DEVELOPMENTAL ORIGINS OF DISEASE

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The basis of epigenetics is founded in fetal development and is heavily influenced by grand maternal and maternal behaviors that influence in utero life of the fetus. This influence seems to be multigenerational as well because of the inheritance of meiotic stem cells in females. It has been known for years that the mother’s behavior during pregnancy clearly effects the child’s outcomes when born. The extent of this effect however has never been studied in depth until recently. It appears that the mother’s diet, metabolism, and exercise status during pregnancy has profound effects on the fetus and likely set the “epigenetic switches” on the child’s DNA. These changes seem to set the child up for neolithic diseases and the chronic diseases we see in America today. For the last thirty years childhood obesity studies have shown a dramatic change in NHANES curves that measure obesity in children. We now see young children and infants with chronic diseases that adults used to get later in their life. Most of the focus of researchers in childhood obesity, like Robert Lustig, have focused in on postnatal environmental factors in childhood as the major cause. He views fructose consumption as a major culprit in his writings. It appears that new science is showing the problem likely starts earlier than just the child’s behavior postnatally. It appears what the mother eats during the pregnancy and how she exercises presets the child’s metabolism switches. David Barker recently hypothesized that poor nutrition in utero can influence the fetus’s chance of developing chronic diseases in adult life. It appears epigenetic modifications mediate these findings. More recent data showed that over eating and maternal obesity predispose the offspring to metabolic diseases postnatally. In 2011, we now have several studies linking pregnancy exercise to modest reductions in birth weights. It is well established that high birth weight children are associated with increased risk of adult onset chronic diseases. Since we know maternal diet plays a role in childhood development the question is now can exercise during pregnancy modify postnatal development as well?

The effects of exercise in pregnancy have been looked at many times, but the studies were not well designed. This resulted in many studies showing conflicting evidence on the impact of exercise on fetal development. It appears the best current data shows that gestational birth weight has a huge impact on future disease risk. The curve depicting that data is not linear; it is U shaped. This means that low and high birth weight children will face the highest risk of developing chronic neolithic diseases. Since we know that leptin resistance is tied to obesity and anorexia the finding that a U shaped curve in offspring is hardly surprising. We also know that the leptin status of the mother directly effects her fecundity and oocyte development in the human embryo. It appears life outcome may be set by the mother’s current energy status that is signaled to the fetus. That signal is transduced by the child’s resultant growth trajectory until age 6. At age six, our energy expenditure and metabolism seems to be hardwired and trends to adult growth curves as well. What is more remarkable, is that it appears the overweight mothers (LR) may lower the offspring’s risk of disease by initiating exercise in the the last two trimesters of pregnancy. It appears the type, timing, volume, and intensity of exercise is yet to be worked out by research. The reduction of fetal birth weight from her exercise seems independent of the mother’s leptin status. It does however change the leptin status of the placenta and core blood the fetus sees in utero. The exercise program used in Sarah Hopkins studies reduced fetal birth weight by 143 grams and this small change had large effects on IGF1 and IGF-2 signaling. Moreover, serum leptin increased in response to exercise late in pregnancy and there was a trend toward exercise blunting increases in serum free fatty acids that were observed in the non exercising group. The exercise group all had normal birth-weight children that were deemed healthy. This begs the question can exercise in the last trimester of pregnancy of overweight mothers reduce the birth weight of their children to confer a lowered risk of neolithic disease? Hopkins and Cutfield work clearly show that maternal exercise effects are carried over to the fetus.

Might the study of the developmental origins of human disease lead us to the development of the origins of disease prevention? It appears that this question is ripe for study. It also appears that the epigenetic behaviors of the mother can be conferred directly to the offspring. Not everything passed upon to the child appears to be hard wired genetic determinism. In fact, it appears that the in-utero environments plays a much greater role in setting up the child’s metabolism and the signals that activate the genes that ultimate lead to their adult phenotypes. This is a very radical new way of looking at how evolution works. Many who follow evolutionary biology and medicine will have to rethink disease prevention if it become clear scientifically that the major determinants of disease risk are set early in life. It also suggests that the diet we are best suited for in adult life may be predicted by our adiposity and muscle mass at age six. Why age six you ask? Future adult BMI trends to the BMI of where the child is at six years old. So it appears that early postnatal life has a massive influence on the risk factors for disease in later life. The first six years of life tend to resemble a catch up or catch down situation compared to the in utero life that was experienced by the fetus. This may explain why so many people respond differently to adult dietary modifications. The in utero exercise and or diet may not be the driver of the long term health benefit. But It could set the stage for postnatal catch up. This postnatal catch up seems to correlate well with adult growth trajectories and how they respond to certain diets. It appears that the diet we maybe best suited to can be elucidated if we know what signals our genes have been sensitized too by the first six years of our life and what happened in utero.

CITES:
Hopkins et al, Exercise training in pregnancy reduces offspring size without changes in maternal insulin sensitivity. J Clin. Endocrin. Metab. 2010; 95(5):2080-08

Hopkins et al. Exercise in pregnancy: weighing up the long term impact on the next generation. Exer. Sports Sci. Rev 2011; 39:120-07

Hanson et al. Developmental plasticity and development origins of non – communicable diseas: theoretical considerations and epigenetic mechanisms. Prog Bio. Physio. Mol. Bio. 2011; doi:10.1016/j.pbiomolbio.2010.12.2008

http://jama.ama-assn.org/content/306/2/206.long

Comments

  1. So this means that my mom's bout of Hepatitis B during her 9th month of pregnancy with me could have a lot to do with my obesity. She was not overweight at the time, but has since become overweight in her older years. I was a normal weight at birth, but was always one of the heavier kids in class. Both my siblings are taller and have maintained a healthy weight. BTW over the last 5 years I've lost 70# and have about 50 more to go to get to "healthy". I'm finding hope in your blog that the last 50 are possible. Thank you! PS: do you have any tips to flip epigentic switches set by Hep B or even tests to ask my doctor to run?

  2. Poisonguy says:

    From a father of two (a two and six year old), this was a great article to read. Both our kids were born with basically the same weight (3.1 kg or 6.8 pounds, which is I believe in the normal range). Curiously, though, my wife was overweight for the first pregnancy but not for the second. Our six year old is slim and active, while our 2 year old is a tad chubby (but seems to be slimming). Both were breastfed (first for 4 months and the second for over a year). Seems to be the opposite of what would be predicted, no? Glad to see the six year old is on the right track.

  3. patricia knigge says:

    Are they following the children long term or just through birth weight?

  4. Doc!

    I have just started reading your site and was struck by the 1st Levee. So my question is does this mean that you are a believer in Antoine Bechamp's pleomorphic theory rather than Pastuer's germ theory? I would be interested in seeing a post on your views of the two! I believe in Bechamp! Ok back to your quilt…

    Dave

  5. It seems that the father has far less influence on procreation then I thought. They simply provide the trigger to start the process.

  6. dr. k said:

    "It appears the best current data shows that gestational birth weight has a huge impact on future disease risk. The curve depicting that data is not linear; it is U shaped. This means that low and high birth weight children will face the highest risk of developing chronic neolithic diseases.:

    Could you tell as the healthy range of birth weight? My oldest daughter was over 8 pounds at 3800 grams. I did research that set 4000 grams as the start point for large babies.

  7. here is info on large babies:

    http://en.wikipedia.org/wiki/Large_for_gestationa

  8. @V 4000 gms is the point. You would do well however to think about how your child responded 0-6 yrs old. It appears from my reading we need to really get kids to eat correctly early. Maybe they instinctively know not to eat veggies and stick with meat. I wish I had this insight when my kids were young. I hope some peditricians begin to read this data because the epigenetic story is likely to be a huge one for human disease propagation

  9. @Dave……I have a synthesis view. Levee one is my true revolutionary belief. That is why it is at the top. I think all the other levees directly allow levee one to occur. The key to understanding the Quilt is understanding how we can modify our lives to make levee one come to fruition. That is precisely how I practice now.

  10. @Chris. Dad plays a huge role too. We determine the sex and there is some evidence that men do have some minor epigenetic effects on children

  11. thx for your quick reply. my child born at 3800 grams was not pudgy/overweight 0 to 6 years old. when she hit puberty at 12 she started to have the ability to gain weight quickly on the SAD whereas before she was bony. now (15 yo) she is not overweight due to sports and paleo friendly food in the house. she still loves carbs and cooks likes to eat a lot of dumplings and corn on the cob.

    my husband is chinese and although we ate mcdonalds at least once a week, the remaining time we has 66% SAD except we never had soda in the fridge, only occasional juice and mostly ice water, and my husband is chinese and cooked alot of salmon, beef broccoli, and rice etc. for my kids when he was off from work. if it weren't for him, we would have been eating 100% SAD garbage.

  12. i need an edit function 🙁

  13. @V is sounds like your daughter's future will be tied to her choices. I would be concerned with the SAD you ate while pregnant. Pay attn to her as she begins to have babies. You might see some interesting changes in the offspring. I have done this with my entire family and it has been an eye opener for me as a physician. The epigenetic story is one that will change our views on genes from here on out.

  14. I was in Taiwan a full year before I got pregnant and I planned the pregnancy so that I was fit before it,taking vitamins,and eating a SCD or standard Chinese diet except for oatmeal. I had lots of steamed cod with my first pregnancy, but I also ate a lot of dumplings. I had a lot of fat on my body after I gave birth but slimmed down in a year so I could get pregnant a second time, also planned. I was an extremely big baby when I was born so it looks like I carried that forward with my kids although my pregnancies went much more smoothly than my mother's. How about the strory with your kids may I ask?

  15. my kids both have thin grandmoms but one smoked and the other ate a ton of omega 6's. We reversed both problems in our kids as soon as I found out about the epigenetic effects on kids from multigenerational switches.

  16. how did you change their diet? standard robb wolf paleo?

  17. no. My version of paleo. Pedal to the metal with supraphysiologic omega three's in food and a tailored supplement regime that meshed with their clinical symptoms and labs.

  18. about fish oil and surgery:

    http://www.facs.org/surgerynews/2010/fishoil0110….

  19. 1.) do you buy all grass-fed stuff? because of my heavy menstrual bleeding, i can't take omega 3 fish oil as it makes the bleeding worse and i have almost zero ferritin, so i can't mess with heavy bleeding.

    2.) as a surgeon, i would assume you know that fish oil supplements can cause heavy bleeding, no? before shoulder surgery, my husband was told to stop taking fish oil a number of days before. my 15 year old daughter also found her flow increased by fish oil and decreased when she stopped taking it.

  20. from the above link:

    "Anti-inflammatory effects of omega-3 fatty acids are credited with clinical improvement. Another possible beneficial mechanism with fish oil—its ability to decrease thromboxane A2 within platelets and thereby reduce platelet aggregation—may have a downside. "We're seeing excess bleeding in a lot of cardiac patients after surgery," said Dr. Reichert, pharmacy coordinator for surgery at Wake Forest University Baptist Medical Center in Winston-Salem, N.C."

  21. your 'theory' is shortsighted and misogynistic. men directly affect women's health as well as embryonic health. immune system wise and gut flora fauna balance/ imbalance.

    … also directly affecting women's vasopressin/adh Limbic hypothalamus and the HPA axis. eg) men seem to massively affect everyone in proximity in terms of their stress levels and promoting the "can't escape"/freeze fight flight response.

    …. saying epigenetics is about the maternal/mother /grandmother _with ZERO mention of males role in all this_ is all part of the bigger problem in 'medicine'. yes its misogynistic, whether active or "laziness" via not bothering to *thoroughly analyze the science. same reason why 'modern medicine' insisted for decades (till the availability of the internet) that Hashimoto's thyroiditis was the ONLY autoimmune disease that was "not important and required ZERO treatment or assessments".

    scary that these same 'medical experts' are operating 'heavy machinery' like automobiles every day.

    … doctors are not scientists and yet keep claiming they have the analytical ability of scientists is insanity.

    ego is a big part of the problem, including NOT admitting to all patients that 'practicing' doctors do not know a lot and are guessing and prescribing pills

    VS "knowing" .

    ignoring the existing medical science and not admitting it exists has affected *everyone's health, epigentics , genes

    for the last 50 + years.

    hence the massive amounts of autoimmunity and autism spectrum and ADD and depression/CNS related problems.

    • @Mary……you're entitled to your opinion……..enjoy CW modern medicine and the results it dishes out to you and yours.

      When you rely on the current medical literature this is what what you get……..

      http://www.theatlantic.com/magazine/archive/2010/

      I find no solace in bullshit research. The road to Optimal is found in our owners manual we all came with. That owners manual is our DNA sculpted by 2.5 million years of a Randomize control trial That is the best RCT I have ever studied. I am quite glad my sensibilities are different than yours quite frankly.

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