#41

Updated nuance, please see the whole thread. Bottom line it was intended as shorthand that the title “eating too much protein is bad for your arteries…” is misleading as the only “bad for your arteries” atherosclerosis data from this same group came from prior work in murine atherosclerosis models.
By contrast the study focusing on people showed macrophage activation, not definitive progression of atherosclerosis.

For interest, hope that helps: https://x.com/agingdoc1/status/1760994180262736155

Best wishes, Agingdoc

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#42

Sorry, but a bit of a clarification: do you mean if i eat 100g of animal protein i’ll be getting 25g of leucine? I might be eating more like 125-150g daily, mostly animal protein.

Since i eat a heavy animal protein diet and finally figured out a potential safe way to offset methionine, Leucine has now become the thing that stresses me out which likely reduces my longevity through worrying, regardless if leucine actually directly reduces longevity through the ASCVD mechanism as suggested.

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#43

I’m not arguing with you on this, and I’m not an expert on murine versus primate circulatory systems. And I’m eating a heavily animal protein diet and lifting heavily so I’m on a rrain that many of the longevity practitioners on this forum likely aren’t interested in. But when i look at elderly people, or in nursing homes, i don’t see any people who are “muscular”. This could be that muscularity wasnt a thing for that generation. Or it could be the the first generation of bodybuilders used exogenous compounds which ultimately impacted their longevity. Or it could simply be that muscularity is superfluous for longevity, potentially due to leucine levels.

Id very much like longevity and to see history unfold (i guess depending on the history). But id much prefer healthspan (after watching my father suffer decades slide into sarcopenia).

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#44

I would argue that muscular old people do not frequently live in nursing homes.

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#45

I agree. There is the possibility that bodybuilders are in good health. Or the possibility that they drop dead with great healthspan to the very end, like endurance athletes who possibly have stressed their vascular system over time and suffer CVD issues (heart attacks etc in particular). I’m on this train and hope I’m making the correct decision — i certainly am for healthspan. But i want to be reasonable and open-minded as to the potential consequences if i am wrong.

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#46

You must also consider that there aren’t many people who follow Attia’s advice of combining heavy exercise with apoB-controlling medications. Maybe that approach really is the best of both worlds and the only reason why we don’t see athlethes in their 130s is because it hasn’t been tried before.

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#47

Again, I’m with you. I also have high LDL which I’ll need to eventually deal with. I’m considering a PCSK9 inhibitor but haven’t dine it yet. I’m also strongly considering taking a course of nattokinase 1-2x per year to “clean out” my vascular system. I was also hoping fasting might help this but i havent seen specific research in this — its only a hope. And now i apparently need to worry that leucine is contributing to ASCVD. But if I’m able to manage this correctly, i should have good musculature (ie “strong” muscles able to lift lots of weight but not “high volume”/“vanity” muscles that look big but may not be as high quality.

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#48

I had a bit of epiphany several months ago after listening to Kaeberlein and Attia podcast diving deep in to M-tor pathways and watching Netflix “Secrets of the Blue Zones”.

Leucine (also Isoleucine and methionine) is a very potent M-tor activator. Like the above post mentioned, Blue Zones provide the best observation long term outcome “multiple case HUMAN study” that we have. Those people don’t eat a lot meat. Not that they don’t want to but it wasn’t as available or expensive. They consume dairy products in small amounts and eggs. But it seems like the majority of the protein comes from legumes and grains. Thus essentially they consume low amounts of leucine to keep the M-tor from “overactivating”. They also are probably doing bunch of things as well - like exercise through natural movement and farm work, eating lots of herbs, etc. Okinawans for example consume lots of natural genistein and EGCG - two supposed M-tor inhibitors.

Based on that conclusion I significantly reduced my animal protein and also tried confine the majority of leucine consumption to once a day. At this time my animal protein consists of collagen, bone broth (as a base for legume soups), non-fat organic greek yogurt, moderate amount sheep’s cheese, fish/shellfish 2-3/week, 2-3 eggs/week and rarely animal muscle meat. (I won’t go in to why those particular choices because that would require several paragraphs, but collagen/bone broth is relatively low in leucine).

When I came across the study above, it only validated what I was already doing. I am glad to see that study because frankly, I was questioning my diet for the past few weeks. Now I am rethinking my 1 gram per pound protein goal as maybe being too much. That’s about 150-160 grams of protein per day.

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#49

Which probably do not work at all in-vivo.
Tbh I am still not convinced that the Blue Zones observational trials does a good job of taking all cofounding variables into account. It’s difficult to assess whether their eating, sleeping, socializing or activity patterns are what keep them alive for so long or if they live so long for other reasons.
I can see the argument for high protein = high mTOR activity = higher cancer rates as we saw with some mice studies but then again, at which point does the risk outweigh the benefit? 1.6-2g per kg of body weight is ideal for muscle gain and maintainence but does that dose already significantly increase cancer risk compared to 1-1.2g per kg of body weight? Does it only matter if you’re overall in a calorie surplus? Given that rapamycin seems to work even when given intermittently at higher doses, is high mTOR bad if it’s followed by periods of very low mTOR activity? Like cleaning up after a gym session.

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#50

But then again, there is no real downside to eating Tempeh and drinking Matcha, is there?

I think the most compelling part of the Blue Zones, is that the longevity occurs in the different parts of the world and in different ethnicities. So the only thing you really have to focus on are similarities. Which is exactly what you listed. All those commonalities have been validated by many studies. There is probably nothing magical about Okinawa or Sardinia in itself. In fact a lot younger Okinawans adopting western diet suffer the same fate as Westerners.

I think I made pretty clear in my post that M-tor doesn’t have to be persistently suppressed, in fact if that was the case we would just evolve to get rid off it. Same as insulin by the way.

I use a bit higher protein goal since I use majority plant protein and “alternative” animal protein - so there is fudge factor there.

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#51

Do you have any idea what other reasons that could be?

Isn’t the optimum 1.2-1.7 grams of protein per kilogram of body weight per day and any greater than 1.5-1.6 grams wont offer much benefit in maintaining or building muscle? Bryan Johnson is right there with his Blueprint at around 100g of daily protein or around 1.3-1.4 g per kilogram and he is doing just great with his muscle mass.

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#52

My best guesses would be genetics (resistance to cancer, diabetes and plaque formation) and naturally higher activity levels due to environment which also forces older people who are unable to maintain them to move away.

Isn’t the optimum 1.2-1.7 grams of protein per kilogram of body weight per day and any greater than 1.5-1.6 grams wont offer much benefit in maintaining or building muscle?

Muscle gain peaks at 1.6g/kg but older people are recommended even higher doses.

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#53

From an evolutionary perspective, there might be the case of environment specific adaptations that are not so useful today. For example like CETP and PCSK9 so circulating LDL is high in case of famine. Or DHT is crucial in childhood development so shutting it off in adulthood isn’t an option evolutionary. Same can be true of mTOR.

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#54

Do you have a source for this?

Most athletes don’t exceed 1.2-1-7 grams. The bro science is different story.

But as @Dr.Bart already pointed out most young generations (same genetics) adopting different diets and lifestyles don’t life that long and are affected with same aliments and diseases as elsewhere out of the Blue Zones. But Blue Zone principles are really simple, eat not in excess, move a lot but again not in excess and have good social connections. Nothing magical.

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#55

Dr. Stanfield mentioned it in one of his videos.

#56

Maybe he qualifies as a bro scientist. :sweat_smile:

#57

He is currently the world’s greatest hope for a rapamycin trial in humans.

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#58

As discussed elsewhere on this forum this is perceived as a predatory / very bad journal and journal family.

Persistent Issues With the Journal Nutrients and Its Publisher MDPI

Multiple sources describe MDPI as a predatory publisher. Beall’s List of Potential Predatory Journals and Publishers has included MDPI. Additionally, in 2023, hundreds of MDPI journals, including Nutrients, were listed on the predatory publications list by Predatory Reports.

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#59

One can probably extrapolate the effects of persistent mTOR 1 & 2 pathways suppression from the side effects of immunosuppressive level of sirolimus dosing :
https://www.mayoclinic.org/drugs-supplements/sirolimus-oral-route/side-effects/drg-20068199

Although I suspect that non-activation is probably more favorable that inhibition. In biological systems these pathways are not simple on and off phenomena.

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#60

I am not so impressed by rapamycin honestly. SGLT2i seems much more interesting to me for some reason. Maybe because they work so well in clinical trials for different conditions, and of course have a lifespan benefit in mice as well.

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