Methionine/Cysteine restriction increases longetivity AND energy expenditure
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@Serotoninskeptic thanks! That's basically what I've been doing for a while now. I posted a study showing benefts of MR after Just 6h! So if you only eat significant amounts of protein in the evening you have an18h window of "benefits". Intermittent protein fasting.
I feel bad for the normal person they've just adapted to high protein being healthy and now this...
Dare to think.
My X:
x.com/Metabolicmonstr -
@Mauritio Nice, yeah i think this is definitely the most effective and safest way to go about restricting protein. Instead of restricting total protein very low like Ray did in his later years you can instead have periods of fasting from protein while still meeting your protein requirements overall.
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We’re taking a 200 µg dose every other day be reasonable? It’s difficult to get anything but 200 µg dose.
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That's what I ve been suspecting. There is a threshold for the benefits. There is a subjective switch that I feel when Im on MR.
This implies that until the threshold there is no harm and after the threshold the harm increases disproportionetly from consuming excess methionine. That is the problem with the intermittent approach @Serotoninskeptic . I think it is a good idea to limit protein to one meal mostly, but overall protein intake shouldnt exceed 40-70g for most people. Thats at least my current opinion.This is from Peats last Newsletter. His last gift to us.
"There is a threshold effect in exposure to
the harmful amino acids, and this involves a
very sensitive system for detecting their concentration, apparently involving the actin filament network throughout the body. Above
the threshold concentration, methionine
activates mTOR. Increased mTOR shortens
life-span and increases the processes of aging.
Increased fat in the diet increases mTOR,
adding to the effects of amino acids. ""The way these regulators of energy and
aging interact is holistic, and it’s necessary to
understand that organisms make generalizations about their problems. Things that inhibit
mTOR will increase adaptation and organization with expansion of the time horizon, while
things that activate it (methionine, estrogen,
radiation) will accelerate cell growth and
inflammation and activate terminal processes.
Progesterone and estrogen relate to the degree
of mTOR activity through the body as a
whole, not just through a series of receptor
intermediates."Dare to think.
My X:
x.com/Metabolicmonstr -
@Mauritio Yeah this makes sense. Also in the later years of his life Ray clarified that 100g+ would only be useful for an active young person with a 4-5k calorie metabolism. So, the needs decrease with aging as well as with slower metabolism, and activity level. Someone like me who is young in my 20s and active, lifting weights and maintaining at 3.5k-4k calories. I might need close to 100g or more but intuitively I tend to be around 80-100g and don't really go over that. Im still able to build muscle on this amount.
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@Serotoninskeptic yes! He never gave out a recommendation to eat just 50g of protein. It's context specific.
For someone like you it might indeed be necessary to get more than 70g of protein.
I intuitively eat 60-80g if I don't restrict myself.
But I feel like the "threshold" is lower for me. I only feel the switch when I'm around 40-50g per day.Dare to think.
My X:
x.com/Metabolicmonstr -
@Mauritio Yeah I even noticed a huge boost in metabolism and overall energy going from eating 150-200g down to around only 80-100g and increasing my carb intake even further. Most muscle building benefits stagnate around 1g/kg or 1.2g/kg of body weight.
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@Serotoninskeptic And muscle building isn't everything, maybe one can build a little more muscle on a way higher P-diet, but at what cost?
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@Serotoninskeptic said in Methionine/Cysteine restriction increases longetivity AND energy expenditure:
@Mauritio Look into @anabology's posts on FGF21 and the "honey diet." The idea is intermittent protein restriction from morning until dinner eating just fruit, sugar, honey etc. Then meeting your protein requirements at dinner, getting like 1g-1.2g/kg of protein total. Tons of people are getting great results from it including myself. You can read more on his X account and longestlevers.com.
I finally had some time to look into it and I'm on board with most of it. But are you really eating massive amounts of protein with little to no carbs? Sounds like a recipe for high cortisol especially so close to bedtime (no carbs for the next 8h).
I think if you kept carb intake throughout the day that would be a better idea.Dare to think.
My X:
x.com/Metabolicmonstr -
@Mauritio You can do carbs at dinner too, I think the lower carbs at dinner thing is more for weight loss purposes and just to not overeat calories at dinner. If youre doing the diet mainly for health benefits and longevity purposes and dont care about weight loss than its not necessary.
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Increase of FGF21 in humans leads to reduction in liver far in clinical trial .
"Furthermore, some researchers have recently synthesized a long-lasting FGF21 fusion protein, PsTag600-FGF21, and found that it enhances liver FAO and reduces hepatic steatosis and inflammation via the FGF21-adiponectin-IL17A pathway [47]. Encouragingly, in a phase 2a trial of efruxifermin (long-acting Fc-FGF21 fusion protein) in patients with NASH, patients with stage F1-F3 NASH showed a significant reduction in liver fat fraction after treatment [48]."
FXR activation might increase FGF21.
FXR agonists:
androsterone , bile acids , progesterone/pregnenolone metabolites, diosgenin, certain polyphenols e.g.cafestol,
..."Finally, activation of FXR also increases FGF21 transcription and expression. In vitro studies have also shown that FXR can induce FGF21 production by inducing the expression of FGF19, but this has not been confirmed [65], [66]."
https://www.sciencedirect.com/science/article/pii/S0753332222009660?via%3Dihub
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Sodium butyrate supplementation increases FGF21
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Palmitoleic acid increases FGF21.
https://pubmed.ncbi.nlm.nih.gov/27925195/Interestingly overfeeding carbohydrates also increase palmitoleic acid AND FGF21.
https://pmc.ncbi.nlm.nih.gov/articles/PMC5220397/Macadamia nuts are a good source of this omega 7 MUFA .
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Very interesting new study on protein restriction in humans.
They looked at high carb,low protein and high fat low protein .What they found:
Low protein (8%) :
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Increases metabolism by about 20%
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Does NOT matter if you do high carb, low protein or high fat low protein. Both increase metabolism by 20%
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When high protein diet resumes, meatbolism and FGF21 goes down
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Quickly increases FGF21.
63% within 90 minutes of a low P-meal -
Increases metabolic rate after only 3h
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No muscle loss after 5 weeks of low protein
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No change in free T3 and noradrenaline
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Insulin sensitivity seems to be equal on high carb and high fat diet
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Electron transport chain proteins and OXPHOS proteins were upregulated, while ATP synthase was downregulated, suggesting a "wasting"/ uncoupling of energy.
Although UCPs were not upregulated.
All of this downstream from FGF21 upregulation. FGF21-KO mice did not show changes in ETC and OXPHOS proteins.
Limitations/Remarks:
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The high fat diet was not a ketogenic diet. It still contained 40% carbs!
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The high carb diet was not a low fat diet. Still contained 21% fat.
So maybe the results would have been even better with a high carb, low protein, low fat diet. Leveraging the randle cycle.
Other studies showed that the deciding amino acids are methionne and cysteine (and maybe Tryptophan)
The absolute amount of methionine was very different on high carb (~2.5g) vs. the high fat diet (~1g) . Making the comparison less fair.In any case it seems clear now that you can loose weight/ increase metabolism on a non-ketogenic high fat-low protein diet, which I wasn't convinced of before.
"...to prevent weight loss, it was necessary to increase energy intake consecutively in the following weeks of the LPHC intervention, and at the end of week 5, energy provision was increased by 19% (2.4 ± 0.8 MJ) in the LPHC diet (Fig. 2g). This increase in energy intake was accompanied by a 270% elevation in fasting plasma FGF21 levels at week 5 compared with pre-intervention (Fig. 2h). The increased energy intake was not attributed to alterations in physical activity level,..."
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@Mauritio said in Methionine/Cysteine restriction increases longetivity AND energy expenditure:
Here's a highly interesting study focusing on to what degree selenium supplementation can replace methionine restriction. And the answer is: to a surprisingly large degree, but not completely.
MRs benefits on weight were completely repeated by selenium supplementation. They were almost immune to weight gain on high fat diet.
The mice fed selenium even had a little bit more lean mass, although were also bit longer.
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))))The authors hypothesize that all of this is downstream from IGF-1 reduction. They cite a bunch of studies showing IGF-1 reduction being critical to (some) MR benefits.
And selenium reduces IGF-1 to a similar degree as MR.FGF21 was not the same in both groups. Selenium had almost no effect on it in young male micr. This is why selenium only partially replicates MR. As discussed many times in this thread FGF21 is central to MR's benefits and I think the increase in klotho is downstream from it as well. So that is missing when taking selenium, hence why I don't think selenium supplementation will have as drastic of an effect on longevity as MR.
That was in younger male mice, in older female mice the effect on FGF21 was pretty drastic so there might be sex or age specific effect going on.The authors fed sodium selenite but also checked selenomethionine, which was quite a bit less effective for whatever reason. They checked different dosages so it probably wasn't that.
So if you want to replicate this study using sodium selenite is your best bet.
Unfortunately Brazil nuts contain mostly selenomethionine so that won't be perfect either .Body weight on selenomethionine
@DavidPS this might interest you.
Ever since I posted the above study, I've been wondering why selenomethionine was so much less effective than sodium selenite.
This study might give some answers.
Sodium selenite was able to reverse liver fibrosis in vivo via its metabolite hydrogen selenite, which degrades the excessive collagen in fibrotic tissue.
Sodium selenite yields more hydrogen selenite than selenomethionine. And its pathway towards hydrogen selenite is more straight forward.So maybe the impressive benefits of sodium selenite in terms of replicating MR are due to a metabolite?
Not sure, but worth a mention. And another won for sodium selenite.
The HED in the liver fibrosis study was around 1mg, 3 times per week for 4 weeks.
That's around 430mcg per day, which is pretty high. But I wouldn't be surprised if a lower dose over a longer time had a similar effect. -
@Mauritio what about selenoneine
