Re: And what do you plan to do about it? (was:]Methionine and Brain Function)

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#1: The answer depends on your premise.#2: Sugar is not very healthy in excess but not toxic in moderation. Probably still will be. The hugeeffort into treating type II diabetes may come up with new ways to mitigate high BG or insulinresistance.#3: Depending on full understanding of mechanism, any amount of CR may be discredited. Popular understanding is that CR is tricking the body into a specific response. If you can trigger the response without the CR you have the benefit without the downsides, but very little in nature ever works that way.JROn Feb 26, 2008, at 7:26 PM, Francesca Skelton wrote:Here’s what I would like to throw out to the group.  Let us suppose that methionine restriction (and some other amino acid (glycine?) are the reasons that CR works (through eating less of them and also eating mainly a low calorie, plant rich diet). If one assumes the above to be true, does this now mean that one can eat as many calories of non-methionine (non-glycine) rich foods one wants to eat?2)  And  does that mean that some foods are no longer demonized? Such as sugar. I’ve been using sucralose for 8 years now and limiting all desserts – is dessert off the “bad” List?  Most serious CRONIES do something similar.3)  We’ve had on on-going argument about extreme CRON and moderate CRON and this group has taken the moderate stance (BMI between 18.5 and 22 or so - see our files for studies citing these numbers for longest life).  If the above amino acids prove to be the reasons that CRON works, would that prove that extreme CRON has lost the argument? IOW, it’s unnecessary, and potentially dangerous?4) Some high methionine foods (legumes) are contradictorily associated with greater longevity.  What are we do to with this contradictory information?Right now I’m not changing anything in my diet and hedging all my bets.  That includes moderate red wine (for longevity insurance), low sugar, and CRON.  But I’d be interested in hearing what if anything the others are planning to do with this information, if anything.From: Rodney <perspect1111 >Reply-To: < >Date: Tue, 26 Feb 2008 21:46:58 -0000To: < >Subject: [ ] Methionine and Brain Function   Hi folks:I do not remember seeing this one previously:"These beneficial [Methionine restriction] induced changes  ..........  can play a key role in the protection against aging-associated neurodegenerative disorders."Rejuvenation Res. 2007 Dec;10(4):473-84 Methionine restriction decreases endogenous oxidative molecular damage and increases mitochondrial biogenesis and uncoupling protein 4 in rat brain.Naudí A <http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed & amp;Cmd=Search & amp;Term=%22Naud%C3%AD%20A%22%5BAuthor%5D & amp;itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVAbstractPlusDrugs1> , Caro P<http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed & amp;Cmd=Search & amp;Term=%22Caro%20P%22%5BAuthor%5D & amp;itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVAbstractPlusDrugs1> , Jové M <http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed & amp;Cmd=Search & amp;Term=%22Jov%C3%A9%20M%22%5BAuthor%5D & amp;itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVAbstractPlusDrugs1> , Gómez J<http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed & amp;Cmd=Search & amp;Term=%22G%C3%B3mez%20J%22%5BAuthor%5D & amp;itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVAbstractPlusDrugs1> , Boada J<http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed & amp;Cmd=Search & amp;Term=%22Boada%20J%22%5BAuthor%5D & amp;itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVAbstractPlusDrugs1> , Ayala V <http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed & amp;Cmd=Search & amp;Term=%22Ayala%20V%22%5BAuthor%5D & amp;itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVAbstractPlusDrugs1> , Portero-Otín M <http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed & amp;Cmd=Search & amp;Term=%22Portero-Ot%C3%ADn%20M%22%5BAuthor%5D & amp;itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVAbstractPlusDrugs1> , Barja G <http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed & amp;Cmd=Search & amp;Term=%22Barja%20G%22%5BAuthor%5D & amp;itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVAbstractPlusDrugs1> , Pamplona R <http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed & amp;Cmd=Search & amp;Term=%22Pamplona%20R%22%5BAuthor%5D & amp;itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVAbstractPlusDrugs1> .Department of Experimental Medicine, Faculty of Medicine, University of Lleida-IRBLLEIDA, c/Montserrat Roig 2, Lleida, Spain.Aging plays a central role in the occurrence of neurodegenerative diseases. Caloric restriction (CR) mitigates oxidative stress by decreasing the rate of generation of endogenous damage, a mechanism that can contribute to the slowing of the aging rate induced by this intervention. Various reports have recently linked methionine to aging, and methionine restriction (MetR) without energy restriction also increases life span. We have thus hypothesized that MetR can be responsible, at least in part, for the decrease in endogenous oxidative damage in CR. In this investigation we subjected male rats to exactly the same dietary protocol of MetR that is known to increase their life span. We have found that MetR: (1) decreases the mitochondrial complex I content and activity, as well as complex III content, while the complex II and IV, the mitochondrial flavoprotein apoptosis-inducing factor (AIF) and ATP content are unchanged; (2) increases the mitochondrial biogenesis factor PGC-1alpha; (3) increases the resistance of brain to metabolic and oxidative stress by increasing mitochondrial uncoupling protein 4 uncoupling protein 4 (UCP4); and (4) decreases mitochondrial oxidative DNA damage and all five different markers of protein oxidation measured and lowers membrane unsaturation in rat brain. No changes were detected for protein amino acid composition. These beneficial MetR-induced changes likely derived from metabolic reprogramming at the cellular and tissue level can play a key role in the protection against aging-associated neurodegenerative disorders. PMID: 17716000 Rodney.    

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oops didn't see #4:Contradictory evidence highlights how there may not be simple answers to complex questions.JRBeans beans they're good for your heart,the more you eat the more you......  :-)On Feb 26, 2008, at 7:26 PM, Francesca Skelton wrote:Here’s what I would like to throw out to the group.  Let us suppose that methionine restriction (and some other amino acid (glycine?) are the reasons that CR works (through eating less of them and also eating mainly a low calorie, plant rich diet). If one assumes the above to be true, does this now mean that one can eat as many calories of non-methionine (non-glycine) rich foods one wants to eat?2)  And  does that mean that some foods are no longer demonized? Such as sugar. I’ve been using sucralose for 8 years now and limiting all desserts – is dessert off the “bad” List?  Most serious CRONIES do something similar.3)  We’ve had on on-going argument about extreme CRON and moderate CRON and this group has taken the moderate stance (BMI between 18.5 and 22 or so - see our files for studies citing these numbers for longest life).  If the above amino acids prove to be the reasons that CRON works, would that prove that extreme CRON has lost the argument? IOW, it’s unnecessary, and potentially dangerous?4) Some high methionine foods (legumes) are contradictorily associated with greater longevity.  What are we do to with this contradictory information?Right now I’m not changing anything in my diet and hedging all my bets.  That includes moderate red wine (for longevity insurance), low sugar, and CRON.  But I’d be interested in hearing what if anything the others are planning to do with this information, if anything.From: Rodney <perspect1111 >Reply-To: < >Date: Tue, 26 Feb 2008 21:46:58 -0000To: < >Subject: [ ] Methionine and Brain Function   Hi folks:I do not remember seeing this one previously:"These beneficial [Methionine restriction] induced changes  ..........  can play a key role in the protection against aging-associated neurodegenerative disorders."Rejuvenation Res. 2007 Dec;10(4):473-84 Methionine restriction decreases endogenous oxidative molecular damage and increases mitochondrial biogenesis and uncoupling protein 4 in rat brain.Naudí A <http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed & amp;Cmd=Search & amp;Term=%22Naud%C3%AD%20A%22%5BAuthor%5D & amp;itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVAbstractPlusDrugs1> , Caro P<http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed & amp;Cmd=Search & amp;Term=%22Caro%20P%22%5BAuthor%5D & amp;itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVAbstractPlusDrugs1> , Jové M <http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed & amp;Cmd=Search & amp;Term=%22Jov%C3%A9%20M%22%5BAuthor%5D & amp;itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVAbstractPlusDrugs1> , Gómez J<http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed & amp;Cmd=Search & amp;Term=%22G%C3%B3mez%20J%22%5BAuthor%5D & amp;itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVAbstractPlusDrugs1> , Boada J<http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed & amp;Cmd=Search & amp;Term=%22Boada%20J%22%5BAuthor%5D & amp;itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVAbstractPlusDrugs1> , Ayala V <http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed & amp;Cmd=Search & amp;Term=%22Ayala%20V%22%5BAuthor%5D & amp;itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVAbstractPlusDrugs1> , Portero-Otín M <http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed & amp;Cmd=Search & amp;Term=%22Portero-Ot%C3%ADn%20M%22%5BAuthor%5D & amp;itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVAbstractPlusDrugs1> , Barja G <http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed & amp;Cmd=Search & amp;Term=%22Barja%20G%22%5BAuthor%5D & amp;itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVAbstractPlusDrugs1> , Pamplona R <http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed & amp;Cmd=Search & amp;Term=%22Pamplona%20R%22%5BAuthor%5D & amp;itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVAbstractPlusDrugs1> .Department of Experimental Medicine, Faculty of Medicine, University of Lleida-IRBLLEIDA, c/Montserrat Roig 2, Lleida, Spain.Aging plays a central role in the occurrence of neurodegenerative diseases. Caloric restriction (CR) mitigates oxidative stress by decreasing the rate of generation of endogenous damage, a mechanism that can contribute to the slowing of the aging rate induced by this intervention. Various reports have recently linked methionine to aging, and methionine restriction (MetR) without energy restriction also increases life span. We have thus hypothesized that MetR can be responsible, at least in part, for the decrease in endogenous oxidative damage in CR. In this investigation we subjected male rats to exactly the same dietary protocol of MetR that is known to increase their life span. We have found that MetR: (1) decreases the mitochondrial complex I content and activity, as well as complex III content, while the complex II and IV, the mitochondrial flavoprotein apoptosis-inducing factor (AIF) and ATP content are unchanged; (2) increases the mitochondrial biogenesis factor PGC-1alpha; (3) increases the resistance of brain to metabolic and oxidative stress by increasing mitochondrial uncoupling protein 4 uncoupling protein 4 (UCP4); and (4) decreases mitochondrial oxidative DNA damage and all five different markers of protein oxidation measured and lowers membrane unsaturation in rat brain. No changes were detected for protein amino acid composition. These beneficial MetR-induced changes likely derived from metabolic reprogramming at the cellular and tissue level can play a key role in the protection against aging-associated neurodegenerative disorders. PMID: 17716000 Rodney.    

[Guest guest]

Hi All, Would not severe CR result in severe methionine restriction? Cheers, AlFrancesca Skelton <fskelton@...> wrote: Let us suppose that methionine restriction (and some other amino acid (glycine?) are the reasons that CR works (through eating less of them). We’ve had on on-going argument about extreme CRON and moderate CRON and this group has taken the moderate stance (BMI between 18.5 and 22 or so - see our files for studies citing these numbers for longest life). If the above amino acids prove to be the reasons that CRON works, would that prove that extreme CRON has lost the argument? IOW, it’s unnecessary,

and potentially dangerous?

Be a better friend, newshound, and know-it-all with Mobile. Try it now.

[Guest guest]

Hi Francesca:

Here are my answers to your questions, within the text:

>> Here¹s what I would like to throw out to the group. Let us suppose that> methionine restriction (and some other amino acid (glycine?) are the reasons> that CR works (through eating less of them and also eating mainly a low> calorie, plant rich diet).

> 1. If one assumes the above to be true, does this now mean that one can eat> as many calories of non-methionine (non-glycine) rich foods one wants to> eat?

At face value, Yes. But I would not go to a 3250 calorie diet (and in consequence weigh 370 pounds) just on the basis of this. I would first want to see lifespan studies done in mice comparing 1) Normal 'ad lib'; 2) normal 40% restricted; 3) ad lib food volume with 40% MET restriction; 4) ad lib food volume with 60% MET restriction; 5) ad lib food volume with 80% MET restriction; 6) ad lib of high caloric density foods (to induce obesity) with 40% MET restriction.

After looking at the average and maximum lifespans of these mouse groups, I would feel I had a much better idea about what I ought to be doing.

> 2) And does that mean that some foods are no longer demonized? Such as> sugar. I¹ve been using sucralose for 8 years now and limiting all desserts ­> is dessert off the ³bad² List? Most serious CRONIES do something similar.

If this is important information we would need to see studies of high sugar, MET-restricted diets. Oils, sugars and desserts are examples of calorically dense foods. If we fill ourselves up with them we will become obese. It will take a lot of evidence to prove to me that obesity with low MET is healthy. Of course it almost certainly is healthier than obesity with high MET.

> 3) We¹ve had on on-going argument about extreme CRON and moderate CRON and> this group has taken the moderate stance (BMI between 18.5 and 22 or so -> see our files for studies citing these numbers for longest life). If the> above amino acids prove to be the reasons that CRON works, would that prove> that extreme CRON has lost the argument? IOW, it¹s unnecessary, and> potentially dangerous?>

AFAIK no research has been done yet to determine the BMI associated with greatest longevity for individuals on an optimally-restricted-MET diet. And I wouldn't want to hazard a guess as to what it would be, either. It will be necessary to dissociate the effects of too much MET from the effects of too many other calories. My GUESS is that they are both harmful, but perhaps in different ways. It will probably take a couple more decades of research to sort this all out.

In the shorter term, it would be very interesting to know how CVD and cancer risk factors are related to MET intake. Such an investigation might be able to come up with answers more quickly than a series of mouse lifespan experiments.

> 4) Some high methionine foods (legumes) are contradictorily associated with> greater longevity. What are we do to with this contradictory information?

I don't agree that beans have a high MET content. I would like to know the source of the *data* supporting this claim.

> > Right now I¹m not changing anything in my diet and hedging all my bets.> That includes moderate red wine (for longevity insurance), low sugar, and> CRON. But I¹d be interested in hearing what if anything the others are> planning to do with this information, if anything.

Some time ago I shifted my diet to avoid foods with a high MET content per calorie. The elimination of egg whites being the single most classic example. I would like to average one gram of MET per day, if possible. Beyond this I have made no other changes to my diet. So you might say I am on (or aiming at) a basicly low-fat diet of 1800 calories with one gram of MET. But I am not fanatical about my pursuit of these numbers.

Rodney.

> From: Rodney perspect1111@...> Reply- > Date: Tue, 26 Feb 2008 21:46:58 -0000> > Subject: [ ] Methionine and Brain Function> > Hi folks:> > I do not remember seeing this one previously:> > "These beneficial [Methionine restriction] induced changes .......... can> play a key role in the protection against aging-associated neurodegenerative> disorders."> > Rejuvenation Res. 2007 Dec;10(4):473-84> Methionine restriction decreases endogenous oxidative molecular damage and> increases mitochondrial biogenesis and uncoupling protein 4 in rat brain.

> Department of Experimental Medicine, Faculty of Medicine, University of> Lleida-IRBLLEIDA, c/Montserrat Roig 2, Lleida, Spain.> > ................................ These beneficial> MetR-induced changes likely derived from metabolic reprogramming at the> cellular and tissue level can play a key role in the protection against> aging-associated neurodegenerative disorders.> > PMID: 17716000 > > Rodney.

[Guest guest]

Not necessarily. For example if you’re eating lots of egg whites (as one example) as a main protein source.

Extreme CR is too difficult for most people. And it can have detrimental side effects: osteoporosis, loss of libido, anorexia, feeling cold, extreme hunger and obsession with food, anemia, discomfort upon sitting, depression, malnutrition unless done correctly. You have posted telling us you’ve suffered some of these health consequences . Besides, from what we know, extreme CRON is not for us old fogies (it leads to shorter, not longer, life in older mice) .

We have studies in our files that longer life means a BMI between 18.5 and 22ish rather than very low BMI’s. See the file: “Extreme CRON vs. Moderate CRON” under “CRON Science”.

From: Al Pater <old542000@...>

Reply-< >

Date: Wed, 27 Feb 2008 09:43:06 -0800 (PST)

< >

Subject: Re: [ ] And what do you plan to do about it? (was:]Methionine and Brain Function)

Hi All,

Would not severe CR result in severe methionine restriction?

Cheers, Al

Francesca Skelton <fskelton@...> wrote:

Let us suppose that methionine restriction (and some other amino acid (glycine?) are the reasons that CR works (through eating less of them).

We’ve had on on-going argument about extreme CRON and moderate CRON and this group has taken the moderate stance (BMI between 18.5 and 22 or so - see our files for studies citing these numbers for longest life). If the above amino acids prove to be the reasons that CRON works, would that prove that extreme CRON has lost the argument? IOW, it’s unnecessary, and potentially dangerous?

Be a better friend, newshound, and know-it-all with Mobile. Try it now. <http://us.rd./evt=51733/*http://mobile./;_ylt=Ahu06i62sR8HDtDypao8Wcj9tAcJ >

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Some time ago, we discussed how WHEY, SOY, and YEAST proteins have

from 30% to 50% less methionine than proteins from EGG WHITES, FISH,

BEEF, or CHICKEN. So, basically by replacing meats with legumes and

whey you can achieve substantial methionine restriction.

Don't forget that methionine is considered an *essential* amino acid.

I suppose that there would be some very bad consequences from

restricting methionine excessively.

I have a table with amino acid compositions of various proteins at the

bottom of this page:

http://www.scientificpsychic.com/fitness/aminoacids1.html

Tony

>

> Sorry about that. I was mistakenly lumping soybeans, legumes, and other

> beans. Legumes (except for soy) and beans are low MET apparently so that

> contradiction is not longer applicable.

>

> For me that makes Met restriction much easier.

>

> I can now see that it may be possible to go on a ³low MET¹ diet and

> occasionally ³splurge² on treats now and then that I previously shunned.

> This may be a lot more fun than CRON is, if the MET (and some other

amino

> acid) theory proves to be the reason that CRON works.

>

>

>

> From: Rodney <perspect1111@...>

> Reply-< >

> Date: Wed, 27 Feb 2008 19:48:50 -0000

> < >

> Subject: [ ] Re: And what do you plan to do about it?

> (was:]Methionine and Brain Function)

>

>

>

>

>

> Hi Francesca:

>

>

> > 4) Some high methionine foods (legumes) are contradictorily

associated with

> > greater longevity. What are we do to with this contradictory

information?

>

> I don't agree that beans have a high MET content. I would like to

know the

> source of the *data* supporting this claim.

>

> >

> > Right now I¹m not changing anything in my diet and hedging all my

bets.

> > That includes moderate red wine (for longevity insurance), low

sugar, and

> > CRON. But I¹d be interested in hearing what if anything the others are

> > planning to do with this information, if anything.

>

> Some time ago I shifted my diet to avoid foods with a high MET

content per

> calorie. The elimination of egg whites being the single most classic

> example. I would like to average one gram of MET per day, if possible.

> Beyond this I have made no other changes to my diet. So you might

say I am

> on (or aiming at) a basicly low-fat diet of 1800 calories with one

gram of

> MET. But I am not fanatical about my pursuit of these numbers.

>

> Rodney.

>