Metabolic Flexibility: What It Is, How It Is Measured and What Improves It
Metabolic flexibility is the ability to switch between burning fat and burning glucose depending on what fuel is available. It is reduced in insulin resistance, and regular exercise and weight loss are the usual ways to improve the underlying problem. It is a useful research concept, but it is measured in laboratories rather than in routine care.
- Researchers measure it with the respiratory quotient (RQ), which reflects the mix of fat and carbohydrate being burned, during fasting and after insulin or glucose; the calculation has known biases.
- Endurance training raises muscle’s capacity to burn fat, one reason trained people tend to be more flexible; no single type of training has been shown to be best.
- In insulin resistance, muscle burns relatively more glucose while fasting and switches less well to glucose after insulin, a pattern described as “metabolic inflexibility.”
- Hunger when you skip a meal or an energy dip after a sugary meal are common experiences, not reliable tests of metabolic flexibility.
- Time-restricted eating lengthens the overnight fast, but whether it improves metabolic flexibility itself has not been established.
Metabolic flexibility is the capacity to adapt fuel use to fuel availability.1 The idea was developed by David Kelley and Lawrence Mandarino, who showed that insulin-resistant muscle burns more glucose while fasting and less after insulin, the opposite of what an older theory had predicted.2
What Metabolic Flexibility Means Physiologically
In a flexible person, fat supplies much of the body’s energy during an overnight fast, and fuel use shifts toward glucose after a meal or during harder exercise. In insulin-resistant muscle the pattern is blunted: it burns relatively more glucose while fasting and switches less after insulin, which may help explain the fat that builds up inside muscle cells in insulin resistance.2 One review cautions that much of the apparent inflexibility seen in insulin clamp studies reflects reduced glucose uptake; after accounting for it, flexibility did not differ in obesity, with or without type 2 diabetes.1
Popular accounts link poor flexibility to hunger when meals are missed, energy crashes after sugary meals and trouble sustaining exercise without carbohydrates. These experiences have many causes, so they are not a reliable test.
Training and Diet
Moderate endurance exercise, often called Zone 2, is mainly fueled by fat, and endurance training increases mitochondria and the enzymes muscles use to burn fat. Diet also shapes fuel use: in a study of elite ultra-endurance athletes, those on a long-term very-low-carbohydrate diet had peak fat-burning rates 2.3 times those of equally trained athletes on a high-carbohydrate diet, with no difference in resting muscle glycogen.3 Training can restore flexibility where it is impaired: in a small controlled study, 12 weeks of combined aerobic and resistance training, three 45-minute sessions a week, restored mitochondrial function and metabolic flexibility in 18 men with type 2 diabetes to the levels seen in healthy controls, and improved their insulin sensitivity.4 For most people, regular aerobic and resistance exercise, plus weight loss where needed, are the most dependable ways to improve insulin sensitivity.
Put this research into practice: Biomarker Reference Tool
References
- 1Galgani JE, et al. "Metabolic flexibility and insulin resistance." Am J Physiol Endocrinol Metab. 2008;295(5):E1009-17. PubMed · DOI
- 2Kelley DE, Mandarino LJ. "Fuel selection in human skeletal muscle in insulin resistance: a reexamination." Diabetes. 2000;49(5):677-83. PubMed · DOI
- 3Volek JS, et al. "Metabolic characteristics of keto-adapted ultra-endurance runners." Metabolism. 2016;65(3):100-10. PubMed · DOI
- 4Meex RC, et al. "Restoration of muscle mitochondrial function and metabolic flexibility in type 2 diabetes by exercise training is paralleled by increased myocellular fat storage and improved insulin sensitivity." Diabetes. 2010;59(3):572-9. PubMed · DOI
