Managing Your Mitochondria: Exercise

A couple weeks ago, I wrote about how becoming an efficient fat-burner helps mitochondrial function, and last week I went over some of the nutrients and supplements most important for your mitochondria. All good and all useful, but today I’m going to talk about another route: exercise. It makes intuitive sense that mitochondria are profoundly affected by exercise, doesn’t it? They are the power plants of the cells (and that goes for muscle cells), they are the organelles that convert fat, protein, and glucose into usable energy – and continuously producing ample amounts of cellular energy to lift heavy things, run really fast (or really far at a slower pace), or jump high is what exercise is all about. What I like about exercise is that it’s an entirely self-contained lifestyle modification. Modifying your energy pathways from sugar to fat and obtaining certain nutrients requires eating different foods and different amounts of those foods, and supplementing (obviously) requires taking supplements. But exercise is entirely up to you. If you want to. It’s a subtle distinction, but an important one. And an empowering one, if you ask me.

If your interest in mitochondria was piqued over the last few weeks, and you’re the type to focus on lifestyle modifications before supplementations, this post is for you. If you want to improve your exercise performance by increasing the effectiveness of your muscle mitochondria, this post is for you. If you want to reduce age-related muscle atrophy and promote better, more robust health, this post is for you. In other words, this post is for you. All of you. Now, exercise may not be sufficient to keep your mitochondria happy and healthy, but it’s a vital piece of the whole picture.

How does it work?

Remember how I mentioned that getting your body to create new mitochondria requires a stressor, a challenge to the system? Well, the presence of AMPK, or amp-activated protein kinase, is how we know that such a stressor has been applied. What’s AMPK? AMPK is a metabolic regulator that increases mitochondrial biogenesis (in addition to a number of other roles that I won’t discuss). Many things can stimulate AMPK, like caloric restriction, fasting, ketosis, and exercise. What do you notice about all four? CR requires restricted caloric intake, fasting removes caloric intake entirely, ketosis restricts glucose intake, and exercise depletes stored energy; the common thread is that these are all energy-depleted states. So, AMPK increases mitochondrial biogenesis as a response to the lack of cellular energy and an adaption to the applied stress. AMPK is the marker to look for when assessing mitochondrial enhancement potential.

Today’s about exercise, though, so let’s dig into the research and see how specific types and intensity levels of exercise influence AMPK expression. Shall we?

Most research into exercise and mitochondria has revolved around traditional endurance training. Classic stuff – long slow distance, jogging, cycling. And endurance exercise works, don’t get me wrong. I’m no fan of long slow cardio anymore, but it does have the ability to increase mitochondria. I’ll give it that. In fact, though I’m biting my lip as I type this, “cardio” is the best way to increase AMPK and induce mitochondrial biogenesis. It’s quite basic, actually. Slow twitch muscle fibers, the ones employed in endurance training, contain the most mitochondria, so it’s natural that training that targets slow twitch fibers will also target more muscle mitochondria.

It even works in elderly patients with old, presumably creaky muscles, for whom performing between four and six light-medium cardio sessions (cycling, treadmill, or brisk outdoor walking) per week for 12 weeks increased mitochondrial content of muscles. And more recently, here (although trained elderly individuals exhibited less of an AMPK response than untrained elderly).

Just be wary (as always) of chronic cardio. One of cycling’s greats, Greg Lemond attributes his degenerative mitochondrial myopathy to overtraining. I suppose training for the Tour’ll do that.

Of course, who ever said that cardio had to be chronic?

High-intensity interval training is just as, if not more effective than regular endurance training, and sprint training works great, too. Now, a word on sprinting and HIIT. Most studies blur the lines between high intensity interval training and sprinting. The language blends into itself. What I’d call a series of all-out sprints with plenty of recovery time in between, they might call high intensity interval training. Without full texts and full study set-up descriptions for everything, we can’t know whether the training was true sprinting or HIIT. Thus, in lieu of better information I’ll discuss both together.

From Gibala et al comes an interesting study in which four 30 second “all-out” cycling sprints interspersed with four minutes of rest activated AMPK signaling. The authors speculate (but don’t test) that the increased AMPK probably resulted in mitochondrial biogenesis and improved glucose and fat oxidation. In another study earlier this year, that same crew of researchers confirmed that the same sprint training protocol – 30 sec on, four minute rest, four times – does increase mitochondrial biogenesis through activation of AMPK. They called it high intensity, but it sounds like sprinting to me.

HIIT is probably best for certain populations, like the time-strapped, the impatient, the former marathoner-living-in-Malibu-with-a-burning-desire-to-get-work-over-with-so-he-can-play, the obese, and those with type 2 diabetes. Yes, in type 2 diabetics and the obese, activating AMPK and spurring biogenesis requires higher exercise intensities. The mitochondria are slower to respond, probably because their ability to tap into fat for energy is blunted. If your mitochondria aren’t burning energy, you’re not sending the “low energy” signal that stimulates AMPK. If you’re not releasing AMPK… well, you get the point.

How about strength training? Lifting heavy things is good for you. On that, we can agree. And when you tack it onto an endurance training regimen, the degree of mitochondrial biogenesis surpasses that of endurance training alone. But in and of itself? The evidence is mixed. Hypertrophy training, which employs higher reps (10-12 reps), more volume (4-5 sets), and less weight (because, well, you’re lifting the weight more times), decreases muscle mitochondrial density. You are literally expanding the size of your existing muscle fibers without generating a commensurate number of new mitochondria, so they become more “spread out.” This is because hypertrophy training specifically, and strength training generally, doesn’t stimulate as much AMPK expression. If it did, hypertrophy training wouldn’t really result in any actual hypertrophy, since AMPK inhibits mTOR (mammalian target of rapamycin), the premier muscle building agent in the mammalian body. (This is why excessive cardio can inhibit lean mass accumulation.)

On the other hand, strength training does stimulate AMPK in some studies. For example, 10 sets of 10 reps of leg extensions at 70% of 1-rep max increased AMPK for over an hour post-workout, after which mTOR increased and muscle protein synthesis upregulated. So lifting gets you a quick AMPK boost, though not as acute as with extended endurance training. The upside is that strength training also boosts mTOR, which preserves and builds muscle, whereas endurance training is inherently catabolic. You still should lift – especially if you’re during endurance work. As Jamie so eloquently explains, resistance training can actually improve endurance performance, most likely via the boost to mitochondrial function and growth explained in the study above.

Whoops, I almost forgot walking. Now, I love walking, as you already know, and it does improve health, but it doesn’t appear to do much for the mitochondria (at least in type 2 diabetics, who, as you remember, require greater intensity to ramp up AMPK). Casual walking just isn’t physically-demanding enough to force adaptation from the mitochondria. Of course, it’s all about context. If walking around the block leaves you breathless, you might be working your mitochondria. Keep walking regardless. I’m just sticking this here to be as thorough as possible.

Try not to hone in too much on the mitochondria issue, though. I often decry “nutritionism” for its attempts to reduce the worth of a food to a single constituent micro- or macro-nutrient, and I don’t want you chasing mitochondria. Remember: this stuff is supposed to be fun. It’s supposed to enhance your life on a subjective (and objective, lab-verified, if you wanna go that route) level. You could happily go about your life and enjoy fantastic athletic performance without ever learning about mitochondria, let alone tailoring your training to wring every last drop of performance out of every last organelle in your muscle fibers.

Besides, if you want an idea of what being a mitochondria-chaser might be like, just visit the treadmills next time you’re at the gym. Watch the folks that are putting in upwards of 30 minutes. Do they look happy? How’s their body comp? How are their lifts – if they even lift weights at all?

Exactly. The proof is in the pudding, regardless of what a study tells you is optimal. But that doesn’t mean it’s not good to know.

Me? I’ll pass on the extended bouts of cardio (and its numerous drawbacks), max out my mitos through a Primal eating plan and actually enjoy my workouts.

So, will this change how you exercise?

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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72 thoughts on “Managing Your Mitochondria: Exercise”

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    1. Actually, if you were a cro-magnon, for example, you’d have a larger brain, so you’d be far more capable of understanding this post than a modern man.

      You can thank wheat for the shrinkage.

      Save the caveman jokes for the car insurance commercials. 🙂

      1. There is no relationship between brain size and intelligence, this theory was proven to be false decades ago.

  1. Mark, not to but in but for sprinting I found a great diversion. I am married to my best friend. She and I do everything together, she is lost 84 pounds in the last 12 months and changed our lives. Back to the point..a game of tag works wonders for sprinting.
    Running until you fall down laughing and gasping for air.

    1. I second that! I have trained by dog to never bring the frisbee back after I throw it, and to run any time I come near him. So I just chase him around until one of us (usually me) needs a breather.

      1. Hahaha, my dog loves playing keep away. I can never get him to bring me the ball. He WANTS me to chase him, so I do.

  2. I’ve really enjoyed this series of posts and it’s helped satisfy my scientific brain that I can do less, but more intense!

    In fact this year I’ve done so much less, but can now lift more than ever, and am as lean as I’ve ever been and happy, on embarrassingly little ‘training’ by my former standards, heck, by any standards! That’s my pudding-proof!

  3. According to , mitochondrial myopathy is genetic. Wikipedia agrees.

    1. So are diabetes and Alzheimer’s. Doesn’t mean they can’t also be triggered by lifestyle.

  4. Great post! I love confirmation that my thoughts on exercise are right-on. It is tough to stay true when everyone around you tells you more is always better!!

    1. I agree! We are always told that more is better…but seldom it’s true. Everything should be in moderation, even things that are good for us.

  5. Looks like I’m already doing it right by lifting heavy 2x weekly, sprinting 1x weekly, walking a lot, and working up to some short-distance running (3-5K) a couple times a week. You know, basically following the PB rules we’re all supposed to be following anyway. 😀

  6. Thank you for finally explaining what mitochondria is and what function it serves. My head suffered from scientific terminology overload by the last two posts where you mentioned mitochondria. This post actually makes the subject actionable. Thank you. Many of us would understand these biological components and biological processes better if they were communicated through (or at least supplemented by) diagrams. I have read the “Primal Blueprint”, the “21 Day Total Body Transformation”, and over one year’s worth of posts, and I’ll be darned if I really understand the function and processes of glucose, glycogen, gluconeogenesis, DHA, EPA, etc… Maybe it’s because I live in a PowerPoint-slide world, but I understand things more easily in images and charts (with process flow arrows). Now it’s time for me to run through the woods. That’s something I can understand :).

  7. Mark,
    I have a question regarding sprinting and the mitochondria. Normally I sprint on a soccer field, go all out, walk back, catch my breath, and go again. The rest is maybe two minutes by my 10th dash. Now that NH is covered in snow, I’ll be switching to one minute all out, one minute rest on an exercise bike.
    From the sound of it, more rest time might be better. should I increase my rest time between sprints to maximize mitochondial superbness?

    1. 4 minute warmup, 30 Seconds level 10 out of 10, 90 seconds level 3, Try that 5 times to start, 1 minute is a loooooong time to sprint on the stationary bike.
      You’ll be done and exhausted in fourteen minutes my way. Crank up your ipod for the sprints to help give you a boost.

  8. “HIIT is probably best for certain populations, like the time-strapped, the impatient, the former marathoner-living-in-Malibu-with-a-burning-desire-to-get-work-over-with-so-he-can-play, the obese, and those with type 2 diabetes. Yes, in type 2 diabetics and the obese, activating AMPK and spurring biogenesis requires higher exercise intensities.”

    Pretty sure you will find research that says that heart patients benefit most from this type of exercise too!

  9. nice. I like this post. my backyard is enough of a gym for me. with a boulder to roll, a backpack with gravel/sand, a tire to hit and swing, 2 5 gal. container to lunge around. (still working on climbing a tree)my mito will be happy as I went I “play” in my paleo-playground.

  10. I’m an exercise novice, almost pre-diabetic, morbidly obese, tired woman who wants more energy and to dodge the type-2 bullet (among other things). So THANK YOU for this series on mitochondria.

    This last post left me confused about one thing: what’s the difference between sprinting and HIIT?

    1. I thinkthe difference is that the sprint duration is defined by when you start to lose speed in your all out effort. And in a sprint session you would do that a couple of times. From my understanding, HIIT is more structured where you might go for 30 seconds even if you had more in the gas tank or not, and sometimes the effort is not “all out” sometimes it’s “90%”. Then one would take a more specified period of rest time. HIIT can also be applied to a bunch of forms of cardio, kind of like a blanket term. Other than that I think it’s pretty well the same thing, max effort cardio for a short duration of time… I prefer the sprinting style of training, feels more natural to stop when you want to stop and less hassel to worry about with timming things.

      1. Thank you, DComeau. Your reply (and Diane’s below) give me an idea of how to distinguish them.

  11. Mark, it seems you are describing a type of Frank-Starling curve with mitochondria, or ad you have developed, a carbohydrate curve. There is a sweet spot which is followed by a drop off where instead of being a useful stress becomes a damaging one. This is seen in all nature as certain levels of stress can induce adaptation while chronic and severe ones do harm. I applaud you in ALL your good work. As a doctor, I have to say, you do very good work, and I have learned a ton from you. You have reminded me that anatomy physiology and biochemistry are the backbone of being a doctor who can actually help and heal. Kudos.

  12. Mark this is another of those crucial points of differentiation between the dogma of CW and the scientific approach of paleo/primal. Exercise (for weight loss) has nothing to do with calories and is all about fat metabolism / mitochrondrial biogenesis.

    Was there a comparison between sprints/HIIT and steady state cardio?

    Even if long steady state cardio increases AMPK the most, perhaps it’s more elevated to offset any mitochondrial catabolism / inflammation.

    Keep up these great posts.

  13. Could you elaborate more on chronic cardio vs running a couple times a week? Does running 7x a week mean it’s chronic cardio? I am bit lost on this issue..

  14. Would a 1-5 mile run once a month optimize the mitochondria? in the context of strength training , sprinting , and frequent slow moving.

    Could there be other adaptations that cancel out or diminish the mitochondria boosting effects of “chronic cardio”?

    1. I’ve been wondering that myself. I’ve never been a runner. Then My Crossfit box made us do a 5K one day just to show that you don’t have to do 5K’s to be able to do them. I finished in 26:40, which from what I hear is an OK time for a first time runner at 51 years old doing a 5K. That was about a month ago. So will 1 5K every month or two be helpful or harmful? I’m at a new Crossfit box now and they are getting a gang together to do a run in December. I’m trying to decide to participate or not.

  15. I love it when Calorie Restriction and Paleo metabolic signaling pathways converge!

  16. Great post Mark !

    I have a rare disease, called mitochondrial myopathy. In short: My mitochondria do not produce enough ATP to keep things running properly. This creates lots of problems. Depending on the percentaje of affected mitochondria (heteroplasmy), you can just die few days after birth or you can use a near normal lifespan. Serious stuff.

    I have tried *everything* since I was diagnosed with this disease 5 years ago (I am 41 now), including popping 30+ pills a day, doing aerobics 2 hours+ a day and all kind of insane stuff. What realy works for me is a combination of heavy weight training and HIIT (I do hill sprinting). The rational behind this:

    1. As you said weight training does not clearly induce mitochondrial biogenesis by itself. However, it has an important effect that is not mentioned in your post: It activates muscle satellite cells. These cells are actually stem cells that are “dormant” in the muscles, waiting to replace damaged muscle tissue. As a bonus, these cells are mutation-free, so they help to reduce the percentaje of mutant, non-functional, mitochondria. Note that we all carry some mutant mitochondria in our bodies, so this is good for everybody.

    2. HIIT will just activate mitochondrial biogenesis via the AMPK pathway, as explained in your post. Given this, our new, fresh, mutant-free mitochondria created in 1. will start “reproducing” to create new muscle tissue with young mitochondria.

    These two steps can be rewritten as follows:

    1. Lift heavy things
    2. Sprint once in a while

    Sounds familiar ?

    The scientific paper that started it all: “Gene shifting: a novel therapy for mitochondrial myopathy”

    1. Luis, thank you so much for taking the time to write this comment. I have a friend who might have a mitochondrial myopathy. I’m hoping the article you linked will inspire him to be more proactive about his health.

  17. Lift heavy, and play ultimate frisbee. Done. I feel great. And I like what I’m doing.

  18. Top post….8 months on the 80/20 and have dropped the easiest 20lbs ever

  19. I differentiate between HIIT and sprints — for me HIIT is running at about 80% Max HR for 1 min alternating with 2 min slow down for 8 sets — that makes 20 min.

    Sprint — that’s all out with panting and such for 30 secs followed by 2 min or more cool down — I am not doing more than two of these at this point, but I’m working up!

    Plus I do 10-20 min on my rebounder daily (10 min at a time usually) sometimes just a health bounce and sometimes jumping for joy.

    1. This comment was helpful for me, Diane, in distinguishing between HIIT and sprints. Thank you.

  20. I so enjoy the intelligent thoughtful responses in the comment section after one of Mark’s post. I learn so much from you all.

  21. Great article Mark. I like how you provide lots of information that people can use to make their own informed choices.

    I know Grok probably (definitely) didn’t do it but would hula hooping leisurely for like 20 minutes be in the slow and constant movement class and thus be good or would it count as high rep low weight type stuff and thus not be great?

    I like hooping while I watch tv and intermittently doing it as quickly as I can for like 10 seconds (it looks epileptic) then recover.I like to think of it as interval hooping but maybe it doesn’t quite work like that…

  22. I love combining kettlebells/dumbbell work with jump rope. I’ve noticed that walking up hills seemed easier than it should when I’m consistant with this combo. 40 minutes tops, and I’m done. Oh, and I never go to failure, and jumprope between sets, (no rest). Now if I would just discipline my diet!!!

  23. Is Knox’s Orginal Gelatine a good form of gelatine to supplement with?

    1. Knox is certainly better than those artificially colored and flavored gelatine packs that also have aspertame.

      But they’re insanely expensive. I found a bulk 5lbs beef gelatin package on Much better than paying $2 for something like 1 oz of gelatin.

      Of course you’ll get the best gelatin from grassfed animal sources by making stock, but the powder isn’t all that bad and it stores for a very long time as long as you keep it dry.

  24. Stumbled onto your blog this week and am enjoying reading many of your posts. I particularly like the fact that they don’t skim the surface but dig into the meat and data and research to back up your claims. Particularly enjoyed this article about the value of exercise to our cells. Looking forward to continuing to browse your blog.

  25. Muy importante esto del manejo de la mitocondria para mantener la energia y retrasar el envejecimiento

  26. Thank you for clarifying the difference between sprint training and HIIT (with sprint training you have longer rests, and HIIT you keep moving, yes?)

    Don’t think this will actually change the way I train, but interesting nonetheless.

  27. For my mitochondria and general primal movement improvement I’ve been booking it up snowy forest hills with a backpack on, leaping, vaulting, and climbing as fast as possible over logs, tree roots, rocks etc and pulling on and pushing off them to propel myself forwards. I catch my breath at the top and then run back down taking it easier with light, loping, and sliding strides and repeat until tired. Feels awesome, especially when fuelled with raw honey and cocoa/dark chocolate.

  28. Hi Mark,
    I am a type 1 diabetic and I got this life burden when I was 28 years about 8 years ago. At the time I was eating a very high carb vegetarian diet. There is no diabetes anywhere in my family. I was like your poster child for what not to do!!
    I found your website when I was googling glucose control, and I read and loved the Primal Blueprint. What can type 1’s do specifically to hone in on controlling blood sugar? It’s a daily battle, but low carb, less insulin shots is the best way to keep everything in line. Any advice would be greatly appreciated!!!!!!!

  29. A: Yes, this will change my workout regime. Thanks for letting everyone know this!
    1 day of Steady Cardio 2-4 kilometer
    1 day of Static resistant training doing really hard bodyweight excercises (stand on two hands while doing pushups, abdominal plank while balancing on my hands and turning 90 degrees with foot and one hand.

    1 day of Explosive weight training or HIIT playing Soccer.

    So i can perhaps get the best on both worlds. Fast type IIA+B with slow fibers and mitochondrial biogenesis also.

  30. Ummm – Greg Lamonde has attributed his mitochondrial myopathy to overtraining in conjunction with lead poisoning from the buck shot lodged in his organs from his hunting accident. He says that excessive training releases more of the lead, thus damaging his mitochondria. Given that most of us don’t have lead pellets in our bodies, and few of us will ever train anywhere as hard as Greg did, it is misleading to imply that overtraining will kill our mitochondria. (Read “The Science of Fitness”)

  31. I am reading a book by Greg Le Mond and Mark Hom regarding mitochondria, fitness, power and endurance. Greg wrote of his mitochondrial myopathy as attributed to poisoning from lead pellets left in his body after a hunting accident. Please check out these facts. It was not chronic cardio that got him.

  32. Hi Mark,

    I’ve been advised to build my mitochondria after having my RMR tested (which was very slow) and energy expenditure. It turns out im burning barely any fat with exercise.

    I was advised to increase fast twitch muscles via hit training, and high reps, low weight training

    I’m reading mixed advise on the internet on what is best,

    Just wondering what your thoughts are on this?