Too Much Methionine Appears to be Bad For Mammals

I'm sure you all know by now that restricting the amino acid methionine in the diet provides many of the health and longevity benefits of calorie restriction - in mice, at least. This is only the case for methionine, not any of the other essential amino acids that must be obtained through diet, and the resulting changes in biochemistry are not exactly the same as calorie restriction. This suggests that, for example, the loss of visceral fat associated with calorie restriction also plays an important role in extended healthspan and longevity.

Per recent research, it looks like too much methionine is a bad thing - biochemical measures of damage and good operation that are improved by lowering methionine intake are instead made worse when methionine is supplemented in the diet. This worsened set of metabolic processes occurs in addition to any further unpleasant effects produced by the visceral fat tissue most of us would gain in boosting our methionine intake the easy way - by eating more.

Methionine restriction without energy restriction increases, like caloric restriction, maximum longevity in rodents. Previous studies have shown that methionine restriction strongly decreases mitochondrial reactive oxygen species (ROS) production and oxidative damage to mitochondrial DNA, lowers membrane unsaturation, and decreases five different markers of protein oxidation in rat heart and liver mitochondria. It is unknown whether methionine supplementation in the diet can induce opposite changes, which is also interesting because excessive dietary methionine is [damaging to the liver] and induces cardiovascular alterations.

Because the detailed mechanisms of methionine-related [liver demaage] and cardiovascular toxicity are poorly understood and today many Western human populations consume levels of dietary protein (and thus, methionine) 2-3.3 fold higher than the average adult requirement, in the present experiment we analyze the effect of a methionine supplemented diet on mitochondrial ROS production and oxidative damage in the rat liver and heart mitochondria.

...

It was found that methionine supplementation increased mitochondrial ROS generation and percent free radical leak in rat liver mitochondria but not in rat heart. In agreement with these data oxidative damage to mitochondrial DNA increased only in rat liver, but no changes were observed in five different markers of protein oxidation in both organs. ... These results show that methionine supplementation in the diet specifically increases mitochondrial ROS production and mitochondrial DNA oxidative damage in rat liver mitochondria offering a plausible mechanism for its [ability to cause liver damage].

Less oxidative damage should be taken as better, although it's not always that simple; in some circumstances a little oxidative damage can spur the body to better repair and prevention efforts in the future. Here, however, more oxidative damage is a bad thing. You'll recall the role of mitochondrial reactive oxygen species (ROS) in the damage of aging per the mitochondrial free radical theory of aging - increased damage to mitochondria and increased production of mitochondrial ROS are not good for long term health.

The lesson to take away from this - as for many other related research results - is that diet affects your long term prospects for health and degenerative aging on a sliding scale that is measured in calories and methionine intake. More calories and more methionine is worse for you. Fewer calories and less methionine, assuming you're still obtaining the optimum level of required nutrients, is better for you.

ResearchBlogging.orgGomez, J., Caro, P., Sanchez, I., Naudi, A., Jove, M., Portero-Otin, M., Lopez-Torres, M., Pamplona, R., & Barja, G. (2009). Effect of methionine dietary supplementation on mitochondrial oxygen radical generation and oxidative DNA damage in rat liver and heart Journal of Bioenergetics and Biomembranes DOI: 10.1007/s10863-009-9229-3

Comments

So meat and fish is bad eh ... :-(

Posted by: Erik at July 31st, 2009 1:37 PM

Researchers have speculated that vegan diets may offer benefits related to lowered intake of methionine:

http://www.longevitymeme.org/news/view_news_item.cfm?news_id=4015

Given the culture of veganism, I suspect that this speculated benefit would be hard to pick out from the effects of lowered calorie intake and other general health practices in demographic studies.

Posted by: Reason at July 31st, 2009 2:03 PM

If excess methionine contributes to aging, does this mean that SAM-e for is not a good idea, or is S-adenosylmethionine a different thing?

Posted by: Marlyne at August 2nd, 2009 8:54 PM

Does anybody know how much methionine is likely to be too much? I seem to remember one rat or mouse study using 0.4% of calories, but that only increased lifespan by about 10% I think. At that level 1.5mg per day is the rough target for a calorie restricted 1400 calorie diet - which seems doable. If anyone knows different I'd be grateful to know more.

Posted by: Darren Hackleton at August 3rd, 2009 7:56 AM

i snowboard so i weight train and cannot keep adequate muscle without adequate protein intake. i have seen no good information on how to restrict methionine without restricting general protein intake. how to single out methionine!!?? only way i see is using soy protein isolate.

Posted by: chuck at November 2nd, 2009 5:41 AM

"Fewer calories and less methionine, assuming you're still obtaining the optimum level of required nutrients, is better for you."

No, not particularly better, but what it can do is reduce fertility (in fruit flies). It seems once you're doing CR you can actually benefit from upping your methionine intake because it restores your fertility level without resetting your longevity to the non-CR normal.
http://www.physorg.com/news178984012.html

Posted by: donjoe at December 2nd, 2009 11:31 PM

I am delighted to learn of the research findings but a tad confused as to application in diet (additional or separate to caloric reduction). My confusion results from this article ( link: http://www.healthnews.com/natural-health/amino-acids/methionine-essential-sulfur-containing-amino-acid-643.html ). I paste here an outtake of two relevant paragraphs which, in part, address concerns my own as well as both Darren and Chuck. The article suggests that soy and grains are excellent resources of methionine.

Now what?!

The paragraphs:
"Methionine can be found in meat, as well as fish, eggs, and dairy products. For vegetarians, grains and soya beans are a good source, but beans belonging to the legumes are not. Natural and synthetic methionine is also available in supplements, as well as those containing SAMe, in either capsule, tablet or powder form.

Requirements of methionine vary according to a person’s body weight, but most average-size adults need approximately 800-1,000 mg per day. Children need twice that amount, and infants require five times that amount."

Posted by: Thomas at December 3rd, 2009 11:44 AM

Too much methionine is bad if it is not taken with a methyl donor. The high levels of methionine will lead to high levels of homocysteine - high levels of homocysteine are bad for the heart. That is why sam-e needs to be taken with b-vitamins, and methionine needs to be taken with a methyl donor and b-vitamins.

Posted by: adam at January 10th, 2010 1:10 PM

Are they talking about DL-Methionine or L-Methionine?

Posted by: Rudie at January 12th, 2010 4:21 AM

It's tough because one one hand some suggest CR animals do better with higher protein content, but in fact there is a lot of methionine in most protein sources. There may not be much methionine in soy, but too much soy might also be linked to neurodegenerative effects.

I generally defer to Michael Rae of the CR Society on these nutritional matters. It's his opinion that it's not feasible to try methionine restriction in humans to the level that's found to extend lifespan in mammal studies, but it's probably wise to make sure you just don't get *excess* methionine. See: http://www.crsociety.org/archive/read.php?2,205045,205045#msg-205045

In another recent post, he posits doing CR and Methionine restriction together may well be dangerous: http://www.crsociety.org/archive/read.php?2,202511,202520#msg-202520

So I wouldn't swap CR for Meth restriction, unless a lot more evidence for Meth restriction comes out, and would instead just make sure to not get more Meth than the RDA.

Incidentally, I also remember a meta study of meat diets, vegetarian diets, and vegan diets, and veganism didn't due particularly well when it came to all-cause mortality - vegetarians did best. It may be because vegans aren't doing enough Meth restriction to get a true anti-aging effect.

Posted by: kim at April 17th, 2011 2:08 PM

Methionine is required by mamals to form nails (Hard bit on the end of your fingers) I understand from my Vet eating to many raw eggs removes Methionine from the body.

Posted by: Eric at May 5th, 2011 6:11 AM

I had been intentionally consuming methionine foods (tahini sauce, Brazil nuts) when I drink alcohol because I'd read some studies showing it is linked to reduced colon cancer risk among alcohol consumers, my one bad habit.

There's also studies showing it reduces lung cancer risk. However interestingly I found studies showing it increases cancer growth rates in individuals that already have cancer because cancer cells use more methionine than healthy cells.

I'm skeptical of diet studies like this on animals. What do these rats eat for example, some sort of kibble fortified with synthetic vitamins? What about a human body that's consuming a plant based diet high in phytonutrients, folic acid, b vitamins, getting vigorous exercise etc. Surely one or more these things may work synergistically with methionine to actually have a net benefit in the long run.

What if we overlook something such as methionine having some sort of protective effect against certain environmental toxins on our bodies over an 70+ year lifespan where as these rats are just exposed to the lab environment.

Posted by: Pete at April 4th, 2012 2:08 AM

Your need for methionine is largely dependent on your genetically programmed rate of DNA methylation. Those who have a reduced rate of methylation can benefit greatly from increased intake of methionine to counteract this deficiency. Everybody is different; human health research must be considered carefully. Something that is harmful to one person may fill in a genetic hole for another.

Posted by: Richard Hibbs at December 1st, 2012 10:25 PM

Low-carb. diets have also been said to promote better health and longer life. It is hard to see how to combine all these themes.

I currently eat a mainly plant-based diet which is fairly low in carbs. say 100 g/day and slightly lower than average in methionine. Reducing the methionine any more would probably mean increasing the legumes and therefore also the carbs. I have no idea whether this would give any benefit.

I am a naturally thin person. Weight is not an issue, but health is.

Posted by: UK patient at August 28th, 2013 2:41 PM

Without being a scientist, it is my conclusion that only a scientist should fool around with exogenous S-Adenosylmethionine (SAMe) - not humane - not pets. No one taking oral SAMe can predict whether the responses will be beneficial or severely harmful. This is not to in any way imply that pharmaceuticals are properly prescribed; they are not, and there is no reason why this is so.

Posted by: Jake at November 10th, 2014 6:42 PM

Would someone having a low protein, low fat diet high in green leafy vegetables be at risk of unhealthy levels of methionine? I routinely eat a breakfast including a heaping plate of steamed kale, collards, or broccoli, all of which I believe are high in methionine. Wouldn't low levels of meat protein (therefore, low fat calorie), even with high levels of plant methionine, beneficially compensate for the "badness" of high methionine?

Posted by: Britt Peacemacher at June 1st, 2015 10:47 PM

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