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What is Metabolic Flexibility? And what’s Zone 2 got to do with it?

The state of this country’s metabolic health is, or should be, a scandal. According to the CDC, roughly half of Americans are diabetic or prediabetic. The patients in my practice are very health conscious so I don’t treat cases of obvious metabolic dysfunction all that often. However, there’s a concept that has emerged from the worlds of metabolism research and exercise physiology which I find very useful because it sheds light not only on serious problems with the regulation of glucose and insulin, but also suggests ways the rest of us who don’t struggle with these issues can perform at a higher level and safeguard our long-term health. It is: metabolic flexibility.


A 2022 paper from the Mayo Clinic Proceedings, “Metabolic Flexibility and Its impact on Health Outcomes” does a good job laying out how to understand this admittedly broad concept. Metabolic flexibility is defined here as the body’s ability to rapidly and efficiently switch back and forth between fat and glucose as a fuel source.


Why is that important? Glucose, broken down from dietary carbohydrate, is the body’s primary fuel when we have to exert ourselves beyond a certain point, a point that differs by individual. If we’re unfit or we’re eating more calories than we’re burning off, or both, we become over-reliant on our stored glucose (glycogen) to power the body which usually means we’re secreting more insulin than is good for us. We become metabolically inflexible. The downstream effect is reflected in those dismal national diabetes/prediabetes statistics.


The most impactful way I know for people to enhance metabolic flexibility is exercise, a very specific type of exercise, known as Zone 2. In Zone 2 training, you move your body at a moderate intensity – it could be running, cycling, swimming or maybe just taking a brisk walk – anywhere from roughly 60 to 70% of your maximum heart rate. The fitter you are, the higher up in that wide range you’ll be working. A handy rule of thumb for being “in the zone” -- put in as much effort as you can while still being able to talk, in full sentences. 


What makes Zone 2 so beneficial is that you’re working hard enough to develop your cardiorespiratory fitness but comfortably enough so that you’re burning fat as your main fuel. You can go, if you wish, for a long time – the body stores far more energy in fat than it does in the glycogen stored in the muscles and liver.


Fat is only burned in the cell’s powerplants, the mitochondria, so the more time you spend in Zone 2, firing your mitochondria-rich slow-twitch muscles, the more you promote the creation of new mitochondria (“mitogenesis”) as well as the destruction of older mitochondria who have passed their sell-by date (“mitophagy,” the mitochondrial equivalent of autophagy). You are, in effect, building a bigger, and more efficient, aerobic engine.


The more effortful zones of exercise certainly have their place in a work-out program. I’ll discuss the metabolic benefits of HIIT (high-intensity interval training) in a future  post. But know that the higher you go up the effort/heart rate scale, all the way up to a zone 5 sprint, the more glucose you burn , the more wear and tear on the body (oxidative stress, inflammation, immune system depletion, etc.) and the shorter duration you can sustain. That’s why elite endurance athletes typically spend 80% of their work-outs in Zone 2, which provides the foundation for their harder efforts. “Go slow to go fast,” is the coach’s mantra. It’s a lesson that people who are going all-out during three or more spinning sessions a week would do well to heed.


Most importantly, Zone 2 training benefits spill over into everyday life, for the athlete and non-athlete alike. For a relatively unfit person, a regular long walk could translate to enhanced metabolic flexibility. Instead of immediately switching to a glucose burn when they rise in the morning, the formerly sedentary should be able to do more everyday activities burning fat, thereby lowering blood glucose and insulin levels, and lowering the risk for any chronic “disease of aging” you can think of.


I’ve focused my attention here on exercise and metabolic flexibility but that’s only half the story. The other half is eating, or more accurately, not eating. Putting the body into a fasting state – be that the natural fast that occurs at night when we’re asleep or a conscious effort to restrict meals to a shorter time window –pushes the body to burn fat for fuel. I’ve adopted a “time-restricted eating” approach to mealtimes, expanding the daily fast. These days, when I wake up, I’m no longer hungry and I can do a Zone 2 (or even slightly above) workout without any strain, putting off my first meal of the day until noon. For me, it’s an efficient way to maintain a healthy weight and body composition. I’m off the glucose drip.

(You can get the major take-aways from the video below.)

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