Metabolic flexibility is the ability of the cells to switch between fuel sources like fat and glucose. Metabolic inflexibility has been described in a range of conditions including obesity, T2DM, fatty liver, CVD, PCOS, and physical inactivity .
When you eat a meal, the glucose you consume is available for the cells to use for energy. Since it’s the cells’ preferred fuel source, the metabolic switch is flipped to burn glucose. This prevents glucose from building up in the blood and causing high blood sugars.
When fasting 4+ hours after a meal or during prolonged exercise when glucose availability is limited, the cells will flip the metabolic switch to burn fat for fuel. This prevents low blood sugar levels and reserves the available glucose for the brain, which cannot store glucose and requires a constant, steady supply.
In the early post meal period (0 to 2 hours after eating), most fatty acids are trapped, so they cannot be burned for energy. In the late post meal period (4 to 6 hours after eating), more fatty acids escape and can be burned for energy.
Chronically consuming too much glucose and fat (and protein for that matter) can lead to metabolic meltdown . The cells don’t know what fuel to use. They become very inefficient at burning fuel and making energy—and it builds up as fat instead. This further exacerbates the problem.
It’s analogous to peak hour traffic. When there’s heavy traffic, drivers become less observant, everything slows down, it becomes congested, and there’s an increased risk of collisions. The same thing happens in the body as the tension between fat and glucose escalates.
This congestion causes the metabolic switch to get stuck in the middle. When this happens, the mitochondria (the energy powerhouse of the cell that turns glucose and fatty acids into energy) sends out stress signals to prevent more glucose from being taken up by the cell, causing insulin resistance .
A high fat meal will suppress glucose oxidation (burning glucose for energy) and high glucose and insulin levels suppress fat oxidation (burning fat for energy)—so the burning of fuel is suppressed over all.
There are no whole foods that are high in fat and carbohydrates; they are either high in fat or high in carbohydrates. The only exception is dairy, which is high in both fat and carbohydrates, but the evolutionary purpose of milk was to feed infants to promote growth and weight gain. However, today the most commonly consumed and popular foods are high in both fat and carbohydrates, and can contribute to metabolic meltdown.
What affects metabolic flexibility?
Exercise increases metabolic flexibility. Moderate to high intensity exercise pushes the metabolic switch over to burn carbohydrates/glucose while lower intensity exercises for prolonged duration flips it over to burn fat.
2. Snacking and overeating
Lack of exercise and constant snacking or overeating causes the switch to get jammed. I generally don’t recommend constant snacking, but you also want to avoid consistently consuming large meals (especially ones that are heavy in the carbohydrates and fat).
3. Intermittent fasting
Intermittent fasting and time-restricted feeding improves metabolic flexibility. Prolonged periods with no energy intake (calories) helps to flip the metabolic switch to burn fat.
4. Keto diet
A keto diet actually makes you more metabolically inflexible because the high fat intake causes the cells to fill up with fat. When the cell is full of fat, it ignores insulin—the cells don’t need glucose because they have plenty of fat to burn. This means that when you eat food containing carbohydrates, you are unable to effectively flip the metabolic switch over to burn glucose.
5. Reduced fat intake
A low fat, whole food, plant-based diet can help improve metabolic flexibility. By reducing fat intake (particularly saturated fat), the body only has to deal with the fat reservoirs on your body and the carbohydrates coming in from each meal. As long as you don’t overdo the carbohydrates and stay away from the processed and refined kind, your body will slowly adapt. Be patient—depending on how much fat has accumulated in the cells, it may take some time.
6. Choose the right fats
The type of fat you consume also matters. Saturated fat is more likely to fill up cells, clogging up the traffic and causing the metabolic switch to get stuck. Unsaturated fat tends to be used primarily for making things and is less likely to clog up the traffic . Saturated fat is predominantly found in animal products like meat, poultry, fish, dairy and eggs. Unsaturated fat is predominantly found in nuts, seeds, avocado, extra virgin olive oil, algae/seaweed, and fish oil.
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 Metabolic Flexibility in Health and Disease, Bret H. Goodpaster and Lauren M. Sparks, REVIEW, Cell Metabolism, VOLUME 25, ISSUE 5, P1027-1036, MAY 02, 2017
 Metabolic Inflexibility: When Mitochondrial Indecision Leads to Metabolic Gridlock, Muoio, Deborah m, Cell, 04 December 2014, Vol.159(6), pp.1253-1262
 Metabolic flexibility in the development of insulin resistance and type 2 diabetes: effects of lifestyle, 2009, E. Corpeleijn, W. H. M. Saris and E. E. Blaak, obesity reviews 10, 178–193
 A Difference in Fatty Acid Composition of Isocaloric High-Fat Diets Alters Metabolic Flexibility in Male C57BL/6JOlaHsd Mice. Duivenvoorde, Loes P M ; van Schothorst, Evert M ; Swarts, Hans M ; Kuda, Ondrej ; Steenbergh, Esther ; Termeulen, Sander ; Kopecky, Jan ; Keijer, Jaap, PloS one, 2015, Vol.10(6), p.e0128515