I don’t think chronic mtor activation is an inherent feature of protein intake, provided you’re active, you’re not constantly eating, and you don’t have low-grade inflammation to begin with.
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Can you point to anything she said that was wrong in the podcast?
This is a good article, which supports the “more is better, with diminishing returns” results on protein intake in general
mccoy
#103
You took the right decision. I just went on, but this is, unfortunately, one of the worst episodes of the Drive, and not just because of the protein bias, there was little actionable advise beyond the protein maximization suggestions we already know. They turned out also to be unreasonably biased against the epidemiological studies. Besides that, I strongly criticize the reductionism to chemistry of the guest, and his hostility about the definition of processed foods, stating that everything we eat is processed (and missing the real point of the definition).
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Not accurate: they said that if you’re obese and trying to lose weight, it makes more sense to base your consumption on your target weight. If you’re 300 lbs, and want to get down to 220, consume the amount of protein for someone that is 220.
I didn’t hear that, but in terms of percentage of gains, it’s probably the same. But since you’ve already lost a lot of muscle by that time, the absolute muscle gain is much smaller. So, not so good news.
Exercise is absolutely necessary, but If you’re lifting without adequate intake of protein, then you run the risk of further reducing lean mass, or just spinning your wheels.
There are many studies that show that sarcopenia can be reversed with resistance training and protein intake, the fact that many people suffer sarcopenia tells me that one of the causes could well be lack of protein and resitance training. I could point you to 5-10, if needed.
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Beth
#105
Thx for adding feedback.
You are correct that she did say that is the practical way for most people to do it, but this is the part of the video where she said it’s ‘ideally’ based on lean mass with dexa. (My first YouTube clip. Old dog, new trick and all!) It was a super quick comment and easy to miss. I was surprised, and excited (protein is a PIA for me:), so it jumped out at me! This means that it would be hard to only hit the RDA, at least for anyone I personally know.
I went to my dexa and figured out what I need, and according to lean mass, I very often get the 2 grams per kg, I almost always get 1.6, and my worst day might be 1.2. And I’m vegan!
If she is correct, and someone has now shared a paper with me, so it seems she is, and Attia didn’t correct her, so I feel it’s ok to now reduce my protein intake even more because I’m way overshooting the 1.6 most of the time.
Thx, I do understand protein and resistance training helps with sarcopenia. What I was trying to say is I only hear that most people are already consuming much more protein than the RDA without trying, so it ‘seems’ to me the issue to avoid sarcopenia is resistance training and not so much protein … but if you have seen many studies where people are only hitting the RDA, I do believe you.
I do realize if one is much much much older and perhaps in poor heath, yeah, then you are probably not eating enough protein, or even calories for that matter. You don’t see a lot of chubby 95 year olds running around.
I welcome any more thoughts because I’m still learning and it’s very interesting to me.
@mccoy Yeah, I got the feeling that dismissive response to ultra processed foods was in defense of his protein bar… especially because he was so condescending about certain people writing in their substacks
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Davin8r
#106
It could be considered chronic if repeated multiple times daily, just like spiking blood sugar once may not be a major problem, but spiking it repeatedly throughout the day becomes more of the definition of chronic IMO.
What I’m not clear on is how much mTOR is activated in other tissues from a 20-30g protein bolus. If it’s mainly just happening in muscle, then it maybe it doesn’t negatively affect the overall aging process. When this question came up, they didn’t answer it effectively at all.
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Your best bet is to avoid eating then, since eating is anabolic. Or sleep more, since we don’t ingest anything when sleeping.
I don’t think spikes at the issue, it is chronic elevation that is. Exercise spikes mtor too, but it would be foolish to avoid it.
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mccoy
#108
That is basically the explanation of the reason of his protein maximization scheme; no longer optimization, like he used to propose 10 years ago. He seems to want to bypass the hunger problem by proposing protein shakes. But for people who exhibit a frugal phenotype, even a single protein shake may constitute almost a full meal.
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mccoy
#109
This is an interesting aspect. Sure thing, and this observation is coming from the bodybuilding arena, mTOR seems to become insensitive to leucine after a certain threshold.
I also remember Dave Sabatini, probably the man in the world who knows mTOR better, saying that chronic overamplification of mTOR does not happen in normal conditions but only in some cancer pathologies. I’ll see if I can retrieve the exact sentence.
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Davin8r
#110
What a lame attempt at creating a straw man. We’re talking about high protein intake and excessive mTOR stimulation and health outcomes, not avoiding anything/everything anabolic. If you don’t understand nuance and just want to be insulting, you should probably hang out on Reddit instead of a serious discussion forum like rapanews.
Davin8r
#111
mTOR activity increases for up to several hours after a high protein meal. 2-3 hours x 3 meals/day is anywhere from 6-9 hours per day. Increase that to 10-15 hours/day for those who are eating 5 meals. So where do we draw the line between acute vs chronic?
mccoy
#112
I tried to interrogate GPT5 with reference to Sabatini’s statement, and the result is interesting. Chronic overamplification is a pathological state, but modest chronic elevation of activity with age and overnutrition may accelerate the aging process. The model of a continuum appears to be sensible.
This is the summary for those who are in a hurry.
### Short synthesis and practical takeaways
*** Sabatini’s statement is logically and empirically grounded: malignant, mutation‑driven chronic overactivation of mTOR is principally a cancer phenomenon; normal tissues show regulated, often episodic activation, and chronic high‑amplitude activation without genetic/pathologic drivers is uncommon1 (probability statement above).**
*** Nevertheless, modest sustained upregulation of mTOR signalling in ageing and overnutrition is real and biologically important for healthspan; it is not the same as the oncogenic, cell‑autonomous activation seen in cancer but is a plausible target for nutritional, behavioural and carefully dosed pharmacologic interventions (probability of contribution to ageing phenotypes ≈ 40–70%).**
*** Practical interpretation: avoid conflating “no chronic overactivation in normal life” with “mTOR irrelevant to ageing”; instead recognise a spectrum from transient physiological pulses → chronic modest elevation in ageing/metabolic disease → oncogenic constitutive activation in cancer, each requiring different strategies and risk‑benefit calculus.**
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Davin8r
#113
OpenEvidence certainly doesn’t mince words, but at the same time I’m remembering what Attia said in the Rhonda Patrick interview, which was basically “show me the human studies proving adverse effects of high protein intake”.
"What are the potential adverse effects of high protein intake on non-muscle tissues, specifically as it relates to mTOR activation?
High protein intake can lead to chronic activation of the mechanistic target of rapamycin complex 1 (mTORC1) in non-muscle tissues, which is associated with several potential adverse effects, including increased risk of metabolic diseases (such as insulin resistance and type 2 diabetes), organ hypertrophy, cancer, neurodegenerative disorders, and accelerated aging.
mTORC1 is a central nutrient sensor that integrates amino acid signals, particularly from branched-chain amino acids and methionine, to regulate cell growth, metabolism, and autophagy across various tissues.[1-2] Chronic overactivation of mTORC1 due to excessive protein or amino acid intake can disrupt metabolic homeostasis. For example, persistent mTORC1 activation in the liver is linked to hepatocellular injury and carcinogenesis.[3] In the kidney, high protein intake can drive mTORC1-mediated renal hypertrophy and dysfunction, and dietary protein restriction or mTORC1 inhibition can attenuate these effects.[4-6]
Metabolic consequences include insulin resistance and increased risk of type 2 diabetes, likely due to mTORC1-induced degradation of insulin receptor substrate proteins and impaired insulin signaling.[7] Additionally, mTORC1 overactivation is implicated in the pathogenesis of obesity, cancer, and neurodegenerative diseases, as it promotes anabolic processes and suppresses autophagy, leading to accumulation of damaged proteins and organelles.[1-2][8]
Organ hypertrophy (e.g., heart, kidney, spleen) has been observed in animal models with chronically elevated amino acid levels and mTORC1 activation, and these effects are reversible with mTORC1 inhibition.[5] The effects are tissue-specific and may not uniformly affect all organs.
In summary, chronic high protein intake can overactivate mTORC1 in non-muscle tissues, contributing to metabolic, oncogenic, and degenerative pathologies.[1-3][5-8]"
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mccoy
#114
I’ve done an interesting experiment, letting two AI’s debate between themselves. I simply asked GPT5 to read the answer of Openevidence and judge.The main drawback apparently is that there is not decisive evidence from human trials. Maybe this is what Attia meant by absence of evidence, but perhaps he should have said ‘absence of overwhelming evidence’, and that doesn’t mean evidence of absence.
Short answer (probabilistic)
There is strong, consistent experimental and mechanistic evidence that high amino‑acid exposure can activate mTORC1 in many non‑muscle tissues and produce pathological changes in animals and cellular systems (probability ≈ 85–95%). Translating that to humans, however, the evidence that routine high dietary protein in free‑living adults causes clinically meaningful increases in rates of insulin resistance, organ hypertrophy, cancer or accelerated ageing is much weaker and more context‑dependent (probability of a clear, generalisable harmful effect in typical older adults ≈ 20–40%). Uncertainty is moderate‑high because animal/cellular mechanisms are compelling but human outcomes data are heterogeneous, confounded and limited in causal RCTs.
Davin8r
#115
So it seems we absolutely have mechanistic reasons to believe that higher protein intake may not be optimal for long-term health (even as it maximizes muscle growth/preservation from resistance training), but showing evidence of actual harm in the real world is more challenging with the limitations of epidemiologic evidence using dietary recall data from free-living adults with so many potential confounding variables. And mechanistic data doesn’t always translate into real-world effects, or even if it does, the effect size may be very small.
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Even if more protein intake results in higher cancer incidences in the real world, does that outweigh the positive effect on sarcopenia and infections? The net effect is most important.
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mccoy
#117
Barring the extreme cases of sarcopenia and infections, which would by themselves grant a specific strategy, the answer is not known and probably is different for every single subgroup of individuals. That’s why we should probably seek an optimization in the intake of protein rather than a maximization as reiterated by Peter Attia and others.
There are a few ways to estimate the optimum regime, basically, after having obtained what we consider a sufficient degree of muscularity, we should decrease the amount of protein (all other things being equal) until we see that we are losing bicep and thigh diameter (using appendicular muscle mass as a proxy for whole body muscle mass). The above constitutes and optimization. Of course, maximization, like Peter Attia says, is far simpler than optimization. In my opinion, Dr. Attia errs in two important aspects:
- Maximization for some people, the frugal ones, may be impossible or very distressing hence harmful
- The muscle-centric hypothesis is far from being proved. Where is the evidence that elevated protein may be harmful to human beings? All right, but…where is the evidence that prioritizing muscle mass increases longevity?
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So basically you are suggesting a min-max approach of minimizing protein intake while maximizing muscle mass. 1.2g/kg (lean mass/total mass(?)) of protein appears to be ideal for maintenance. Given a person weighing 80kg, that is roughly 100g of protein per day or 410 calories which makes up about 15-20% of a person’s daily calorie intake.
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mccoy
#119
Basically, yes, keeping protein as low as possible while keeping musculature as high as (practically and functionally) possible. The grams should be calculated per kg of ideal mass, which is a very approximate concept, but I would say what the reference mass would be at about 12% of adiposity.
It is hard to specify an exact number, because of many other parameters influencing muscle tissue mainteinance. In my case, for example, I’ve noticed that the glucose signal is as much if not more potent than the amminoacid/protein signal in activating muscle tissue growth. Also, lots of aerobic exercise decreases the energy input, increasing the AMPK and consequently pulling the brake on mTOR. The DIAAS index of protein composition and digestibility is very important and last the utilization of protein is different in different individuals. In fact, it has been shown that protein requirement is a random variable and not a constant number.
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