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40% CR in mice mimics therapeutic fasting in humans


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#31 xEva

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Posted 19 August 2010 - 03:44 AM

I guess I missed your arguments at the point where we entered the realms of magic. I am sure with the right "mind-body" :wacko: techniques ...

Ha-ha, I'm not surprised. Why not bring it up with whoever pinned mid-body techniques resources at the top of the CR section of ImmInst? Maybe they will be able to fill you in on this..


...you easily can live without a number of vital vitamins and minerals for decades, not even needing energy/kcal to maintain your body, let alone extensive exercise. Also it is unfortune, that those stuff appears to be uninvestigable by any scientifical methods. How unfortune. How really, really, unfortune.

"Mind-body" techniques lead to self-reported, not-adhering to scientifical standards, results that even contradict the most basic laws of physics, most prominently energy conservation in closed systems - oh wait, let me guess: mind-body-people get their energy requirements out of thin air, or they alter their DNA so they can produce encymes to digest cellulose and rocks. Am I going to become an esoteric Rasputin now, per definition relying on (scientifically) unproven stuff or do I stay with the most basic findings of physics, chemistry and biology? Try guessing.

You're wrong, simply because you obviously know nothing about it. There are numerous --hunderds if not thousands!-- studies of the effects of mediation, yoga and qigong on various aspects of physiology, diease, etc. I'm not giving you references, because I'm getting tired of spending my time on educating you spoiled little brats here. If you're interested, you'll google it yourself. If not, that's your loss, not mine.
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#32 Guest

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Posted 19 August 2010 - 03:56 AM

I am well aware of the effect of meditation and yoga - there are even reliable studies showing considerable influence on heart functioning etc. But the effects of mere meditation or yoga do not enable breaking the laws of physics. Living an active life on 300 kcal a day for years is utter nonsense, no matter how urgently Miss Russia claims otherwise.

#33 xEva

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Posted 19 August 2010 - 04:30 AM

I am well aware of the effect of meditation and yoga - there are even reliable studies showing considerable influence on heart functioning etc.

Good! There is hope for you after all, lol. Now expand your awareness with qigong and bigu and see if it changes anything in your view.

#34 JLL

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Posted 19 August 2010 - 09:54 AM

Everybody defending her keeps saying all hear miraculous feats are "well known facts" and "documented". Where are those documents? Has anyone here actually seen them? I doubt it.

And no, it's not difficult to see how her experiments could have benefitted the Soviet union. "Listen, comrades, I know food is scarce these days but guess what -- you can live a healthier life by eating only 400 calories a day! Hooray!"

#35 xEva

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Posted 19 August 2010 - 03:10 PM

Everybody defending her keeps saying all hear miraculous feats are "well known facts" and "documented". Where are those documents? Has anyone here actually seen them? I doubt it.

And no, it's not difficult to see how her experiments could have benefitted the Soviet union. "Listen, comrades, I know food is scarce these days but guess what -- you can live a healthier life by eating only 400 calories a day! Hooray!"

Are you saying this in a way of an apology for bringing in a moot point about 15-60min breath holding into the discussion?

As I already said, the Soviet establishment was opposed to her ideas, which caused her to leave her prestige work at the Institute of Space Research at the Russian Academy of Sciences. As far as miraculous feats, there are real people whom she cured of incurable diseases with application of her system and diet who testify for it. And yeah, some of them participated in her desert treks, which never happened in isolation or secrecy. To the contrary.


Regarding this picture, I just learned that it was taken in the beginning of 1987, when she is 71, not around 90 as I assumed earlier:


Posted Image



#36 JLL

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Posted 19 August 2010 - 07:28 PM

No, I'm definitely not apologizing for the breath thing. How do you know those people were cured? How do you know she's 71 in that picture? And even if she is, so what? It's proof that old ladies can run in snow in a damn bathing suit, not proof that you can live on 400-600 kcal per day.

Edited by JLL, 19 August 2010 - 07:28 PM.


#37 xEva

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Posted 20 August 2010 - 01:41 AM

No, I'm definitely not apologizing for the breath thing.

:|o I'm shocked! you committed a cardinal sin against truth and feel no remorse whatsoever? shame on you


How do you know she's 71 in that picture? And even if she is, so what? It's proof that old ladies can run in snow in a damn bathing suit --barefoot!-- not proof that you can live on 400-600 kcal per day.

You're so right. No I don't know kaka about anything. I exist in virtual reality of cyberspace where only certain collections of electrons frozen in a domain called pubmed constitute what I can reasonably call a reality. Reality to which I may one day aspire... which of course means that today I have a choice to limit myself by a certainty that it is damn impossible to live on 400-600 kcal per day --in which case I'll remain exactly where I am now-- or I can open up to the possibility that a right study will find its way into pubmed some X years from now, and by then I could be already living on this little kcals per day (and who knows, maybe even less!) --OR-- I would bite my own elbows in chagrin that I have not considered the route when the turn opened up before me... :blink: I'll go think about it.

Edited by xev, 20 August 2010 - 01:43 AM.


#38 Guest

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Posted 20 August 2010 - 12:51 PM

One honest suggestion: please teach your (future) children the right mind-body technique and after that put them on a 300-600 kcal a day diet. According to the next Uri Geller this greatly will benefit their health status and survival. James Randi might be willing to supervise them. Also vitamins and minerals don't matter, as your children will be able to synthesise them internally.

#39 JLL

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Posted 20 August 2010 - 06:15 PM

No, I'm definitely not apologizing for the breath thing.

:|o I'm shocked! you committed a cardinal sin against truth and feel no remorse whatsoever? shame on you


Did I now? I said:

Googling her name brings only pages that make Mercola look like a respectable doctor. She holds her breath for 15-60 minutes and walks across deserts without drinking water? I'm calling major BS on her old ass.


That is, pretty much the only websites you can find about this lady are ones that attribute all kinds of miraculous feats to her (with no references, obviously). It was not *my* claim that she holds her breath for 15-60 minutes, nor is it my claim that she walks across deserts. But the fact that this kind of nonsense is all the info you can find on her casts serious doubt over her. Sure, you can find strange claims about most famous people, but then, you can also find reliable info.

Should we just take her word for these things? Or yours? I don't think so. Remarkable claims require remarkable evidence, and all we have is the former, not the latter.
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#40 xEva

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Posted 21 August 2010 - 10:53 AM

Unbelievable! A Demagogue like you should have worked for the Propaganda Department back in the Soviet times. That's the point: why do you knowningly bring up disinfo and then make the case against her based on this?

No, she does not claim ability to hold her breath for 15-60 mins or walk across deserts without water. YOU DO. Stop doing it.
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#41 Guest

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Posted 21 August 2010 - 12:31 PM

I think you are misinterpreting the point in JILL's post.

#42 xEva

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Posted 21 August 2010 - 01:50 PM

I believe JLL is adept at spotting home-made webpages and knows exactly how to treat such info. And yet he brought it into the discussion, and we're still chewing on that piece of kaka. Besides, it's off topic in this thread. Nough said.

#43 Michael

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Posted 26 September 2010 - 03:32 PM

An Interview with Dr. Thomas N. Seyfried

It must be recognized that caloric restriction in mice is not the same as caloric restriction in humans. Basal metabolic rate is about 7-8 times greater in mice than in humans. A 24-hour fast in mice is comparable to a 6-7-day fast in humans. We recently published a paper showing that a 40 % CR in mice mimics a full therapeutic fast in humans. Thus, the health benefits attributed to CR in mice can be realized in humans who engage in water only therapeutic fasting for at least three to four days.[/size]

Among other things he says there that one needs to fast at least 7-10 days a year (water only) in order to reap the benefits seen in 40% CR in rodents.

Discuss smile.gif

Ed Masoro (may he live long!) gets really annoyed seeing people pursue intuitive-sounding notions that he debunked in the 1980s.

Leaving aside issues of circadian rhythm vs. rate of aging etc, it's been shown repeatedly that the TIMING of Calories doesn't matter: as long as the total intake of Calories is restricted, the apportioning thereof doesn't matter. Notably, see (1-3):


gallery_727_15_34453.jpeg
AL vs 25% CR, apportioned as: "1) a single meal beginning at the onset of darkness (meal-fed in darkness, MFD); 2) a single meal beginning at the onset of light (meal-fed in light, MFL); and 3) six smaller meals at intervals of ~2 h beginning at the onset of darkness and ending near the onset of light, a regimen intended to approximate the pattern of ad libitum feeding (pattern-fed, PF). These schedules of food restriction were implemented with an automatic feeding apparatus (18), which controlled the timing and duration of food accessibility."(1)

gallery_727_15_29362.jpeg
Group A (61 rats) ad libitum. Group B (61 rats) were restricted to 60% in a single daily meal. Group B-2 (50 rats) were restricted to 60% provided in two daily meals at 0700 h and 1500 h.(3)

Similarly, as repeatedly documented in the past, there is no distinct lifespan effect of alternate-day fasting/intermittent fasting/every-other-day feeding that doesn't boil down do Calories.

References
1. Nelson W, Halberg F. Meal-timing, circadian rhythms and life span of mice. J Nutr. 1986 Nov;116(11):2244-53. PMID: 3794831; UI: 87085847

2. Nelson W. Food restriction, circadian disorder and longevity of rats and mice. J Nutr. 1988 Mar;118(3):286-9. Review. PMID: 3280755; UI: 88171757

3. Masoro EJ, Shimokawa I, Higami Y, McMahan CA, Yu BP. Temporal pattern of food intake not a factor in the retardation of aging processes by dietary restriction. J Gerontol A Biol Sci Med Sci. 1995 Jan;50A(1):B48-53. PMID: 7814779; UI: 95114284

4. Caloric restriction in C57BL/6J mice mimics therapeutic fasting in humans.
Mahoney LB, Denny CA, Seyfried TN
Lipids Health Dis 2006, 5:13.

Edited by Michael, 12 November 2015 - 10:02 PM.


#44 pamojja

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Posted 26 September 2010 - 04:59 PM

Ed Masoro (may he live long!) gets really annoyed seeing people pursue intuitive-sounding notions that he debunked in the 1980s.

...

Similarly, as repeatedly documented in the past, there is no distinct lifespan effect of alternate-day fasting/intermittent fasting/every-other-day feeding that doesn't boil down do Calories.


Appreciate your response. But what is it that makes you believe mice/rats metabolism would apply to human one to one?
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#45 Guest

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Posted 26 September 2010 - 06:18 PM

Ed Masoro (may he live long!) gets really annoyed seeing people pursue intuitive-sounding notions that he debunked in the 1980s.

...

Similarly, as repeatedly documented in the past, there is no distinct lifespan effect of alternate-day fasting/intermittent fasting/every-other-day feeding that doesn't boil down do Calories.


Appreciate your response. But what is it that makes you believe mice/rats metabolism would apply to human one to one?


No one claims that rodents metabolism applies one to one. Even between humans there are considerable differences. The question is whether this kind of eating response is sufficiently preserved in primates. In absence of other information it is a reasonable working hypothesis. If you know of any other study suggesting otherwise (suggesting there are relevant differences to eating sheme responses at isocaloric diets when done in primates), please enlight us.

Also for the claim of the paper, that 40% CR in mice = resembles fasting in humans (and the interpretation that this means humans have to starve to reach mice-like CR), it should be noted that the authors never compared it to the existing data on human CR-subjects. Instead they use blood markers from a dozend different fasting studies - which do actually show considerably differing values in some cases.

However, if you are looking at data from people doing CR
http://www.ncbi.nlm....les/PMC2020845/

you see, that CR-values are within the range of people doing short term fasting - they are even better than some of those of short-term fasters and resemble the rodent values more closely (although this is admittingly hard to judge, since they do not provide any data on insulin, body fat, LDL/HDL and so on for the mice). No, this study doesn't cast much doubt on transferability of CR from animals to humans; they just didn't had a look at the actually available data for human CRON to discuss them instead of the short term fasting.

Edited by TFC, 26 September 2010 - 06:30 PM.

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#46 Ben

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Posted 26 September 2010 - 06:40 PM

Similarly, as repeatedly documented in the past, there is no distinct lifespan effect of alternate-day fasting/intermittent fasting/every-other-day feeding that doesn't boil down do Calories.


So, averaged out, it's the total calorie intake over a life-time, rather than any special effects one may get from the fasted state itself?

#47 xEva

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Posted 28 September 2010 - 01:24 AM

Similarly, as repeatedly documented in the past, there is no distinct lifespan effect of alternate-day fasting/intermittent fasting/every-other-day feeding that doesn't boil down do Calories.


So, averaged out, it's the total calorie intake over a life-time, rather than any special effects one may get from the fasted state itself?

I wish this were true, 'cause I'm not a CR type. I am a faster type. It's easier for me not to eat at all than muster all that sustained discipline that CR requires.

This reminds me of a post on a Russian fasting forum in response to an introductory CR article. The reference quote was, "Mice that ate half the calories lived twice as long" and the reply was, "still, both groups ate the same amount of food". Which in turn reminds me of some old believes that a person is destined to have just so many breaths in life, and those who breathe the slowest live the longest. Here too, the message seems, we are destined to eat just so many calories in life, and those who'll stretch them the longest will live longer too. I hope it's thrue, 'cause then my way of CR, which oscillates from feast to famine, is as good as any other, no?

#48 Michael

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Posted 28 September 2010 - 04:31 PM

Similarly, as repeatedly documented in the past, there is no distinct lifespan effect of alternate-day fasting/intermittent fasting/every-other-day feeding that doesn't boil down do Calories.

So, averaged out, it's the total calorie intake over a life-time, rather than any special effects one may get from the fasted state itself?

Well, it's at least the total calorie intake over a few days rather than a fasting effect: I doubt that you can do extended fasting or radically-low-Calorie eating for a week, followed by a week of AL eating, and average it out. There are animal studies on that kind of pattern too, albeit only on a very range of somewhat artificial outcomes (mostly interaction with chemical carcinogenesis) and the effects aren't too favorable (mostly enhancement). There are no lifespan studies.

I wish this were true, 'cause I'm not a CR type. I am a faster type. It's easier for me not to eat at all than muster all that sustained discipline that CR requires.

Well, tht only works if your total Calorie intake really is reduced, and you really are tracking your nutrition to know that you're getting enough of all your essential nutrients. I'm also not convinced that the kind of ongoing catabolism during an extended fast is really good for one -- might eat too much into the heart or other internal organs -- or that an 'overdose' of nutrition followed by a long period of micronutrient deprivation is a good idea, either. I'm somewhat speculating, tho'.

This reminds me of a post on a Russian fasting forum in response to an introductory CR article. The reference quote was, "Mice that ate half the calories lived twice as long" and the reply was, "still, both groups ate the same amount of food".

Yeah, again, that really doesn't work: the life extension comes from concommitant Calorie restriction, and if there isn't any, lifespan is not extended.

it's thrue, 'cause then my way of CR, which oscillates from feast to famine, is as good as any other, no?

Again, only if your total Calorie intake really is reduced, and you really are tracking your nutrition to know that you're not malnourished.

#49 xEva

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Posted 01 October 2010 - 01:35 AM

This reminds me of a post on a Russian fasting forum in response to an introductory CR article. The reference quote was, "Mice that ate half the calories lived twice as long" and the reply was, "still, both groups ate the same amount of food".

Yeah, again, that really doesn't work: the life extension comes from concommitant Calorie restriction, and if there isn't any, lifespan is not extended.

Michael, that was a joke. When I first saw it I too missed it. The point is that in their lifespan both, the long-lived CR mouse and the short-lived ad lib one, ended up eating the same total amount of food.



I wish this were true, 'cause I'm not a CR type. I am a faster type. It's easier for me not to eat at all than muster all that sustained discipline that CR requires.

Well, tht only works if your total Calorie intake really is reduced, and you really are tracking your nutrition to know that you're getting enough of all your essential nutrients. I'm also not convinced that the kind of ongoing catabolism during an extended fast is really good for one -- might eat too much into the heart or other internal organs -- or that an 'overdose' of nutrition followed by a long period of micronutrient deprivation is a good idea, either. I'm somewhat speculating, tho'.


it's thrue, 'cause then my way of CR, which oscillates from feast to famine, is as good as any other, no?

Again, only if your total Calorie intake really is reduced, and you really are tracking your nutrition to know that you're not malnourished.

Actually, it's me who is not convinced that the human CR the way it is practiced can match the benefits of a real fast. For example, what is the blood pH and what are the blood ketones levels of a person on CR?

What I don't get is how you people, in search of activated sirtuins, autophagy and cellular repair mechanisms, missed the meaning of the word starvation, which precipitated it all. Its main characteristic is not just in low glucose but in the concurrent high ketones with concomitant drop in plasma pH. Do you get these markers on CR? To what extent?

When you apply mice CR studies to yourself, you seem to overlook the fact that a mouse looses 10% of its body weight in 24 hours. It takes about a week for an average human to loose that much weight, and it may take more than a month to loose that much weight for a fat human. In 48 hours, a mouse looses 20% of its weight, which is reached by an average human in more than a month of fasting on water only.

These are the facts you people seem to glance over when you apply the rodent CR studies to yourselves. The point is, for mice and rats 24 hours of food deprivation constitutes a real long-time fast. When they are fed every other day, this is comparable to a human eating every other week. At least! Actually, it takes a bit longer than a week for an average human to get into the same metabolic zone as a 24h-fasted mouse.

But... If you prefer to sweep these data under the rug and close your eyes on the fact that it is starvation that activates the cellular repair you are after, then... what can I say? hope you're right, for your sake.


As for the safety of real fasts, it's safer not to eat at all than eat little something that it not enough to sustain you. Within a reasonable timeframe of course. As it is obvious that one should start eating slow and light when coming out of a long fast. So, when I said that I prefer to oscillate between feast and famine, I actually eat mostly light, sometimes fast and there are rare "holidays" when I pig out. So, overall, in a year, I probably eat the same amount of food as a person on CR. I should count calories of course, but I lack discipline to do it daily for a year.

#50 e Volution

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Posted 01 October 2010 - 06:00 AM

These are the facts you people seem to glance over when you apply the rodent CR studies to yourselves. The point is, for mice and rats 24 hours of food deprivation constitutes a real long-time fast. When they are fed every other day, this is comparable to a human eating every other week. At least! Actually, it takes a bit longer than a week for an average human to get into the same metabolic zone as a 24h-fasted mouse.

OK forgive me if I am missing something here, but doesn't it follow from your logic that alternate day feeding for mice (which you equate to a week fasted in humans) SHOULD give LE, which it doesn't?

#51 xEva

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Posted 01 October 2010 - 07:01 AM

OK forgive me if I am missing something here, but doesn't it follow from your logic that alternate day feeding for mice (which you equate to a week fasted in humans) SHOULD give LE, which it doesn't?

I don't know what alternate day feeding should give. What I do know is that you cannot directly apply rodent data to humans.

And don't get me wrong, I believe that any form of CR will give LE compared to ad lib, but it won't be anything extraordinary. My point is, if you want serious results, you should fast seriously. The serious results happen when key metabolic markers reach certain values. Do you reach those values on CR?

#52 e Volution

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Posted 01 October 2010 - 07:42 AM

I don't know what alternate day feeding should give. What I do know is that you cannot directly apply rodent data to humans.

My understanding is it doesn't. From JLL's (a forum member) post:

Does Intermittent Fasting Increase Lifespan?

In summary, it looks like intermittent fasting extends lifespan in rats and mice only when it is accompanied by calorie restriction. It does not mean that the animals are also put on CR; rather, they just naturally end up eating less (unlike humans, who tend to be very flexible and good at compensating for calories). And, in the rare cases that the animals actually do eat twice as much the next day, their lifespans are not increased.


And don't get me wrong, I believe that any form of CR will give LE compared to ad lib, but it won't be anything extraordinary. My point is, if you want serious results, you should fast seriously. The serious results happen when key metabolic markers reach certain values. Do you reach those values on CR?

Slow down, im in the fasting camp (but only because CR does not fit with my current lifestyle) but I am less convinced about it's LE benefits than you are. I do still believe it is very beneficial however, combined with a Paleo diet it is the only way I've ever been able to effortlessly stay at a very low body fat % without counting calories...

#53 Michael

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Posted 01 October 2010 - 10:00 AM

This reminds me of a post on a Russian fasting forum in response to an introductory CR article. The reference quote was, "Mice that ate half the calories lived twice as long" and the reply was, "still, both groups ate the same amount of food".

Yeah, again, that really doesn't work: the life extension comes from concommitant Calorie restriction, and if there isn't any, lifespan is not extended.

Michael, that was a joke. When I first saw it I too missed it. The point is that in their lifespan both, the long-lived CR mouse and the short-lived ad lib one, ended up eating the same total amount of food.

Ah, ok: this is what used to be called "lifetime energy intake." I misunderstood what you were saying, and thought it was a repetition about a widely-accepted myth about EOD.

I wish this were true, 'cause I'm not a CR type. I am a faster type. It's easier for me not to eat at all than muster all that sustained discipline that CR requires.

Well, tht only works if your total Calorie intake really is reduced, and you really are tracking your nutrition to know that you're getting enough of all your essential nutrients. I'm also not convinced that the kind of ongoing catabolism during an extended fast is really good for one [...]

it's thrue, 'cause then my way of CR, which oscillates from feast to famine, is as good as any other, no?

Again, only if your total Calorie intake really is reduced, and you really are tracking your nutrition to know that you're not malnourished.

Actually, it's me who is not convinced that the human CR the way it is practiced can match the benefits of a real fast. For example, what is the blood pH and what are the blood ketones levels of a person on CR?

To what long-term, prospective studies, with health outcomes (not surrogate markers), would you point to support the long-term health benefits of a regimen of intermittent prolonged fasting -- and fasting not linked up with other dietary or religious practices (such as near-vegetarianism in Greek Orthodox monks)? And there are no data at all, to my knowledge, that ketones or blood pH, intermittently or chronically, are reliable predictors of health outcomes in normal, healthy humans (as opposed to epileptics); do you have any to cite?

What I don't get is how you people, in search of activated sirtuins, autophagy and cellular repair mechanisms,

I'm not in search of any of that: I'm in search of retardation of the biological aging process, which occurs in a a wide range of species on CR and under a wide range of conditions; the phenomena you mention here are CR-associated changes that some people think may be mechanistically involved in the effect, but it would be silly to go after them for their own sake. The CR data validates interest in these possible mechanisms, not vice-versa.

What I don't get is how you people [...] missed the meaning of the word starvation, which precipitated it all.

First, the word 'starvation' isn't what precipitated it all. The titles of the first reports in this area were in fact "The Effect of Retarded Growth Upon the Length of Life Span and Upon the Ultimate Body Size"(1) and the much more obscure, but earlier, "The Effect of Retardation of Growth upon the Breeding Period and Duration of Life of Rats." In none of these reports were the animals starved: they were fed fewer Calories. And, second, the fact that something gets started out of interest in one area doesn't mean that one should continue to fixate on it. Science is full of examples of new advances that have emerged in the process of testing, and invalidating, the original hypothesis. "The retardation of growth" as the mechanism of CR is actually a good example of that.

When you apply mice CR studies to yourself, you seem to overlook the fact that a mouse looses 10% of its body weight in 24 hours.

Mice on CR (ie, the ones that have actually been shown to live longer and healthier) are not allowed to lose weight at this rate.

These are the facts you people seem to glance over when you apply the rodent CR studies to yourselves. The point is, for mice and rats 24 hours of food deprivation constitutes a real long-time fast.

And the studies show that you don't need a 24 h fast to get the CR effect. Please see my graphs.

References
McCay CM, Crowell MF, Maynard LA. The effect of retarded growth upon the length of life span and upon the ultimate body size. J Nutr. 1935 Jul;10(1):63–79.

2. Osborne TB, Mendel LB, Ferry EL. The Effect of Retardation of Growth upon the Breeding Period and Duration of Life of Rats. Science. 1917 Mar 23; 45(1160):294-5.

#54 kismet

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Posted 01 October 2010 - 12:35 PM

a potentially overlooked argument:
Additionally, (at least some important) CR effects have been replicated in larger mammals like dogs, cattle and primates whose metabolism should not be considerably 'faster' than ours. Perhaps, xEva is unaware of the data, but I think it also invalidates hir argument.

Edited by kismet, 01 October 2010 - 12:37 PM.


#55 xEva

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Posted 01 October 2010 - 09:26 PM

...this is what used to be called "lifetime energy intake."

Ha! funny that it came up. I'm curious, is there anything to it?


To what long-term, prospective studies, with health outcomes (not surrogate markers), would you point to support the long-term health benefits of a regimen of intermittent prolonged fasting...? And there are no data at all, to my knowledge, that ketones or blood pH, intermittently or chronically, are reliable predictors of health outcomes in normal, healthy humans (as opposed to epileptics); do you have any to cite?

Okay, I see now that there are 2 issues here, CR that slows down the rate of damage and periodic prolonged fasts, a.k.a. starvation, that activates cellular repair mechanisms. The distinction is clear to me now: with your sustained CR you seek to minimize the damage and so to last longer, while I, with my fasts, fix the damage that has already occurred. Well then, if there is anything indeed to the "lifetime energy intake", then, assuming that my total calories per year match yours, then my CR method should be superior to yours, won't you think?

Regarding the studies, these would be all the studies constantly cited on ImmInst. They all seek to mimic the benefits of starvation with compounds like resveratrol or anything that triggers autophagy, or apoptosis of defective cells, etc.

And yes, the point of all ketogenic diets, including the original one for epileptic children, is to mimic the metabolism of starvation. It's funny how many people that are on ketogenic diets for various reasons are not aware of this fact. And I hope that by now we all know that starvation is characterized not just by low glucose, but also by low plasma pH and high ketone levels (around 5-7 mmol/L).


What I don't get is how you people, in search of activated sirtuins, autophagy and cellular repair mechanisms,

I'm not in search of any of that: I'm in search of retardation of the biological aging process..

Fair enough..

.. the phenomena you mention here are CR-associated changes that some people think may be mechanistically involved in the effect, but it would be silly to go after them for their own sake. The CR data validates interest in these possible mechanisms, not vice-versa.

Hm... maybe.


When you apply mice CR studies to yourself, you seem to overlook the fact that a mouse looses 10% of its body weight in 24 hours.

Mice on CR (ie, the ones that have actually been shown to live longer and healthier) are not allowed to lose weight at this rate.

Not allowed? That's the rate they loose weight after 24h of food deprivation. That's a fact. As is the fact that metabolic markers of 40% CR mice match markers of week+ starving humans.


These are the facts you people seem to glance over when you apply the rodent CR studies to yourselves. The point is, for mice and rats 24 hours of food deprivation constitutes a real long-time fast.

And the studies show that you don't need a 24 h fast to get the CR effect. Please see my graphs.

You keep on mixing apples with oranges. Those are CR effects on humans, compared with 24h fasting humans, which is not a fast proper, but a temporary abstinence from food, with metabolic markers that an average mouse probably reaches daily after a 3h break from eating. And yet you constantly cite rodent CR to justify your rosy expectations of human LE due to CR.

But.. surely, with your CR you will prolong your LS, and so will most likely reach into 80s and 90s and maybe even 100s. But it won't get you anything extraordinary. Hey, my grandma lived 94 and she spent 19 years in Siberian camps, and even after she came out, her whole life, she had to economize on food. On the other hand, her sister, who ran to the US in her 20s, lived only till her mid 70s. That's just to show you that CR is and has been practiced in so many ways by humans throughout the ages, and the max LS it can give is well known.

#56 kismet

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Posted 02 October 2010 - 02:42 PM

Please, will you just look at the graphs saying "pattern-fed"? ;) You are the one extrapolating rodent weight-loss rates to human CR. Thus your argument that is based on rodent data can be refuted using rodent data.

And doesn't the data indicate that you must slowly ease into (adult-onset) CR to reap most of the benefits anyway. That's the second argument that comes to mind additionally to those MR mentioned. Your proposed regimen seems not better, but outright dangerous. If anything, I am surprised criticism has been so mild, though, I may be wrong.

Can you address all the critics?

Edited by kismet, 02 October 2010 - 02:45 PM.

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#57 xEva

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Posted 02 October 2010 - 06:57 PM

Please, will you just look at the graphs saying "pattern-fed"? ;) You are the one extrapolating rodent weight-loss rates to human CR. Thus your argument that is based on rodent data can be refuted using rodent data.

Hey kismet! Glad to see you - long time no see, hehe. You are right about the graphs. They are of mice, not humans, but it does not change the point of my argument, and that is: we tend to overlook these very relevant facts about the differences in our metabolisms when we project the effects of rodent CR to ourselves.

Add to this collection of facts another tidbit: that a mouse eats a quarter to a third of its weight daily. Make it a quarter of its weight for a healthy mouse, cut it by 40%, to a drop in its food to 15% of its weight. Compare this to humans. And now recall that a mouse will loose 10% of its body weight after a 24h food deprivation. To me these numbers imply that these 40% CR'd mice are brought to a point where their energy expenditure is barely covered.


And doesn't the data indicate that you must slowly ease into (adult-onset) CR to reap most of the benefits anyway.

Which data? Regardless, I agree that to become metabolically fit takes time and practice. Whether you plunge into it right away or ease into it slowly, to actually arrive there will still take about the same time. For example, it takes 8 to 12 days for a beginner, fasting on water only, to enter ketosis -- and it takes just a bit longer, about 2 weeks+, for a person to adjust to a ketogenic diet. In both cases the mechanisms of transitioning from one metabolic state to another are similar. How easy we go from one mode to another is the question of our metabolic fitness. To me it's strange that instead of seeking "metabolic flexibility" as a marker of health, most people are fixated on a particular diet for life.

How about these tidbits of ketosis trivia: we are born and spend our first days in ketosis, and young children and women, especially pregnant ones, enter ketosis quicker than adult males. To me this means that we are born quite metabolically fit, but tend to loose it with years due to the mere lack of practice.

Your proposed regimen seems not better, but outright dangerous. If anything, I am surprised criticism has been so mild, though, I may be wrong.

Actually, I do not propose any regimens (well, aside from inviting all to experience the ketosis of starvation for themselves). I do not call for fasting every other week (for a week) to match EOD rodent CR. I only align these facts side by side to illustrate the differences in rodent and human metabolisms. It is these comparisons that bring forth the equivalence of a 40% CR'd mouse to a human in ketosis of starvation.

#58 xEva

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Posted 28 October 2012 - 03:16 AM

Another fact in support that, metabolically, a 24h-fast for a mouse equals a 7-day fast for a man. This time is it in regard to FGF-21 (Fibroblast Growth Factor 21), a hormone shown to extend lifespan in mice by 30% without food reduction:

In fasting mice, FGF21 is doubled after 24h [2]. In a human, 7 DAYS of fasting will finally increase it by 75%. [1]

http://www.pnas.org/...6/26/10853.full
"...in humans, circulating glucagon concentrations spike after 3-5 days of fasting and then decline, whereas plasma FGF21 levels increase only after a 7-day fast."


Refs.

[1] http://www.ncbi.nlm....pubmed/18680716 The circulating metabolic regulator FGF21 is induced by prolonged fasting and PPARalpha activation in man. (2008)

[2] http://www.sciencedi...6291X07013083 PPARalpha is a key regulator of hepatic FGF21. (2007)

Edited by xEva, 28 October 2012 - 03:16 AM.


#59 Michael

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Posted 28 October 2012 - 01:46 PM

FGF-21 (Fibroblast Growth Factor 21), a hormone shown to extend lifespan in mice by 30% without food reduction

Despite what both the popular press and even the abstract of the paper has said, the FGF21-Tg mice did, in fact, reduce their food intake: food intake is reported in g food/g mouse/3days, and is unchanged or even slightly increased in Tg vs WT mice -- but body weight was reduced by ~1/3 in males and by even more in females, so actual food intake was also cut by >30%. (Despite the widespread misunderstanding, long-term CR does not reduce food intake per unit of metabolic mass). And lifespan was increased by ~30%.(3)

As Alex Pickering has pointed out on the CR list, prima facie, a 30% reduction in food intake and a 30% increase in lifespan sure looks like (not-so-)'crypto-CR.' It's at least possible that this reduction in Calorie intake is entirely secondary to dwarfism imposed by overexpression of FGF21, and plays no role in its life-extension effect; it's also entirely possible that the reduction in Calorie intake is entirely responsible for the effect. Or, that 'crypto-CR' accounts for most of the benefit, with some additional effects specfic to the extra FGF21. But 'crypto-CR' is the null hypothesis, and this study is consistent therewith.


Reference
1: Zhang Y, Xie Y, Berglund ED, Coate KC, He TT, Katafuchi T, Xiao G, Potthoff
MJ, Wei W, Wan Y, Yu RT, Evans RM, Kliewer SA, Mangelsdorf DJ. The starvation hormone, fibroblast growth factor-21, extends lifespan in mice. elife.
2012;1:e00065. doi: 10.7554/eLife.00065. Epub 2012 Oct 15. PubMed PMID: 23066506;
PubMed Central PMCID: PMC3466591.

#60 xEva

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Posted 28 October 2012 - 02:20 PM

That mice restricted themselves voluntarily in response to FGF21 is beside the point in this thread. The point here is that physiologically and metabolically, a day of starvation for a mouse equals a 7-day fast for a man.

But this voluntary self-restriction is certainly something to note for a suffering with pangs of hunger beginner cronie. Exercise and cold induces expression of FGF21 in various tissues ;)




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