A Little Methionine Restriction Research

Calorie restriction is definitely good for you, provided that you maintain an optimal intake of micronutrients in your smaller diet. There is a tremendous weight of evidence for the benefits of calorie restriction in animals and a large weight of evidence for benefits in humans: it improves near all short term measures of health, slows down the progression of near every measure of degenerative aging, and extends healthy life in most species. Research publications are usually more understated in their evaluation of calorie restriction, of course. See this, for example:

Caloric Restriction: Implications for Human Cadiometabolic Health

Evidence from animal studies and a limited number of human trials indicates that calorie restriction has the potential to both delay cardiac aging and help prevent atherosclerotic cardiovascular disease via beneficial effects on blood pressure, lipids, inflammatory processes, and potentially other mechanisms.

The candidate list of mechanisms by which calorie restriction likely delivers its benefits include reduced visceral fat, increased levels of autophagy, altered mitochondrial function, and metabolic changes caused by reduced levels of methionine in the body. All of these on their own have been shown to extend life and improve measures of health in animal studies. Many other measurable changes result from calorie restriction, but identifying which of them are definitively primary and which are definitively secondary is still a work in progress.

Methionine is one of the essential amino acids that your metabolism doesn't manufacture. You have to obtain it in the diet, and it's an essential component for the cellular manufacture of new protein machinery. There are all sorts of studies in mice and rats showing that if you keep the same dietary calorie level but strip out much of the methionine then the animals involved live longer, and exhibit many of the same changes in metabolism as occur from reduced calorie levels. Here is a recent example:

Methionine restriction affects oxidative stress and glutathione-related redox pathways in the rat

Lifelong dietary methionine restriction (MR) is associated with increased longevity and decreased incidence of age-related disorders and diseases in rats and mice. A reduction in the levels of oxidative stress may be a contributing mechanistic factor for the beneficial effects of MR. To examine this, we determined the effects of an 80% dietary restriction of Met on different biomarkers of oxidative stress and antioxidant pathways in blood, liver, kidney and brain in the rat.

Male F-344 rats were fed control (0.86% methionine) or MR (0.17% methionine) diets for up to six months. Blood and tissues were analyzed for [levels of the natural antioxidant] glutathione (GSH). related enzyme activities and biomarkers of oxidative stress. MR was associated with reductions in oxidative stress biomarkers [and] erythrocyte protein-bound glutathione after one month with levels remaining low for at least six months.

Levels of free GSH in blood were increased after 1-6 months of MR feeding whereas liver GSH levels were reduced over this time. In MR rats, GSH peroxidase activity was decreased in liver and increased in kidney compared with controls. No changes in the activities of GSH reductase in liver and kidney and superoxide dismutase in liver were observed as a result of MR feeding. Altogether, these findings indicate that oxidative stress is reduced by MR feeding in rats, but this effect cannot be explained by changes in the activity of antioxidant enzymes.

You might compare the comments above with the two calorie restriction research papers I pointed out earlier today - you'll quickly see the similarities, such as the fact that the behavior of antioxidants and oxidants in metabolism is complex and hard to tie to the observed benefits in health and longevity. All in all it is convincing to argue that methionine sensing is at the heart of the metabolic changes that produce the benefits of calorie restriction:

From the practical standpoint of day to day effort and willpower, I'd say that that there isn't much difference between eating a calorie restricted diet and a methionine restricted diet. The latter is harder by far to organize, I think. You certainly couldn't do it without a lot of research, extra food preparation, and meal planning, and there are few resources out there to help you short-cut the process. Calorie restriction, on the other hand, just requires you to keep count and be sensible, plus of course to have a willingness to be hungry for some time every day. It's that latter item that most people find a challenge, in this age of ubiquitous, cheap, tasty food. Calorie restriction also has a far greater weight of supporting evidence for benefits to health in humans, which is probably the most important factor of those mentioned here, but every choice you make has trade-offs.


MR is a very promising standalone treatment for early stage cancers. MR is a powerful adjunctive treatment to enhance the effectiveness of cytotoxic agents.

MR is easy to implement once one understands the methionine content per 100 grams of specific foods and food groups. Google "The Methionine Project" for an easy to understand chart of foods and their methionine level.

Fruits are very low in methionine and most vegetables are quite low. Soy, sesame and some nuts and seeds are high. Animal protein has the highest levels of methionine.

MR naturally restricts caloric intake because high fat foods are limited and one eats mostly foods with low caloric density. Also, most low methionine foods with the exception of oils and processed sugars have a high nutrient density and are loaded with antioxidants.

Posted by: Mark at June 16th, 2013 2:24 PM

Thanks to Mark for the above comment. I found this article really interesting as I have been looking for an anti aging diet that doesn't have to do with calorie restriction - not that calorie restriction is ineffective, I just personally find it very difficult to eat less.
A methionine-based diet seems like the perfect alternative since most of the foods on that list has the effect of being very filling. I'll be giving it a try. Thanks!

Posted by: Janet Kam at June 17th, 2013 11:19 PM
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