Fat Science: Methionine restriction causes weight loss in mice


Last time we talked about the new fad of intermittent fasting that has most of the benefits of calorie restriction on longevity and good health without the pain of being hungry all the time. But intermittent fasting does involve being hungry part of the time and that part of the time is still hard. Could there be an even better way? How does this form of torture work? Methionine restriction might be at least part of the answer to these questions.

Methionine is almost always the first amino acid in the chain of amnino acids that make up all the proteins in your body. It is one of the essential amino acids that you can’t make from scratch. So it has to come from what you eat. That means you can’t remove methionine totally from your diet or you will eventually die. Methionine is also one of the two amino acids together with cysteine (not an essentially amino acid) that contains sulfur. In the short term, removal of only methionine from the diet can reverse diet-induced obesity and promotes insulin sensitivity in mice, and methionine restriction also protects a mouse model from spontaneous, polygenic obesity and diabetes.

A recent report shows some of how this works and some of how it probably doesn’t work in mice. (1) The data shows that wild type male mice who are induced to be obese by a high fat diet who are then fed a methionine restricted diet lost 45% of their body weight. Otherwise similar mice continued without methionine restriction gained 8% at 8 weeks after diet initiation. So food intake other than methionine, remained similar throughout the experiment. (Remember though, as we’ve told you many times, humans don’t get obese by eating a high fat diet like mice do.) They also repeated the experiment with the same results in mice with genetic manipulations that prevented the rise of adiponectin and fibroblast growth factor 21 that was seen during methionine restriction. So these were two things that were not causal factors in this process.

It has been seen that methionine restriction promotes a futile lipid cycle and apoptosis and autophagy in fat and other body tissues. Futile lipid cycle means that calories are burned without making energy that can be used in the body other than heat production. This happens in brown fat. This is a way for animals to stay warm. Apoptosis is the programmed death of cells and autophagy is the process of getting rid of some of a cell’s internal structures to conserve energy and/or to rebuild. Methionine restriction extends lifespan and healthspan across different species. The same benefits we saw with calorie restriction and intermittent fasting.

If you kids want to try this at home most fruits and vegetables contain very little methionine. Beef has the highest content of methionine at 0.680 g/100 g. Poultry, lamb, veal, game, finfish, shellfish, pork, dairy and egg all contained more than 0.4 g/100 g. Most legumes, though protein dense, are lower in methionine. (2) Maybe those vegan diet eaters are on to something.


However in my anecdotal experience it is harder to avoid methionine – it’s in bread and beer from the yeast, and almost everything – than it is to just not eat anything and then you’re back to starving again. Unless you want to go on a non-food highly processed diet that’s even harder.

1. Cooke D. et al. Weight Loss and Concomitant Adipose Autophagy in Methionine‐Restricted Obese Mice is Not Dependent on Adiponectin or FGF21. Obesity April 20,2020. https://doi.org/10.1002/oby.22763

2. Ables GP, Johnson JE. Pleiotropic responses to methionine restriction. Experimental Gerontology 2017;94:83-8. https://doi.org/10.1016/j.exger.2017.01.012

John DiTraglia M.D. is a Pediatrician in Portsmouth. He can be reached by e-mail- [email protected] or phone-354-6605.

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