Blame weight gain on the brain

Many people claim they are addicted to food. That may not be too far from the truth.

Over millions of years of evolution, our brains have adapted to provide us a reward for successfully ingesting food. The hormone dopamine appears to be the key link in this reward process. But to complete the circuit, dopamine has to interact with its receptor. It has been known for many years that the ability of dopamine to combine with one of its receptors (the D2 dopamine receptor) is compromised in obese individuals compared to normal-weight individuals (1). This led to the hypothesis that obese individuals overeat as a way to compensate for the reduction in the dopamine reward circuits just as individuals with addictive behaviors (drugs, alcohol, gambling, etc.) do when their dopamine levels are low. It is also known that food restriction up-regulates the number of D2 receptors (2). This likely completes the reward circuit.

This effect of increasing D2 receptors is confirmed in obese patients who have undergone gastric bypass surgery that results in calorie restriction (3). This may explain why gastric bypass surgery is currently the only proven long-term solution of obesity. More recent studies with functional magnetic resonance imaging (fMRI) have indicated that unlike women with a stable weight where the mere visual image of palatable food increases the reward activity in the brain, that response is highly reduced in women who have gained weight in the past six months (4). This suggests that the dopamine reward circuits are compromised in women with recent weight gain, thus prompting a further increased risk for overeating in those individuals to increase dopamine output.

So does this mean that the obese patient with a disrupted dopamine reward system has no hope of overcoming these powerful neurological deficits? Not necessarily. There are a number of dietary interventions to increase the levels of dopamine and its receptors. The first is calorie restriction, which is only possible if you aren’t hungry. The usual culprit that triggers constant hunger is a disruption of hormonal communication of hunger and satiety signals in the brain. It has been shown that following a strict Zone diet can quickly restore the desired balance that leads to greater satiety (5-7). The probable mechanism is the reduction of cellular inflammation by an anti-inflammatory diet (8-10).

Another dietary intervention is high-dose fish oil that has been demonstrated to both increase dopamine and dopamine receptors in animals (11,12). This would explain why high-dose fish oil has been found useful in the treatment of ADHD, a condition characterized by low dopamine levels (13). Finally, high-dose fish oil can reduce the synthesis of endocannabinoids in the brain that are powerful stimulators of hunger (14).

I often say that if you are fat, it may not be your fault. The blame can be placed on your genes and recent changes in the human food supply that are changing their expression, especially in the dopamine reward system. However, once you know what causes the problem, you have the potential to correct it. If you are apparently addicted to food, the answer may very well lie in an anti-inflammatory diet coupled with high-dose fish oil.


  1. Wang GJ, Volkow ND, Logan J, Pappas NR, Wong CT, Zhu W, Netusil N, and Fowler JS. “Brain dopamine and obesity.” Lancet 357: 354-357 (2001)
  2. Thanos PK, Michaelides M, Piyis YK, Wang GJ, and Volkow ND. “Food restriction markedly increases dopamine D2 receptor (D2R) in a rat model of obesity as assessed with in-vivo muPET imaging and in-vitro autoradiography.” Synapse 62: 50-61 (2008)
  3. Steele KE, Prokopowicz GP, Schweitzer MA, Magunsuon TH, Lidor AO, Kuwabawa H, Kumar A, Brasic J, and Wong DF. “Alterations of central dopamine receptors before and after gastric bypass surgery.” Obes Surg 20: 369-374 (2010)
  4. Stice E, Yokum S, Blum K, and Bohon C. “Weight gain is associated with reduced striatal response to palatable food.” J Neurosci 30 :13105-13109 (2010)
  5. Ludwig DS, Majzoub JA, Al-Zahrani A, Dallal GE, Blanco I, and Roberts SB. “High glycemic-index foods, overeating, and obesity.” Pediatrics 103: E26 (1999)
  6. Agus MS, Swain JF, Larson CL, Eckert EA, and Ludwig DS. “Dietary composition and physiologic adaptations to energy restriction.” Am J Clin Nutr 71: 901-7 (2000)
  7. Jonsson T, Granfeldt Y, Erlanson-Albertsson C, Ahren B, and Lindeberg S. “A paleolithic diet is more satiating per calorie than a mediterranean-like diet in individuals with ischemic heart disease.” Nutr Metab 7:85 (2010)
  8. Pereira MA, Swain J, Goldfine AB, Rifai N, and Ludwig DS. “Effects of a low glycemic-load diet on resting energy expenditure and heart disease risk factors during weight loss.” JAMA 292: 2482-2490 (2004)
  9. Pittas AG, Roberts SB, Das SK, Gilhooly CH, Saltzman E, Golden J, Stark PC, and Greenberg AS. “The effects of the dietary glycemic load on type 2 diabetes risk factors during weight loss.” Obesity 14: 2200-2209 (2006)
  10. Johnston CS, Tjonn SL, Swan PD, White A, Hutchins H, and Sears B. “Ketogenic low-carbohydrate diets have no metabolic advantage over nonketogenic low-carbohydrate diets.” Am J Clin Nutr 83: 1055-1061 (2006)
  11. Chalon S, Delion-Vancassel S, Belzung C, Guilloteau D, Leguisquet AM, Besnard JC, and Durand G. “Dietary fish oil affects monoaminergic neurotransmission and behavior in rats.“ J Nutr 128: 2512-2519 (1998)
  12. Chalon S. “Omega-3 fatty acids and monoamine neurotransmission. Prostaglandins Leukot Essent Fatty Acids 75: 259-269 (2006)
  13. Sorgi PJ, Hallowell EM, Hutchins HL, and Sears B. “Effects of an open-label pilot study with high-dose EPA/DHA concentrates on plasma phospholipids and behavior in children with attention deficit hyperactivity disorder.” Nutr J 6: 16 (2007)
  14. Watanabe S, Doshi M, and Hamazaki T. “n-3 Polyunsaturated fatty acid (PUFA) deficiency elevates and n-3 PUFA enrichment reduces brain 2-arachidonylglycerol level in mice.” Prostaglandin Leukot Essent Fatty Acids 69:51–59 (2003)

Nothing contained in this blog is intended to be instructional for medial diagnosis or treatment. If you have a medical concern or issue, please consult your personal physician immediately.

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About Dr. Barry Sears

Dr. Barry Sears is a leading authority on the impact of the diet on hormonal response, genetic expression, and inflammation. A former research scientist at the Boston University School of Medicine and the Massachusetts Institute of Technology, Dr. Sears has dedicated his research efforts over the past 30 years to the study of lipids. He has published more than 30 scientific articles and holds 13 U.S. patents in the areas of intravenous drug delivery systems and hormonal regulation for the treatment of cardiovascular disease. He has also written 13 books, including the New York Times #1 best-seller "The Zone". These books have sold more than 5 million copies in the U.S. and have been translated into 22 different languages.

50 thoughts on “Blame weight gain on the brain

  1. Morning-
    my brain is telling me i’m hungry after 4 hrs. is this normal,or should i torture myself and push it to eating on the 5 hr. mark? i have craved high carb. foods and given in.what do you think?

    • You should be striving for five hours. If you go the Resources section of, you will be a hormonal adjustment diagnostic chart that will help you make adjustments so that you can make the five hour time point. Not everyone is genetically identical, that’s why you may need a little fine-tuning.

  2. Excellent post. New approach to understand obesity. It reminds me Dr Daniel G Amen ideas, focused on brain to explain many diseases and problems. Also Dr Amen recommends antiinflamatory diets like specially Zone.

    • Excellent. Actually I bought some Dr Amen books based on your praise for his work in those (‘back cover’) books (Its really difficult to find praises of others books from you Dr Sears; I understood it when I read about Zone diet trials made by Dr Amen inside these books).

  3. I feel very much identified with everything you said in this article. As I said in a previous post, I am addicted to food and had also had a gastric bypass. However, I could never reach my desired weight even with the operation and now I gained 20 pounds. I began today with a “Zone Plan” (as I remember from your books). Your scientific approach in your books is very appealing to me, however in your website I only find suggestions to buy specific processed products. I would like to know if there is a place where you have orientations on an anti-inflamatory diet based on natural products. I agree that most of your products will make easier to follow the diet, but as I don’t live in the USA I’m not sure I can always buy them.

    Please explain more the link between the dopamine action and the caloric restriction. Thank you.

    • On you will find hundreds of classical Zone meals as well as thousands of others in my books. Unfortunately to get the same levels of satiety as will automatically generated by the Zone Foods, your will have to pay very close attention to balancing the macronutrient composition of every meal using the Zone Block method as also explained on

      Calorie restriction is more easily accomplished if you are never hungry. Increased dopamine levels in the brain bring greater reward with fewer calories.

    • An anti-inflammatory diet is one that has been clinically demonstrated to reduce existing levels of cellular inflammation. The Zone diet consistently been shown to do that in carefully controlled clinical trials.

      The foundation of an anti-inflammatory diet is eating adequate amounts of low-fat protein at every meal, with most the carbohydrates coming from vegetables with limited amounts of fruits, and adding a dash of fat low in omega-6 and saturated fats. The secret is following for a lifetime.

  4. I find it puzzling that Dr. Sears continually blames cellular inflammation for most illnesses and and to follow an anti-inflammatory diet but he does not explain how a person can tell how much cellular inflammation the person has besides by paying for an expensive AA/EPA test available in 1 lab in Canada.
    Dr.Sears explains that your AA/EPA ratio must be in balance to control inflammation and this can be accomlished by taking his Zone Omega 3 and eating in the Zone but it’s not possible to tell if inflammation is being controlled other than having the expensive test done at regular intervals.
    I never see Dr. Sears explaining any of this. After I had the AA/EPA test done once 9 months ago, the test revealed I needed to eat more ‘out of the Zone’ to get my AA/EPA balanced. All of this scientific information published by Dr. Sears looks impressive but after a person follows the plan, the rest is only a guessing game as to the outcome. With diabetes, a person can regularly test his blood sugar. With hypertension, a person can regularily test his blood pressure. With inflammation, a person can only guess and hope and pray.

    • The reason you test for cellular inflammation is the same reason that you test for cholesterol. You can’t look at a person and guess their levels of either cellular inflammation or cholesterol or blood sugar levels. People hate to give blood, but they are more likely to give a finger prick of blood. We are finishing up our clinical validation of our finger prick AA/EPA test and it will be available to physicians after our lab gets its final inspection as a certified diagnostic lab.

      I think you totally misinterpreted your results. If the AA/EPA ratio is low (assuming it was done with isolated plasma phospholipids), then you simply need to take less fish oil, not eat outside the Zone.

      • Re AA/EPA ratio: I’m worried I’m getting too much O-3 and not enough O-6. Is that possible? (I eat all sardines every day for protein).

        I read that there’s a continuum – that the opposite of inflammation and autoimmune disease is susceptibility to disease and cancer. Shouldn’t there be a balance between the “good” and “bad” eicosanoids? If that is true, are there good rules of thumb for balancing them?

          • The balancing of “good” and “bad” eicosanoids was the foundation of the Zone diet 16 years ago and that has not changed. This is like having a balance of “good” and “bad” cholesterol.

            If you follow an anti-inflammatory diet you will achieve that balance. You can define it precisely by looking at the AA/EPA ratio in the blood, just as you determine the balance of “good” and “bad” cholesterol in the blood.

            I consider low blood pressure to be less than 90/60. The higher the blood pressure, usually the greater the level of cellular inflammation.

  5. You suggest that high-dose omega-3 fatty acids may help with food addictive behavior. Could you please define “high-dose”?

    Thank you.

    • Levels of fish oil reach in EPA and DHA increase the levels of dopamine brain that provides greater reward with the intake of less calories. The high levels of EPA inhibit the formation of endocannabinoids in brain that give rise to hunger. EPA also inhibits the levels of cellular inflammation in the adipose tissue, liver, and muscle cells that cause insulin resistance thus elevating insulin levels that make you constantly hungry.

      I define high-dose fish oil as any dosage greater than 2.5 grams of EPA and DHA per day.

  6. For weight reduction to happen, and “stick”, the whys of why people overeat are important to discover and correct. I’m mostly referring to emotional eating, but your information makes me think there is a physiological reason for the emotional eating. Is this why I can do well for 3-4 weeks, then have major cravings that can derail me? (that and the monthly hormone cycle for women). Fascinating, thank you for the info.

    • The primary cause of emotional eating is increased stress caused by increased cellular inflammation. The increased inflammation is addressed by the increased secretion of cortisol from the adrenal glands. Cortisol increases insulin resistance and that results in greater hungry that is most rapidly reduced by the intake of junk food rich in high-glycemic load carbohydrates.

      Bottom line, decrease cellular inflammation, less cortisol is required to help reduce the inflammatory response.

    • An anti-inflammatory diet is one that has been clinically demonstrated to reduce existing levels of cellular inflammation. The Zone diet consistently been shown to do that in carefully controlled clinical trials.

      The foundation of an anti-inflammatory diet is eating adequate amounts of low-fat protein at every meal, with most the carbohydrates coming from vegetables with limited amounts of fruits, and adding a dash of fat low in omega-6 and saturated fats. The secret is following it for a lifetime.

      You can give yourself a little more dietary leeway by consuming at least 2.5 grams of EPA and DHA per day.

  7. Greg,
    An average maintenance dose of the purified Zone Omega 3 is 4 capsules or 2.5 grams. Anything over this is high dose. Now you are asking a similar question that I’ve been asking i.e. how much do I need? When I had prostate cancer, an average high dose for prostate cancer is about 12 capsules but, since I has the (expensive) AA/EPA test done and my inflammation was so low, a Sears rep recommended I only take 8 capsules daily. Do you see the confusion?
    I sincerely wish and hope Dr. Sears stops preaching in generalities and starts becoming specific.

    • I certainly don’t see confusion is making a credible suggestion based on science and powerful clinical test. If your blood pressure was too low, your physician would suggest reducing the amount of hypertensive drug you were using.

  8. CB in DC,
    My common sense tells me overeating is more of an addiction than any other reason. I believe the cure, like any other addiction, is will power. I believe those who promote diet plans won’t readily admit this because it’s not in their best interests. I am addicted to food because it tastes so darn good and satisfies me. Smoking satisfied me until I used will power and quit 9 years ago. I tried gum, I tried patches. Only will power worked. Crutches prolong the addiction.
    Dr. Sears has the best information on eating to be healthy and why people are more addicted than others but he won’t use this term addiction. Maybe I should write a book.

  9. Jockobono, Don’t get me wrong, I know “will power”, “focus” whatever you call it is necessary for success. I just wondered if this sentence, “This led to the hypothesis that obese individuals overeat as a way to compensate for the reduction in the dopamine reward circuits just as individuals with addictive behaviors (drugs, alcohol, gambling, etc.) do when their dopamine levels are low” means it can be more difficult to stick to that focus. I agree that the Zone is very healthy, and for me, not difficult to follow because I don’t get hungry – but that 4th week rolls around, and it’s much more difficult. Dopamine? The monthly hormonal roller coaster women get? Let us know when your book comes out!

    • CB – when I start to crave something (same cycle!) I just have some. It is not the end of the world, and it keeps me on track because when I eat junk I feel like junk and do not want to go off the “good” stuff very often. With other diets I would lose weight after lots of hard work and agony, reach my goal….. and go back to all the junk I loved! With the Zone you can eat right MOST of the time and indulge SOME of the time.

    • You are correct. Hormones change constantly, especially stress-related hormones. The best you can do is try to control as much as possible by diet and lifestyle (exercise and stress reduction).

  10. Thanks Dr. Sears for all your work, and for taking questions on the web. I also sometimes succumb to emotional/stress eating and feel so terrible that I regret it and immediately return to the Zone diet. I can feel the difference physically. I’m very grateful for all the information you have given us. One question, will you be having a Zone cruise in the summer sometime soon so that teachers, who can’t take off during the year, can participate? I called a representative and she said had had one not too long ago, but I missed it. Thanks.

    • A summer cruise is something that I should consider, however, I believe most of the desirable summer cruises have too short of time at sea to hold the educational seminars. Nonetheless, I will check it out.

  11. Dr.Sears,
    You said, “If your blood pressure was too low, your physician would suggest reducing the amount of hypertensive drug you were using.”
    Now, how would my physician know my blood pressure was too low? With a test, right? A very very low cost test. Now, how would I know if my inflamation was too low or too high? How would I know if I had any inflammation, or how much? With a very very expensive test, right? How many times does a person have to have this AA/EPA test, this expensive AA/EPA test? More than once a year? I have my blood pressure tested every week or so.
    I guess what I am trying to say is that all your scientific knowledge is of little use to us to cannot it put into practice.
    And you misunderstood me about eating out of the Zone to get my AA/EPA in balance. I did exactly what I was told, and as you said, I did not take 12 capsules of your Omega3 daily for my cancer. I only took 8, which a normal dose is 4, and I ate a few egg yolks to raise my AA to get my AA/EPA in balance, which I consider eating out of the Zone.

    • The first cholesterol tests were also very expensive. If you are giving millions per year, the cost comes down. Unfortunately, the medical establishment is not at that point of recommending that number of tests.

      If expense is a problem, then I recommend using the Eicosanoid Status Report in the Tools section of It is free and I have used with great success for more than 25 years. In the same Tools section you can find a simple test to help you adjust your protein to carbohydrate balance to achieve better insulin control. That test is also free.

  12. Dr. Sears,
    FYI, you might understand my reason for being argumentative if I give you a brief report of my Nutrasource Diagnostics Inc. Omega Score results from July 23, 2010. It is worth mentioning also that, at this time, a biopsy revealed I had aggressive high risk prostate cancer.

    Omega Whole Blood Score = My Score 11.27 (For those who are not familar with the score results, Whole Blood Scores in the highest quartile (6.6% – 10.2%) were associated with an 80% lower risk of sudden death compared to individuals with whole blood scores at 2.1%-4.2%)

    Omega-3 Serum Equivanence Score = My Score 12.77 (A total Omega 3 Score >= 7.2 is associated with a 32% risk reduction in heart disease compared to a score of = 4.6 is associated with a 70% reduced risk of death from fatal ischemic heart disese as compared to a score of < 3.5.

    Omega-3 Index Red Blood Cell Equivalence Score = My Score 11.06 (An RBC omega-3 value of 8-11% offers the greatest protection against sudden myocardial infarction.)

    My Lipids: Saturated – 31.38, Monounsaturated – 24.06, Polyunsaturated – 44.56
    My Ratios: AA/EPA ratio (SIP)) – 1.02, Omega-3/Omega-6 ratio – 0.37, Omega-6/Omega-3 ratio – 2.73
    I won't post the list of 29 of My Whole Blood Fatty Acids except
    Arachidonic Acid C20:4n6 (AA) 9.58 % by weight,
    DGLA C20:3n6 – 0.90% by weight,
    EPA C20:5n3 4.50% by weight.

    I would imagine this test I had proves a lot more than an Eicosanoid Status Report would prove and that I am pretty much In The Zone and yet I developed cancer and I am always hungry. What more can a person do?

  13. Correction to the above:
    The paragraph that reads – Omega-3 Serum Equivalence Score – My Score 12.77 (A total Omega-3 score >7.2 is associated with a 32% risk reduction in heart disease compared to a score of <5.0
    EPA + DHA Serum Equivalence Score My Score – 10.70 (A total EPA + DHA Score < 4.6 is associated with a 70% reduced risk of death from fatal ischemic heart disease as compared to a score of <3.5

    • Usually any cancer takes decades to develop. Our ongoing studies at Harvard Medical indicates that high dose fish oil appear to increase the production of a protein that stops the metastatic spread of prostate cancer into other tissues.

  14. Jockobono, have you ever considered checking your Vit D levels? The test is named 25 hydroxy-vitamin D and is also called 25(OH)D. If your interested in learning about the significance of Vit D in the human body, I would recommend doing a web search for the Vitamin D Council website, which is quite informative.

  15. Ms T,
    For what reason do you suggest I have my Vitamin D levels checked? Exactly what makes you think I should have my Vitamin D levels checked?

  16. I’m assuming, because I haven’t seen anything written anywhere by Dr. Sears directly linking cellular inflammation to cancer, that cancer is a result of cellular inflammation and learning I had cancer, even though my inflammation (AA/EPA) was ideal at the same time the cancer was discovered, what is the benefit of testing for inflammation?

  17. Hi there, I’m glad to discover a lot of very helpful information right here, it’s a really great webpage. Many thanks for this good blog posts! I’m going to save your blog and take the rss feeds also… I hope you will keep posting your posts continually as you have one devoted subscriber here.

    • All diets are defined by their macronutrient composition regardless of the ingredients. The time at which those food ingredients became part in the human diet defines their inflammatory potential with the earliest food ingredients usually be the least inflammatory.

      The best estimates of the macronutrient composition of the Paleolithic diet in East Africa was a Zone balance of 40% carbs, 30% protein, and 30% fat with the fat being low in omega-6 fatty acids and very high in omega-3 fatty acids. Since that type of diet would have only included paleolithic food ingredients, their impact on the inflammatory response would be lower than more modern food ingredients (such as grains, dairy, the refined ingredients). The book The Paleo Solution states nothing about the macronutrient balance of the diet. It could be a vegan Paleolithic diet, a ketogenic Paleolithic diet or even the PaleoZone diet depending the macronutrient composition. In essence, the Zone gives you definition and direction for constructing an anti-inflammatory diet whereas the Paleo Solution leaves you without a clue implying their is some intrinsic inner knowledge that will lead you to the correct macronutrient composition for optimal control of inflammation.

      If you read my first book, The Zone, published in 1995 you will find Chapter 8 devoted to showing how the Zone diet was developed based on the principles of paleolithic nutrition.

  18. Dr.,

    I have never asked a question on a blog, ever! So please take it easy on me if I mess up.

    I have been doing the Zone Diet for a while now, but I was not super tight to it. Within the last six weeks, I got super tight on the diet. I have lost some weight, but I am SO HUNGRY. I can barely stand it. After losing 2 or so lbs a week, I am having hard time staying on the diet. I am ravenous from the time I wake up until I eat a final snack right before bed. Sometimes I wake up so hungry I can’t go back to sleep. So I am hoping for help.

    I am about 240. According to Dr. Sears body fat calculator I am about 27% fat. So I have some weight to lose. I workout, very intensely, 3-4 times a week. I finished P90X, now I modified the workout to fit my needs. The body fat calculator says 18 blocks a day. I am currently doing that.

    I am starting to cheat, a lot. It started with a little and now it is much more because I am so hungry. I need help. I feel very good about my weight loss so far and P90X has whipped me into shape. I can’t explain how much better I feel in terms of my attitude and just myself in general. I am starting to panic because I am starting to have a hard time sticking with the diet and I don’t want to go back where I was. I would like to lose another 20 lbs before I go into more of a maintenance mode. If I can get to 200-210, I would go crazy.

    I would like to thank you for your advice in advance.


    • I would suggest using the hormonal adjustment guide found in the Resources section of The key to the Zone diet is never being hungry between meals. Since everyone is not genetically identical, you have to balance the protein to glycemic load that fits your metabolism and genetics.

      One of the easiest ways to alter the hormonal balance of any meal to make greater amounts your carbohydrates coming from non-starchy vegetables. Another method is to increase the intake of omega-3 fatty acids to reduce the cellular inflammation in the adipose tissue that prevents the release of stored fat to can be made into chemical energy needed to drive the body. This is explained in more detail in my most recent book, Toxic Fat.

    • Why is it that so many people think that either they’re on a diet or they are “cheating”? Either you choose to follow guidelines or you choose to go outside the lines. It is always your choice. You can choose your destination and follow a clear road or try to reach your destination through a forest of unseen obstacles.

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