Here are a few definitions:

“Metabolic Flexibility is the ability of a system (i.e., whole organism, organ, tissue, or cell) to adjust fuel oxidation to fuel availability.”

Galgani et al. 2008

“Metabolic Flexibility is the ability to switch back and forth between the two major energy substrates – glucose and fat – based on availability and need.”

  1. Stanton

“Metabolic Flexibility enables you to (1) transition between fats and carbohydrates so you can burn more fat when you’re not exercising; and (2) use carbohydrates when you are exercising to fuel that activity and perform at a higher level.”

Dr. Mike T Nelson

Metabolic flexibility is basically the ability to switch from one fuel source to the next; typically this means the ability to switch between burning carbs and burning fat.   Humans need the ability to use both lipid (fat) and carbohydrate fuels and transition between them depending on activity level and nutrient availability.  All those people you see who can “eat whatever they want” most likely have excellent metabolic flexibility.

Fuel source: Fat ←→ Carbs

Metabolic flexibility is the ability to switch from one fuel source to the next; from fats to carbs and carbs to fat.  Metabolic inflexibility is just the opposite; the inability (or limited ability) to switch from one fuel source to the other.

Why We Need Metabolic Flexibility         

It allows us to safely and effectively utilize a wider variety of nutrients.  When we are metabolically flexible we can indeed “eat whatever we want,” be it a juicy steak or a fat sweet potato. 

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

It’s hypothesized that metabolic inflexibility may also play a role in various disease processes such as diabetes and metabolic syndrome.  So along with better body composition, being metabolically flexible may promote health and wellness.

It also 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. That being said, 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.

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 Causes Metabolic Inflexibility?

There are two main issues.  First, your mitochondria are dysfunctional.  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 (toxins, poor diet, nutrient sparse foods, stress, poor sleep, etc.) they don’t work as well.  

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 and it makes utilizing your stored body fat in between meals very difficult.  Also, 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.  Remember that one of insulin’s main functions is to drive energy into cells.  If there’s already too much energy floating around, the last thing your body needs is to jam even more in.  So it turns down insulin sensitivity, which is not good.  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.

This leads into more discussion on insulin:

A key to understanding all of this is the vital role the storage hormone insulin plays.  In a healthy state with normal insulin metabolism, humans can effectively switch from a primarily fat metabolism to a carbohydrate metabolism, and vice versa. 

In simple terms, when levels of insulin are low, the body is in fat burning mode.

When insulin is high, the body is shifted towards carbohydrate metabolism (and fat storing mode).

As a side note, having more muscle allows your body to have better utilization off both fats and carbs, since muscle is very metabolically demanding.  I discuss this further in another blog post on the importance of muscle mass!

During fasting conditions, someone who’s very metabolically flexible will be able to tap into stored body fat. The cool thing is that individuals who are metabolically inflexible can also do this, so fasting becomes a way to increase metabolic flexibility.

Assessment of Metabolic Inflexibility

(Thanks to Mike Nelson on this section)

1 – High Insulin

Taking in a whey protein drink with some simple carbs on a relatively empty stomach is an effective way to jack insulin levels up. I recommend people try this as their breakfast a few times during the week and monitor their reaction.

If you feel like collapsing face-down in your drink and spilling it all over the table, you probably have an issue with high levels of insulin and the resulting crash from it.

If you feel great, there’s no problem.

2 – Low Insulin

For this test, I recommend you do some fasting.  Basically water/tea/coffee only; there is no consumption of any calorie-containing foods or liquids.

In a fasting condition, there’s no food coming in to stimulate any increase insulin.  If you find that you can’t make it more than two hours, you’re probably inflexible to burning body fat.   If you can easily go for 5-6 hours, that’s much better.

Ideally a 24-hour fast is best since there’s data showing insulin levels reach their lowest point at around the 24 hour mark.  However, if you can only get to 16-18 hours that’s fine too.

Practical Application

If you’re very metabolically flexible, eating some “bad” foods from time to time (or often as in this case) shouldn’t be an issue, as your body can convert them into fuel without many side effects.

Try simulating the conditions for high and low levels of insulin and note your response. If you feel like a puddle after a protein and carb drink, you’re more intolerant to high levels of insulin. This means it’s time to add in some more low intensity cardio exercise or even a fast as fasting has been shown to improve insulin sensitivity.

If you can’t make it more than two hours without some food, you’re impairing your body’s ability to burn that spare tire, so work to slowly increase your spacing between meals. I like to have clients do about one 24 hour fast per week if their goal is to drop fat and increase their metabolic flexibility.

Much of this throws what we think we know on its head, but I encourage you to experiment. You just might be pleasantly surprised!

How to Improve or Reset Metabolic Flexibility

First, exercise:  No you can’t out-exercise a bad diet (we will discuss nutrition later) but exercise is crucial to improving insulin sensitivity and metabolic flexibility.  Regular training—both strength and aerobic—directly counters metabolic inflexibility.  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 activity, 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 eating (Paleo, or Keto style) 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.  As a rule, stick with eating most of your complex carbs after a workout.  Vegetables can be eaten anytime!

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 and see how you respond:

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?

If all or most of your answers are positive, congratulations, you’ve got metabolic flexibility!  If not keep working at it!  Thanks to Mark Sisson on this section. 

Need more help?  Contact me for my nutrition guide or for online coaching/Q and A!

Live great,
Dr. Eric

 

References

Kelley D. E., J. He, E. V. Menshikova, V. B. Ritov. Dysfunction of mitochondria in human skeletal muscle in type 2 diabetes. Diabetes. 51(10):2944-2950, 2002.

Arslanian S., C. Suprasongsin. Insulin sensitivity, lipids, and body composition in childhood: is “syndrome X” present? J Clin Endocrinol Metab. 81(3):1058-1062, 1996.

Nistala R., C. S. Stump. Skeletal muscle insulin resistance is fundamental to the cardiometabolic syndrome. J Cardiometab Syndr. 1(1):47-52, 2006.

Oakes N. D., P. Thalen, E. Aasum, et al. Cardiac metabolism in mice: tracer method developments and in vivo application revealing profound metabolic inflexibility in diabetes. Am J Physiol Endocrinol Metab. 290(5):E870-81, 2006

Stump C. S., E. J. Henriksen, Y. Wei, J. R. Sowers. The metabolic syndrome: role of skeletal muscle metabolism. Ann Med. 38(6):389-402, 2006.

Henquin J. C., M. Nenquin, P. Stiernet, B. Ahren. In vivo and in vitro glucose-induced biphasic insulin secretion in the mouse: pattern and role of cytoplasmic Ca2+ and amplification signals in beta-cells. Diabetes. 55(2):441-451, 2006.

Goodpaster B. H., J. He, S. Watkins, D. E. Kelley. Skeletal muscle lipid content and insulin resistance: evidence for a paradox in endurance-trained athletes. J Clin Endocrinol Metab. 86(12):5755-5761, 2001.

Goodpaster B. H., D. E. Kelley. Skeletal muscle triglyceride: marker or mediator of obesity-induced insulin resistance in type 2 diabetes mellitus? Curr Diab Rep. 2(3):216-222, 2002.

Goodpaster B. H., S. Krishnaswami, H. Resnick, et al. Association between regional adipose tissue distribution and both type 2 diabetes and impaired glucose tolerance in elderly men and women. Diabetes Care. 26(2):372-379, 2003.

Kelley D. E., B. H. Goodpaster. Skeletal muscle triglyceride. An aspect of regional adiposity and insulin resistance. Diabetes Care. 24(5):933-941, 2001.

What can be done?

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 Flexib