Epigenetics, or What I Mean by “Reprogram Your Genes”

EpigeneticsYou can’t change your genes. But you can program them.

The modern world presents a number of problems for our genes. The world we’ve constructed over the last 50 years is not the environment in which our genetic code evolved. Our genes don’t “expect” historically low magnesium levels in soil, spending all day indoors and all night staring into bright blue lights, earning your keep by sitting on your ass, getting your food delivered to your door, communicating with people primarily through strange scratchings that travel through the air. So when these novel environmental stimuli interact with our genetic code, we get disease and dysfunction.

The genes look bad viewed through a modern prism. They get “associated” with certain devastating health conditions. But really, if you were to restore the dietary, behavioral, and ambient environments under which those genes evolved, those genes wouldn’t look so bad anymore. They might even look great.

This is epigenetics: altering the programming language of your genes without altering the genes themselves.

Think of your genome as computer hardware. If you were to program your computer you wouldn’t be changing the hardware; you would be changing the software that tells the computer what to do. So just as we talk about reprogramming or programming a computer and don’t suggest that the hardware itself has changed we likewise can talk about reprogramming our genes without suggesting that the genes have changed.

Okay, so how does this play out in reality? Are there any good examples of epigenetics in humans?

One of the most striking cases of the environment altering gene expression was in an old study of a homogeneous population of Berbers from North Africa.1 Researchers studied desert nomads, mountain agrarians, and coastal urban residents. All were Berbers with low genetic variance. These people had very similar genetic patterns—were from the same basic genetic stock—but very different living situations.

The researchers analyzed the white blood cells of the group “to study the impact of the transition from traditional to urbanized lifestyles on the human immune system.” Berbers from urban environments had evidence of upregulated respiratory and immune genes, for example. Those same genes lay more “dormant” in nomadic and agrarian Berbers.

Overall, gene expression between the three groups varied by up to one-third based on geographic location and corresponding lifestyle. In their conclusion, the authors lay out the foundation of everything we talk about on this blog and in this space:

“Diseases due to genetic factors in urban populations may bear little resemblance to the impact of the same genetic factors in traditional societies.”

Did you get that?

“Bad genes” aren’t bad in traditional environments. The trick, of course, is figuring out what makes up the traditional environment and whether you can replicate it in the modern world.

Let’s look at a specific example: Tobacco.

Epigenetic Effects of Tobacco

Tobacco smoking “silences” the MTHFR gene via hypermethylation.2 Since MTHFR is the gene that constructs the proteins we use to activate thousands of other genes, suppressing MTHFR suppresses all those genes that rely on MTHFR-related proteins for activation. This disrupts numerous physiological systems and can set the stage for things like birth defects, cancer, and heart disease. It’s an epigenetic disaster, and it’s one reason why smoking increases the risk of so many different diseases.

Tobacco also induces hypermethylation (overactivation) of the GCLC gene which controls glutathione production. This causes a suppression of glutathione levels, an increase in oxidative stress, and initiation of COPD (chronic obstructive pulmonary disease).3 GCLC is meant to deal with more moderate levels of toxins and irritants; these can actually have a beneficial hormetic effect that triggers higher levels of glutathione and less oxidative stress. In this case, tobacco represents a supranormal stimulus that turns a helpful gene harmful.

Or how about the genetics of obesity?

Epigenetics and Obesity

For the last decade, we’ve been inundated with the idea that obesity is caused by your genes. That some people are just destined to be be overweight. Sure enough, there are dozens of genes linked to an elevated risk of obesity and overweight.

Only genes can’t wholly explain the huge rise in obesity rates over the last hundred years because genes don’t change that fast. People used to be thin, and now they aren’t, and they have the same basic genetic profiles.

The real problem is that almost everyone in the western world exists in a shared food environment which is obesogenic. If you live in America, you’re awash in drive-thrus, Big Gulps, and inexpensive, delicious processed food that’s been engineered to interact with the pleasure centers in your brain. Most modern countries are in similar boats, and obesity rates are climbing across other nations as they adopt our food-ways and work habits. The genes aren’t changing (at least, not quick enough to account for the stats), the environment is changing.

Because the environment has changed for everyone, and most people never really question its obesogenic nature — they eat the pizza, they buy the processed food, they sit for eight hours a day at work and watch TV for four, they slog away on the treadmill—researchers looking for the genetic origins of obesity miss or discount the effect of environment. Almost everyone whose genetic data they’re examining is exposed to the same obesogenic food environment, and its ubiquity masks its effects. And because some people appear to have genetic profiles that protect them against obesity, researchers lay the blame at the feet of the genes.

The “epigenetics of obesity” is more accurate than the “genetics of obesity.”

Let’s see a few more examples.

Exercise Non-responders Epigenetics

Some people carry an “exercise non-responder” gene. by most counts, it’s 15% of the population. For these folks, doing standard “cardio” doesn’t do much. It may even impair insulin sensitivity, raise blood pressure, lower HDL, and leave cardiovascular fitness unchanged.4

If the idea of someone being an exercise “non-responder” sounds ridiculous and unbelievable, you’re right. It turns out that while regular cardio is neutral or even detrimental to this genetic profile, high-intensity training confers the normal benefits you’d expect from exercise5. I’d also guess that resistance training would work as well.

It’s not the genes that are faulty. It’s the (exercise) environment that’s faulty.

MTHFR Mutation Epigenetics

MTHFR mutations often impair folate absorption or conversion of folic acid into bioavailable folate, and they increase the requirements of others nutrients like choline and vitamin B12. In the modern food environment bereft of vegetation and nutrient-dense animal products, those mutations cause huge issues. In a traditional food environment full of vegetation and nutrient-dense animal products, or supplemental forms that mimic the active food forms, they aren’t as bad.

If you eat a lot of vegetables (a good source of folate), you weaken the link between MTHFR mutations and kidney cancer.6

If you have some of the common MTHFR mutations, you need to eat more dietary choline (eggs, liver).7 Doing so preserves methylation status.8

PUFA Metabolism Epigenetics

Your genes also affect fat metabolism. Some mutations in the FADS1 improve the ability of a person to elongate plant omega-3s into long-chained omega-3s like the fish fats EPA and DHA. In the context of a low-fish diet, they can still make the EPA and DHA they require to function as long as they eat some alpha-linolenic acid. This mutation is more common in populations with a long history of farming.

Another mutation impairs the ability of a person to elongate those plant fats into animal-type EPA and DHA; they need to eat a high-fish diet or supplement with fish oil to get the omega-3s their bodies need. That’s the boat I’m in—I fucntion best with a steady supply of long-chained omega-3s in my diet, probably because my recent ancestors ate a lot of seafood. This mutation is more common in populations with a shorter history of farming, or a longer history of reliance on seafood.

What’s the point of all this?

There are multiple future possible versions of you. It’s up to you to decide which version you will become. It’s up to you to make lifestyle choices that direct genes toward fat burning, muscle building, longevity and wellness, and away from fat storing, muscle wasting, disease and illness. The day-to-day choices we make—whether it’s what to pack for lunch, or hitting the snooze button and missing the gym, or even sneaking a cigarette break—don’t just impact us in the short-term (or even in ways that are immediately clear to us). That can make this scary, but it can also be empowering.

You can fix yourself. You can be better. Your genes can work better. Everyone, no matter how dire their circumstances or how “poor” the cards they were dealt were, can forge their own epigenetic destiny.

You can’t ignore the genes. They still matter. You have to figure out, of course, how your particular genes interact with diet, exercise, sleep, sun, nature, socializing, and every other lifestyle behavior. That’s the journey you’re on. That’s the journey we’re all on—it’s what this website and movement are about.

There’s a lot we don’t know about this topic. What if I don’t have a study I can refer to? What if I don’t sign up for a DNA analysis—am I out of luck?

Use your intuition when you don’t have a study or haven’t defined an epigenetic mechanism: Does it feel right? Does it feel wrong? Are you getting good results? How’s your energy? How’s your performance? Those subtle (or not-so-subtle) cues from our subconscious and direct feedback from our waking life are where true knowledge and wisdom lie. After all, your genes “want” you to do the right thing. If we’re cued into our subconscious and we’ve led a generally healthy way of life, we become more sensitive to those messages. Those flutters of doubt or little urges we get are the body’s way of telling us we’re headed for epigenetic ruin or success.

Listen to those, or at least consider and don’t ignore them.

This is what The Primal Blueprint, The Keto Reset Diet, The Primal Connection, and even Primal Endurance have all been about. It’s why the sub-title of my first book is “Reprogram Your Genes for Effortless Weight Loss, Vibrant Health and Boundless Energy”. And it’s what we talk about (either directly or indirectly) day-in and day-out here at Mark’s Daily Apple.

Now I’d love to hear from you. Do you have any questions about epigenetics? About how we can alter our genetic destiny through modifying our environments?

Leave them down below.

About the Author

Mark Sisson is the founder of Mark’s Daily Apple, godfather to the Primal food and lifestyle movement, and the New York Times bestselling author of The Keto Reset Diet. His latest book is Keto for Life, where he discusses how he combines the keto diet with a Primal lifestyle for optimal health and longevity. Mark is the author of numerous other books as well, including The Primal Blueprint, which was credited with turbocharging the growth of the primal/paleo movement back in 2009. After spending three decades researching and educating folks on why food is the key component to achieving and maintaining optimal wellness, Mark launched Primal Kitchen, a real-food company that creates Primal/paleo, keto, and Whole30-friendly kitchen staples.

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76 thoughts on “Epigenetics, or What I Mean by “Reprogram Your Genes””

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  1. Good post! It seems like a lot of people get confused about this, but that’s understandable, as epigenetics isn’t necessarily widely-understood even by lots of biologists–it tends to be more of a niche specialization. We do indeed have tremendous control over which genes, or variants of genes (through alternate splicing and the like) are expressed, and a lot can be done with this to improve our health and fitness. Keep up the good fight!

  2. Wonderful videos! I am so excited by this concept – what control we have over our lives. Thanks, Mark!

  3. Great Post Mark. Outside of Body By Science (chapter 8’s Genetic factor), I have yet to hear anyone else discuss Epigenetics in training circles. I’ts an amazing area that, upon researching, most people will find encouraging and hopefully will have them cursing there parents genes a little less.

  4. That’s a great video. People are starting to realize more and more that what they eat, and their habits and lifestyles really do affect their health and all aspects of their lives. You are what you eat!

  5. By adopting a paleo/primal lifestyle, I have lost weight, gained confidence and strength, banished depression, discovered I had smooth and clear skin. Is this reprogramming my genes? It doesn’t matter! It just feels great!

    I feel that I am becoming the absolute BEST I can be!

  6. wow.. really powerful stuff. Almost makes me want to put down this caffeine filled Central Nervous System Stimulator… almost…

    I’m always amazed be the quality of the content and research that you post on your blog Mark. It is truly amazing to see the dedication and thought you put into every one of your posts.

  7. As always, thanks for the post. I am constantly amazed by how much great information I get from this site and that it is all free! I did by the book this week, so I don’t feel too bad.

  8. This subject has fascinated me since I learned about it. I have recently learned that I have a mild, at least at this point, elevated platelet count that is probably caused by something in my environment switching on the accelerator that regulates my platelet count.

    Apparetly, a pill that will switch off the accelerator is in the works but meanwhile I am experimenting with using my mind to switch it off. I am curious if this is possible and will find out when I take my next blood test next month. It will be a nice surprise if it does, both for me and my doctor.

    Does anyone know if there is any evidence that one can control the switching on or off of these epigenes with one’s mind?

    1. Okay Sharon this is very weird. I have the same platelet disorder as you and my name is Sharon as well. Could it be that we look exactly alike?….

      I have the JAK2 mutation so I too have been wondering since something switched this on, is there something that can switch it off? No one seems to know. At least I have not found anyone who thinks so. I did try the mind thing to no avail but that doesn’t mean it might not work for you.

      So far nothing that I do makes any difference in my count except the drug I am taking. Even though it is a serious chemo drug, with a serious amount of possible side effects, so far, no side effects for me.

      Last time at the Hematologist the PA said some people’s platelet count goes back to normal even though they have the JAK2 mutation but she had no idea why. I wanna know why!

      Since we now have two Sharons on this site I am changing my moniker to SunshineSharon. Always wanted to be a hippie but never got the outfit right.

      1. Ha! I see what is going on. I clicked over to a past article rather than staying on the current article. I was talking to myself.

        Staff….can you cancel this and the previous reply that you are moderating? I will go back to Sharon….sorry, I am an idiot

  9. Fascinating.

    As a father of identical twins I thought this post was very interesting.

    Fills me with a rather ominous sense of responsbility however!

  10. Speaking of your book, I just got it on Tuesday, and it’s really inspirational. I went out to fetch some antioxidant rich fruits you suggested, like blueberry and raspberry, along with some spinach and tomatoes for salads.

  11. Thanks Mark for the post and Samson for the videos. Can’t wait to show my family since they think I’m a food Nazi. Your book is great and love the responsibly slim.

    I look forward to coming here everday.

  12. I know that a primal-like approach to health and fitness reprogrammed my genes and completely changed me inside and out.

  13. Thanks for sharing — epigenetic research needs more coverage. Diet and exercise have a huge influence on gene expression, but so do other environmental factors like artificial light, population density, air quality, and other realities of modern life. Given the 30% success rate of placebos, maybe our thinking influences genetic expression as well.

  14. For those interested, Bruce Lipton’s The Biology of Belief is a good primer on epigenetics.

  15. Mark, Great post! Lots of information. I was wondering if anyone can give me advice on living w/ non primal eaters (my parents) i love them dearly but they like to order pizza a lot and have me do runs to pick up ice cream. they also eat a lot of grains. i am doing ok but would love some tips on how to avoid “the bad stuff” 🙂
    Thanks for your time.

    1. I live with one. I have it easier since I am allergic to wheat which is mostly what she eats. I just make sure I have plenty of Primal snacks around and eat good Primal meals so I am not hungry when she brings it in. She eats potato chips I eat an apple or grapefruit or some carrot sticks or even a couple of pork rinds.

        1. I eat them a couple times a week as a crunchy snack. I only buy the plain which are just pork skins and salt no added junk. The flavored often have msg so be careful. The brand I buy has 9 grams of protein in a 1/2 oz and no carbs at all. Much better than potato chips if you need a crunchy fix with fat and protein.

  16. “There are multiple future possible versions of you. It’s up to you to decide which version you will become.”

    This is a great quote. Thanks Mark.

  17. Fascinating stuff! The scientists are giving us more all the time but sadly many jump on the chance to have an excuse for being unhealthy or overweight.

    I’ve been an overweight youngster and defeated that with exercise and nutrition. Primal living has taken me one step further. Others may find some inspiration in my story at http://www.lmdfitness.com/about/

    I honestly believe in the power of nutrition!

    1. Come to think of it, my mom used to get rid of her migrains by giving them the ‘dingbats’ as she called it.

  18. Awesome stuff and timely! My friend and I were just having this discussion after learning a mututal friend of ours was diagnosed with cancer (41 years old!). She didn’t understand where I was coming from with my ideas of “reprogramming”. I sent this to her. 🙂

  19. This gives me more of an arsenal against my own mind when I start to think my genetics can defeat me. Thanks!

  20. Awesome videos! Goes to show you that living a healthy lifestyle significantly reduces your chances of developing any type of deadly disease! Better start as early as possible… lucky for me I am only 21 🙂

  21. Thank you for posting this. As someone with a biology degree, this is all elementary stuff to us. But the general public doesn’t really understand genetics.

    Yes, twins may have the same “blue print”, but that doesn’t mean that “blue print” has to be followed in the same way. Gene expression (i.e., what genes are turned on or off, and how much of it) plays a much greater role in our resulting make up than the actual code itself. Gene expression is affected by environment, lifestyle and diet.

  22. As an identical twin that was recently diagnosed with Parkinson’s, I found this terribly interesting and it should be a comfort to my twin. I wonder if there is anything one can do to change the epigenes in a mature person? And is there a therapy where I could use his epigenes to correct mine?

  23. I was talking to a friend on mine about the choices we make and how they affect our families and future generations. He was telling me how the Native American cultures when weighing decisions and choices, would consider how the choices they were about to make would affect there families 7 generations from today. Not necessarily that they always did a good job with their choices, but it’s amazing to me how this post ties right into that. Depending on whether you choose to eat that corporate raised steroid beef, get that flu vaccine, smoke those cigarettes, or go binge drinking, will dictate how soon your family will have any number of diseases appear, and how quickly in future generations. Amazing stuff. So next time you are having a craving for something bad, think of your kids, or great great great grand kids you don’t have yet! Choose well!

  24. Here is a picture of two mice…Same mother and father…The difference is the mother of the mouse on the left was fed extra folic acid while pregnant.
    (Couldn’t upload the pic Mark …If you would like to see it ..tell me where to email the picture…you will want to post this)

  25. awesome post here Mark! I wish more research would be focused in these areas to truly show the ADA and Big Pharma they have it all wrong. Its so clear to us but so many people still chalk up being fat to their genes.

  26. wow! those 2 videos were really great. i love nova too! so interesting…

  27. Okay, so they fed the mice extra methyl groups to turn off the fat gene. So, natural question, what foods have methyl groups in them?


    1. Those mice had a genetic disposition to particular disease in which one symptom is weight gain. Eating what they ate isn’t going to do anything except turn off that expression of their genome.(it won’t make you skinny)

  28. Have been aware of the importance of real eating styles that give one health and vitality. Your material proves to be outstanding.

    I do have one comment to the negative. A study of ionic energy absorbtion in food digestion reveals pork, shellfish, skin fish and crustations have to high an energy level. It is much the same as many appliances hooked up to a wall outlet whereby they cause big current draw which burn out the wires or constanly trip circuit breakers.

    After a while, the circuit breakers fail to work and things burn up. This is how such meats and seafood act in our intercellular communication. To much current! Hence, we get auto-immune diseases. A Dr. Beddoe did the study. It is best not to eat such critters. Ancient diet laws do have a basis in fact!

  29. Wonderful vids, thanks.

    Explains why even though my family line if very fertile and I have a strong desire for motherhood, something’s been telling me “not yet”.

    I can’t start eating healthy when I find out I’m pregnant… We both need to be healthy before conception.

  30. As the voice over says something about the choices we make and being responsible about what we pass to our children, the last scene shows the mother feeding her twins at McDonalds! AHHHHH!!! Yummy trans fat fries washed down with some tasty High Fructose Corn Syrup yogurt. Just thinking about that hurts my Epegenomes.

  31. I understand the concept of epigenetics–barely. I’m not a biochemist. The Nova video makes it sound like expression is fixed. It doesn’t say anything about changing the fat mouse’s diet to turn it into a skinny one.

    Is there really any evidence that a primal diet will change one’s epigenetics? If so, where?

    I’m not saying that a primal diet won’t work, I’m just questioning the mechanism. Does it really take “gene reprogramming” for a low-carb diet to cause a move away from an insulin-dominated metabolism?

  32. Thanks, David. Unfortunately that doesn’t really answer the question. Everything on that page talks about a parent’s or grandparent’s diet modifying the epigenetics of the offspring except this quote:

    “For adults, a methyl deficient diet still leads to a decrease in DNA methylation, but the changes are reversible with resumption of a normal diet.”

    But nothing I’ve seen indicates that the agouti gene can be retroactively suppressed. And I’ve found no evidence of any specific epigenetic changes that can be caused by switching to a primal diet.

    So there may be something there or there may not. The power of the primal diet could just be that our bodies work better when the insulin mechanism isn’t overloaded.

  33. Has there ever been a double blind placebo controlled study(s) to back up the claim that The Primal Diet will reprogram my genes? The Primal Diet is a FAD, complete with its own program of powders and pills. All based on the ancient art of vitamin formulation techniques found in a cave in Southern France.

  34. This is AMAZING and I TOTALLY GET IT. I have identical twin daughters. Genetically they are the same, yet one was born with a genetic heart defect. The specialists at the university hospital where they were born got into an argument about whether it was because of something they were exposed to in the womb or if it occurred naturally and why. I was in good health, had never smoked or consumed anything bad yet it happened. They still don’t understand why. But she is fine now and its myself that I’m working on. Great stuff!

  35. That was so interesting, ive always thought to myself about this, I’ll checked it out further now

    just bought marks 21 days transformation book, should be interesting when it arrives!

    thanks for all your work!!!


  36. Very interesting! Hopefully they have just scratched the surface of this research.

  37. Hi morning, I have read your site. My problem is i dont have diabeties by i realise sometime all of my energy jus goes and i cannot move all i an do it lay down to i recovery, IM realising its happenning because of the foods i eat. Sometime it makes me sleepy or tire and sometimes i feel when my energu level drop. I writing to you because i want to overcome this situation regain my energy and be healthy