Fetal programming: Gene transformation gone wild (Part II)

In part 1 of this blog, I discussed how dietary changes can alter gene expression and how those epigenetic changes can be mediated from one generation to the next by fetal programming. This is very clear from animal studies. One of the most frightening studies was published a few years ago (1). In this study, genetically identical mice were split into two colonies. For the next three generations they were fed exactly the same number of calories with exactly the same balance of protein, carbohydrate, and fat. The only difference was that one group had a diet rich in omega-6 fatty acids and low in omega-3 fatty acids, and the other had a better balance of omega-3 to omega-6 fatty acids. After three generations the mice fed the high omega-6 fatty acid diet were grossly obese.

In addition, the mice with high omega-6 fatty acids had fatty livers and enlarged hearts and kidneys, all indicative of major metabolic disturbances.

This also happens with the brain. It has been demonstrated that removing omega-3 fatty acids and replacing them with omega-6 fatty acids over three generations makes animals a lot dumber, probably due to significant reductions in neurotransmitters, like serotonin and dopamine (2-5). Not only are they dumber, but their offspring also show a strong preference for junk food. (6)

How could this happen in such a short period of time? The answer is fetal programming induced by increased cellular inflammation. If this cellular inflammation is maintained by an inflammatory diet, there will be a constant driving force to maintain these epigenetic effects from one generation to other.

The next question is how long does this epigenetic programming have to be continued until it becomes a permanent part of the gene structure. One indication might be found in the development of lactose intolerance in those populations who have been exposed to dairy products for thousands of years. Seventy percent of the world’s population can’t digest these dietary products because they have lost the ability to maintain the necessary enzyme production after weaning from mother’s breast milk. Those who have been constantly exposed to dairy products after weaning have developed an epigenetic programming that seems to be permanent.

These epigenetic changes in humans may take place in only one generation. This is the suggestion of a new article to be published in Diabetes that indicates more than 25 percent of the explanation for childhood obesity could be predicted by prenatal epigenetic changes at birth (7).

As long as our epidemic of cellular inflammation continues to be fueled by the Perfect Nutrition Storm, we can expect our children to continue to become fatter, sicker, and dumber (8).


  1. Hanbauer I, Rivero-Covelo I, Maloku E, Baca A, Hu Q, Hibbeln JR, and Davis JM. “The Decrease of n-3 Fatty Acid Energy Percentage in an Equicaloric Diet Fed to B6C3Fe Mice for Three Generations Elicits Obesity.” Cardiovasc Psychiatry Neurol: 2009, Article ID.867041 (2009)
  2. 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)
  3. Zimmer L, Delpal S, Guilloteau D, Aioun J, Durand G, and Chalon S. “Chronic n-3 polyunsaturated fatty acid deficiency alters dopamine vesicle density in the rat frontal cortex.” Neurosci Lett 284: 25-28 (2000)
  4. Moriguchi T, Greiner RS, and Salem N. “Behavioral deficits associated with dietary induction of decreased brain docosahexaenoic acid concentration.” J Neurochem 75: 2563-2573 (2000)
  5. Chalon S. “Omega-3 fatty acids and monoamine neurotransmission.” Prostaglandins Leukot Essent Fatty Acids 75: 259-269 (2006)
  6. Ong ZY and Muhlhausler BS. “Maternal “junk-food” feeding of rat dams alters food choices and development of the mesolimbic reward pathway in the offspring.” FASEB J 25: S1530-6860 (2011)
  7. Godfrey KM, Sheppard A, Gluckman PD, Lillycrop KA, Burdge GC, McLean C, Rodford J, Slater-Jefferies J, Garratt E, Crozier SR, Emerald BS, Gale CR, Inskip HM, Cooper C, and Hanson MA. “Epigenetic gene promoter methylation at birth is associated with child’s later adiposity.” Diabetes 60: doi: 10.2337/db10-0979 (2011)
  8. Godfrey KM, Lillycrop KA, Burdge GC, Gluckman PD, and Hanson MA. “Epigenetic mechanisms and the mismatch concept of the developmental origins of health and disease.” Pediatr Res 61: 5R-10R (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.

25 thoughts on “Fetal programming: Gene transformation gone wild (Part II)

    • Omega-6 fatty acids are simply the starting point for the build-up of arachidonic acid (i.e. Toxic Fat) that is molecular building block for the generation of a wide number of very powerful inflammatory hormones known as eicosanoids. The diet rich in refined carbohydrates speeds up the production of arachidonic acid. The more you reduce the levels of those inflammatory hormones, the better you age. The extent of the build-up of cellular inflammation in the body can be determined by the ratio of arachidonic acid (AA) to the omega-3 fatty acid eicosapentaenoic acid (EPA). The higher the AA/EPA ratio in the blood, the more your body is under inflammatory attack that leads to acceleration of chronic disease and faster aging.

      The Zone diet was developed to reduce the levels of cellular inflammation.

  1. Hi Dr. Sears
    I learned of you from NIWH, and have been following you since. I appreciate all your are williing to share with us, and do hope it keep going for many others.
    Best regards,

  2. Dr. Sears,

    Since first reading your original Zone book many years ago every scientific study I’ve seen since regarding silent inflammation, omega 3:omega 6 ratio, eicosanoids, endocrine hormone expression resulting from glycemic load of food, etc. etc. have all backed-up your theses. Keep up the good work. I wish everyone (especially the kids) followed your scientifically-backed advice.



    • It’s the title of one of my chapters of my most recent book, Toxic Fat. It refers to the fact that a number of nutritional factors have to occur simultaneously to increase cellular inflammation. Unfortunately, those three factors (increased omega-6 fatty acid consumption, increased consumed of refined carbohydrates, and decreased omega-3 fatty acid consumption) first occurred in America about 40 years ago and now are spreading world-wide.

  3. The study states that the mice were fed the same number of calories but not how many calories.
    The number of calories apparently were too many, both those fed more Omega 6 and those fed more Omega 3.
    Seems to me that those fed more Omega 6 would not be obese if their calories had been restricted.
    This study resembles a political poll. The outcome is determined by the choice of wording.

    • The number of calories fed both groups were exactly those prescribed in all animal feeding protocols to maintain a healthy weight for that particular species. This was an iso-caloric study to look at the trans-generational effect of an imbalance of omega-6 to omega-3 fatty acids and the effect on epigenetics. Other studies studies have demonstrated that intelligence is weakened after three generations of the same feeding patterns.

      A study is determined by the quality of the research, not wording.

  4. As a dietitian, I have been concerned about the lack of omega-3 fatty acids in the diet of children and how this could affect them. Most foods that kids eat do not have many omega-3′s. Schools in an effort to save money have reduced time spent in physical education, nutrition and food prep. classes. This “savings” will come back to haunt us. I find low income mothers, who need to know how to prepare healthy meals from low cost ingredients, have little knowledge of food preparation and tend to use more fast food and prepackaged food with higher sodium and fat and fewer whole grains.

    • I agree that the lack of attention on food preparation may be the greatest national security threat we face today as it leaves unprepared to compete in the new world of globalization.

  5. Jocko must be a 3rd generation omega 6′er because he doesn’t seem to have enough grey matter to comprehend the study nor enough intelligence to seek out the study dr.sears refers to.How about just googling omega 3 fats study?I just did and got a return of 11 million hits in less than 1 sec.Take your choice of which to read, but realize this:Animals and people don’t overeat if they are satisfied and there is little nutrition in a substance that is contained in a box or bag.Processed “food” to enhance it’s shelf life isn’t going to do a body good.

    • It’s the hormonal signals processed in the hypothalamus that tells us to stop eating. These can be easily disrupted by cellular inflammation. In an animal study, the number of calories available each day is controlled by the investigator. If an animal is hungry, they just have to get used to it until the next feeding session. In the real world, if a person is constantly hungry because their satiety signals are disturbed, they can simply find more cheap, processed food to curb their hunger.

  6. The point I was making was that not every study is done by quality. Some/many studies are specifically done to arrive at a particular outcome.
    Many animals eat themselves to death and don’t know when to stop. The feedings must be controlled. Same with people. They are addicted to food. Many times this can only be accomplished by will power and intelligence. This is the reason for the gastric bypass operations.
    At first, Dr. Sears made no mention of an “iso-caloric” study.
    People don’t necessarily eat cheap, processed food to curb hunger. If you overeat only Dr. Sears recipes (expensive unprocessed food) and eat negligible Omega 6 you will gain weight/body fat.
    Paul, what does intelligence have to do with seeking out the study that was mentioned? I don’t have the time to do investigative work on everything I read. I simply questioned the fact that the amount of food in the study was not originally specified by Dr Sears. And to exaggerate never wins any debate; less than 1 second to do a search?

  7. Can an individual reverse this? When pregnant, my diet was high in omega 6 and probably had little omega 3 as i don’t eat fish. (i’d never heard of omega 3 supplements and formulas weren’t supplemented with dha to bring it to my attention until later…not that it would have helped since I breast fed). Ironically, I felt something changed in my body as a result of my 2nd (and last pregnancy) and I have struggled with weight ever since. My concern is my child, while very active and a healthy weight now, seems very “addicted” to carbs and snack foods. I am afraid he might be a victim of epigenetic changes because of me and may face weight/health issues in the future.

    If I try to reduce his refined carbs and meet his sweet tooth cravings with a zone snack and give him an omega 3 supplement, can this reverse the epigenetic changes or only try to help control them? What daily dosage of omega 3 and polyphenals would be appropriate for an 80 pound 10 year old? thanks

    • Once those epigenetic changes are set in the womb you have to keeping fighting them for a lifetime. This means paying very close attention to an anti-inflammatory diet in order to manage cellular inflammation. I would recommend a minimum 2.5 grams of EPA and DHA per day plus at least 8,000 ORAC units (about 10 servings of vegetables and fruits) to provide adequate anti-oxidant protection for the omega-3 fatty acids.

  8. Your article is very timely. Highlights the real need for some action globally on this one. thank You Michael.

  9. Dr. Sears,
    I am a follower of your Zone Diet and studies and theories since the Zone Files years and I had many discussions with Anne Marie Blacker who never doubted you on anything so Anne Marie and I had many disagreements. I created many Zone recipes and posted them at your Zone Files.
    You seem to simplify everything. People don’t always eat because they are hungry. I eat more when I am not active. I have to use will power and concentrate on not eating. I have to deliberately restrict my eating and I usually eat zonefully but still I have to count calories and almost starve myself when I think of something good and delicious to cook or bake and it has nothing at all to do with hunger. Yet when I am active, as now starting up a garden, I am reminded to eat by feeling sick fro lack oif food.
    Not to be disrespectful but many times you are preaching to the choir. My internal cellular inflammation couldn’t be better and yet I developed cancer. My weight is about 10 pounds too much.
    I respect you as a scientist but it seems to me you are preaching to the choir and lumping all people into one catagory. (rant over!)

    • All human physiology is ultimately driven by hormones. This is especially true in the case of hunger. It is basic biological function like breathing that must be maintained. That being said, the complexity of the hormonal interactions behind hunger and satiety is still being discovered. When you think of something in the brain, you create a hormonal response that allows you to respond to past memories. The power of those memories may be enough to drive you to physical action.

  10. I’m keeping your diet ant I’m very pleased of it. I reached the weight that I wished. I would like to continue to eat in the Zone but I don’t like to loose weight more. What have I to do?I am from Bulgaria and the information here is very scarce.

    • When you are following the Zone diet, you are eating as if you are already at your ideal weight. Once you reach that weight, you don’t change the diet just maintain it. Don’t be concerned about the weight as much as your per cent body fat that you can calculate using the Body Fat Calculator. If your per cent body fat drops too low (below that of an Olympic athlete) then begin to add more monounsaturated fat to your diet in order to maintain an appropriate body fat percentage.

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