How to Boost Autophagy with Fasting and Exercise

The most commonly cited inducer of autophagy is dietary restriction, which gives new meaning to term fasting “cleanse.” How long do you have to go without eating? It’s probably longer than you think. If you go online or read popular press on the subject, you might get the impression that you can boost autophagy by just skipping a meal here or there or narrowing your daily feeding window to lengthen your overnight fast. Even in the medical literature, you’ll read that autophagy is “rapidly upregulated as early as 30 min after access to nutrients has been limited and reaches a plateau of maximal activation around 4 to 6 hours post-starvation.” But that’s talking about rodent models or cells in a petri dish. 

Starve humans for four days, and we lose less than two percent of their body weight. Fast mice for just two days, and they lose a remarkable 20 percent of their body weight. That’s like people going without calories for a month. In humans, autophagy doesn’t really maximally ramp up until 24 to 48 hours of fasting, which is too long to go unsupervised. Fasting longer than 24 hours, and particularly three or more days, should only be done under the supervision of a physician and preferably in a live-in clinic. However, moderate dietary restriction over the long-term may also work. 

Muscle biopsies were taken from volunteers of the Calorie Restriction Society who maintained a body mass index of 19 (averaging about 130 pounds at 5’9”) by restricting their daily caloric intake for 3 to 15 years. Compared to muscle samples taken from control group volunteers, the muscles from the dietary restriction group expressed significantly higher levels of autophagy genes. However, the caloric restriction group also had healthier diets. 

The enzyme AMPK activates autophagy. So, anything that suppresses AMPK activation, like saturated fat intake, may also suppress autophagy. Palmitate is a type of saturated fat found in junk food and concentrated in meat and dairy. Inversely, the enzyme mTOR represses autophagy. So, anything that stimulates mTOR, like animal protein, may also suppress autophagy. So, the apparent lower levels of autophagy in the regular diet group compared to the Calorie Restriction Society members may have been a result of the quality of their diets rather than the quantity.

Dietary restriction has been called the “safest way” to stimulate autophagy, but that distinction probably belongs to exercise. In mice, 30 minutes of exercise increased autophagy levels by 40 percent and reached a maximum at 80 minutes. In people, it may take longer. Twenty minutes of cycling at about 50 percent VO2 max (half of maximal aerobic capacity) failed to induce autophagy, but 60 minutes at the same moderate intensity did. One study of 60 minutes of cycling at 70 percent VO2 max failed to show an effect, but this may be due to delayed timing of the post-exercise biopsies.

Overall, 60 minutes or greater of moderate to vigorous aerobic exercise is recommended to stimulate autophagy. High-intensity interval training—interspersing moderate cycling with 30-second sprints (followed by rests to keep the overall power output the same) didn’t seem to make a difference, and there are insufficient data to characterize the autophagy response to resistance exercise.