Tuesday, January 29, 2013

Why Do We Eat? A Neurobiological Perspective. Part I

As with all voluntary movements, eating food is an expression of activity in the brain.  The brain integrates various inputs from around the body, and outside the body, and decides whether or not to execute the goal-directed behaviors of food seeking and consumption.  Research has uncovered a lot about how this process works, and in this series I'll give a simplified overview of what scientists have learned about how, and why, the brain decides to eat.

The Gatekeeper of Voluntary Behaviors

Let's start at the broadest level.  The brain has the capacity to drive feeding behavior at any time of day.  Why do we only seek food and eat it at some times and not others?  Why do we perform any behavior at specific times and not others?  The brain contains a sort of 'gatekeeper' function that selects among all possible behaviors at any given moment, executing those that are currently the most relevant. 

This gatekeeper function is integrated with the reward system*, centered in the basal ganglia.  This system is responsible for selecting/motivating all voluntary behaviors, including the seeking and consumption of food.  Stimulating this system in the right way can strongly influence feeding behaviors (1, 2).

The neurotransmitter dopamine is a critical element of the reward system.  Mice lacking dopamine are a fascinating case study in the function of this system-- they have no motivation to do anything.  Their behaviors almost all remain latent and they just sit in their cages, not eating or drinking until their dopamine is chemically replaced (3)**.  Dopamine-deficient mice can still react to things-- if you place food in their mouths, they'll chew and swallow; if you startle them, they'll jump; if you place them in water, they'll swim.  However, when they swim the path they take through the water is random, compared to the goal-oriented path a mouse would usually take to try to escape.  Dopamine-deficient mice still have the ability to move their bodies, and they can still react to certain things using hard-wired behaviors, but they are totally unable to execute voluntary, goal-directed behaviors.  They're constitutionally apathetic toward everything, including food.

Conversely, increasing dopamine levels in mice increases motivation to eat, increases food intake, and increases body weight (3b)**.

The reward system is a gatekeeper through which all voluntary behaviors must pass to be expressed.  Whether or not the reward system selects/motivates a behavior depends on a variety of inputs.  Keep this in mind, because it's central to the process of food intake regulation. 

What is Hunger?

In addition to being a sensation, hunger is a motivational state.  When a person or animal is hungry, he is motivated to seek and consume food.  That motivation can make people run many miles in pursuit of a gazelle with nothing more than a spear and a water bottle (in the case of hunter-gatherers), or on a smaller scale, it can make you move a fork from your plate to your mouth.  Seeking food and eating it represents the reward system motivating those behaviors rather than other potential behaviors, because the brain has decided based on various sources of input that eating is a high priority at that moment.

Hunger is Only One of the Reasons We Eat

Researchers have divided eating into two categories, which are important to understand: 1) 'homeostatic eating', in which food intake is driven by a true need for energy, and 2) 'non-homeostatic eating', in which food intake is driven by other factors.  Eating in response to hunger is mostly homeostatic, while eating for pleasure, emotional/stress reasons, social reasons, or just because it's mealtime, is non-homeostatic.  As I'll explain in more detail later in this series, non-homeostatic factors determine food intake at least as much as homeostatic factors in the modern food environment.  Here's Dr. Hans-Rudolf Berthoud, a researcher who has written extensively on this topic (4):
The initiation and maintenance of ingestive behavior is co-determined by metabolic and non-metabolic factors. Among the latter, environmental cues, as well as reward, cognitive, and emotional factors, play an important role, particularly in human food intake in the modern world.
A common sense example is all we need to begin to understand this.  The holiday season is the scenario in which Americans are most likely to overeat and gain fat.  That's not because we're suddenly hungrier on Thanksgiving-- holiday weight gain is driven almost exclusively by non-homeostatic overeating: the presence of readily accessible, delicious, energy-dense, diverse food, and social eating and drinking.  The average American overeats during the holidays, gains fat, and hangs on to most of it indefinitely (5):
In subjects who completed one year of observation, the weight increased by an average of 0.32 kg during the holiday period and 0.62 kg over the entire year, suggesting that the period contributing most to yearly weight change is the six-week holiday period.
Holiday weight gain accounts for about half of total annual weight gain in American adults, and is therefore an excellent example of non-homeostatic overeating leading to weight gain (5).

Another example of non-homeostatic eating is soda consumption.  People don't choose calorie-dense soda over plain water because they're hungry or thirsty-- they choose it because they like soda.  Most people only weakly compensate for the extra calories they drink by eating less later.

As obvious as it sounds, we eat because we're motivated to eat, and there are many factors that can motivate us to eat.  These factors are recognized and processed by many specialized hardware 'modules' in the brain, and forwarded to the reward system to determine if they are sufficient cause for action.

When we're trying to understand what causes obesity (and how to reverse it), the most important question is not "what makes us eat?"-- it's "what makes us eat more than what we require for leanness?"  To answer that question, we need to understand both homeostatic and non-homeostatic eating-- the motivations driven by hunger and factors other than hunger.  That's one of the reasons why models that focus exclusively on hunger and satiety fail to explain human eating behavior in the real world.

The other reason such models fail is they don't take into account the system that regulates long-term energy balance and body fat mass (the energy homeostasis system).  This system influences the circuits that govern reward and satiety, adjusting motivation and hunger in accordance with current energy stores.  For example, if you've under-eaten for a day, or weeks, your energy homeostasis system detects the energy deficit and responds by making you hungry and motivated to seek food.  If you've overeaten, it detects the excess energy and responds by reducing hunger and the attractiveness of food in subsequent meals (6)   In some people, it can also compensate by cranking up energy expenditure (7).  The degree of compensation for excess energy intake varies between individuals, and is one of the factors that determines a person's susceptibility to fat gain (7).

A Neurobiological Model of Food Intake Regulation

Let's start with this diagram, illustrating the key systems that govern food intake.  It will be highly simplified, but sufficient to illustrate the central points.  Each colored shape loosely represents a functional and anatomical brain 'module' specialized for a particular task (or set of tasks).  As we proceed, I'll fill in the other modules that converge on the reward system (and thus determine our motivation to eat), and the external factors they respond to:


As you can see, the reward system receives a number of inputs from other brain regions, makes a decision about what behaviors to motivate, and allows those behaviors to be expressed through regions of the brain that control muscular movements (motor systems).  Every time you buy food at the grocery store, every time you eat out of hunger, every time you eat out of boredom, every time you drink an alcoholic beverage, every time a fork moves from your plate to your lips, it's happening because of coordinated activity in these brain systems.

In the next post, I'll continue to unveil this model by exploring homeostatic eating.


* I ran this post by two researchers who work in reward-related fields and are familiar with these circuits, to verify its accuracy. One of them commented that although it's commonly called the 'reward' system in the scientific literature, he thinks a more intuitive name for the function I'm describing is the 'action selection' system. I'm going to keep calling it the reward system just for consistency (with previous blog posts and the literature), but I do think his point is worth noting.

** Dopamine replacement does not quite bring them back to the level of a normal mouse, and consequently dopamine-deficient mice eat less and are leaner than normal mice.  Conversely, mice with more dopamine eat more and weigh more than normal mice.  These are obvious predictions of the food reward hypothesis.  Lowering food reward reduces the motivation to eat, whether that is accomplished by genetic manipulation or by eating food that is inherently low in reward value; increasing food reward increases the motivation to eat.

38 comments:

Rafael. B., PhD. said...

This is just great. Thanks. I guess you will be tying up this to your food reward hypothesis
http://realfoodisgreat.blogspot.com

Martin H Inderhaug said...

Hello!

Maybe this is interesting reading for you?

Great site you got, by the way!

http://www.smartinder.com/2012/10/02/it-should-be-healthy-but-should-it-also-be-slow/


Best,
Martin

Karg said...

Anyone who has kicked an opiate habbit can testify to the effects dopamine removal.

You are left with a 6 month period of your life where you essentially do not have natural dopamines. Its a very grey time, you have no energy or motivation. It is nearly impossible to feel happy, love, joy, sorrow, sadness...

Roger Butler said...

st“'homeostatic eating', in which food intake is driven by a true need for energy”
Two questions come to mind. Is it only energy needs that drives this or are there systems for detecting particular vitamin or minerals deficiencies, e.g. salt, that stimulate the eating of food that will make good such deficiencies? Also, presumably an implication is that anyone who is overweight never experiences homeostatic eating (because her/his fat represents available energy). - Roger Butler

meegs34 said...

I do like the phrase "action selection system."

People who don't understand what "reward" really means assume that non-rewarding food has to taste bad.

Non-rewarding food can taste very good, the difference is it doesn't trigger the action of more eating.

Stephan Guyenet said...

Hi Roger,

There are only a few nutrients that are known to be monitored by the body such that food preferences are adjusted accordingly. Salt is one of them, as you mentioned. As far as I know, it is not generally the case that people or animals will overeat to make up for nutrient-poor food.

You said "presumably an implication is that anyone who is overweight never experiences homeostatic eating (because her/his fat represents available energy)"

I understand why you would come to that conclusion, but it's not the case. The problem is that overweight people have a higher setpoint around which the hypothalamus regulates energy stores. Therefore overweight people experience hunger in response to declining energy stores just like lean people. Whether you're hungry or not is not so much about your actual energy stores, it's about your brain's perception of your energy stores.

That's the main crux of why it's hard to lose fat. I'll try to address this in upcoming posts.

Sanjeev said...

> are there systems for detecting particular vitamin or minerals deficiencies
___
Google for deficiency symptoms - even trusted medical works like the Merck Manual are at least partially up on the internet now.

Hunger and/or excessive drive to eat is almost never a symptom, but lack of hunger is VERY frequent.

Sanjeev said...

It only stands to reason, IMHO

the absolute amounts of nutrients are important but in many cases the ratios are important

If one's body forced overeating to remedy a deficiency, that would run the risk of getting a toxic amount of other nutrients ...

... WITH NO GUARANTEE that the deficiency would be fixed. In fact, since the environment-plus-body system has proven that it cannot provide enough of some specific nutrient, there's a good case to be made that overeating will leave the body DEFICIENT in some nutrients AND OVERDOSED in others.

Ted Burke said...

A very thought-provoking post! I always enjoy reading your blog.

Dylan said...

This blog is endlessly fascinating. Thanks Stephan.

Mary said...

A lot of that extra holiday eating is sweets. Maybe the extra fructose is increasing leptin resistance. Just a thought.

George Henderson said...

Sanjeev, you're making sense.
An animal fed a diet completely lacking in B complex vitamins will die eventually, but an animal fed the same diet with normal amounts of only one of the B vitamins will die sooner.

"what makes us eat more than what we require for leanness?"
Omega 6, anandamide, and the craving for fructose (yup, this theory makes the food reward hypothesis credible at last).
When the CSPI agitated to replace tallow with seed oils at MacDonalds, they didn't realise that their intervention was going to fuel an explosion in soda consumption a few years later.
MacDonald's aren't complaining.
Nice one, CSPI.

Sue said...

Mary excess calories is the issue.

George Henderson said...

Mary and Sue can both be right.
If abnormal omega 6:3 ratios are driving excess caloric consumption, and those calories tend to be fructose and glucose to begin with, then we can ALL be right.
We really do have a mixed model that accommodates FRH, CICO and CIH, and also includes: microbiota; fructose, seed oil and grains as food toxins; and any other sane suggestions that might be forthcoming and that aren't contradicted by the evidence.

"instead of thinking outside the box, think about the box".

Mary said...

Sue,

Because of a schedule change a month ago, I have increased my morning hiking to around 25 miles per week from 10 miles. Has my weight changed? No, it has stayed within the same 2 lb weight band as before. Likewise, if I go out and have an unusually large meal, I can hardly sleep that night because I will be hot. I have found that if I avoid all sweets during the holiday period and just eat the meats and cheeses, I will not gain the 2 to 3 lbs I used to. I know this is just a n=1.

Recently, I decided to have a slice of chocolate cheesecake when I ate out - I rarely eat sweets. Talk about hyper-palatable, I was craving more cheesecake for several days. This is what I think Stephan will get into. You cannot gain weight unless something drives your fat setpoint higher and that will be hyper-palatable food. I find sweets are that for me and I gain weight when I eat them.

Mary said...

Actually, I should clarify the above; when I regularly eat anything with more than a very small amount of sugar in it, I gain weight. I also limit my fruit consumption to a small amount at any one time.

Thanks Stephan, I find this blog very valuable.

Katerina Bent said...

To Stephan: you use the term "setpoint" but I was taught that the setpoint theory had been debunked, because of several problems. Are you just using this as a general term?

By the way, some of you might be interested in this post:http://katerinabent.blogspot.com/
I talk about a few interesting research studies done on hunger and eating.

Sue said...

Mary, do you know how many calories you eat. Could be that you gain weight with sugary foods because they tend to be more calorie rich and you eat more of them.
When you increased your exercise you may have inadvertently increased calories consumed and hence no weight loss.

jimpurdy1943@yahoo.com said...

Stephan, is it possible that our gut bacteria could be the most important driving force behind hunger? After all, they are the gatekeepers between food in our intestines and our bloodstream. And gut bacteria, like people, want to survive, which requires that they get the nutrients that feed them.

It is well known that out gut microbes have many effects on our metabolism and our behavior. And since "good" microbes like bifidobacteria use fiber, it seems reasonable that they would initiate processes that would make their human hosts hunger for more fiber.

For many years I have struggled with obesity and food cravings. Recently, I decided to try a little self-experiment to see if I could stop my food cravings by feeding inulin and FOS fiber to my gut bifidobacteria.

I started on an extremely low-calorie diet (a few eggs daily), and I began taking VSL #3 probiotic capsules, and Jarrow inulin/FOS powder.

The results were fascinating, and exactly what I had hoped: my hunger stopped, my blood pressure dropped, my diabetic blood sugar readings improved, and my weight is dropping nicely.

Does it make sense that all these developments could have been caused simply by feeding inulin and FOS fiber to my gut bacteria?

Stephan Guyenet said...

Hi Katerina,

I'm not sure what you mean when you say the setpoint idea has been "debunked". If you define the setpoint as a rigid number that is genetically fixed throughout life, then yes it's not correct-- but no one actually believes that version of it.

If you define the setpoint as a loosely defended number that the brain attempts to bring the body back to after short-term changes in body fatness, then it is clearly correct. There is no doubt that the body 'defends' current fat stores against changes in the short to medium term, and there is also no doubt that this reflects the activity of relatively well-characterized homeostatic circuits in the brain.

It would be absurd at this point to think that there is no mechanism in the body that defends against changes in fat mass, and so some version of the setpoint (or settling point, or whatever you want to call it) is going to be correct.

But the level of fat mass that is 'defended' can be altered by a variety of circumstances, including diet, age, inactivity, drugs, and other factors. This is what trips people up when they think about the idea.

Hi Jim,

You're doing an uncontrolled experiment so it's hard to know what's having the effect. You're essentially going on a very low-calorie diet that's very simple/repetitive and mostly protein. Many people find that this kills their appetite. So I don't know if the effect has anything to do with the fermentable fibers.

Mary said...

Sue, You are kidding right? There was nothing "inadvertent" about my increasing calories with increased exercise, my appetite went up and I ate more.

My neighborhood has plenty of overweight people walking daily or riding bikes and wondering why they aren't losing weight. I was one of them for many years. It took a diet composition change for me to lose over 30 pounds. I stopped eating whole grains, anything with added sugar in it and my daily beer with dinner. I increased protein and saturated fat. If anything the caloric density of my diet has increased and my calories consumed stayed about the same. My energy level is much better, I no longer have low blood sugar crashes daily and I sleep less. I have increased my leptin sensitivity, lowered my fat mass setpoint corrected my metabolism and lowered my fasting insulin. I would like to figure how to lower my setpoint by another 10 lbs. Stephan has a post on lowering the "setpoint".

http://wholehealthsource.blogspot.com/2010/01/body-fat-setpoint-part-iv-changing.html

Mary said...

Before I get accused of being very low carb, I am not. I eat vegetables, including potatoes, some fruit, meat and fish, and small amount of grass fed butter and aged cheese. I eat only a moderate amount of carbohydrate any one time.

Before losing the weight, I had to have a snack before exercising or I would become shaky, sweaty, confused and hardly able to talk - all the symptoms of low blood sugar. This would also happen if I went too long between meals, forcing me to eat small amounts of food every 2 to 3 hours. Cutting calories, just left me lethargic, taking lots of naps due to the blood sugar crashes and I did not lose any weight.

For me the key to losing weight was the diet change from low fat, moderate calories. I had to be convinced that increasing protein and saturated fat would not kill me. I would give a big part of the credit to Gary Taubes and his latest book and also to Stephan and other some other blogs. I know Gary is a dirty word on this blog. I know insulin is only part of the story, but since I have suffered with hypoglycemia my whole life, Gary's arguments resonated with me personally. I only did the very low carb diet for 2 weeks. My athletic performance suffered, which may have been do to the lack of glycogen. In addition, to the hiking, I do a strength building workout every other day, but I have been doing this and the hiking for many years. My hiking is on rutted dirt roads, trails and cross country and is over hilly terrain. It is more interval training since I hike uphill as fast as I can and coast downhill and the hills are steep. The morning hike and workout are done in the fasting state, before I eat and while my insulin levels are likely to be at their lowest. My goal is to make my metabolism efficient at switching back and forth between burning fat and glycogen.

Dave said...

@Mary What would Gary Taubes say the answer is for me, a physically active person who can't shake about 20 lbs of unwanted fat even while on a ketogenic diet because while the diet worked to reduce hunger for about 6 months, that effect wore off and I regained some weight. His insulin hypothesis doesn't even begin to explain that.

Not to mention the composition of my diet did have zero effect on my energy levels or my weight status. For my body a calorie really is a calorie except for the LC diet did have a temporarly appetite blunting effect, but it very well could have been from removing highly processed foods and/or increased protein.

Mary said...

Dave, Sorry about your struggle with weight loss. I can relate as I unsuccessfully tried to lose weight for over a decade. I never said that Gary Taubes had all the answers, or even the right answers, just that he persuaded me to try very low carb for a short time, about 2 weeks and that I could safely eat more saturated fat. Stephan persuaded me to eliminate grains though I do occasionally eat some white rice. I will probably add brown rice back using Stephan's soaking solution method, though I wish there was more than one study (done in China) on this method.

I only lost 1-2 pounds during the very low carb 2 weeks, which was discouraging for me, because the anecdotal evidence was that I should have lost a lot more due to retaining less water. It took me 10 months to lose 30 pounds and I have been weight stable for the last 2 months. I still need to lose at least 10 more pounds and I feel stuck right now.

Stephan, feels that very low carb should be done for only a short time, and that is what most of the low carb diets out there recommend. I suspect that cutting out the whole grains helped for 2 reasons: I may be sensitive to gluten and I eliminated the phytic acid and other anti nutrients in the bran of whole grains. I was already eating home cooked unprocessed food and all of the grains in my diet were whole. I have experimented with my diet composition and suggest you do the same. The safest carbs to add back are probably potatoes, sweet potatoes and white rice. Start off with a small amount with meat or fish. You may have to gradually rebuild your tolerance to glucose.

Finally, there is a lot of individual differences and you need to experiment and find what will work for you. There is a lot of valuable info on this site and I recommend searching here using some of the labels. Good luck.

Sue said...

Mary you said you increased your exercise but your weight hasn't changed. Like you were questioning why. You didn't mention that you ate more.

chris said...

Curious about the dopamine mice, since DA increasing drugs promote leanness.

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stephers said...

I am also curious about the dopamine mice, since serotonin increasing drugs tend to suppress dopamine, which has the effect of suppressing sex drive and sexual sensation, but increases appetite and weight gain; whereas dopamine increasing drugs like amphetamines tend to reduce or eliminate appetite and in fact are often used for weight loss. The brain seems rather complex!

Paul N said...

Stephan wrote, in response to Roger;

"There are only a few nutrients that are known to be monitored by the body such that food preferences are adjusted accordingly. Salt is one of them, as you mentioned. As far as I know, it is not generally the case that people or animals will overeat to make up for nutrient-poor food. "

I think this is a bit of an over-simplification. While this is true for most people, most of the time, there is one situation where it is not - that would be pregnant women.

They are often driven to eat things they would not normally eat, and to not eat things that they do normally eat. And this changes in the different stages of pregnancy. Overall, they end up getting a very wide variety of micronutrients, much more than normal.

This suggests to me that a system for nutrient based food preferences exists, but is not strongly active most of the time. I think (for non-pregant people) it comes into action only in response to a deficiency, and even then, some people, like vegans, train themselves to ignore/suppress the cravings.

Pregnancy would seem to be a case of the body/brain being pro-active and not waiting for a deficiency.

The well known effect of pregnant women having heightened taste/smell sensitivity shows the system can be up-regulated.

Sanjeev said...

to my reading it's almost a nonsequitur.

lacking is proof that any of that is in any way linked to deficiencies.

the comment reminded me of this

copy & past for work safety:
http://theness.com/neurologicablog/index.php/anomaly-hunting/

geneticpotential said...

The very last paragraph regarding mice and dopamine I have a question about. Kenneth Blum in his studies showed that a lack of dopamine increased sugar cravings (http://www.springerlink.com/content/b475224658w86007/). IN my practice I have successfully used amino acid therapies such as tyrosine to mitigate food cravings in some people. Just curious as to what your thoughts are regarding that mice study showing that mice will eat less. Do mice not have non-homeostatic eating tendancies? Thanks a bunch

Jane said...

@Sanjeev
The fact remains that an important satiety hormone (uroguanylin) works by activating an enzyme which is known to be dependent on manganese/magnesium. Therefore Mn/Mg are in some sense satiety signals. This does not mean hungry people seek out foods high in Mn/Mg, of course. Quite the opposite. But during our evolution it would have been difficult to avoid them.

Uroguanylin is very new, and very hot. Here is a 2012 Nature News & Views article about it. Tell me if you can't get it, and I'll pick out some choice quotes for you. Or perhaps you can persuade Stephan to write a post about it.

'Gastrointestinal hormones: Uroguanylin—a new gut-derived weapon against obesity?'
http://www.nature.com/nrendo/journal/v8/n1/full/nrendo.2011.206.html

Sanjeev said...

there are too many micro-mechanistic phenomena that make no difference in the end when tested over the whole system over a reasonable time.

It's basically the fallacy of composition and I've fallen for that stuff too many times in my life.

Until there are multiple well controlled randomized controlled trials I'll give it a pass on changing my behaviour.

Sanjeev said...

After all, how does one conclude insulin from carbs (but not protein) is the ONLY thing worth worrying about?

Fallacy of composition: confusing a tiny part of the whole for the whole

I fell for that one myself

How did Lustig convince so many through that Youtube video that Fructose is poison? Partly through fallacy of composition.

I didn't fall for that one.

Jane said...

@Sanjeev
Can't blame you for not wanting to hear about YET ANOTHER wretched hormone. As if there weren't enough already. Especially if you're eating white rice, let's say, and have convinced yourself that removing the manganese and magnesium isn't a problem.

Joseph Carr said...

Our everyday energy comes from food. And food comes with many varieties, and varies across every nation or continent. But given all the difference, we must all consider its true essence, and that is being healthy. We must always watch what we eat and prefer the healthier ones to maximize our body’s full potential and to boost our immune system.

Joseph Carr

Keith C. Collins said...

What do you feel is the perfect diet for a 50 year old male with metabolic syndrome (5 foot 11, 220 lbs)? The only diet I ever lost weight on was the Atkins diet, went all the way down to 189, but low energy levels a bit of non-normal depression had me off the diet after 5-6 months. The good news is I did not gain weight for almost a year (helped insulin resistance?) but then after a three years gained back to 210 lbs, then later 220. Want to diet much healthier this time and looking for some advice.

nbc said...

You should read the following article - http://www.cell.com/trends/neurosciences/fulltext/S0166-2236(13)00005-2