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Methionine Restriction as a Life Extension Strategy

Plant-based diets may prove to be a useful nutrition strategy in both cancer growth control as well as lifespan extension because these diets are naturally lower in methionine.

September 20, 2013 |
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Supplementary Info

Sources Cited

V. Agrawal, S. E. J. Alpini, E. M. Stone, E. P. Frenkel, A. E. Frankel. Targeting methionine auxotrophy in cancer: discovery & exploration. Expert Opin Biol Ther 2012 12(1):53 - 61.

M. F. McCarty, J. Barroso-Aranda, F. Contreras. The low-methionine content of vegan diets may make methionine restriction feasible as a life extension strategy. Med. Hypotheses 2009 72(2):125 - 128.

M. C. Ruiz, V. Ayala, M. Portero-Otín, J. R. Requena, G. Barja, R. Pamplona. Protein methionine content and MDA-lysine adducts are inversely related to maximum life span in the heart of mammals. Mech. Ageing Dev. 2005 126(10):1106 - 1114.

M. López-Torres, G. Barja. Lowered methionine ingestion as responsible for the decrease in rodent mitochondrial oxidative stress in protein and dietary restriction possible implications for humans. Biochim. Biophys. Acta 2008 1780(11):1337 - 1347.

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E. Boedeker, G. Friedel, T. Walles. Sniffer dogs as part of a bimodal bionic research approach to develop a lung cancer screening. Interact Cardiovasc Thorac Surg 2012 14(5):511 - 515.

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K. Yamagishi, K. Onuma, Y. Chiba, S. Yagi, S. Aoki, T. Sato, Y. Sugawara, N. Hosoya, Y. Saeki, M. Takahashi, M. Fuji, T. Ohsaka, T. Okajima, K. Akita, T. Suzuki, P. Senawongse, A. Urushiyama, K. Kawai, H. Shoun, Y. Ishii, H. Ishikawa, S. Sugiyama, M. Nakajima, M. Tsuboi, T. Yamanaka. Generation of gaseous sulfur-containing compounds in tumour tissue and suppression of gas diffusion as an antitumour treatment. Gut 2012 61(4):554 - 561.

H. Y. Guo, H. Herrera, A. Groce, R. M. Hoffman. Expression of the biochemical defect of methionine dependence in fresh patient tumors in primary histoculture. Cancer Res. 1993 53(11):2479 - 2483.

D. E. Epner. Can dietary methionine restriction increase the effectiveness of chemotherapy in treatment of advanced cancer? J Am Coll Nutr 2001 20(Suppl 5):443S-449S; discussion 473S-475S.

E. Cellarier, X. Durando, M. P. Vasson, M. C. Farges, A. Demiden, J. C. Maurizis, J. C. Madelmont, P. Chollet. Methionine dependency and cancer treatment. Cancer Treat. Rev. 2003 29(6):489 - 499.

B. C. Halpern, B. R. Clark, D. N. Hardy, R. M. Halpern, R. A. Smith. The effect of replacement of methionine by homocystine on survival of malignant and normal adult mammalian cells in culture. Proc. Natl. Acad. Sci. USA 1974 71(4):1133 - 1136.

D. Pickel, G. P. Manucy, D. B. Walker, S. B. Hall, J. C. Walker. Evidence for canine olfactory detection of melanoma. App Anim Behav Sci 2004 89(1):107-­116.

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McCarty MF, Barroso-Aranda J, Contreras F. The low-methionine content of vegan diets may make methionine restriction feasible as a life extension strategy. Med Hypotheses. 2009 72(2):125-8.

Acknowledgements

Images thanks to windsordi and Ed Yourdon via Flickr and thanks to Ellen Reid, Maxim Fetissenko, PhD, and Laurie-Marie Pisciotta for their keynote help.

Transcript

This recent review, (noting that vegan diets, in part because they tend to be naturally low in methionine, an amino acid and thus a “building block” of protein), may prove to be a useful nutritional strategy in controlling cancer growth) also looked at methionine restriction and lifespan extension. It seems that the less methionine there is in body tissues, the longer different animals tend to live. But what are the possible implications for humans?

I've talked before about the free radical theory of aging, the concept that aging can be thought of as the oxidation of our bodies just like rust is the oxidation of metal, and methionine is thought to have a "pro-oxidant effect." So the thinking is that lower methionine intake leads to less free radical production—the creation of so-called reactive oxygen- and fewer free radicals would slow the rate of DNA damage, which slows the rate of DNA mutation, slowing the rate of aging and disease, thereby potentially increasing our lifespan.

There are three ways to lower methionine intake. The first is caloric restriction—they call it dietary restriction here, meaning you cut your intake of food in half, for example, by only eating every other meal. That would lower your methionine intake. Or, because methionine is found concentrated in certain proteins, you could practice protein restriction across the board, eating a relatively protein deficient diet. The third option is eat enough food, eat enough protein, but just eat plant proteins that are relatively low in methionine.

Caloric restriction is hard, because you walk around starving all the time. Something like every-other-meal eating is never likely to gain much popularity as a pro-longevity strategy for humans, so it may be more feasible to achieve moderate methionine restriction, in light of the fact that plant-based diets tend to have low levels of methionine. As we've seen, plant proteins tend to be lower in methionine than animal proteins.

Yes, protein restriction across the board can be performed to avoid the hunger of caloric restriction, but again, methionine restriction could also be performed emphasizing low-methionine, high quality vegetable sources of protein. Among foods containing plant proteins, legumes are especially rich in essential amino acids, offering excellent substitutes for proteins of animal origin.

The fact that beans have comparably low methionine has been classically considered a disadvantage. But given the capacity of methionine restriction to decrease the rate of free radical generation in internal organs, to lower markers of chronic disease, and to increase maximum longevity, this “disadvantage” is actually a strong advantage. And it fits well with the important role of beans in healthy diets like the traditional Mediterranean diet. Interestingly, soy protein is also especially poor in methionine, and it is widely considered that soy-containing foods have healthy effects in human beings.

On a population-wide level, folks could benefit from just lowering their protein intake, period. "The mean intake of proteins [and thus methionine] of Western human populations is much higher than needed. Therefore, decreasing such levels has a great potential to lower tissue oxidative stress and to increase healthy life span in humans while avoiding the possible undesirable effects of caloric restriction.” We're eating around double the protein we need, so the first thing doctors can recommend is just that decreasing the intake of protein has a large potential to bring health benefits.We can also get our methionine even lower by eating a plant-based diet.

The reason why plant-based diets are so protective is not known. Yes, vegetables contain thousands of phytochemicals, but separately investigating their possible protective roles would be an impossible task. The idea that the protective effect is not due to any of the individual plant food components, but to a synergic “combined effect” is gaining acceptance. However, based on the relationship of excess dietary methionine to vital organ toxicity, as well as its likely mechanism of action through increases in free radical generation, the possibility exists that the protective effects of plant-based diets can be due, at least in part, to their lower methionine content

This is not a new idea. It was proposed back in 2009, but is only now gaining increasing acceptance in more mainstream scientific circles. Therefore, "The low-methionine content of vegan diets may make methionine restriction feasible as a life extension strategy"

To see any graphs, charts, graphics, images, and quotes to which Dr. Greger may be referring, watch the above video. This is just an approximation of the audio contributed by Ariel Levitsky.

To help out on the site please email volunteer@nutritionfacts.org.

Dr. Michael Greger

Doctor's Note

For an explanation on how and why plant-based diets are an effective dietary methionine restriction strategy, see the last video Starving Cancer with Methionine Restriction.

For background on the free radical theory of disease, see Mitochondrial Theory of Aging.

Plant-based diets can also mimic other benefits of caloric restriction, such as improving levels of the "fountain of youth" hormone DHEA. See The Benefits of Caloric Restriction Without the Actual Restricting.

Americans Are Living Longer but Sicker Lives. That's why we need a diet and lifestyle that supports health and longevity. I have a whole presentation on the role diet can play in preventing, arresting and even reversing many of our top 15 killers: Uprooting the Leading Causes of Death, one of my Top 10 Most Popular Videos of the Year.

I've touched previously on the irony that animal protein may be detrimental for the same reasons it's touted as superior in Higher Quality May Mean Higher Risk.

What other properties do magic beans have? See Beans and the Second Meal Effect. What about intestinal gas, though? Check out my blog Beans and Gas: Clearing the air.

For more context, check out my associated blog post: A Low Methionine Diet May Help Starve Cancer Cells and How Plant-Based Diets May Extend Our Lives.

If you haven't yet, you can subscribe to my videos for free by clicking here.

  • Mr.fungi

    Mushrooms are even better

  • http://treegrower.org/ Calvin Leman

    T Colin
    Campbell’s book: Whole: Rethinking the science of nutrition explains why Dr
    Greger reports “The reason why
    plant-based diets are so protective is not known.”

    Nutrition is
    a wholistic idea and cannot be known by reductionist research.

    • Thea

      Calvin: I also thought of Campbell when I saw this (excellent) video.

      Here’s the part that got me (around 4:05): “The idea that the protective effect is not due to any vegetal food components, but to a synergistic (combined) effect is gaining acceptance…”

      This is what Campbell has been saying for *years*!!! And it makes perfect sense to me. It must be a huge relief for Campbell if his points are finally getting some notice.

  • Ronald Chavin

    The plant-based diet that Dr. Greger always recommends in his videos (high in legume protein and dried fruit sugars) greatly increases flatulence and is therefore not practical for most working class Americans. The Japanese in Japan, who typically must live in a room with only one-seventh of the living space that Americans occupy at home, have learned to eat foods that don’t cause anywhere near as much flatulence as Dr. Greger’s recommendations. The extremely healthy foods that the Japanese in Japan eat that don’t cause much flatulence include: natto (fermented whole soybeans), tofu (soybean curd with 90% of the fiber removed), edamame (baby whole soybeans with about half of the flatulence-causing raffinose bred out), unsweetened soymilk (fiber removed), green tea, fish, shellfish, brown seaweeds (wakame, kombu, arame, mozuku, and hijiki), red seaweeds (nori and ogo), mushrooms (fresh shiitake, dried shiitake, maitake, reishi, enokitake, buna-shimeji, bunapi-shimeji, hon-shimeji, hatake-shimeji, king oyster, nameko, hiratake, and matsutake), konnyaku slices (zero calories), shirataki noodles (zero calories), sukiyaki (uses shirataki noodles), brown rice, white rice, wholegrain buckwheat noodles, tomatoes, daikon (giant white turnips), and green vegetables. Strangely enough, rice is the only plant starch that does not cause flatulence:
    http://metamodern.com/b/wp-content/uploads/2009/11/gapminder_spending_health_L.png
    http://userdisk.webry.biglobe.ne.jp/014/143/38/N000/000/000/121333176807216106944.png

    • M85

      I eat large quantities of beans and legumes in general and i have very little flatulence: i tend to digest them really well. I’ve heard some people say that legumes cause them flatulence but these are often meat eaters who eat them quite rarely, perhaps the human body gets used to them over time.

      • Tushar Mehta

        Me too – and i also know dozens of vegans who also eat so many legumes and have only some have gas issues. When it happens to me, a good probiotic helps. I choose one with over 10 billion CFU and over 10 different species. I bought a bottle a year ago and still have lots left since a single tab does the job – like hitting a reset button on the gut bacteria!

        • b00mer

          Me three! The only time I have issues is when I go off my usual diet, e.g. during travel (still vegan, but not as whole vegetable/grain/bean-based, and higher fat). During travel I’m fine, but when I get back to my usual diet, I’m off for a day or two. Healthy Librarian shared a study once showing that even just one day of high fat (high sugar too? don’t remember) eating severely disrupted the gut population.

          If anyone’s interested in gut population, the Healthy Librarian (she has a blog and is on fbook) is really into it and posts a lot of interesting studies.

          • cyndishisara

            I eat tons of beans and have no flatulence. As doctor Greger says your body has a fast learning curve when it comes to beans, we adopt fast!

    • Toxins

      Dr. Greger will cover flatulence of beans in one of his upcoming videos

    • Darryl

      The α-galactosides like raffinose responsible for flatuence also promote beneficial intestinal bacteria like Bifidobacterium and Lactobacilus. Given the short generation times and rapid adaptation of gut microbiota to habitual diet, feeding the good bacteria with resistant starches may be a good deal more effective than popping probiotic supplements.

      I found that when I first adopted a vegan diet almost 4 years ago, I indeed produced more gas and had bouts of diarrhea for almost a month, until my digestion and gut microbiota adapted. Thereafter its been smooth sailing, with little more gas than when I was an omnivore.

      Its also plausible that the lower sulfur content of many plant foods compared to animal foods could reduce intestinal production of hydrogen sulphide, dimethyl sulphide, and methyl mercaptan, the compounds most responsible for malodiferous flatuence. It seems opinions on the net markedly on this point, though.

      • Ashwin Patel

        Yes, commensal Bacteria are known to thrive on intestinal mucin which contains Sulphur. In view of this fact, is there any point in worrying about the Sulphur conten of Plant food or Animal protein?

    • Stephen Lucker Kelly

      What? I eat beans all the time and legumes and I rarely fart. I fart more after eating fats to be honest.

    • abstract

      Simply soak the beans/seeds/nuts over night and throw away the water. and u can even freeze them for later use. And remember to chew your food slowly.

  • Steven Christensen

    Doctor, I know this study is way to small to be remotely conclusive, but the results seem very interesting:

    http://news.yahoo.com/lifestyle-change-may-reverse-ageing-cells-112550336.htmlhttp://

    I am interested in your thoughts about it.

  • Ashwin Patel

    Methionine is an essential Amino Acid. Just because it may be pro-oxidant does not mean we should restrict it in our diet. Oxygen is an Oxidant and may be the cause of ageing. Should we all stop breathing?

    • LP

      No, but we only need 21% oxygen, in higher concentrations the negative effects are amplified.

    • fargo_r

      Ashwin: Your logic is loose. These articles are about “restriction” not elimination of Methionine. Oxygen comes to us limited to 21% and there is little can do about that (other than live a very high altitude). Methionine comes to us in a great or lesser amount depending on what we eat. It may be essential…but we don’t need very much. More may be worse….just as more oxygen can be worse. Elimination of either is not good…or advised here.

  • Linda

    Thank you for this enlightening research video summary… I will pass the link for this on to those with cancer!

    Love your sense of humor… “Doctors can now bring their Lab to the lab… gives a whole new meaning to pet scan”! Too Funny!

  • Southlander

    Outstanding information. I’m slowly but surely going vegitarian. Don’t know if I’ll ever be vegan (72 years is a lot to make up for) but we’ll see what the future holds. Don and I CAN! :-))

    • Thea

      Southlander: I wanted to give you some encouragement.

      re: “slowly but surely”

      That’s the way to think of it. You are on a path. I just encourage you not to limit where you will end up. My parents are in their late sixties and early seventies. They went vegan about a year ago I think. For *years* my father swore that he would never go vegan. He wasn’t even vegetarian.

      I kept up a polite sharing of information, including Dr. Greger’s videos. And then both of them started to get some unpleasant health news. They finally got serious about eating a healthy diet. It has been really great for both of their healths. While they could do better about staying away from oils and processed grains (me too for that matter!), both of my parents’ health by several measures have significantly improved since they went vegan.

      So, you don’t have to go cold turkey. And you shouldn’t expect miracles. But I do encourage you to set your end goal to be as healthy as possible. Because I totally agree: You and Don CAN!!!

  • Plantstrongdoc M.D.

    Are there any arguments against a whole food plant based diet? You feel better, you look better, you are more disease free, you smell better, you live longer and the food taste better. The bulk of evidence support a WFPD as the best diet for humans.

    • http://www.DonForresterMD.com/ Don Forrester MD

      I know of no arguments against a whole food plant based diet. In my experience it is a journey and changing your behaviors from shopping, cooking and eating out in the world takes time. We also have to reorder our priorities to include setting aside time for our new nutritional behaviors and working on fitness… aerobics, strength, flexibility, balance and stability.

  • Ben

    It take prescribed fish oil. Am I swallowing “methionine bullets”?

    • Toxins

      Fish oil is an extremely concentrated source of pollutants. It is strongly advised against.
      http://nutritionfacts.org/topics/fish-oil/

    • cyndishisara

      Anytime you extract a fat especially a poly unsaturated fatty acid (PUFAs) you have problems with oxidation. This is why whole foods are best.

  • fineartmarcella

    I am a raw vegan, I was told a few months back that raw beans are toxic, do you know if they are, and if they are, then are kidney, pinto, black beans ok if sprouted?

    • Toxins

      Beans contain many anti nutrients and protein inhibitors when consumed raw, sprouting does significantly reduce these chemicals.

  • Enola Knezevic

    The recommended intake of methionine + cysteine for me is 1 g a day. I track my nutrient intake with cronometer.com. It’s impossible to get less than 100%. I usually get 1.2 g of methionine a day, and even more cysteine. That’s with a vegan, mostly whole food diet. My protein intake is usually 75 g a day, but even when I get only 45g of protein a day, I get way more methionine + cysteine than recommended.

    The famous life extensionist and calorie restrictor Michael Rae says that methionine restriction is impossible in humans, because plant foods (he is not a vegan, but avoids animal products) still contain too much methionine. He practices methionine moderation as well as cysteine moderation and leucine moderation.

    It would be awesome to be able to buy foods with methionine removed (at least for cancer patients), but I don’t expect it in near future.

    • Tobias Brown

      This seems to be an important point in this discuss which Dr Greger hasn’t tackled yet, or maybe I’ve missed something. If we at the beans and legumes that he recommends, it’s going to be very hard to have “low protein”, say 45 g for a 70 kilo person, and thus of methionine. I’ve been using Cronometer too and after a month set to lose 2 pounds per week (which, BTW, is too fast for me), that is, at a net calorie intake of 1400 calories per day, still my protein level is 66 grams (lost 8 pounds during this period down to 168 lbs). In the last week I tried reducing lentil consumption and protein averaged down only 3 points, with methionine remaining fixed at .8 grams. I would really like to see some commentary on this question. Oh yeah, once I resume eating at maintenance level, I expect protein to be up near 75 grams. I’m on a strict plant-based diet where I restrict nuts, seeds to only 1 oz per day, and when I eat lentils or peas, it’s 5 ounces.

  • dina

    Good morning,
    Me and my husband are on a daily basis eating brocolli, sesame seeds(in the form of tahini), and pumpkin seeds, in order to protect our selves from heart and cancer problems.
    Now by this new theory of methionine restriction, we will have to take the above mentioned food out of our lives?Is this true?
    Thanks in advance for you reply.

    • b00mer

      Hi dina,

      Methionine is an essential amino acid, meaning it is required that you ingest it, and also, that it is present in all natural whole foods. So 1) you do need to eat some, and 2) you couldn’t completely eliminate it even if you want to. The idea here is just to not go overboard on methionine (by eating animal products with extremely high amounts of it).

      To put things in perspective:

      An entire medium head of broccoli contains about 80 mg methionine, a Tbsp of tahini contains 90 mg, and a couple Tbsp of pumpkin seeds contains 100 mg. Even though these could possibly be higher values compared to other plant foods, compared to a serving of beef, chicken, or fish, which average closer to 1100-1600 mg, you can see that even these plant foods have relatively low amounts of it.

      As an average height, slim female, my daily requirement of methionine is 600 mg/day. I eat a WFPB diet, with plenty of vegetables including a LOT of broccoli (my favorite!), beans, whole grains, and usually some sunflower, sesame, or pumpkin seeds daily. With that I average only about 110% of my daily methionine requirement. I wouldn’t want to go below 100%, since it is essential, but I’m happy to be on the lower end. Contrast that with eating just a single chicken breast, *with nothing else*, and I would already by at about 250% of my daily requirement. You can use cronometer.com or the USDA food databases to track these things yourself if you would like.

      So while there are other issues at least involving seeds (omega-6 and overall fat content) to be aware of, I don’t think you should worry about methionine content. And definitely don’t cut back on the broccoli! :)

      • Tobias Brown

        Thank you for trying to flesh out this issue and for providing your details. Fellow Cronometer users.

  • lucidvu

    I’ve seen low methionine status in people eating omnivorous diets. There are various situations where repleting methionine has been beneficial. One example is with methylmercury exposure (MeHg).

    “In summary, our results show that Met(hionine) pre-treatment produces pronounced protection against the toxic effects induced by MeHg and/or the MeHg-Cys complex on mitochondrial function and cell viability. Consequently, this amino acid offers considerable promise as a potential agent for treating acute MeHg exposure.”

    Modulation of methylmercury uptake by methionine: prevention of mitochondrial dysfunction in rat liver slices by a mimicry mechanism.
    Toxicol Appl Pharmacol. 2011 Apr 1;252(1):28-35. doi: 10.1016/j.taap.2011.01.010. Epub 2011 Jan 27.

  • goo

    Is S-adenosylmethionine (SAM-e) the same as Methionine? I’ve recently seen SAM-e advertised at Trader Joe’s as a remedy for depression, liver problems, joint pain and premature ejaculation. Are these claims supported by research? What are the potential side effects? Are there any food sources of SAM-e?

  • cris

    What are your thoughts on morning a plant that’s high in methionine but said to fight Cancer?

  • cris

    That’s moringa …not morning a below

  • narroway

    Thank God for Dr. Greger.

  • Patrick

    Interesting!

    I wonder if Methionine can be found in all food rich
    in proteins, are there a higher rate of cancer patients in health clubs for
    instance, or people who eat a lot of protein rich food just to increase their
    muscle tissue…

  • DontGetIt

    Just to go off on a tangent, since everyone is talking beans and flatulence – what I’ve learned in my 1 1/2 years eating vlf vegan is that if I chew my food a lot more thoroughly then I did before the change in diet it greatly reduces the problem. Chewing apples, and beans, and anything with an outer husk gives the small intestine a chance to digest much more efficiently, and therefore less food to ferment and cause issues in the big intestine. My theory, anyway…

  • DL Stephens

    OK, then…should I keep or toss out the $4.00 bottle of BRAGG’ Liquid Aminos All Purpose Seasoning I just bought that has methionine in it? HELP, please, I don’t want to fuel cancer cell growth!!!

  • Stephen Lucker Kelly

    What is classed as low? 0.5g? Lower?

  • Tobias Brown

    Even when I cut out bean and lentils from my strict plant-based diet (limited to 1 oz of seeds per day plus a teaspoon of ground flax) my total protein intake remains close to 70 grams (65-67), and this during my weight-cutting effort where my total daily intake is restricted to 1900 calories. So, I don’t see how plant-based can be adapted to the level of 40-50 grams of protein per day, especially while consuming bean and/or lentils, even at modest amounts. What would this type of diet look like? Does anyone here have their protein intake this low? What does your diet consist of?

  • Vladimir

    And what about the Methionine in protein shake? Good or bad compare to meat intake?