Well-Being//

The Connection Between Mitochondrial Flexibility and Energy

Here's how it can affect your day-to-day.

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Morocko/ Shutterstock
Morocko/ Shutterstock

The crux of the twenty­first­century energy crisis comes down to the title of this chapter. If you’re feeling the weight of fatigue you just can’t shake, I would wager that the scenario I’m about to describe is quietly unfolding inside all your cells. It’s a bold assertion, I realize. But the vast majority of people today are in­ advertently bombarding their cellular energy system with too much fuel. And that is the conundrum at the core of The Energy Paradox: You are overfed but simultaneously underpowered. That’s because there’s a mismatch between the conditions required by your four quadrillion energy workers—otherwise known as your mitochondria—and the nutrition they’re getting from you. Deprived of the raw materials they need to create energy, and yet bombarded with literally tons of inferior­grade fuel, they’re being forced to take some desperate measures to try to keep energy pro­ duction on track.

I can assure you that mitochondrial dysfunction is at the root of not only widespread fatigue, but also many of the illnesses that affect millions of people today, including heart disease, cardiomyopathies, diabetes, metabolic syndrome, cancer, obesity, autoimmune conditions, and neurodegenerative diseases. In fact, persistent fatigue is a warning sign that your mitochondria are overtaxed and unsupported, and may be on the brink of staging a strike. For obvious reasons, you don’t want your essential workers curtailing efforts or shutting down factory lines, which starves your cells, tissues, and organs of the energy they need to function. On some level, you could say that all disease is a function of an energy deficit. Illness stems from the “dis­ease” of the mighty mitochondria.

Mitochondria have the ability to process different fuels in slightly different ways to produce ATP. A single mitochondrion can process three different fuel substrates, all of which carry carbon atoms: glucose or other simple sugars from carbohydrates, amino acids from protein, or fatty acids and/or ketone bodies from fats. To use your car engine as an example again, in a car, there is strict delineation: It either runs on gasoline or diesel, and pity the hapless driver who gets them mixed up at the pump! But your mitochondria have a special gift: They are flexible, not fixed in their ability to use different fuels.

Your digestion system is brilliantly designed to process all of these fuel sources in a specific order. Picture a plate of salmon (protein and a bit of fat), some spinach (glucose and fiber), and sweet potatoes (glucose from starch plus fiber) all drizzled with olive oil (fat). All three types of fuel need to eventually make it into the energy­making assembly line, but they don’t come in simultaneously. The simple carbohydrates are broken down the fastest. Starch, a more complex carbohydrate, takes a bit longer to break apart, but both become glucose, which is absorbed quickest of all fuels, so your mitochondria typically process this first. Proteins have to be digested and broken down into amino acids before they can be absorbed from your gut, so they arrive for processing in cells later; even then, they have to be transformed into glucose or another compound called pyruvate via a process known as glycol­ ysis before they can enter the energy assembly line. Ingested fats usually arrive last, as they are absorbed totally differently through the gut wall; they enter your lymph system and take a circuitous route around your body to eventually get into your bloodstream and then your cells. Since this example of an “ideal” meal contains whole, unprocessed ingredients with the fiber intact—like the spinach and the sweet potato—your digestion and absorption of the different components takes place slowly, so that your mitochondria don’t become overwhelmed by too many fuels arriving at once. The “wholeness” of these foods, requiring a lot of breakdown into components, literally acts as stoplights and speed bumps as the food molecules vie to make it up the on­ramps and onto your mitochondrial energy highway; it allows them to merge in gradually. This ability of mitochondria to switch between several different fuel sources to generate ATP with ease is called metabolic flexibility. Metabolic flexibility is the cornerstone of a healthy energy system and indeed of all health and longevity: Without it, your energy production can start to break down. Having metabolic flexibility ensures that your mitochondria can keep your body and brain powered, even when one type of fuel runs out, such as when supplies of glucose are low or, more mundanely, every night when you are asleep and not eating. By design, your mitochondria shift to a slow burn at night, doing repair work and taking it easy like any workers would hope to after a busy day. With no new food to process, they would normally shift to using excess fuel that’s been stored in your fat cells. When there’s no incoming food (hopefully you aren’t sleep eating!), these stored fats are released into your circulation as free fatty acids (FFAs)—think of them as your slow burn fuel. Under certain conditions, your mitochondria can also burn ketones, a special type of fat produced in your liver from fatty acids when sugar supplies stay very low for a significant block of time, such as when you have not consumed carbohydrates in your diet, have not eaten for about twelve hours, or have burned up all your stored sugars (glycogen) through intense exercise. Ketones, as you’ll learn soon, are highly supportive in your quest for mitochondrial health and mental clarity too, but probably not in the way you think.

You might compare this “flex fuel” system to a hybrid car. While it is running on gasoline (glucose), the battery is getting recharged (fat storage), and this stored electrical energy is available to draw from once the gas is gone or the gas engine is off. Likewise, at night, when you are not eating, mitochondria draw on your “battery” power in the form of FFAs and/or ketones to create ATP.

Having the ability to use a full range of fuel sources offers a host of benefits. First, it means that when you stop eating at the end of the day, you don’t keel over—your body simply burns stored fuel. Second, it means that your brain, which is quite a glucose hog normally, can still function in the lean times too. In fact, you make ketones during “tough times” to keep your brain neurons alive, not for anything else. We will return to this subtle but very important point again and again. You make ketones for your brain neurons when glucose is running low. Unlike all other cells in our body (except red blood cells), our brain can’t use liberated free fatty acids to make energy (they literally cannot get into the brain easily and in a timely fashion), but it can use both ketones and butyrate, the latter made by your gut buddies, to make ATP.

Third, mitochondrial flexibility allows your energy system to accommodate periodic fluctuations in food source and availability. Think of your ancestors—the hunter­gatherers from whom you evolved. When they had a successful hunt or forage, perhaps after some tough and hungry days, they didn’t just have a nibble, they’d eat their fill. They learned to process a big influx of one kind of fuel—say the protein from wild game or a rush of carbohydrates from a wild berry bounty or beehive—and then, once that was finished, switch fuels on a dime and start burning stored fats in the lean times that inevitably followed. This skill set of metabolic flexibility is innate to your mitochondria’s design but can be lost when you consume refined and ultra­processed food too frequently — and worse, combine that with a sedentary lifestyle.

Returning your mitochondrial function to good working order is the key to restoring flexibility and making more energy.

Excerpted from The Energy Paradox: What to Do When Your Get-Up-and-Go Has Got Up and Gone, March 16, 2021. Harper Wave.
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