Can protein breaks provoke too much autophagy?

Reader Arash raised the interesting question whether the intermittent dietary protein restriction used in protein breaks could cause excessive autophagy.   This is important because too much autophagy can kill cells in certain settings, like oxygen deprivation in the brain (cerebral ischemia).

Excess autophagy apparently does not occur with intermittent protein restriction, because autophagy is self-limiting in this circumstance.  Restricting dietary protein, which is made of amino acids, deactivates mammalian target of rapamycin complex 1 (mTORC1), leading to protein degradation in cells by autophagy, which frees up amino acids, leading to reactivation of mTORC1 and consequent inhibition of autophagy again.

Laing explains:

[I]ncreased intracellular free amino acids produced during autophagic degradation can reactivate the mTORC1 signaling and thus downregulate autophagy, serving as a self-limiting feedback loop in autophagy regulation. …

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Why take protein breaks?

This blog presents an idea that, based on current research, appears likely true and may save your life:

Taking intermittent “protein breaks,” when you eat very little or no protein for 2-4 consecutive days while eating plenty of carbohydrate, can slow aging and prevent, delay, or reverse — at least partially — many diseases including obesity, type 2 diabetes, autoimmune disorders, and brain diseases such as Alzheimer’s and Parkinson’s.

If you take protein breaks, you must follow each by a period of eating adequate amounts of protein.

This hypothesis awaits confirmation by randomized human clinical trials, but is consistent with prior studies in humans, other animals, and living cells.

Because no clinical trial has yet been done to establish the efficacy of protein breaks in humans, I cannot recommend them.  But I recommend you consider them with your doctor.