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.

Stay on track no matter where you are! Instantly download the Primal and Keto Guide to Eating Out

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 specific examples.

Epigenetics and COVID-19

COVID-19 is one example of epigenetic differences that we’re living through right now. Epigenetics partially explains why coronavirus affects some people mildly, while it’s devastating for others.23 More and more research is pointing to biological mechanisms behind how severe the disease is, but one thing is for sure: severe respiratory symptoms are caused by an excessive inflammation response in the lungs.

Epigenetic variation means that people can get the same strain of the same virus, and have completely different experiences.

Now, how to control it? I don’t know for sure – if I had a definitive answer, I could literally save the world.

For now, I know that a common thread is inflammation, so I am doing all I can to keep my inflammation low. I’m hopeful that further research will reveal ways to turn down the genes responsible for the intensity of the inflammation response. That way, if I’m exposed, I don’t have inflammation from the virus stacking on top of everyday inflammation. I can’t know for sure whether or not that is a good strategy, but keeping inflammation down is a good idea anyway, so I’m going with it.

Epigenetic Effects of Tobacco

Tobacco smoking “silences” the MTHFR gene via hypermethylation.4 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).5 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.6

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 exercise7. 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.8

If you have some of the common MTHFR mutations, you need to eat more dietary choline (eggs, liver).9 Doing so preserves methylation status.10

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.

If you'd like to add an avatar to all of your comments click here!