Methionine/Cysteine restriction increases longetivity AND energy expenditure
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Here is another very interesting mouse study on MR/CR.
Mice on MR were resistant to weight gain, hepatic steatosis and insulin resistance on a high fat diet, despite the mouse strain being especially susceptible to obesity. And despite the fact that the mice were eating more and had better absorption of food.
Their hormone levels were altered. FGF21 was increased 16 fold. And leptin was decreased by 95%, so the mice were really leptin and thus insulin sensitive.
As can be seen in the image below, SCD1 decreased a lot. SCD1 converts saturated fatt acids into unsaturated fatty acids. So through restricting methionine you indirectly lower PUFA in your body. High SCD1 is also implicated in all kinds of diseases, so lowering it will be healthy overall.
As usually mice on MR show lower bone density . And
"...levels of the collagen degradation marker, CTX-1, were significantly higher in the MR animals on HFD by 83%..." . So it seems like their body was trying to get more collagen from their bones , possibly as a reaction to the low protein consumption overall. Which leads me to speculate that you could prevent the bone loss through a generous dietary supply of collagen/ gelatin . -
@Mauritio FWIW I notice that the methionine content of the cheeses correlates pretty well with the protein content.
https://fitaudit.com/categories/mlk/protein -
@annis good point. That makes sense and is more practical.
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@revenant said in Methionine/Cysteine restriction increases longetivity AND energy expenditure:
Both methionine and cysteine are used by the body to grow hair. I wonder if going very low would result in hair loss. How are the met/cys-restricted rodents looking in terms of fur?
These last days since your message I have noticed a lot more hairs in my sink and I couldn't attribute it to anything else than my diet change.
So today i had the first normal protein day for the first time in like 10 days. And I already notice less hair loss, so there seems to to be a connection.
I did not eat a lot more protein, so maybe there is a dose resembling a compromise between minimal hair loss and maximal metabolic benefits.
The intermittent approach might help out here as well.I also seem to be have lost my desire for meat or at least it decreased. In the last 10 years there wasn't a week where I didn't eat meat, probably not even 3 days in a row. But now I don't crave it much anymore, even a good boar bratwurst didn't seem so appealing to me anymore. I still crave milk protein though .
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Another reason to supplement taurine on MR.
Not only does it lower methionine absorption, but it is drastically reduced in livers on MR."Thus, MR caused a 20-fold downregulation of taurine in WT and an 11-fold downregulation in LmnaG609G/G609G livers..."
Another thing that i personally noticed is that MR seems to have an effect on bile. This study shows that bile acids are changed, for example cholic acid is drastically increased.
The enzyme Cyp39a1 was increased on MR, which is an alternative pathway for bile acid synthesis, suggesting that the primary pathways are downregulated somehow .
Another interesting observation was that MR decreased hair loss in a model of accelerated aging mice.
"Despite their reduced size (Figure 6A), Zmpste24−/− MR mice had a 21% increase in median survival and an almost 28% increase in maximal survival (Figures 6B and S6A) and showed a healthier aspect, mostly apparent by a reduced loss of hair and improved atrophy of hindlimbs (Figures 6C and S6B)."
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Dropping in to say this is my favorite thread on the forum right now. Keep up the good work, I check in here frequently.
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I think there is merit in methionine and cysteine restriction but I love food and don’t want to live on for instance sweet potatoes, lentils and rice.
I start the day with a few glasses of milk, which is my breakfast. I am thriving on this diet. I am thinking about making a change as a temporary measure to see how it would be to restrict protein for 2 days a week or so.
I am not really into lentils or any legumes as I didn’t tolerate them well in the past.
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@Ecstatic_Hamster
You could eat ice cream. For most people it's even tastier than milk and some ice creams have less than 1g of protein per 100g.
I actually eat a lot of milk products on MR like cream, ricotta cheese, ice cream,... No lentils or legumes.
Lots of juices and fruits. -
@forty thanks
It's my favorite subject ATM, too. I haven't been that interested in a topic in quite a while.
BTW protein restriction is also the last big change that peat talked about before he died. So we could see it as a last pointer in which way to go. -
@Mauritio said in Methionine/Cysteine restriction increases longetivity AND energy expenditure:
@Ecstatic_Hamster
You could eat ice cream. For most people it's even tastier than milk and some ice creams have less than 1g of protein per 100g.
I actually eat a lot of milk products on MR like cream, ricotta cheese, ice cream,... No lentils or legumes.
Lots of juices and fruits.That’s a good point. Interesting…
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@Mauritio said in Methionine/Cysteine restriction increases longetivity AND energy expenditure:
@revenant said in Methionine/Cysteine restriction increases longetivity AND energy expenditure:
Both methionine and cysteine are used by the body to grow hair. I wonder if going very low would result in hair loss. How are the met/cys-restricted rodents looking in terms of fur?
These last days since your message I have noticed a lot more hairs in my sink and I couldn't attribute it to anything else than my diet change.
So today i had the first normal protein day for the first time in like 10 days. And I already notice less hair loss, so there seems to to be a connection.
That is a bit worrying, although I would think lack of those amino acids would not necessarily result in increased shedding but thinner/slower hair growth.
FWIW, I did a high-protein diet for 3 months and then low-protein for 3 months and my hair seemed to grow longer than normal on the high-protein diet and slowed down on the low-protein diet. But the high-protein diet caused weight gain also.
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@revenant It is indeed. Maybe it was a coincidence, I ll have to try it a few more times.
This also reads like methionine is important for hair:
https://pubmed.ncbi.nlm.nih.gov/8721497/ -
"All cancer types are addicted to methionine, which is a fundamental and general hallmark of cancer known as the Hoffman effect."
There is a lot research being done on MR as a cancer treatment. In this case it worked quite well the volume decreased and remained stable . The treatment also involved chemotherapy,temozolomide and and enzyme called methioniase, which breaks down methionine.
Taking methioniase would be an easy way to selectively reduce methionine and cysteine in the body. I couldn't find it as a supplement but there are certain bacteria producing it.
"l-Methioninase from the newly isolated Methylobacterium sp. has promising characteristics towards anticancer drug developmental studies."
This case study is even more impressive the tumor was rapidly growing and after the beginning of the treatment, which included methioniase and MR the tumor markers came quickly back down to normal
That one is impressive as well. Glioma has a 5 year survival of 6.8% and 2 out of 5 mice were cured, no mice died. Not too bad.
"In the orthotopic nude-mouse model, the combination of TMZ and a methionine-deficient diet was much more effective than TMZ alone: two mice out of five were cured of glioma by the combination. No mice died during the treatment period. Methionine restriction enhanced the efficacy of TMZ in MGMT-negative glioma without inducing MGMT, demonstrating potential clinical promise for improved outcome of a currently incurable disease."
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In this study they looked if taurine supplementation was able to reverse some of the benefits of MR .
They found out the opposite: taurine further decreased adiposity on a MR-diet.
So it looks safe and useful to supplement taurine on MR.
Interestingly on a normal-methionine /control-diet, taurine did not decrease adiposity, only on MR."Taurine supplementation of MR rats did not restore weight gain or hepatic Scd1 expression or indices to CF levels, but further decreased adiposity."
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@Mauritio said in Methionine/Cysteine restriction increases longetivity AND energy expenditure:
Methylobacterium sp.
Are you considering trying to source Methylobacterium-sp for research/experimentation? I hope anyone who finds a source or undertakes an experiment will share details and provide reports -- to see if methionine/cysteine restriction could be achieved by methionase or a methionase-generating bacterium.
Two sources come up on the first results page from a not-so-thorough search:
https://webshop.dsmz.de/en/bacteria/Methylobacterium-sp-oxid-48.html -
@T-3 no not really.
The prices of the products you listed are astronomical and I'm not even sure if they're for human consumption.I was looking for a methioniase supplement but I didn't find anything.
Dare to think.
My X:
x.com/Metabolicmonstr -
@Mauritio I have a reliable source. One month worth of methioninase is a thousand usd.
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@Ecstatic_Hamster are you experimenting with it? If so how long, and any noticeable effects?
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@Mauritio - This is continues to be a great thread. In the link below, Dr. Peat explains what Broda Barnes discovered when he doubled his protein intake.
Dr Ray Peat - Blood Tests, Hormones, Protein Intake, & Ray's Carb List
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@evan-hinkle said in Methionine/Cysteine restriction increases longetivity AND energy expenditure:
@Ecstatic_Hamster are you experimenting with it? If so how long, and any noticeable effects?
No not right now. I am moving more to lower protein and more plant options.
