Food reward, a factor in obesity

 “I think food reward offers the most compelling explanation for the US/global obesity epidemic.” 

Stephan Guynet 
In studies where the food intake and energy expenditure of subjects are carefully monitored over a period of weeks to months (which tends to average out day-to-day fluctuations) a remarkable balance between calories consumed and calories burned was observed. When various mammals, from mice to monkeys, are either overfed or starved for a few weeks, their weight soon returns to normal levels when free access to food is resumed. Crucially, our mammalian bodies seem to be able to regulate feeding based on the amount of energy available in the food we consume, not just on the volume of that food.

The above quote David Linden, suggests the body controls body weight by registering the amount of energy in food. This theorizing usually leads to the white adipose tissue derived hormone leptin and particularly its effect on the hypothalamus. Leptin, in general, correlate with adipose tissue mass. But the energy the body needs comes from two places: food and stored energy. Increasing use of stored energy will make animals and human eat less. Any energy-sensing control system must register the total amount of energy available, both from foods and from fat and glycogen stores. From this point of view, obesity could to be caused by the body not having access to its own stored energy and so continues to signal for food intake. Alternatively, the stored energy is readily available, but somehow an obese person experience feelings of hunger and craving that overpower any signal telling the brain that there is enough energy available. This scenario makes it likely that obesity is caused by a malfunctioning control system.

Stephan Guyenet has created quite a stir lately with his posts about food reward. Several of the posts have over 100 comments, some more rational than others, but people clearly have strong feelings about this. I think one of the reasons some people feel personally offended by his writing, is that they feel food reward lends support to overweight being caused by lack of willpower. This is definitely not Stephan’s intent, nor does his reasoning indicate willpower as a major factor. Nevertheless, willpower is a major part of food reward, as one of the opposing forces to a physiological drive to consume rewarding foods.

The theory of food reward is a theory of how foods affect our feelings, stimulate our behavior and how some foods appear addictive and promote addictive behavior. This seems lost on many. Food reward does not and cannot explain how we fatten. To find the answer to this we need to look at the physiology of the fat cells. Basic biochemistry still applies and some foods are more fattening than others, although as it seems, Stephan does not think so and he even uses his belief that macronutrients doesn’t matter as an argument in favor of the food reward theory. But the theory itself is a theory of why we (over)eat, not a theory of how we gain fat.

Even though the theory of food reward is not about willpower, willpower invariably enters into the equation. Many physiological drives can be affected by conscious thought. Stick your hand in ice water and your head tells you to pull it out (or your spine), but you can keep it submerged by willpower, some longer than others. Highly rewarding foods do, according to Guyenet, cause obesity in susceptible people, just like drugs may make addicts of some (often the same people). Still, I cannot see that food reward argues more strongly for willpower as a part of obesity, than other rational theories.

The theory of food reward is actually mostly about carbohydrates as most of the data relating to it is from the studying of sweet foods. As Hans-Rudolf Berthoud put it 

For nonsweet palatable foods (typically high-fat foods), there is less convincing evidence for development of dependence…” [1]
So it seems the key questions are:

– do sweet foods cause addiction and increased energy intake with subsequent obesity?

– do sweet foods cause obesity (fat storage) with following addiction or addiction like behavior possibly caused by metabolic clues?

As we undoubtedly fatten differently and not everyone becomes obese despite similar obesogenic environments, we can conclude that addiction to high palatability foods is 1) genetic and that preexisting differences in reward functions cause obesity; 2) intake of palatable foods is in itself addictive and leads to obesity; or 3) obesity (the excess storage of energy in fat tissue) cause changes in reward functions thus further accelerating obesity.

As many lean people also eat large amounts of highly rewarding foods, it seems unlikely that the food itself can be to blame. So, either food reward is secondary to the harmful effects of sugars/grains (sweet food not found in hunter gatherers): these foods create excessive fat storage in obesity prone people and this cause addictive behavior towards the very same foods; or it is the primary cause of obesity: people prone to weight gain have physiological measurable differences in parts of the brain that cause an addictive intake of fattening foods.

Although I enjoyed the posts about food reward I was left with very many unanswered questions after reading:

The reasoning 
Stephan uses the fact that hunter-gatherers are lean in support of rewarding foods causing obesity in non HG societies, arguing that one of the reasons hunter gatherers are lean is because their diets are bland (although I think many HG’s would disapprove of their diets being called bland). This argument could go both ways. Because if the foods that drive fat gain also promote addictive intake of the same foods, then traditional diets can be as tasty as any, just as long as they do not contain these particular foods. As long as they don’t, there is no reason to think blandness is the cause of leanness.

Although lean traditional people’s diets are more unrewarding then say a SAD diet, this does not mean that we in the west become obese because our foods are not.

Also we have to ask: if obese people remove fattening foods, which are the same as those considered highly rewarding, will the addictive behavior/strong cravings for the fattening foods subside? I know from experience that many who struggle with strong cravings, lose their cravings when switching to a LCHF diet. The fact that some feel cravings even after some time on low carb diets, does not favor a set-point hypothesis. It could just indicate a dietary insufficiency, like the lack of salts or some fatty acids. As the cravings usually disappear before a considerable weight is lost, it is unlikely that the cravings were caused by the obesity itself. Often, it seems that cravings disappear when people regain the ability to burn fat.

Burning fat, or having a functional metabolism will make us eat less. The oxidation of fat in the liver offers a strong satiety signal [2]. So, even if lipolysis is high in obese, hunger will not go down if somehow the burning of fat in the liver is restricted. This is sort of a “metabolism argument”: One of the things that separate those prone to obesity and insulin resistance from the rest, is a poor and broken metabolism. They rely on glucose (glycogen) for fuel and have poor fatty acid oxidation in combination with blood sugar fluctuations and cravings, so fat is stored rather than burned as it should. Resolving the metabolism issues will in many reduce the cravings and rewarding foods are no longer an issue.

Another important question to ask is: how often during the day and how much hyperpalatable, highly rewarding foods do people who become obese actually eat?

If people become obese without consuming highly rewarding foods (something I consider very possible) then the theory of food reward argues strongly that this type of obesity is mostly due to lack of willpower, as there is no addiction to blame.

The “bland food” study from 1965 Stephan writes of can be used to support a “food reward” theory, but there are many other ways of explaining why the overweight people lost weight while the lean did, not. If the obese ate high sugar/grain and franken-fat diets, that also happen to be palatable once you get used to it, then of course they lost weight on the liquid diet.

The first volunteer continued eating bland food from the machine for a total of 70 days, losing approximately 70 pounds. After that, he was sent home with the formula and instructed to drink 400 calories of it per day, which he did for an additional 185 days, after which his total weight loss was 200 lbs. The investigators remarked that «during all this time weight was steadily lost and the patient never complained of hunger or gastrointestinal discomfort.» This is truly a starvation-level calorie intake, and to eat it continually for 255 days without hunger suggests that something rather interesting was happening in this man’s body.

This isn’t really that interesting. With all likelihood the man could have lost an equal amount of weight eating real foods that are far more rewarding but not fattening. It has been known to happen.

I think decreased fasting insulin occurs as a result of weight loss…

Stephan Guyenet 

Another important point is that the body fat “setpoint” is still a theoretical point, and any theory based on the setpoint hypothesis is equally hypothetical. 

As one would expect if food reward influences the body fat setpoint, lean volunteers maintained starting weight and a normal calorie intake, while their obese counterparts rapidly lost a massive amount of fat and reduced calorie intake dramatically without hunger. This suggests that obesity is not entirely due to a «broken» metabolism (although that may still contribute), but also at least in part to a heightened sensitivity to food reward in susceptible people. This also implies that obesity may not be a disorder, but rather a normal response to the prevailing dietary environment in affluent nations.

Lean people have good access to their own body fat and high fat oxidation rates. They have a better working liver than obese, and they definitely had a better pre experiment diet than the obese. The above results can be explained exclusively by a broken metabolism theory. There is no need to involve food reward.

Some people may be inclined to think «well, if food tastes bad, you eat less of it; so what!» Although that may be true to some extent, I don’t think it can explain the fact that bland diets affect the calorie intake of lean and obese people differently.

Most diets affect lean and obese differently. These people are per definition quite different metabolism wise, and foods affect metabolism. Once again, the fact that one of the many diets that affect lean and obese differently are bland, does not lend much evidence for palatability playing a major part in obesity.

Although the rewarding abilities of different foods might explain some of the reason we overeat on fattening foods there are very many other ways you are likely to gain weight. As David Pier points out in the comments section:

Excess fructose? Too high an omega-6/omega-3 ratio? Too much omega-6? Too little omega-3? Too much polyunsaturated fat in general? Too little saturated fat? Micronutrient (choline, minerals, etc.) deficiencies? Excess total carbohydrate? Superstimulating hyperpalatibility? Over-availability? Excess insulin (cause and/or effect)? Gut flora (cause and/or effect)? Lack of fiber (insoluble and/or soluble)? Multi-generational epigenetic changes? Artificial sweeteners? Endocrine disruptors? Sleep disturbances? Psychological causes essentially independent of all hormonal homeostatic mechanisms?

In his third post, Guyenet writes about the review of low fat non energy restricted diets where overweight lost more weight than lean:

In other words, low-fat groups reduced their calorie intake by an average of 271 calories per day, and lost 7.5 pounds (3.2 kg). When they considered only people who started off overweight, they lost 12.8 pounds (5.8 kg). The investigators noted that the results were similar no matter what the duration of the trial, because weight loss plateaued fairly quickly.

Then he writes

This is all without any instruction to reduce calorie intake, therefore we can assume these dieters were eating to fullness.

No you can’t assume that. These are participants included in non blinded weight loss trials. I would say it’s a safer bet that they were in fact restricting their food intake.

The best low-carbohydrate diet study I’ve seen was published in 2008 in the New England Journal of Medicine (3). 322 «moderately obese» participants were placed on a low-carbohydrate diet, a calorie-restricted low-fat diet, or a Mediterranean diet, for two years. The low-carbohydrate group’s carbohydrate intake decreased by 130 grams per day, which is about half of a typical person’s total intake, and neatly corresponds to the reduction in calories of 561 per day, despite not being instructed to reduce calorie intake.

At two years, the low-carbohydrate group had lost 10.4 lbs (4.7 kg), which is very similar to the average weight loss seen in low-fat diet trials.

There are two major issues here. 1) The study by Shai et al is a horrible study: The Atkins based diet came with recommendations of getting fat from vegetable sources; By 24 months, carbohydrates constituted 40% in the low carb group and 50% in the low fat group. The low fat diet went from baseline fat intake of 31,4% to 30% (no reduction at all); the aurhors left out baseline energy intakes and only reported reductions; The study also used intention to treat analyses. The weight loss in the low carb group for the 272 who completed the study was 5.5kg in the “low carb” and 3.3kg in the “low fat” group. After 6 months the study diets were not very dissimilar.

If this is the best low-carbohydrate study Guyenet has read, he needs to read the other studies. Low-carbohydrate diets usually outperform low fat diets, as long as carbohydrate intake is kept restricted. This outperformance is despite low fat groups having caloric restrictions while low carb groups can stuff themselves as much as they want. His reasoning that low carb and low fat perform equally is flawed in so many ways, and he uses this reasoning to support a food reward hypothesis.

I think the reason very low-carb ketogenic diets cause fat loss is the same reason extreme low-fat diets cause it: they have a greatly reduced reward value.” 

Stephan Guyenet 

The fact that participants in the Lindberg study lost weight without caloric restrictions does not mean food reward had anything to do with it. Once again, if certain foods themselves cause fattening, and we restrict these foods, weight loss is likely to occur. There is no need to blame blandness.

Messing about with dopamine signaling can cause obesity in animal models, and there are differences in dopamine receptors between «normal» people and those prone to addictive behavior. It is not strange that messing about with the brain will cause all sorts of things, but it does not mean obesity is caused by food reward.

There is more reasoning to discuss, but this post is getting way to long. Is there really enough available evidence to justify calling food reward a dominant factor in obesity? If there is, I can’t say I found evidence of this in Stephan’s posts.

And as Paul Jaminet pointed out:

Likewise, we’re all familiar with young people who eat massive quantities of junk food and remain slender. The high food reward diets, even toxic and malnourishing diets, seem not to cause weight gain until some kind of metabolic damage occurs.

It seems that metabolic damage – the disease of obesity – is a prerequisite for food reward to matter.

Obese people should eat boring diets
Guyenet even offers tips on how to make food less palatable and more bland. But does this mean that there are people out there who have tried all the obvious ways to lose weight, like reducing inflammation and cutting back on carbs, who have not succeeded and are left with trying to make food not taste good?

The most palatable foods are those packed with fat and sugar. These foods are the first to go on any dietary strategy. Do we need to make the rest of the diet bland?

Guyenet offers a range of advice for losing weight based on food reward theory. For example:

Don’t snack. In France and many other countries with strong food traditions, snacks are for children. Adults eat at mealtime, in a deliberate manner.

And yet, if snack in itself do not seem to cause obesity, why not snack?

Don’t add fat to your food. That doesn’t mean don’t eat fat, it just means keep it separate from your cooking. If you want to eat butter, eat it separately rather than mixing it in with your dish.

…I don’t know what to say about this…but I know I don’t like it.

Some of his advices are meant mostly for those who struggle to lose weight, but I fear if anyone would follow them, they would die of boredom instead:

Eat only single ingredients with no flavorings added. No spices, herbs, salt, added sweeteners, added fats, etc. If you eat a potato, eat it plain. If you eat a piece of chicken, eat it plain. It can be in the same meal as other foods, but don’t mix anything together. If you would like to keep salt in your diet, dissolve it in water and drink it separately.

There are more of course. Most make sense, but they also make sense without considering food reward.

Importantly, all the studies used to support the award theory can also be used to support different theories. While they do no not falsify a reward theory they do not provide strong supportive evidence. But this is how science works. Stephan is right in offering the theory and he might turn out to be spot on. It will be interesting to see what future studies will reveal. We need some RCT’s to enlighten the causation between food and dopamine response and function, well any kind of RCT in this field would be important. I would like to make foods that are highly rewarding (measured by dopamine response or something fancy, that make people crave them, and that does not contain anything inherently fattening. Then I would give people free access to it to see if they got fat. Wonder what it could be?

«Some people have lost fat simply by avoiding carbohydrate or fat. I’ve heard people say that a low-carbohydrate diet in particular curbs their cravings and allow them to have a healthy relationship with food again (although others have developed strong cravings on low-carbohydrate diets). I believe this is mostly, if not exclusively, driven by the fact that carbohydrate and fat are major reward factors.»

Stephan Guyenet


1. Berthoud HR, Lenard NR, Shin AC: Food reward, hyperphagia, and obesity. Am J Physiol Regul Integr Comp Physiol 2011, 300: R1266-R1277.

2. Friedman MI, Harris RB, Ji H, Ramirez I, Tordoff MG: Fatty acid oxidation affects food intake by altering hepatic energy status. Am J Physiol 1999, 276: R1046-R1053.

The satiating effects of protein

«The mechanisms by which protein may affect satiety remain elusive.» 

Halton and Hu 2004 [1]

“Although the immediate satiating effect of dietary fat may be comparatively weak, there is no doubt that ingested fat does inhibit feeding.” 

Leonhardt 2004 [2]

LCHF opponents keep throwing out the same old argument, that fat is the least satiating macronutrient and that all that fat might thus make people hungry and unable to stay with the strategy. Eventually the low satiating effect of fat will cause people to gain weight. This is claimed despite the existence of several studies showing that people put on ad libitum high fat diets experience less hunger, lose weight and all over seem perfectly fine.

Protein, it is said, is the most satiating macronutrient. So the best dietary strategy is replacing fat with proteins and keeping carbs high.

My colleagues in dispute seem very eager to have me agree that protein is very satiating and that we at least should have this as common ground.

But my own experience urges me not to agree. If I reduce my fat intake and eat more protein, as I sometimes do, for example in periods of stress where I eat too much eggs and lean meat and forget about the fat, I feel horrible. My blood sugar drops and over time lethargy hits in. What’s more, I soon feel hungry and start craving fat/carb combos. Simply eating fat eases my symptoms. Eating carbohydrates would probably also ease my symptoms, but we all know that is no good long term solution.

So are proteins especially satiating?

Weigle et al [3] placed 19 subjects sequentially on the following diets: a weight-maintaining diet (15% protein, 35% fat, and 50% carbohydrate) for 2 wk, an isocaloric diet (30% protein, 20% fat, and 50% carbohydrate) for 2 wk, and an ad libitum diet (30% protein, 20% fat, and 50% carbohydrate) for 12 wk.

Weigle is good for a laugh. Here’s from the introduction of the article

“Both low-fat diets (2– 4) and low-carbohydrate diets that are high in fat and protein have been shown to cause a decrease in ad libitum caloric intake and significant weight loss in humans. Thus, it appears that diets with fat contents at opposite extremes have the same therapeutic result, despite evidence that excessive dietary fat intake promotes obesity. This paradox could be explained if it is the high protein content rather than the lower carbohydrate content of low-carbohydrate diets that offsets the deleterious effect of high fat intakes and results in weight loss.” 

Quite the paradox there. Hope someone will resolve it someday. 

Weigle is often cited for showing that proteins are satiating. But measurements of hunger and fullness showed that even though hunger was reduced and fullness increased during the isocaloric diet, they returned to baseline with the ad libitum diet despite constant protein content. The reason the study is sited is because calorie intake dropped with higher protein. However, satiety and calorie intake did not seem to correlate. 
As in all similar studies, the high protein diet differed from the low protein diet in many aspects even though carbohydrate intake remained constant. Below is an example of what the two different diets might contain. 

So can we conclude that the hunger (temporarily) and body weight dropped because of the higher protein content? Of course not. That would be silly. It might be the proteins, but it might be any one of the other differing dietary factors.

Weigle and colleagues also wrote that

“It is likely that a reduction in dietary fat by 15% of total energy contributed to weight loss in the present study.”

This is a very strange thing to claim, as several studies where subjects are put on high fat diets reports significant weight loss and reduced hunger.

Weigle concluded thusly

“An increase in dietary protein from 15% to 30% of energy at a constant carbohydrate intake produces a sustained decrease in ad libitum caloric intake that may be mediated by increased central nervous system leptin sensitivity and results in significant weight loss. This anorexic effect of protein may contribute to the weight loss produced by low-carbohydrate diets.” 

Skov et al [4] randomized 65 subjects to two ad libitum fat reduced (30%) diets for six months. One with 12% energy from protein and one with 25% from protein. Weight loss in the low protein group was 5.1kg and 8.9kg in the high protein group. By labeling the diet higher in protein a “high protein diet” our focus is drawn away from the fact that the high protein diet also had significantly less carbohydrates. This is a recurring problem; how should the diets be labeled? The labeling wouldn’t actually be problem if the researchers remembered to properly discuss the effects of reduced carbohydrate intake or reduced glycemic index. This, however, is often not done and when a diet labeled “high protein diet” is discussed the protein content usually get the major part of the attention.

Skov and his Danish research fellows later wrote that

“The mechanisms responsible for the larger weight loss caused by an HP diet may be attributed to a greater satiety and fullness, and also the thermogenic effect of protein.” 

But of course, they might be right. A number of studies have compared hunger and satiety in the hours following consumption of a single meal, and have come to the conclusion that a high-protein meal is more satiating. So to say that a high protein diet suppresses hunger might be a correct statement, but it’s still a bloody unfair statement. Because what matters is the long term effect on hunger, and what actually cause the decreased hunger. The studies looking at single meal effects are usually poorly controlled and there are many confounding factors. Also, the protein content of high protein meals is often very high, ranging from 40% to 75%, and most of the studies have very few participants.

One of these studies, from Stubbs et al [5] (60% protein), found that there was no difference in subsequent energy intake despite acutely reduced hunger following a high protein meal. This was one of the more well controlled single meal studies.

Thomas Holton [1] notes that

“There are, however, some methodological issues concerning this type of research. Satiety appears to be influenced by a wide variety of factors including palatability, food mass, energy density, fiber and glycemic index. When using real foods, it is difficult if not impossible to control for all of these influences at the same time while still delivering different amounts of protein.” 

Fat is often considered the least satiating macronutrient from these single meal studies. But it might not be that simple. Mark I Friedman found that hepatic ATP, or the energy availability of the liver, exerts a strong effect on feelings of hunger. What is important, is that there’s fuel available, be it glucose or fat. A theoretical satiating effect of proteins is their conversion to glucose by gluconeogenesis thus providing more fuel for the liver.

A quote from Friedman

“Hyperphagia associated with the development of obesity is accompanied by a metabolic state that fosters the deposition of fat in adipose tissue, the largest fuel storage compartment. This shift in fuel partitioning toward storage is independent of and occurs before the change in food intake in nearly every animal model studied. According to the model presented here, overeating results because fuels that would otherwise be oxidized to produce ATP in a detectable manner are redirected into fat stores.” [6] 

And what redirects fuel into fat stores? I’ll leave it to you to figure this one out yourself. The point is that according to Friedman’s work, a higher fat diet will reduce hunger by making both glucose and fat more available for oxidation.

Daniel H. Bessesen [7] also believes that what separates obesity prone and those prone to leanness are differences in the trafficking of fat. He writes

“It may be that a preferential delivery of dietary fat to metabolically active tissues including liver and skeletal muscle allows more accurate sensing of dietary fat in a manner that promotes more accurate coupling between dietary fat intake and oxidation. Conversely, preferential delivery of dietary fat to adipose tissue may impair nutrient sensing and promote weight gain.” 

On low carb ketogenic diets, hunger is often drastically reduced within a matter of a few days after initiation of carb restriction. With fasting or starvation we see a drop in hunger with increased ketone body concentration. This satiating effect is often attributed to the ketone bodies themselves, in particular beta-hydroxybutyrate, but according to Friedman’s theory it could just as likely be caused by the increased internal energy availability that occurs when lipolysis and fat oxidation (with a subsequent increased ketone body production) are increased. 

Some studies also suggest that you will experience a stronger hunger if you eat some food as mostly carbs, than if you eat no food at all. 
The belief that high protein diets are especially satiating seem similar to the belief that high fat diets are fattening. Of course they might be, but as I said, it would be a bloody unfair statement. In animal studies high fat diets often do cause obesity, but normally only in the presence of a substantial amount of carbohydrates (or crazy amounts of frankenfats). The term “high fat diet” does not imply minimal carbohydrates. High protein diets might decrease hunger, but higher protein diets are usually lower in carbohydrates, sugars and have a lower glycemic index. Attributing the decreased hunger to the proteins might be just as much off target as attributing weight gain to fat.

Halton and Hu illustrates this point when they term many low carb study diets, high protein, low carb diets. Like the much sited study by Samaha et al [8]. In this study the low carb diet was a 1630kcal, 22% protein, 41% fat and 37% carbohydrate diet. Protein intake was well below 1g per kilo body weight. It produced a greater weight loss than a 1576kcal, 16% protein, 51% carbohydrate and 33%fat diet. The results can hardly be attributed to the proteins alone. Holtan and Hu, in their review of high protein diets and satiety, forget to discuss the potential long term satiating effects of increased fat intake.

Monika Leonhardt [2] seem more open and writes

“Fat seems to be less satiating than carbohydrate and might therefore lead to passive overconsumption [4]. Yet, in rodents, the efficacy of a high-fat diet to induce hyperphagia appears to be related to the energy and carbohydrate content of the diet. Therefore, overeating of high-fat diets is presumably not due to the high fat content alone. This assumption is in line with recent studies in humans showing that a high-fat, low-carbohydrate diet reduced rather than increased voluntary energy intake.” 

Leonhardt continues to suggest that overeating on a high fat diet might be, amongst others, due to

“the high energy density of such diets in combination with their carbohydrate content” 

“the usually low postprandial oxidation of ingested fat in the presence of carbohydrates.”

That protein exerts some acute satiating effect compared to carbohydrate and fat is hardly a good point. It is an interesting observation, but not an argument in favor of high protein diets. People put on high fat low carbohydrate diets also feel their hunger disappear and shed weight without caloric restriction. The high protein diets seem to stem from the cognitive dissonance of the upholders of the traditional dietary dogma. First fat was fattening, now it seems carbs are equally so. What they are left with are diets low in both fat and carbohydrates, diets that do not consider any of the important roles of the vast variety of fatty acids available to the body. I’ll eat my hat the day some anthropologist can show me a traditional human population thriving on a high protein, low fat, low carbohydrate diet. Fat matters.


1. Halton TL, Hu FB: The effects of high protein diets on thermogenesis, satiety and weight loss: a critical review. J Am Coll Nutr 2004, 23: 373-385.

2. Leonhardt M, Langhans W: Fatty acid oxidation and control of food intake. Physiol Behav 2004, 83: 645-651.

3. Weigle DS, Breen PA, Matthys CC, Callahan HS, Meeuws KE, Burden VR, Purnell JQ: A high-protein diet induces sustained reductions in appetite, ad libitum caloric intake, and body weight despite compensatory changes in diurnal plasma leptin and ghrelin concentrations. Am J Clin Nutr 2005, 82: 41-48.

4. Skov AR, Toubro S, Ronn B, Holm L, Astrup A: Randomized trial on protein vs carbohydrate in ad libitum fat reduced diet for the treatment of obesity. Int J Obes Relat Metab Disord 1999, 23: 528-536.

5. Stubbs RJ, van Wyk MC, Johnstone AM, Harbron CG: Breakfasts high in protein, fat or carbohydrate: effect on within-day appetite and energy balance. Eur J Clin Nutr 1996, 50: 409-417.

6. Friedman MI: Control of energy intake by energy metabolism. Am J Clin Nutr 1995, 62: 1096S-1100S.

7. Bessesen DH: Update on obesity. J Clin Endocrinol Metab 2008, 93: 2027-2034.

8. Samaha FF, Iqbal N, Seshadri P, Chicano KL, Daily DA, McGrory J, Williams T, Williams M, Gracely EJ, Stern L: A low-carbohydrate as compared with a low-fat diet in severe obesity. N Engl J Med 2003, 348: 2074-2081.

About hunger

Much has been said about hunger. The sensation is often considered largely under cognitive control. An overweight person seeking counselling is asked to eat less, despite claiming to already be hungry most of the time. Hunger is in this case simply considered by the treating authority to be suppressed by a strong will of mind. Sadly, it doesn’t work that way.

Many theories have however been presented in an attempt to explain hunger through physiological processes. Amongst these are hunger and satiety centres, the glucostat and lipostat theory and body weight set point. Unfortunately most of these fail to explain the observations in a satisfactory way. There is however a less known hypothesis which manages to explain most observations quite well. The consequence of this hypothesis however, is that macronutrient intake may play a very important role. Not because they contain different amounts of energy, but because they influence our metabolism in different ways.

Hunger might seem easily understood, as we get hungry when we don’t eat and feel sated when we do. But this is a gross oversimplification. If we fast, we may feel extreme hunger during the first day or two, but then as ketone body production sets in and fat metabolism is up regulated, hunger is diminished despite the complete lack of food. In some cases people feel hungry most of the time and satisfying the constant hunger may cause obesity and even death. This makes no evolutionary sense. Why is a body creating hunger signals when it obviously has more than enough energy in its stores and is obviously consuming more than enough energy to maintain it’s weight? The simple answer is that stored energy is not necessarily available for use, and the amount of energy ingested also does not necessarily reflect the amount of energy available for use.

In the 1950s, Jean Meyer presented the glcostatic theory. This hypothesis was used (and unfortunately still is) to explain how our blood glucose level controls our sensation of hunger and satiety. It states that a low blood glucose level stimulates an increased hunger and food intake, while high glucose levels will stimulate satiety. The theory is not easily rejected and may indeed seem plausible. In early studies, scientists succeeded in inducing increased food intake in rats and increased hunger in humans, by using insulin to reduce glucose levels. In addition, hypoglycaemia (low blood sugar) in diabetes was known to be associated with increased food intake. Also, the knowledge that our brain is strongly dependant on glucose for fuel further increased the plausibility of the theory. But, although glucose level does influence our feeling of hunger it is however unlikely that it controls our total food intake and low glucose might just be an effect rather than a cause. One good argument against a glucostatic theory is that affecting fat metabolism, independent of glucose levels, can increase hunger.

As we grow our different body tissues grow in unison, but after we become adults most of the change in body size is due to changes in fat tissue size. The lipostatic hypothesis claims that any change in body fat is followed by a signal to either increase or decrease food intake.  I’ll admit that from an evolutionary point of view this seems plausible, but the number of observations that fails to be explained by this hypothesis are many. Unfortunately, many consider this hypothesis close to a fact even today, but now it goes under the name of the body weight set-point hypothesis.

One of the strongest arguments in support of the lipostatic hypothesis has been based on the hyperphagia (fancy word for great hunger or eating a lot) and obesity that result following ventromedial hypothalamic (VMH) lesions. During the 40’s and 50’s it was found that damage to specific hypothalamic areas (VMH lesions) provoked dramatic alterations in food intake and body weight. These lesions caused an increased food intake in most animals studied. As it was assumed that the hypothalamus was the control centre of hunger and satiety, the increased food intake in these studies was thus assumed to be a result of increased hunger. Also, people with the genetic condition known as Prader-Willi, are known to have a voracious appetite. This genetic condition affects the hypothalamus as well and it was once again assumed that this genetic error affected the hunger/satiety centre of the brain thus causing increased food intake.

Although VMH lesions were originally used in support of a lipostatic hypothesis, the very same studies provide evidence for the improbability of the same hypothesis. The fact that hunger occurs in rats with VMH lesions despite the presence of an internal excess of metabolic fuels suggests that the size of the fat depots becomes important to feeding only if the animal has access to them. Access is a key point here. 

It was later found that although VMH lesions did indeed cause increased food intake, the very same lesions also disrupted fat metabolism in favour of increased fat storage (partly due to increased insulin secretion) thus making fat depots unavailable. Hyperphagia has been associated with obesity and large energy storage in fat tissue, but it has also been shown that in most animal models, the increase in fat storage occurs prior to increases in food intake. In other words, increase in fat storage (the unavailability of fat for fuel) increases hunger and thus food intake. This is an extremely important point. Increased hunger may very likely be caused by increased fat storage and not the other way around, as is the general interpretation. In support of the above-mentioned, scientists has successfully increased both the power and the duration of satiety, simply by inhibiting fat storage.

Even in the Prader-Willy syndrome, the hyperphagia observed might very well be secondary to fat storage. They might be eating because they are getting fat, and not the other way around. They might be eating because most energy is locked away in fat depots, and the rest of the body is starving. Our body gets its energy either from its stores or from food. If the stored energy is unavailable the body is left with no other choice than to increase hunger. I have unfortunately only seen one study described where a low carbohydrate diet was administered to people with Prader-Willi, but it does provide some interesting clues. Remember that reducing dietary carbohydrates most often will cause a decrease in fat storage. If hunger is caused by large fat storage, reducing the storage would presumably decrease hunger, as has been done with medications in other studies. In the study described in ”The Prader-Willi syndrome”, by Holm et al it seems that carbohydrate restriction does indeed reduce hunger effectively, even in people with Prader-Willi. The mechanism behind the reduction in hunger is presumably the decrease in fat storage and thus an increased release of stored energy from fat tissue.

In the genetic rat models of obesity fa/fa rats and ob/ob rats, their defect genetics makes them overweight even with calorie restriction. The effect of their defects is an increased fat deposition. This increased storage of energy in fat tissue causes a concomitant hyperphagia and decreased energy expenditure.

Low blood sugar may also provide a strong stimulus for hunger, as the glucostatic theory claims. But, the reason for a fall in glucose levels may be caused by a low fat oxidation. If little fat is oxidized and ketone bodies are not being produced our body is more dependant of glucose for fuel, and blood sugar falls quickly. In the studies where insulin was used to stimulate hunger, it also stimulated fat storage. Insulin makes all fuels less available fore use. 

It may not even be the low glucose level in it self that makes us hungry. It may simply be the low total amount of energy available. A combined inhibition of fatty acid and glucose metabolism produces a far greater eating response than would be expected from inhibiting the metabolism of each component separately. A combined inhibition may even produce hunger when the metabolic inhibitors are given in doses that alone do not stimulate eating. This increase in food intake would not be expected if signals from glucose and fat metabolism controlled feeding independently, and indicates that changes in glucose and fat metabolism influence feeding through a common mechanism. The likely place for this regulation would be the liver.

Mark I. Friedman and Edward Stricker elucidated the mechanisms of how macronutrient composition affects hunger as early as 1976. They wrote that the stimulus for hunger and satiety were likely the result of alterations in oxidative metabolism within the liver. Their reasoning makes unnecessary previous hypothesis such as hunger and satiety centres, glucostat, lipostat, and body weight set point.

More recent work by Mark Friedman makes it clear that liver ATP production is an important regulator of hunger. Although intake of the different macronutrients affects hunger it doesn’t seem likely that quantitative changes in the use of these nutrients would provide a stimulus for hunger. Compensatory changes in the use of other fuels would limit the significance of this. It is more likely that hunger occurs whenever the immediate availability of utilizable metabolic fuels is reduced below some critical level.

The consequence of all this is that a diet with little carbohydrates and generous amounts of fat makes us lean much because this diet provides a constant flow of available energy for the liver, both from food intake and from body energy stores, and this makes us less hungry.