Managing Your Mitochondria

In Monday’s “Dear Mark” post, I briefly outlined a few of the benefits to having healthy, abundant mitochondria, and in the past, I’ve alluded to the damaging effects of statins on mitochondrial function. All good, yeah, but a couple brief paragraphs in the middle of a Monday post aren’t enough. Mitochondrial function and mitochondrial biogenesis – the growth of new mitochondria – deserve more than that. Like, their own post. Today, I’m going to dig a little deeper. I’m going to lay out why growing more and healthier mitochondria (mitochondrial biogenesis) is good for your health, your longevity (and compression of morbidity), and your energy levels. I’ll explain why becoming a fat-burning beast optimizes mitochondrial function, and I’ll go over why this is so important if you’re looking to transform your body.

What’s funny is that we weren’t even “supposed” to have mitochondria, according to most scientists. Over a billion years ago – as the story goes – mitochondria were free-living prokaryotes (organism without a nucleus) making their own way in a pretty chaotic world with naught but their own DNA. Back then, everyone seemed to be uni- or multi-cellular, the oceans were crowded, and cell membranes were fluid (some might say downright porous), so there was a lot of casual interaction between eukaryotes (who had nuclei) and prokaryotes (who did not). Folks had no concept of condoms, of course, and eukaryotes have always been single-minded. A casual connection is made, a semi-porous membrane somehow gets a whole lot more porous, some enzymes are exchanged, and before you know it that little prokaryote has been engulfed by the eukaryote. It starts as sheer lust, but eventually turns into a lasting, mutually beneficial, endosymbiotic, loving relationship. The prokaryote becomes part of the eukaryote, contributes some DNA, changes its name to mitochondrion (hey, this was the swingin’ Proterozoic, when Prokaryotes’ Lib was going strong and where the lack of a nucleus didn’t preclude an organism from determining its own name) and starts producing energy for the cell – just like it did as an individual bacterium. The rest is history.

Fast forward to today, and mitochondria are present in nearly every cell in every organism in the world. Single-celled organisms might have but a single mitochondria, while individual human liver cells, for example, contain between 1000 and 2000 mitochondria each. They’re obviously pretty important.

I’d even venture a “very important.”

The primary role of mitochondria is to extract energy from nutrients to produce adenosine triphosphate, or ATP, which our body uses to create energy for a whole host of cellular processes. We are constantly using ATP, whether we’re sprinting, walking, breathing, pumping blood through our cardiovascular system, or doing long division. Think of a physiological process, and ATP is probably involved. Without mitochondria, then, we wouldn’t be able to get much of anything done. We simply wouldn’t be.

This whole ATP production process, however, comes with a hitch: the creation of free radicals. Whenever mitochondria produce ATP, whether from glucose or from fatty acids, free radicals are created as a byproduct. It sounds horrible, but they are an unavoidable consequence of ATP production, and healthy mitochondria can usually deal with a normal amount of free radicals (with the help of endogenous antioxidants like glutathione) before they do too much damage. If the free radical load is too great, however, either because you have too few mitochondria doing the work or because the mitochondria you have are not working properly, some will escape and do damage. Since free radicals have no electron, they will “steal” electrons from the first thing they encounter, stabilizing itself but rendering the victim unstable. Given free reign, free radicals can damage mitochondrial DNA (leading to mutagenesis, sap telomerase stores (remember, telomeres act as material for cell repair, so you don’t want to run out prematurely), oxidize proteins (including lipoproteins like LDL, which if oxidized can promote atherosclerotic plaque), and speed up the aging process by increasing oxidative stress.

It comes down a simple numbers game: the more mitochondria you have and the more efficient they work, the more spread out the workload. And when your mitochondria aren’t overburdened, there’s less free radical creation during ATP production. There’s less waste production.

The mitochondria’s other roles include, but are not limited to: steroid hormone (like testosterone and estradiol) synthesis, lipid metabolism, insulin/glucose regulation, and cellular calcium homeostasis. I’m a big fan of natural testosterone production (and estradiol’s not too shabby, either), metabolizing fat seems like a good thing to do, and I’m all for proper insulin sensing and glucose regulation. And cellular calcium homeostasis? Man, there is nothing quite like having adequate – not too much, not too little – calcium levels in my cells. Feels good.

By now, I imagine it’s become quite apparent that you want high numbers of high-functioning mitochondria in your cells. But how do you do it? How do you make your mitochondria work better? How do you make more mitochondria?

You have to understand how the body adapts to stress. When imposed demands challenge our bodies, our bodies make structural (and neurokinetic) changes to prepare for any future demands. Ergo, you lift something heavy for a few sets of five reps, and do so on a regular basis, and your muscles will grow, your bones will get stronger, and your connective tissue will adapt to deal with those heavy loads. Stress your body, recover from it, and grow stronger for next time. This is just how the body works. It adapts to what’s demanded of it.

It’s pretty similar for our mitochondria. When current levels and quality of mitochondria are inadequate to meet an imposed demand, we grow more of them and/or we improve the function and efficiency of the ones we have. When circumstances arise that require more or better mitochondria than we currently employ, the body will respond. We don’t make new mitochondria or improve our existing ones just for kicks, just like we don’t build lean muscle mass by sitting around. We have to give our bodies a reason to do it. We have to challenge our cells.

There are tons of supplements, including minerals, amino acids, and antioxidants, that boost mitochondrial function and even engage biogenesis, but I won’t get into that today. There are plenty of lifestyle modifications that challenge our mitochondria, especially physical activity. Resistance training and endurance training both improve mitochondrial function and increase mitochondrial resistance to degradation, and on Monday I mentioned how lifting heavy things and sprinting both increase mitochondrial biogenesis. But those are topics for another day, too.

The single most fundamental – and simple – way to improve mitochondrial function is to turn away from relying on sugar-burning and transform yourself into a fat-burning beast. See, mitochondria burn fatty acids cleaner than they burn carbohydrates. Generating ATP via fats/ketones produces fewer free radicals, because it’s more efficient, whereas generating ATP via carbs produces more. As a result, glutathione can do its job and our ketone-burning mitochondria have to divert less attention to cleaning up free radicals. This doesn’t just make mitochondrial ATP production from ketones more efficient; it has the potential to render it downright anti-inflammatory, too. When we dip into a full-fledged ketogenic diet, cut back on bad carbs, or intermittently fast, we are switching over to fat-burning. When we switch over to fat-burning, our mitochondria do the same. Heck, that’s what we mean by “fat-burning.” There’s even evidence that ketosis can spur mitochondrial biogenesis, albeit thus far only in rats.

In my new book I present my Primal prescription for becoming a fat-burning beast. In fact, one of the reasons I wrote the 21-Day Total Body Transformation is because untold millions of people are languishing in sugar-burning land and their mitochondria aren’t burning quite as cleanly as they could. The “transformative” aspect of the 21-Day Total Body Transformation is the epigenetic switch from sugar-burning to fat-burning. And improving mitochondrial function and (if that rat study pans out in humans) increasing mitochondrial biogenesis are at the heart of this switch.

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 “Managing Your Mitochondria”

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    1. Medium chain fatty acids found in coconut oil can definitely increase your metabolism, but in order to reach ketosis, from what I understand one have to cut down on the carbs. Not just increase the fat intake.

      1. MCTs are enough to go ketogenic, since they are metabolized in the liver directly to energy and ketone bodies. In fact MCTs are used in diets for epileptics to get them ketogenic without going too low-carb, where definiency symptoms — dry eyes, kidney stones, impaired immunity — can develop.

    2. 50 grams of carbs a day or less seems to be a good rule of thumb to get into the ketosis state. I think I would eat a lot of greens for my veggies…

      I think coconut oil may help! Pure, clean energy.

      1. Under 50 grams of carbs a day will eventually get you to ketosis, but I wouldn’t stay there long especially you are physically active. Stinky breath, crankiness, and sluggishness isn’t something to look forward to… I find that flirting with ketosis then carbing-up is a good approach.

        Virgin coconut oil is killer fuel. And delicious.

        1. My experience with ketosis is the opposite of what you list: no bad breath (I asked the sig-o), better moods (less crankiness, again judged by my sig-o), and very good energy levels.

          I feel lousy after eating carbs; not immediately (they certainly offer a burst of energy), but an hour or two later when the blood sugar levels begin to drop. Talk about crankiness then!

          I think people vary – not everyone will experience the symptoms you list.

          1. John, same here. The lower the carbs, the better. The higher the carbs (even 50 a day) is when I start getting autoimmune symptoms again. Lower the better.

        2. Ditto John, I spend most of my life in or around the ketosis level and that’s what keeps me mentally healthy (a recovered bipolar person since Primal). Carbs make me anxious, want to eat everything in sight and generally feel like I’m regressing to former less well years.

        3. John and Kelda,
          You raise a very good point – some people tend to tolerate ketosis better than others. My clients tend to struggle with workouts and mental clarity in ketosis, but certain people do seem to function well. I think it probably boils down to the quality of the foods that they’re eating… Atkins-style ketosis (processed meats, few vegetables) is much different than Primal ketosis where you prioritize quality foods. I’m glad you’ve both found a good balance!

        4. I have pretty severe ADD and going strict paleo for 30 days a while back gave me more mental clarity. I attribute it to less sugars (possibly gluten as well although I’m not intolerant normally) and an increase of animal fat and cholesterol. I felt the underlying ADD issues seemed to clear up, although not necessarily the learned behaviours. I also felt a more consistent energy no spikes and valleys, although I like it I didn’t NEED coffee in the morning anymore to wake me up. Definitely not cranky. Just a guess but the bad breath could have been from the detoxification process. I have gone back and forth in my diet trending to paleo but I definitely feel better and have less brain fog on a strict paleo diet.

        5. My wife is type-1 diabetic and stays in ketosis (between 0.5-0.9 mmol/L) constantly to manage her blood sugar. She also intermittent fasting. Her breath is fine. Her mood is much better than when she eats carbs. Her energy level is more steady.

          When she first went into ketosis, however, the first week produced bad breath. After that, there’s been nothing. That was nine months ago.

    3. Ketosis can’t happen if there is a surplus of carbs, make fats, meats and veggies your primary calorie intake and yes, add good fats like coconut oil.
      Hope this helps


      1. I tolerate ketosis very well. I’ve had epilepsy since the age of 15 (51 now). I recall ketogenic diet being discussed, but was told I’d get fat and have heart disease. Once I went primal 5 years ago, I cycle in and out of ketosis depending on what I’m eating. I have not had a seizure since I was 27 in spite of reducing medication drastically.
        I did have one kidney stone, but not from diet, I don’t think. My dad and both brothers have had 2-3 each, and all in their 20’s and 30’s. The only one I’ve had was 3 weeks ago, at age 51. So I can’t blame diet at least based on family history since I’ve had just one and much later… If correlation were causation, then ketogenic diets prevent them.

        1. The fatty acids in coconut oil dissolve kidney stones, just one more reason to use coconut oil. Google ‘coconut oil dissolves kidney stones’.

  1. Yet another reason to go primal and ditching all the high sugar junk that’s out there! 😀

  2. I can feel my mitochondria getting healthier by the minute. Go fat burning.

  3. My understanding of the optimal keto zone is not only reducing carb intake but reduced protein intake as well. You can enter this zone easier when you bump your fat intake up above carb and protein in take.

  4. As a professional science writer, I approve of the second paragraph of this article.

  5. Very educational! I didn’t realize glucose-to-ATP generated more free radicals than fat-to-ATP.

    Would love to read more about mitochondria, especially the “inefficient” variety found in brown fat which are responsible for thermogenesis. Another great example of natural selection using lemons to make (sugar-free) lemonade.

    “Stress your body, recover from it, and grow stronger for next time.” So many people seem to forget that second step, and in so doing miss out on the third.

  6. Your second paragraph gave me a huge grin this afternoon. Thanks for the smile!

  7. Another clear, concise and motivating explaination. Thank you Mark! Understanding how and why it works makes all the difference.

  8. I remember in my freshman year of high school, one of my Biology class assignments was to create a 3-D representation of a cell and its internal workings. The mitochondria’s work fascinated me more than any other cellular function, and to this day that assignment has been my favorite from that class. A book from my childhood, ‘A Wrinkle in Time’ by Madeline L’Engle, was written about the concept of space/time travel which centered around mitochondrial function… fascinating little things, aren’t they? =)

    1. And I thought I was the only one that remembered the whole mitochondria thing from that book!

      1. I loved that book! But are there really farandolae inside the mitochondria?

  9. Free radicals have a role. Once again it’s the imbalance of free rads to antioxidants. Everything in balance….

    1. I am losing my phobia of free radicals. I think they serve a purpose and we obviously got here without supplementation. The following link is a study of mitochondrial function in worms.
      They deprived the worms of glucose, got them burning fat, spewing lots of free radicals and living longer.
      Then they gave them antioxidant vitamins, dampened free radical production, and the life extension disappeared.
      Peter has a nice write up on this study, and another blogger put it well — that it’s not about wear and tear but rather wear and repair.
      ot: i’ve loved mda and mark for years, but for better or worse the site is getting commercial.
      …still lots of good info and inspiration.

  10. great piece, nice to know that there are even fewer reasons to take statins, and more reasons to lift stuff plus eat more fat…mmmmm

  11. awesome blog post Mark! My coach preaches this same thing to me all the time when I veer off course and begin relying on sugars more than I should. I can definitely feel it too. It seems that if we do what our bodies were made to do, lift heavy, rest, eat natural ancient foods and practice being awesome everything tends to fall in place. I like your comment on Calcium levels too something I’m coached on quite a lot with regard to muscular fatigue that I’ve battled with off and on for years but now have under control.

  12. It’s worth noting that all mitochondral DNA is passed on maternally.

    So next time you’re cranking out serious BTU’s/wattage thanks to some fat-burning, thank your mom and your grandma. They gave that ability to you, quite literally.

  13. I am new to the Primal lifestyle but feel much better since I started (only a week ago). But I do have one question. Can anyone tell me what a post-workout meal would be like on the Primal Blueprint lifestyle? Should we want to boost insulin immediately following an anaerobic workout by intaking 40 or so grams of fast carbs in order to allow IGF (Insulin Growth Factor) to work and push aminos into the muscle tissues which in turn aids muscle growth or would we still stick with a lower carb post workout meal?

    1. Nope, you are best not eating for an hour or two. You don’t need to be replacing carbs, allow the body to naturally replace the stores used. It’s another conventional wisdom myth that you need to refuel. You exercise again once your body feels recovered.

    2. I previously used a sports drink that contained 10g whey protein, 2g fat, 60g carbs, plus vitamins and minerals, based on the best “science”. Resulted in muscle gains – and unwanted flab gains too, plus a little uncomfortable abdominal bloating. Since adopting Primal lifestyle, use a whey protein powder providing 20g protein, 2g fat, 2g carbs, mix with coconut milk providing additional 2g protein, 24g fat, 4g carbs. Same muscle gains. No bloating. Hours of satiety. And tastes much better too!

      1. Thank you for clearing this up for me. I have all the same symptoms with the ‘conventional wisdom’ as you state. I will definitely try adding some coconut milk to the whey shake. One immediate thing I notice is that I am never hungry while on this program.

        1. I agree with the never being hungry thing – I’ve been Primal for just about 6 months now, and I am NEVER hungry, despite how little I eat, or if I’m fasting. Isn’t it awesome?

        2. Are you still overweight? Because if you are at a healthy weight, exercising SHOULD give you an appetite.

          Being hungry sometimes isn’t a bad thing.

          Now if you’ve still got a bunch of extra fat lying around, obviously appetite suppression is your friend! 🙂

  14. Makes me feel hungry – 10am BST – shall go and enjoy my latest favourite:-
    pork mince mixed with an egg and flavour of the day, cooked in butter. Yum!

    Being a keen amateur fossil-hunter I particularly enjoyed para 2.

    Thanks Mark

    1. Russel…good luck with that…I tried it and found that Mark’s stuff is so full of information and links that it would lead to little sleep time!!!

  15. Researchers are now using flow cytometry to assess mitochondrial health as an indicator and precursor to future inflammatory diseases. They’re finding that the mitochondria are one of the first organelles to be affected by poor lifestyle and can actually show severe damage – their by being the new hot trend in research.

    1. …which could partly explain why metabolic flexibility is often damaged in the formerly obese, even if they have attained a healthy weight.

  16. Hey Mark-

    Nice post. Anything to add about autophagy? It’s interesting because a lot of new cancer drugs are targeting the mTor pathway…which in theory induces autophagy, including mitophagy (mitochondrial autophagy). Kill 2 birds with one stone, eat healthierand reduce free radical production, while favoring an anti-cancer biochemical environment…makes sense to me! 🙂

  17. “We have to give our bodies a reason to do it. We have to challenge our cells.”

    What about fat burning is challenging our cells to produce more mitochondria? Isn’t it just making there job easier? Wouldn’t a poor diet do that seeing as it would introduce MORE free radicals?

    I’m 100% on board with the primal diet, and have been- I’m just confused on this point. Thanks!

    1. I think the impetus is high-intensity workout taxing the mitochondria more than they can ‘handle’ which leads to up-regulation of mitochondria production. When you exhaust organelles (like mitochondria) the body tends to make more; when you fail to use them they get resorbed (roughly).

  18. So sugar feeds cancer cells, “bad” yeasts, can make good yeasts over produce, and also inhibits mitochondria… I’ll stick with my borderline ketosis state!

  19. Isn’t mitochondrial destruction a result of medical treatments? Especially statins, certain antibiotics like Bacrtim/Septrim, anti-HIV drugs and some types of chemotherapy?

  20. Hi I eliminated carbs and sugar and started exercing with 20lb weights for20mins with breaks in between. Is this a good routine?

  21. this is the first time I’ve understood properly what free radicals are and now understand why I need to keep them at bay. Very well explained, thanks a lot Mark!

  22. I think it’s really important that people understand the difference between sugar burning and fat burning. You actually broke it down in a way that is easy to understand!

  23. One thing though. Free radicals have electrons, they are just missing one so they will “streal” this missing electron from what ever has the higest energy state (less energy needed for the radical to “steal” the electron), most often double bonds..

  24. Just a quick note – not sure if someone else caught this yet, but radicals are missing a single, unpaired electron. Atoms are more stable when electrons exist in pairs, and thus, a radical will grab an electron wherever it can and perpetuate the production of more radicals. From a chemistry standpoint, the generation of free radicals, once started, can only be quenched by two radicals coming together to form a stable molecule with all electrons existing in a paired conformation.

    1. I noticed the same mistake. Single, unpaired electrons are in a state of energy instability. electron pairs are much more energetically stable, so free radicals tend to rip electrons from other chemicals in order to have a pair of them. Let’s get the science right.

  25. “And when your mitochondria aren’t overburdened, there’s less free radical creation during ATP production. There’s less waste production.”

    Hey, I think I missed something. Was it explained why there is more free radical creation when the stress on the individual mitochondria increases? That rather important bit of news seems to be stated in passing (again unless I missed it). I thought that all mitochondria were “supposed” to release free radicals, so what is happening that makes the amount that they release dependent on their stress level?

  26. Mitochondria are basically there to sustain the human body until it dies. After that they feast on the corpse. Its a nice wotking relationship.

  27. how much less free radical production is produced from ketones compared to carbs? Anyone have a ratio?

  28. There appears to be a mitochondrial disorder in my family as a lot of deaths have resulted from this disease, the children living only up to 4 months. What can I do to prevent from handing down this dysfunction to my children? Can I correct this genetic disorder by strengthening my own mitochondrion?

  29. Sorry but a stoppes reading your article when you wrote « free radicals has no electron… ». Science is important to support an informational text. This is wrong information. Here ´s the right one: free radicals miss one electron to be stables molecules so they steel one from another one as soon as they can.

  30. This all makes sense to me, thanks Mark. I know I’m 9 years late to the party here, but I wonder if anyone can clear this up for me: I keep seeing studies that conclude that saturated fat intake impairs mitochondrial function. Is that only in the context of high carb intake too? Trying to understand how that fits into this picture. Thanks.