Meet Mark

Let me introduce myself. My name is Mark Sisson. I’m 63 years young. I live and work in Malibu, California. In a past life I was a professional marathoner and triathlete. Now my life goal is to help 100 million people get healthy. I started this blog in 2006 to empower people to take full responsibility for their own health and enjoyment of life by investigating, discussing, and critically rethinking everything we’ve assumed to be true about health and wellness...

Tell Me More
Stay Connected
September 12 2018

The Definitive Guide to Metabolic Flexibility

By Mark Sisson
35 Comments

Metabolic flexibility is the capacity to match fuel oxidation to fuel availability—or switch between burning carbs and burning fat. Someone with great metabolic flexibility can burn carbs when they eat them. They can burn fat when they eat it (or when they don’t eat at all). They can switch between carbohydrate metabolism and fat metabolism with relative ease. All those people who can “eat whatever they want” most likely have excellent metabolic flexibility. So, why does it really matter, and how does it happen? Let’s get into the weeds today.

Why We Need Metabolic Flexibility

There are many good reasons to want more metabolic flexibility:

It allows us to safely and effectively utilize a wider variety of nutrients. If we enjoy metabolic flexibility, we can eat a purple sweet potato and a grass-fed ribeye.

It means we can tap into different fuel sources to power different activities.

Most importantly, it means we can trust our bodies. The more metabolically flexible we are, the less we have to micromanage our macronutrients and calories. We can just eat and, as long as we stick to whole foods, the satiety signaling we receive will generally be accurate and reliable.

You can certainly overload the system. Any metabolic system, however flexible, will crumble under the weight of an entire cheesecake. Overall caloric content still matters.

But metabolic flexibility gives us, well, more flexibility. More room for error. And being metabolically inflexible comes with real consequences.

  • You get sleepy after eating carbs.
  • You can’t go five hours between feedings.
  • You refer to meals as “feedings.”
  • You get the midday crash every day after lunch.
  • You must snack to sustain your energy levels.
  • Fasting is difficult, and if you manage to power through the discomfort, you get worse results than you were expecting (muscle loss, very little fat loss).
  • You can’t function without a steady stream of stimulants, like coffee, tea, or worse.

What’s going on here, exactly?

What Causes Metabolic Inflexibility

There are two main issues. First, your mitochondria situation is messed up. Mitochondria are the power plants of the cells. They’re the structures that process the fuel (food) and turn it into useable energy. The fewer you have, and the more dysfunctional they are, the more impaired your energy production and the less flexible you are.

People with poor metabolic flexibility carry fewer mitochondria in their muscles. A 2007 study took muscle biopsies of age-matched metabolically flexible and inflexible subjects. The flexible subjects had far higher mitochondrial density and burned more fat on a high-fat diet.

People with poor metabolic flexibility have dysfunctional mitochondria that produce less energy than healthy mitochondria. If your mitochondria are subject to too much oxidative stress, they don’t work as well. If they contain an inordinate proportion of linoleic acid in the mitochondrial membrane, they don’t produce as much energy.

Having too few mitochondria that don’t even work all that well severely limits the amount of energy you can produce. It makes switching between fuels difficult. It makes utilizing your stored body fat in between meals very hard, and it makes snacking almost inevitable. And if you’re not burning the fuel you’re taking in, you’re contributing to energy excess—perhaps the most fundamental cause of insulin resistance.

The body’s natural reaction to an excess of energy is to become insulin resistant. This makes sense when you realize the ultimate purpose of insulin is to drive energy into cells. If there’s already too much energy floating around, the last thing your body needs is to cram more in. So it turns down insulin sensitivity, and that’s when the trouble really starts.

If you are insulin resistant, you’ll have a harder time burning glucose and storing glycogen, and your ability to burn your own body fat will be impaired even further. Think about it:

If you eat a sweet potato and your cells aren’t responding to insulin, you’ll need extra insulin just to shove the carbs into muscle and burn it for energy.

If you eat a sweet potato and your insulin stays elevated for hours, those are hours you won’t be burning fat.

If you eat a sweet potato and your insulin skyrockets because your cells are so resistant they need progressively larger doses just to do what they’re supposed to do, you won’t be burning much fat.

It’s a double whammy. Bad mitochondrial function and insulin resistance.

What can be done?

How To Regain Lost Metabolic Flexibility

Follow this list in order.

First, exercise: You’ve probably heard that “you can’t out-exercise a bad diet.” Hell, I may have said it a few times. This is true, but there’s more to it than that. Just off the top of your head, who’s going have better luck with different sources of fuel consumed together, like fat and carbs. The guy who sits on the couch in a state of perpetual insulin resistance, eats a baked potato with butter and gains a pound? Or the CrossFitter who’s so insulin sensitive the insulin receptors in his quads quiver when the waiter brings the bread basket and can get away with it?

Regular training—both strength and aerobic—directly counters metabolic inflexibility by addressing the two main offending factors. In the metabolically inflexible, it increases insulin sensitivity and restores the ability to burn fat. Certain types of training, like intense intervals and long, slow, easy aerobic work, actually increase mitochondrial biogenesis—the creation of new mitochondria. Between improved insulin sensitivity, restored fat burning, and more (and better) mitochondria, exercise is the first thing you should be doing to regain metabolic flexibility.

Next, get fat-adapted: After at least a week of training, move on to fat adaptation. You can do this with basic low-carb Primal, or you can go full keto (ideally if you’ve been mostly Primal for a while) and speed up the adaptation process. This will enhance mitochondrial function, improving their fat-burning abilities, and even increase mitochondrial biogenesis.

After you have 4-6 weeks of fat-adaptation under your (shrinking) belt, you can tailor your carb intake to your activity level. If you want to eat more carbs, make sure you’re training hard and long enough to clear out muscle glycogen and upregulate insulin sensitivity.

Finally, start integrating foods and nutrients that support metabolic flexibility:

Magnesium: Magnesium deficiency increases mitochondrial oxidative stress, inhibiting mitochondrial function and promoting energy overload. Magnesium deficiency has also been linked to insulin resistance.

Polyphenols: A range of polyphenol-rich foods appear to have pro-flexibility effects, including dark chocolate and colorful produce.

Omega-3 fats: Long chained omega-3s (found in fatty fish and fish oil) can improve mitochondrial function by crowding out excessive linoleic acid in the mitochondrial membranes.

How to Track Your Flexibility

Answer these questions—hopefully in the affirmative. If not, just take it as information you can act on.

  • Are you waking up in a state of mild ketosis every morning? Metabolically flexible people will quickly switch to the “fasted” state upon cessation of food. A good night’s sleep is enough to get the ketones flowing, even if you had a few carbs at dinner.
  • Can you handle the food you eat, the fuel you introduce?
  • Can you burn your own body fat between meals?
  • Can you eat carbs without spiking your blood sugar and falling asleep an hour after?
  • Can you skip a meal without issue?
  • Are you snacking less—or not at all?
  • Can you store the carbs you eat as muscle glycogen, or do they end up being converted into fat in the liver?
  • Are your workouts getting better?
  • Do you have more energy?
  • Is your mood improved?

Congratulations. You’ve got metabolic flexibility.

So, how do you fare here? Are you flexible or inflexible? If you were and aren’t anymore, what changed? What’d you do right? What needs your attention? And what questions come up?

Thanks for reading, everyone. Take care!

References:

Macinnis MJ, Zacharewicz E, Martin BJ, et al. Superior mitochondrial adaptations in human skeletal muscle after interval compared to continuous single-leg cycling matched for total work. J Physiol (Lond). 2017;595(9):2955-2968.

Menshikova EV, Ritov VB, Fairfull L, Ferrell RE, Kelley DE, Goodpaster BH. Effects of exercise on mitochondrial content and function in aging human skeletal muscle. J Gerontol A Biol Sci Med Sci. 2006;61(6):534-40.

Malin SK, Haus JM, Solomon TP, Blaszczak A, Kashyap SR, Kirwan JP. Insulin sensitivity and metabolic flexibility following exercise training among different obese insulin-resistant phenotypes. Am J Physiol Endocrinol Metab. 2013;305(10):E1292-8.

Ukropcova B, Sereda O, De jonge L, et al. Family history of diabetes links impaired substrate switching and reduced mitochondrial content in skeletal muscle. Diabetes. 2007;56(3):720-7.

Zheltova AA, Kharitonova MV, Iezhitsa IN, Spasov AA. Magnesium deficiency and oxidative stress: an update. Biomedicine (Taipei). 2016;6(4):20.

Serrano JCE, Cassanye A, Martín-gari M, Granado-serrano AB, Portero-otín M. Effect of Dietary Bioactive Compounds on Mitochondrial and Metabolic Flexibility. Diseases. 2016;4(1)

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

35 thoughts on “The Definitive Guide to Metabolic Flexibility”

Leave a Reply

Your email address will not be published. Required fields are marked *

  1. Super Awesome post Mark!
    However one question comes to mind, regarding the questionnaire you gave at the end to determine metabolic flexibility. Some of those questions seem difficult to answer such as “Can you store the carbs you eat as muscle glycogen, or do they end up being converted into fat in the liver?” and “Can you burn your own body fat between meals?”. How would you go about measuring and quantifying that?
    Thanks for the article as always.

    1. “Can you store the carbs you eat as muscle glycogen, or do they end up being converted into fat in the liver?”

      Your blood sugar, triglycerides and body composition (over time) can quantify that.

      “Can you burn your own body fat between meals?”

      If you can you skip a meal (easy-day), not get hungry and have a constant supply of energy (not too much, not too little), then you’re probably burning your own body fat between meals. If you want to quantify further, use a ketone meter and make sure that it’s above 0.5mM.

    2. Carbs almost never get stored as fat. Unless you eat a massive amount of it, in a large calorie surplus.
      And even in that case, just a small part of it get converted.

      1. Not true… not even close. If you don’t immediately use those carbs for short-term energy (this is most people), and if you don’t soak up those carbs into tissue (this is most people), they get repackaged by the liver into triglycerides for long-term energy storage.

        Look around… we’re swimming in a sea of obesity, fatty liver and elevated triglycerides… hmmm.

        1. If you are not in a (large) calorie surplus, absolutely not. This has been studied and demonstrated.

          Turning carbs to fat is very costly, and happens only in last resort.

          Carbs per se don’t make you fat.

          1. However having a carb-centric diet will often provoke unnecessary hunger as has been widely discussed elsewhere, making a sufficient calorie surplus for fat gain much more likely. If something like this were not going on we wouldn’t see people who are eating low-fat and trying to stay lean still getting fatter and fatter.

      2. Above one’s carbohydrate threshold, they indeed convert to fat. This is basic biochemistry.

        1. Exactly! Where else would that energy go? Energy is neither created nor destroyed. It only gets converted to other forms. In an animal biological system, potential energy is stored as lipids and in plants, polysaccharides for the most part. Plants store lipids in seeds like mammals store glycogen in muscle.

  2. I was just reading another article blaming keto eating for low thyroid, specifically poor T4 to T3 conversion. They never mention whether any of the people in the typically short (couple of weeks) study happened to be fat adapted or metabolically flexible.

    In the most recent one I read it did mention that after a 30 day fast, ingestion of carbs quickly restored normal T4 to T3 conversion (contrasted to breaking the fast with fat), but never mentioned the possibility that periodic carb refeeds could accomplish the same thing for long term adherents of nutritional ketosis.

    So add to your list of metabolic flexibility benefits the preservation of healthy thyroid function.

    1. Interesting. Mark did a post on keto and the thyroid a while ago and briefly addressed the T4 / T3 issues. He wasn’t able to conclude however whether the decrease was a symptom of low carb or the increase was a consequence of high carb. I wish I knew the answer.

      Personally, I was keto for about 10 months and, otherwise felt great, but was showing signs of decreased thyroid function. My body temp was consistently in the 96 and 97s and my libido dropped. I added back in more primal carbs such as fruits and sweet potatoes and it seems to be helping. I’m curious if a cyclical keto approach would have been beneficial.

  3. Menopause impacts that flexibility. Biting the bullet and doing lower carb. Clothes are looser, exercise easier. I hate that reality but it is what it is. I will stick with it for six weeks, see where I’m at then.

    1. I’m post-menopause and am interested in what you’re doing and the results you’re achieving.

  4. By the way, this is why I suspect carnivorous diets work in some people. Plant polyphenols and phytochemicals are hormetic, which means they slightly disrupt homeostasis.
    People whose homeostasis has been systematically abused and cut to pieces over a lifetime of self-denial of metabolic health will hardly appreciate more disruption, even from plants, and so animal organs and fats are a safe refuge; metabolic flexibility from fat adaptation, anti-inflammatory effect from ketosis (just the right amount of hormesis), and molecular biodirectors directly nourishing corresponding organs that have been malnourished (and functionally deficient/erratic) for so long.

    1. Since our inception we (Sapiens) have consumed nose-to-tail nourishment… up until just recently.

      If one had their thyroid removed, not only would Thyroid glandular still work, it would be necessary for life because each and every cell requires thyroid hormone (T3) for energy metabolism and mitochondrial signaling. Same goes for the pancreas… if one had their pancreas removed, pancreas glandular (and pancreas producing enzymes and peptides such as insulin) would be necessary to sustain life. As it relates to having the spleen removed, our biology still expects spleen producing peptides such as tuftsin, splenopentin and splenin which further support and modulate the immune system (by stimulating macrophages and enhancing natural killer (NK) cell activity). The thymus gland is no different, our biology still expects thymus producing peptides such as thymosin, thymopoietin and serum thymic factor in order to heal and be healthy.

      The elegance of animal physiology is that glands secrete peptides and other chemical-like substances that exert downstream effects at the cellular level. Eating nose-to-tail organ meats, bone marrow, liver, kidney and the prized kidney fat (suet), etc, etc is in harmony with our evolutionary past. It’s the same nourishment that our DNA evolved with that enabled us Sapiens to reach the top of the food chain. It’s the same nourishment that our DNA still expects today (in the modern world) to be our strongest, healthiest and happiest.

      So yeah, develop that metabolic machinery… become metabolically flexible but don’t deprive your biology of the raw ingredients it needs to be truly nourished.

      1. To put this into context, the fact that carnivorous diets work so well in exactly the nutrient-deprived demographic you’ve just described appears to corroborate that our body not only works well on organs, but also that organs shift the organism from a state of aimless disease to equilibrium (presumably because our genetics and our nutrition are more aligned).

        My hypothesis: The fat adaptation leads to reestablishment of overall metabolic homeostasis, while the consumed organs reestablish homeostasis in a more decentralised and targetted fashion, affecting specific subsystems. It appears to come down to the dichotomy between fuel and peptides… we’re generalists in the former, specialists in the latter.

  5. Great article! I have been low carb for several years and launched into Keto almost 3 months ago.. i am post menopausal and insulin resistant( although i no longer need metformin) I do the blood tests and am in Keto. I tried intermittent fasting but have really struggled with it- hungry, irritable and exhausted. I do workout a lot mostly aggressive hiking 3 times a week and hiit training. I am very confused and frustrated at not being able to fast.
    Also, some of the questions about being metabolically flexible seems like you would need testing. Not sure how to know if food is being converted into fat in my liver. Some of the questions are easy to answer.
    Thank you for your articles and I appreciate the focus on mature women. It does seem like out struggles are different.

  6. If you are in a ketogenic state for too long will you lose the ability to burn carbs? How long in ketosis before this is a problem?

    I have been experimenting with the carnivore diet and I really like it, but my biggest concern is if I ever do go back to having an occasional sweet potato will I have lost the ability to break it down easily?

    1. You will always retain the ability to burn carbs because too much sugar in the blood is dangerous and the body knows it. My own experience with adding a little plant material back to carnivore reminded me why I went carnivore to begin with. GERD, bloat, gas. YMMV. Carbohydrate tolerance is also definitely an individual thing. A sweet potato is WAY too much carbohydrate for me. I don’t “earn” carbs when I exercise intensely. I let my body decide how much it needs and make them itself. Better for my system to let it auto-regulate carbs than to throw in exogenous carbohydrate and spike everything. That’s coming from the background of a body that would be diabetic if fed carbs but normal A1c without them.

      1. Humans are omnivores, not strict carnivores. Hence our small mouth and teeth, lack of fangs, lack of claws and long digestive track. If you have gut symptoms when eating healthy carbohydrates from plant based foods it is likely a problem with your gut microbiome, not an issue with the plants/carbs themselves. Think SIBO or something along those lines. Consider seeing a functional medicine practitioner to have some gut testing performed. Plants are packed with vitamins, minerals, phytonutrients and healthy fiber and eating a plant based diet is associated with long-term health and longevity and can be incorporated with healthy animal products (grass fed beef, organ meats, free range eggs, etc.

  7. Completely off topic but when did Mark move from California to Miami????

    1. He mentioned it in some of his blog posts. It’s been awhile now.

  8. I was on keto for 3 months and didn’t lose weight (or shrink waist)… and I do have rolls of fat to lose. I tried variations (more fat, less fat, more protein, less carbs etc..) Mark seems to imply in the article that fat adaptation happens automatically, and after a small period of time. This has not been the case for me. I have physical disabilities and can only walk (no jumping or running or heavy lifting possible) After 6 months of doing keto I have withdrawn to low carb/Primal. Feeling very discouraged because I am pretty sure I am not fat adapted and not metabolically flexible. I’m tired a lot, I am hungry a lot, I get brain fuzz when eating too many carbs, etc. Where do people like me find answers?

    1. Fat adaptation/ketosis should kick in within 3-5 days of cutting out carbs. But keto is not a magic bullet; it won’t work for everybody. Still, if you cut way back on carbs (and assuming your daily calorie consumption didn’t stay the same or increase — no matter what you are eating, you still have to eat fewer calories than you burn) and didn’t see any weight loss at all, it’s probably worth talking to a nutritionally enlightened doctor to see what they have to say. Unfortunately most docs will just be horrified that you were eating a lot of fat and will cut the conversation short, but if you can find a good one, maybe they can help you track down what’s going on. Probably a good idea to get some blood work done and see if something’s wonky with thyroid or hormones or some other thing that messes with metabolism. And if you can walk, do it — exercise doesn’t have to be intense to be effective. Best of luck to you!!

    2. I too tried keto for months and months and did not notice the supposed results. I was alwsys hungry,tired etc. I have found making sure I ate chicken liver to get B vitamins and some shellfish + increasing carbs . to about 50 g or even up to80g per day from starchy veg or sometimes even white rice with butter as part of a meal have helped me and may be worth a try. I also eat 60 -90g protein per day and lots of fat. I empathise and feel that this would make a great subject for a post from MDA as I rarely see information about what to do when this amazing energy and metabolic flexibility just doesn’t seem to happen with keto. Personally I feel very energized when I have eaten enough liver which sounds random but given that it is full of Iron and B vitamins it is not surprising and I think for me I need to eat it more than once a week which seems to be the recommended amount and I know you can get too much vitamin A from eating a lot of it but may be worth checking into this.

    3. Keto did not work for me either. Carnivory did. Lost 30 lbs and cured my autoimmune disease. Now 1 yr carnivore.

  9. Thanks Mark
    10 years ago I would get hungry mid morning, and crave sugars. I would have snack on simple carbohydrates all the time. At lunch I would have bread as a staple and always felt tired afterwards. And I did think that was normal. However, for at least the last 3 years I have cleaned up my diet. Way less carbs, at least 50%, in the from of biscuits, cakes , chocolates, lollies. Reduced wheat intake by more than half (breads, pastries, pasta). The result – my body works better, no sleepy moments in the afternoon, more energy, make it through to lunch without trouble now. Cope with a ten hour plus fast at night, and sometimes eight hours during the day and never go hypoglycaemic. I probably drift in and out of ketosis now, but haven’t made the full dietary changes yet
    Even back then, I used to think that my diet was okay. And I guess most others from the western world have similar thoughts, never knowing how much better their bodies can perform.
    Pete D
    I used to th

  10. Great info Mark. Very pertinent timing for me at this time….but something in my experience is making me wonder what is happening. Maybe someone might be able to give me some insight. Background: went whole food keto a year ago. and with the combination of some EF and TRE lost 50lbs in about 10 weeks. Stayed weight stable for a month over the holidays. Then possibly in combination with adding some every other day resistance training and time on keto, the appetite suppression of started to wear off in the new year. I went from about 14-1800 kcal during the weight loss phase to 3500-4k+ and added more protein(~2g/kg lbm), but surprisingly stayed at the same weight for the next 8 months while doing daily omad(22/2). Prior blood work I was T2D, IR, HbA1c 8.6, TG 1300, low HDL, higher ldl, high FBG. After 3 months, A1c was 5.2, TG less than 100, HDL up(tg/hdl- .38), BG well under 100….so all met markers seemed pretty good. Still wanted to drop that last 15-20 lbs and lean out but was ok with being at a pretty healthy weight, eating that much, gaining a bit of muscle and at least not gaining. During the last 8 months my energy has been very good for the most part, but have noticed in the last couple months that I have started feeling weaker at times. Thought maybe I was starting to add in a few too many carbs(was getting up to 50-100), so I tried pretty close to ZC/carnivore for a bit to see if it might help. I wasn’t losing any weight and it wasn’t too bad adapting to it but as soon as I added intense 2hr hockey games 3 days a week I tanked(btw, had np with hockey last Jan- April with omad and lchf). Made me wonder if I just didn’t have enough glycogen to sustain the output of the hockey plus training and some bike riding as well…..felt like something had changed since 6 months ago. I knew carb cycling was an option, but was super nervous about adding more back in case I started slipping back into the habits that got me obese in the first place….plus, since I thought I was still IR, I would start getting carb/sugar cravings again. Based on the article though, I gathered there might be a good chance I was now pretty IS, so tried some carbs out. Had some extra berries, hummus and brown rice at the end of a couple of good salad/protein meals and found I didn’t get the usual cravings afterward so I figured everything was pretty good(plus had more energy the next morning for workout and bike ride). I did find about 5 or 6 hrs later I did feel “hungrier” than usual though. I thought that having been well fat adapted and I could easily go without eating at any time over the last year, that that wouldn’t happen. It almost felt like I had low BG, but checked and it was around 95. I figured based on the article that I should be able to cycle in some carbs now and not feel that way(transfer seamlessly over to fat burning) …wondering what might be going on? Is it just the newness of doing this? Still IR?

    1. Hi Dan,
      You may consider upping your salt intake. I suffered from overtraining symptoms and a loss of strength and endurance after a run of excellent form. I’m a road cycling enthusiast and it was frustrating. I threw more carbs at it and that didn’t help. Finally came across the book “The Salt Fix” and decided to up my salt intake. Not only did the cramps I had always dealt with disappear, my performance returned. I have to consciously ingest more salt. Apparently there is a genetic component, but Carnivore/Keto also increases salt demand. Consider giving a try and see if that helps.

  11. Many thanks to Mark for providing this conscise overview of Metabolic Flexibility. But more importantly adding the links to the references from which he obtained this significant information.

  12. I’m skinny fat female and I’ve been sticking on it for along time even though I count my Cals and macros. That’s why I think I’m metabolic inflexible. When I eat carb + protein with minimum fat meal I feel hungry but if I add fat ( +13g) I feel good.. I still can’t figure out if I’m metabolically flexible or not.