On Methionine Restriction

Levels of the essential amino acid methionine in the diet appear to be involved in generating the beneficial effects of calorie restriction on health and longevity. Some portion of the resulting changes in the operation of metabolism is based on sensing low levels of methionine. It is thus possible that humans might obtain benefits comparable to those generated by calorie restriction from a sensibly constructed low-methionine diet with a normal calorie intake. The research in support of this supposition is still sparse in comparison to that for calorie restriction, however.

It was first reported in 1993 that rats subjected to a diet restricted in methionine (MR) enjoyed comparable life spans to rats that were on caloric restriction (CR). In the first experiments, methionine was reduced to ⅕ its normal level in the diet, and growth of the rats was severely stunted. We can't live entirely without methionine - the body would not be able to make any proteins at all. Restricting methionine is likely to have impacts on growth, health, and wellbeing that are as yet unstudied in humans. Rats fed a diet without methionine developed steatohepatitis (fatty liver), anemia and lost two thirds of their body weight over 5 weeks. In one experiment where methionine was severely restricted but not eliminated entirely, ⅕ of the mice died, and the other ⅘ went on to live longer than control mice.

Here's a clue about why methionine is special. The instructions for making proteins is coded into DNA, via the genetic code, which specifies words of 3 DNA letters, each corresponding to one of the 20 amino acids. The genetic code also contains "punctuation", instructions to start and stop. The "start codon" is also the word for methionine. Every chain of amino acids that the body constructs begins with methionine. No methionine - no protein synthesis. A shortage of methionine means that the body is inhibited in making every kind of protein. More genes are expressed (more proteins synthesized) as the body grows older. Perhaps methionine restriction is putting a brake on this production of extra proteins that are not produced when we're young, and that contribute to aging.

Methionine restriction in practice involves eating foods that are low in methionine. Though all protein has methionine, some protein sources are much lower in methionine than others. All animal sources (including milk and especially eggs) are high in methionine. So a methionine-restricted diet is a vegan diet, not just any vegan diet, but a subset of vegan protein sources. There appear to be no general rules. For example, almonds are a good source of low-methionine protein, but Brazil nuts are terrible. Even a strict vegan diet would only reduce methionine intake by about 1/2. Extrapolating from the rodent experiments, we may need to reduce by ~ 3/4 before crossing a threshold where benefits kick in.

Link: http://joshmitteldorf.scienceblog.com/2013/05/13/could-cutting-this-one-nutrient-make-you-live-longer/


A simple approach to Methionine restriction is to take Glycine which causes the liver to remove Methionine from the body. Glycine is cheap and can be used as a sweetner.

Posted by: tom Blalock at May 19th, 2013 4:56 PM

A methionine restricted diet requires eating a high quantity of fruit, no nuts or seeds and minimal grains and legumes. A vegan diet typically provides much more than sufficient protein. Methionine restriction can shrink tumors by inhibiting protein synthesis in cancer cells. Because cancer cells exhibit dysfunctional cell cycle restriction checkpoints, they first cell cycle arrest and then enter apoptosis after methionine is repleted.

Periodic fasting is an option for cancer patients with sufficient fat stores and low tumor burden.

Posted by: Mark at May 20th, 2013 4:48 PM

"A methionine restricted diet requires eating a high quantity of fruit, no nuts or seeds and minimal grains and legumes. A vegan diet typically provides much more than sufficient protein. "

A handful of nuts a day is said to be almost as beneficial as exercise, and can be practically linearly combined with the benefits of exercise. There are some nuts that are very low in protein, one is macadamias. A handful of macadamia intake should have very little effect on total methionine intake.

Posted by: Darian Smith at February 19th, 2014 2:32 PM

Ok, I'm very inteested. But, I have Marfan Syndrome, a connective tissue disorder (which is how I found this page)....
If my homocysteine levels are too high and I need the right balance 0f B6, B9.folat, and B12, where do I get them on a low-methionine diet (without taking pills)? I have been on a pescetarian whole foods diet for years with mostly good results, according to cheap blood tests.
What about omega-3s ?Zinc? Iron ?
I think eating NO meat except fish high in omega-3s might work....along with no wheat (mostly gave it up long ago)or corn....
Calorie Restriction has still proved the best method. I think I'll simply greatly lessen my methionine foods. I already eat low-calorie...usually.
Any thoughts?

Posted by: Wynn H at January 21st, 2015 5:30 PM

I found I have uterine cancer and read that many cancers thrive
on methionine. I routinely add B's Amino Acids to many things I cook and am attempting to transition to a macrobiotic diet as I knew it from friends in 1980's. I can see that I have a lot to learn. I tend to overdo the nuts. Macrobiotic diet requires tons of whole grains, tofu, can't see it as low in methionine. I am unable to exercise unless I can find a pool or good swimming hole. I read about Macadamia nuts when I thought I might have a problem with oxalates. I have so many factors to try and consider and my brain get overwhelmed with information these days. I guess I'll keep looking for answers. I'm also visually impaired so it's hard to read, but I do love Dr. Gregor and will be watching more of his videos. If there's an answer, it will probably be there. I welcome other suggestions.

Posted by: Connie Jean Conklin at June 25th, 2020 3:47 PM
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