AMPK and mTOR: How Often Can We Make the Switch?

by Nils Osmar. April 15, 2022

In his book about mTOR and AMPK called “The Switch“, James Clement writes about the possible benefits of switching from one of these key metabolic states to the other.

AMPK can be triggered by fasting, which also activates autophagy (the deep cleaning of our cells) and (if the fast goes on for three days or more) apoptosis (the removal of senescent cells from our bodies). (See article: AMPK Activation of Muscle Autophagy ) The longer we fast, the more deeply our AMPK is activated, and the deeper our autophagy and apoptosis.

AMPK and Life Extension

Lab animals who are kept in a state of AMPK activation, either by being fasted or being fed diets low in leucine or calories, often have unusually long lifespans, sometimes living up to 50 percent longer than their litter-mates.

mTOR is associated with growth, which can be good or bad, depending on what’s growing, It supports the growth of muscle and a robust immune response, but can also support the growth of cancer under some circumstances.

When AMPK is switched “on”, mTOR is usually switched “off”, and vise versa. Current research suggests that if we want to live long lives, AMPK should be activated most of the time.

Both Are Important

mTOR can be thought of almost like a fire. It isn’t “bad”. It just shouldn’t be allowed to burn out of control. We need some mTOR activation to maintain and build muscle mass as we age, prevent sarcopenia, and support our immune health. See article: “mTOR as a Key Regulator in Maintaining Skeletal Muscle Mass“

But we need breaks from mTOR so that autophagy, apoptosis, and AMPK can become activated.

Clement suggests that it’s good to have AMPK activated (and mTOR switched off) about 3/4ths of the time. One way to do this would be to eat fewer calories. People who follow the CRON diet, “Caloric Restriction with Optimal Nutrition”, follow largely plant-based diets. (See article: “The ups and downs of caloric restriction and fasting: from molecular effects to clinical application“)

So we might try eating CRON diets nine months out of the year, as he suggests. then eat higher calorie, higher leucine, more animal-based diets the other three months.

We Can Also Make the Switch Weekly…

Another approach could be to segue between AMPK and mTOR once a week You might eat a plant based diet four or five days a week, then eat mostly animal foods the other two or three days.

…Or Daily

Another would be to make the switch daily. This study suggests that when we eat a high protein, high leucine meal, mTOR is fully activated (which usually has the side effect of switching AMPK off) within 3 hours. (See study: Leucine-Enriched Nutrients and the Regulation of mTOR Signalling and Human Skeletal Muscle Protein Synthesis)

We know that AMPK is activated in the morning after fasting. So the transition from mTOR to AMPK activation and back again can be made at least once within a 24 hour period.

The Trick is the Timing

Since AMPK is “on” when we wake up in the morning because in a fasted state (assuming that we didn’t get up in the middle of the night to gobble up some food) our actions shortly after waking can determine whether the AMPK activation continues or ends.

One way to continue it so would be to fast for a while after we get up, by postponing or skipping breakfast. If we don’t eat till noon, we’ll have extended our period of fasting, which moves us into autophagy, ketosis and AMPK activation, from 12 to 17 hours.

Another approach, which should in theory work just as well, would be to go ahead and eat in the morning, but choose foods which don’t activate mTOR. This is easy; we just need to eat foods very low in protein and carbohydrates. (Fats don’t trigger the activation of mTOR or AMPK; protein and carbs are what we need to be aware of).

For Example…

I got up at 5:30 this morning, had a glass of water, then had a cup of coffee. Coffee is an AMPK activator and promotes autophagy. So far so good.
I work out three days a week. Today’s a non-workout day. So I didn’t have to think about coordinating anything with my workout schedule.
I sometimes fast until noon or 1 pm (or even fast all day). But today, at 9 a.m, I had breakfast: a vegan smoothie I call a Fasting-Mimicking Smoothie (recipe here). The main ingredients are avocado, tomato, and a very low protein, very low carbohydrate green powder (which also gives me five or six servings of vegetables) plus some sea buckthorn berry powder (an AMPK activator which supports stem cell differentiation).
I also ate some olives and munched on a couple of baby carrots.
This breakfast gave me a nice infusion of nutrients, including a high dose of oleic acid (a sirtuin gene activator found in both olives and avocados). But it had only a few grams of protein, all from plant sources, and only a few grams of carbs, and the foods were all low-glycemic, so there was little risk of it taking me out of ANMK activation, autophagy or ketosis.

Time Your Supplements

I took my NMN boosters and sirtuin activators along with it:

HealthThroughNutrition PQQ (20 mg)
Jarrow CoQ10 (200 mg)
DoNotAge NMN (1.5 grams)
DoNotAge NR (0.5 grams)
DoNotAge SIRT6 Activator (3 capsules)
DoNotAge Resveratrol (500 mg)
Parsley or apigenin (500 mg)

Some of them raise NMN; all of them are AMPK activators and support autophagy.

Then Switch on mTOR at Lunchtime

Around noon or 1 pm, I’ll have a meal with some plant and animal protein (leaning into animal-based foods for this meal). For example, I might have:

A big green salad along with some lentil or bean soup along with some sardines, chicken or tuna.
Scrambled eggs with sardines or anchovies and broccoli and tomatoes. seasoned with onions, garlic, rosemary,
Grass-fed organic ground beef with broccoli and tomatoes and a big green salad on the side, seasoned with onions, garlic and rosemary.

All of these contain animal-based foods and are high in protein and rich in leucine, because I want to activate mTOR with this meal and shut off AMPK. I want the growth pathways activated. So I also take my testosterone boosters and hGH boosters with this meal.

Around 6 or 7, I might eat a meal that’s more plant-based and lower in animal-based foods, and take an AMPK activator such as berberine or benfotiamine along with it. Then I usually fast again till the next morning. So my AMPk and mTOR activation would look like this (blue is AMPK). If I wanted to dampen the mTOR activation further, I could choose more plant-based food, or just eat one meal a day. Then the image would be even more blue.