How to Induce Autophagy

Autophagy, from the Greek for “self-eating,” is one of the most basic and most essential processes for maintaining cellular homeostasis. Although you probably don’t think about yourself as an ambulatory collection of cells, that’s exactly what you are. Every second of the day, each of your cells is creating and using energy, communicating with other cells, relaying sensory information, churning out proteins, immune system components, and other chemicals, and doing all the other things that add up to you

That’s hard, busy, sometimes messy work. Things can go wrong. Parts wear out. Your cells need a way to keep themselves in tip-top shape by removing broken or dysfunctional parts, cleaning out clutter, and fending off attack from outside invaders. Enter autophagy. It’s cellular pruning, and it’s an important part of staving off the worst aspects of the aging process and allowing cells to operate normally. 

Interest in autophagy has really taken off. Whereas I mostly used to get questions about how to lose weight, get stronger, maybe improve digestion, now many people want to know about longevity and “maximizing” autophagy. Before getting into specific strategies, let me preface this by saying that the autophagy literature is anything but definitive. Most studies take place in yeast and mice, not humans. We don’t have tools to measure autophagy as it’s occurring in the human body. Most importantly, we don’t know what constitutes optimal levels of autophagy. While it’s generally true that autophagy is a beneficial and desirable process, there’s also plenty of evidence that dysfunctional autophagy contributes to the proliferation of cancer and other diseases.1

Rather than trying to maximize autophagy, it makes more sense to ask what otherwise healthy practices can also promote this important cellular housekeeping. Here are a few of my favorites.

Fasting for Autophagy

Fasting is by far the most effective lever we can pull in terms of upregulating autophagy, at least based on what we know now. Nutrient or energy deprivation trigger an increase in autophagy so that our cells can degrade and recycle old or broken cellular components to reuse for building blocks and energy. 

This was crucial for our ancestors’ survival through lean times. While I don’t think our paleolithic ancestors were miserable, wretched, perpetually starving creatures scuttling from one rare meal to the next—the fossil records show incredibly robust remains, with powerful bones, healthy teeth, and little sign of nutritional deficits—they also couldn’t stroll down to the local Whole Foods for a cart full of ingredients. Going without food from time to time was a fundamental aspect of life for most of human history. 

Consequently, not only are we well adapted to surviving periods of food shortage, we actually benefit from taking a break from eating once in a while. Good things happen when we fast, autophagy being high on the list. There are no definitive studies identifying ideal fasting guidelines for autophagy in humans, unfortunately. Longer fasts probably allow deeper levels of autophagy, but shorter fasts are no slouch. 

While I’m a big fan of intermittent fasting, not everyone shares my enthusiasm. For folks who don’t want to fast or for whom fasting is contraindicated, there are other ways to induce autophagy.

6 More Ways to Induce Autophagy Besides Fasting

Anything that puts the cell under stress should ramp up autophagy. Remember that stress isn’t always bad or maladaptive. Many forms of stress are hormetic, meaning they cause you to become stronger and more resilient in the face of future challenges. The following all operate under that principle.

1) Try keto

Low insulin and low blood sugar, both hallmarks of the fasted state, are two physiological markers that regulate autophagy. Ketogenic diets also reliably keep insulin and blood sugar down. A study in mice found that autophagy increases rapidly in the livers of mice eating a ketogenic diet.2 Groundbreaking research also suggests that ketone bodies activate metabolic pathways in the brain that trigger autophagy.3 Researchers postulate that this may be one reason why ketogenic diets have anti-neurodegenerative effects.4

2) Train regularly

AMPK is an enzyme whose chief role is to signal energy availability within the body. Anything that activates AMPK likely increases autophagy, along with all sorts of other longevity-promoting processes. Exercise is one such AMPK-stimulating activity. 

With exercise-related autophagy, the biggest effects are seen with lifelong training, not acute. In mice, for example, the mice who are subjected to lifelong exercise see the most autophagy-related benefits. In people, those who have played soccer (football) for their entire lives have far more autophagy-related markers of gene activity than people of the same age who have not trained their whole lives.5

3) Train hard

In studies of acute exercise-induced autophagy, the intensity of the exercise is the biggest predictor of autophagy—even more than whether the athletes are in the fed or fasted state.6

4) Drink coffee

At least in mice, both caffeinated and decaffeinated coffee induce autophagy in the liver, muscle tissue, and heart. This effect persists even when the coffee is given alongside ad libitum food. No fasting required.7 It’s possible that many of the benefits associated with coffee consumption—lower inflammation, less oxidative stress, lower rates of cancer risk, cognitive decline, and diabetes—are due, at least in part, to coffee stimulating autophagy.

5) Eat turmeric

Curcumin, the primary phytonutrient in turmeric, is especially effective at inducing autophagy in the mitochondria (mitophagy).8 In an in vitro study of lung adenocarcinoma (cancer) cells, the addition of curcumin increased AMPK activity and autophagy.9

6) Consume extra virgin olive oil

The anticancer potential of its main antioxidant, oleuropein, likely occurs via autophagy.10

Putting These Tips into Practice

Autophagy isn’t something that you can micromanage, so it’s also not worth stressing about. If you’re not currently a coffee drinker, you don’t have to start. But if you’re not regularly using extra virgin olive oil as a dressing, maybe give it a try.

The point is, rather than trying to eke out the most autophagy you can—something that might not be a great idea anyway—think about stacking healthy choices together with the goal of creating an all-around healthy Primal lifestyle: Eat a variety of foods that contain polyphenols. Get plenty of movement, including some high-intensity exercise once in a while. Consider trying a Keto Reset or dabble with intermittent fasting. Autophagy will happen naturally as part and parcel of these actions. 

What say you? Is autophagy on your radar as an important health goal, or do you consider it less important than other longevity factors? Let me know in the comments.

About the Author

Mark Sisson is the founder of Mark’s Daily Apple, godfather to the Primal food and lifestyle movement, and the New York Times bestselling author of The Keto Reset Diet. His latest book is Keto for Life, where he discusses how he combines the keto diet with a Primal lifestyle for optimal health and longevity. Mark is the author of numerous other books as well, including The Primal Blueprint, which was credited with turbocharging the growth of the primal/paleo movement back in 2009. After spending three decades researching and educating folks on why food is the key component to achieving and maintaining optimal wellness, Mark launched Primal Kitchen, a real-food company that creates Primal/paleo, keto, and Whole30-friendly kitchen staples.

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