#1

Consuming too much protein–specifically the amino acid leucine–can activate the mTOR pathway, leading to athersclerosis and heart disease. The piece includes a good paragraph on how microphages arrive to chomp on the sclerotic material, inadvertently take in too much leucine, triggering their own mTOR path, which kills them.

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#2

Yes. And experiments show isoleucine and methionine restriction extends lifespan with an effect size competitive with the best interventions. This may be where the benefit of caloric restriction comes from.

Both are called “essential” because the body doesn’t produce them. But perhaps that is a misnomer.

Notably plant proteins are generally lower in these. Though tofu has a significant amount.

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#3

This article, published last year in “nature metabolism”, supports the position on limiting protein intake for longevity:

Identification of a leucine-mediated threshold effect governing macrophage mTOR signalling and cardiovascular risk | Nature Metabolism

This all seems pretty straight forward if you are in your 30s or 40s. However, at age 72 I struggle to balance this advice with the desired to avoid sarcopenia.

Part of my daily regimen is a whey & collagen protein shake that includes about 25 grams of protein from the whey. Is this too much?

I’m considering continuing the collagen part daily but reducing the whey part to a couple times a week after exercise.

What do you think?

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#4

I think your strategy is fine. A slight bias towards higher protein after 50 or 60 seems like a good idea as sarcopenia is a big issue and I’d personally trade off a slightly shorter lifespan for higher quality and more activity during the last 20 years of my life.

This is a personal decision I think (the trade-off on more or less protein) and you’ll see plenty of cases being made pro and con, and if you’re also taking rapamycin you’re lowering mTOR anyway (whether you’re eating protein or not).

The cardiovascular risks (broadly speaking as we get older) are the key concern, so I would keep a strong focus on keeping APOB as low as possible: 心血管健康

From the paper you cite:

High protein intake is common in western societies and is often promoted as part of a healthy lifestyle; however, amino-acid-mediated mammalian target of rapamycin (mTOR) signalling in macrophages has been implicated in the pathogenesis of ischaemic cardiovascular disease. In a series of clinical studies on male and female participants (NCT03946774 and NCT03994367) that involved graded amounts of protein ingestion together with detailed plasma amino acid analysis and human monocyte/macrophage experiments, we identify leucine as the key activator of mTOR signalling in macrophages. We describe a threshold effect of high protein intake and circulating leucine on monocytes/macrophages wherein only protein in excess of ∼25 g per meal induces mTOR activation and functional effects. By designing specific diets modified in protein and leucine content representative of the intake in the general population, we confirm this threshold effect in mouse models and find ingestion of protein in excess of ∼22% of dietary energy requirements drives atherosclerosis in male mice. These data demonstrate a mechanistic basis for the adverse impact of excessive dietary protein on cardiovascular risk.

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#5

It’s a confusing topic, indeed! I will say that even Valter Longo, who is an advocate for lower protein, says after age 60-ish you should add more.

EDIT: I recommend everyone enter what they eat for a few days into the free website Cronometer. It will give you a very good idea of how much protein you are actually consuming. Most people forget that even veggies contribute. That might help guide you on if you need protein shakes. As a WFPB person, I do.

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#6

Yes, In the recent Attia and Kaeberlien Longevity podcast they say in food it is protein and then calories as your focus. At one time Attia was not so gung ho-ish on protein, now he is fixated on this now. Lol

Past 8 years plus, since I was 59 years - now almost 67 years, I eat a pound of steak every other day and feel great - muscles great - gut health great. Calcium and Plaque at zero - heart of a person under 35 years. If your genetics like it - mine are of North European… go for it.

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#7

I would emphasize determining your tendency to form plaque by taking a coronary calcium scan which will indicate your propensity to form arterial plaque. It is a quick low dose CT scan with no dye. My lipid numbers were great until my mid 60s, yet a scan showed I have a, presumed genetic, tendency to form plaque. If I could have a do over, I’d test at the age of 40. Even if no plaque (score 0) I’d test again at 50. Repeat each decade until you have a plaque score that indicates starting a statin or other drug to reduce your APOB to a very low number < 50 or lower — after starting the statin the test does not provide further useful information. Lp(a) is an independent risk factor and is measured by a simple blood test. I too happen to have Northern European heritage — there is significant genetic variation in cardiovascular disease propensity in every ethnic group. But if you test early enough to catch an incipient problem this is a major killer that you can easily treat and very likely prevent.

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#8

I agree this is the best way with our current understanding. Just low isoleucine and/or methionine, but normal/high in the rest. You got the best of both worlds.

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#9

Isn’t it rather leucine that flips on mTOR pathway in macrophages stopping them from eating plaque in arteries?

https://www.nature.com/articles/s42255-024-00984-2

#10

Sadly, I can’t enter the full study but my first thoughts were:

  • we already knew leucine is the most potent driver of mTor. And you need mTor for daily survival.
  • in mice, the aminoacids that gives life extension is the restriction of isoleucine and methionine, not leucine.
  • maybe a side effect of too much leucine is artheroesclerosis, but I wouldn’t follow a lifestyle change based on a weak link (for now :slight_smile: ). I prefer focusing on blood pressure and normal lipids and wait for the big guns to be developed.

What do you think?

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#11

Powe, this is so well said.

I don’t know how often one should get a CAC, but I do think everyone should at least get a couple, just as I think everyone should wear a cgm for at least for two weeks.

My story…
I had a CAC in my early 40s and the number was crazy high. I did it again a few years later at my husband’s urging with his hopeful thinking that maybe I was just too young and I was being compared to other 40 year olds who would have little or no plaque at that age. It was then much worse. The cardiologist said these lovely words… “it’s not if you will have a heart attack, it’s when”. :slight_smile: (I’ve since had some docs say not necessarily).

Then when I moved here at almost 50, my new doc insisted I repeat a CAC when he was doing my executive physical because he was sure those other scores were mistakes because I don’t look like a heart attack on a stick (I should have said no, but I acquiesced). And it was worse, once again. He held my hand and said it’s not your fault… it was sweet, but I already knew this. The new cardiologist said please never do one again, we know everything we need to know.

So, even though I started out with a bunch of plaque, even within 10 years, my numbers were growing, so anyone can be fine and then look completely different at their next one.

My older sis and brother just did theirs, and while they appear to be extremely healthy and have great diets, their numbers were each high 300’s. Oh, to only be in the 300s :slight_smile:

My husband, who was used to be huge red meat eater, had a CAC of 0. Instead of a new CAC he is doing the Cleerly test in a couple of weeks to see if anything in him has changed over the years.

Having said all of that, @Agetron is a genetic freak and will outlive us all :slight_smile:

#genesmatter

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#12

I try cycle them all: Leu, Ile, Met (from eating fish) balanced with Gly on anabolic exercise days (mTOR, IGF-1 days), and cut them a day before fasting and Rapa/Acarbose dosing to a few days after.
The personal cycle length balancing autophagy but slow wound healing (worsening that from diabetes) against muscle gain but inflammatory reaction (from rheumatism) is the hard part.

#13

I only know of mice lifespan studies with isoleucine and methionine. Maybe leucine itself has just not been tested that way yet? It does seem like leucine restriction could be good too.

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#14

Thanks Beth, tbh, longevity runs on my father’s Scottish side and mother’s Czech side. No medications at all and no supplements at all. Perhaps I won the lottery with Scottish/Czech combination. Genetics could also explain why I seem to be a rapamycin super-responder.

I concur on at least starting with a Cornary Calcium Scan - easy-peasy. It was MAC on this site who said you might look great on the outside - but you better check under the hood. At 64-years, when my score was zero - I was a bit perplexed too. I expected something statistically based on age alone I should have a 3. Which is why 2-years later a few months ago at 66 years - I did it again - because I didn’t believe the results! Once again score was zero. At my age now it should be minimal of a 6. Still holding on to zero. Let’s see in 2 more years.

My family lineage on both sides has never experienced cancers or heart issues. All huge meat and potatoes eaters. Let’s see how it goes.

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#15

Any binary macronutrient manipulation has failed us in the past.
Low carb, low fat or low protein are all wrong answers.

After years of research and I think I am finally grasping which carbs and fats are actually beneficial and which ones are not.

It is same for protein, albeit it seems to be more complicated. Amino acids are not just simple building blocks but can also act as mediators that promote health. I am still trying to wrap my head around it but the benefits of lysine, taurine or glutamine are undeniable. It seems like every single amino acids and/or its metabolite has a specific function.

Science will eventually sort this out in decades ahead however we already have great observational studies of diets that tend to include the right carbs, rights fats and right type of protein - blue zones studies are awesome because they show arguably the healthiest diets in various part of the world that allows tremendous flexibility. Whether its Okinawa or Sardinia - they all have similar breakdown in macros.

Bottom line is across all those populations they get majority of their protein from plant sources. It is possible that at least part of their healthspan and longevity stems from not activating the M-TOR.

Personally I have IBS so I cannot handle the amount of legumes that would be necessary to reach those levels. I average about 1.5 grams protein/kg about 50% coming from animal sources (with benefits) Greek yogurt (probiotics), goat cheese-Pecorino (pentanoic acid, SFAs), eggs (omegas, choline, etc), fish - sardines (omegas, taurine, etc). and other 50% coming from collagen (low methionine and leucine, high glycine) and rest from whole grains/seeds, mushrooms, veggies and fruits.

I tend to adjust my diet based on new information. Currently my APOB is 69 and LDL 78 at age 51 without pharmaceuticals, body fat is about 12-15% - so my current diet (+exercise) seems to work for me.

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#16

It is possible that protein in plants comes with greater amount of other benefits, like improved gut health due to resistant starches and fiber in legumes or polyphenols.

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#17

Collagen is not a great source of protein for triggering protein synthesis, IE: building muscle. Whey on the other hand is probably the best.

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#18

A better test is a CTA (CLEERLY) test which uses advanced AI to determine your SOFT (unstable) plaque. Even people with a zero CAC score can have a heart attack from a soft plaque rupture. I know someone who has.

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#19

I suggest that you get the CLEERLY test as well. My CAC is VERY high (800’s) but my CLEERLY test showed that although I have significant soft plaque, it’s spread out over several areas so there is no more than 22% blockage in any one artery which was the first bit of good news I’ve had regarding my heart health in years.

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#20

Lowering uric acid is my next health objective. Hyperurecemia, in both men and women, has a high mortality rate, driven by metabolic and CV disorders. One class of drugs, SGLT2, can lower serum acid by 10-15%. Another, Allipurinol or Uloric, can lower it by 50% or more. I just used 500 mg of quercetin, which lowers levels by 11%, to suppress a painful flare-up of gout. And the supplement luteolin is said to be even better than quercetin.