What's Wrong With The Low-Protein, Low-Leucine Approach to Life Extension?

by Nils Osmar. September 16, 2023
This post is not intended as, and should not be taken as, medical advice.
See full Medical Disclaimer

Dr. Valter Longo recently did an interview in which he reiterated his often-stated position that high protein diets will shorten lifespan. He used the opportunity to recommend his “longevity diet”, which is very high in carbohydrates and low in protein. It’s roughly based on a Mediterranean diet, but is lower in protein than most folks in the Mediterranean actually eat.

Contrary points of view

Longo’s approach has many adherents. But some prominent people in our community, like Dr. Peter Attia, Dr. Gabrielle Lyon, and Dr. Don Layman, take an opposite approach, pointing out the problems that can develop when we eat too little protein, including muscle wasting, a greater tendency toward dementia, and a poor immune response. Living longer will have little benefit if our minds, bones and muscles fail and we spend the last couple of decades in a decrepit state in a nursing home.

So who’s right?

Both “sides” are making valid points.

Dr, Longo is correct that in lab animals, high protein diets tend to be associated with shorten lifespan. Animals fed low protein and/or low leucine diets (sometimes) live significantly longer than their littermates fed “normal” diets.

This is because eating high protein (or high leucine) (or high calorie), (all) are associated with the over-activation of mTOR. Eating low protein does increase lifespan in many species of mice.

This comes at a cost, however. One is that muscle wasting is common on a very low-protein diet. Another is the eventual collapse of the immune system. Some strains of mice (though not all) do live up to 50% longer if their AMPK is activated almost full time by eating low calorie or low protein, because their aging is being slowed. But they would die in the wild very quickly; their long lives in the lab are only possible because they’re protected from exposure to disease.

Two pathways

mTOR (which is activated by high protein, animal-based diets and the amino acid leucine) is the growth pathway; AMPK is the longevity pathway. In a sense they’re like opposite ends of a teeter totter; when mTOR is “up”, AMPK is “down”, and vise versa. (This is a bit oversimplified, but is a summary of a general principle.)

Eating low protein or low leucine — and going plant based rather than animal based — is one possible way to shift into a high AMPK, low mTOR metabolic state, and it’s possible it could lead to longer lifespans in human beings, as it does in many animal species.

Even if this turns out to be true in people, though, it does not mean, though that we all need to eat low protein or low leucine diets. It’s a path toward longevity, but not the only path. If we choose to go in the opposite direction and eat more protein, more leucine, and/or more animal-based diets, we can still prevent the over-activation of mTOR by fasting (including intermittent fasting and time-restricted eating) … or taking rapamycin… or taking AMPK activators such as berberine. And we can do so without the risk of immune collapse and sarcopenia.

The low protein problem

I have deep respect for Dr. Longo’s research, and have done his “fasting mimicking diet” several times. I appreciate his insights into the profound benefits of fasting. But my experience runs contrary to his more general dietary recommendations.

When I ate a diet similar to the one Dr. Longo recommends — limiting myself to around 50 grams of protein, most of it plant-based — I did feel a bit more energy initially. But after a few days, I started feeling tired, and started rapidly losing muscle. And I started catching colds, which I hadn’t experienced for years.

It was a dreary reminder of what I experienced when I was vegan. I was sliding rapidly into sarcopenia. See the image on the left, showing me three years ago when I was 67 years old.

Adding protein and animal-based foods back into my diet helped me start building muscle

When I added more protein into my diet (see the second image) and resumed eating animal-based foods, this was reversed. I’m currently eating about 1 gram of protein per pound of body weight and have been continuing to build muscle… and I’ve gone back to never getting sick.

If I was sitting around gobbling up food (eating and snacking with no breaks) all day, I might be on a path to a shortened lifespan. But I’m not at all worried about my current approach shortening my life, because:

I take rapamycin (which suppresses mTOR and activates AMPK).
I take berberine (another AMPK activator)
I don’t eat all day. I do time restricted eating, which often involves fasting for most of the day. Fasting activates AMPK even more strongly than eating a low protein, low leucine diet. I’m fasting, meaning that my AMPK is activated, for 16-20 hours a day. My eating window, during which mTOR is activated, is usually around 4-8 hours.
My strategy is to activate mTOR strongly around mealtime, and activates AMPK the rest of the day.
I also do occasional 24 hour, 36 hour and 48 hour fasts, as well as several 72 hour and 96 hour fasts over the past few years.
Incidentally, many people following a meat-only diet, i.e., the carnivore diet, do something similar in one sense: they tend to eat only one meal a day and fast the rest of the time.
I’m not on a carnivore diet myself. But like them, I include meat in my diet. (Last night’s dinner was 1/3 pound of grass fed organic ground beef simmered for about an hour with some onions, garlic, carrots, celery, and mushrooms, and a little organic corn starch to make gravy.) (It came at the end of a day during which I was mostly fasting.) (i.e., I was switching between activating mTOR around mealtime and AMPK the rest of the time.) So I have zero concerns about shortening my life by strongly activating mTOR.
If the activation of AMPK is key to longevity, I suspect that they’ll live even longer than people on Longo’s “longevity” diet.

Not medical advice

This article is not intended as, and should not be taken as, medical advice. I’m not advising that people eat any particular diet or take any particular supplement(s), just reporting on what I’m doing. Supplements, like medications and other interventions, can have side effects; I would encourage people to research both possible benefits and side effects before starting on any supplementation regimen, and consult with a medical professional about any issues which might have a medical component. See full Medical Disclaimer

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