Anabolic Fasting vs. Autophagy Diet: A Clash of Health Fads

[01dragonslayer]

Many people that follow intermittent fasting argue that it increases longevity by inducing autophagy. Lo and behold, this has led to the coining of terms like "autophagy diet" and "autophagy fasting" that are frequently employed to lure the general population into health fads. Then there's the "anabolic fasting" diet, which is completely at odds with the concept of intermittent fasting as a trigger of autophagy (we'll discuss this in more detail below).

Autophagy is exceedingly complex from a physiological perspective; it's not the usual "on-off" switch that self-professed fitness gurus portray it to be. Frankly, most cellular metabolic processes are controlled by a dimmer switch instead of being turned completely on or off at any given time.

So before you jump on the fasting bandwagon in hopes of living until you're 150, let's get you up to speed on what autophagy means, how it works, and the factors that play a role in the autophagic process.

What Is Autophagy?​

The term autophagy literally means "self-eating" and is used to describe the homeostatic "cleansing" of cellular materials such as mutant proteins, dysfunctional organelles, and other cytoplasmic components [1]. Since autophagy is an essential life-sustaining activity in cells, it is implicated in various health conditions, notably neurodegenerative diseases and cancer.

Some people like to use the analogy of autophagy being like a garbage truck coming around to pick up the trash every so often. This comparison is accurate, to an extent (autophagy is more akin to recycling than it is trash removal).

But consider what happens when the garbage/recycling truck misses its weekly collection? Things start to pile up, right? The same thing happens in your cells when autophagy is inhibited. Cellular "waste" in the form of faulty proteins and organelles accumulates, throwing off homeostasis.

Over time, those faulty cell components can manifest disease and expedite the aging process [2]. Hence, autophagy needs to keep up with the trash-collecting demands of cells to maintain basal conditions.

The good news is that autophagy is a constitutive process in cells, meaning it's always "active" in the background at varying degrees [3]. When someone claims they fast to induce autophagy, they're really arguing that so many hours of calorie restriction turns the autophagy dimmer switch up a bit.

But eating doesn't all of a sudden turn the autophagy switch "off" in cells. In fact, some nutrients, like trehalose (a sugar), induce autophagy [4]. Likewise, various drugs and hormones can influence autophagy. Distinct sex steroid profiles are ostensibly why males and females exhibit different levels of autophagy [5].

SIGNS OF AUTOPHAGY​

Unless you have a very sophisticated microscope, there is no practical way of observing the signs of autophagy with the naked eye. Even if you're an intermittent fasting enthusiast, autophagy is not palpable or conspicuous on the surface.

But tumor progression, or lack thereof, could be considered a marker of autophagy (though an ambiguous one). Since dysregulated autophagy may precede diseases like cancer and Alzheimer's disease, you might argue that such conditions are readily observable "signs of autophagy," albeit not very precise.

On a molecular level, signs of autophagy may include an increase in autophagic vacuoles (autophagosomes) within the cytosol of cells, a reduction of mitochondria and other organelles, or enhanced clearance of mutant proteins [6].

Researchers often use a fluorescent protein fused to molecules that are known to associate with the membrane of autophagosomes, namely microtubule-associated protein 1 light chain 3 (LC3) and sequestosome 1 (p62) [7]. When placed under a fluorescent microscope, these molecules allow scientists to view signs of autophagy on a cellular level.

Does Intermittent Fasting Induce Autophagy?​

It's been known for some time that many organisms regularly undergo periods of nutrient deprivation (i.e. fasting) as a means of maintaining their fitness and longevity. Research suggests that this practice of intermittent fasting benefits the host by inducing autophagy and "cleaning out" its cells [8].

The increase in autophagic activity from fasting appears to be pronounced by the 24-hour mark, reaching its peak around 48 hours. Thereafter, it's likely that autophagy is actually inhibited through a survival mechanism as the body becomes completely starved.

Indeed, research has shown that intermittent fasting/nutrient deprivation increases autophagy but not the expression of genes that control autophagy [9]. Naturally, this means recurring fasts are necessary to trigger marked increases in autophagy.

But remember, autophagy is a constitutive cell process that is always somewhat active in the background; calorie restriction and acute fasting transiently enhance that background noise.

Things get even more convoluted when you factor in the typically nonspecific nature of autophagy and variance between different body tissues. For example, the brain is considered a "metabolically privileged" organ; the body will preferentially use its own resources (e.g. catabolize peripheral tissues) to supply energy to the brain when you fast.

HOW DOES FASTING TRIGGER AUTOPHAGY?​

Research has uncovered several cellular pathways that regulate autophagy (10). Trying to detail each of them and their integration into health and longevity is beyond the scope of this article, so we will focus on what appears to be the primary impetus of autophagy: mTOR inhibition.

mTOR is the acronym for a protein kinase (read: enzyme) called the mechanistic target of rapamycin, which was coincidentally named after observations that the drug rapamycin inhibits this enzyme. As an essential energy-sensing enzyme, mTOR is the veritable "gatekeeper" of anabolic processes in cells. Fitness enthusiasts are likely familiar with mTOR as the "master regulator" of muscle protein synthesis [11].

Intuitively, inhibiting mTOR means your cells aren't going to be building much of anything, including muscle proteins.

So, why does fasting inhibit mTOR?

Since mTOR is an energy-sensing molecule, and the point of fasting is to deprive cells of energy (calories from nutrients), fasting effectively blunts mTOR and its effector molecules [12]. Another energy-sensing molecule, adenosine monophosphate-activated protein kinase (AMPK), is activated during caloric restriction, which directly inhibits mTOR pathways [13].

AMPK is great for burning body fat and inducing autophagy but not so great for building muscle and other lean tissues (e.g. bone and skin). Hence, extensive fasting is not anabolic; it's the complete opposite: catabolic.

"Anabolic Fasting": A Cellular Contradiction​

The seesaw-like interplay between AMPK and mTOR infers that "anabolic fasting" is a biological contradiction. The very reason fasting increases autophagy is because of the former's catabolic nature.

If you regularly fast to induce autophagy, be mindful that you're not going to be building muscle during that time. It should be fairly intuitive that your cells are not prioritizing anabolic processes when energy (calories) are scant. You can't "have your cake and eat it, too" when it comes to diets that incorporate fasts.

Still, that doesn't stop fitness "influencers" from repurposing conventional intermittent fasting approaches under the guise of silly monikers like "anabolic fasting" and "autophagy fasting." It's disappointing that these alleged health "experts" paint a black-and-white picture of the human body when promoting their spin on trendy diets — most of which are already circumspect from a scientific standpoint.

To be fair, autophagy is essential for maintaining muscle mass and reducing muscle protein breakdown during a fast. But as we will discuss in the next section, more autophagy doesn't always translate to more health benefits.

Is Autophagy a Wholly "Good" Process?​

Whether you fast daily or not, your cells exhibit autophagy. And if you're in good health, odds are you don't need "more" autophagy; more isn't necessarily better just because something is generally "good."

Autophagy may be "good" by virtue of its role in cellular housekeeping, but as with most things in the body, excess autophagy comes with its own ramifications, even muscle atrophy (loss). Cells need a proper balance of autophagic flux to stay healthy and robust.

Too much autophagy perturbs cellular homeostasis by removing necessary components for normal biological activity; too little autophagy also disrupts homeostasis by allowing dysfunctional cellular components/damaged proteins to accumulate. In either scenario, the risk of disease increases.

Should You Fast Regularly for Healthy Aging?​

The presumed benefits of increasing autophagy via intermittent fasting are consistently exaggerated in health and fitness subcultures. There is a paucity of research in humans on fasting's effects on lifespan (aging), and extrapolating data from microorganisms like yeast is a bit irrational.

Now, that's not to say you shouldn't fast if it suits your lifestyle, nor that the benefits of intermittent fasting are bogus. Fasting may be an effective strategy for certain subpopulations, particularly those who struggle to lose weight by eating frequent, small meals throughout the day.

In that sense, fasting is a tool for self-control on a calorie-restricted diet. But calorie restriction, not the fasting component, likely accounts for the longevity benefits of such meal patterns [14].