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.https://www.eurekalert.org/pub_releases/2008-12/aafc-ilc122308.php‘>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).https://www.ncbi.nlm.nih.gov/pubmed/22666405‘>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 exercisehttps://pubmed.ncbi.nlm.nih.gov/18098291/‘>6

If you have some of the common MTHFR mutations, you need to eat more dietary choline (eggs, liver).https://pubmed.ncbi.nlm.nih.gov/20220206/‘>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.


The post Epigenetics, or What I Mean by “Reprogram Your Genes” appeared first on Mark’s Daily Apple.

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how to measure ketonesKeto is unique compared to other diets because there is an objective marker that tells you if you’re on the right track. With an easy at-home test, you can confirm that you are, in fact, in a state of ketosis.

Regular readers probably know I’m not a big data tracker. My energy, sleep, workout performance, stamina, and enjoyment of life tell me almost everything I need to know about how well I’m doing. Nevertheless, I get that some people love to play the self-quantification game. In some medical situations, measuring ketones is advisable, even necessary, as well. I’m not a total curmudgeon about it. Heck, I’ve been known to check in on my blood glucose and ketones from time to time.

If you’re thinking about testing, you should become familiar with the three different methods. Each has its own pros and cons. You’ll want to pick the option that’s right for you.

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

What Exactly Are You Measuring?

Let’s back up and do a quick refresher on ketogenic diets. These are any diets where carbohydrate intake is restricted below about 50 grams of total carbs per day. When you restrict carbs, you are really restricting how much glucose the body has to meet its energy needs. Without much glucose coming in, the body needs an alternative fuel source, especially for the brain, which doesn’t run well on fat. That fuel source is ketones.

The liver produces ketones from fatty acids when insulin levels are low and liver glycogen (stored glucose) becomes depleted. This happens when you follow a very-low-carb diet, fast, or engage in sustained exercise.

When your liver is producing measurable amounts of ketones, you are said to be in ketosis. This is not to be confused with ketoacidosis, a potentially fatal medical emergency. Keto diets don’t lead to ketoacidosis because the body has a safeguard that prevents ketone levels from becoming dangerously high: insulin. When ketones rise, the pancreas releases insulin, which in turn hinders the release of fatty acids from stored body fat. Fewer fatty acids in the bloodstream mean less substrate (material) for the liver to turn into ketones.

This feedback mechanism keeps ketone levels in safe ranges unless your body can’t produce insulin. Individuals with type 1 diabetes and very advanced type 2 diabetes are at risk for developing ketoacidosis for this reason. Diabetics often monitor their ketones to make sure they are within safe ranges.

For the rest of us, measuring ketones is just a way of checking whether or not we are actually in a state of ketosis. We might want to know that for a number of reasons, discussed later.

Meet The Ketones

In ketogenesis, fatty acids are metabolized in the liver to create ketone bodies. The primary ketone body is acetoacetate (AcAc), which can convert into beta-hydroxybutyrate (BHB). AcAc also spontaneously breaks down into a third ketone body, acetone.

The body primarily uses AcAc and BHB for energy. Although acetone can be converted into pyruvate, it’s generally considered a waste product.

How to Test Ketones at Home

There are three ways to test your ketones at home:

  1. Urine test strips, which measure AcAc
  2. Blood tests, which measure BHB
  3. Breath tests, which measure acetone

Urine Ketone Test Strips

How it works:

You can purchase urine ketone test strips online or in many pharmacies. They are cheap, costing only pennies per strip. Don’t confuse them with urine pH strips.

Simply collect your urine in a sample cup or pee directly on the strip. After a set time—usually 15 seconds, but some strips take longer—the end of the strip will change color. Compare the color on the strip to the key on the package to get your ketosis level. Rather than giving you an exact readout, the color tells you if your urine does not register any AcAc, or if it shows low, medium, or high levels.

It’s straightforward but not foolproof. For one, if you let the strip sit for too long before you interpret the results, the test can be inaccurate. Urine strips also tend to overestimate the amount of AcAc present and can give false positives.https://pubmed.ncbi.nlm.nih.gov/12081817/’>2 Results can be affected by how well hydrated you are, too.

Although urine tests are shown to correlate decently well with blood and breath tests in diabeticshttps://pubmed.ncbi.nlm.nih.gov/12081817/‘>4 AcAc in the urine is considered “spillover.” When you first start a keto diet, your cells aren’t great at utilizing ketones, so some get excreted. You’re measuring ketones the liver made but the body can’t use. As you become more keto-adapted, there should be less spillover.

Most keto dieters do find that their urine ketones decline over time. That’s a good thing, indicating less waste; but it also means the urine tests become less useful. It’s very common for experienced keto dieters to have low or no measurable ketones in their urine despite having plenty in their bloodstreams.


  • Least expensive method of testing
  • Does not require blood—no finger pricks


  • Least accurate, especially after keto-adaptation period
  • Affected by how well hydrated you are
  • Does not tell you exact ketone levels

Blood Tests for Ketones

How it works:

Blood tests measure the level of BHB in the bloodstream. This is considered the gold standard in ketone testing. They require an initial investment in a meter, plus ongoing purchases of test strips. You also need a lancing device and sterile lancets to prick your finger and draw a droplet of blood. If you’re planning on testing several times a day, it can get expensive fast, not to mention your sore fingertips.

The two most popular meters in the U.S. are the Keto Mojo(™) and Precision Xtra. Both also measure blood glucose, but you need separate test strips. The Precision Xtra meter runs around $25 depending on where you purchase it. Ketone test strips cost about $1.20 each, and glucose test strips about $0.65.

You can get a Keto Mojo starter kit on the company’s website that includes the meter, lancing device, 10 lancets, 10 ketone test strips, 10 glucose test strips, and a travel case for $59.99. Additional ketone test strips cost $49.50 for a 50-pack. Glucose test strips are $14.99 for a 50-pack. They also offer a Bluetooth connector for $9.95 that allows you to upload your test results to an app.

Understanding blood test results:

Your meter will give you a reading of 0 or “Lo” if you aren’t in ketosis. On a typical keto diet, you might be anywhere from 0.3 to around 2.0 mmol (millimole). Fasting and exercise can each drive BHB up to 4.0 mmol or higher. Ketoacidosis occurs above 10 mmol.

In The Art and Science of Low Carbohydrate Living, renowned researchers Jeff Volek and Stephen Phinney proposed that ketosis begins at 0.5 mmol. The designated 1.0 to 2.5 mmol as the “optimal ketone zone.” Don’t get too hung up on these numbers, though. Some individuals produce high levels of ketones on a normal keto diet, while others barely register any unless they fast or use exogenous ketones (which contain BHB). I have friends who have been strictly keto for years and consistently hover around 0.3 or 0.4 mmol. We don’t really understand why these individual differences exist. I’ve offered some hypotheses, but it’s still a bit of a mystery.

Anyway, higher numbers don’t mean that you’re doing better than the next person. In certain medical situations, such as for seizure control, high BHB levels are desirable. For the average person doing keto for weight loss or general wellness, there’s no evidence that it makes a big difference. More recently, Phinney and Volek have started to talk about the “effective therapeutic range”—where you can expect to reap benefits from being in ketosis—as being anywhere between 0.5 and 4.0 mmol.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4737348/‘>6

Breath acetone does reliably correlate with blood BHB. Multiple studies also show that acetone readings are correlated with weight loss when participants follow a calorie-restricted diet.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5097355/‘>8 Blood tests were otherwise fairly steady throughout the day, with a modest decline in the afternoon. Urine tests showed higher ketones as the day progressed, also with a small mid-afternoon dip. The highest levels occurred before bed, at 10 p.m.

Do You Need to Test?

No, but there are some reasons you might want to.

As I said up top, those using a ketogenic diet therapeutically might need to track ketone levels. For certain conditions like epilepsy, patients might aim for ketone levels of 4.0 mmol or higher.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4367849/’>10 A blood BHB measurement is required to calculate GKI.

You might want to track your ketones if you’re running an n=1 experiment. Maybe you want to see what happens when you eat more protein or carbs, or you’re gauging your reactions to certain foods.

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