Metabolic Flexibility

Published by Nick Williams on

This has intrigued me for some while now. I can use intermittent fasting for up to 24 hours, feel no hunger, have amazing energy and mental clarity. So I think my body can use different fuel sources at will. But can it? In this article I am going to delve deep into one of the most trendy terms in Nutrition right now. Metabolic Flexibility.

First off, let’s define Metabolic Flexibility.

The most contemporary answer relates to which fuel source is used when moving from fed to fasted states and broadly refers to physiological adaptability (1). In short, can the body change from using glucose to fatty acids or ketone bodies for its fuel source? Can we train ourselves to be able to use glucose or fatty acids interchangeably?

Glucose, the bodies preferred choice (mostly!).

Our brains and muscles have differing energy needs and fuel demands. The brain uses glucose as its primary source but has limited ability to store glucose. In starvation, the brain will use ketones made in the liver (2). In contrast, our muscles have large glycogen (stored glucose) stores and will again use glucose first. For muscles, we also use the glucose from the breakdown of fatty acids or use ketones for energy when glucose is depleted (2). Our heart uses fatty acids from triglycerides for its preferred energy source (6).

We all have differing body types and therefore differing stores of glucose. 600g is quoted as an average level of glycogen stores with an average of 500g (muscles) and 100g (liver) (3,4).

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In 1963 (5) it was proposed that the body runs on a glucose – fatty acid cycle. Too much glucose in the body would not allow the fatty acids in adipose tissue to be broken down and used for energy. It was also proposed that too much adipose tissue would create insulin insensitivity (5). So, clearly looks like we need a balanced approach and our body needs some glucose.

Carbohydrates out of the diet

If we were to take out all carbohydrates from our diet (less than 25g a day is often quoted, as it’s virtually impossible to eliminate completely), it would take anywhere upwards of 2 days to burn through all our glucose stores. More commonly 4 to 7 days.

This is the ketogenic diet. We move into ketosis and use ketone bodies for energy. It’s not pretty to start with (just google keto flu) but once through this stage you can feel a sense of euphoria, great energy and mental clarity as the body burns a totally different fuel.

But that is an extreme diet. I don’t want to do that all the time. Personally, I believe there are benefits of this if it is done occasionally. But on a long term basis can we get all the nutrients we need? An article from 2019 (7) recognised that there is not enough long term evidence in humans to say whether this will cause harm or not.

However, the ketogenic diet or modified Atkins diet is considered to have beneficial effects on epilepsy (8).

Intermittent Fasting

Simply put this is ‘taking a break from eating’ (7). Ok, now we are talking!

  • IF – Intermittent Fasting (umbrella term)
  • ICR – Intermittent Calorie Restriction (24 hour fasting twice or more a week)
  • ER – Energy Restriction (reducing energy intake on a short term basis)
  • TRF – Time Restricted Feeding (8 hour eating window)
  • PF – Prolonged Fasting (24 hour fasting or more)
  • ADER – Alternate Day Energy Restriction (one day eating, one day with less than 25% energy intake)
  • CER – Continuous Energy Restriction (reducing energy intake indefinitely)

So, looks like I’ve been using time restricted feeding (often) and prolonged fasting (occasionally).

It brings us to the four phases of metabolism. Fed (3 hours), Post absorptive (up to 18 hours after eating), Fasting (18-36 hours after eating) and Starvation (36-48 hours+) states.

  • Fed: Glucose UP, Use of Free Fatty Acids (FFA) DOWN. Glycolysis used (breaking down of carbohydrates for glucose) (7).
  • Post Absorptive: Gluconeogenesis begins (a process in the liver -breakdown of fats and proteins for energy). But this can’t last because the need for glucose is higher than can be made in this process. We then get Lipolysis (breakdown of fats for energy) in the adipose tissue (7).
  • Fasting: Starting to use fats as primary fuel source. Muscle protein starting to be used for energy (7).
  • Starvation: using FFA solely as fuel source. (7)

This next bit is really interesting. Overnight fasting will create more FFAs, more growth hormone and if we continue our fast further into the day we start to use fatty acids for fuel. Bingo!

Benefits of intermittent fasting

  • According to research (7) there maybe some benefits to weight loss. This is usually because the eating window is reduced. There is simply not enough time in the day to ingest as many calories.
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  • Insulin sensitivity is improved with fasting (the opposite to resistance often thought of with Type 2 diabetes).
  • Autophagy (the clearing away of unwanted cells in the body) is initiated with intermittent fasting. If you are interested in this please check out (10), it is very interesting research into the support of various conditions.
  • There is some evidence that IF can improve cognition, although the studies on whether it improves life span are not conclusive.

So let’s get back to Metabolic Flexibility

It would seem that my intermittent fasting does allow me to start using different fuel sources. I 100% feel the difference in the way my body works in this state. If I stop eating at 6pm, by 11am I am starting to get the mental clarity.

Is it easy to do to start with? No, it’s not. Does it massively change your mindset once you have achieved it? Yes, it does. In my opinion, once you have managed a 17 hour fast on around 5 occasions it becomes second nature.

Do I like breakfast? Yes. But not all the time. I really enjoy metabolic flexibility, there are a host of benefits. It might be worth giving it a try!

Do I think that I can take part in resistance training during this stage? Not sure. I think we need a separate article on this!

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  1. Goodpaster, B. H., & Sparks, L. M. (2017). Metabolic Flexibility in Health and Disease. Cell Metabolism, 25(5), 1027–1036
  2. Bio Chemistry, 5th Edition. Berg JM, Tymoczko JL, Stryer L.New York: W H Freeman 2002.
  3. Murray, B., & Rosenbloom, C. (2018). Fundamentals of glycogen metabolism for coaches and athletes. Nutrition Reviews, 76(4), 243–259
  4. Jensen, J., Rustad, P. I., Kolnes, A. J., & Lai, Y.-C. (2011). The Role of Skeletal Muscle Glycogen Breakdown for Regulation of Insulin Sensitivity by Exercise. Frontiers in Physiology, 2.
  5. Randle, P. J., Garland, P. B., Hales, C. N., & Newsholme, E. A. (1963). THE GLUCOSE FATTY-ACID CYCLE ITS ROLE IN INSULIN SENSITIVITY AND THE METABOLIC DISTURBANCES OF DIABETES MELLITUS. The Lancet, 281(7285), 785–789
  6. Grynberg, A. Demaison, L. Fatty Acid Oxidation in the heart. Journal of Cardiovascular Pharmacology. 1996.
  7. Stockman, M.-C., Thomas, D., Burke, J., & Apovian, C. M. (2018). Intermittent Fasting: Is the Wait Worth the Weight? Current Obesity Reports, 7(2), 172–185
  8. D’Andrea Meira, I., Romão, T. T., Pires do Prado, H. J., Krüger, L. T., Pires, M. E. P., & da Conceição, P. O. (2019). Ketogenic Diet and Epilepsy: What We Know So Far. Frontiers in Neuroscience, 13
  10. Antunes, F., Erustes, A., Costa, A., Nascimento, A., Bincoletto, C., Ureshino, R., … Smaili, S. (2018). Autophagy and intermittent fasting: the connection for cancer therapy? Clinics, 73(Suppl 1)


None of the information written in this article should be considered as medical advice. It is your responsibility to consult your doctor before considering any form of nutritional approach.

Nick Williams

Nick Williams is a qualified and insured Nutritional Therapist. He is a member of BANT and registered with CNHC. He supports individuals and groups improve their health through the use of nutrition and lifestyle. He is a qualified mentor with the European Mentoring and Coaching Council. He is also a tennis coach and content developer for the UK's Tennis Coaching qualifications.