The Definitive Guide to Metabolic Flexibility

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!


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)

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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