27 replies to this topic

[mat]

Hello

I read a lot of stuff, in the last few years, about calories restriction so much that I became an ardent follower until recently when I finished to read the following book

http://intensedf.com/Content/Health/Book/WhoShoulReadThisBook.aspx



This book states that the effect of calorie restriction is not related to the restriction of calories but to the fact that with calories restriction we are actually doing a Methionine restriction that is the real cause of the benefits we get from this practice.



On top of that, it states that the French paradox can be related in some way to the Methionine.



If the book is right we do not need to starve ourselves to get all the benefits of the calorie restriction but it is just enough to reduce the quantity of Methionine in our diet.



I decided to follow this new approach because despite been very interested in getting all the benefit of caloric restriction I find some times very hard to stay on a low calorie diet .



I just started few weeks ago to reduce the quantity of Methionine in my diet and I have increased the quantity of calories to remove the feeling of starvation. I hope this will allow me to get the same benefits with much less pain.



What do you think about my choice? Who agrees with my choice and who does not? And why?



Any advice is welcome



Thank you

[mat]

So no one is on a methionine restriction??

that is strange with methionine restriction you get same results as CR with less hassle

[mat]

Methionine restriction decreases mitochondrial oxygen radical generation and leak as well as oxidative damage to mitochondrial DNA and proteins
Sanz, A., Caro, P., Ayala, V., Portero-Otin, M., Pamplona, R., Barja, G.
FASEB J. 2006; 20:1064-1073. [Abstract] [Full Text] [PDF]

[Michael]

So no one is on a methionine restriction??

that is strange with methionine restriction you get same results as CR with less hassle

While this analysis of the data is repeatedly advanced by the main researchers involved, it remains, at best, an unproven hypothesis -- and until firmed up, it's a dangerous distraction.

[VictorBjoerk]

french paradox is not due to methionine restriction? they eat lots of foie gras,fish,meat,cheese which all contain a lot of methionine

[mat]

french paradox is not due to methionine restriction? they eat lots of foie gras,fish,meat,cheese which all contain a lot of methionine

That is true but they also drink a lot of wine (alcohol)

The author of the book that I read says that our body uses Methionine to destroy alcohol in the alcohol metabolism.

This could explain why a moderate quantity of alcohol is good.

The French paradox is: French people eat a lot of animal food as many other population buy because they drink a lot of wine the alcohol in this wine reduces the damage caused by the large quantity of Methionine this is why they have less problems.

We can summarise this with

High animal food diet >>>>> large quantity of Methionine = high damage

High Animal Food diet + alcohol >>>> small quantity of Methionine because it is used to destroy alcahol = less damage

(in animal food the quantity of Methionine per g of protein is 3 times what can be found in vegetables-fruit this could be another reason why animal food are so unhealthy)

It is true that Methionine restriction does not have the quantity of data that are available for CR, but reading that book I am quite convinced that CR is nothing less than a Methionine restriction. It makes a lot of example where Methionine restriction could be used to explain some longevity effect like for example the fact the women live longer than men.

If you want to exploit a mechanism to slow down longevity you need to know what is working in that mechanism to optimise it.

Carbohydrate and fat restriction do not case increase in lifespan while proteins and Methionine do!!!

I do not want to convince other people but my advice is to have a good look to this approach and than you make a decision.

Edited by Michael, 19 July 2009 - 11:32 PM.
Cleaning

[Mortuorum]

Theoretically, does methionine restriction then require the cessation of supplements such as NAC on account of their structural origins?

Edited by Michael, 19 July 2009 - 11:32 PM.
Trim quotes

[nameless]

Wouldn't vegans and vegetarians have lifespans similar to what CR people should expect, if methionine restriction is the reason? Or is there significant methionine in non-animal protein?

Another way to examine this theory is to look at the dietary data for specific populations, especially long-lived ones, and compare their methionine intake.

Edited by nameless, 09 July 2009 - 11:44 PM.

[kismet]

Wouldn't vegans and vegetarians have lifespans similar to what CR people should expect, if methionine restriction is the reason? Or is there significant methionine in non-animal protein?

AFAIK the methionine restriction in rodent studies leads to drastic weight-loss, similarly to CR, which is the reason why it was suggested to be crypto-CR. If there really wasn't enough met in plant products we should see vegans basically "wasting away" (as if they started CR, despite an isocaloric diet). I suppose there's definitely enough met for maintenance in their diet...

Edited by kismet, 10 July 2009 - 12:07 AM.

[niner]

I just started few weeks ago to reduce the quantity of Methionine in my diet and I have increased the quantity of calories to remove the feeling of starvation. I hope this will allow me to get the same benefits with much less pain.

Mat, how did you manage to reduce methionine in your diet? I looked into it briefly but it seems like Met is in everything. At least it's high in some foods that I don't really want to stop eating. Are you sure that you are getting all the amino acids you need, yet restricting Met sufficiently? Does anyone know what the effect of Met restriction is on autophagy?

[remig]

The body can inter-convert cysteine and methionine but synthesize neither, so the two together are considered a single essential amino acid pair. Any natural source of protein will have plenty of cysteine/methionine. Beans have the lowest cys/met protein percentage of common foodstuffs yet bean protein contains over 70% of the cys/met content of the same amount of meat protein. A low cys/met diet with adequate protein intake would therefore be very difficult to design outside of a lab environment. Certainly NAC (n-acetly-cysteine) supplements would be precluded.

The studies on methionine restriction (Meth-R) have not determined that restriction of other essential amino acids do not produce the same effects.
To quote from one study :

In weighing the merits of these different mechanistic ideas, it would be particularly helpful to know if life-span extension could be induced by restriction of any essential amino acid or whether instead Meth-R was unique in this effect. Timiras and her colleagues have reported a series of studies focused on tryptophan restriction (see ( 32 ) and references cited therein), which suggest that diets low in tryptophan may delay the onset of age-dependent pathology in many organs and extend survival in Long-Evans rats.
...
Despite these uncertainties, the evidence that low-tryptophan diets, like low-methionine diets, may be able to extend rodent life span argues against mechanisms based on the special role of methionine per se in intermediary metabolism and suggests that mechanisms based on altered translation, altered hormonal profi les, or hormesis deserve special attention.

The effect of limiting any essential amino acid in the diet is the same as restricting protein generally. Whenever essential substances are lacking in the cell, the cell consumes some portion of itself (autophagy) to obtain a supply of them. Though the mice or rats in the studies are receiving adequate overall protein, it is likely when amino acid levels are marginal that there are periods of amino-acid starvation (during sleep perhaps) when autophagy would be induced. This autophagy has a side-benefit of possibly clearing the protein aggregates and degraded organelles that the constitutive recycling systems of the cell cannot handle and this may explain the life extension benefits.

[Forever21]

Wouldn't vegans and vegetarians have lifespans similar to what CR people should expect, if methionine restriction is the reason? Or is there significant methionine in non-animal protein?

Another way to examine this theory is to look at the dietary data for specific populations, especially long-lived ones, and compare their methionine intake.

grains are high met.
egg whites are high met.
its a met-fest for vegans and vegetarians.

[becomingwiser]

There is no proven method to extend lifespan, not calorie restriction, not anything. The calorie restriction theory may have some merit but the experiments are full of holes.

People need to stop jumping on the latest fad on the life extension bus and just accept that we're all going to get old and die, the end.

[JLL]

There is no proven method to extend lifespan, not calorie restriction, not anything. The calorie restriction theory may have some merit but the experiments are full of holes.

People need to stop jumping on the latest fad on the life extension bus and just accept that we're all going to get old and die, the end.

So why did you jump on the imminst.org bus?

[okok]

Taking the easy route and looking at empirical data -

Vegan diets are supposed to be low in methionine, but they don't seem to have longer life expectancy. Anyone have any studies, know more?

[kismet]

Vegan diets are not low met.

[okok]

The low-methionine content of vegan diets may make methionine restriction feasible as a life extension strategy

Summary
Recent studies confirm that dietary methionine restriction increases both mean and maximal lifespan in rats and mice, achieving “aging retardant” effects very similar to those of caloric restriction, including a suppression of mitochondrial superoxide generation. Although voluntary caloric restriction is never likely to gain much popularity as a pro-longevity strategy for humans, it may be more feasible to achieve moderate methionine restriction, in light of the fact that vegan diets tend to be relatively low in this amino acid. Plant proteins – especially those derived from legumes or nuts – tend to be lower in methionine than animal proteins. Furthermore, the total protein content of vegan diets, as a function of calorie content, tends to be lower than that of omnivore diets, and plant protein has somewhat lower bioavailability than animal protein. Whole-food vegan diets that moderate bean and soy intake, while including ample amounts of fruit and wine or beer, can be quite low in methionine, while supplying abundant nutrition for health (assuming concurrent B12 supplementation). Furthermore, low-fat vegan diets, coupled with exercise training, can be expected to promote longevity by decreasing systemic levels of insulin and free IGF-I; the latter effect would be amplified by methionine restriction – though it is not clear whether IGF-I down-regulation is the sole basis for the impact of low-methionine diets on longevity in rodents.

Edited by okok, 20 July 2009 - 03:37 PM.

[kismet]

Vegan diets are supposed to be low in methionine, but they don't seem to have longer life expectancy. Anyone have any studies, know more?

Vegan diets are not low met, not low enough to show easily measurable benefits at least. Let me explain (or actually, I'll just generously quote M's response). When talking about "low met" in the context of life extension per se (max. life span extension á la CR) and in the context of this thread named "methionine restriction" we are talking very, very low met indeed. This is not just "low" met; it is dangerously low met and cannot be achieved using any normal diet:

The MR used in these studies to get a life-extension effect is quite severe -- a 0.17% Met, zero-cysteine diet, vs. a 0.86% Met diet, corresponding roughly to getting a dangerously-low 263 mg of Met+Cys in a 70 kg human (RDA 1330 mg). Moreover, it's not clear how one would attempt to reduce the riskiness of this without also potentially blunting the benefits of restriction: any metabolic defect induced by chronic Met deficiency could be the key to its life-extending effect. Humans given low-Met diets for experimental chemo or because of congenital postload hyperhomocysteinemia wind up eating basically nothing but potatoes,a few vegetables, and a customized super-low-met amino acid shake. With the very low level of evidence supporting its benefits, this was clearly a crazy risk IAC....

Furthermore, any restrictive diet has to be implemented ensuring optimal nutrition (ON). Most standard vegan diets, however, fail to supply many semi-essential nutrients. This problem alone might outweigh all the small benefits of a vegan diet, which is only relatively low in met and only in some cases. Emphasis mine:

In practice, a high-protein, low-methionine diet is one composed of a lot of non-grain vegetarian protein [!= most vegan diets!]. All legume proteins are good, and lentils are exceptionally noteworthy as being high %protein, low-Calorie, and unusually low-Met even for a legume, per gram of protein and per Calorie. Dairy (aside from whey) is moderate in methionine, and Quorn, despite its eggwhite content, is also pretty acceptable (certainly compared with meat).

Also, notice that perhaps low met is not enough, but it should be also high in Pr (or maybe it shouldn't be depending on what you make of the IGF-1 data), while being low in met to show most benefits. Most vegan diets are rather low in P, though.

Additionally we do not know if there are no risks inherent to real MR in humans:

Finally: some time ago, I looked into the possibility of trying to reap any potential benefits of MR, while avoiding side effects by taking related nutrients (cyst(e)ine, folic acid, betaine, etc) to accomplish some of its other functions. A consideration of many papers on the subject (especially (9,10) and the accumulating evidence of risk from high-dose folic acid and other methylating nutrients) convinced me that, as "engineer's logic" always suggests in such cases, it's a mug's game to attempt to second-guess metabolism.

In short:
Most vegan diets are unhealthy in the first place and this may overshadow any benefits derived from their relatively low met content, assuming they are lower in met to begin with.

Edited by kismet, 20 July 2009 - 05:56 PM.

[nameless]

A couple of methionine questions (and please excuse if they are dumb questions, as I haven't studied this issue besides just glancing over posts here):

Has methionine or protein intake been studied in long-lived populations? If so, did any such populations consume a diet that was mostly low protein or low methionine?

Have there been any rodent studies testing other amino-restriction/longevity theories? That is, besides the tryptophan study mentioned here. Perhaps it's not just methionine, but restriction of other amino acids would have the same effect?

Have there been any rodent studies showing excess methionine decreasing lifespan?

And there is also the issue that even if methionine /protein restriction does work in people, that it may not work for humans outside of lab conditions. Immune or health problems from severe restriction perhaps would kill you off before you reached old age.

[okok]

Have there been any rodent studies testing other amino-restriction/longevity theories? That is, besides the tryptophan study mentioned here. Perhaps it's not just methionine, but restriction of other amino acids would have the same effect?

Lowered methionine ingestion as responsible for the decrease in rodent mitochondrial oxidative stress in protein and dietary restriction possible implications for humans.
López-Torres M, Barja G. Department of Animal Physiology II, Faculty of Biological Sciences, Complutense University, Madrid 28040, Spain.

Available information indicates that long-lived mammals have low rates of reactive oxygen species (ROS) generation and oxidative damage at their mitochondria. On the other hand, many studies have consistently shown that dietary restriction (DR) in rodents also decreases mitochondrial ROS (mtROS) production and oxidative damage to mitochondrial DNA and proteins. It has been observed that protein restriction also decreases mtROS generation and oxidative stress in rat liver, whereas neither carbohydrate nor lipid restriction change these parameters. This is interesting because protein restriction also increases maximum longevity in rodents (although to a lower extent than DR) and is a much more practicable intervention for humans than DR, whereas neither carbohydrate nor lipid restriction seem to change rodent longevity. Moreover, it has been found that isocaloric methionine restriction also decreases mtROS generation and oxidative stress in rodent tissues, and this manipulation also increases maximum longevity in rats and mice. In addition, excessive dietary methionine also increases mtROS generation in rat liver. These studies suggest that the reduced intake of dietary methionine can be responsible for the decrease in mitochondrial ROS generation and the ensuing oxidative damage that occurs during DR, as well as for part of the increase in maximum longevity induced by this dietary manipulation. In addition, the mean intake of proteins (and thus methionine) of Western human populations is much higher than needed. Therefore, decreasing such levels to the recommended ones has a great potential to lower tissue oxidative stress and to increase healthy life span in humans while avoiding the possible undesirable

Has methionine or protein intake been studied in long-lived populations? If so, did any such populations consume a diet that was mostly low protein or low methionine?

I'm no expert on this subject either, but I wondered, as mentioned above, on the possible benefits of a vegan diet, and why it doesn't seem to confer any life extension.

1. Has it conclusively been shown that vegan diets are unhealthy? (if not,)
2. Met-reduction being modest in a vegan diet, nevertheless this should show. (also in regard to many advise for a 'soft' met-restr.)

just playing devil's advocate a bit.

[bkaz]

Though the mice or rats in the studies are receiving adequate overall protein, it is likely when amino acid levels are marginal that there are periods of amino-acid starvation (during sleep perhaps) when autophagy would be induced. This autophagy has a side-benefit of possibly clearing the protein aggregates and degraded organelles that the constitutive recycling systems of the cell cannot handle and this may explain the life extension benefits.

That's an intreresting thought, sleep would be a perfect time for autophagy, - it's a difficult process, best done when cells are at a full rest. Is there any evidence that autophagy mostly happens during sleep? That would go a long way to explaining function/benefits of sleep. Also, that would suggest that resveratrol & curcumin are best taken before sleep?

[DrEvil]

Hi

What I found interesting is that in a study on rats, rats
placed on a high methionine diet , died earlier than normal rats
and in another study rats placed on a low methionine study
lived 30% longer.
http://uwaging.org/g...gene.php?id=535
and
http://uwaging.org/g...gene.php?id=398

Anyhow for those that are interested in it here is a list of the percentage of protein that is methionine:
(can anybody tell me how to post a spreadsheet table in here.?):

Source : percentage of protein that is methionine : Onion 0.17% lettuce ice berg 0.67% Mushroom, portabells 0.70% Gelantine (powder, dessert) 0.80% fava beans 0.80% lentils mature cooked 0.85% WaterCress 0.91% Tofu 0.93% AlfaAlfa 0.94% Cabbage 0.94% Mushroom , white 1.00% okra 1.05% lettuce butter 1.11% beets 1.12% Soya beans 1.21% mung beans 1.22% Mushroom, oyster 1.27% broccoli 1.35% Beans kindney 1.51% Walnuts 1.55% Wheat 1.62% Amaranth 1.67% Rye 1.68% Oats 1.85% Barley 1.85% Spinach 1.85% Emu, oyster steak 1.90% Cashew 1.99% Lamb Brains 2.00% Millet 2.01% Lamb Kidney 2.01% Chicken breast 2.0% Lamb liver 2.16% Quinoa 2.19% Mussels 2.25% Oyster 2.26% Squid 2.27% Egg yolk 2.38% Beef 2.50% Fish 2.50% Mollusks, whelk 2.50% Beef jerky 2.51% Lamb trimmed 2.57% Milk 2.59% Cheese-emmentaler 2.61% Chicken breast no skin 2.62% Chicken with skin 2.65% Pork 2.65% Duck 2.71% Shrimp 2.79% Lobster 2.81% Crab 2.82% Fish Bass ( fresh water) 2.96% Fish herring 2.97% sesame seeds 3.38% Egg white 3.66% Brazil Nuts 7.06%

Protein in grams for same list:

Source (100g) Protein (g) Onion 1.76 lettuce ice berg 0.9 Mushroom, portabells 2.15 Gelantine (powder, dessert) 6.63 fava beans 26.5 lentils mature cooked 17.86 WaterCress 2.3 Tofu 8 AlfaAlfa 32 Cabbage 1.28 Mushroom , white 3.09 okra 2 lettuce butter 1.351 beets 1.61 Soya beans 33.152 mung beans 25 Mushroom, oyster 3.31 broccoli 2.82 Beans kindney 23.58 Walnuts 15.23 Wheat 13.68 Amaranth 13.56 Rye 14.76 Oats 16.89 Barley 27 Spinach 2.86 Emu, oyster steak 22.81 Cashew 18.21 Lamb Brains 10.399 Millet 11.02 Lamb Kidney 15.739 Chicken breast 14.73 Lamb liver 20.38 Quinoa 14.12 Mussels 11.9 Oyster 7.05 Squid 15.58 Egg yolk 15.86 Beef 20 Fish 20 Mollusks, whelk 40 Beef jerky 39 Lamb trimmed 24.52 Milk 3.2 Cheese-emmentaler 30 Chicken breast no skin 16.7 Chicken with skin 18.6 Pork 21 Duck 25 Shrimp 20.317 Lobster 18.8 Crab 18.29 Fish Bass ( fresh water) 18.86 Fish herring 17.961 sesame seeds 25 Egg white 10.9 Brazil Nuts 19

Source:
http://www.acaloriec...ature-seeds-raw http://www.acaloriec.../search/spinach

observation:
Egg and milk are both high in Methionine, yet in humans it is generally believed that vegans live shorter then vegetarians ( so milk, eggs with high methionine assist vegans) .
Fish is very high in Methionine , yet it is believed that people that eat fish but no meat live at least as long as vegetarians. ( so fish with very high methionine helps vegetarian diet or does not make it worse.)

Perhaps vegans have deficiency and vegetarian diet is still too high in methionine
that replacing some diary with fish is not going to make enough difference in total methionine and the other added benefits of fish (omega oils), more then make up for that.

Edited by DrEvil, 08 August 2009 - 05:17 PM.

[DrEvil]

Hi
Did some search on the internet into vegans and vegetarians. Turns out their homocysteine levels are higher than those of omnivores humans:
http://content.karge...ArtikelNr=12827
click on free abstract link. The reason is Vitamin B 12 deficiency.

One of the benefits believed of methionine restriction is a reduction in the conversion of methionine into homocysteine, which causes oxidative stress ( alzheimers etc.) . Vitamin B12 helps reduce homocystein. Anyhow you guys all know this.
So the reason that methionine restriction does not seem to increase live span in vegans and vegetarians is Vit B12 deficiency.

So this means that methionine restriction in humans may well extend life span and maybe more easier to do than calorie restriction !!

[VidX]

Bump?

[stephen_b]

Forty percent methionine restriction decreases mitochondrial oxygen radical production and leak at complex I during forward electron flow and lowers oxidative damage to proteins and mitochondrial DNA in rat kidney and brain mitochondria (PMID 20041736, Rejuvenation Res. 2009 Dec;12(6):421-34).

Eighty percent dietary methionine restriction (MetR) in rodents (without calorie restriction), like dietary restriction (DR), increases maximum longevity and strongly decreases mitochondrial reactive oxygen species (ROS) production and oxidative stress. ... We conclude that methionine is the only dietary factor responsible for the decrease in mitochondrial ROS production and oxidative stress, and likely for part of the longevity extension effect, occurring in DR.

Nice to see experiments attempting to tease out the differences in how MR and CR effect longevity.

Edited by stephen_b, 12 January 2010 - 05:03 PM.

[resveratrol_guy]

I've been following this thread with great interest, as perhaps we've found a way to extend life without being so hungry. I've run across some good relevant evidence lately that MR is(n't) effective:

Pro: "The Blue Zones" is a epidemiological book about four geographically and culturally disjoint centenarian hotspots (called "blue zones") and their habits. While I was astonished to find that many of them eat starchy foods like rice and tubers, and even whole grain (gag!) tortillas, a common theme in the book was the severe restriction of meat intake, with the exception of seafood in the Okinawan case. But given that the Okinawan group was also moderately CRed (whereas the other three were not), their total methionine intake was still likely restricted compared to a full-calorie industrial diet. (NOTE: Please don't take this as an endorsement of potatoes for office dwellers. Centenarians tend to walk or exercise modestly all day long, so their blood sugar is probably not elevated for long enough to matter.)

Con: The study below reports, in an investigation of CRed Drosophila fruit flies, that "However, methionine alone was necessary and sufficient to increase fecundity as much as did full feeding, but without reducing lifespan." In other words, if you're on CR and want your sex drive back without losing your CR benefits, then methionine might as well be Viagra.

http://www.nature.co...ature08619.html

This evidence leads me to the following hypothesis, which could be tested somewhat well in humans by looking at biomarkers of aging and sex drive, without actually waiting a century to see who lives the longest:

Methionine isn't a switch. It's a dial, rather like resveratrol. Turn it as close to off as possible (given that it's an essential amino acid), and you live a long time without much sex drive. Turn it part way on, and your sex drive comes back, but you still live long. Max it out, and your lifespan crashes back to that of a junkfood addict; on the plus side, you're horney as ever.

I hope the SENS institute, or some other bio think tank, starts investigating MR more thoroughly...

Edited by resveratrol_guy, 12 March 2010 - 01:46 PM.

[aramalin1]

Am J Physiol Regul Integr Comp Physiol. 2007 Sep;293(3):R1046-55. Epub 2007 Jun 13.

Restriction of sulfur-containing amino acids alters claudin composition and improves tight junction barrier function.

Skrovanek S, Valenzano MC, Mullin JM.

Source

The Lankenau Institute for Medical Research, 100 Lancaster Avenue, Wynnewood, PA 19096, USA.

Abstract

Restriction of sulfur-containing amino acids (SCAA) has been shown to elicit a similar increase in life span and decrease in age-related morbidity as caloric restriction. The singular importance of epithelial barrier function in both physiological homeostasis and prevention of inflammation raised the issue of examining the effect of SCAA restriction on epithelial tight junction structure and permeability. Using a well-described in vitro, epithelial model, the LLC-PK(1) renal epithelial cell line, we studied the effects of SCAA restriction in culture medium. Reduction of methionine by 90%, cysteine by 50%, and total elimination of cystine resulted in dramatically lower intracellular pools of these amino acids and their metabolite, taurine, but the intracellular pools of the non-SCAA were all elevated. Cell growth and differentiation were maintained, and both confluent cell density and transepithelial short circuit current were unaffected. Certain tight junctional proteins, such as occludin and claudins-1 and -2 were not altered. However, claudins-3 and -7 were significantly decreased in abundance, whereas claudins-4 and -5 were markedly increased in abundance. The functional result of these structural changes was improved barrier function, as evidenced by increased transepithelial electrical resistance and decreased transepithelial (paracellular) diffusion of D-mannitol.

[stephen_b]

Cysteine supplementation reverses methionine restriction effects on rat adiposity: significance of stearoyl-coenzyme A desaturase (PMID 20871132).



From the abstract, "Our results indicate that anti-obesity effects of MR are caused by low cysteine and that dietary sulfur amino acid composition contributes to SCD1 regulation."