tankasnowgod
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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.
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-
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
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