Eat Less, Get Hungry

Telling an obese person simply to eat less rarely succeeds. Is it because they are weak-willed individuals or is there something more complex going on? New research indicates the latter. A new article in Cell Metabolism showed that during extreme calorie restriction, the levels of fatty acids begin to rapidly rise in the blood as the body begins breaking down stored fat for energy. These newly released fatty acids from the fat cells can then enter into the brain (the hypothalamus to be exact) and cause the self-digestion of cells in the hunger neurons (1). This self-digestion of the cells in the hunger neurons produces a rise in the very powerful hunger hormone (AgRP) from the same bundle of neurons. Not surprisingly, the urge to eat becomes almost overpowering. This begins to explain why very low calorie diets can cause rapid weight loss, but are rarely successful in keeping the weight off.

This is why very low calorie diets that promise quick weight loss invariably cause the rapid release of stored fatty acids that promotes constant hunger. This is clearly not a sustainable way to maintain long-term weight management.

Of course the question might be whether it is all fatty acids or just one that causes the problem of cellular death in the hunger neurons? I believe the answer comes back to the usual suspect, arachidonic acid (2). It has been known for 20 years that when you put obese individuals on a very low calorie diet there is a rapid increase in the levels of arachidonic acid levels in the blood (3). Arachidonic acid can easily cross the blood brain barrier and enter into the hypothalamus. Since arachidonic acid is a powerful promoter of cell death (4), increased concentrations inside the hypothalamus may be the primary accelerator of the death of the hunger neurons. Increased levels of arachidionic acid in the blood are also the underlying cause of insulin resistance because of its effect on the generation of cellular inflammation (2). So as you build up the levels of stored arachidonic acid in the fat cells, caused by the Perfect Nutritional Storm (2), you are almost ensuring constant hunger when you try to lose weight quickly by following very low calorie diets. To make matters even worse, as arachidonic acid levels also build up in the brain increasing the production of endocannabinoids (5). These are the hormones that give you the continual munchies (they are related to the active ingredient in marijuana).

So is there any good news in all of this research? Yes as long as you develop a lifetime dietary strategy for reducing arachidonic acid and the cellular inflammation it causes as well as following a reasonable low calorie diet that supplies adequate levels of fat to moderate the release of stored fatty acids from the fat cells. It means following an anti-inflammatory diet with adequate protein using low-glycemic load carbohydrates and fats very low in omega-6 fatty acids, but adequate in monounsaturated and omega-3 fats.

That’s why you never want to start any type of weight loss program without adding omega-3 fatty acids to counteract the released of stored arachidonic acid from the fat cells. Not only will these omega-3 fatty acids reduce the degradation of the hunger neurons thereby reducing the release of powerful hunger hormones during calorie restriction, but they will also inhibit the release of endocannabinoids in the brain (6). The combination of the two events will ensure weight loss without hunger and that’s sustainable.


  1. Kaushik S,Rodriguez-Navarro JA, Arias E, Kiffin R, Sahu S, Schwartz GJ, Cuervo AM, and Singh R. “Autophagy in hypothalamic AgRP neurons regulates food intake and energy balance.” Cell Metabolism 14: 173-183 (2011)
  2. Sears B. Toxic Fat. Thomas Nelson. Nashville, TN (2008)
  3. Phinney SD, Davis PG, Johnson SB, and Holman RT. “Obesity and weight loss alter serum polyunsaturated lipids in humans.” Amer J Clin Nutr 53: 831-838 (1991)
  4. Pompeia C, Lima T, and Curi R. “Arachidonic acid cytotoxicity: can arachidonic acid be a physiological mediator of cell death?” Cell Biochemistry and Function 21:97-104 (2003)
  5. Kim J, Li Y, and Watkins BA. “Endocannabinoid signaling and energy metabolism: A target for dietary intervention.” Nutrition 27: 624-632 (2011)
  6. Oda E. “n-3 Fatty acids and the endocannabinoid system.” Am J Clin Nutr 85: 919 (2007)

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.

51 thoughts on “Eat Less, Get Hungry

  1. Did I get this right? If you go on a diet, be sure to take cod liver oil so you don’t get hungry? I know you don’t mean cod liver oil per se, but I can’t remember the name of the good stuff right now.

    • Cod liver oil is pretty disgusting, but omega-3 fatty acids are key to prevent hunger during any type of diet. I feel that the rapid release of arachidonic acid from the adipose tissue is one of the worst things to happen at any time in your life. The omega-3 fatty acids help modulate its negative effects.

  2. Hi Dr. Sears,

    Thanks for this excellent commentary. Outstanding as usual.

    I have a question regarding the link between dietary linoleic acid and AA levels in the body. Whether dietary LA actually raises AA in vitro appears to be a big source of controversy in the medical literature. See for example, the recent publication: “Increasing dietary linoleic acid does not increase tissue arachidonic acid content in adults consuming Western-type diets: a systematic review” Nutrition & Metabolism 2011, 8:36.

    Can you give us your opinion on why many of these studies seem to show little link between dierary LA and AA in the body, particulary when consuming a typical Western diet? It seems like the connection between dietary LA and AA levels in vitro is very complicated, and that reducing LA levels in the diet may not drop AA levels very much. I therefore wholeheartedly agree with you on the importance of consuming large amounts of fish oil to increase the denominator in the AA/EPA ratio, as there seems to be very little disagreement in the literature that fish oil raises EPA levels dramatically! But are there perhaps more effective ways to lower AA than restricting LA levels in the diet, given that this is still controversial, or is this currently the best aproach avalilable?

    Thanks again.

    • You also need elevated levels of insulin coupled with depressed levels of EPA to accelerate the metabolism of linoleic acid into arachidonic acid. It is slow process that is like Chinese water torture. The levels of linoleic acid in the America diet have increased by more than 400% in the past century, whereas the levels of long-chain omega-3 fatty acids have decreased by 90%. Couple this with increasing insulin induced by more refined carbohydrates and you have the Perfect Nutritional Storm that I described in Toxic Fat.

  3. I am a thin petite woman. I want to follow anti-inflammatory lifestyle but I don’t want to lose wheight. In fact I want to gain some weight. What should I do ? Thank you. Elena

    • great info, wish Dr. Sears would talk again re this key info: Dennis Prager radio; &/or CBNTV w. Pat Robertson who had this crucial info [on CBN NEWS] that could aid many worldwide to be healthier. Relatedly: Barry noted in 1 book [?Week in the Zone?]to use widemouth thermos to slow cook healthful oatmeal grain – put oatmeal in widemouth thermos: pour boiled H20 over; stir well; seal; leave overnight; in a.m.; voila; slow cooked oatmeal w. low glycemic index. Is this correct? & please we beg you, since we’ve looked allover, where do you find/buy wide-mouth thermos that is easily cleanable & that 1 can get one’s hand into to clean aptly; so 1 doesn’t need to buy/use special soft cleaning brush/soft cleaning pads equipment to avoid damaging widemouth thermos’s interior. E-m’d Dr. Sears re this 8/8/11, but received no reply. Tx.

      • I just went to a local hardware store in Marblehead about 12 years ago to get one. Of course that type of store no longer exists as they have been replace by the Home Depots of the world.

  4. Pingback: Around the Web; Post-AHS Edition | Perfect Health Diet

    • It is not the “anti-inflammatory” effects of short fatty acid, but their relative lack of “pro-inflammatory” effects. Both coconut oil and butter are very low in omega-6 fatty acids. This doesn’t mean they are perfect. The longer chain fatty acids in butter can bind to toll-like receptor 4 to activate NF-kappaB that turns on inflammatory responses. The short chain saturated fats in coconut will go directly to the liver to use up glycogen stores making it more difficult to stabilize blood sugar levels. The best way to treat inflammatory conditions is to reduce the intake of omega-6 fatty acids and increase in the intake of omega-3 fatty acids as well as maintain stable levels of insulin to prevent the overproduction of arachidonic acid. You can measure your success by the AA/EPA ratio in the blood.

      All PaleoZoner’s should read the review article in the British Journal of Nutrition on Paleolithic Nutrition published in 2010 that suggested that a Paleolithic diet consisted of about 6-14 grams per day of omega-3 fatty acids if you want to maintain an anti-inflammatory diet for a lifetime.

        • The short chain fatty acids in coconut are really termed medium chain triglycerides (MCT) go direct via the portal vein to the liver where they are rapidly metabolized to carbon dioxide and water. This uses up stored glycogen. They were initially developed at Harvard Medical School for supplying high calorie intake to burn victims. Unfortunately, the initial patients starting dying more rapidly due to the rapid oxidation of the MCT. When the MCT are mixed with long-chain triglycerides, this effect doesn’t happen.

      • Personally, as nutrition journalist I encourage in fats to consume extra virgin olive oil, organic (ideally grass fed) butter and/or ghee, extra virgin coconut oil and to supplement purified EPA-DHA fish oil. Altough I could disagree in original Zone plan in some saturated fats, essentially I am totally agree, the most important thing is to avoid high and very high Omega 6 oils, and also consume antioxidants like polyphenols to avoid Omega 3 oxidation. Thanks!

    • I just had the opportunity to read Guyenet’s blog. Unfortunately, I never saw the word “inflammation” mentioned once in the blog. It is cellular inflammation that causes insulin resistance, it is cellular inflammation that causes leptin resistance in the brain, it is cellular inflammation that causes disturbances in the satiety mechanisms in the hypothalamus. Nor did I read anything about glucagon or the wide variety of gut hormones that influence the hypothalamus. I explained this complex interplay in my book Toxic Fat. I guess he never read the book.

      I agree it is not simply carbohydrates per se that is the problem, but it their effect on increasing arachidonic acid which in turn increases cellular inflammation via pro-inflammatory eicosanoids. This has been the primary foundation of the Zone Diet since The Zone was published in 1995 and still is today.

      When causes increased cellular inflammation is the increase of omega-6 fatty acid intake (approximately a 400-800 per cent increase in the last century in America). If you have diet rich in unrefined carbohydrates, but low in omega-6 fatty acids (as many primitive diets are), it is very difficult to make arachidonic acid. However, add omega-6 fats in the form of refined vegetable oils (now the cheapest form of calories in the world) and simultaneously reduce the intake of long-chain omega-3 fatty acids (especially EPA) to such a primitive diet and obesity rapidly increases due to increased cellular inflammation.

      • Many thanks. I have noted, maybe I am wrong, you have focused in last years in your articles more attention in last years in remarking Omega 6:3 issue rather than Carbohydrates issue.

        I think Guyenet believes he is refuting Carbohydrate hypothesis, but its no the case, most who promote a carb restricted diet (specially refined ones), included Taubes I would say, dont say obesity is all due to this, nor ‘exclusively’ due to Omega 6 even when it can have a much more important role. Because obesity is not just caused in all population exclusively by just one thing. Obesity is multifactorial. And its very interesting last research, as you have pointed also, in brain as a master control center, also to explain obesity. As your good friend Daniel Amen points.

        But saying obesity is multifactorial shouldnt reduce our emphasis in promoting the reduction of linoleic acid and refined carbs -I think specially sacarose and isolated fructose and other byproducts like high fructose corn syrup-.

        Thanks again from Mediterranean zone

        • In my first book, The Zone, I had twice as many chapters devoted to eicosanoids compared to insulin. I believe my contribution to nutrition was being the first to explore the relationship between increased insulin levels and increased inflammation.

  5. What is the role of AA in testosterone production and it there a balance to be made between high enough circulating AA to ensure adequate building blocks for testosterone vs low enough AA to minimize inflammation?

    This question is being asked by a 35 year old male who obviously needs to think about these things. :)

    • There is very little direct effect of AA on testosterone production, but potentially an indirect effect on disruption of hormone signaling pathways in the hypothalamus, pituitary, and the testes. I generally recommend keeping the AA levels in the isolated plasma phospholipids between 7 and 9% of the total fatty acids and well as keeping the levels of EPA in the isolated plasma phospholipids greater than 4% of the total fatty acids.

  6. Egg yolks are a very rich source of arachidonic acid (AA). AA is critical for human health. Without adequate levels, we could never mount inflammatory responses against microbial invaders and injuries would never heal. However, at higher levels, excess AA can generate auto-immune responses in which the body attacks itself or causes disruption in hormonal signaling networks. In essence, you need a zone of arachidonic acid that is not too high, but not too low.

    • All of these chemicals will increase inflammation as they can activate the innate immune system which is the most primitive part of our immune response that is responsible for inflammatory responses.

  7. I have been in the zone diet since last February. Something “funny” happend to me. I did not use to eat fat before, at all. Since I started the zone diet, of course started eating fat and started getting acne as well!!! Pimples aren’t big, they’re huge!!! I did not think it was food related; however this last two weeks, trying to find a solution, i reduced intake of fat to the minimum (1 block per meal, except in the mornign, i get no fat because i get my fish oil dose) and voilà acne desapeared!!
    Has this ever happend to anyone? Am I still in the zone with this fat intake reduction?

    • That is an odd observation since the acne is a form of inflammation. My first thought is that is that stored arachidonic acid might be released from the fat cells. This is usually a very transitory effect. Nonetheless, cutting back on the total fat will have no adverse effects, especially if you are taking adequate levels of omega-3 fatty acids at the same time.

  8. Dr. Sears,
    Do you have concerns with using teflon cookware? I have been using a stainless steel fry pan to cook my egg whites. While I have heard it’s safer, it takes a long time to clean after. Comments would be appreciated.

    • The ideal cookware is either cast iron or stainless steel with copper bottoms (even harder to clean) because of the better heat transfer. I feel the more expensive Telfon cookware is OK because of a better bonding process, and if the ease in cleaning allows you to use it more often then the trade-off is worth it. Nonetheless if you see any breaks in the surface of the Telfon then you should probably discard the cookware.

  9. My husband has been on a weight-loss journey for 10 months and has lost 212 pounds. He’s done this by himself by a combination of exercise and most importantly totally changing how we eat. I am in the process of re-reading The Zone, which I’ve had since the ’90s. Our diet is surprisingly similar. My husband has been averaging 20 pounds loss a month; but for the month of August he only lost three pounds. We’ve been eating the same and he’s stepped up his exercise even. What might be causing this plateau & how does he get past it? Thanks for the help!

    • A recent article in Lancet demonstrates the weight loss (and more importantly fat loss) is much slower that most people expect. If your husband’s clothes contain to fit better and he is getting stronger, then this means he is losing fat and gaining muscle mass simultaneously. That is the Holy Grail of weight reduction even though the scale seems disappointing. At this point in his weight loss program, he should be using the Body Fat Calculator to determine his fat loss not the scale which can distinguish between fat loss or muscle gain. Losing 3-4 pounds of fat per month is a very realistic and noble goal.

  10. This isn’t related to the blog post but since you tend to answer questions of all sorts in the comments section, I’ll ask anyway. :)

    Any estimated time of release for the new dephinidins supplement you talked about earlier this year?

      • Hi, Dr. Sears,
        I have your polyphenols plus and fish oil. While waiting for your new blueberry supplement to come out, if I were to purchase a supplement somewhere, such as IHerb online, to begin a regime, what should I look for to ensure I’m getting a good product?

          • What changed in the polyphenol capsules that took the ORAC value from (i think) 1200 to 8000? I’ve been and avid customer of your fish oil for years but haven’t regularly purchased either the capsules or the Sea Health Plus since I consume a large quantity of berries and veggies every day. Also, do you still recommend the Sea Health Plus to assist with absorption? What in the Sea Health Plus helps with that above and beyond the polyphenol content?

          • The 8,000 ORAC units reflects the total anti-oxidant activity using five separate tests that quantifies different free radical quenching activities. The 1,200 ORAC units only reflects one the five groups of free radicals. The other free radical tests have only recently become available.

    • Usually when you say “imbalance” of women’s hormone’s, this implies decreased estrogen. As estrogen levels drop, insulin levels increase making it easier to accumulate excess body fat and more difficult to get rid of it. Furthermore, decreased estrogen can no longer inhibit the lipoprotein lipase in fat cells also making it easier to accumulate fat.

  11. I want to replace 2% Lactaid milk with home made almond milk. I will be using it in the Zone protein shake and my coffee. Is his acceptable? The cow’s milk creates a lot of gas and mucous.

    • That would be a good choice especially since it has a better fatty acid composition.

      A lot of people have problems with dairy products due to three factors; (1) presence of lactose, (2) sub-chronic allergies to dairy protein,and (3) dairy protein has a much greater effect on insulin release than does egg, fish, or beef protein.

  12. I am now not sure where you are getting your information, but great topic. I needs to spend some time finding out much more or figuring out more. Thanks for magnificent info I used to be looking for this information for my mission.

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