-3 (the UCP in muscle), and ketones also reduce the mitochondrial gradient, which is what UCPs do.

So much we don't know.

Diana said...

" The alleged reason that insulin increases appetite is because it supposedly locks away fat, causing internal cellular starvation."

I'm no trained scientist, but even I can tell that this makes absolutely no sense.

(Dave, I realize you are not contending this, you are providing what LCers contend.)

The whole notion of internal cellular starvation sounds like junk science.

Jane said...

That paper Gretchen linked is really interesting. I just found another that might interest Stephan. While long-term intermittent hypoglycemia did not change hypothalamic NPY or POMC expression (Gretchen's paper), 1-3 episodes of mild hypoglyemia did.

'Hypoglycemia reduces sympathoadrenal responses to subsequent hypoglycemic bouts by an unknown mechanism. To assess whether such hypoglycemia-associated autonomic failure is due to actual brain damage, male Sprague-Dawley rats underwent 1-h bouts of insulin-induced (5 U/kg i.v.) hypoglycemia (1.6-2.8 mmol/l) 1 or 3 times on alternate days. Rats remained alert and were rescued with intravenous glucose at 60-80 min. Plasma epinephrine and corticosterone responses were significantly reduced during the second and third bouts. ..... non-coma hypoglycemia produces apparent apoptotic cell death with reduced NPY and POMC expression selectively in the ARC. This may contribute to the reduced counterregulatory response following repeated bouts of hypoglycemia.'
http://www.ncbi.nlm.nih.gov/pubmed/10905492

Please Stephan, write a post about this!

donny said...

Stephan and Dave, thanks for the replies.

Stephan said;

"I think more research needs to be done in the area of blood glucose and food intake (despite the fact that a huge amount of research has been done already), but I can say with confidence that post-meal hypoglycemia (or "reactive hypoglycemia") is rare in the non-diabetic general population, including among obese/overweight people. Blood glucose will frequently dip below the typical fasting level after a carbohydrate meal, but not enough to qualify as hypoglycemia.

There was a lot of interest in this a few decades back, and so researchers studied non-diabetic people who claimed to have "hypoglycemia" based on subjective symptoms. It turned out that almost none of them were hypoglycemic during the times that they were experiencing symptoms they attributed to hypoglycemia (hunger, brain fog, the shakes, low energy, etc)."

As important as avoiding hypoglycemia after a large carbohydrate intake is maybe, how you get there. If the body is trying to drive glucose up, various hormones, increased consumption, etc. are available. Restricting intake, or meal length, might force a somewhat different counter-regulatory response to avoid undershoot of blood glucose--so that in an ad-lib situation, increased food intake might serve a greater role.

Dave said;
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What Stephan said about hypoglycemia. The insulin hypothesis seems to change, depending on what evidence one presents to the believer they are debating at the time.

Back in the day low-carbers used to preach that the problem with carbs is that they are converted to fat. This is how they made the case for low-fat diets promoted by the USDA causing the obesity epidemic. But of course it turns out de novo lipogenesis has an insignificant effect on fat stores in the human body.
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I think for a lot of low-carbers, myself included, while we may have started low-carb after being convinced by Atkins or Eades or Taubes etc., that "carbs drive fat drives insulin," we continued low-carb based on a more direct bit of information. We cut carbs. We lost weight. We think it must work somehow. If someone questions our ideas about how it works, it's only natural that we twist about, try to find a way for our direct observation to continue to be true. Perhaps, since the belief that insulin causes obesity was in a very real sense a part of the causual chain that made us healthier and lighter--that is, the idea that insulin causes obesity made us lighter, whether it's true or not--this makes us particularly loathe to give the idea up.

That said, I don't think we can lump people who think that insulin leads to obesity into a homogenous group. We need to differentiate, in my opinion, between a very specific Insulin Hypothesis, pretty much synonymous with the Carbohydrate Hypothesis proposed by Taubes, and various ways in which insulin and carbohydrate might be implicated in obesity. continued

donny said...

People who accept or lean towards a palatability/reward hypothesis of obesity get accused often enough of reverting to a gluttony/sloth view of obesity. At risk of generalizing while engaged in a diatribe against generalization... low carbers have a tendency to suggest that appetite is impossible to control, long term, unless carbohydrate is restricted. Are we saying that obesity is caused by gluttony and sloth? Why should the idea that restriction of palatability, and how we are exposed to food cues generally, controls appetite, be taken to say that obesity is caused by gluttony and sloth? In both situations, we are saying that a change in the environment will have an effect on appetite, body fat stores, and the tendency to be active. (At least, I seem to remember Stephan saying something along the lines of that last bit about activity).

I don't think de novo lipogenesis is necessarily off the hook; de novo lipogenesis isn't just a source of new fat, it's also part of a signalling cascade that has effects on the storage of fat and the use of fat for energy vs glucose.

Sorry for being so blabby. Usually social anxiety doesn't let me do this kind of multi-post.:)

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