Thursday, May 26, 2011

Food Reward: a Dominant Factor in Obesity, Part IV

What is Food Reward?

After reading comments on my recent posts, I realized I need to do a better job of defining the term "food reward".  I'm going to take a moment to do that here.  Reward is a psychology term with a specific definition: "a process that reinforces behavior" (1).  Rewarding food is not the same thing as food that tastes good, although they often occur together. 

Food reward is the process by which eating specific foods reinforces behaviors that favor the acquisition and consumption of the food in question.  You could also call rewarding food "reinforcing" or "habit-forming", although not necessarily in an addictive sense.  Food reward is a perfectly normal and healthy part of life, although I believe it can be harmful if it exceeds the bounds of what we're adapted to.  Food reward is essential for survival in a natural environment, because it teaches you what to eat and how to get it through a trial-and-error process. 

Researchers have demonstrated in rodents and humans that pairing a flavor with a source of calories makes us gradually enjoy the flavor more*, whether or not it remains paired to calories afterward (2, 3).  That's called a "conditioned flavor preference", and it's a simple demonstration of food reward in action.  The brain senses the ingested calories and assigns a positive reward value to the cues (flavor, location, etc.) associated with the calories, after which we'll be more likely to eat something that contains the preferred flavor.

As another example, rats prefer to hang around a place where they have repeatedly received rewarding food (4).  Have you ever seen a child run after an ice cream truck?  After a certain time, our motivation to obtain a food that we perceive as rewarding increases, and so does our consumption of it.  Rats accustomed to eating human junk food will endure foot shocks and extreme temperatures to obtain it, even when much healthier unprocessed rodent chow is freely available (5, 6).

Here's the fundamental concept that I think explains a lot of obesity in industrialized nations.  We live in a more or less Darwinian economic framework (capitalism).  Food manufacturers are in constant competition, and any food that sells poorly will rapidly disappear from stores.  How do you get people to buy your product?  You produce something that causes them to come back and buy it again.  In other words, the goal of processed food manufacturers is to create a product that maximally reinforces purchase and consumption behaviors-- food reward!  If the product is not extremely rewarding, it won't sell because it's competing against other products that are extremely rewarding. Only the most rewarding products survive.

It doesn't matter whether or not you like the Little Debbie cake once it's in your mouth.  It doesn't matter how you feel afterward.  The only thing that matters is whether or not you'll buy another one tomorrow.  That's food reward. 

*I say flavor, but technically I mostly mean smell.  The tongue can detect five tastes, while the nose can detect thousands of smells.  Both flavor and smell are important for reward.


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EL 66K said...

Stephan, you said: "It doesn't matter whether or not you like the Little Debbie cake once it's in your mouth. It doesn't matter how you feel afterward. The only thing that matters is whether or not you'll buy another one tomorrow."

Then, it's possible to become dependent on a food you don't enjoy, or that apparently does not give you direct pleasure? Am I understanding it right?

Andrew Wallace said...

Thanks for the clarification, Stephan. This food reward concept seems like quite a big paradigm shift to me, but when I think about it, it probably shouldn't be.

I've spent most of my adult life in Japan and Korea, where the traditional food culture hasn't been completely lost. When talking about the longevity and leanness of the Japanese, people harp on about low-fat and seafood, but here in Japan, the concept of "usuaji" or "thin flavour"is synonymous with healthy eating.

Usuaji is definitely not the same as "bland" though. In fact, the more expensive the restaurant is, typically the "thinner" the seasoning gets. Instead of strongly sweet or salty or meaty, you're supposed to appreciate instead the flavours of the ingredients themselves, be it the seasonal vegetables, plain rice, miso soup and sashimi of a traditional home-cooked meal or the crab brains, squid tentacles, trout seamen, boiled clams, seared bonnito, salmon roe, duck eggs, wild mountain yam, and natto rolls I had for dinner at a nice restaurant a few nights ago (plenty of nutrient-dense foods there).

Contrast this with Australia, where I grew up, and where a coherent traditional food culture has largely been lost. Australian food (and American food too, I imagine) is a combination of the greatest hits of the Neolithic world (ie. the most rewarding, dishes from around the world) and industrially processed convenience food (ie food that's been engineered by corporations to be as rewarding as possible).

Shouldn't be a surprise then that despite being obsessed with food and flavour (there's not a show on TV without a food segment here), Japanese are still lean (though getting less so as the flavours get less subtle) while all my old friends back home are now sporting pot bellies. Perhaps a little "usuaji" appreciation is in the answer.

Mirrorball said...

I knew we could blame it on capitalism. ;)

taw said...

I'd still like to see how you can measure "food reward", even approximately.

Todd Hargrove said...

Blaming it on capitalism? You mean you're not an Austrian school libertarian like every other paleo blogger?!

Mirrorball said...


Serve two different foods to rats/humans/other animals. Measure how much of each food has been consumed after a considerable time interval (sereval days, weeks) has elapsed. Divide the two amounts and there you have a measure of relative food reward. If you set a certain food as a standard, you can even build a scale of food reward relative to the standard food. I think this method would work.

Helen said...

People keep mistaking Stephan for a Paleo blogger. He's pro-Paleo, but has never been Paleo per se, as far as I know. Maybe that explains the lack of an Ayn Rand angle. ;)

Was Ayn Rand Paleo?

ItsTheWooo2 said...

If food reward causes obesity, why can I eat absolutely anything I want as long as my glucose is balanced I will feel satisfied and energetic and not gain weight? I can eat chocolate, I can eat cake. Its only when my insulin and glucose go to hell that I start eating a lot and feeling tired and crappy.

If food reward causes obesity, why is it that when I decreased my subcutaneous leptin injections I became far less energetic and talkative (a change others noticed), as well as prone to eat more? Leptin affects energy and appetite via dopamine, peripheral thyroid hormone conversion, and modulating glucose tolerance (toward higher glucose levels and glucose intolerance).

If food reward causes obesity, why can I eat anything I want if I inject low dose leptin and maintain a low % of carbohydrate in the diet?

This is such a cop out and you write it as if you've discovered something profound. "Guess what guys, gluttony causes obesity, but I'm going to use a nicer sounding word called "food reward" to describe what is plain old gluttony". THey've been saying gluttony is the cause of obesity for decades. It wasn't true then, and it isn't true now that you are calling it "food reward".

Saying "food reward" causes obesity is like saying "oxygen reward" causes elevated respiratory rate. It may be true , technically. Breathing is very rewarding. Not breathing is anxiety and panic producing leading to frenzied life or death fight for air. Breathing more and increasing oxygen intake feels really good and relaxing when your chemoreceptors freak out telling you that you need more o2 (and need to get rid of co2).

However, ultimately, YOU ARE EXPLAINING NOTHING. Yes, perhaps "oxygen reward" LEADS to increased breathing, but what is the underlying defect which makes oxygen so chronically rewarding? What is wrong with this person's body that they breathe so much more than everyone else? Emphysema? Bronchitis? Metabolic acidosis?

Normal people maintain a respiratory rate between 10-20 per minute with a regular rhythm. When there is a break down in regulation of oxygen/co2/acid base balance then this starts to go to hell. The way one breathes may change (e.g. sharp sighing breaths with a prolonged exhale in ketoacidosis), and the rate will change (an increased rate is observed in all hypoxic situations).

If you think regulation of body fat and calories is ANY DIFFERENT than the regulation of oxygen and carbon dioxide you're no more educated than the rest of the world who looks at fatties and says "gee get some self control you fat slob, what a glutton".

Food reward is a dominant factor in obesity. LOL.

ItsTheWooo2 said...

Okay, lets assume you're right. My question to you is this. Why does the thin person freak out with joy over a delicious cheesecake, eat the whole THING, but then later their body compensates and they feel reaaally full and reeaaaally energetic AND don't even store much of it as fat?

Why does the fat person do the same thing, meanwhile their insulin levels sky rocket, their liver churns out triglycerides, their peripheral glucose tolerance goes to hell (leading to a greater synthesis of body fat as fat cells remain relatively insulin sensitive for a long time), sky high levels of insulin lead to adipocyte hyperplasia just like a tumor, and there is NOT a compensatory decrease in appetite or increase in energy thereby which because all of that delicious cheesecake was efficiently stored in adipose tissue (both enlarging existing cells as well as growing new ones, like a tumor). They sit and don't fidget, move, talk fast or ramble or run about like an energetic child. They lay there tired in spite of having consumed 3000 calories, and they will do it again the next day, because there is NO compensation for the increased food... because the food is being shunted to their adipose in a one way chute, with no capacity to access it due to chronically elevated insulin and numerous endocrine/nervous system derrangements.

Meanwhile your thin friend... is running about and has so much energy to spare that they run for recreation, is quite motivate dand energetic by personality and can eat whatever he or she wants, even a whole cheescake, and will NOT GAIN WEIGHT because their metabolism dumps food into energy and heat vs dumping it into an ever expanding adipose depot.

Your "food reward" hypothesis explains none of that... because when it comes down to it, OBESITY IS A METABOLIC CONDITION, it is neurological, endocrine, it has nothing to do with mindlessly eating food over and over again because it tastes good. Because in a working body, food stops tasting good when you are burning tons of fat and glucose. When your dopamine levels are high, you rapidly experience nausea and vomiting if you attempt to eat more. When your hands are warm with energy and you're running about, eating too much is a nauseating proposition.

I WISH you had my metabolism and endocrine situation, you would stop writing these silly borderline offensive torrents of dialogue regarding how fat people are like rats who just eat because their primitive brains have a positive reinforcing feeling from the food.

Ever get food poisoning? Why does your most delicious awesomest food look nauseating? Answer: neurotransmitters (dopamine, serotonin) responding to toxins make it impossible to eat.
FACT. The same thing happens when you are really full, assuming you are not afflicted with the condition of obesity. Normal people feel nauseated when they try to eat too much. Fat people rarely do, because fat people have no dopamine receptors to speak of secondary to compensatory downregulation in result of high glucose levels (and in a cycle, high glucose leads to low dopaminergic tone, leads to high glucose...).

I mean this is just too ridiculous. I can forgive "regular" people for being so foolish but I expect more from someone who spends most of their time contemplating the biological underpinnings of obesity.

jd said...

You obviously have strong feelings related to this topic.
It would help others more, I suspect, if you keep it a bit more cordial and constructive.

Stabby said...

Indeed, food manufacturers compete to produce the product that creates the greatest food reward and thus becomes the preference of the subject. Pizza pops taste great, better than X product, better than broccoli. Broccoli tasted terrible now to those who have associated pizza pops with high reward. The subject will choose his favorite brands when given the chance, but it doesn't follow from this strong preference born of greatest food reward that he is necessarily going to "overeat" this food to the point that he isn't going to be able to burn off the calories, he only choose it over other stuff and develops a love affair with it.

Obese people when completely uninhibited by images of their ideal self-concept will binge in a combination of food reward...and hunger, and indeed they will eat more of the more rewarding foods than they will of the less rewarding foods. But this doesn't demonstrate that it was the food reward that caused the fat accumulation in the first place, we are only observing food reward in the context of obesity or an obesity-causing diet (ensure rats, guys eating the goo, etc).

To the point, none of the studies used thus far have controlled for leptin sensitivity in attempting to demonstrate food reward to be behind obesity. Foods that use hyperpalatability to become preferred are usually one and the same as those that cause leptin resistance through inflammation. Most lab rat diets certainly cause weight gain, based upon PUFA intake. Paul Jaminet cited a study in his book where 3 groups of rats had different amounts of body fat on isocaloric diets with the only difference being linoleic acid content.

Indeed taking someone who is obese and giving them goo decreases their appetite but the solution to a problem never has to be a reflection of the cause of the problem.

Steve said...

If I've been following Stephan's theory correctly, I don't think it's really incompatible with what ItsTheWooo2 is saying.

Poisonguy said...

I think a lot of people don't like this "Food Reward" theory because it's not very sexy. It might as well be called "It's calling my name" Food Theory of Obesity. However, it's deeper than that and Stephan knows this, and I suspect he's just teasing his readership to stretch out the number of posts on this series. As mentioned, obesity is a metabolic dysfunction and can't be explained away by "food reward" unless food reward can be explained at the cellular level. Well, anyone who's followed food reward for a while (it's not a novel idea) knows that there are mechanisms described at the cellular level that explain alterations to normal food reward mechanisms. And guess what. It involves central leptin and insulin resistance and their effect on dopamine, etc, to be brief. My guess is that this will be address in a subsequent post by Stephan. Be patient people.

For those who can't wait, in 2006, Lustig published a nice review of his version of the food reward theory ( He also has linked it to fast food in 2005 (

Emily Deans, M.D. said...

+1 @Poisonguy - food reward is mediated through the neurotransmitter systems, omega 6, sugar, wheat (dairy???) all could potentially annhilate the feedback loop depending on individual vulnerability. At the far end of the human scale there are those who struggle with binge eating (often obese but not always, and 1/3 of people seeking treatment for obesity are binge eaters) - behaviors, thinking, and food habits are very similar to patterns in alcohol or drug addiction. It's a valid line of inquiry.

"paleo" as it were addresses two specific pieces of the food reward issue - decreasing the amounts of industrial "hyper palatable" foods (a la Kessler's End of Overeating). Also promoting disgust for those foods. In my mind the most interesting part of Kessler's book is about the disgust factor - it is how vegetarians quit meat, for example.

I'm sure Stephan knows more about these neurotransmitter systems and I'm anxious to read more!

admin said...

Ayn Rand was not measurably paleo. John Galt ate bread. However, since A is A and Ayn Rand is always right about everything, it's safe to say that she is still "essentially" paleo. To fully understand this, you need to either study Objectivism or get horribly drunk at a Teabagger party.

Rafael B. said...

Stephan, can you put a search gadget on your blog? It is really simple with blogger. Thanks

Dragan said...

"It doesn't matter whether or not you like the Little Debbie cake once it's in your mouth. It doesn't matter how you feel afterward. The only thing that matters is whether or not you'll buy another one tomorrow. That's food reward."

I think this paragraph (and possibly the whole post) needs to be refined... at present it makes it seem like the notion of "food reward" is an academic novelty that's more or less useless in practice because it simply renames something we see all the time, i.e., people like certain foods.

majkinetor said...

There is truth in both ItsTheWooo and Stephan thinking, IMO.
Once food pathways are damaged it becomes question of metabolic changes. Before that, it might have to do with reward system.

My experience.

1. As soon as I eat fruit, I get more hungry to the extent that I can't wait next meal.
2. If I eat almonds, nothing like that happens.
3. If I eat 25g of chocolate with less then 85% of cocoa (~4g of sucrose) I don't get much of the reward. If I eat other types of chocolate with more sucrose, I have hard time to stop eating it.
4. If I drink coffee, I can ignore hunger much more effectively, or I am not feeling it at all. Cocoa drink doesn't have that effect on me.

So, increasing returns to specific foods which are problematic to begin with, given the appropriate context leads to the obesity and syndrome X.
One underlying mechanism of such reward is via opioid receptors which are specifically activated by sweet taste receptors.

In the paper Brain Mechanisms of Sweetness and Palatability of Sugars conclusion of Mr Takashi is that "Glycemic carbohydrates represented by sucrose are highly caloric and very palatable. It is no wonder that most organisms accept these eagerly. Humans must have a strong will to control themselves to avoid over-consumption."

Now, lets expand this story. Its known that ability of people to feel reward is influenced by the number of specific receptors in the brain. The number of those are different in the different people. There are different receptors involved, for instance canabinoid (CB1) or dopamine receptors.

Popularly known as munches, overeating upon marijuana exposure is well known and used medically in specific conditions (AIDS wasting, chemotherapy sickness, anorexia nervosa etc.). Once it was thought that THC might cause schizophrenia, however, its now realised that preference of such people for marijuana is consequence rather then cause - patients are depressed because there might be something wrong genetically with their CB1 receptor activation via Anandamide which causes blissful state and improves appetite. So they compensate by endogenously activating CB1 via THC which makes them feel better. Other people don't have such problems so they don't feel desire for THC that much (if it was beeing consumed before).

There is also similar thing in monogamy and polygamy rodents were studied (see Dopamine Regulation Of Pair Bonding In Monogamous Prairie Voles). The conclusion is that level of bonding (emotional reward, love) is proportional to number of dopamine receptors. When dopamine receptors are upregulated, pologamy rodents start to prefer specific partrners.

All this means that the activity of food reward systems differ among different individuals quite a lot, and that environmental toxins or life style choices might influence those pathways to a big extent.

In software enginering there is phenomena called coupling. Low coupling is considered a sign of a good design because it minimizes the chance that changing any part of the system will propagate (ripple effect). (Un)fortunatelly, human system and generally life on this planet is highly coupled. This means that changes in different parts may ripple trough the system and that concentrating on single cause can be effective for single individual but not for whole community.

Oktay Usta said...

nice blog


Poonam Tawhare said...

Buy yourself a little treat that's equal to the amount of weight you've lost: When you lose the first 5, spend $5 on yourself. When you lose the next 5, spend $10 on yourself, etc. Just make sure you spend it on something silly or something you would never normally spend money on!
Get Generic Drugs online at low price

Asad Haider said...

Regarding capitalism: it is interesting to note that the elements of Darwinism that correspond to the social dynamics of capitalism are actually derived from capitalism. This is because as Darwin was trying to explain his data, he relied on the work of Thomas Malthus, the English political economist who articulated his fear of the poor in terms of overpopulation. A great little essay by Stephen Jay Gould on the different possible interpretations here:

Asad Haider said...

Oh, and thanks for the great blog.

Lorna said...

Just listened to your podcast, which just blew my mind. Amazing!
As I was listening, a number of examples of people thriving on bland diets occured to me:
1) Just about anyone Weston A. Price studied.
2) People who lived on rationing here in the UK during the second world war. It provide a good range of nutrients and sufficient calories, but by all accounts, very dull. All my WW2 knitting patterns have a 34" chest. However, by the mid-50s adverts for weight reducing diets and much larger knitting patterns creep in.
3) Here in the UK, there is a explorer called Bruce Parry, who does TV series called 'Tribe' amongst others. He goes to live with a variety of tribes for a month at a time. In interviews, he has said the worst aspect of the food is not the yucky foods like insects and intestines, but the bland and repetitive nature of the food. He does tend to lose weight during these trips.
Love your stuff. Lorna

Erk said...

Steve, I've been enjoying your blog for several months now and have been thinking much about a "set-point".

Does the set-point theory imply that there is a finite target? I think it must as the body can't measure or produce an analog of 'infinite', can it? This is problematic since I think it is clear that many individuals seem to gain weight with no end in sight.

This seems to imply that there is merely a signal to gain, maintain, or lose adipose tissue.

antispirit said...

I think that the problem is that there's all this talk of behavior. There ain't as much talk of neurochemistry. It's easy to talk of neurochemistry because it's so precise. In the case of behaviorism, you can only see behaviors associated with obesity. I would wager that (again from a behavioral perspective) the obesogenic acts are not directly observable. That is, they are so subtle so as to be absent from our behavioral nomenclature. Pavlov's pooches salivated on command, more or less. Who's to say that your brain (or pancreas, or adrenal gland, or whatever) cannot "salivate" on command?

It's still not about gluttony. It's still not your fault. It's still a matter of hormones. In my unprofessional opinion, at least.

antispirit said...

Question to the smart kids: Do dietary restrictions increase "food reward" value of those things restricted? Or rather, do you think that they do?

Richard said...

Regarding 'bland food': I lived in Taiwan for two years, one of those years lived with my wife's family and ate a very traditional chinese diet. I would have to say from my experience that there food is very bland in general (not always though), and was able to keep my weight low the entire time without thinking about it. Now we live in Canada and my wife is always commenting on how we 'westerners' have to flavour everything: we can't just eat blueberries, we have to put cream and sugar on them, or make jam. My wife eats corn on the cob plain, while I put butter, salt and pepper. They find red beams sweet and use it as a topping for dessert or for icecream. I think what happens is we desensitize ourselves to natural flavours and need to reverse that so we can appreciate bland food and minimize cravings for salty/sweet/fatty foods.

Carl M. said...

Capitalism is indeed at fault. Get rid of capitalism and we get food shortages and labor camps (lots of aerobic exercise there!) ;-รพ

Seriously, the market process requires active consumers to work properly. This is why the medical market doesn't work worth a toot: the consumer is not the shopper; the insurance companies are. Integrative medicine doctors who don't take insurance post fees on the wall.

This is a problem that has more to do with culture than economic form. Regulation alone doesn't fix the problem. Where you have a bunch of health conscious yuppies, state organic standards work. Nationally, they don't. The federal government dumbed down the definition of organic.

If enough people want true organic, they will get it regardless of government action. Polyface Farms works against the government to raise meat and eggs in a more natural setting.

Anyone who doesn't think the stripping down of food isn't the cause of obesity should try this experiment: trying eating food that isn't processed at all. That is, do the Guy-Claude Burger thing and eat everything raw and unmixed and of reasonably close to wild varieties. Slimness is foreordained in short order. Completely unprocessed food sends some very powerful "had enough" signals even when they are delicious to start with.

Richard said...

Sorry about all the mistakes in the last post..typing fast.

Regarding Food Reward: A guy I work with, his wife is a psychologist working in an Obesity Clinic, where obese people sign up for the program and are only fed/allowed to eat 'Optifast' by Nestle, which is a meal replacement drink. her role as a psychologist is to help the patients dissociate food from reward, or pleasure from eating. SO, this experiment you metioned from the 70s still seems to be going on in one form.

Jeff Borsato said...

my question is:

what food supplement out on the market can one obtain that is flavorless and doesn't contain a variety of industrial ingredients?

i was considering trying Seth Robert's flavourless oil approach but its not as appetizing

Charlie said...

@Todd Hargrove; funniest thing I've read this morning.

Although Nassim Taleb isn't exactly an Austrian....

antispirit said...

Jeff- corn or potato starch?

Mike said...

"After reading comments on my recent posts, I realized I need to do a better job of defining the term "food reward"."

Do you?

The (slightly arrogant) implication is that people didn't understand what you'd said. But perhaps they did, and your repeated insistence - because t's really no more than that - doesn't add anything.

"It doesn't matter whether or not you like the Little Debbie cake once it's in your mouth. It doesn't matter how you feel afterward. The only thing that matters is whether or not you'll buy another one tomorrow. That's food reward."

What that is is an unlikely scenario.

You've certainly found some interesting phenomena, but that doesn't mean this theory explains everything and cannot be challenged. And a theory that explains everything also explains nothing.

Have you deliberately looked for evidence that would challenge the theory? have you tried to falsify it?

allison said...


The follow-up explanation is very helpful. Can you expand briefly on the role of salt in food reward? That is the one that is causing me some significant cognitive dissonance. I suspect that eating or drinking salt isn't the problem, but rather the combination of salt with other foods.

Stargazey said...

ItsTheWooo2 brought out some points that are relevant to this discussion. When you have experienced the realities of morbid obesity, it becomes frustrating to read an academic discussion stating that a major factor in body weight setpoint may be determined by food reward.

If it were easy to lose massive amounts of weight by eating bland liquid food through a straw, there would be dispensers and packets of the tasteless food available at every Wal-Mart. The scientists who invented the system would be living on their own private island somewhere and would be hailed by grateful ex-fatties from all over the world.

The fact that this isn't the case indicates that something is wrong with the theory. Factors far more powerful than food reward are behind the relentless drive to eat in people who are already obese. Some obese people do choose voluntarily to eat more than they should. But in a society where food is easily obtained, many find it impossible to spend their days gritting their teeth and ignoring the repeated drive to eat and eat and eat again. When they realize that their appetite will not release its grip, many of them decide that they will go ahead and eat things that taste good to them, since they believe that they have no hope of winning the battle.

I'm putting this out for consideration because the theoretical discussions here do not match the personal experience of many of us who have been or are morbidly obese.

Susan said...

Thanks for this and the podcast. I have been eating "paleo" + small amounts of dairy for several months now. Read Good Calories, Bad Claories, The Paleo Solution etc. and became convinced that it was worth a try. Lost 35 pounds almost instantly and without a struggle. No more joint pain and sore feet.
But without changing anything, the weight loss came to a halt. If I understand "set point" and "reward" correctly, this might well be the answer. I am now excited to tinker with my mostly meat and veg diet to see what will happen.
I do think, however, that taste might have alot to do with the reward factor. I am not that big on sweets, but notice that at less than 72% cacao I am likely to eat more than one piece of chocolate. Since listening to your podcast with Kessler, I have also started wondering what might be prompting my brain to assign a reward value. I think it might be salt. I am going to try cutting it out almost entirely and see what happens.

Todd Hargrove said...


I don't think that Stephan’s food reward theory necessarily implies that losing weight would be easy. Even if eating bland food reduces your need for calories, it does not necessarily reduce your need for reward. Perhaps there is a reward set point just as there is a fat mass set point. If this is true, it would suggest that moving the weight set point down by eating less palatable food would fail unless it also reduced the reward set point. Perhaps this explains the emotional struggles that some people have with losing weight, and why people can tend to trade one addiction for another.

I recall developing a chocolate addiction as soon as I cut wheat and went paleo. Some people seem to need less reward than others - there are buddhist monks and then there are people who are very prone to develop addictions to gambling, food, porn, etc.

WilliamS said...

This notion of "food reward" is not just a "psychology term," as Stephan characterizes it, but specifically a term deriving from the behaviorist tradition within that field. In this regard, it might be useful to review what is still probably the most fundamental critique of that general approach to understanding human behavior, Noam Chomsky's 1959 review of B.F. Skinner's "Verbal Behavior." It is framed in a different context of course (language rather than eating), but it speaks directly to the value of behavioristic concepts such as "reward" for understanding real-world human behavior ("play-acting at science," in Chomsky's unsparing view). In addition to the fundamental conceptual and methodological critique, Chomsky's comments about the extrapolation of concepts useful in discussing highly controlled laboratory experiments to real-world human behavior seem particularly relevant here.

tradingkellys said...

It would be helpful if the certain commenters who are aghast that Stephan has done a 180 and is now embracing the gluttony view of obesity need to actually listen to his podcast or wait for his final posts.

Nothing Stephan has said makes obesity a willpower issue; in fact it further supports the idea that food choices and quantity of food eaten are brought about by incredibly powerful forces in your body. We all understand the role hormones have in that; this is just building on it.

Just look at his stages of implementing this theory. They should all look familiar. (I am not quoting Stephan here: These were my notes on what I thought I heard and my understanding and interpretation of it.)

Stage 1: Eliminating sodas & snacks; not eating any source of liquid calories; not eating calories between set meals.
Stage 2: Eliminate all processed foods; cook everything slowly at home.
Stage 3 Reducing sugar, salt, and meatiness. Make food very simple: Eat food totally plain.
Stage 4 [not recommended]: Restrict macronutrients. Either restrict all carbs or restrict fats.
Stage 5 [not recommended]: Eat a monotonous, bland diet. Get enough nutrients, but make it repetitive and not attractive / palatable. Ex. 20-potatoes-a-day-guy.

Lauren said...


"If it were easy to lose massive amounts of weight by eating bland liquid food through a straw, there would be dispensers and packets of the tasteless food available at every Wal-Mart. The scientists who invented the system would be living on their own private island somewhere and would be hailed by grateful ex-fatties from all over the world"

I'm not sure this is true. When someone is alcoholic, there is a rational solution but they cannot see it. In spite of horrible consequences, they continue to drink and spiral downward. Just because there is a solution doesn't mean that people will see it. Reward can trump reason.

In terms of reward, I was also thinking about the difference between chewing coca leaves and injecting cocaine. The former gives you energy and allows you to work longer. The latter makes you put your baby in the microwave (okay, maybe that was meth but you get the idea). Eating a piece of sourdough bread with meat and salad is different that eating Little Debbie cakes.

I agree with Steve:
"If I've been following Stephan's theory correctly, I don't think it's really incompatible with what ItsTheWooo2 is saying."

luckybastard said...


i definitely can sympathize with your point regarding the frustration of practical application of abstract scientific hyptothesis for those who have experience battling obesity(i am one of those). i must tell you though, there are programs that have morbidly obese people drink the same packet of food for each meal several times a day for as long as it takes to get them to a normal setpoint. i know because around the time i went paleo and dropped 60 lbs, a larger gentleman on my job went on one of these programs and lost 140lbs in the same period of time. is that the way people should do it? i don't know. he lost a lot of muscle mass with his and looked deflated at the end while i actually gained muscle mass and only lost fat during my experience. i guess it depends on on what one's goals are from a health and aesthetic perspective. the only thing i notice now though is that he is having a hard time now adjusting to real food because he is very paranoid by what different foods will do to his weight. as for myself, i actually just eat whole foods and worry less about macronutrient ratio knowing that my setpoint is pretty consistent where it is now. i think the psychosomatic response to people losing weight via a very bland diet is also something to consider for trying to get them adjusted to a feasible manner of maintenance eating for their particular lifestyle.

Stargazey said...

@luckybastard: i must tell you though, there are programs that have morbidly obese people drink the same packet of food for each meal several times a day for as long as it takes to get them to a normal setpoint.

I didn't know that. But according to the Food Reward theory, they would have to keep drinking those same packets indefinitely or their setpoints would go back up.

Mirrorball said...

@luckybastard and @Stargazey

Aren't these programs based on very low calorie diets (VLCD)? I'm not sure blandness is a goal. I think the point is providing all essential nutrients and enough protein to spare muscles with as few calories as possible.

Stargazey said...

@Mirrorball, the bland liquid diet I originally referenced was the one here in Stephan's post. The volunteers were "allowed to consume as much of the liquid diet as they wanted, but no other food."

My hypothesis was that if this actually worked, the dispensing machines and the liquid diet formula would be available at the local Wal-Mart, just like weight-loss drugs, exercise machines and low-fat alternatives to conventional foods. The free market would see to it. My guess is that the diet does not work in the long term, but I could be wrong of course.

Mirrorball said...

"the bland liquid diet I originally referenced was the one here in Stephan's post"

But I was talking about the program in luckybastard's comment. I don't think it's the same as the study in Stephan's post.

"My hypothesis was that if this actually worked, the dispensing machines and the liquid diet formula would be available at the local Wal-Mart, just like weight-loss drugs, exercise machines and low-fat alternatives to conventional foods."

I doubt it. There are plenty of naturally bland foods. Do people buy them? No, they buy the hyperpalatable ones with a billion calories per serving.

Derek said...

Wow...some of you obviously hold some strong emotional ties to certain ideas regarding nutrition, metabolism & diet. From a psychological standpoint, you do realize that a strongly emotional reaction, especially a strongly negative one, reveals a vulnerable area that you are protecting from harm, right?

In no way does such a childish reaction convict Stephan, or anyone else, of any error in the information they've presented. It only reveals the attacker's compromised emotional state.

Food for thought.

Ms.Pearl said...

I am shocked at the ad hominem attacks on a man who is one of the most open and least egotistic people out there, scientist, or not. He does not need my defense.

Stephan is devoloping a theory. That is the basis of science. If the theory does not hold water with scientific testing, he will abandon it. He is not trying to blame anyone for their behavior. If you are finding that your reaction to his theory is very emotional, maybe the problem lies with you.


mem said...

++++++ points to Derek and Judy. Absolutely on target.

malpaz said...

i agree with stephen and itsthewoo, however not everyone is like itsthewoo and has leptin to inject post eating disorder(as she does) enabling them to eat whatever and not gain by artificially controlling their hormones via leptin. it pretty much throws your theory itsthewoo out the window. its like telling a diabetic as long as they inject their insulin they can eat whatever, which is true to an extent.

your own food reward problem, and you do have a problem as you said not injecting yoruself leads to overeating and weight gain hence and uncontrolled food reward system, and you theory is not applicable at all...not even 1%.

also put, you have no dog in this debate because you take a human hormone to change every action and reaction from your hypothalamus to your liver-pancreas communication, so IMO, get real.

leptin sensitivity is something that should spike and lower naturally and seasonably. vitamin D enhances leptin sensitivty and sucrose/fructose available in the summer is handled 100% better in a body with adequate vitaminD level- hence the seasonability. leptin sensitivity becomes more resistant on a high fat, ketogenic or 'winter' diet because of the hormonal reaction in the body.

injecting yoruself with leptin everytime you eat like a diabetic for the rest of your life

i do think everything from the unnecessary celebration of food(people eat doritos all happy at a party but they didnt earn those doritos) to the ceremony aspect of food is lost and replaced with a socially acceptable crunch.

i think stephens food reward idea would be better if named differently, prehaps leptin killer because ultimately the foods causing this food reward problem are centered around the brain becoming resistant to leptin and the fat cells not releasing it. if it didnt, then the brain would malfunction, and when the leptin was released from fat cells, the glucose clearance rate is normal, the insulin and BS rise is normal, and the food being eaten becomes unpalatable

bluetooth.Enabled said...

Each individual may not have control over their metabolism, but they do have a say in what and how much they decide to put in their mouth. Food reward may not fully explain why the obese are obese, still eating in excess won't help the obese become less obese either.

Helen said...

I agree with Ms. Pearl and Derek - Stephan is about the least egoistic, least biased researcher-thinker-blogger I have come across. I believe he's engaged in honest inquiry, a process bound to have both hits and misses. He's brave and generous enough to air his evolving ideas publicly rather than just in journals and academic conferences. I'm interested to see how his thinking develops over time. I've already learned a lot from him.

ItsTheWooo2 said...

JD -

Perhaps I am emotionally invested in this. You would be, too, if you had numerous obesity related conditions by the time you were 18 years old. I've a mood disorder (which I do think is strongly related to my metabolic disorder) and at my most depressed I could hardly talk to people and could not leave my house, brush my hair, shower, slept all day. I have had severe PCOS which is horrifying. Reactive hypoglycemia had me crying and anxious ever 1.5 hrs after eating for most of my childhood and teen years and no one knew why - "lol, fatty probably can't be without food, typical fatty". No one has sympathy when a fat 11 year old is crying and freaking out about food. People don't know what blood sugar is, and that sometimes the fattest people are the most energy deficient. When you are 9 years old and having a panic attack in a mall an hour and a half after your farina breakfast due to low sugar, that's not a particularly fond memory.

By the time I was 20, I was almost 300 pounds.

I now know more than 99.9% of the world about obesity and what causes it and as a result I am 115 pounds and have maintained my weight loss for 7 years. My personality is totally different before when I was afflicted with uncontrolled metabolic disorder, my mood problems are no where that severe and I actually enjoy being alive most of the time now, lol (and starts to err back to that state when my glucose is imbalanced - my mood and metabolism have a cyclical relationship; I tend to gain weight and become lethargic when I am getting depressed, and similarly when I mess my metabolism up I start to trigger my mood problems - they are co-related and I have learned that dopamine plays a role in all of this, which then relates to the seasonal patterns of my moods as well as weight gain trends... it can start at EITHER END, low dopamine can lead to glucose disorder, and glucose disorder leads to impaired dopamine signaling).

I've had to spend 30,000 in skin removal surgeries, almost none of it paid for by insurance companies. And still my body is ruined. I have lost a lot of hair from PCOS, my height is stunted, I became extremely obese. I spent years in depression. None of that needed to happen if only doctors knew what they were doing and cared... if they KNEW WHAT I KNOW.

The reason I am so angry is because Stephan is one of the few people out there who seem to kind of get it, so it's very disheartening when I see this back pedaling to "well I guess it was gluttony all along, all we need to do is eat bland food and we won't be fat." It's so very, very very wrong, extremely wrong and its upsetting because my life was (and continues to be) impaired by this biologically real problem which has NOTHING AT ALL TO DO with enjoying food. Some of the thinnest people I know love food the most.

I don't get angry when a regular person who knows NOTHING says "hey look at that fatass, boy they need some self control" but I do get a bit angry when someone I respect says "guess what - palatability of food is what causes obesity, lol! and awesomeness of oxygen also causes asthma!"

ItsTheWooo2 said...

I'm extremely observant, introspective, I've learned SO MUCH over the years. Subcutaneous leptin replacement, even at a very low dose (0.04mcg/kg) is enough to completely make me metabolically like a thin person, assuming I maintain a semi-low carb diet. If I eat a lot I just run around a lot. I have tons of energy. I always feel warm.

Weight loss in an obese person to truly correct obesity entirely will cause hypoleptinemia (translation: it is impossible, because hypoleptinemia will rapidly correct itself in all but the insane .... normal people without razor sharp obsessive motivated personalities will rapidly eat more and move lless thus self correct hypoleptinemia). This is why obese people never lose all their weight - if they try to get their body fat down, their leptin levels become deficient and this drop in leptin prompts hunger, coldness, fatigue. I am psycho, so I am one of the few people who can force off weight (if I am so inclined) and I tend to think thats because my dopamine system is quite sensitive and malleable. I get very OCD and intense in response to food restriction, sort of like a stable form of anorexia nervosa - I can do anything I want, my brain responds to food deprivation like stimulants (dopamine receptors are upregulated, serotonin goes down, and my already perfectionistic intense personality is augmented and I am unstoppable). When I was extremely food restricted and underweight I was completely crazy and intense I would spend hours cleaning and running around unable to stop. However, most people do not have the potential to respond to food restriction this way and do not get this specific obsessive fixated motivated thing in response to starving (which I also think is related to my mood disorder - I have a mild bipolar condition so I think I am very sensitive to anything which may be stimulating such as food restriction). Look at people who do CRON - they are all high on starvation. However, like I said, only a minority of the population responds to food restriction like this and most of them DONT have the co-occurring potential to obesity so all in all its relevant only to myself.

Dopamine agonists do much of what leptin does, as leptin works by modulating secondary dopamine system in the brain. Low leptin (and starvation) depletes dopamine levels which prompts hunger and fatigue. This is why dieting people abuse caffeine and nicotine and illicit stimulants as well. They are correcting a starvation-induced brain defect of decreased dopamine levels, so they feel normal (not hungry and not tired). As stated previously, people who can restrict food are generally good at upregulating dopamine receptors to starvation and so they do not feel the hunger and fatigue as much as others, in fact they may have no appetite and feel quite energetic paradoxically so. Thus CRON and anorexia nervosa et al.

If it was as simple as not eating palatable food, obesity would not be as problematic as it is.

No, obesity is a metabolic disorder, enjoying food excessively is merely the hallmark of that disorder - it is the way the body tries to maintain equilibrium in a disordered state. When the cells are not using energy normally, because of impaired mitochondrial function, because of a shift in energy use secondary to low dopaminergic tone (low dopamine -> glucose intolerance due to a cellular preference for fatty acids leading to elevated glucose in the blood and compensatory hyperinsulinemia which leads to increased appetite). Just like breathing a lot is a hallmark of acidosis, because increased respiration blows off co2 (acidic) and increases o2 (base) eating a lot all the time every day with no compensation of low appetite and increased energy, is a hallmark of things being very wrong in your brain or body.

ItsTheWooo2 said...

But yea, palatability of food simply does not figure in. I do not find food all that rewarding by personality, never have. When I was fat I ate a lot because I was hungry all the time. Now I eat less because I am not hungry. I can eat anything I want - cookies, cake, chocolate. Chocolate is actually a dietary staple because it does not have a lot of carbohydrate in it, and guess what, it keeps me thin because it does not cause hyperinsulinemia and hypoglycemia. I can eat cheesecake for a meal assuming it isn't very sugary, and feel super energetic and full. Why? cheesecake is low in carb and high in fat/protein. Coffee with a lot of cream and splenda is delicious and very rewarding to me, but it makes me feel full and super energetic. Why? Fat plus low carb = low insulin. Caffeine = high dopamine. Self explanatory if you understand obesity.

If I tried to eat gummi bears to an equal calorie portion of cheesecake, coffee with cream, I would be soooo destroyed its not even FUNN-AY. And guess what, gummi bears are gross and nasty to me, not at all rewarding. Or jam on bread? So screwed I would be. Shaking with hypo and ravenous in a few hours. Similarly, jam on bread is pretty gross to me.
Change the jam to sugar free, the bread to diet bread (low starch), and add a lot of peanut butter? Now it tastes GOOD, and I feel full and energetic for a looong time.

So yea, the "food reward" thing has zero relevance to my situation and I suspect the majority of fat people. Fat people like Oprah do not realize why they eat a lot any more than people in ivory towers do. They confabulate reasons such as "its because I use food for comfort", when in reality they only find food comforting because their neurotransmitters and metabolism and endocrine system is backward. If they were high on dopamine and low insulin / balanced glucose/adequate leptin levels they would no longer find food so comforting and rewarding. They'd find other things way more stimulating than food, and similarly if they tried to eat too much their dopamine and serotonin signaling would be like "whoa, vomit this stat, too much too much!!!111"

It's funny, when I was a kid I used to watch Oprah on TV as she would preach to fat people that they really are emotional eaters they just don't realize it. Even at 12 years old I would think to myself "no, I am actually just hungry. I don't like food all that much. I eat and never feel full. I am never full. I am fat because my body does not use food like my thin friends." even as a KID I knew there was something wrong in a physical sense; I am super observant and noticed thin people never behaved like me - after eating they were energetic and tended to move around, whereas for me it was the opposite and after eating I became more fatigued and tired. They easily seemed to feel nauseated from fullness whereas I never felt nauseated from food, I only felt physical pain from fullness but never nausea.

Then when I became thin, surprise surprise I started acting more like a thin person ASSUMING I maintained a low carb diet. I could now feel nausea from eating too much (in fact while in the obese phases of this disorder, I was nauseated 24/7 on a low carb diet, presumably because my fat cells were hemorrhaging fatty acids due to normal insulin levels being unable to keep it in any longer - result being that I was always "full" and finally using my fat for energy).

ItsTheWooo2 said...

This is long winded and no one is reading it, but yea, if you want to know why I am so INTENSE about this, live my life and you'll totally understand why. When you have memories of where I've been, and where I am now, and to have the knowledge which makes the difference between here to there, you'll feel the same way when you read someone like stephan say "food reward is a dominant factor in obesity". SO TRAGICALLY WRONG.

My whole life can be described as that of an ant trying to climb a hill against all odds, defeating obstacles and finding health and wellness and sanity and functioning...I'm tired of the world making it more difficult for the truth to get out ...and this in a microcosm is precisely that.

And thank you if you read any of that long winded nonsense, but things get quite frustrating after awhile, having ALL THIS KNOWLEDGE and having no capacity to apply it, AND being constantly told it's not valid (no, really, the thing is that you like junk food SO MUCH you keep eating and eating it - thats why youre fat - BEYOND WRONG, why does farina make me ravenous which tastes like cardboard meanwhile cheesecake tastes awesome so does creamy coffee with splenda but this keeps me full and energetic and humming along?)

Derek said...

So let me get this straight. If someone such as Stephan posts articles that don't match up with "all this knowledge" that you already have, then they are "tragically wrong" as well as "making it more difficult for the truth to get out"? Does that about sum it up?

If this is the case then I guess he should just turn the blog over to you. That would be the only way it would line up perfectly with all of your hard-earned nutritional & metabolic mastery.

This is not sarcasm, either, by the way. I'm just using your own words to show you how biased and self-serving your arguments really are. Part of the beauty of the blogosphere is that numerous knowledgeable people such as Stephan get to share their insights. I wouldn't have it any other way.

By the you happen to have a PhD in neurobiology and professionally study the neurobiology of body fat regulation? Stephan has a lot of credibility with a lot of people because he combines credentials with excellent insight and a desire to get to the truth no matter what it looks like.

ItsTheWooo2 said...

I don't have a phd in the neurobiology of body fat regulation, but I have lost 160 pounds and kept it off 7 years and this was not at all by accident, luck, or surgery.

Can ANYONE ELSE here say that, and if so, what do you think about this "food reward" stuff? It's funny how it's always the people pontificating from afar who support this nicer sounding label for gluttony.

Here's a question. If food reward causes obesity, why does some of the grossest food make me eat more and gain weight (pretzels, rice cakes, bread and jam)... but if I modify those nasty foods to taste BETTER I actually eat less and feel more energetic? Say I swap a rice cake for almonds. Energy for days and no appetite.
Lets say I ditch the full starch bread and sugared jam, for low carb bread and sugar free jam PLUS add high fat/high protein/low carb peanut butter. Full, satisfied, and tons of energy.

Food reward has no role what so ever in my weight control and I suspect this is true for anyone who figures out how to lose weight and keep it off, because food reward DOES NOT CAUSE OBESITY. It may, howeve,r worsen existing metabolic disorders. If given a choice between potato chips or rice cakes, a person who's hungry all the time and really enjoys food because of that hunger, will certainly choose the yummier tasting food (which is clearly potato chips). However, "hunger" and "yumminess" self terminates in a person who is not actively becoming obese, because in a weight stable person, there is a point where you stop thinking food is yummy, you become nauseated, you feel sick upon the prospect of eating more. Unless, of course, your fat cells are an insulin sensitive one way depot of body fat under hyperinsulinemic conditions. Then food never stops being yummy no matter how much you eat, and if you DO experience fullness it is very temporary. Trust me I've been there.

CarbSane said...

Stargazey wrote: ItsTheWooo2 brought out some points that are relevant to this discussion. When you have experienced the realities of morbid obesity, it becomes frustrating to read an academic discussion stating that a major factor in body weight setpoint may be determined by food reward.

If it were easy to lose massive amounts of weight by eating bland liquid food through a straw, there would be dispensers and packets of the tasteless food available at every Wal-Mart.

I agree but this leaves out one factor - choice. If folks know and believe low carb foods are slimming, for example, then why do we ever eat anything else? Outside a metabolic ward, those bland liquid dispensers would probably be next to the ice cream freezer.

I think this academic view does, however, go quite a way to explain the obesity epidemic. IOW, why so many more of us at younger and younger ages are getting fatter. I'm still not getting the setpoint thing. Perhaps rather than re-setting it just overrides. That makes more sense to me based on my experiences.

As to ItsTheWooo2, I think what you are describing (and I'm not familiar with your situation other than reading your posts here) is akin to that of the kids Lustig treats. Lustig works with hypothalamic obesity - kids who've had radiation treatment for brain tumors leading to a dysfunctional hypothalamus. Lustig's work, however, tells us little about how a person that starts out normal eventually becomes obese. Hope that makes sense. Congratulations on your success!

As to ItsTheWooo2

WilliamS said...

This notion of "food reward" is not just a "psychology term," as Stephan characterizes it, but specifically a term deriving from the behaviorist tradition within that field. In this regard, it might be useful to review what is still probably the most fundamental critique of that general approach to understanding human behavior, Noam Chomsky's 1959 review of B.F. Skinner's "Verbal Behavior." It is framed in a different context of course (language rather than eating), but it speaks directly to the value of behavioristic concepts such as "reward" for understanding real-world human behavior ("play-acting at science," in Chomsky's unsparing view). In addition to the fundamental conceptual and methodological critique, Chomsky's comments about the extrapolation of concepts useful in discussing highly controlled laboratory experiments to real-world human behavior seem particularly relevant here.

luckybastard said...

Having lost a signifcant amount of weight before doing it different ways every time, i can attest to the fact that there are a myriad of ways to knock the lbs on given a person's particular situation. that weight staying off depends as much on the person's lifestyle and idiosyncrasies. i communicate with other formerly obese and some have gotten it off and kept it off with calorie counting/restriction, low carb, low-fat, and paleo. paleo has worked the most effective for me in loss and maintenance(low-fat only worked when i was killing myself in the gym, low carb wasn't sustainable in the long-term for me and i'm not a calorie counting type person). i don't think there's any once "right" way to lose the lbs, however, i do believe that the pathways that stephan has helped me to understand, via this blog, are the main thoroughfares that each of these diets feed into to get fat loss results.


i think many drs and scientists who are seriously looking at obesity would agree that leptin signaling is where the focus should be now. my question for you is, do you think that subcutaneous leptin injections is the answer for the majority of obese people? if good effective eating habits can be learned by an obese person and adapted into their lifestyle, do you think that would be more "natural" than injections? have you considered that maybe your situation is an anamoly or that you're specific case is an outlier?

Ed said...

Hi Woo,

I read most of your comments, but not all.

I think a missing link for you is that perhaps you don't understand the mechanisms hypothesis well enough.

I hope I get this right.

"Food reward" affects body fat setpoint. The "thermostat" for the body fat setpoint is the hypothalamus. The hypothalamus takes input from pleasure center nerves as part of its decision as to what the setpoint should be. Hence the input of "food reward" in the setpoint setting.

How does the hypothalamus know when the setpoint is achieved, when it is too high or too low? It knows via leptin signalling.

Fundamentally, the body fat setpoint concept is a hormone signalling concept that takes into account the pleasure center input into the hypothalamus.

Additionally, the setpoint can get out of whack through other problems, for example hypothalamus inflammation. Like putting a towel over your thermostat.

As some others have noted, I'm not sure that your experience is incompatible with this model. Your experience could be explained by one of the steps of the model gone awry. For example, you mentioned you had emotional problems. I could imagine that this is related to the neurotransmitter system that Emily Deans wrote about. If that system, which has inputs into the hypothalamus, were to cause the hypothalamus to either move to a higher setpoint, or through some mechanism to become insensitive to leptin, then your symptoms would match the expected results.

Additionally, just the fact that you have to inject leptin to maintain your current low body fat setpoint, is consistent with the hypothesis -- your hypothalamus is operating at a higher setpoint, and you are tricking the system with exogenous hormones to maintain the current lower setpoint.

None of this is intended to trivialize your or other folks circumstances. This is certainly far more complicated than I understand, and Stephan so far has elaborated far too little about the mechanisms and components of the model to be able to apply it to anything but the simplest scenarios. If only Stephan had the urge to write and elaborate like Peter! Peter gets accused of being complicated and obtuse, so I guess there's a trade-off there. (I wonder if we can tweak Stephan's elaboration setpoint.)

I encourage you to keep an open mind, for although you are more educated than 99.99% of the population, I feel that this model might yet lead to further enlightenment.

ItsTheWooo2 said...

Malpaz -

You're right, not all of us have subcutaneous leptin to inject status post severe weight loss (my history of mild eating disorder is completely different, FYI - just as much as a heroin addict has only a superfluous overlap relationship to someone who needs pain killers due to chronic pain).

Yes, we DON'T have subq leptin... but my whining and ranting is an attempt to change that. Because, for obesity which has already occurred, leptin augmentation is ABSOLUTELY ESSENTIAL to effortlessly and naturally maintain a lean state. This is because insulin doesn't just make fat cells expand, it also makes them multiply. More fat cells means you NEED more fat mass. Body fat is an endocrine organ, period. You can NOT just deplete your body fat and act like "okay, now you will feel and behave just like a naturally thin person!" It doesn't work like that. A hypotrophic fat cell does not make leptin normally. A woman who has a BMI of 22 (but used to weight 300) is nowhere NEAR in the same position as a woman who has a BMI of 22 and has never been overweight. The 300 pound woman who has dieted down to a BMI of 22 has numerous hypotrophic adipocytes which do not make leptin normally, and her leptin level will be very low. She will feel tired and hungry all the time even if she is no longer dieting and losing weight. She may even have starvation sequelae such as hypothalamic amenorrhea, in spite of a "healthy body fat level", because for her insulin damaged body "healthy body fat" is actually underweight.

Just like a cancerous tumor, insulin makes fat cells multiply, and those fat cells do not go away when you lose weight. Some of them do, most of them don't. They stay small, hypotrophic, giving the body an uneven look (all bones and horror in the shoulders, but the thighs and but are full of fat - why? Answer: butt and thighs are very sensitive to insulin stimulation thus fat cell multiplication, shoulders are not. Shoulders are an accurate representation of the nature of your fat tissue - jutting bones in shoulders means your fat cells are tiny, and are not making leptin, no matter what you weigh or clothing size).

This is why fat people do not become uniformly obese, they become obese in specific areas. The reason for that is obese people are very sensitive to insulin in their fat tissue, AND only in specific body sites. Women generally means thighs, butt, hips, breasts, upper arms as well as stomach. Men, stomach, upper body, face/chin.

The truth is leptin is REQUIRED to healthfully and happily remain thin after weight loss especially for females (testosterone is dopaminergic and may replace much of leptin's metabolic effects - the female reproductive system becomes highly sensitized to leptin at puberty, and there is a three fold increase in leptin for women, an effect separate from the increase in body fat as estrogen increases leptin receptors and leptin level - testosterone has the opposite effect and suppresses leptin, desensitizing the body somewhat to the need for leptin).

I'd rather hear the truth rather than hope on a prayer far fetched and sketchy theories that if we just ate bland food we would all be thin and feel great. IF ONLY.

ItsTheWooo2 said...

Here's a novel idea. What is important for weight loss is not necessarily important for weight maintenance and vice versa. To correct obesity it's all about correcting hyperinsuliemia - you need to get that insulin down, you need to mobilize fat out of the fat tissue. Stable low insulin & blood sugar, fat easily being released from the fat cell, it all happens from there. Basically you need to do some kind of diet or exercise program which results in a decrease in insulin, AND it has to be maintainable for life. For the overwhelming majority of obese people they will find this is a reduced carbohydrate, reduced calorie diet. It needs to be healthy enough and enjoyable enough that you can do it every day forever.

To maintain the post obese state it's all about correcting hypoleptinemia - you need adequate leptin levels to tell your brain "hey, we DIDNT just lose 180 pounds - april fools! Lets keep feeling awesome and satisfied and energetic and making energy in spite of the fact our fat cells are super duper small, because leptin injected in our stomach is telling our brain and body that our fat cells are normal sized." Because the KEY to maintaining your weight forever, is having your metabolism work like that of a person who never lost weight, and this is possible via leptin augmentation. Not having leptin amounts to starving your entire life - feeling cold and tired and hungry and if female having amenorrhea if the leptin deficiency is severe enough.

It is not appropriate to compare a post obese person using leptin, to a diabetic using insulin. The analogy is only appropriate if you mean a type I diabetic, because that is exactly the situation a post obese person is in (fat cell hypotrophic leads to hypoleptinemia and its consequences, much like beta cell death leads to hypoinsulinemia and its consequences). A type II diabetic using insulin is typically masking metabolic disorder, which is not at ALL what replacement leptin is doing for me. I literally do not make leptin after weight loss, my leptin level was like <2. For comparison, someone with severe lipodystrophy makes about <1 of leptin, and a typical female can expect to have a level around 10-20 assuming she is lean. Men make less leptin but then again men need less leptin due to testosterone being so dopaminergic (and this may be why men find it easier to lose weight - their physiology is not tied down to body fat).

I do not believe in th eleptin resistance theory of obesity either, so that argument is invalid as well. In case you did not understand, I TOOK VERY LOW DOSE LEPTIN, 0.04mg/kg which only raises basal leptin by about 10-15 effectively speaking (later on due to non-neutralizsing antibody generation the measured serum leptin may be much higher, but again most of this is not bioavailable, it is just attached to antibodies and so skews the levels measured in blood tests... but in a person making no antibodies 0.04mg/kg will bring leptin up 10-20 ng/ml. Which is approximately low normal female range.

Again, post weight loss, successful weight loss, meaning NO OBESITY remaining, will always result in hypoleptinemia. This rarely occurs, because hypoleptinemia is a self limiting obstacle to further weight loss unless you are a motivated nutter like myself. Normal people typically eat a lot and stop losing weight at that point in order to correct and stabilize the hypoleptinemia.

This has nothing to do with taking abnormal amounts of leptin and creating an abnormal situation in your body, and besides, that doesn't even work for obesity because obesity has nothing to do with leptin (weight loss, on the other hand, DOES).

Leptin resistance is highly controversial and in my experience has no relationship to obesity at all. I am very sensitive to even small amounts of leptin. This would not be expected if leptin resistance causes obesity.

ItsTheWooo2 said...

luckybastard - IMO the scientific community is completely wrong about obesity and has been for decades, so I am not at all surprised that they are chasing this "leptin resistance" bullcrap to nowhere.

It is ALL based on false hypotheses that have been falsified so many times but they still pursue it because their arrogance and lack of curiosity and willingness to admit their foundations were wrong in the first place promotes tons of unproductive research directions.

How did the leptin resistance idea come about? I will tell you.

In 1995 or so they discovered a new hormone called leptin. In certain strains of mice who become fantastically obese (mice who are congenitally leptin deficient), it turns out that giving these mice leptin injections results in a total correction of their obesity and the neuroendocrine abnormalities typified of it.

Of course they were super duper excited and the patent to leptin sold to amgen and so the research began.

However, when they tried these injections in obese HUMANS they discovered it had no effect what so ever on their obesity. It was also discovered that obese people had elevated leptin compared to thin people, not low leptin.

Leptin did cause weight loss in one group of overweight humans and that is humans with partial or complete leptin deficiency. This is a very rare group of people and usually cosanguinous (as leptin deficiency causes infertility it is rarely found in nature).

Rather than these scientists stop and reexamine their original hypothesis - that a lack of leptin signaling may have nothing at all to do with obesity - instead they IRRATIONALLY modify their hypothesis to state that obese people do not listen to leptin and that is why they are fat. There is ZERO evidence for this statement, other than the fact that their wonder drug didn't work.

ItsTheWooo2 said...

In my experience as a fat person who is also not stupid, weight loss and weight gain are not as simply defined as opposites of each other. It is totally possible for your leptin receptors to be saturated, but to STILL become pathologically overweight, assuming your glucose metabolism is FUBARed.

Science has this one track mind about obesity and tends to apply situations which are true some of the time, and assume they must be true all of the time.:
"Well, if bolstering leptin deficient signaling causes eating less some of the time, then any time one eats too much it must be because leptin doesn't work. Therefore, all obese people who are eating too much must be doing so because they are leptin resistant, as we have already found they are not leptin deficient".

It would be like saying:
"well, if one does not buy frappiccinos from starbucks and saves $200 a month as a result, that means every time someone goes broke its because they are clearly going to starbucks too often. Therefore, all broke people go to starbucks way too often." Nevermind the fact most poor people don't even drink starbucks.

If leptin resistance caused obesity most of the time, then my story could not have happened. My entire metabolic/endocrine/nervous system situation would not have altered itself in DAYS upon inducting to a very low carb diet. In people who are congenitally leptin deficient it does not matter at all much if they low carb high carb low fat high fat - they are starving 24/7 because their brain is not seeing the leptin signal. Their whole body is under the impression they are starving to death 24/7, thus hyperphagia and decreased T4->T3 and higher cortisol output and hypothalamic amenorrhea and diabetes upon eating (glucose intolerance) etc etc etc.

My brain clearly gets the leptin signal, and gets it well, its just that HYPERINSULINEMIA due to an UNRELATED BLOOD GLUCOSE DISORDER which has no relationship to leptin signaling, was causing pathological body fat gain, and this pathological body fat gain caused hyperphagia and a totally different set of symptoms from leptin deficiency.

Obese garden variety humans have no phenotypical similarities to leptin deficient humans. If you do some research you will see this, that the leptin deficient (no leptin signaling) obese person is a very different animal from garden variety obese.
Everything about garden variety obesity suggests leptin is working adequately however something else is wrong causing pathological fat gain. That something else, most of the time, is hyperinsulinemia secondary to glucose disorder.

Hey, science is wrong ALL THE TIME. This is nothing new at all.
Remember when they said fat causes heart disease, but oh wait it's not all fat it's just bad fat, but wait it turns out fatty acids are super healthy and actually we require essential ones to not feel and look horrible and get very sick? Oh wait, omega 3 fatty acids actually PREVENT heart disease. Woops. And wait, cholesterol drugs cause dementia and brain decline. And that margarine crap actually causes sickness meanwhile we were telling everyone its so much healthier than butter. But lets not say that too loudly or else our financers will be upset.

Leptin injections will not help people presently obese, HOWEVER in people who have learned to control their hyperinsulinemia thus deplete their body fat, leptin injections are necessary to mimic a normal weight non-obese state, just like insulin injections are necessary for a type I diabetic who wishes to mimic a healthy normal pancreas. The post obese person has obliterated their body fat, just like autoimmunity destroys the type I pancreas. Hyperinsulinemia in an obese person permanently increases the # of fat cells in their body requiring a very large volume of body fat in order for normal leptin production - "normal weight" no longer applies to these people because they will find it impossible to truly be normal weight any more.

ItsTheWooo2 said...

Leptin is only relevant in two conditions:
1) body fat atrophy (post weight loss, lypodistrophy, etc)
2) congenital leptin deficiency/insufficiency.
This is because leptin regulates minimum body fat mass and does not regulate obesity, other than to say that when leptin is abnormally not being made a person can become obese (or when a person has leptin resistance they can be obese but thats veeeery rare, just as rare as pathological leptin insufficiency).

There are, I am quite sure, rare cases of leptin resistance, of leptin receptor mutations, which cause obesity, where in which leptin can never help (even if the person loses weight, leptin replacement will be of no benefit as their receptors do not work properly). However, fortunately for most fat people, this is only rarely a case in obesity and most of us have leptin receptors functioning normally. As I said, I am very leptin sensitive and my highest weight was 280 lbs. I did not get fat because of leptin I got fat in spite of it - insulin trumps leptin and insulin is regulated by a lot more than leptin.

Helen said...

Hi ItsTheWoo -

I think one way you misunderstand what Stephan is saying is that he's categorically *not* saying that thin people and obese people are metabolically identical, just that thin people have better self-control. I think he's saying that a "highly palatable diet" is triggering the conditions of obesity in some people because of their metabolic profile, while it does not do that in thin people.

Since a tendency to gain weight seems to be the norm in America, at least, it seems that whatever conditions we're experiencing (whether it's the nature of the food supply or other factors) are not compatible with most people's metabolic profiles.

Although I've had only minor problems with my weight, I can relate to what you way about dopamine. I'd be interested in whether other dopamine agonists - I'm thinking behavioral - can substitute for eating highly palatable food in most people, or if a tendency to being particularly affected by food reward is something unique in the spectrum of disordered dopamine signaling.

My current dopamine agonists are internet addiction and orthorexia. I suspect that I'm not unique among the readers of this blog! ;)

Stargazey said...

@ItsTheWooo2, I've only lost and kept off 70 pounds, but my experience parallels yours. After seven years, the excessive hunger is still there, even when I eat bland food. The drive is nothing like it was on my old high-refined-carb diet, but it doesn't go away. And yes, I can "choose" to eat less, but having a constant battle raging in my brain is not a pleasant way to live.

The idea of a permanent leptin deficiency seems to be a plausible explanation for the apparent drive to regain some of my lost weight. Fortunately I take exogenous T4 and T3, so I'm not cold and lethargic all the time. But I need to use tricks like caffeine and fat fasts with coconut oil to keep my appetite under control. I've often wondered why so many women do low-carb and never make it to goal. Your hypothesis about the need for exogenous leptin in women who have lost large amounts of weight deserves at least a couple of clinical studies to see if it is a valid explanation.

malpaz said...

itsthewoo...i agree with everything you said, i never persay disagreed. BUT, my beef is how you explain it...

if i get it correctly, you lost weight and rather induced an anorexic dopamine agonist like reward system in your brain. this is exactly the same brain i have. regardless of the situation, i come from a incredibly bad anorexia background, however i DO NOT have the leptin i need in my brain despite being the same BMI as you give or take. i know for a fact that a LOW DOSE LEPTIN would correct my hypothalamic amenorrhea, however i do not have that kind of money.

i am more interested in how to get the brain to start working correctly again in the absence of an exeng. hormone injection.

so please, share your knowledge :)

Might-o'chondri-AL said...
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Derek said...


My own weight loss seems to parallel Stargazey's in pounds lost, in that I lost 65 lbs, going from 250 to 185. I started with a BF% of 40 and now am at 15 (I gained about 15 lbs of muscle in the process via weight training).

My question to Wooo is at what point would you define someone as obese enough to encounter the "permanent" problems you seem to be advocating here? Where's the line? How many pounds? Is a BF% of 40 not high enough to meet the definition?

The reason I ask is because my weight loss does NOT match what you describe. I have NO PROBLEM keeping the weight off and NO PROBLEM with uncontrollable hunger. I DO NOT need leptin or any other exogenous hormone. I have lots of energy. My mood is fantastic. So when you say that leptin is A MUST for someone who's already been obese you are obviously exaggerating more than just a little. In fact I would go so far as to say that you WANT this to be true in order to give credence to your own actions. However, I can categorically say that your position is FALSE.

The first 25 lbs was due to a low carb paleo diet and vigorous exercise. I plateaued there and couldn't lose another pound no matter what I did. Then I switched to more of a Mediterranean type diet with low to moderate carbs (focusing on fish for protein and keeping most of the grain out). This cut my SFA intake drastically. I dropped another 15 lbs.

Lastly, I did what Stephan seems to be advocating in that I stopped trying to increase the palatability of my food by using various cooking methods and lots of spices, sauces, etc. I began to focus solely on whole foods as close to their natural state as possible. No more grilling, frying, spicing, saucing, sweetening, etc. I consumed lots of legumes, fish, olive oil, veggies, fruit, nuts, salads. I eat a few eggs but not a lot. My meat intake has dropped off a cliff. Everything is minimally processed if at all. The food is not "bland", it is natural in it's flavor. Big difference.

Guess what? The pounds began to pour off me like water. Whereas the low carb paleo and even the Mediterranean diets were a bit of a struggle, this manner of eating has become easy. My set point has most definitely lowered in response to eating nothing but whole, natural, unprocessed, unflavored, mildly cooked food. I did this by "instinct" long before Stephan began this series of posts.

Am I the exception? No...I would say that YOU are the exception. Yet you seem so badly to want to be the rule. Why is this?

Stargazey said...

@Derek, Wooo wrote quite a bit, but one of the relevant sections is here:

The truth is leptin is REQUIRED to healthfully and happily remain thin after weight loss especially for females (testosterone is dopaminergic and may replace much of leptin's metabolic effects - the female reproductive system becomes highly sensitized to leptin at puberty, and there is a three fold increase in leptin for women, an effect separate from the increase in body fat as estrogen increases leptin receptors and leptin level - testosterone has the opposite effect and suppresses leptin, desensitizing the body somewhat to the need for leptin).

You, Stephan and most of the commenters here are male. I am female and so is Wooo. I don't know if Wooo's statement about leptin sensitivity in males vs. females is true, but if it is, that could account for the difference between your experiences and ours.

Mirrorball said...

I'm female, lost weight from 200 lb to 124 lb. I also have no problem keeping the weight off and no problem with uncontrollable hunger. I have lots of energy and have been exercising more than ever. I eat simple home-cooked food, lots of carbs from starchy vegetables, but also meat, poultry and fish. I don't take hormones either and intend to make sure I never will, because it seems exogenous leptin make you rude and arrogant and unwilling to even listen to different views.

Stephan Guyenet said...

Hi Itsthewoo,

I understand that my post struck a nerve for you, but I'd appreciate it if you could be more level- headed about it. You are misinterpreting what I wrote as well as the scientific literature surrounding leptin signaling.

I do not believe that obesity is caused by gluttony or sloth, but I do believe it results predominantly from food choices, which do eventually lead to energy imbalance due to alterations in the homeostatic mechanism. One of the ways to alter fat mass homeostasis is food reward, and I think that's a dominant route to obesity and perhaps the most common. I do not consider it a "moral failure" to eat unhealthy food that is under your nose, socially accepted and in some cases even considered healthy. I think one of the main problems is simply a lack of accurate information.

I can't claim that food reward is the cause of obesity in all people. It's possible that it was something else in your case.

Your characterization of the evidence for leptin resistance is flippant and incomplete. Leptin signals in large part through STAT3 signaling, and leptin fails to phosphorylate STAT3 in obese animals when injected into the brain even at a massive dose. I do think it's possible that the alternative hypothesis-- that the homeostatic mechanism is working at full tilt in obesity but simply being overrun-- will turn out to be correct, but at this point it seems like the less likely possibility. I'd be happy to discuss that hypothesis if you calm down.

Stephan Guyenet said...

Ps- leptin does cause fat loss in common obesity, it just doesn't cause enough to make them lean. Yet, as you know, Rudy Leibel's group has shown that leptin replacement corrects the metabolic compensatory response (lowered metabolism and thyroid, etc) that occurs in obese people who have dropped weight by restricting calories.

Derek said...


Yes, I considered the possibility of different reactions between men & women. However, I still disagree that the body can be "broken" and beyond repair, therefore necessitating exogenous leptin injections.

There are natural ways to accomplish just about any metabolic goal. For example, I just read a study where men & women engaged in weight training. After 6 weeks the men showed substantial increases in testosterone, but in women it took 8 weeks to show similar results. Bottom line? Testosterone can be increased in women with weight training although it may take more time than in men. And if testosterone can mediate some of the effects of leptin then it stands to reason that vigorous, sustained weight resistance training in women can be beneficial in this area.

Using a natural method takes more time, much more effort and can be a psychological and emotional test. However, in the end the results are better and are permanent as long as you maintain your lifestyle changes. And one of the biggest benefits is massively increased self-esteem which allows one to live their life without the need to attack others who disagree in order to defend one's health choices. The vulnerability is removed.

It would be nice to "retire" from a healthy, vigorous, hard-working lifestyle and have the results be maintained until you pass on. Real life isn't that way, though. As a case in point, most of the diabetics I've known are more than happy to use insulin as a replacement for effort and diligence. But later in life they have all suffered, sometimes tremendously. I've known one person, my dad, who never graduated from metformin to injected insulin and who also has remained very vigorous in his physical activity and work. Guess what? His health is fantastic. Strong as an ox and looks 15 years younger than his age (he's 70). It's a testimony to what sustained effort over long periods of time can do.

I hope Wooo doesn't take this personally, but in my opinion modern America is filled with individuals who have been greatly compromised by modern culture including diet and who do not resemble our hardy, vigorous, hard-working ancestors many of whom had a mindset of overcoming challenges with sustained effort over long periods of time until the goal was reached. For modern Americans it seems leptin injections would be psychologically, although not physically, appropriate.

Helen said...

Derek -

You said: "However, I still disagree that the body can be 'broken' and beyond repair, therefore necessitating exogenous leptin injections."

Are you talking only about obesity or about other conditions?

Although there are many conditions in which self-help can lead to health improvements, and many common ones for which that should be the primary approach, if you are talking about all diseases, your argument is easily falsifiable.

Mario said...

Thanks ItsTheWooo2! You have answered some questions that have been troubling me for a long long time and that could'nt be answered from any of the nutrition bloggers I am aware of. Maybe it is a prerequisite that one was once obese enough to actually comprehend what metabolically dysregulated means.

Anyway, reductionist science is not the way to explain obesity. Is'nt that also why medical science is failing so bad?!?

Anyway, thank you!

To the person that questioned the PhD status of ItsTheWooo2:

You have lots to learn!

bluetooth.Enabled said...
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Stargazey said...

Here are two of the Rudy Leibel articles that Stephan referenced earlier.

Low Dose Leptin Administration Reverses Effects of Sustained Weight-Reduction on Energy Expenditure and Circulating Concentrations of Thyroid Hormones

Low-dose leptin reverses skeletal muscle, autonomic, and neuroendocrine adaptations to maintenance of reduced weight

Might-o'chondri-AL said...
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Derek said...


Not saying drugs are necessarily bad, just not preferable. Not first choice. That's all. No need to take my position to the extreme. I didn't.

Derek said...


You quoted my comment verbatim and then proceeded to expand upon it in a way that is clearly not in my wording.

Is leptin a treatment for all diseases and conditions? If not, then you added substantially to my comment. That's not what I said. I specifically referred to leptin injections. Nothing else. I think that is perfectly clear in the words of mine which you quoted.

Derek said...

For anyone who supports the leptin injections post-weight-loss, how long do you think the treatment would need to continue to maintain the status quo? Till death do you part? Does that sound like a reasonable solution? Not to me it doesn't. I guess that's my point in a nutshell.

Helen said...


It wasn't perfectly clear to me - that's why I asked. You did give a couple of other examples that didn't have to do with leptin injections.

Anyway, thanks for clarifying.

Derek said...


I haven't always felt this way, but I do strongly prefer the natural way over the synthetic in any situation in life at this point. Sometimes it bleeds through a little strongly. I guess I felt the need to counter Wooo's over-the-top diatribe against Stephan as I felt it was way over the line. Sorry if I was too heavy handed. Anyway, you're welcome.

Might-o'chondri-AL said...
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Sara said...

This is a very interesting discussion and a super fascinating subject. As Stephan has said, it's not the 'whole' picture with eating behaviour, but it is a part of the picture that is worth looking into. There is actually quite a bit of hard research into food reward and appetite which I'm reading in my 'spare' time...

As mentioned by another poster, I am interested in whether starvation does something permanently to the food reward feedback system or to some other eating trigger. This is purely because I have five cats that I used to feed ad libitum. Since I took on two strays (at different times) that were both starving when I got them, I've had to stop this. Both previously starving cats have continued to eat like starving strays even though one is now just over a normal weight and one is distinctly fat.My other cats, that have been well fed since birth, are all sleek. I would be interested in what anyone else thinks about this and if it might be related to some disruption of food reward. The reason I do not blame their food bingeing on psychological trauma is that when I change the brand of catfood they all eat less for a while, so I think it's a smell/taste thing (I don't think cats taste much, do they?).

Healing that said...

At first, the concept of "Food Reward" is unclear to me. thanks to this clarification, I understand it better now.

Austin said...

Hi Stephan,

Do you believe food reward also changes with diet?

For example you or I may find a simple potato rewarding where as most would not. I have found rotating foods to help and this is agreeable to the concept of seasonality as well.

Hi mit-o'chondri-Al,

Thanks for your comments on interleukin-6 and increasaed leptin activity via STAT3. That was news to me and explains why intervals reduce hunger in many. Also what are your thoughts on exercise, TNF and it's induction of insulin resistance in this hormonal milleu?

bluetooth.Enabled said...

@Derek: guess I misinterpreted, sorry.

Eugene said...

Here is what I think is happening. There are two factors for eating too much.
1. Hunger.
2. Feel good from food.

I am sure we had all experienced situations when we were full and by no means hungry and yet devouring that tasty food.

What is probably happening is that we are addicted to the dopamine releasing effects of certain over-rewarding foods.

By not eating any overly-rewarding foods, we eventually withdraw from the addiction and return to normal hunger-driven eating habits.

The set-point for hunger can be inaccurately set regardless of whether we have some kind of food-reward addiction or not.

I suspect that both (if they are indeed independent enough) need to be healed in order to achieve a lean state.

If I am correct, then the only way is to heal both inflammation/leptin resistance AND withdraw from food as a drug.

I think it is totally possible that in many people the problem could be mostly addiction-related and thus they would be most helped by lowering the food-reward.

In others it could be mostly set-point related and they need to focus on eliminating certain foods as well as promote anti-inflammatory properties.

I do not however think that set-point is actually effected by food-reward. I think food-reward literally overshadows the signals of being satiated. Just like drug users take drugs in a manner that overshadows their self-preservation instincts.

Chris said...

Hi mit-o'chondri-Al

So does Woo need intense exercise instead of injections?

Alan said...

>> If it were easy to lose massive amounts of weight by eating bland liquid food through a straw

it was done, and it was easy. And our bloghost explained that very clearly.

did you even TRY it before attacking it?

Kevin Croke said...

Hi Stephen

Do you (or maybe Emily Deans M.D) think that reducing your food reward might have beneficial psychological effects by reseting Dopamine levels?



Stargazey said...

So does Woo need intense exercise instead of injections?

Excellent question, Chris! And would she need to do the exercise every time she ate?

CarbSane said...

@Derek: Why should that not be considered part of the solution?

A Type 1 diabetic must inject insulin until death do they part ...

A person with impaired thyroid function or no thyroid gland at all must take thyroid hormone until death do they part ...

What is so repugnant to you about a formerly obese person taking leptin injections until death do they part if so need be to correct for the hormonal deficiency?

I gotta say, after reading Stargazey's Liebel links I'm thinking about it myself. I've not had difficulty maintaining substantial (around 100 lbs) weight loss, but I remain overweight and am unable to lose more b/c it is difficult to muster the determination to eat even less than I already do.

Might-o'chondri-AL said...
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bluetooth.Enabled said...

@CarbSane good point. Maybe some, perhaps for moral reasons, will rule out drug intervention as a possible choice, but who are they to judge others for how they choose to correct a condition as harmful as obesity?

@those judging Woo2, Disagreeing about whether that choice is right for you is fine, but telling someone else that they're wrong for making their choice, especially when you haven't even experienced the same condition, is like an attack in its own right.

Chris said...


Thanks - that is helpful

Might-o'chondri-AL said...
This comment has been removed by the author.
bentleyj74 said...

My one day experiment with this left me painfully STUFFED at 1303 calories with macro breakdown falling at 51% carbs 31% fat 18% protein.

It's worth mentioning that had I eaten only according to hunger I would have skipped dinner...I considered it...but decided to see what a full day would look like if I didn't. I was under 800 prior to eating dinner.

bentleyj74 said...

Also...nutrition data doesn't like my menu today and says it's strongly inflammatory. Not sure what that means or what the criteria are but potatos get a negative rating and sweet potatos get a positive one. Butter is a negative rating also.

mem said...

I believe there are multiple pathways to obesity. And in the last 20 -30 years or so, I do believe that Stephan's food reward theory, as I am understanding it, has become an increasingly important factor. But this is not to say that obesity does not have neuro-endocrine/biological drivers as well. I believe that there are many what you might call "simple starts" to obesity in these times which do indeed center around food reward. What gets tricky is what happens along the way as obesity progresses in years and degree of obesity. I believe that many people, particularly today, much more so than when I was growing up, (I am closing in on 58,) do indeed start at a simple place of overeating in response to food reward and the number of meals that are eaten away from home and quite literally, on the run. If this goes on long enough with the industrialized-food-like-substances that we are all too familiar with, then I believe that the story changes. We are all familiar with the diseases and disorders related to obesity and I believe that often, long before these make themselves known, there are neuro-endocrine changes that take place that are largely sub-clinical, or at least are not experienced in any discomforting or perhaps intelligible way by the person. I also believe there are other prominent pathways in which neuro-endocrine changes/HPA axis changes precede obesity, such as in persons who have experienced adverse childhood events which correlate with substantial increased risk of obesity/eating disorders among many other conditions/disease states. Up until relatively recently, I think that persons with child abuse histories *might* have made up a noteworthy percentage of the total obese, and especially the morbidly obese. Now, that percentage is dwarfed by the "obesity epidemic," whose main feeders I believe are huge changes in the food supply in the last 40 years, along with huge changes in the delivery and marketing of that supply and the amount of SUGAR and in particular, high fructose corn syrup in the vast majority of products. Along with this, I believe we have experienced a great increase in what are viewed as positive cultural behaviors, which are to my mind NOT positive at all. And some of these behaviors lead to inner states that I believe produce a real craving for REWARD.Heightened anxiety related to high levels of chronic work stress, poor sleep and a high level of existential angst which is all too common in life today can also produce what is interpreted as hunger and perhaps IS actual hunger in some if not many cases.(A high car diet certainly did this for me!) I think we are far less sophisticated and evolved animals than we think we are and perhaps we begin to lose our way and have difficulty interpreting what it is that we are really experiencing and what it is that we really need.This has not been a full statement of "the problem" as I see it, but just a glance. I have about 12 years experiece of low carbing/ancestral eating and lost 90 lbs over two years, hitting goal weight in about Sept 02. I have to say that I disagree heartily with the idea that if Stephan's food reward theory were substantial, that there would be "stations" set up everywhere for "bland feeding" (which isn't the point anyway) and the problem would be solved. This link has much to say about that idea:

Stargazey said...

Mem said, there would be "stations" set up everywhere for "bland feeding" (which isn't the point anyway) and the problem would be solved.

I don't believe I said that. I said dispensers and packets of the tasteless food would be available at every Wal-Mart. What I implied is that they would be available for purchase on the diet aisle right next to the Atkins bars and Slim-Fast shakes. (While Paleo folks may not eat Atkins bars and Slim-Fast shakes for weight loss and weight maintenance, enough people do that it pays Wal-Mart and Sam's to devote significant shelf space to both items.)

I have seen nothing like the set-up Stephan describes either in magazines, or on the internet, or at Wal-Mart. That implies to me that while the 1965 study found significant weight loss in the short term, it probably did not hold up for the long term. In fact, it appears that it did not hold up long enough for the investigators to do a second study. (Stephan, please correct me if I'm wrong on that.)

bentleyj74 said...

It would be a marketing nightmare.

bentleyj74 said...

Atkins bars and slim fast shakes both promise to taste like dessert items.

I'm trying to think just exactly how I'd sell something that promises basically to be so UNsatisfying and UNrewarding short of literal starvation.

"We'd have to break fingers to make you eat too much" is a tough tough selling point especially if there is no means of controlling that it is your only food option.

Stargazey said...

You can sell starvation, though. It was called Kimkins and made a bundle of money for Kimmer. It could produce 100-pound weight loss in the short term, but it certainly did not work in the long term. And I suspect that the bland-food-through-a-straw diet subjects also regained their lost weight.

That's why our earlier discussion of leptin is so important. If there is something that could sustain a weight loss into the long term, that would be a real breakthrough.

Mirrorball said...

"It would be a marketing nightmare."

I can imagine the infomercial: "Meet the No Flavour Diet Shake. While competing products boast a range of amazing flavours that you will love such as chocolate, strawberry and vanilla [an obese model is shown drinking the competing product and loving it], the No Flavour Diet Shake is tasteless and you are guaranteed not to enjoy it [a slim girl drinks a glass of NFDS with a neutral expression]. Drinking the No Flavour Diet Shake is such a forgetable experience that you'll be skipping meals automatically and you will lose weight without trying. [Testimonial. Before and After pictures shown.] 'What I like about the No Flavour Diet Shake is that it's really bland. I mean, just about any food tastes better than it. In fact I would have never bought it again if the pounds weren't dropping like flies.' Call now and get your No Flavour Diet Shake, the no pleasure solution to weight loss."

bentleyj74 said...

I agree that you can sell starvation in the short term...that's pretty much what slim fast does, yes?

I'm not familiar with kimkins but I don't think it's a valid comparison if what I'm currently experiencing has any value as a tool of measurement.

It's been...what? 4+ hours since I completed my 1300 or so calories?

I'm stuffed. STUFFED. I am not at all confident that I could eat a cookie if my life depended on it.

At 1300 calories of 100% nutritious inexpensive unadulterated real food.

The experiment wasn't selling starvation either. People had total freedom to eat to appetite...not something slim fast or atkins bars will fact they are sure to promise that you MUST not exceed your easily exceedable daily allowance if you want to lose weight.

bentleyj74 said...

"The no pleasure solution to weight loss"

Ha! That's hilarious. I love it.

mem said...


If, as in the Eades link, they couldn't even keep terminally ill folks in a cancer trial that basically involved their eating about the equivalent of Atkins at induction level, how many days do you think obese folks would go consuming packets of tasteless liquid and not eat anything else? It would be a "free market" disaster!

silversteph14 said...


Did you try the potato diet or were you eating a variety of foods? Just wondering.

bentleyj74 said...

I ate a variety of foods. Only one largish potato actually. 2 bananas. 1 cup of rice. 1/3C of black beans.

Those were my bland starches du jour.

I also had cafe au lait, tuna salad, braised chicken breast, a hardboiled egg, a sprinkle of cheese, a get the idea.

Stargazey said...

@bentleyj74: I agree that you can sell starvation in the short term...that's pretty much what slim fast does, yes?

No. but if you don't know that, I won't be able to convince you otherwise.

It's been...what? 4+ hours since I completed my 1300 or so calories?

I'm stuffed. STUFFED. I am not at all confident that I could eat a cookie if my life depended on it.

I'm glad that you're stuffed on 1300 calories. If you're able to lose more than 20% of your body weight, talk to me in two years and tell me how you're doing at maintenance.

@mem: If, as in the Eades link, they couldn't even keep terminally ill folks in a cancer trial that basically involved their eating about the equivalent of Atkins at induction level, how many days do you think obese folks would go consuming packets of tasteless liquid and not eat anything else?

(1) The 1995 version of tasteless liquid had 50% carbs, so it wouldn't apply to the terminal cancer patients who couldn't stick to Atkins induction. (2) There are thousands of people who have lived for years on low-carb, and they don't even have terminal cancer. You can find many of them over at Low-Carb Friends. (3) Amazingly, some people who do have done low-carb for many years will use Slim-Fast shakes and Atkins bars (neither of which taste that great) to help maintain a long-term weight loss. So (4) if the bland-food-through-a-straw diet actually worked long-term for weight loss, there are some people who would buy it and make the sacrifice because being thin is worth it to them. My opinion is that it probably doesn't work long-term, but feel free to disagree with me.

paleotwopointoh said...

I've lost 20% of my body weight and maintained the loss for 2 years, through a pregnancy and current nursing. I gained a dozen or so pounds during pregnancy, but they were gone after delivery.

paleotwopointoh said...

Hm. Got cut off. I don't eat much in the way of carbs, though I do eat some. I eat a pretty high fat diet with a lot of fatty meat consumption. I also don't run from fruit and fibrous veggies, and I have potatoes now and again. But in general I am pretty lowcarb.

ItsTheWooo2 said...

@ luckybastard 5/28 5:31am
Why do you assume a "natural" solution has anything to do with this? Sometimes "unnatural" is the prescription. If you work in healthcare you quickly realize diseases are sometimes helped and cured by "unnatural" things. If you get a URI, a zpack will knock it out. There is no zpack tree and that's fine, it works and that's all that matters. Sometimes when an old man's hip gets worn down to bone, an "unnatural" prosthesis being surgically placed will cure him. Vitamins and paleo eating will not cure him.

When you truly get thin, you'll realize it doesn't matter how RIGHT you do it... if your endocrine system is sending a constant signal that you are starving to death, via lack of a leptin signal due to VERY SMALL FAT CELLS, you will either feel like crap 24/7 or alternatively you will give in and gain weight. End of story. Are you a person who is now thin, who used to be fat? If not, you really can't understand what I mean by that. Note that females have a much more difficult time with fat loss because of how leptin dependent we are... men find it much easier to get to a relatively low body fat as stated previously testosterone replaces leptin, whereas estrogen does the opposite and creates a greater dependence on it.

ItsTheWooo2 said...

I understood it well. What makes you think that disagreement means lack of understanding? I told you from my personal experience food taste has nothing to do with my weight status, in fact I usually feel better and happier when my diet is more enjoyable, but it never affects my weight either way, only the state of my metabolism/endocrine system/nervous system does. I do not disagree with set point theory- leptin clearly regulates minimum body fat, thus minimum set point. I only disagree that the taste of food or palatability of diet has any role in it what so ever, and making my diet more enjoyable has only helped me to maintain diet adherence if it did anything at all.

Depression is not an emotional problem, it is a biologically real problem. I go through phases where I see no point in being alive, my body is heavy, I feel a lot of pain physically and emotionally, I am very tired, I am wearing blinders, it's horrible and functioning is difficult to impossible depending on the severity. It is just as real as diabetes, it is a problem in my brain, my nervous system. The fact it is real is why sleep deprivation and bright light therapy will resolve it because these affect my nervous system. I have an extensive family history of mood disorders and mental illness. I have been diagnosed with bipolar disorder.

ItsTheWooo2 said...

@ stargazey 5/28 7:07

Actually the need for leptin status post weight loss is well recognized. The thing is no one cares because there is this false idea that injectible drugs are unprofitable. No one wants to investigate mainstream application of subq leptin for post obese people, they would rather use the findings to develop an oral drug which targets just one or two of the effects of leptin (fact: THIS WILL NOT WORK). The leptin research is being used to try to develop oral drugs which mimic some of the brain effects.

Here's one article describing a 2005 study which found leptin replacement completely prevents weight regain:
"Why lost weight can creep back on"

There were more studies done. A lot of them. No one cares. No one cares because injecting your abdomen every day is a hard sell to a group of people who expect to be told that all they have to do is eat bland food and they will magically turn into jessica alba.

This idea that obesity is entirely correctable via "natural" interventions and simple dietary changes is part of the reason we will never SEE real effective treatments like sub q leptin status post weight loss. It's a shame. Thus my ranting and frustration as I have personally lived the awesomeness of leptin replacement... it pisses me off a cure is right in my grasp but it is ultimately impossible because of stupid thinking and idiots who run things.

And I would NEVER take the pill form of any leptin-based designer drug... it would be rife with complications as all wrong answers are. Leptin after weight loss is as natural as insulin after type I diabetes. It's a cure.

bentleyj74 said...

It will be interesting to see how this plays out. I grew up on a diet very similar to what Stephan described so it isn't difficult at all for me to recreate [or sustain].

I came very close to his macro ratios without deliberation. Listening to his description gave me a pretty good idea what that would look like and actually I don't find it unpalatable at all.

I was suprised by how densely nutritious it was.

re palatability...I do agree that there is a [for lack of a better word] natural aversion or "off switch" to most unprocessed and unembellished foods.

It is very very hard to over ride the flavor change when you are tasting the food itself and not sauce/butter/seasoning.

I could eat 6 cookies in a row if I wasn't too polite or embarrassed but not 6 bananas [and probably not even 2].

ItsTheWooo2 said...

malpaz -
I think I may have misunderstood your earlier posts. I apologize.

If you yourself are recovering from anorexia, and are still presently experiencing hypothalamic amenorrhea, please be aware that your amenorrhea will very likely terminate if your body fat becomes sufficient. Many women who are recovering from HA are actually very underweight. Don't pay attention to BMI it has no basis in science or biology what so ever. All that matters is your body fat. If you have very thin skin thickness, it's likely you are still too thin in body fat in order to make enough leptin. Many women who are extremely muscular will have normal BMIs when in truth they are underweight severely due to emaciated body fat. In the leptin clinical trial I participated in, most of the women were like this - they had HA because they were severely underweight in terms of body fat, but their BMI was normal by technicality of being a body builder.

Another reason anorexic women remain amenorrhetic is that their diets are severely nutrient deficient after recovery. YOu must eat dietary fat to avoid HA. Dietary fat is absolutely essential to make reproductive hormones work. You must have adequate zinc levels. Due to eating disordered thought processes many anorexic women tend to be vegetarian which cause fat and zinc deficiencies, causing HA. You must eat adequate calories and aim for 2000 per day.

Post obese people like myself are a different animal from anorexic eating disordered women, because the problem is not that our fat cells are simply too small... but they are TOO NUMEROUS. Even if I were to gain enough body fat to stimulate leptin production adequately, the numerous fat cells mean this would bring me to a level of body fat that is socially and emotionally unacceptable. In a sense, I can not be thin by natural means any longer because of the damage to my body secondary to morbid obesity. I have way too many fat cells.
In a woman who has never been morbidly obese she does not need to worry about sub q leptin injections - if she restores normal weight and eats a healthy diet she will make enough leptin, because her fat cells are normal. They are not excessively numerous as mine are. A morbidly obese person has THREE TIMES as many fat cells as a normal person. IN terms of endocrine functionality that means she requires THREE TIMES the fat mass for normal endocrine function. The only alternative is leptin replacement plus weight suppression.

A pure dopamine agonist will only intensify hypothalamic amenorrhea from starvation, as dopamine suppresses leptin. Do not use dopaminergic drugs to try to restore your menstrual cycles, it will have the opposite effect due to leptin suppression which will prevent follicle development.

Dopamine only helps amenorrhea which is a direct result of dopamine deficiency - the sort of amenorrhea obese women get like PCOS will be helped by dopamine agonists. Obese women have ovulation difficulties (which is dopamine regulated), whereas emaciated women have problems developing a follicle (which is related to leptin and serotonin deficiencies).

As a rule of thumb, serotonin is dominant during the development of the ovarian follicle, but catecholamines surge during periovulation. If this is thrown out of balance so will menstrual cycle. Dopamine suppressive medications like antiemetics or GABAergic agents will prevent ovulation. Dopaminergic drugs like stimulants will cause a total arrest of the system like hypothalamic amenorrhea in a woman who is already thin.

Rob said...

This probably isn't pertinent but seeing paleotwopointoh's comment I'd thought I'd share. My weight has fluctuated quite a bit since I was a baby (I'm 22.5 now and male).

Infancy to ~Age 4: Very chubby
Age 4 - 10: Skinny
Age 11 - 16: Overweight then OBESE
Age 17 - 19: Skinny
Age 19 - 20: OBESE, my body fat was roughly 37% and because my bone structure, it wasn't very obvious

And it was at age 20 I began my first diet (moderate deficit, high protein) which lasted more or less continuously for a year. There were weeks where I stopped but I was determined. I did some form of resistance training the entire time.

I lost over 20% of my weight. My body fat is now ~14% and I've maintained it for over a year. How? Being mindful of how many calories I'm eating (I know the range of my calorie needs since you're never going to know the exact number as it will fluctuate day to day), keeping the protein high: ~175g a day usually, I don't restrict specific foods and always compensate for days where I know I've eaten in excess (which isn't often).

I also continue to lift weights; in fact right now I'm in a middle of a bulk, eating in a moderate surplus on lifting days and at maintenance on rest days.

I know exactly why MY weight has fluctuated so much, my activity levels were the highest when I was at my leanest. At my peak weight I was very sedentary, no longer walking to class often and having a part time job. I was living with a roommate and drinking beer and fast food daily. However even during my naturally skinny days I was still eating "junk food" daily but again, I was active.

ItsTheWooo2 said...

@Derek -

Regarding the point in which one "needs leptin" , is highly individual and affected by many factors such as present body weight (thinner people in terms of body fat pounds have less leptin), high body weight (the fatter you were, the more leptin you probably need), age when weight was gained (younger weight gain means more fat cells were created), and sex (women need way more leptin than men and are much more leptin dependent than men as men are naturally dopaminergic via testosterone).

I am a prime candidate for someone who has everything against them in terms of leptin. I was super fat (an enormous 280), I am now super thin (a measly 115 at 5'5), I have been fat since childhood and rapidly gained a LOT weight after puberty, and I am a female. Woops, looks like every single factor that affects leptin is against me. No surprise my leptin levels were like negative a million. I probably have a gazillion fat cells given how rapidly I gained weight as a child, and right now my body fat is low even by "normal" standards. I am very thin. After skin removal surgery I wear a size 0. My waist is like 24 inches and my hips are 35.

And you, sir, are a dude, who really isn't all that thin for a man (you are thin but not extremely so), so you can't possibly even begin to relate to what I am going through, or others. Testosterone is dopaminergic and replaces much of leptin's effects, and allows easier loss of body fat and maintenance of low body fat.

And might I add, losing 65 pounds on a man is not nearly the same as losing 160 pounds on a 5'5 female.

I assure you, you never want to experience the way I felt when I was thinner than I am now, for it was truly horrible. The problem is NOT "plateauing" as you seem to think... the problem is having every starvation symptom (google "minesotta starvation experiment) and feeling like the walking dead and never ever being able to stop wanting to eat.

Given the simple interventions which are working for you, I suspect you were never counting your calories. Which means you weren't putting much effort into controlling your weight. Yes for a person who is not watching their calories it is obvious that eating less palatable food will result in eating less.
Unless you were also watching your calories, carbs, fat, protein grams, it is IMPOSSIBLE to say why this intervention works for you. For all we know, eating "bland" food means you are eating less sugar and starch and so your appetite dropped.

ItsTheWooo2 said...

@Stephan 5/28

First I would like to apologize for how intense I was before. I was reluctant to join this discussion because I knew it would be "too much" when I did, and I probably should have stayed out... but here we are. I am sorry, I respect your work, you are very intelligent and I can appreciate you are trying to understand something so complex and challenging as what causes obesity and how to resolve it.

"Ps- leptin does cause fat loss in common obesity, it just doesn't cause enough to make them lean. Yet, as you know, Rudy Leibel's group has shown that leptin replacement corrects the metabolic compensatory response (lowered metabolism and thyroid, etc) that occurs in obese people who have dropped weight by restricting calories."

So, if you do see that leptin has no effect on obese people who are presently obese, but it DOES have an effect on obese people who have reduced their weight... doesn't that suggest to you maybe leptin resistance is not causing obesity... maybe leptin is a passive actor in obesity and has nothing to do with its etiology, other than to say that injecting more leptin will not alter and rectify the derrangments causing an upward trend in body fat? This would be expected if leptin does not prevent obesity, but merely prevents starvation.

I suspect that what might be correct is insulin, when high, or other derangements pertaining to obesity, may FUNCTIONALLY INHIBIT leptin signaling somehow. This is not a true resistance but it is more a functional and temporary situation of the endocrine system to allow body fat gain, similar to how thyroid hormone conversion is temporarily blocked by a low leptin level. Starving has almost all symptoms of hypothyroidism, however one is not hypothyroid - the problem is that their T4 is being converted into rT3, meanwhile it is not being converted into T3 very well. This causes hypothroidism in a sense, but it is functional and rapidly correctable by adjusting leptin level.

Just like it is wrong to focus on the low T3 when dealing with a person who is hypoleptinemic, I feel it is wrong to focus on leptin signaling in a person who is obese (unless it is known that person is leptin deficient or has a leptin receptor mutation). This is probably a downstream effect of the obesity process, facilitative of symptoms (weight gain) but ultimately not causative.

karl said...

Wooo is not wrong - but people that lack leptin is a minority.

What I find incongruent in Stephan's take, is that I see no explanation of why I could only lose and maintain weight loss on low-carb (3 years now) - total failure with even medium carb diets (80-100g).

I think there is too much that we don't know to say with any confidence that we know how it works. Do interleukins play a role, dietary lectins? (which kinds? - there are many)

Do the lowcarb diets work by lowering trygly and thus reducing lectin resistance - do we know any of this with confidence?

Evan said...

Damn, reading all these comments is making me hungry

ItsTheWooo2 said...

@ Might-o"chondri-AL 5/28 2:14

Leptin injected into subcutaneous tissues enters the blood supply and is diffused past the blood brain barrier where it exhibits central effects. I participated in a significant clinical trial which used leptin replacement to treat hypothalamic amenorrhea (it was recently published, if you're curious, I am patient J). This is not a joke, they measured numerous endocrine paramaters affected by leptin, namely TSH FSH and LH, and there is clear cut evidence my leptin receptors in my brain were being activated (or else my LH and FSH would not have normalized, and my TSH would not have increased). There is NO DOUBT the leptin receptors in all brain regions were being acted on upon by leptin.

And, speaking subjectively as a patient, the difference in the way I feel about food, feel in GENERAL is so radically astronomically different, there is absolutely no doubt the subcutaneous injections works centrally.

Think about this logically. If subcutaneous hormone injections did not affect the blood, then insulin therapy would be totally ineffective. But insulin therapy is quite effective subq drug delivery is an efficient way to get drug into blood. Once in blood, it passes BBB where it does stuff to your brainz.

I did not use leptin for 7 years. I wish. I maintained my weight without leptin for the 1st 5 and and I have only used leptin in the last 2 years.

For 3 months I went without leptin 2 winters ago as part of the study. I gained weight RAPIDLY. I went from 53 kgs to 57 kgs in that time frame. 3 months. Note I do have a mood problem with seasonal component and this is prior to discovering light therapy, so I suspect some of the weight gain was simply compounded by the season... I was depressed at the time and that exacerbated the weight gain.

I ran out of my supply 1 week ago. So, we will see what happens. I will be a study of 1... what happens when you use recombinant human leptin for 2 years, and then quit? Am I screwed for life? We'll see, fun times!

Note, I am way more tired, WAY more tired, and my mood is very dim. It feels like I feel when I am in winter fog. I suspect my dopamine levels have dropped like a rock, and I also suspect my T3 levels have dropped. I have been using tyrosine supplements which helped for a few days, but they seem to be working less well lately (most likely my tyrosine hydroxalase will down regulate itself very quickly ).

I had regular ovulatory menstrual cycles while using leptin. Prior to using leptin, I had been totally amenorrhetic for 4 years (which correlates with my wieght maintenance). Will I return to hypothalamic amenorrhea? We'll see! I hope not as estrogen deficiency exacerbates all of my symptoms by causing central leptin insensitivity.

ItsTheWooo2 said...

@sara 5/28 5:53
You are very observant. It is indeed shown that starving prenatally and early postnatally permanently wires an organism for obesity. The way this occurs seems to be via leptin; extremely low leptin before and after birth somehow alters the animal's metabolism. Evolutionarily speaking, this makes perfect sense - if you are born into a nutrient deprived environment you are more likely to survive if you store fat easily. This has been replicated over and over again, starving during pregnancy predisposes to obesity later in life.

Interestingly enough it seems as if becoming very obese and having high leptin does the same thing. This gives credit to the idea that part of the process leading to obesity somehow blocks leptin from working in the brain. (Not necessarily leptin resistance, but a functional deactivating of leptin signaling, similar to thyroid hormone not being converted into its active form in response to food restriction).
"Our study suggests that prenatal nutrition can shape future susceptibility to obesity through alterations in leptin sensitivity and changes in energy metabolism during adult life."

ItsTheWooo2 said...

@ Chris 5/29
No, I don't. Intense exercise would only worsen my leptin deficiency, make my hypothalamic amenorrhea more intractable, and exacerbate my extreme hunger that I had experienced prior to leptin therapy.

Come on people, be logical. If intense exercise made you less hungry, obesity would be solved stat. In the real world where I live, intense exercise makes you more hungry and worsens signs of starvation like loss of body fat extreme hunger and amenorrhea in females.

Seeing as mitochondrial was wrong about such basic pharmacokinetics of leptin use (he does not seem to understand that injecting a drug sends it right to your brain via your blood), I would be just as skeptical of any other prescriptions he doles out (such as his advice to exercise intensely to reduce appetite and increase leptin - lols).

ItsTheWooo2 said...

@ mitochondrial BTW I'm not trying to be disparaging; your comments are interesting... but sometimes when you focus on the pieces you miss the big picture. A peripheral leptin injection DOES exhibit central effects, so the argument that I have never experienced the central effects of leptin replacement is simply wrong.
I suspect you are taking research done on animals who have abnormalities that would prevent diffusion of leptin into the brain and then extrapolating it to those without such defect, like myself and all of us.
ASk a heroin addict if jabbing a needle full of junk makes them feel good, ask them if their brain is stimulated by it. Yes, yes it is.

Regarding your observation that the gonadal state of the person is a very good indicator of leptin signaling, this is brilliant and I myself came to the same conclusion years ago. IF LEPTIN played a role in obesity, we would observe obese people to be hypogonadal, such as I was before using leptin. We do not observe this. In fact the obese are HYPERgonadal and enter an early puberty due to high leptin and insulin levels.

Women often develop PCOS (a disorder where so many follicles are stimulated, normal ovulation is thereby disrupted from high levels of estrogen combined with poor central dopaminergic tone, inhibiting the LH surge, leading to cysts and hyperandrogenism and infertility... exhausted inositol synthesis via glucose metabolism or genetic defect in synthesizing d-chiroinositol may also play a role). In obese males we see similar hypergonadism leading to baldness and signs of high estrogen (testosterone aromatizes into estrogen). Obese men develop baldness and breast development because their testicles produce way too many hormones; these are metabolized into DHT (which kills hair follicles) and estrogens (leading to boobs). It's sorta like being on steroids, without all the muscles, lol.
The high levels of estrogens in the body of the obese man lead to elevated sex hormone binding globulin, which deactivates his tesosterone (in nature, the only time men have elevated estrogen is when their testosterone is too high - increasing SHBG makes sense; nature did not predict obesity and we did not evolve genetics to cope with it properly without causing severe endocrine disorders).
On the other hand, in the obese female, elevated insulin leads to DECREASED SHBG, which makes her already excessive testosterone production more problematic because there is more free testosterone.

The hypergonadism of garden variety obesity is mediated by high leptin and high insulin together.

In leptin deficient humans, none of this occurs. They don't even enter puberty. Their reproductive state is nothing like that of a typical obese human which is marked by hypergodnadism. It is universal that when body weights increase, age of onset of puberty decreases. Garden variety obesity is HYPERgonadal, arguing for evidence of excessive leptin activity combined with excessive insulin activity.

ItsTheWooo2 said...


Another major role in the "obesity epidemic" is the fact that our metabolism is imprinted prenatal and postnatal.

If your mom was slightly pudgy and just a smidge prediabetic, you will be fat and gestational diabetic, and your daughter will be obese and get full blown diabetes at 45, and her daughter will be even fatter and have diabetes earlier, etc.

All those "healthy thin people" a few decades ago were actually not so healthy, and their high insulin and leptin while pregnant programmed your mother to be a little heavier, which in turn made you even fatter.

Why do we have obese, diabetic toddlers? Because their mothers are 250 pounds and had out of control diabetes while pregnant, that's why.

I have observed my own family, generations get fatter and have worse blood sugar situations , which has no relationship to diet, simply the vulnerability has become more severe due to a progressive prenatal programming for it.

ItsTheWooo2 said...

@bentlyj74 5/29

If I ate that diet I would be starving, just saying. IMO bananas are delicious so I don't know why you would include them in a bland diet. Cheese is also very tasty and salty.

Man I would be STARVING if I ate that, lol. I would need to be amped up on amphetamines or manic or something to not feel hungry on that. HA HA HA.

I mean, dude, when I imagine a "bland" diet i'm thinking wheat or flour or boiled potatoes with no salt and chicken breasts with no seasoning and the skin removed and your dietary fat is taken via tablespoons of oil while you hold your nose. Cheese on rice with two bananas on the other hand is awesome.

(judging by how much I am talking about food can you TELL I quit my leptin, lolz).

malpaz said...

Woo- thanks. only question i have is why does leptin cure anorexia induced HA once weight is restored and diet is up to par(plenty of dietary fat)....the trials have been done, the results speak for themselves. the women who had recovered and restored weight(whatever that means) and had not regained their period take leptin injections, and they get their periods back. just like you when you lose weight, lose your period, you take leptin, it comes back.

both cases are direct problems of tanked leptin. leptin does just come up like it should in an anorexic just because they gain weight. the brain doesn't process shit correctly so it F*cks up the leptin as well as the rest of the body's hormones. however, leptin injections have ALWAYS shown to restore energy balance signaling in the brain and restoring periods in anorexics(or over exercised women who wont sit on their @$$).

while you hail that leptin is the 'cure for obesity' this is only true once someone has lost weight, BUT holds true as wellllll for an anorexic post recovery who has also lost weight unintentionally but gained it back. you never meant to gain weight with screwed leptin, i never meant to lose weight with a f*cked brain. the leptin problems are the same. you maintain your weight and hormonal functionvia leptin, and i can almost guaranteeeeeeee i would if i had access to leptin

Social Innovation Prize said...

I can find almost no information on leptin injections. How much do they actually cost/
Who prescribes them?

Woo, I may have missed it, but how were you able to get them?


James Kimbell said...


Your comment that "Bananas are delicious" made me think of something. Because I too think bananas are delicious, but I couldn't get fat on them if I tried. I probably couldn't even maintain weight.

There are those, like me and I'm guessing many others, for whom the FIRST banana is delicious - but the seventh is impossible. This isn't true of all foods, though: I could eat way more calories worth of ice cream before the ice cream becomes off-putting. (It's possible that I would instinctively undereat the next day, and end up balanced out, but I'm not sure.)

Then there are those for whom bananas are hyper-palatable in the way ice cream is. Maybe not to the same degree, but still enough to gain weight eating to appetite. Maybe this is a lack of leptin, or a bad glucose metabolism, or who knows. (You probably know a lot more than I do.)

Then there may be those for whom ALL food acts as hyper-palatable. I know Helen mentioned family members seeking out plain starchy foods, and you've mentioned taste being irrelevant to your appetite.

Do you think there's something to these categories I've just made up? And do you think it is possible for one person to move from one category to another?

Stargazey said...

@Social Innovation Prize,

From what I can find on Google, synthetic leptin is r-metHuLeptin and is manufactured by Amgen of Thousand Oaks, CA. It is probably administered under an Investigational New Drug application to the Food and Drug Administration.

If r-metHuLeptin is an investigational new drug, the FDA has not approved it and it can't be prescribed by a regular physician, even off-label.

Ideas: (1) We could write to Amgen and let them know that there would be enough interest in r-metHuLeptin in the low-carb/paleo community to make it worth their while to perform efficacy and tolerability studies. (2) Shire Pharmaceuticals has a history of taking up underutilized drugs and selling them successfully to niche markets. We might write to them and see if they would be interested in taking over the patent.

bentleyj74 said...

@ James

I'm wondering about those things too. I do see people over eat bland starchy staple type foods but not in the context of low fat/low seasoning/low stimulation and with food monotony to more closely mimic the environment of a nonobese population.

Take bananas for example again [the banana chronicles!]. I grew up eating them as a staple food. They frequently rotted on the counter before being eaten.

My friend on the other hand ate banana BREAD and the flavor and smell of banana causes her to feel cravings. She thinks she probably COULD eat at least 4 bananas in a row although we haven't put it to the test.

My household was not a baking household...things tasted like what they were. Whole wheat tastes bitter to me, I profoundly dislike it until it is doctored up. Some people could eat their way through a loaf of whole wheat bread without any embellishment at all.

Alternatively beer tastes bitter but will get you drunk so maybe your brain decides it tastes good anyway.

So I'm left it because it's bland or because it's unrewarding when "reward" is understood to be basically getting just a little bit high. And if so...are there some rewarding qualities that are inherent and some that are individual?

James Kimbell said...


I like where you're going with the idea of cravings, and I think we should all be more careful distinguishing cravings and hunger. (Even if it's not possible to draw a 100% clear line between the two.)

Two things from my experience I want to add:

First, there are times when I do crave a specific food and only that food. When I crave chocolate, I can eat pounds of something else and still crave chocolate when I'm done. Not sure if that's because I'm craving calories associated with chocolate (and incorrectly ignoring those in other foods), or craving a nutrient, or craving a drug-like property of the chocolate. I've never been tried to or needed to lose weight, but perhaps this phenomenon is one reason why people on restricted diets can gain weight.

Second, I want to point out that combinations of foods can be more palatable than either food on its own. If eating bananas, I could probably stuff down three or four comfortably. But if eating bananas and nuts at the same time, I could eat more bananas PLUS all those nuts. (Yes, I have done this before.) Even though it's more bulk, more calories, etc., the palatability factor makes the difference. The combination not only tastes better, but "goes down" smoother somehow. Many people may have the same experience with potatoes and butter.

James Kimbell said...

Clarification: It may not be clear from my post, but basically what I mean by "cravings" is desire for a specific food, where "hunger" is desire for food in general. These seem like completely different things when they happen to me, although the experience may be different for those with different metabolisms, etc.

Kencade said...

I believe the two best theories for explaining a successful insulin-focused approach to weight loss in terms of food reward are:

1. The low-carb approach decreases the flavor-calorie association by minimizing foods with a high glycemic index.

2. For those suffering from hyperinsulinemea, high carb sources of energy (starches and sugars) provide a reward--albeit temporary--in elevated mood and energy. The reward is lessened as the low carb diet enables the use of fat as a source of energy.

Mark said...


The problem with the theory of food reward is that it may be merely an effect, not a cause.

I have had several relatives all go through periods of severe depression. They all gained weight during the depression. My oldest brother gained 30 pounds (and he was a skinny child, the kind that drank Coke and ate cookies constantly). By the way, post-depression, he's thin again. And he didn't diet.

When we're depressed, we seek out foods with a high reward value. I've been there myself. Moreover, I'm sure certain foods help alleviate depression *temporarily* while others don't. If I'm feeling down, a doughnut and a chocolate milk sounds outstanding. When I'm feeling great about life, those choices aren't interesting to me. Other thoughts flood my head: looking good in my suit, feeling fit for my date on Friday with the cute girl down the hall, etc. Depression makes us seek out things that make us feel good. We stop thinking of positive thoughts for the future.

Perhaps a better test for the hospital floor would've been to give the obese patients Xanax and psychotherapy to disassociate food from reward. Then observe their food choices.

I've never met a fat person who didn't use food as a reward - this is true. (And, yes, I've known a lot of fat people.) However, I've rarely met a fat person who was *genuinely* happy or not anxious. As Wooo said, depression is a real physical problem. If anything, Omega-6 laden veggie oils, which certainly cause depression, probably indirectly promote eating based on food reward.

Again, is food reward a cause? Or merely effect?

I don't mean to reduce obesity to a single variable problem, but nothing has helped this former fat kid keep the pounds off than staying far and clear from vegetable oils. Once I stopped eating those, and began supplementing with Omega-3, I suddenly didn't want all the candy, Coke, and brownies. I just naturally stopped thinking about it.

lightcan said...

Stephan said that there is variability between individuals regarding food reward and that those that have dopamine receptor problems (sorry for the simplistic definition) might be more prone to overeating because the reward circuit overrides the homeostasis one.
I am one of those who eats a big dinner with rice, meat and cabbage and then although full I'm thinking about chocolate truffles. It is the fat, the sweet taste, and the particular chemicals in chocolate that create the anticipation and the desire. Yes, also prone to depression too and not able to cope with stress at all.

Re. Woo's comments I found this

It's exactly what she says.

Stephan has a link to this site on the main page, so he must have read it too.

paleotwopointoh said...

I can barely finish a whole banana and prefer to eat them, if at all, as close to green/unripe as possible. I don't find highly sweet foods hyperpalatable. My preference is strongest for sour and/or fermented foods. I suspect that plays into things quite a bit in terms of weight issues.

Might-o'chondri-AL said...
This comment has been removed by the author.
Might-o'chondri-AL said...
This comment has been removed by the author.
Derek said...


I can concede that there are likely major differences between male & female responses to weight training and other forms of intense exercise, and also that weight-loss strategies between the genders are also likely to look somewhat different.

As for my own dietary experience I was actually much hungrier when I was eating VLC with lots of meat and SFA. After switching to my current whole foods, moderate carb, low meat, unprocessed diet my appetite has decreased significantly.

Your supposition that lowering starch helped me is incorrect. The things I crave most are sugar, animal fat and meat. And yes, I do also crave fast-acting starches such as white potatoes and rice. However, eating a diet high in legumes and sweet potatoes has the opposite effect. Thus for me, starch is not the explanation but rather high GI starch. Low GI starch has an appetite-lowering effect for me (except for pasta which is low GI but which causes cravings for me; must be the wheat).

I've learned through experimentation what lowers my set point: whole, unprocessed foods in the form of legumes, sweet potatoes, yams, fruit (except bananas which is probably due to their high GI combined sugar and starch content), nuts, MUFA such as olive oil, fish, veggies, lower GI non-gluten grains, coconut oil/milk/cream.

The foods that will stoke my appetite like a raging inferno: sugar, animal fat especially SFA, rice, wheat, white potatoes, dried fruit (figs, raisins, etc), fast food, highly processed food, and recipes that are made highly palatable via sauces, intense spices, or multiple ingredients that greatly increase texture, flavor or calorie density. These have a direct appetite-increasing effect on me within hours of consumption.

To me it looks like food reward is going to prove to be a highly individualized response.

Stephan Guyenet said...

Hi Itsthewoo,

OK, don't worry about it.

You aren't the only person who feels the term "leptin resistance" doesn't accurately describe what's happening in obesity. For example, Lightcan mentioned the bariatric MD Dr. Arya Sharma, who recently wrote a blog post titled "why hyperleptinemia is not leptin resistance". That was based partially on an interaction he had with Dr. Rudy Leibel. These guys are serious scientists/physicians and I respect their opinions greatly. There are other scientists I also greatly respect who think leptin resistance is an accurate descriptor.

The basic idea advanced by Sharma and others is that the leptin system is designed to protect against weight loss, not weight gain, therefore adding more leptin to the system beyond a basal concentration does not reduce fat mass. What happens with leptin in obesity is not directly analogous to what happens with insulin in type 2 diabetes, because you can't fully correct the problem by jacking up the hormone.

Here are the reasons why I think leptin does defend against weight changes in both directions, and "leptin resistance" is probably an accurate descriptor:

1) The brain clearly requires more leptin to feel "satisfied" in obesity than in leanness. If circulating leptin drops to a normal "lean person" level in an obese person, the body will think it's starving and will initiate a compensatory response (hunger, metabolic efficiency, etc). Leptin levels in a weight-reduced obese person (weight loss due to simple calorie restriction) are still typically higher than in someone who has always been lean ( That suggests the leptin signal is dampened in obesity, in other words that the brain is resistant to leptin.

2) Leptin is required for the extended hypophagia that follows overfeeding in rodents and helps bring them back to their pre-overfeeding weight. That suggests it does help to protect against weight gain beyond just at basal levels.

3) In humans, observational studies have shown that overfeeding on one day is followed by a compensatory decrease in calorie intake roughly 3 days later. That parallels what's seen in rodents.

4) Interventions that prevent the development of leptin resistance in the brain prevent diet-induced obesity in rodents. These revolve around suppressing inflammatory signaling or molecular feedback inhibitors of leptin signaling like SOCS3 and PTP1B.

5) Human overfeeding studies have shown (for the most part) that people, whether lean or overweight, will "defend" against fat gain just about as potently as they defend against fat loss. The fact that obesity can occur regardless of this mechanism apparently remaining somewhat intact in the overweight is consistent with the hypothesis that the brain gradually loses its leptin sensitivity, requiring more fat mass to feel "satisfied".

For those reasons and others, I side with the obesity researchers who feel the term "leptin resistance" is accurate. That said, I think there's still much to learn, and I look forward to seeing if the hypothesis continues to hold up.

ItsTheWooo2 said...

@ malpaz 5/30 7:05
Leptin will work for anorexic females ... however, leptin is NOT an appropriate treatement for such a person because the anorexic female needs to restore body fat and proper nutrients. There is NOTHING wrong with her body , her fat cells are normal, her brain (in regard to weight control) is normal. Someone like myself, a morbidly obese female, is in a TOOOTALLY different situation. My fat cells do not make leptin normally any longer even if my body fat is "adequate". Even if my diet is fabulous and I take in a lot of nutrients and zinc, I will never make leptin normally. I will only make leptin normally if I regain a good amount of my lost body fat, which would make me overweigh tor obese.

Do you see the difference?

It would be like using amphetamines for someone who has narcolepsy (a disease where the brain does not make stimulants properly due to hypocretin abnormalities), vs using amphetamines for someone who has an addiction to abusing amphetamines. One is an appropriate therapeutic replacement, the other is an inappropriate treatment.

It is simply false to say that anorexic women have leptin systems which are damaged. If anorexic women gain body fat to a normal level AND eat properly (zinc, protein, fatty acids, calories adequately) AND stop compulsively excersizing, then such women will be in a true recovery, their leptin will recover, and their menstrual cycles will as well. There is nothing wrong with her fat tissue or brain which would otherwise propel her to obesity - she just needs to get control of her disorder adequately before she will menstruate again.

The problem is that many anorexic women gain body fat but their diets are still very disordered... or many anorexic women have good diets, but their calories are severely deficient still and so they fail to gain adequate body fat... or their body fat is okay and their diet is okay but they are still compulsively exercising. Until EVERY ASPECT of the disorder is controlled and in remission, the anorexic female will still have starvation sequellae, such as leptin deficiency and HA. And, in this case, HA is a blessing... it would be a tragedy for her to get pregnant while still exhibiting some facets of disordered behavior. Not only would it be dangerous for her but it would promote birth defects in the child.

As I said in my original post you, malpaz... if you are still suffering from HA, and you are in recovery for anorexia, it is highly likely that this will terminate if you concentrate on your recovery. BMI means nothing. BODY FAT is all that matters when it comes to weight. Also, diet and calories are extremely important - zinc deficiency is very common in anorexics due to an unwillingness to eat meat. Overexercising is another problem many anorexic women have and this will hasten/worsen hypothalamic amenorrhea. You do not need leptin, you need better control of anorexia. Leptin is only appropriate when there is a disorder of leptin signalling, such as in myself (due to severe obesity, I do not make leptin normally at a low body weight). Your leptin system is working as intended. The reason you have HA is because your eating disorder is not controlled well enough at this point in time.

ItsTheWooo2 said...

@Stephan 5/30 10:21

It seems like Leibel/Sharma have come to the exact conclusions I have come to. The only small disagreement I have with these gentleman is they seem to think it is necessary to replace leptin to the level it was before weight loss. I do not think that is necessary, in my experience a very low dose replacement was totally effective.

Regarding your arguments...

1) No, I don't agree. Speaking as someone who WAS obese, I NEVER felt satisfied. I was NOT weight stable, I was actively and chronically growing fatter and I was hungry all the time. When I would wake up after an overnight fast, this was the only time I ever felt true satiety.

In my case it seems as if my leptin system works fine, but a drive to fatten due to glucose metabolism disorder and endocrine impact thereby is mitigating what would otherwise be a passive state of weight stability.

The reason leptin levels are higher in a weight reduced obese person is because weight reduced obese people are still fat. Most people can only manage a partial correction of obesity, probably due to inadequate control of glucose metabolism combined with the life or death fight against dropping leptin. When you consider the fact most dieted people are still probably eating inadequately to control their insulin/glucose metabolism disorder, PLUS they most contend with relative leptin deficiency... it's obvious why they plateau out.

I am the only person I know who is truly THIN after being OBESE.... and guess what, my leptin level was comparable to someone with lipodystrophy, it was almost undetectable.

The truth is, when weight reduced people are compared to non-dieted people and body fat level is controlled for it is shown that they are VERY hypoleptinemic, relatively and/or absolutely when compared to the nondieted controls.

ItsTheWooo2 said...

2) IN this sense, rodent endocrine system is not comparable to human endocrine system. In rodents leptin causes a total wasting of body fat, it does not due this in people. In rodents leptin works more to completely waste body fat, almost like inducting type 1 diabetes will (although, obviously, without the severe complications of insulin deficiency). In human beings, injecting lots of leptin will never cause total emaciation as people do not seem to use leptin this way, all it does is prevent weight regain and cause some degree of weight LOSS but i t typically will not cause total emaciation.

You are aware that in human beings, regardless of if they are fat or thin, injecting leptin WILL NOT cause severe weight loss to emaciation , right? It does in rodents, not in people. There may be an evolutionary reason rodents react this way to leptin but it doesn't seem applicable for humans.

3) I do not understand how this supports a theory of leptin resistance. Yes, if one is not presently afflicted with the disease of obesity, if one is NOT being compelled to pathologically store fat via hyperinsulinemia, I would completely expect a day of over feeding to result in decreased appetite for 3 days. This does not prove that leptin resistance causes obesity, because the possibility still remains that the pathology driving obesity is something other than leptin. If one if hyperinsulinemic with very sensitive fat tissue, it would be totally expected that overfeeding would not cause a compensatory decrease in appetite - why would it, the insulin will shunt nutrients into fat cells and not allow them to be released adequately. This does not mean leptin is involved at all, all it means is that high insulin is more powerful than adequate leptin signaling. Which I could already have told you simply by living my life and observing. ... and is in line with my idea that leptin is totally unrelated to most cases of obesity, it is just a passive actor preventing starvation, which does not come into effect if one is afflicted with a disease that causes pathological body fat accrual.

NOTE: when I was taking leptin, if I ate a lot of glucose, I still became ravenous and insatiable. Leptin injections did NOT fix my glucose problem, my obesity. All it did was prevent me from trying to regain my lost weight while maintaining my low carb insulin reducing diet.

ItsTheWooo2 said...

4) RODENTS ARE NOT OBESE HUMANS. Rodents are BRED to become fat, they are SELECTED for genetic mutations which may have no relevance what so ever to human obesity. It may be possible that "diet induced obesity" in rodents is specifically a problem with leptin receptor loss - it remains to be shown this is at all applicable to human diet induced obesity. It is highly unlikely it has any reole.
There are no type 1 diabetic rodents, just rodents who have had their pancreas killed by drugs (STZ). Almost all humans who are type 1 diabetic are so because of autoimmune diseases. There are NOT lab rats with a comparable disorder.
Saying that humans must have leptin resistance because fat rats do, is like saying type 1 diabetic people are diabetic because they took STZ. Humans who have type I diabetes do so for TOTALLY unrelated reasons to STZ rats. I mean, completely and utterly DIFFERENT. The only similarity is that neither makes insulin.
Similarly, rats who get fat on high fat diets, probably have NO SIMILARITY to humans who get fat in america. Why would you assume they do? Evidence seems to suggest that a very high fat diet is highly effective to lose weight in at least a subtype of obese prone humans (such as myself). That right there is a good argument that why I became fat has no relevance what so ever to whyy some "DIO" mouse becomes fat.

4) Again, DIO in rodents probably has no relationship to human obesity, just as STZ diabetic rats have no relation to type I diabetic humans pathophysiologically speaking. These animals are bred to mimic SYMPTOMS, not PATHOLOGY.

5) Perhaps it is true some fat people maintain a stable obese weight, with no drive to gain, with no endocrine abnormalities... but I do not think this is the majority of fat people. It certainly WAS NOT ME. Most fat people are in an upward trajectory of gain, however slowly or quickly. They are not weight stable. They are not "defending a high weight" but actively accruing body fat month after month year after year. This continues until the system goes to pot, fat cell coping is exhausted, and very likely then diabetes sets in.

Poisonguy said...

"3) In humans, observational studies have shown that overfeeding on one day is followed by a compensatory decrease in calorie intake roughly 3 days later. That parallels what's seen in rodents."

I have two young children who we basically feed ad lib; we let them eat to their satiety levels (don't force them to finish their plate). I often comment to my wife that they go through 2-3 days cycles of "not eating well" followed by a day of "eating really well." So, that comment struck a cord with me.

luckybastard said...


yes, i am a formerly obese person who is lean now. i've been lean for a year with an appetite that is apropos for my lbm- i'm 225@16%bf. i eat 2-3 lbs of meat a day, anywhere from 50-100g of carb- mostly glucose- on nonworkout days. i strength train 2-3 days a week and on those days i can take in anywhere from 150-300g of starchy carbs on that day. i don't count calories and i'm not a hungry at all. in fact, most days i eat 2-3 meals inside of an 8 hour window. i fast for 24 hours once a week.

i was a kid with weight issues from birth. i can't remember a time when i wasn't fat. (i weighed about 340 when i graduated from hs)i admitted to my brothers this weekend that i look in the mirror and don't recognize the person there. i don't work out long- i do powerlifting for 30 min 2-3 days a week- but that along with a lacto-paleo diet has enabled me to drop the weight, never feel hungry and have complete and total control over my hunger and cravings. i'm not a scientist so i don't know the mechanisms behind what i've done but i've used what i've learned over the last few years and have helped other obese people achieve similar results. it's more the fact that i've helped a good number of people from various backgrounds reverse whatever was going on with them with a simple eating plan that basically tried to return them to eating in the way their body has evolved to eat. there's not one person who was serious enough to reverse years of derangement(and i'm under no illusion that this is difficult work for some people) who it hasn't worked for. i think the experiences you've had are real and i'm happy that your therapy works for you but from my experience of dealing with myself and a good number of other obese people, you're an outlier. but i very well could be wrong.


do you think there is a role that fasting- whether daily 16-20 hour fasts or weekly 24-36 hour weekly fasts- can play in the area of getting appetite and indulin sensitivity under control? the people i've worked with who've incorporated some fasting seem to do better in the area of controlling cravings and their appetite normalizes in pretty short order.

Might-o'chondri-AL said...
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Stephan Guyenet said...

Hi Luckybastard,

It's entirely possible. There was a paper that recently came out on intermittent fasting that was really the first one to test the effectiveness of a type of IF that's similar to what you see people doing in the paleo community. It worked well for weight loss and health improvement (

Hi Itsthewoo,

The body of the typical obese person will initiate an anti-starvation response when it still has an amount of fat and circulating leptin that greatly exceed the lean level. That suggests they require more leptin for normal "baseline" leptin signaling, just like a type 2 diabetic requires more insulin to function like an insulin-sensitive person. If that doesn't demonstrate the concept of leptin resistance, then I don't know what does.

You seem to think results from rodent studies aren't relevant to human leptin signaling. I can tell you that the rodent and leptin literature on leptin are remarkably similar. As a matter of fact, I can't think of a single aspect of leptin signaling off the top of my head that's different between the two species.

Diet-induced obesity in rodents and human obesity actually appear to be quite similar states, as far as I can tell. Hormones change in the same way, systemic inflammation changes in the same way, diabetes and atherosclerosis risk increase, even brain activity changes in a similar way (e.g., hypothalamus and reward centers).

I see people use the argument "mice aren't little humans" a lot. While that's true, and we have to always remember it, the disturbing fact is that people often use that statement to selectively disregard a whole body of work that disagrees with them. When you have rodent data and human data that are broadly consistent and mutually buttressing, disregarding the rodent data will only hold back your understanding of a process.

You mentioned that the rodent studies where chronic leptin administration causes their fat mass to disappear have not been replicated in humans. I'm not sure that's true. In this study, at the highest dose, lean people lost roughly 7 kg of fat mass over 24 weeks of leptin treatment ( That's a lot of fat loss for a lean person, in fact it's about the same as the total amount of fat on my body right now.

Might-o'chondri-AL said...
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Malibu said...

woo i am just not understanding ...your 'using' leptin to control the weight you 'want' to be because i assume you suppose you are 'supposed' to be this weight. what if that just isnt the case? your making the same argument at me. not to mention a quick pubmed search SHOWS RESULTS that anorexics do not have normal leptin signaling post weight restoration, not to mention maintain LOWER levels of leptin and higher body fat as well as reduced metabolisms. show me one 'recovered' anorexic who has not turned into a binge eater or who is not disordered any longer and maintains a normal BMI symptom free. doesnt exist, just like your idea that an obese person who lost weight cant maintain their weight.

again, the results are in the studies. have you ever looked at the amylin-insulin connection to leptin. it is pretty interesting as well and very food reward/control

Cat said...

Correct me if I'm wrong, but it was my understanding that while food reward is RELATED to food palatability, it wasn't EQUAL to food palatability.

Many of the posts I've read here seem to be conflating food reward with taste. Saying that consuming food with a very high reward value will make you fat is not the same thing as saying that consuming foods that are very delicious will make you fat.

malpaz said...

Regulation of leptin secretion from white adipocytes by insulin, glycolytic
substrates, and amino acids

The aim of the present study was to determine the respective roles of energy substrates and insulin on leptin secretion from white adipocytes. Cells secreted leptin in the absence of glucose or other substrates, and addition of glucose (5 mM) increased this secretion. Insulin doubled leptin secretion in the presence of glucose (5 mM), but not in its absence. High concentrations of glucose (up to 25 mM) did not significantly enhance leptin secretion over that elicited by 5 mM glucose. Similar results were obtained when glucose was replaced by pyruvate or fructose (both 5 mM). L-Glycine or L-alanine mimicked the effect of glucose on basal leptin secretion but completely prevented stimulation by insulin. On the other hand, insulin stimulated leptin secretion when glucose was replaced by L-aspartate, L-valine, L-methionine, or L-phenylalanine, but not by L-leucine (all 5 mM). Interestingly, these five amino acids potently increased basal and insulin-stimulated leptin secretion in
the presence of glucose.

Unexpectedly, L-glutamate acutely stimulated leptin secretion in the absence of glucose or insulin. Finally, nonmetabolizable analogs of glucose or amino acids were without effects on leptin secretion. These results suggest that 1) energy substrates are necessary to maintain basal leptin secretion constant, 2) high availability of glycolysis substrates is not sufficient to enhance leptin secretion but is necessary for its stimulation by insulin, 3) amino acid precursors of tricarboxylic acid cycle intermediates potently stimulate basal leptin secretion per se, with insulin having an additive effect, and 4) substrates need to be metabolized to increase leptin secretion. arious proteins stimulate leptin secretion in the presence of insulin or glucose. But only glutamate was found to stimulate leptin in their absence. This makes glutamate an excellent candidate for the protein regulated by leptin. The effect of other proteins on leptin secretion is likely an artifact of their interaction with glutamate, under the influence of insulin.

Glutamate metabolites feed into the krebs cycle at several points. Fat cannot be metabolized for energy without this cycle, which explains the apparent control by leptin of appetite which disappears once fat is depleted. This is clearly true. Not a theory, just an observation.

malpaz said...

Poorly-regulated glutamate causes excitotoxicity in the brain, killing neurons. This is a protein needing careful regulation. The idea that disregulation of leptin/glutamate metabolism is involved in some neuro-degenerative disorders seems obvious. True by definition, even. They've even found that leptin activates glutamate receptors, without making the connection. There are also plenty of glutamate receptors in the gut.

Protein appetite is increased after central leptin-induced fat

Leptin reduces body fat selectively, sparing body protein. Accordingly, during chronic leptin administration, food intake is suppressed, and body weight is reduced until body fat is depleted. Body weight then stabilizes at this fat-depleted nadir, while food intake returns to normal caloric levels, presumably in defense of energy and nutritional homeostasis. This model of leptin treatment offers the opportunity to examine controls of food intake that are independent of leptin's actions, and provides a window for examining the nature of feeding controls in a "fatless" animal. Here we evaluate macronutrient selection during this fat-depleted phase of leptin treatment. Adult, male Sprague-Dawley rats were maintained on standard pelleted rodent chow and given daily lateral ventricular injections of leptin or vehicle solution until body weight reached the nadir point and food intake returned to normal levels. Injections were then continued for 8 days, during which rats self-selected their daily diet from separate sources of carbohydrate, protein, and fat. Macronutrient choice differed profoundly in leptin and control rats. Leptin rats exhibited a dramatic increase in protein intake, whereas controls exhibited a strong carbohydrate preference. Fat intake did not differ between groups at any time during the 8-day test.

Might-o'chondri-AL said...
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ItsTheWooo2 said...

@james kimbell 5/30
If you want to know my real feelings on the food palatability thing, I tend to think that people who like food the most are those who are usually easily able to control their weight. Having a sensitive palate and getting pleasure from food is a sign that your dopamine system is quite sensitive and working properly (dopamine controls metabolism FYI, via the hibernation response). It's when you stop being able to taste food or enjoy it fully that you must worry about obesity, and IMO I think my fragile dopaminergic system (easily too much or too little, probably relates to my mood disorder as well) is a big reason why I have such wild shifts in weight (super fat, super thin).

I think people tend to forget that weight is only measurable over days weeks or months. Humans are designed to go through phases of over eating and under eating. We are hunter gatherers, remember? Just because you pig out at a buffet does not mean your leptinz brokez oh noez. All it means is that there is a ton of awesome food, so caveman genes say chow down now.

It's usually thin people who really enjoy one or two foods and eat a lot of them - enjoying food is a sign of having a working metabolism because your dopamine is ping ponging well. Fat people gorge themselves with highly sensational foods and barely experience them because their PET scans light like a dim bulb in regard to dopamine signalling. It's not the over eating that makes them fat, it's the nervous system and resultant metabolic/endocrine abnormalities. They eat because they have no dopamine signaling (just like an animal preparing for hibernation - the switch to hibernate is NO DOPAMINE) which makes them glucose resistant which makes them hyperinsulinemic which makes them eat. They eat because dopamine not working makes you store fat, and not use glucose, which makes you eat to fuel the fat gain.

Fat people eat a lot because they are hungry but they don't really taste much or enjoy much. I know when I was obese this is exactly my situation. I never really enjoyed food, I was compelled to eat it due to an insatiable, unsatisfiable hunger, and the weight gain never stopped. I enjoy food much more now that I am thin and no surprise, because I have a very very sensitive dopamine system (and is shown food restriciton/weight loss causes dopamine receptors to upregulate like crazy).

Anyway, as I was saying... ONE MEAL or ONE DAY of over eating means nothing. I laugh at all these people who are like "TODAY I ATE A BLAND DIET AND I ONLY ATE 1200 CALORIES CLEARLY THIS IS THE SOLUTION TO OBESITY". Talk to me after 4 months. Talk to me when you get down to a low body fat.
You can eat a lot today, you can eat nothing tomorrow, but these small meaningless blips in eating are irrelevant to the long term picture of weight status.

You can go to your favorite ice cream shop and eat sundaes until you burst... the question is, is your body compensating for that eating? The next day, or two, is your appetite lower and do you have more energy? If so, then you are weight stable and you are not presently afflicted with obesity.

It doesn't MATTER if icecream sends you into an eating frenzy. All that matters is, is your weight going UP or DOWN?

Palatability doesn't matter... the nervous system and endocrine system does. Weight stable people usually love food, or some foods, and will have control problems with their favorite foods. That's called being a normal human being. Liking food doesn't make you fat, ironically the opposite is true - people who have dim dopamine don't enjoy food much and this nervous system situation causes hibernation (which never terminating becomes obesity).

ItsTheWooo2 said...

@James Kimbell
Regarding your clarification...
I personally don't experience cravings, and whenever I do, it's in the context of hunger.
As I stated, I think people focus too much on how their eating behavior is at meals or for one day ("Today I was very hungry" vs "today I had no appetite"). Something as physiologically vital as body fat status is not so easily altered by one pleasurable meal (which you over eat) or one unpleasurable meal (which you refuse to hardly eat). Perhaps, at that meal, or for ONE day, your appetite will shift wildly. If you hav ea day where you go to your favorite ice cream shop, your calorie intake for that day might be twice as high as usual. If you have a day where you only eat bland food, you might only eat half y our usual calories.

Talk to me in a month or a year, and tell me how your calorie intake shifted. UNLESS YOU HAVE A METABOLIC, ENDOCRINE, NERVOUS SYSTEM DISORDER, your weight will remain stable. Food pleasure will only affect eating behavior over a very short term period of time. I expect - and enjoy - over eating my favorite foods. I know my body will compensate with decreased appetite later, assuming I do not f*ck my insulin up. Even with my leptin signaling, I still do compensate for over eating - I make leptin, after all. I would just copmensate BETTER if my leptin levels were adequate.

The only thing that prevented my body from com,pensating for over eating was hyperinsulinemia driven by a high carbohydrate diet. Then I am driven to eat, and eat, and eat, and gain, and gain, and gain, and there is never a compensation, I am limited only by how tasty and how available are the calories. The problem is NOT yumminess of food, the problems is NOT calorie density... the problem is plain and simple and no more complex than this:


People who are thin either have normal/low insulin, OR they are resistant to its fattening effects (due to genetic mutations or fat cell resistance).

Taubes really does have it right, sorry guys. Obesity is all about insulin. Insulin however is not as simple as carbs... it's about a lot more than carbs, but ultimately for control of obesity carbs is a big part of it.

gunther gatherer said...

@ All,

None of this explains why indigenous cultures still eat up to 3500 calories a day. In the case of the Inuit, much more. Bland diet or not, they have no obesity.

What they do have is a system which has never been broken.

Incidentally, I tried this for 2 weeks, was hungrier than usual (even eating plain potatoes, which admittedly were not nice to eat) and gained noticeable fat.

Low food reward can definitely have applications for young people or those who have never been obese (and to prevent it in modern populations). But when physiological functions have already been damaged, your best bet still remains VLC. Maybe the problem was once in the hypothalamus, but the time you're fat, this problem has moved to the liver and pancreas.

Going back to VLC brought me back to ideal weight in 2 days. Didn't have to hate every bite to do it either.

James Kimbell said...


thanks for responding. I hadn't thought about it, but I do suspect you're right about weight-stable people enjoying food more than overweight people, contrary to popular opinion.

I also think you're right about how the short term is misleading - and I said in my post earlier that I suspected overeating on ice cream might be compensated for the next day. Although, as with all this stuff, I'm not sure, and I don't want to pretend that I am sure, because there are sooo many factors.

I wonder, for example, about the person who eats ice cream EVERY day - will that person overeat again and again and gain weight, or will his/her appetite adjust even in the presence of this hyper-palatable food? And if that person does get fat, how can we say it was the palatability and not the sugar or some property of dairy or something else? (This is one reason why rat experiments are helpful: you can isolate variables better than you can with humans.)

Roberto said...
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Roberto said...


Your outlook on dopamine signalling seems very speculative to me. Could you provide a reference for your statement that obese people have consistently low dopamine signalling?

If carbohydrates are driving obesity, why would we see weight loss in the tube feeding study Stephan mentioned? They were eating 50% of their calories from refined, quickly absorbed carbohydrate. The same insulin driving effects would have resulted from that diet, yet their appetite plummeted and they lost enormous amounts of weight.

john said...


Their calorie intake from the tube was extremely low; they lost lots of fat --> their total calorie "intake" was mostly fat.

Roberto said...


I realize that, but the question is why did their calorie intake drop so low?

The diet was ad libitum. They were allowed to eat as much as they wanted but had little appetite when they were switched to the bland food.

If you switched them to a diet with 50% of its carbs from Coke and Snickers that wouldn't have happened.

Itsthewoo dismisses the palatability factor, but that's the best explanation for why those people lost weight without the hunger and hypometabolic consequences that most face on calorie restricted diets and even on carb restricted diets.

I'm happy that Itsthewoo enjoys her low-carb diet, but for many it becomes quite monotonous and boring. I'm restating what Stephan has already said, but its possible that what effectiveness low carb dieting offers has nothing to do with insulin. Especially when a lot of protein rich, low-carb foods are known to spike insulin.

The palatability factor best explains why so many diverse, highly restrictive diets offer weight loss - veganism, low-carb, low-fat, paleo. Come to think of it, I've lost weight on all of those strategies.

Roberto said...

Whether this palatability theory will provide any lasting strategies for weight loss obviously remains to be seen. It's a pretty bitter pill when you tell a person the solution to leanness is to never again enjoy the food they eat. Personally, I don't think the average person could maintain good emotional health doing that. It's one thing to sequester yourself in a hospital ward sucking on a tube for a couple months, no doubt being paid to do so. It's another to take that strategy into the real world where you are constantly exposed to tastier options, and where food plays a very important role in social interaction.

I've been contemplating this strategy:

Eat ridiculously bland food until you reach your desired weight or as close to it as you can. Then switch gears.

Eat relatively palatable food one day (not McDonalds and Baskin Robbins) and eat exceedingly bland food the next. Continue this process.

Place a mild calorie deficit on the palatable day, ad libitum on the bland day.

Basically do damage control while you are eating palatable food, while overall eating an ad libitum, non calorie restricted diet.

That way you don't completely deprive yourself of enjoyable food.

On the palatable days the theme should still be to avoid overly stimulating, processed junk and to prepare as much of your food from scratch as possible.

And this aversion to unpalatable food seems to be immediate. I can't picture someone gorging on the bland day. The re-exposure to palatable food could potentially keep you sensitized to the appetite reducing effects of bland food. But who knows.

Roberto said...

And I must mention, we still don't know if this palatability theory can even be applied to real food. Tube feeding and boiled potatoes are not remotely the same. This is all so academic. Near as I can tell, the only evidence we've seen that this theory has any application to real food, in a really impressive way, is the "20 potatoes guy".

I think we've been around the blogosphere long enough to know that if weird, boring diets solved obesity we would have seen it happen by now.

gunther gatherer said...

Once again, food reward does not explain what is happening with hunter-gatherer societies, who have no obesity on 2700-3500 kcals/day or even higher. Are they eating less because of a "bland" or "unrewarding" diet? Would a hungry HG even consider it unrewarding to finally eat?? This is all very subjective.

In fact they are eating more than most obese dieters in the West, who fail to lose weight and in some cases even gain weight.

We're going to have to face the fact that for some people, weight loss will be a difficult battle, or at least one with limited success, due to damage already done by eating the SAD. It's not because they are weak-willed or don't exercise. It's not even their fault. It's just because something is "broken".

It would be nice if we concentrated our efforts on what that "broken" element is, and discussed whether it's possible to repair, instead of constantly returning to the same old (useless) efforts to reduce calories, whether carb calories, fat calories or "tasty" calories.

I'm not doubting for a minute that eating a boring diet will make you eat less, and that eating high sugar will make you crave more, but let's not assume that that's why indigenous societies are lean. Regardless of their food source, they all certainly enjoy eating on a comparable level or we wouldn't have survived until now.

Finally, the studies Stephan is citing do not follow the subjects for their lifetime, which is the ONLY way to measure true weight loss. Starvation studies work for weight loss too. But who can stick to those for a lifetime?

Leptin has its place in this scheme, and so does psychology, but I think reducing obesity down to the palatability of the diet is simplistic.

Why do squirrels fatten up before winter on the SAME amount of nuts? Why do bears and tons of other mammals do this too on the SAME amount of calories? They didn't change their food intake at all. Food reward does not explain this.

Stephan Guyenet said...

Hi Gunther,

What matters is energy balance, not just energy intake. Hunter-gatherers have a very high energy expenditure, much higher than the average person today. Still, the numbers you cited for calorie intake are on the high side. Some HGs consumed that much, many consumed less.

Hunter-gatherers do not have the magical ability to get rid of excess calories. They're just in energy balance: energy in = energy out.

The results of the studies I cited cannot be explained by any intrinsic property of macronutrients, or any hormone including insulin. They're also consistent with long-term diet and obesity trends from every culture I'm aware of.

Squirrels and bears fatten for the winter because they are genetically programmed to do so. When winter ends, they lose the fat. That of course has nothing to do with palatability, as squirrels will fatten in the laboratory under controlled diet conditions in response to a changing light cycle. This seems to be related to genetically programmed seasonal changes in leptin sensitivity. Humans are not genetically programmed to gain fat seasonally, and we certainly aren't programmed to get fat and stay that way as we do today.

Beth@WeightMaven said...

@Roberto, I'm currently essentially an "n=1" experiment following a low food reward diet (that's largely paleo+dairy based).

I eat more carbs than most low-carbers (including rice & peas, thanks Paul Jaminet ;), but my appetite is very much diminished from when I was SADing. My food isn't bland, but I do tend to eat the same things most days of the week -- very little of it processed (except for Saturday evenings when I let myself eat whatever I want).

So I'm not sure that people need to avoid high reward foods forever or even until they are at goal. I'm betting that we just need to keep their frequency low -- and especially avoid stringing a bunch of high reward meals together.

I think the latter (e.g., the cruise ship phenomenon) is how I've gotten myself in trouble in the past.

@gunther, I tend to agree with the "broken" concept. I've mentioned Gabor Mate's video in the past. Watching it, you can see how brain development could affect food reward wrt obesity. Throw in prenatal issues like mother's diet, and it nicely explains why you don't see this in hunter-gatherers who aren't eating SAD foods.

Beth@WeightMaven said...

One other thing, I'm working on a blog post on this subject and whipped up this graphic re food reward.

As Stephan mentioned, it has as much to do with smell as taste hence I used flavor. But as I understand it, the reward doesn't come from the taste/smell/flavor ... it's the association that we make with what's actually rewarding about the food. Those are probably the substances that ping our opiate receptors (like sugar, dairy and wheat) among other things.

This is what makes modern industrial foods (that Stephan called "professionally designed" in his podcast) an issue. They carry both high flavor and high reward, so a la the Lays commercial, most of us really can't eat just one.

BTW, anyone see Dr. Briffa's post on MSG, glutamate and leptin resistance today? With all the things in the modern diet that affect appetite, the wonder isn't that 2/3rds of us are overweight or obese, the wonder is that we all aren't!

Richard said...


How would you explain babies that are naturally 'fatter' at birth, or tend to be fatter during infancy with the food/reward theory? Would this be due to the mother's diet primarily? My brother's wife and mine both had baby girls at about the same time...both babies were fed essentially the same diet (the same formula even), yet our daughter was/is fatter than my niece despite the obvious genetic link and same diet.

Just curious. Thanks,

Might-o'chondri-AL said...
This comment has been removed by the author.
Jenna said...

Richard, I have the same query. I have two sisters, we were all raised on a whole food diet, with the same mother. We look completely different however; our body shapes and fat to muscle ratio is very different. Also we put fat on at different rates as we grew up. My younger sister for instance is quite muscley and has very little fat on her, you can see this as she has quite a strong form, definition, and strength. She eats lots of sugary foods, and is very lean. She has stayed this way since I can remember. My eldest sister on the other hand also started off very lean, but into her teens put on quite a lot of weight. Seeing what she eats, it is definately not a case of too many calories, if anything she doesn't eat enough, and thats simply because she does not have the appetite. She like my younger sister eats a lot of sugar. How can palatability explain this difference? There was a clear difference in body composition from a very young age to reaching puberty. I would say that my younger sister has a body form very similar to my father, very skinny, but, high muscle tone, and strong forms, they also have the same kind of appetite, cravings etc. My elder sister I think is more like my mother, my mother holds much more fat to her frame, and has less muscle to fat it looks like. So, this is where I am quite skepticle of calorie control and body weight, as there is such clear difference, and I'm not entirely sure what creates this apart from genetics. Neither do much exercise, and neither does the age gap seem to explain these differences.

Stephan Guyenet said...

Hi Richard,

Newborn fat mass is somewhat related to maternal fat mass, but it isn't necessarily a problem. Up to a point, heavier babies end up healthier later in life.

Hi Jenna,

Different people have different levels of susceptibility to the harmful effects of the modern diet. Not everyone will become obese eating fast food, drinking soda, and not exercising. It just changes the likelihood.

Sarah said...

I take Wellbutrin and Adderall for depression. I think both helped reduce my urge to overeat. Probably that is due to the fact that they increase levels of dopamine. Going low carb has helped even more. I noticed recently that when I kept feeling uncomfortably hungry for hours after a meal, I finally quit feeling hungry after I drank just a half cup of coffee. I didn't feel hungry until six or seven hours later. ( It's hard to concentrate on or enjoy anything when you're hungry like that.) It seems to me that dopamine stops the feeling of hunger.
I wonder about the Kitavan diet where they eat a high proportion of carbohydrates in the form of root vegetables and fruit and "it's reported" a low proportion of fats and low protein. They stay very healthy on this diet. So, is it because they don't eat grains that they are so healthy, or is it because they eat low fat with their carbs?
I have been way too overweight for a long time, and tried to diet several times, but couldn't stick with it. Going on a diet just seemed to make me feel more fixated on food. I would say most of the time food doesn't taste that good to me.
I have noticed that foods with more subtle flavors that don't depend on sweet or salty or tasting rich tend to be more satisfying.

Poisonguy said...

Stephan, does your food reward theory address the amounts of fat (added fat), sucrose and salt added to fast and processed food?

Jee said...

Hi Stephan,

Interesting series -- can't wait for the next post...

Is there any evidence to suggest that quality of fat affects satiety? In my own experience I've noticed that when I eat plenty of animal fats, butter, whole cream, coconut oil, etc., I can't overeat. I get 'fat fullness' so to speak, which for me is a mild nauseous response -- it's not that I can't fit more food in my stomach physically, just that every bite beyond satiety is a bit revolting, no matter what the food. To contrast that to refined oils, I used to be able to eat junk food almost without end, even after a full meal without such an immediate response (I'd just feel like crap much later.) Has anyone else had a similar experience?

Lucas Tafur said...
This comment has been removed by the author.
Lucas Tafur said...

Just to chime in:

I havent been morbidly obese and I am relatively young. However, I had MetSyn at age 12. I had a hypertensive crisis (reached 180/120 or such if I remember well. TG were almost 400) and I weighted 82kg.

Always struggled with body fat and high body weight through my teen years. Because of this, I started training but eating a high carb diet. All good, but to MAINTAIN my weight I had to exercise every damn day. Minimum 30-45min of cardio. Until I discovered low carb.

After trying different "types" of low carbohydrate diets, I am confident I have restarted my metabolism. I have corroborated this during the last weeks. I have been so busy lately that I havent been able to exercise for more than 1 day per week, 30 minutes of resistance exercise. All other days of the week are basically fasting + coffee + water for all day and eating a big meal in the night (sometimes after a 24h fast). Calculating my meals during the week gives me an average of 2800-3000kcal, 11-15% protein, 70-80% fat and 5-9% carbohydrates. I am 74kg at aprox 9% bodyfat. This should be my theoretical calorie maintaining level.

So what has this to do with food reward? Well, I share many of the "paleo" principles but dont apply others for myself. Im a big dairy eater. The food I eat has to have flavor. Lately, probably because of stress, I have been drinking some diet soda. Has my weight increased? Do I immediatly need to eat more? No.

For instance, every single day I eat 1.5 cups of cream with 1tsp vanilla extract and stevia. Not paleoish. Highly processed. Very rewarding. I put salt amost to everything I eat. All this while reducing drastically my physical activity levels. So you have less calorie expenditure + increased food reward = maintained weight (actually I have lost some pounds). In a formerly young age MetSyn.

My opinion is that food reward is only a factor in obesity if it incites eating high sugar/trans fat stuff.

ItsTheWooo2 said...

"My opinion is that food reward is only a factor in obesity if it incites eating high sugar/trans fat stuff."

Exactly my belief only you said it so much more succinctly.

ItsTheWooo2 said...

@mightochondrial 5/30 1:01pm (Pt 1)

REgarding the pharmacokinetics of leptin administration -

I'm really having trouble following your logic as well as stephans, you seem to be citing observations as definitive evidence of hypothalamic leptin hypoactivity / resistance, when from my perspective those same observations in NO WAY support your purported mechanisms.

If fat people who have NOT lost weight show no response to leptin, however fat people who DID lose weight DO respond to leptin, explain to me how this is evidence that peripheral injections of leptin exhibit no CNS effects? It is evidence, however, that leptin plays no role in mediating weight loss from an obese state, and only plays a role in preventing weight gain assuming obesity is controlled for.

Leptin injected peripherally absolutely exhibits CNS effects, there is no doubt. I had an MRI done. It is plainly evidenced by the energy use of my brain (leptin deficient = hyperactivity in appetite centers of brain; leptin replete = appetite centers metabolic activitiy is normalized status post leptin injections). Yes, I literally had an MRI done. This was shown. Proof.

Not to mention the fact that numerous pituitary hormones were normalized after leptin injections - in fact, this is the whole way leptin treats hypothalamic amenorrhea (which is the main condition being studied in the clinical trial I participated in).

Early on in leptin therapy, peak leptin level occurs 3 hours status post injection. However, later on in leptin therapy when the body makes antibodies to leptin, the peak may occur several hours later, or at unpredictable times. Most people will make antibodies to leptin sooner or later, making it difficult to detect the leptin peak because it will no longer be predictable due to the confounding variable of antibodies.

After 3 months of leptin therapy I began making antibodies, which interfered with measuring my serum leptin level accurately since the antibodies bind to the leptin causing the results in a blood test to be outrageous (early on my levels while taking the 0.08mg/kg dose were around 20... at month 3 the level began to rise, and at the end of the study the level was around 80 or so, a ridiculous reading even though my dose never changed). Early on in the study my dose was high-physiologic @ 0.08, this was later reduced because my response was so fantastic (I was the only participant who was leptin deficient PURELY... all other participants were either extremely low body fat/excessively muscled, or over exercising, or eating shitty diets with few calories... my problem was more or less purely leptin deficiency so I responded exquisitely to the drug and my dose was lowered with no loss of symptom control). Most of the other participants were female body builders, athletes, low grade eating disorders... I was the only subject who was an ex-fattie, who didn't exercise, who ate lots of dietary fat and zinc, who had a body fat level in the 20s, etc. My hypoleptinemia was a direct result of having previously been hugely fat, and now being thin.

Very few people out there need leptin injections. Most women who benefit from them, need to just eat more and exercise less... the very few who do need them, such as myself, are few and far between because there are very few peple out there with valid disorders of body fat atrophy (acquired lipodystrophy, congenital lipodystrophy, congenital leptin deficiency, and extreme massive weight loss from extreme obesity to a normal low body fat - are pretty much the only valid conditions justifying its use, and VERY few people have any of these conditions, most obese people only partially correct their obesity and so have plenty of leptin left).

ItsTheWooo2 said...

@mitochondrial 5/30 1:01pm (pt 2)

You wrote:
"I don't see that ALL your response is from free leptin getting across the brain blood barrier, it's a long way to go ; we have leptin receptors in the adipose tissue, skeletal muscles, islets of pancreas, spleen, heart, lung, small intestine and adrenals (with men also receptors in testes). There are at various kinds of leptin receptors, with the "soluble" kinds forming a feedback loop with free leptin; then there are the "short" trans-membrane leptin receptors and the "long" leptin receptor isoforms inside cells that are essential to leptin being able to act in that tissue cell."

I never argued ALL of my response was due to central leptin effects. A huge portion of it was , however.

1) Correcting my estrogen deficiency was a direct result of the central effects, for example. No leptin, no FSH/LH, no ovaries working, no estrogen. No estrogen means bad, bad things. Estrogen is very vital for female wellbeing. We hear a lot about how important testosterone is for men's health, what gets lost in the shuffle is that estrogen is for women's health the same thing as testosterone for men. Old ladies gain weight after menopause as a direct reaction to the ovarian shut down - body fat makes estrogen, and so they maintain equilibrium. Thin women have the most difficulty with menopause for this reason and many eventually resort to HRT just to avoid depression fatigue and various other dysfunctions. This is all related to the wonderful feedback loop between nutrition and female fertility.

2) Helping my brain recover from depression and obsessive compulsive thoughts was a central effect of leptin (this is shown in animals, leptin protects the brain from stress mediated damage via regulating cortisol activity while upregulating BDNF activity - animals given leptin injections are immune to stress induced depression, FYI, and all seriously mentally ill people have abnormally low leptin prior to treatment)

I remember the day after using leptin for the first time, I was sitting in a public place and I felt this sense of total happiness and contentment. I hadn't felt that way ... ever.

3) Much of my appetite reduction was a central leptin effect (and yes, there was MRI evidence, thxumuch) . Trust me, you don't want to know that hunger. All food no matter how trivial looks delicious. You don't crave junk food, you crave protein and fat and you never want to stop eating.

ItsTheWooo2 said...

@ micochondrial (pt3)

The peripheral leptin effects I obviously experienced was the increase in energy. Leptin allows T4 to convert to T3 normally, fT3 will go up HEAPS after leptin is replaced, and indeed my fT3 levels became normal after leptin, and they dropped after leptin was withdrawn. This was perceived subjectively as having a lot of energy, vs having a lot less energy.

A major symptom I get when off leptin is that I need to eat food... if I go a few hours without eating I become very cold. I need the continuous source of calories to keep my T3 up, if I go a few hrs sans food I get cold and listless even if I ate a lot the day before. When I am taking leptin, my body works normally and I can go a long time without eating, without feeling half dead. I will only be hungry but I won't be cold and barely able to move.

Another peripheral effect of leptin is more normal glucose tolerance and insulin dynamics. I was able to eat way more carbs on leptin. Now that I am off leptin my glucose is more fragile and I have to go back to stricter low carb.

But yea, must of the leptin effects are central.

I am 1-2 weeks post leptin, I am really hoping I don't become amenorrhetic again... because, estrogen deficiency makes everything so much worse. Estrogen deficiency compounds leptin deficiency in a cycle, you know (no estrogen, no leptin recetpors, it's like being even more hypoleptinemic ).

I really don't want to resort to estrgoen replacement, after all I have functional ovaries and I am not concerned with birth control, and given my mood disorders and weight problems I am scared HRT may have unintentional consequences in either mood or weight. But I suspect in a few weeks I will find myself at a doctors office taking the estrogen, because what can you do, my ovaries do not work because I am hypoleptinemic, because I have a disease that no one cares to treat properly, because popular opinion is that leptin has no role in weight maintenance and fat people who have lost weight are just like thin people.

montediaz said...


I.F. definitely is the reason I dropped 60 pounds. My experience is a bit different though. I had zero hunger and had to remind myself to eat every other day. I had crazy surges of energy during this time and no loss of strength. If anything I was getting stronger.

One crazy thing I noticed is that I had absolutely no desire for "palatable" foods. I was surrounded by pasta, pizza, burgers, etc etc. I didn't have to tell my body not to eat it, I was totally indifferent. Food didn't matter anymore.

What's interesting is that my food choices were not restricted when I did decide to eat. Typical meals were standard SAD fare: Burgers, burritos, nachos, pasta, pizza, Gatorade, etc etc.

When my situation changed and I stopped I.F. the hunger and the weight spontaneously came back....

ItsTheWooo2 said...


The reason anorexics sometimes remain hypoleptinemic is because they ARE STILL DISORDERED. Just because an anorexic gains a few pounds so that their BMI is no longer under that magic 17.5 number by no means suggests that they are free of disordered behavior.

As I said previously, the majority of "recovered" anorexics who remain hypoleptinemic are still disordered. They refuse to eat enough calories. They refuse to eat meat and do not take supplements. They may have normal BMI but their body fat is deficient. They purge. They exercise excessively.
I used to have a mild eating disorder, I spent a lot of time conversing with seriously eating disordered people on support forums. IT became clear to me those who failed to recover menses after "restoring weight" were doing lots of unhealthy things, like binge eating junk food, not eating meat, not taking zinc, purging, etc. Yes, if you do that, you will remain hypoleptinemic. You may have adequate body fat but nutrition is very important too for leptin level. I have never met an eating disordered person who could not restore menses, if they truly were at a healthy weight and eating healthfully. I have met lots of eating disordered people who were still compulsively exercising or binging and purging junk food, and failed to recover menses, yes.

Bulimics sometimes get HA too, even though they aren't underweight. Why? A diet of starving combined with junk food binges is not conducive to fertility and will cause leptin deficiency too. Zinc deficiency causes leptin deficiency for a reason - zinc is a major component for growth of tissue, and zinc deficiency in a female will prevnet reproduction. Overexercising will also cause leptin deficiency. Zinc deficiency goes along with protein deficiency, and it is incompatible with fertility. A disordered person who is not eating meat and is only binging and purging cotton candy is not healthy enough to have a child. You need protein and zinc to grow a fetus, and the body naturally turns off leptin and fertility when these are deficient.

Leptin is reactive to so much more than body fat, especially for people who are normal weight.

The difference between people with eating disorders, and people in my situation, is that I did everything right and still became amenorrhetic - I had a body fat over 20%, I never exercised, took my zinc, ate a ton of protein, ate heaps of fat, no binging/purging/fasting and still no menses. The resons for that is my body fat refused to make leptin even though it should have been, and the reason it refused is because of my prior history of obesity.
Find me an anorexic who can say that. Find me one eating disordered person who is totally free of unhealthy starvation behavior, who still doesn't get menses. Eating protein and balanced diet with enough fat and zinc, with enough body fat, with no compulsive exercising or fasting or purging? You can't find such a person because she does not exist, because her body will totally make leptin in that situation, because her fat cells work normally. My fat cells, on the other hand, do not.

I have no doubt leptin injections will help eating disordered people - however they aren't appropriate because they have a mental illness which forces them to starve themselves and eat very unhealthfully, their leptin output is otherwise normal assuming they live like normal people and stop all the disordered behavior.

ItsTheWooo2 said...

@ Roberto

Dopamine is a major regulator of hibernation response. In animals who hibernate completely, administering dopamine agonists wills top the hibernation process.

What we need to understand is hibernation is not black and white; seasonal adaptation exists on a gradient of many animals who live in climates where there are large seasonal shifts, hibernation merely represents an extreme manifestation of it. Squirrels hibernate... however humans just gain weight, slow down, dim their mood, sleep more, move less, and may become infertile if they are thin. THe "winter blahs" represent a seasonal adaptation which is basically mild hibernation.

I believe garden variety obesity and carbohydrate sensitivity is essentially a nervous system disorder where the person is born with genetic traits which make them hypersensitive to detecting signs of seasonal shift. Sort of like SAD, except in your body fat and metabolism. One powerful signal for impending winter is an increase in carbohydrates. Humans vary in their capacity to detect and respond to seasonal shift - those from recent nomadic tribes or hunter gatherers do it best, as they most depend on the weather trends for survival. Those from established agricultural societies in asia and europe have lost this capacity to some extent and are less prone to carbohyrate mediated obesity/glucose problems.

Now, in an environment which is logical to these genes, an increase in carbs occurs before winter, and so triggers higher insulin, fat storing and increased appetite, etc. It is self terminating as the season is. Obesity never occurs, the extra weight is merely an advantage.

However, in a modern agricultural environment, carbohydrate excess is a year round proposition. As a result of hunter gatherer genes living in an agricultural worold, the genes to fatten remain hyperactivated due to year round carbohydrate excess, as do other seasonal adaptation signs like decreased motivation and energy and movement, and increased sleeping and blood sugar. For the person with these genes, the increase in glucose from the food triggers dopamine receptor downregulation - the same thing occurs in hibernating animals where by which dopamine receptors downregulate themselves and the animal enters hibernation. The lower dopamine sensitivity then triggers all of the symptoms we associate with seasonal adaptation, as well as with human obesity (moving less, eating more, being apathetic, gaining body fat, glucose tolerance impared).

When you give dopamine agonists to obese people, you observe their obesity improves. SO does diabetes and glucose tolerance.

When you give dopamine antagonists to healthy, non-obese mentally ill people, they develop personality and metabolic profile identical to a garden variety obese person. Their mood and motivation dim, which is great for manics and schizophrenics. Crazy off the wall talking to god? Here, take this haldol, now your brain won't work, good night. Watch the weight pile on and their face freeze and their body not move as they lose the will to spontaneous movement, and their blood sugar increases, and they basically turn into me before I figured out that carbs trigger this bad syndrome in my particular genetic profile.

ItsTheWooo2 said...
There is so much documented on obesity and dopamine, and the finding is consistent that people who are obese have low dopamien d2 binding and this is corrected upon food restriction.

SInce scientists are stupid, they have not yet made the link between obesity and seasonal adaptation/hibernation, even though it is begging to be made and a similar dopamine receptor downregulation occurs in hibernating animals, and obesity usually afflicts recently modernized hunter gatherer populations, and rarely affects people from europe or asia where they have a long tradition of agriculture. Most of the questions around this finding center on "gee, I guess fat asses ate themselves into dopamine deficiency, because they ate so much they burned out their dopamine, lol!" which is a ridiculous assumption.

Cat said...

Woo: "Since scientists are stupid"

So stupid that all of your theories are based upon their work.

If you think that your argument is so clear, why not write a review? You don't have the be attached to an academic organization to do that. Write up your ideas in a well-cited, organized way and then send it off to the appropriate journal and see what the reviewers say. If your argument makes sense, is clearly written and is backed up by evidence, then your paper will be published and maybe you will help to spawn a new line of research.

This seems like a better idea than sitting back and insulting the process upon which you rely so heavily.

Might-o'chondri-AL said...
This comment has been removed by the author.
Lucas Tafur said...


Actually, 2 months ago I went to a trip and did a little "experiment". For 1 week I only ate one big meal of whatever I liked (and I eat BIG). Everyday was a pufa/sugar indulging adventure. I was able to maintain my weight easily. I usually apply this to my clients as well. IF is a very flexible option.

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montmorency said...


"I'm happy that Itsthewoo enjoys her low-carb diet, but for many it becomes quite monotonous and boring. I'm restating what Stephan has already said, but its possible that what effectiveness low carb dieting offers has nothing to do with insulin. Especially when a lot of protein rich, low-carb foods are known to spike insulin."

I would like to refute the "monotonous and boring" argument. I very often eat the same low-carb items at every meal and never get bored with them (fresh meat, eggs, gently cooked in beef dripping, optional cheese, for example).

If I vary them, it is not for variety (except organ meats for the nutrients) but because of availability or lack of.

Others may well think it would be monotonous and boring, but for me it's not. The reward, if there is any, is mainly the feeling of satiety from the meat and fat. (There is a slight feeling of satisfaction from the texture as well, one reason I despise minced (ground) beef, which has none).

This is not the same "reward" that I used to get from sweet fruit, when I used to eat it by the pound. I was going for the sugar hit. I was addicted to fruit.

I don't think I'm addicted to meat. I stop eating it when I've had enough, and don't particularly look forward to the next meal; I just don't think about it; it's fuel, not entertainment.

The insulin response to protein is relatively small as I understand it. I found this link rather interesting:

Quote: "A protein-rich meal leads to release of both insulin and glucagon. The latter stimulates gluconeogenesis and release of the newly formed glucose from the liver to the blood stream. The very moderate rise in insulin associated with the protein meal stimulates uptake of the sugar formed in the liver by muscle and fat tissue.

montmorency said...


"Hunter-gatherers do not have the magical ability to get rid of excess calories. They're just in energy balance: energy in = energy out.

No magic maybe, but it still leaves the question as to why they were in energy balance whereas many in our industrialised societies aren't. Maybe there is something about the quality of calories that modern people consume rather than its quantity.

As to squirrels and seasons, while we are not as extreme as squirrels, I thought there was actually a slight seasonal element to it in humans, with higher circulating insulin generally in the autumn and winter, and lower in spring and summer, making it easier to gain weight in autumn/ winter, and easier to lose in spring/summer.

This would make sense if we think of our ancestors fattening up for the winter by gorging on the sweet fruit that is naturally more plentiful in the wild towards the end of the summer and beginning of autumn.

montmorency said...

@It's the Woo2:

I appreciate your attempt to challenge this leptin quasi-consensus, based on ... what, I wonder. It seems like a lot of assumptions have been made, and some leaps of faith taken, all apparently based on the idea that "obesity is caused by over-eating", instead of regarding it as some failure of fat accumulation.

Also, from the experiences you describe, you probably have more personal leptin experience than any of us, so we should listen to you on that score, at least.

May I ask you the following:

Why, do you think, you were able to reduce your body fat to such a remarkable extent when, as you observe, many other people on similar low-carb diets are not able to get down so low, and permanently stall, at some higher level of body fat than would normally be regarded as ideal?

May I ask you exactly what you were eating and drinking when you were eating low-carb?

Thank you.

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