Methionine/Cysteine restriction increases longetivity AND energy expenditure
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@Mauritio said in Methionine/Cysteine restriction increases longetivity AND energy expenditure:
@Mulloch94 said in Methionine/Cysteine restriction increases longetivity AND energy expenditure:
This is interesting research, I'm glad it's being discussed here. Anecdotally, when I was doing protein restriction a couple years ago I actually felt very good while doing it, and I wasn't even on thyroid during this period. I came to the conclusion that the "low-protein" aspect was more beneficial than the "low-fat" aspect of it. Though I'd imagine they both synergistically aid to some extent.
What set me on that path was stumbling upon some studies that suggested low-protein diets can reduce CRH and ACTH output, and thus quiet that negative feedback loop of stress hormones. I couldn't go long without eating because my liver was malfunctioning and not holding glycogen well.
The low protein diet seemed to stop (or slow down) the gluconeogenesis and subsequent stress response, as I wouldn't get the low blood-sugar "shakes" anymore, however I ran into a new problem of never seeming to get full. I was basically always thinking about food, even after eating. I guess because a almost pure carbohydrate diet doesn't really hit that satiety factor as much as a higher protein diet does, idk.
After successfully implementing thyroid into my regime I can handle higher protein much better, but I do believe a low-protein diet can partially alleviate many of the main issues associate with hypothyroidism if you can stick to it. I'm not really interested in going full low-protein again, but it would be nice to find a complete list of all the high methionine foods, because avoiding methionine and cysteine would be something I'd do, along with tryptophan.
If you dont want to go full low protein, maybe just 2 days a week is doable. If you look at image (a) in the post above, you can see that even 2 days a week at 5% protein caused FGF21 to more than double. And 5% might not even be necessary in rat and the human studies they mostly used 10% which is about 50-75g of protein for most people. Although that sounds more than it is.
How much protein and fat did you eat during those days?
I was hitting around 50 grams during my experiment. I ate mostly baked potatoes (around 2 pounds per day) with fresh salsa. I also made some rice pudding with skim milk, but kept it to one serving per day because I didn't want the milk to give me too much protein. I could probably do this diet again on a limited 2 day weekly basis with no issues at all.
Even now though, I do think I've managed to restrict methionine despite increasing total protein consumption. I didn't exactly plan it out that way (I was more focused on tryptophan), but my main sources of protein now are BCAA's in a morning smoothie with milk and fruit, casein in my afternoon oatbran, and something like hamburger or oxtail for dinner which might be high in methionine but it's got plenty of glycine in it too.
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@Mulloch94 said in Methionine/Cysteine restriction increases longetivity AND energy expenditure:
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Nice, ice cream has only about 2g of protein per 100g. So that is good thing to consider.
Did you notice any issues with libido or muscle strength?I'm wondering about craving too. Im sure you were craving meat at some point , then wouldnt that be a sign that your body needs it ? Not sure, but that would speak for the intermitten approach as well.
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@Mauritio said in Methionine/Cysteine restriction increases longetivity AND energy expenditure:
Nice, ice cream has only about 2g of protein per 100g. So that is good thing to consider.
Yeah, at the time is was doing both low-protein and low-fat. But I have been wondering how well I might respond to a low-protein diet that doesn't emphasize low-fat as well. So I might give ice cream a try too. I'm interested to know whether my satiety is effected if I don't lower fat with my protein.
@Mauritio said in Methionine/Cysteine restriction increases longetivity AND energy expenditure:
Did you notice any issues with libido or muscle strength?
I did notice I would get gassed quicker on my deadlifts and squats. I didn't notice much difference in sexual performance. I wasn't in a active relationship so I wasn't getting laid frequently. My guess is someone who has a more restricted refractory period between encounters might notice a difference. But I've also read higher-protein diets increase PRL (prolactin), so maybe a lower protein diet is actually beneficial in this regard?
@Mauritio said in Methionine/Cysteine restriction increases longetivity AND energy expenditure:
I'm wondering about craving too. Im sure you were craving meat at some point , then wouldnt that be a sign that your body needs it ? Not sure, but that would speak for the intermitten approach as well.
This is something I've heavily considered as well. My personal opinion is if someone does heavy protein restriction for many years they may begin to slowly breakdown muscle tissue. You can look at some of those life-long vegans who eat starch based diets (like 80% carbs) and they're all small and bony. But, like you said, if you only eat that way intermittently this probably won't happen. Low-protein reduces the glucocorticoids you're already sparing your protein.
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Thanks.
I was tryign low fat, low protein yesterday as well.
And I feel like restricting two macro-nutrients is too much. not sure if I could handle that long term. If almost all you eat is carbs, you probably run into satiety problems down the road. Carbs just arent that filling IME. But maybe it would get easier over time, as the animal studies show a shift in substrate utilization towards carbohaydrate oxidation, so maybe the cravings are transitory. -
i think it makes sense to look into the differing methionine and cysteine contens of foods.
For example milk and milk products have a lot less of those amino acids than meat. So you can eat a higher amount of cheese, yoghurt or milk, as compared to meat.
But even amongst cheeses there is a big difference in methionine content. Parmesan for example is very high.
For example : if you ate cheddar or mozzarella cheese instead of parmesan you could eat almost twice as much and still get the same amount of methionine.
If you ate feta you could eat almost 3 times the amount comapred to parmesan.
And if you eat cottage cheese you could eat almost 4 times as much.So if you eat the right type of protein like milk and find a low methionine cheese you can make your life a lot easier while still eating resting methionine.
Another good food is, Cocoa/ Chocolate. It's low in methionine, moderately high in cysteine and low in tryptophan. I think it is also a high quality protein for anabolism, haidut posted a study on that IIRC
Heres a good list:
https://fitaudit.com/categories/mlk/methionineEgg yolks seem to be a lot lower in methionine than whites, another reason to discard the whites:
https://fitaudit.com/categories/egg/methionineThis site even shows the cysteine content:
https://cystinuria.org/methionine-levels/Dare to think.
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Interesting study In humans,showing increase of FGF21 6-fold after seven days. Diet was 9% protein , 71% carbs, 20% fat.
Anybody interested in this diet, should listen to the first 15 minutes of this pod with ray. dropped some gems.
He mentions mTOR inhibition as the major MoA of MR, which I have only sparingly seen mentioned in the studies.
<img src="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7911310/bin/biomedicines-09-00130-g002.jpg" alt="An external file that holds a picture, illustration, etc.
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This is the 30 year old study that a lot of people have mentioned. In which there was a 43% increase in life span in rats.
The researchers make some obervations that are hard to reconcile with some parts of the bioenergetic viewpoint.
They measured GSH and GSSG levels and they were through the roof. In old mice GSH was 278% higher than in old control mice. Now GSSG did not change, meaning the GSH/GSSG ratio increased a lot.
Since the GSH/GSSG ratio is a proxy for the NAD/NADH ratio and for how oxidized the organism is, the mice should be in an extremely reductive state- yet they lived a lot longer and are healthy.The only place where GSH decreases was the liver and kidneys.
They also found that these changes were present as early as 2 months into the diet. While other research suggests that it might take 2-4 weeks for those changes to happen. I'm not sure if those changes would also occur on an intermittent approach, but I read there was a study on that, I just havent found it yet.
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@Mauritio said in Methionine/Cysteine restriction increases longetivity AND energy expenditure:
Thanks.
I was tryign low fat, low protein yesterday as well.
And I feel like restricting two macro-nutrients is too much. not sure if I could handle that long term. If almost all you eat is carbs, you probably run into satiety problems down the road. Carbs just arent that filling IME. But maybe it would get easier over time, as the animal studies show a shift in substrate utilization towards carbohaydrate oxidation, so maybe the cravings are transitory.I have noticed I don''t crave fatty foods as much when I take pyrucet. I'm thinking the more you increase glucose oxidation, the less you fatty foods tasty. However I'm not sure the same can be said about protein.
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Something interesting about all this to me is that before I recognized that I was hypothyroid, I ate a plant based diet, (heavy on fruits, but a fair amount of rice and potatoes) and ate a couple cheeseburgers once a week. Like vegan except for one day a week. I had previously been vegetarian exclusively for about 10 years, (which probably contributed to my hypothyroidism as I in no way avoided PUFAs, and did not consume dairy).
During that period when I first re-introduced beef once a week I have never been healthier. It actually still stands out in my mind as a time when I was incredibly well. I would imagine that I never got more than 75 grams of protein in a day, (6 days a week) and the majority of that would have been from plants, (squash, potatoes, bread, various fruits, some beans). I’m willing to bet with some very modest changes I could probably replicate that diet and fall into methionine restriction pretty easily.
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@Mulloch94 said in Methionine/Cysteine restriction increases longetivity AND energy expenditure:
@Mauritio said in Methionine/Cysteine restriction increases longetivity AND energy expenditure:
Thanks.
I was tryign low fat, low protein yesterday as well.
And I feel like restricting two macro-nutrients is too much. not sure if I could handle that long term. If almost all you eat is carbs, you probably run into satiety problems down the road. Carbs just arent that filling IME. But maybe it would get easier over time, as the animal studies show a shift in substrate utilization towards carbohaydrate oxidation, so maybe the cravings are transitory.I have noticed I don''t crave fatty foods as much when I take pyrucet. I'm thinking the more you increase glucose oxidation, the less you fatty foods tasty. However I'm not sure the same can be said about protein.
It might be true. Im on day 3 and I crave protein slightly less than on day one, certainly not more. The studies show that when you restrict protein, you increase carb and fat oxidation. Fat actually more than carb.
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@evan-hinkle said in Methionine/Cysteine restriction increases longetivity AND energy expenditure:
Something interesting about all this to me is that before I recognized that I was hypothyroid, I ate a plant based diet, (heavy on fruits, but a fair amount of rice and potatoes) and ate a couple cheeseburgers once a week. Like vegan except for one day a week. I had previously been vegetarian exclusively for about 10 years, (which probably contributed to my hypothyroidism as I in no way avoided PUFAs, and did not consume dairy).
During that period when I first re-introduced beef once a week I have never been healthier. It actually still stands out in my mind as a time when I was incredibly well. I would imagine that I never got more than 75 grams of protein in a day, (6 days a week) and the majority of that would have been from plants, (squash, potatoes, bread, various fruits, some beans). I’m willing to bet with some very modest changes I could probably replicate that diet and fall into methionine restriction pretty easily.
You mention you increased your protein and got healthier, how is that related to the protein restriction discussed in this thread? Wouldnt that be an argument against it?
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@Mauritio nah, too many factors. I was eating a pufa laiden vegan diet with a ton of indigestible “foods.” I think the very low protein of one meat based meal a week in combination with a whole food vegetarian diet would probably be a great option.
From this model I went carnivore and incorporated block fasting and one meal a day, (information I didn’t share). So increasing protein to that degree very certainly did not help, (it’s kinda relative right?) I’m looking at the one meat meal a week plus whole food vegetarian, (not dogmatic) as a potential “easy” diet to achieve methionine restriction. Sorry for any confusion.
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@evan-hinkle Ok, thanks.
Dare to think.
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Does anybody know the study where they showed that eating low protein 3 times a week, bascially gave the same benefits on longevity as doing it full time? I ve seen that mentioned but havent found the actual study. That is the last thing on that whole topic that Im really interested in.
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I mean in a lot of these studies restricting protein really means increasing carbs at its expense by quite a significant margin.
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@Mauritio said in Methionine/Cysteine restriction increases longetivity AND energy expenditure:
Does anybody know the study where they showed that eating low protein 3 times a week, bascially gave the same benefits on longevity as doing it full time? I ve seen that mentioned but havent found the actual study. That is the last thing on that whole topic that Im really interested in.
Apart from what's already in this topic mentioning 3 days of restriction (protein in general), there's this one about intermittent methionine restriction/IMR (3 days of restriction).
To the best of our knowledge, we show for the first time that IMR confers to male and female mice the beneficial metabolic effects previously reported for continuous MR. That is, as compared with control-fed mice, animals undergoing the more stringent of two IMR regimens (IMR2) benefit from reduced adipose tissue accumulation, protection against hepatosteatosis, improved glucose homeostasis, and altered circulating levels of IGF-1, FGF-21, leptin, and adiponectin. Despite a much shorter interventional period than continuous MR (only 3 days per week), not only is IMR capable of producing similar health benefits, but other aspects of this intervention are actually superior to classical MR.
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@TexugoDoMel
Thanks! Thats the one I meant.
The results arent as encouriging as I hoped, but still good.They had two Intermittent methionine restricion (IMR) groups, both of them were fed 3 days of a methionine restricted diet followed by a low methionine diet for 4 days in case of IMR1 and a no methionine diet in case of IMR2. They had a continuously methionine restricted diet as a control group
In terms of health effects only IMR2 was really capable of keeping up with continous MR. IMR1 had benefits but not quite as much.
Unforuntely its not really possible for people to have a no methionine diet.
Plus, none of the groups ate any cysteine. And only 0.02% in the diet is able to remove the benefits of MR. So Im increasingly worried about cysteine, since in most of the animals studies on MR, it is 0, which is hard to replicate in humans.
<img src="https://onlinelibrary.wiley.com/cms/asset/5bc56635-0d01-43e0-baf4-fa08c37470ab/acel13629-fig-0001-m.png" alt="Details are in the caption following the image"/>
So continous MR does seem to be quite a bit superior to intermitten MR ,which can also be seen by the other data on liver and hormones in the study.
The longer you restrict methionine, the better.An interesting finding of the study was that alternating high and low methionine days had a similar effect as the 3-4 approach, which underlines the flexibility of this diet.
So if you feel have a good week ,you can have a high protein day once a week and if you have bad week 4 times a week and still get a lot of benefits.<img src="https://onlinelibrary.wiley.com/cms/asset/5bc56635-0d01-43e0-baf4-fa08c37470ab/acel13629-fig-0001-m.png" alt="Details are in the caption following the image"/>Dare to think.
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Cool thread. I’ve been experimenting with high carb/low fat/lowish protein(one protein meal a day probably around 50-60g but haven’t measured). A few things I’ve found:
-to do a low protein/high sucrose diet and still get daily requirements of nutrients, it seems to either require sugar/honey consumption with some nutrient dense foods like milk/liver/meat or copious ripe fruit with some vegetables. For me, I’ve never found the fruit to be great quality in my area so I’ve been trying the former strategy.
-For the sugar diet(not sure what else to call it lol), I’ve found that my gut is exceedingly happy and I’m definitely losing fat. I haven’t noticed any muscle loss, but it is early(2 weeks ish). I also weight lift a few days a week so might have an effect.
-Ive also found that this diet definitely needs more copper/liver consumption. I generally notice I need more copper if I start having histamine reactions to food(copper supplementing relieves this). I don’t tend to eat liver so I’ve been supplementing with 2mg copper daily
-Stabilizing blood sugar is definitely hard with this. I’ve found it has gotten better over time(hopefully it keeps getting even better), but I have to eat often and I find a tiny bit of fat(I use like a quarter teaspoon of higher fat cocoa powder)with the carbs can help prolong satiety.
-I have one meal a day of higher fat and protein for dinner. Definitely have some cravings for it, but that only seems natural as it is the most nutrient dense meal of the day.
-Will update as I go, but this is how I’ve been approaching it so far. -
What Ive been hinting at before: the presence of cysteine restriction in the MR animal studies , but the absence of cysteine restriction in the way we do it and the human studies.
Maybe calling it methionine restriction is misleading and it should be called cysteine restriction!
The authors show that the weight loss benefits require cysteine restricion, not mehionine restricion. So by not restricting cysteine we might not be getting the full benefits."Decreasing the dietary intake of methionine exerts robust anti-adiposity effects in rodents but modest effects in humans. Since cysteine can be synthesized from methionine, animal diets are formulated by decreasing methionine and eliminating cysteine. Such diets exert both methionine restriction (MR) and cysteine restriction (CR), that is, sulfur amino acid restriction (SAAR). Contrarily, SAAR diets formulated for human consumption included cysteine, and thus might have exerted only MR."
This study shows that taurine (another sulfur amino acid) increases the benefits of MR even further. "
NAC on the other removed the benefits of MR.
Just like a small amount of cysteine removed almost all the benefits of MR in this study.
Dare to think.
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@Mauritio said in Methionine/Cysteine restriction increases longetivity AND energy expenditure:
Another interesting find of the above mentioned study is that Cysteine restriction (CR) and not MR, increases a protein called PECK-M by 5-10 times.
This protein has many pro metabolic benefits.
In fact one of the most interesting studies I've ever posted was on transgenic mice that had genetically increased levels of that protein. The benefits of that sound similar to MR/CR, which suggests that many of the benefits of it are due to an increase in PECK-M.These were some of the benefits of over expressing PECK-M in mice:
"The mice were 7-10 times more active !! Beeing able to run 5km at once (a mouse!) They were consuming more food while having less body fat ,which indicates a high metabolism. And they lived almost 2 years longer than normal mice ( normal mice live 2-3 years at max) so they DOUBLED their LIFESPAN !"
That's what I wrote in 2018.These mice also had an extended reproduction window, which is quite interesting because in some experiments life extension comes at the cost of lower reproductive health. So they lived a lot longer and were healthier overall. I've never seen more research on that over the years, yet I've never seen a more robust increase in lifespan in mice in any study.
Edit: just saw that the in the mice they over expressed the mitochondrial and not the cytosolic form of PECK, but i guess their effects are similar
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M Mulloch94 referenced this topic on
