Changing gene expression

I have often stated that the real power of the Zone Diet is to change gene expression, especially the expression of anti-inflammatory genes. What I never realized is how rapid gene expression could occur. Now, new research from Norway gives me the answer (1). It takes about 24 hours!

This pilot study is on the effect of diet on gene expression in healthy obese individuals. Interestingly, when the researchers calculated the estimated daily calorie requirements for these subjects necessary to maintain their weight, they were surprised that they were already eating 250 fewer calories per day than predicted to maintain their current weight. So much for the “fact” that obese individuals are fat because they eat more calories than they need to maintain their weight. In fact, this observation was confirmed in an earlier study in which the number of calories consumed by obese and lean individuals did not vary, but the obese individuals consumed fewer meals consisting of larger servings (2).

So what the Norwegian researchers did was simply maintain the same number of calories the subjects were already eating and change the macronutrient balance to be very close to the Zone Diet (30 percent carbohydrates, 30 percent protein, and 40 percent fat). Then the subjects consumed six meals containing about 460 calories evenly spaced throughout the day so that the total calories consumed at any one time was moderate. Just making those two simple dietary changes resulted in more than an eight-pound weight loss in 28 days. The levels of body fat didn’t change since the number of calories consumed was exactly the same as they were previously consuming. However, it appears that evenly spacing the meals and reducing the calorie size of the meals resulted in less insulin production and therefore less retained water.

Then they looked to see if they could find any changes in gene expression in both the fat cells and the blood with the dietary changes. Amazingly they found dramatic changes in only 24 hours. Of the 16,000 genes they could identify, about 60 percent remained unchanged in their expression, but 40 percent were either turned on (i.e., up-regulated) or turned down (i.e., down-regulated). Interestingly, the changes seen in the first 24 hours were held constant throughout the 28 days of the experiment.

Upon further analysis, the up-regulated genes corresponded to those that had anti-inflammatory properties, and the down-regulated genes were those associated with chronic disease conditions, such as diabetes and heart disease. Furthermore, since these changes in gene expression occurred within 24 hours of the dietary change, they could not be attributed to any change in body weight and fat loss.

Fortunately, I had the opportunity to have dinner with the lead author of the study to discuss her work while I was in Europe last week. She told me that she has expanded the number of subjects in several new trials, and the results remain the same. I also found out that she has been following my work for many years.

This type of study only confirms the power of genetic analysis to demonstrate how a highly structured diet with the correct macronutrient content can rapidly alter genetic expression and hence controls your future health. But the door swings both ways. An unbalanced diet will have just the opposite genetic effects. While I have always been impressed by the power of the Zone Diet, this new experimental data takes my respect for the Zone Diet to a new level of awe, even by me.


  1. Brattbakk H-R, Arbo I, Aagaard S, Lindseth I, de Soysa AK, Langaas M, Kulseng B, Lindberg, and Johansen B. “Balanced caloric macronutrient composition down regulates immunological gene expression in human blood cells-adipose tissue diverges.” OMICS 15: doi:1089/omi.2010.0124 (2011)
  2. Berg C, Lappas G, Wolk A, Strandhagen E, Toren K, Rosengren A, Rosengren A, Thelle D, and Lissner L. “Eating patterns and portion size associated with obesity in a Swedish population.” Appetite 52: 21-26 (2009)
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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.

23 thoughts on “Changing gene expression

  1. Hi, Dr. Sears,
    I have a couple of questions. In addition to teaching acting, voice and movement, I also act myself. Recently, I have been offered a big role in a professional production of a play. The roll requires me to memorize a lot of lines. Additionally, the character should be rather muscular and a bit larger than me. I have been following the Zone since it was first suggested to me during my routine physical in 2002. I am 135 pound, 5’7” male. My physicals are all good. I walk regularly and lift weights-I’m in good shape, especially for my age, 55. I think that I should gain about 7-10 pounds or so for the role. I should also add another weightlifting session per week to my current regime. However, I would like your advice about this. Acting on stage can be similar to an athletic performance in some ways, sometimes even more difficult.

    Also, I do 4 capsules of OmegaRX and 1 capsule of your Polyphenols per day. I’m wondering if increasing my fish oil will help with memorization of all those lines, as well as dealing with the stress of the role? I have not had the blood test, but just use your status report, and 4 f.o. capsules seems to work for me, but I’m not adverse to adding more temporarily, if you advise it. Also, if I do add more f.o., should I add more polyphenols? If you do suggest I add more, how much more?


    • Adding extra fish oil will only increase your cognitive abilities.

      Relative to gaining muscle mass, the key is getting adequate levels of protein (and especially leucine) at every meal to stimulate protein synthesis through activation of mTOR. Couple with this high intensity training will stimulate more muscle development.

  2. Thanks again for your blogs. Would be interested to adjust the research to follow the 3 meal + 2 snack regimen, or “grazing” or fish oil regimen. Suspect less dramatic results than large vs. moderate meals though reduced inflamation indices. Surprising how little direct research done on your program though the studies you cite are extremely convincing and strongly support your conclusions and recommendations. It seems each new diet that actually works is not far from your system. My wife, non-believer, is on Weight Watchers and their points system seems to consider glycemic index indirectly as certain low value items are not charged at all. Might be interesting for you to look into popular programs like WW for Zone compliance, e.g. one (can’t recall at the moment, provides prepackaged food) advertizements discuss glycemic index, and show where your program works within their system (s).


    • It seems that most researchers try to adjust the basic Zone balance of macronutrients to make it unique for them. The published studies that maintain the Zone balance are uniformly robust.

      The Zone Diet is more complex than simply reducng the glycemic index. You also need adequate protein at every meal, low levels of pro-inflammatory saturated and omega-6 fats, and adequate levels of anti-inflammatory omega-3 fats and polyphenols. The Zone Diet requires some thinking, most popular programs are based on the premise of not thinking too hard.

  3. Dr. Sears,

    we did as recommended by you a AA/EPA test and my rtesult is 5,3 and for my girlfriend 8,5

    Based on my little knowledge (from reading your books) i would take 2,5g fishoil for me and 5g for my girlfriend, can you agree to this?

    the test also showed a too low level of linolacid and i got the recommendation to take some Leinöl-shall i do this and how much?

    my girlfriend has several values of the test above the recommended levels will this all go down with the proper amount of fishoil and zone diet? (Can i mail you the testreport and you have a look at it?)

    when is it useful to repeat the test to see if it works well?

    thanks alot


    • I would suggest starting with 2.5 grams of EPA and DHA for both of you. You will not need as much omega-3 fatty acids if you follow a more strict anti-inflammatory diet to reduce AA.

      Don’t worry about the linoleic acid.

  4. what i forgot to ask

    in your book i´ve read to take the fishoil in the evening-is this still valid also for higher amount or is there a better schedule (after each meal and the rest in the evening etc)



      • That is both hkaatbrereing and heartwarming to read of his thoughts. The farm animals are on borrowed time if they are drinking contaminated water, eating contaminated food and breathing contaminated air. The kindness being shown in feeding them until the ultimate end of their lives is touching. No one has a right to complain about the hard choices these farmers are having to make. Linda

  5. For those of us who really don’t want to consume fish oil, what is the vegetarian based equivalent to fish oil (or nearest equivalent) that you would recommend most highly?

    • I would recommed taking a lot of flaxseed oil as about 5-10% is converted to EPA, but the conversion into DHA drops to about 1%. This low conversion into DHA can be overcome by taking an algae source of DHA at the same time as the very high level of flaxseed oil.

  6. How long is the window of insulin impact when you have too many carbs, not enough, or stray off the 40-30-30 to add carbohydrates or protein and affect your insulin levels?
    Lets say I have a banana with 2 teaspoons almond butter but 30 minutes later I have 3 blocks of protein to even it out…does that 30 minutes have to be smaller or will waiting and adding protein even affect my insulin levels? or can it be longer than 30…just curious about the window of getting the amt of macronutrients…

    • I feel that you probably have a 30 minute window to add other macronutrients to level out hormonal response. However, it has been my experience that is easier to start with protein and then add carbohydrates as it takes longer to digest protein and get it into the bloodstream.

  7. What are the absolute best sources of fat to eat with each meal for the necessary fatty acids to load the omega-6 pipeline and have the best effect on your body if I’m already taking an EPA/DHA supplement a day and eating oatmeal 4 mornings a week? I want to charge this lifestyle change head on…

  8. Dr,

    first, thank you for give us the opportunity to interact.

    In order to Gene Expression dynamics, what you really think about compounds like

    - gliadin or generally peptids,
    - wheat germ agglutinin or generally lectins.

    Those compounds are hardly suspected to have an “immunoreactive” load, until to lead, in some cases, to autoimmunity, through gut permebility / molecular mimicry mechanisms.

    I’m really interested in your point of view.

    Thanks, Alessandro.

  9. Lectins found primarily in wheat, grains, and legumes can have inflammatory effects when they bind to receptors of flora in the gut and can initiate inflammatory responses that result in the secretion of inflammatory mediators that can enter into the body. The recent book Wheat Belly describes these potential effects in greater detail.

    That’s why the primary source of carbohydrates should be vegetables and fruits with limited amounts of legumes and strict moderation of grains.

  10. Im 15, and i want to be healthier and fitter so I can join the RAF. I’m 164cm, so thats 5ft 5 i think? And i weigh 11 stone 13. I feel disgusting! Is there any way to loose this weight fast? I want too loose at least 2 stone. But thats just pie in the sky talk. Please help me to achieve my dream weight to get my dream job!!

  11. Dr. Sears

    I just finished reading your book about Toxic Fat and I want to get your take on the HCG diet. and if their are any paralelles to the Zone diet and its end results. Lost 22 lbs on HCG 3 years ago and kept it off through diet and exercise but I am shocked about the possible inflamation through out my body where heart disease run heavily in my family. Does HCG accomplish the same thing, if only in the short term?

  12. Dr. Sears can you please offer some advice I have a 16 year who genetically is predisposed to be on the lighter and shorter side. However, he is an athlete and has been trying to increase his weight and strength. We were referred to your diet but we have no idea on how to get started and how to track his progress.


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