Methionine Deficient Diet Induces Rapid Weight (Fat) Loss in Mice who Ate More, and Moved Less

[tankasnowgod]

This was an interesting short term study. The researchers basically took Methionine Restriction a step further, and fed Obese mice a diet completely free of Methionine. They noticed rapid weight loss, mostly fat, and apparently did it through increasing resting metabolic rate.

Short-term, low-methionine diet slims down obese, pre-diabetic mice

Finely manipulating metabolic processes by limiting intake of a specific building block of proteins caused obese, pre-diabetic mice to shed most of their fat and improve blood glucose control-even though the dietary intervention occurred over a short time span (one month), and their overall...

vitalsigns.medicine.wisc.edu

Scientists speculate that the approach may mimic some aspects of a plant-only vegan diet, since many plant proteins tend to be low in methionine. Because long-term adherence to dietary restrictions is notoriously difficult for many people, the research team investigated whether they could improve metabolic health of mice that were initially placed on high-fat, high-sugar "Western" diets to induce obesity and blood glucose dysregulation, and then shifted for up to five weeks to either the Western diet with defined levels of all amino acids, or the Western diet without methionine. A control group of lean mice on a standard lab chow was used for comparison.

The results were striking. "Feeding a low methionine diet to mice that are obese and pre-diabetic rapidly restored their metabolic health. They lost weight, with a profound reduction in fat - they lost about 70% of their fat in one month. This happened even though they could eat as much food as they wanted and they actually moved less. We referred to them as 'couch potatoes,'" said Dr. Lamming.

Further analysis indicated that the temporary low-methionine diet triggered increased energy expenditure and altered metabolic processes in the liver and fat cells. The beneficial effects of reduced adiposity and improved blood glucose regulation were not dependent on a key regulator of liver metabolism called mTORC1. While both male and female mice showed the physiological changes, scientists did observe sex-specific differences at the molecular level: blood levels of a hormone called Fgf21 that is involved in energy balance regulation was increased in male mice but not female mice.

Short-term methionine deprivation improves metabolic health via sexually dimorphic, mTORC1-independent mechanisms - PubMed

Obesity and diabetes are major challenges to global health, and there is an urgent need for interventions that promote weight loss. Dietary restriction of methionine promotes leanness and improves metabolic health in mice and humans. However, poor long-term adherence to this diet limits its...

pubmed.ncbi.nlm.nih.gov

In this study, we examined the metabolic impact of complete removal of dietary methionine, which we hypothesized would produce similar but more rapid effects on metabolic health than MR. MD promoted glucose tolerance in both male and female mice consuming a normal-calorie diet and resulted in a profound reduction in adiposity. Further, MD rapidly restored metabolic health in both male and female mice with pre-existing diet induced obesity and glucose intolerance, suggesting that MD may be a useful, short-term intervention for the treatment of pre-existing metabolic syndrome. MD induced significant weight loss in mice of both sexes. Although mice lost both fat mass and lean mass during MD, there was a striking and preferential decrease in adiposity, as reflected by a loss of nearly 60% of fat mass in 2 wk and 80% of fat mass over the course of the 5 wk experiment. Contrary to the report of Leib and Knight (45) that mice reject diet lacking a single essential amino acid, we observed that the progressive weight loss of MD-fed mice occurred despite increased food consumption. Instead, MD mice lose weight because of increased energy expenditure, likely because of increased metabolic rate, but not because of increased physical activity, as MD mice tend to move less, not more.

This seems to suggest that the intervention could be used even over a shorter term, as most of the fat loss occurred in the first two weeks.

This sort of extreme protocol can't be recreated with real food, as everything seems to have some methionine in it. Pure Amino Acids would probably have to be substituted for protein, as even gelatin has a little bit of methionine in it.

It did, however, get me thinking about the glycine/methionine ratio. Maybe a more realistic approach would be to follow a very low methionine diet (which would still require avoiding most protein), but increasing levels of glycine very high, brining back in gelatin a potential protein, and/or a glycine supplement. Foods like fruit and potatoes (maybe rice? Masa Harina?) could be used for the bulk of dietary calories (maybe similar to the Kemper diet and potato hack). They said both additional fats and carbs didn't seem to affect weight loss in the mice, so maybe even things like butter and coconut oil could be used (still avoiding PUFA, obviously).

Here is a follow up post discussing how this might be related to a chronic glycine deficit-

Are Humans (and all Vertebrates) running a chronic, lifetime Glycine Deficient?

This is sort of a follow up to the post I did about an experimental Methionine Deficient diet. https://raypeatforum.com/community/threads/methionine-deficient-diet-induces-rapid-weight-fat-loss-in-mice-who-ate-more-and-moved-less.45256/ I happened to be looking at the Glycine/Methionine Ratio...

raypeatforum.com

 

[Rinse & rePeat]

This is exacyly what has been my success in losing 18 pounds, effortlessly, this past 4 months. I cut out all of my meat and seafood, and upped my gelatin, putting it in my milk coffees. I have been talking about it, on the last pages of my two fat loss threads, with before and after pictures.

MORE WEIGHT LOSS TALK

“STARCH and GLUCOSE efficiently stimulate insulin secretion, and that accelerates the disposition of glucose, activating its conversion to glycogen and fat, as well as its oxidation. Fructose inhibits the stimulation of insulin by glucose, so this means that eating ordinary sugar, sucrose (a...

raypeatforum.com

Lose Fat Not Pounds & Seeing Is Believing (before & after pics)

"In one of the studies in which rats had been taught learned helplessness so they would drown in five or six minutes, just being able to see another rat escape would let the informed rat go for days without drowning. Just the recognition that someone else did it can make all the difference." Ray...

raypeatforum.com

 

[tankasnowgod]

This is exacyly what has been my success in losing 18 pounds, effortlessly, this past 4 months. I cut out all of my meat and seafood, and upped my gelatin, putting it in my milk coffees. I have been talking about it, on the last pages of my two fat loss threads, with before and after pictures.

Pretty cool.

So, are you basically drinking Lattes with Gelatin all day, and then having soup for dinner?

 

[Mauritio]

This was an interesting short term study. The researchers basically took Methionine Restriction a step further, and fed Obese mice a diet completely free of Methionine. They noticed rapid weight loss, mostly fat, and apparently did it through increasing resting metabolic rate.

Short-term, low-methionine diet slims down obese, pre-diabetic mice

Finely manipulating metabolic processes by limiting intake of a specific building block of proteins caused obese, pre-diabetic mice to shed most of their fat and improve blood glucose control-even though the dietary intervention occurred over a short time span (one month), and their overall...

vitalsigns.medicine.wisc.edu

Short-term methionine deprivation improves metabolic health via sexually dimorphic, mTORC1-independent mechanisms - PubMed

Obesity and diabetes are major challenges to global health, and there is an urgent need for interventions that promote weight loss. Dietary restriction of methionine promotes leanness and improves metabolic health in mice and humans. However, poor long-term adherence to this diet limits its...

pubmed.ncbi.nlm.nih.gov

This seems to suggest that the intervention could be used even over a shorter term, as most of the fat loss occurred in the first two weeks.

This sort of extreme protocol can't be recreated with real food, as everything seems to have some methionine in it. Pure Amino Acids would probably have to be substituted for protein, as even gelatin has a little bit of methionine in it.

It did, however, get me thinking about the glycine/methionine ratio. Maybe a more realistic approach would be to follow a very low methionine diet (which would still require avoiding most protein), but increasing levels of glycine very high, brining back in gelatin a potential protein, and/or a glycine supplement. Foods like fruit and potatoes (maybe rice? Masa Harina?) could be used for the bulk of dietary calories (maybe similar to the Kemper diet and potato hack). They said both additional fats and carbs didn't seem to affect weight loss in the mice, so maybe even things like butter and coconut oil could be used (still avoiding PUFA, obviously).

Here is a follow up post discussing how this might be related to a chronic glycine deficit-

Are Humans (and all Vertebrates) running a chronic, lifetime Glycine Deficient?

This is sort of a follow up to the post I did about an experimental Methionine Deficient diet. https://raypeatforum.com/community/threads/methionine-deficient-diet-induces-rapid-weight-fat-loss-in-mice-who-ate-more-and-moved-less.45256/ I happened to be looking at the Glycine/Methionine Ratio...

raypeatforum.com

Interesting! I've done low fat and low carb but never low protein.

I'd add urea to the glycine. This way you could get away with even less protein.

 

[Rinse & rePeat]

Pretty cool.

So, are you basically drinking Lattes with Gelatin all day, and then having soup for dinner?

Ha! Ha! No :)
I do usually drink three of my gelatin and milk coffees a day and then maybe have a regular espresso in the late afternoon. I fill in with 2% and nonfat milk, about 3 cups a day which puts me at 60 grams of protein with just those two things, with very little fat. My usual other proteins, lately, are eggs topped with cheese and salsa, a liver taco with hot sauce, a bowl of sprouted brown rice cereal and milk, custard or my homemade cream and egg free ice cream, no soups. Since losing the weight I was concerned about losing more, so I have added in an occasion organic fresh from the oven croissant with lots of butter or my boil and broil wings, and various other Ray Peat "no no's" to keep me from losing any more, and the weight loss has stopped. I actually posted my after picture two pounds up from my "splurges".

 

[tankasnowgod]

Interesting! I've done low fat and low carb but never low protein.

I'd add urea to the glycine. This way you could get away with even less protein.

I was thinking the same thing.

Seven days of supplementing Urea at 60g per day

Urea is one of the more interesting supplements in the Peat world. I am constantly turned off (or outright disgusted) by the taste, always intrigued by the promise, and see some benefits from taking larger doses. Over the past week, I decided to do a course of Urea, averaging about 60g a day...

raypeatforum.com

Since only 13.7g of Urea was able to get the body back to "Nitrogen Balance" that otherwise took 40g of protein, it would seem that Urea has 2.9 times the Nitrogen Value of protein. Maybe the Urea is even providing some of the "high protein" benefits directly, as BUN will be higher in anyone consuming a high protein diet. This could be very useful if you were thinking a high protein diet may be beneficial..... 120g protein plus 30g Urea could have the same effect as 200g protein, and that without extra calories, fat, or what have you. It may be more "cost effective" too..... 30g Urea is going to way cheaper than a Porterhouse with 80g of Protein (though seriously less tasty).

(for reference, if others haven't seen that study)

The Modified MAP might also be useful-

Amino Acid Supplementation For People With Poor Digestion

This topic has come up repeatedly and recently forum member gbolduev raises the issue again, and forum member jyb suggested I post about it. It seems that due to hypothyroidism and other conditions, many people on the forum have a functional protein deficiency due to poor ability to digest...

raypeatforum.com

Since it's supposed to be a short term intervention, this could be a way to get close to replicating the study. I think there are other studies that show Methionine Restriction (not complete deficiency) still show similar weight loss and metabolic improvements.

 

[tankasnowgod]

Ha! Ha! No :)
I do usually drink three of my gelatin and milk coffees a day and then maybe have a regular espresso in the late afternoon. I fill in with 2% and nonfat milk, about 3 cups a day which puts me at 60 grams of protein with just those two things, with very little fat. My usual other proteins, lately, are eggs topped with cheese and salsa, a liver taco with hot sauce, a bowl of sprouted brown rice cereal and milk, custard or my homemade cream and egg free ice cream, no soups. Since losing the weight I was concerned about losing more, so I have added in an occasion organic fresh from the oven croissant with lots of butter or my boil and broil wings, and various other Ray Peat "no no's" to keep me from losing any more, and the weight loss has stopped. I actually posted my after picture two pounds up from my "splurges".

Okay, that does sound a little more complete.

Did you have a liver taco recipe on that thread? Is it good?

 

[Rinse & rePeat]

I am not as much methionine free, with eggs, milk and cheese, but rather lower methionine, by cutting out the meats and seafood, then upping my gelatin, a similar idea without lowering the protein.

 

[Rinse & rePeat]

Okay, that does sound a little more complete.

Did you have a liver taco recipe on that thread? Is it good?

I do have that recipe on my proteins thread.

Okay, that does sound a little more complete.

Did you have a liver taco recipe on that thread? Is it good?

Yes the recipe is on the page linked below. I can get more liver in with less starch making a Tostada with it or I will fry up chunks of braunschweiger and fry it in butter with onions, then toss in some sour cream at the end for a starch free meal.

EASY "PEATY" PROTEINS - Recipes with photos & Step By Step Instructions

RICOTTA FRITTATA 1. Since I just make stuff up as I go along, for this first time making this, I preheated my oven to 375°, but depending on the pan you use, you might want to play it safe at 350°. Gather your ingredients. I used two links of corn & soy free sweet Italian sausage in mine, and...

raypeatforum.com

 

[André Pohlann]

This is exacyly what has been my success in losing 18 pounds, effortlessly, this past 4 months. I cut out all of my meat and seafood, and upped my gelatin, putting it in my milk coffees. I have been talking about it, on the last pages of my two fat loss threads, with before and after pictures.

MORE WEIGHT LOSS TALK

“STARCH and GLUCOSE efficiently stimulate insulin secretion, and that accelerates the disposition of glucose, activating its conversion to glycogen and fat, as well as its oxidation. Fructose inhibits the stimulation of insulin by glucose, so this means that eating ordinary sugar, sucrose (a...

raypeatforum.com

Lose Fat Not Pounds & Seeing Is Believing (before & after pics)

"In one of the studies in which rats had been taught learned helplessness so they would drown in five or six minutes, just being able to see another rat escape would let the informed rat go for days without drowning. Just the recognition that someone else did it can make all the difference." Ray...

raypeatforum.com

I have seen only your last photos. You should messure body fat -a simple caliper should do it-, compare your value and start to be honest with your self.

 

[Rinse & rePeat]

I have seen only your last photos. You should messure body fat -a simple caliper should do it-, compare your value and start to be honest with your self.

Honest with myself?

 

[Riesensackteil]

I wonder if Proline and Taurine offset Methionine in similar fashion as Glycine because they overlap so much

 

[Grapelander]

I wonder if Proline and Taurine offset Methionine in similar fashion as Glycine because they overlap so much

Glycine is the vehicle for hepatic clearance of excess Methionine via glycine N-methyltransferase (GNMT).

 

[Grapelander]

Glycine intake decreases plasma free fatty acids, adipose cell size, and blood pressure in sucrose-fed rats
The study investigated the mechanism by which glycine protects against increased circulating non-esterified fatty acids (NEFA), fat cell size, intra-abdominal fat accumulation, and blood pressure (BP) induced in male Wistar rats by sucrose ingestion. The addition of 1% glycine to the drinking water containing 30% sucrose, for 4 weeks, markedly reduced high BP in sucrose-fed rats.

The protection by glycine against elevated BP might be attributed to its effect in increasing fatty acid oxidation, reducing intra-abdominal fat accumulation and circulating NEFA, which have been proposed as links between obesity and hypertension.

 

[tankasnowgod]

I wonder if Proline and Taurine offset Methionine in similar fashion as Glycine because they overlap so much

As Grapelander stated, Glycine is specifically used to clear Methionine from the body. However, Taurine may be helpful, in reducing Methionine absorption, according to the study posted here-

Taurine Blocks Methionine Absorption

and lowers homocysteine and therefore atherosclerosis Sounds like it might be worth taking if eating out along with your vitamin E and tryptophan transport blockers Taurine and Homocysteine Reduction Taurine can protect against coronary artery disease by favorably modulating blood levels of...

raypeatforum.com

I haven't heard of any mechanisms for proline. It is anti-inflammatory in it's own right, so it's a good amino to consume in it's own right. If it does somehow offset Methionine, I suspect it would be indirect, like being glycine sparing in some way.

 

[gabys225]

Dr. Joel Brind loves glycine, check out his product sweetamine (Sweetamine).

On the fact sheet it contains 8 grams of glycine with taurine and proline as well, less than 1 gram each.

https://www.sweetamine.com/images/Sweetamine-FACTsheet11-26-18.pdf

I always thought it was interesting that he opted for what seems like such a large amount, but when looking at the average methionine intake, it starts to make more sense.

Brind says we have way too much methylation going on, and most people are doing damage with TMG and choline. He says sulfur is very important, but in down stream metabolites like taurine NOT methionine. He states "As to what 'interferes with repairing and rebuilding mechanism of tissues', nothing interferes like inflammation, and nothing fuels inappropriate inflammation like glycine deficiency."

Glycine stimulates the production of glycogen, as well as assisting with detoxification.

Hans posted a study a while back on his collagen blog post saying "Meleendez-Hevia el al. estimated that endogenous synthesis of glycine in healthy humans can satisfy at most only 30% of the metabolic needs for the synthesis of proteins (e.g. collagens). Similarly, humans, young or adult, cannot synthesize a sufficient quantity of proline to repair wound tissues."

Gelatin rich lattes sounds like a great way to consume lots of glycine rich protein. I like the idea of urea.

I wish there was more data on the amino acid ratio of different species of mushrooms. I suspect, and this may be wishful thinking, that there are some amazing AA profile mushrooms right under our nose. Or a combination of a few different species, some potatoes and gelatin and we can be low (at least lower than when consuming meat) methionine with minimal powder consumption possible. Our lovely potatoes can even benefit from the addition of stearic acid.

 

[Andy316]

Does marinating muscle meat with lemon or in brine and cooking reduce its methionine content?

 

[Nik665]

i guess this is why i continue to get lean despite eating almost 3000 calories as my experiment has been all milk and fruit diet. my abs are starting to show despite my legs and arms gaining muscle, i am lookinvg very athletic. :) pretty cool although i do miss runny yolks

 

[Nik665]

Methionine-Restriction Diet (MRD) in Obese Adults With Metabolic Syndrome - Full Text View - ClinicalTrials.gov

Methionine-Restriction Diet (MRD) in Obese Adults With Metabolic Syndrome - Full Text View.

clinicaltrials.gov

 

[Rinse & rePeat]

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