102 replies to this topic

[tunt01]

skotkonung - excellent link. thx for posting it.

i really appreciate your contribution to these forums and read almost every post you make. thx again.

[biochemie]

Ah yes, THAT China study.
Interestingly, I have found a debate between Loren Cordain (a researcher who has focused much of his career on the benefits of the Paleo diet) and Campbell.

Debate in following PDF.

WOW! That is one stellar link! I mean to have the authors of the Paleo diet and The CHINA Study debate their views is priceless.

[kismet]

LOL. Skeptical isn't even the right word. Isn't the RDA for Vitamin D like 400 IU? come on..

Now, slow down with the jumping to conclusions. There is no vitamin D RDA, it's called AI for a reason and implies a much weaker level of evidence. The IOM basically admits that they're clueless what the optimal amount is and are playing it safe. Yeah, the AI is pathetic and outdated, but it's got nothing to do with RDAs and you cannot draw (m)any conclusions from it.
Most RDAs are rock solid. Quite in contrast to what supplement pushers would have you believe. Only some of them need minor tweaking, while most anything else is in the realm of pharmacological mega-dosing and that's a whole other ball game.

Some quick thoughts:

I guess honest bloodwork seems like the ideal solution to find an OBJECTIVE measure of a diet's effect. Still gonna think about this some more and try to put the global picture together.

Bloodwork is an honest lie. It shows weak or moderate correlates to health, but nothing spectacular. It definitely won't tell the whole story (think CRON person/animal vs ad lib; where's the reliable difference in biomarkers?) Good testing is expensive. Not all markers are validated. Etc.

Actually, why not low-moderate carb? There's a bunch of promising epidemiology and animal data re. cancer and no, low or low-moderate carb intake and - that's the mantra for the CRONies - CR'd animals on a high protein diet live longer.
BTW, Bio, did you notice that you started to talk about macros but then continued talking about *animal* protein? Those are two different things. Although, I think that is actually the reason why heavily supplemented zone'ish almost vegetarian/vegan diets are quite popular. There's simply too much evidence in favour of benefical substances found in animal foodstuffs, but all of them can be supplemented.
And I find it rather unlikely that animal protein is necessary unhealthy, if anything I'd blame other nutrients found in meat.

When talking about macros, we shouldn't forget the big picture: it doesn't matter all that much if your baseline diet is fine. Messing with your macros really won't give the best bang-for-the-buck towards life extension and most study data is in line with this train of thought (you know the drill: instead focus on biomedical research, SENS and so on).

Edited by kismet, 18 July 2009 - 12:51 AM.

[biochemie]

Ah yes, THAT China study.
Interestingly, I have found a debate between Loren Cordain (a researcher who has focused much of his career on the benefits of the Paleo diet) and Campbell.

Debate in following PDF.

After carefully reviewing the document, it seems that while cordain's view are well documented with respect to evolution, they do not convincingly portray a picture of long-term optimal health simply because the epidemiological evidence seems to be so one sided.

[biochemie]

Bloodwork is an honest lie. It shows weak or moderate correlates to health, but nothing spectacular. It definitely won't tell the whole story (think CRON person/animal vs ad lib; where's the reliable difference in biomarkers?) Good testing is expensive. Not all markers are validated. Etc.

Hmm.. Please elaborate. Cholesterol,Trig., HDL, LDL, Lp(a), Vit. D, surely blood tests are not completely useless. U seems knowledgeable so I would like to know more about what you meant.

Actually, why not low-moderate carb? There's a bunch of promising epidemiology and animal data re. cancer and no, low or low-moderate carb intake and - that's the mantra for the CRONies - CR'd animals on a high protein diet live longer.
BTW, Bio, did you notice that you started to talk about macros but then continued talking about *animal* protein? Those are two different things. Although, I think that is actually the reason why heavily supplemented zone'ish almost vegetarian/vegan diets are quite popular. There's simply too much evidence in favour of benefical substances found in animal foodstuffs, but all of them can be supplemented.
And I find it rather unlikely that animal protein is necessary unhealthy, if anything I'd blame other nutrients found in meat.

When talking about macros, we shouldn't forget the big picture: it doesn't matter all that much if your baseline diet is fine. Messing with your macros really won't give the best bang-for-the-buck towards life extension and most study data is in line with this train of thought (you know the drill: instead focus on biomedical research, SENS and so on).

So basically you are saying that as long as micronutrient intake is plentiful than macronutrient intake should not be fussed over all that much?

Just out of curiosity, what kind of diet do you follow?

I'm also curious about the low-moderate carb studies you mention. It seemed to me that most of the epidemiological data pointed to high carb (from raw fruits and veggies mostly) being optimal.

I guess the conclusions I'm coming to are that like JackChristopher said a veggie diet with no grains or refined sugar/wheat, etc with a moderate fat content is probably the most straightforward to follow and promotes great longevity and health. With the paleo diet you have to be careful of the sources of your meat and the cooking methods. High O6 oils are a disaster and they are what we cook our meats with all the time! Not to mention that these oils are really sensitive to heat. The meat itself is a plethora of chemistry that was never meant to be in our food sources.

[kismet]

Answers in bold:

Hmm.. Please elaborate. Cholesterol,Trig., HDL, LDL, Lp(a), Vit. D, surely blood tests are not completely useless. U seems knowledgeable so I would like to know more about what you meant.
They are good at predicting some endpoints (incl. death), but they are still lacking. You can't gauge carcinogenesis, aging, cognition, etc Blood markers alone are not good enough to definitely judge a diet superior. They are not enough to predict risk of death. To tell apart Jean Calment from Joe the plumber. To differentiate between a CRONie and someone "just" living healthy. Combine diet and screening (e.g. agatston score, cardiorespiratory function, PWV, etc) and you will get a better picture. Unfortunately, those screening procedures work only/best in the elderly or middle aged.

So basically you are saying that as long as micronutrient intake is plentiful than macronutrient intake should not be fussed over all that much?
Yes, assuming that you also get the essential macros. Wasting a lot of time to manage your macro intake won't necessarily provide any benefits, because there is no proven macronutrient ratio and all those extreme diets (no carb, super low fat, super high carb) are nothing but experimental -- you are "betting" on good outcomes. It's not worth your time if you are interested in good bang-for-the-buck interventions.

Just out of curiosity, what kind of diet do you follow?
Zone'ish omnivorous, but I'm a great fan of zone'ish, CRON, almost-vegan w/ supplementation.

I'm also curious about the low-moderate carb studies you mention. It seemed to me that most of the epidemiological data pointed to high carb (from raw fruits and veggies mostly) being optimal.
I believe you might be confusing micronutrient studies with macronutrient studies (alternatively, if they assessed fruits the results might be skewed because of micro content anyway). Fruits and veggies are not necessarily healthy because of carbs, on the other hand diets rich in fruits (which are rich in some important micro/phytonutrients) tend to be rich in carbs. Mechanistical  considerations and animal experiments (xenografts) certainly support the notion of low carb/keto being protective from cancer.
One review I've seen mentioned but haven't read:
Colorectal Dis. 2005 Mar;7(2):128-32.
Diet and colorectal cancer: implications for the obese and devotees of the Atkins diet.
Fleming ME, Sales KM, Winslet MC.
discussion (German): http://www.team-andr...t135873-45.html


I guess the conclusions I'm coming to are that like JackChristopher said a veggie diet with no grains or refined sugar/wheat, etc with a moderate fat content is probably the most straightforward to follow and promotes great longevity and health. define moderate fat? But you will be surprised if you think a vegetarian diet is straight-forward. There's no credible interventional research showing vegetarian diets to be superior because they probably aren't without supplementation (carnitine, creatine, taurine, possibly some minerals and vitamins, etc) A healthy vegetarian diets is quite a hassle.

Edited by kismet, 18 July 2009 - 08:07 PM.

[Blue]

Animal studies have suggested that the longevity effect from CR is due to protein restriction and maybe especially methionine restriction. Is it not then difficult to argue for a high protein diet? Or even an ordinary protein diet? According to metabolic studies the estimated average requirement is 0.66 g protein per kg per day. 0.8 g protein per kg per day gives enough protein for 95% of the population. While the American diet averages 1.5 g protein per kg per day.

Edited by Blue, 18 July 2009 - 08:23 PM.

[kismet]

Animal studies have suggested that the longevity effect from CR is due to protein restriction and maybe especially methionine restriction.

Not exactly, studies have shown that protein restriction can produce CR-like effects. That is not the same as showing that CR is caused by PR or MR.

Is it not then difficult to argue for a high protein diet? Or even an ordinary protein diet?

High protein CR diets were tested in animals and are known to produce the most pronounced effect on longevity (in rodents). 

[Blue]

High protein CR diets were tested in animals and are known to produce the most pronounced effect on longevity (in rodents).

Source please.

"Caloric restriction (CR) decreases oxidative damage, which contributes to the slowing of aging rate. It is not known if such decreases are due to calories themselves or specific dietary components. In this work, the ingestion of proteins of Wistar rats was decreased by 40% below that of controls. After 7 weeks, the liver of the protein-restricted (PR) animals showed decreases in oxidative protein damage, degree of membrane unsaturation, and mitochondrial complex I content. The results and previous information suggest that the decrease in the rate of aging induced by PR can be due in part to decreases in mitochondrial reactive oxygen species production and DNA and protein oxidative modification, increases in fatty acid components more resistant to oxidative damage, and decreased expression of complex I, analogously to what occurs during CR. Recent studies suggest that those benefits of PR could be caused, in turn, by the lowered methionine intake of that dietary manipulation."
http://biomed.geront...stract/62/4/352

"Previous studies have shown that the decrease in mitochondrial reactive oxygen species (mitROS) generation and oxidative damage to mitochondrial DNA (mtDNA) that occurs during life extending dietary restriction also occurs during protein or methionine restriction, whereas it does not take place during carbohydrate or lipid restriction. In order to study the possible effects of other amino acids, in this investigation all the dietary amino acids, except methionine, were restricted by 40% in male Wistar rats (RESTAAS group). After 6–7 weeks, experimental parameters were measured in the liver. Amino acid restriction did not change the levels of the methionine metabolites S-adenosylmethionine and S-adenosylhomocysteine, mitochondrial oxygen consumption and ROS generation, oxidative damage to mtDNA, amounts of the respiratory complexes I–IV, and the mitochondrial biogenesis factors PGC-1α and NRF-2. On the other hand, adenylate energy charge, mitochondrial protein oxidation, lipooxidation and glycooxidation, the degree of mitochondrial fatty acid unsaturation, and the amount of the apoptosis inducing factor (AIF) were decreased in the RESTAAS group. Amino acid restriction also increased SIRT1 protein. These results, together with previous ones, strongly suggest that the decrease in mitROS generation and oxidative damage to mtDNA that occurs during dietary restriction is due to restriction of a single aminoacid: methionine. They also show for the first time that restriction of dietary amino acids different from methionine decreases mitochondrial protein oxidative modification and AIF, and increases SIRT1, in rat liver."
http://www.springerl...7846740g81gr6p/

[Blue]

More studies

"Caloric restriction (CR) decreases aging rate and mitochondrial ROS (MitROS) production and oxidative stress in rat postmitotic tissues. Low levels of these parameters are also typical traits of long-lived mammals and birds. However, it is not known what dietary components are responsible for these changes during CR. It was recently observed that 40% protein restriction without strong CR also decreases MitROS generation and oxidative stress. This is interesting because protein restriction also increases maximum longevity (although to a lower extent than CR) and is a much more practicable intervention for humans than CR. Moreover, it was recently found that 80% methionine restriction substituting it for l-glutamate in the diet also decreases MitROS generation in rat liver. Thus, methionine restriction seems to be responsible for the decrease in ROS production observed in caloric restriction. This is interesting because it is known that exactly that procedure of methionine restriction also increases maximum longevity. Moreover, recent data show that methionine levels in tissue proteins negatively correlate with maximum longevity in mammals and birds. All these suggest that lowering of methionine levels is involved in the control of mitochondrial oxidative stress and vertebrate longevity by at least two different mechanisms: decreasing the sensitivity of proteins to oxidative damage, and lowering of the rate of ROS generation at mitochondria."
http://www.sciencedi...77cf36c91eb3c59

"Dietary restriction (DR) lowers mitochondrial reactive oxygen species (ROS) generation and oxidative damage and increases maximum longevity in rodents. Protein restriction (PR) or methionine restriction (MetR), but not lipid or carbohydrate restriction, also cause those kinds of changes. However, previous experiments of MetR were performed only at 80% MetR, and substituting dietary methionine with glutamate in the diet. In order to clarify if MetR can be responsible for the lowered ROS production and oxidative stress induced by standard (40%) DR, Wistar rats were subjected to 40% or 80% MetR without changing other dietary components. It was found that both 40% and 80% MetR decrease mitochondrial ROS generation and percent free radical leak in rat liver mitochondria, similarly to what has been previously observed in 40% PR and 40% DR. The concentration of complexes I and III, apoptosis inducing factor, oxidative damage to mitochondrial DNA, five different markers of protein oxidation, glycoxidation or lipoxidation and fatty acid unsaturation were also lowered. The results show that 40% isocaloric MetR is enough to decrease ROS production and oxidative stress in rat liver. This suggests that the lowered intake of methionine is responsible for the decrease in oxidative stress observed in DR."
http://www.springerl...j52gj2000lt0g4/

"n this chapter, studies focusing on the relationship between oxidative stress and aging in different vertebrate species and in calorie-restricted animals are reviewed. Endogenous antioxidants inversely correlate with species maximum longevity, and experiments modifying their levels can increase survival and mean life span but not maximum life span. Evidence shows that long-lived vertebrates consistently have low mitochondrial free radical generation rates and also a low fatty acid unsaturation of cellular membranes, two crucial factors determining their aging rate. Oxidative damage to mitochondrial DNA is also lower in long-lived vertebrates than in short-lived vertebrates. Conversely, caloric restriction, the best described experimental manipulation that consistently increases mean and maximum life span, also decreases mitochondrial reactive oxygen species (ROS) generation and oxidative damage to mitochondrial DNA. Recent data suggest that the decrease in mitochondrial ROS generation would be due to protein restriction rather than calories, pointing out a key role for dietary methionine. Longevity would be achieved in part due to a low endogenous oxidative damage generation rate, but also due to a macromolecular composition highly resistant to oxidative modification, as it is the case for lipids and proteins."
http://www.springerl...3768237532634g/

[tunt01]

blue - i've also been going over those barja papers lately re: methionine restriction. it's hard to dispute the methionine component.

but do you think that recycling methionine from homocysteine still might be the bigger issue here (in conjunction with a generally leaner/lower methionine + animal protein in-take) ?

[kismet]

CR is NOT MR or PR (e.g. quickly skip the text to ref 7):
http://www.mfoundati...p=4037#post4037

And more reading...
http://www.imminst.o...&...st&p=266712

If CR worked via MR, then animals on high protein diets wouldn't enjoy any benefits. They do. Therefore CR is not MR. QED. No one is denying that lowering MR may be benefical, but -- let me re-iterate -- CR is not MR.

Edited by kismet, 18 July 2009 - 09:56 PM.

[Blue]

CR is NOT MR or PR (e.g. quickly skip the text to ref 7):
http://www.mfoundati...p=4037#post4037

And more reading...
http://www.imminst.o...&...st&p=266712

If CR worked via MR, then animals on high protein diets wouldn't enjoy any benefits. They do. Therefore CR is not MR. QED. No one is denying that lowering MR may be benefical, but -- let me re-iterate -- CR is not MR.

Hm. Seem to be a homemade theory here on imminst forum. All the peer-reviewed studies I have cited point to the effect of protein restriction and methionine restriction. Ref 7 is 1989 study on nephropathy in aging rats. Hardly relevant for life extension. Do you have a peer-reviewed study arguing against my peer-reviewed studies?

Edited by Blue, 18 July 2009 - 10:14 PM.

[Blue]

blue - i've also been going over those barja papers lately re: methionine restriction. it's hard to dispute the methionine component.

but do you think that recycling methionine from homocysteine still might be the bigger issue here (in conjunction with a generally leaner/lower methionine + animal protein in-take) ?

The most popular theory seems to be that CR, PR, and MR lowers mitochondrial reactive oxygen species generation and oxidative damage. But there are critics:

http://www.sciencedi...0a58def063a486b
http://www.ncbi.nlm....pubmed/17603300

[kismet]

Hm. Seem to be a homemade theory here on imminst forum. All the peer-reviewed studies I have cited point to the effect of protein restriction and methionine restriction. Ref 7 is 1989 study on nephropathy in aging rats. Hardly relevant for life extension. Do you have a peer-reviewed study arguing against my peer-reviewed studies?

You said that "Animal studies have suggested that the longevity effect from CR is due to protein restriction and maybe especially methionine restriction.", which is contradicted by this paper and many more. What you have shown is that CR, MR and PR have similar effects, not that they are the same. Just read M's posts. I don't know what else you want hear? I'm not entirely sure you understand your study.

Do you have a peer-reviewed study arguing against my peer-reviewed studies?

Yes, indeed, assuming you follow the URLs I posted.

Edited by kismet, 18 July 2009 - 10:45 PM.

[Blue]

You said that "Animal studies have suggested that the longevity effect from CR is due to protein restriction and maybe especially methionine restriction.", which is contradicted by this paper and many more. What you have shown is that CR, MR and PR have similar effects, not that they are the same. Just read M's posts. I don't know what else you want hear? I'm not entirely sure you understand your study.


Yes, indeed, assuming you follow the URLs I posted.

I followed the urls and found only a homemade theory. My study? I cited several. I will add another one:
"Dietary energy restriction has been a widely used means of experimentally extending mammalian life span. We report here that lifelong reduction in the concentration of a single dietary component, the essential amino acid L-methionine, from 0.86 to 0.17% of the diet results in a 30% longer life span of male Fischer 344 rats. Methionine restriction completely abolished growth, although food intake was actually greater on a body weight basis. Studies of energy consumption in early life indicated that the energy intake of 0.17% methionine-fed animals was near normal for animals of their size, although consumption per animal was below that of the much larger 0.86% methionine-fed rats. Increasing the energy intake of rats fed 0.17% methionine failed to increase their rate of growth, whereas restricting 0.85% methionine-fed rats to the food intake of 0.17% methionine-fed animals did not materially reduce growth, indicating that food restriction was not a factor in life span extension in these experiments. The biochemically well-defined pathways of methionine metabolism and utilization offer the potential for uncovering the precise mechanism(s) underlying this specific dietary restriction-related extension of life span."
http://jn.nutrition....tract/123/2/269

So who should we believe? The general consensus among scientists as presented in numerous peer-reviewed studies arguing for the effect of PR and MR? Or the objections of a imminist poster? Why not publish such objections in a peer-reviewed journal if the arguments are so convincing?

Edited by Blue, 18 July 2009 - 11:19 PM.

[Blue]

But we can look at Michael's objection:

The MR effect may be due to crypto-CR? No. "Pair-feeding studies, in which rats are fed the Meth-C diet at the levels consumed by the Meth-R rat group, have shown that the lifespan extension seen in the Meth-R rats is not attributable to their slightly lower per-rat energy intake."
http://www.kaeberlei.../501/miller.pdf

The 1989 study do find that life extension could be achieved in a rat prone to nephropathy by lowering calories without lowering protein and even that this was very slightly better than also lowering protein as the same time as calories. This study does not say that a high-protein diet in general without CR is good. Or that protein restriction alone cannot achieve life extension. Or that CR + normal protein is better than PR or MR. Or that the same effect would be achieved in rats or other animals not prone to nephropathy.

Edited by Blue, 19 July 2009 - 12:14 AM.

[biochemie]

But we can look at Michael's objection:

The MR effect may be due to crypto-CR? No. "Pair-feeding studies, in which rats are fed the Meth-C diet at the levels consumed by the Meth-R rat group, have shown that the lifespan extension seen in the Meth-R rats is not attributable to their slightly lower per-rat energy intake."
http://www.kaeberlei.../501/miller.pdf

The 1989 study do find that life extension could be achieved in a rat prone to nephropathy by lowering calories without lowering protein and even that this was very slightly better than also lowering protein as the same time as calories. This study does not say that a high-protein diet in general without CR is good. Or that protein restriction alone cannot achieve life extension. Or that CR + normal protein is better than PR or MR. Or that the same effect would be achieved in rats or other animals not prone to nephropathy.

Man, i've learned a lot from this discussion. I'm really happy to see the proper debate that is going on. No one can argue blue's data. It speaks for itself. The general consensus from the research i've read does seem to point towards a low protein diet or one whose content would be solely achieved by plant sources. I liked Campbell's rebuttal to Cordain in the link provided :

“The reader may find an example to be helpful. Consider a dietary contest. Suppose that Diet A (a diet nearly exclusively of animal origin) resulted in 100% of individuals living long enough to reproduce, but despite adequate calories available throughout the lifespan, average non-accident/non-violent age at death (thus death was from nutrition-related diseases) was 50 years. Diet B (a diet exclusively of plant origin) resulted in just 60% of individuals living long enough to reproduce (perhaps because they were too finicky to eat meat [or because inadequate calories killed young people]), but if fortunate enough to be presented with an environment of sufficient calories (thus likely avoiding all nutrition related diseases)... life expectancy was 90 years. In this contest, Diet A wins the evolutionary battle, and is adopted. The evidence presented by modern nutritional science suggests that something akin to this may well be the case for humans, who have a large constellation of disease processes that can be laid at the door of animal foods, and effectively reversed with vegan diets (see Ornish, Esselstyn, McDougall, etc.). Seen from this perspective, speculation about human dietary history is a fascinating subject, but is actually irrelevant in the search for optimal nutritional practices. Such practices can only be determined by scientific investigation done in the present time, studying varying dietary practices and determining their comparative outcomes.”

[niner]

Great thread. Forgive me if I've missed it, but has anyone run the experiment where animals on conventional CR are fed additional Methionine (with a few less Calories to compensate energetically for the added Met) to see if Met abolishes the CR effect? ISTM that would prove that the CR effect is mainly or solely due to MR.

[Sillewater]

The China Study: More Vegan Nonsense!

I have never read the China Study by Campbell, but I have come across critics (Eades, Colpo, Chris Masterjohn) that have provided pretty good reasons for why its nonsense. Colpo does a pretty good job of pointing out the major problems. The major problem I have is that his discussion is not related to the data, the data says something else.

I will read it, but from what I know, the Traditional Chinese do not consume a low-animal fat diet, but it is pretty high in plant matter. Traditional chinese medicine puts a lot of emphasis on vegetables (like the bitter gourd melon), but from what I have read over time they're taking more and more of a vegetarian stance, modern influence?

[Blue]

I also found this fascinating. Kismet is right in that CR and MR are not identical even if they overlap. For example:
"Studies in methionine-restricted rats have shown a dramatic increase (84%) in blood glutathione levels in methionine-deficient F344 rats, with a corresponding 66% decline in liver glutathione levels (Richie et al., 1994, 2004). The authors note that these changes are not seen in CR animals, and postulate that the changes may reflect compensatory adjustments to keep glutathione levels within a relatively narrow intracellular range in non-hepatic tissues."

(Which seems somewhat strange since MR animals are also usually restricted to 0% cysteine which like methionine is a precursor to glutathione .)

"The mechanisms by which methionine restriction leads to slower aging are not known, of course, but there are several possibilities worth considering. One set of models would emphasize the similarities in endocrine profiles, and perhaps cellular properties, shared by Meth-R and CR rodents. Thus, for example, declines in IGF-Iand T4, lower glucose, lower insulin and (by hypothesis) improvedinsulin sensitivity might be induced by either diet and lead, throughunknown intermediate steps, to slower aging and resistance tomultiple diseases. More generally, each diet might be imagined to induce a mild stress response, perhaps accompanied by mild increases in chronic levels of glucocorticoids (Sabatino et al., 1991) and compensatory increases in MIF that along with other unknown factors modulate aging and disease risks."
http://www.kaeberlei.../501/miller.pdf

I like the mild stress response theory. It can explain why intermittent fasting every other day without CR also produces similar effects to CR.

Edited by Blue, 19 July 2009 - 05:04 AM.

[Blue]

A human CR study! Not a fruit fly, a worm, a rat, or even a primate study. Of course, we live too long for meaningful mortality statistics yet. But I think that IGF-1 is a good proxy since lowering it seems important in all life extension diets. Inactivating the IGF-1R receptor increases lifespan.

"Reduced function mutations in the insulin/IGF-I signaling pathway increase maximal lifespan and health span in many species. Calorie restriction (CR) decreases serum IGF-1 concentration by ~40%, protects against cancer and slows aging in rodents. However, the long-term effects of CR with adequate nutrition on circulating IGF-1 levels in humans are unknown. Here we report data from two long-term CR studies (1 and 6 years) showing that severe CR without malnutrition did not change IGF-1 and IGF-1 : IGFBP-3 ratio levels in humans. In contrast, total and free IGF-1 concentrations were significantly lower in moderately protein-restricted individuals. Reducing protein intake from an average of 1.67 g kg⁻¹ of body weight per day to 0.95 g kg⁻¹ of body weight per day for 3 weeks in six volunteers practicing CR resulted in a reduction in serum IGF-1 from 194 ng mL⁻¹ to 152 ng mL⁻¹. These findings demonstrate that, unlike in rodents, long-term severe CR does not reduce serum IGF-1 concentration and IGF-1 : IGFBP-3 ratio in humans. In addition, our data provide evidence that protein intake is a key determinant of circulating IGF-1 levels in humans, and suggest that reduced protein intake may become an important component of anticancer and anti-aging dietary interventions. "
http://www3.intersci...398450/abstract

This study looks ridiculously important to me. Humans are not rats. All those doing CR should do moderate PR at the same time.

Edited by Blue, 19 July 2009 - 05:27 AM.

[Sillewater]

Man, i've learned a lot from this discussion. I'm really happy to see the proper debate that is going on. No one can argue blue's data. It speaks for itself. The general consensus from the research i've read does seem to point towards a low protein diet or one whose content would be solely achieved by plant sources. I liked Campbell's rebuttal to Cordain in the link provided :

“The reader may find an example to be helpful. Consider a dietary contest. Suppose that Diet A (a diet nearly exclusively of animal origin) resulted in 100% of individuals living long enough to reproduce, but despite adequate calories available throughout the lifespan, average non-accident/non-violent age at death (thus death was from nutrition-related diseases) was 50 years. Diet B (a diet exclusively of plant origin) resulted in just 60% of individuals living long enough to reproduce (perhaps because they were too finicky to eat meat [or because inadequate calories killed young people]), but if fortunate enough to be presented with an environment of sufficient calories (thus likely avoiding all nutrition related diseases)... life expectancy was 90 years. In this contest, Diet A wins the evolutionary battle, and is adopted. The evidence presented by modern nutritional science suggests that something akin to this may well be the case for humans, who have a large constellation of disease processes that can be laid at the door of animal foods, and effectively reversed with vegan diets (see Ornish, Esselstyn, McDougall, etc.). Seen from this perspective, speculation about human dietary history is a fascinating subject, but is actually irrelevant in the search for optimal nutritional practices. Such practices can only be determined by scientific investigation done in the present time, studying varying dietary practices and determining their comparative outcomes.”

Longevity Among Hunter-Gatherers:A Cross-Cultural Examination

Based on this analysis the life expectancy of hunter-gatherers were pretty high.

Also Cordain has a paper here, and there's a section on longevity. Pretty much has the same points as the paper above.

Evolutionary health promotion: a consideration of common counterarguments.

Eaton SB, Cordain L, Lindeberg S.
Departments of Anthropology and Radiology, Emory University, 2887 Howell Mill Road NW, Atlanta, GA 30327, USA. sboydeaton@mindspring.com
The proposal that Late Paleolithic (50,000-10,000 BP) ancestral experience might serve as a model for prevention research and even, if justified by experiment, as a paradigm for health promotion recommendations is sometimes discounted, before critical assessment, because of reservations based on unjustified preconceptions. Most often such biases involve comparative life expectancy, potential genetic change since agriculture, the heterogeneity of ancestral environments, and/or innate human adaptability. This paper examines these topics and attempts to show that none of them justifies a priori dismissal of the evolutionary approach to preventive medicine. Evolutionary health promotion may ultimately be invalidated because of its falsification by experiment or because another theory accords better with known facts, but these commonly held prejudices should not forestall its thoughtful consideration and investigative evaluation. Copyright 2001 American Health Foundation and Elsevier Science (USA).
PMID: 11817904 [PubMed - indexed for MEDLINE]

In my opinion, what Campbell is saying is just his speculation. I don't think his data actually shows what he says it shows.

Tot Mizaj: Four Characters in Uyghur Traditions of Health, Medicine, and Longevity. Interviewing Hotan County Elders in Xinjiang, P.R.C. with Beijing Educated Uyghurs

This is a interview with some of the oldest Uyghur (muslims) in China. Can't glean much about the macronutrient ratios, but it seems to imply that the centenarians do consume meat (in the form of sheeps). Just like the Okinawans they contribute their longevity to meat-eating.

I like to eat corn flour cakes and yumi zhou, corn porridge. Now I have healthy teeth, so I like to eat grapes and walnuts. I eat a little lamb meat every day, even now. I eat no fried food. I liked to eat meat in a soup with yongaksput, cilantro. I think that eating meat is very useful to my health. In my young days I was not heavy, but I could eat a whole sheep in two days. I only tried to smoke marijuana once because I saw my friends do it, but I never did it again! I have never drunk alcohol in my whole life. I like to take some flower teas like, pinnapsa (mint), which is useful when you get a cold. I don’t drink tea every day. I like to drink soghuk su (cold water), and sometimes, very seldom, I have tea. I think of myself as a charuchen, mumin, (herdsman).

But they also eat a lot of corn.

Effect of nationality on dietary pattern and meal behavior in China.

Ge K, Zhai F, Wang Q.
Institute of Nutrition and Food Hygiene, Chinese Academy of Preventive Medicine, Beijing.
In 1992 a national nutrition survey was conducted in China in approximately 100,000 people of all ages selected with use of a multistage, stratified, random, clustered procedure. Dietary data were collected with three consecutive 24-h recalls. A total of 9304 members of 20 minority nationality groups were included in the survey, accounting for 9.3% of the total sample. Meal behavior varied greatly according to nationality. Almost all Koreans and Tibetans ate three meals daily but 85% of Lahu people ate only two. Members of many other groups, including the Han, the majority nationality group in China, ate between two and three meals a day. People who ate two meals a day usually ate less than did those consuming three meals. The minority groups consumed amounts of dietary energy and protein comparable to those eaten by the majority group, although cereals accounted for a larger portion and animal food a smaller portion of energy and protein intakes. There were no differences in the dietary patterns of men and women of the same nationalities.
PMID: 9094935 [PubMed - indexed for MEDLINE]

Based on this study, the Ugyur consume 45g of animal product per day, but consume 107g/d (based on 281 individuals), most of the protein probably comes from corn, but the protein intake is still high. However this is not specific to the centenarians.

I have had the pleasure of visiting a Ugyur family, and there was a lot of meat, but it may be just because I was a guest at their house, but based on this books account:

Biopsychosocial Approaches to Longevity

on Pg186, it matched closely with what I was served. Especially that lamb kebabs.

A survey of the dietary nutritional composition of centenarians

Abstract:
ObjectiveTo make a survey of the nutritional composition of the diets of centenarians.
Methods Thirty- four centenarians were selected as subjects. Retrospective surveys were made on the variety and amounts of food consumed and their nutritional composit ion. Physical examinations with laboratory tests such as cardiograms, ultrasoni c B rays, and blood, urine and hair tests were performed. Neutron activation te sting was done on hair content. The transmission turbidimetric method was used to measure apolipoprotein content.
Results The main food of the centenarians showed the characteristics of low calories, pr otein and fat but high fiber and mineral content. Laboratory results showed tha t the content of the elements of Cu, Se and Mn in hair was higher (P<0. 01) . Zn was normal. The apoA1/apoB100 ratio was higher than in the contro l group (P<0. 0I), and total cholesterol (TC) was lower than in the control group (P<0. 01).
Conclusions The variety of diet and its nutritional composition may be the main factors infl uencing not only the content of elements in body, but also the levels of apoA1 and apoB100, which may be helpful in preventing arteriosclerosis and form ing and maintaining immunity. The diet of these centenarians might aid in preve nting cardiovascular and cerebrovascular diseases and malignant tumors.
CMJ 2001;114(10):1095-1097

However based on the paper above: a survey of 34 chinese centenarians their diet was low-calorie, low protein, low-fat.

[Blue]

I do not find the diet in some prior period in human development very interesting for life extension purposes. Our selfish genes has little interest in us living long. Only in us reproducing. Even if human development had stayed at a certain stage for the human body to adapt perfectly to the conditions then and we knew exactly what that diet was, then this would still only be a diet that together with your body would maximize your number of surviving children in that environment. Not your health, longevity, or happiness, which evolution will gladly sacrifice if you get more surviving children.

Similarly, anecdotal evidence are not that convincing. At most evolutionary and anecdotal stories can point to what experimental studies to do. Real evidence in science is experimental studies. For instance, those advocating a high protein diet must somehow explain away the human CR + PR study I cited in my last post.

Edited by Blue, 19 July 2009 - 06:02 AM.

[kismet]

....
This study looks ridiculously important to me. Humans are not rats. All those doing CR should do moderate PR at the same time.

Yes, yes, Fontana's argument and it's just mechanistic speclation*, nothing else. 
We should keep in mind that PR (or low IGF-1) is not necessary for the CR effect. (1) We could speculate that adding PR and/or MR to CR would give additional benefits, though. However, there's again the problem that animals fed a high protein diet live the same or longer than their counterparts and that a restriction too severe results in a shortened lifespan. Doing PR, MR *and* CR is way too dangerous. Also PR and CR combined has not shown to be effective in animals. So, I think that he is right in advocating slight methionine restriction & CR. IIRC that's what he's doing. (2) Or, alternatively, and I'm not sure if that is a good idea you could do PR and CR, which would also results in slight MR I guess. I think that's what Dr Fontana advocates. Either way, there's a lot of speculation involved, but you can't go wrong doing just CR...

Again:
(1) http://www.imminst.o...mp;#entry266712
(2) http://www.mfoundati...p=4037#post4037

*we know low IGF-1 levels extend life span in animals, you*assume* low levels will do the same in humans and you *assume* that those benefits will be additive to CR and you *assume* that the animal studies showing high protein CR to be superior or similar cannot be applied to humans. That's pretty much what we call speculation. You are wording it as if your study was a "real" (whatever that means) experimental study. No, it's just a biomarker study...

That is one of the reasons I want to see the IGF-1 data from the primate CR studies.

Edited by kismet, 19 July 2009 - 12:35 PM.

[Blue]

Yes, yes, Fontana's argument and it's just mechanistic speclation*, nothing else.
We should keep in mind that PR (or low IGF-1) is not necessary for the CR effect. (1) We could speculate that adding PR and/or MR to CR would give additional benefits, though. However, there's again the problem that animals fed a high protein diet live the same or longer than their counterparts and that a restriction too severe results in a shortened lifespan. Doing PR, MR *and* CR is way too dangerous. Also PR and CR combined has not shown to be effective in animals. So, I think that he is right in advocating slight methionine restriction & CR. IIRC that's what he's doing. (2) Or, alternatively, and I'm not sure if that is a good idea you could do PR and CR, which would also results in slight MR I guess. I think that's what Dr Fontana advocates. Either way, there's a lot of speculation involved, but you can't go wrong doing just CR...

Again:
(1) http://www.imminst.o...mp;#entry266712
(2) http://www.mfoundati...p=4037#post4037

*we know low IGF-1 levels extend life span in animals, you*assume* low levels will do the same in humans and you *assume* that those benefits will be additive to CR and you *assume* that the animal studies showing high protein CR to be superior or similar cannot be applied to humans. That's pretty much what we call speculation. You are wording it as if your study was a "real" (whatever that means) experimental study. No, it's just a biomarker study...

That is one of the reasons I want to see the IGF-1 data from the primate CR studies.

You claim "animals fed a high protein diet live the same or longer than their counterparts and that a restriction too severe results in a shortened lifespan"? Are you again talking about the the 1989 study that do find that life extension could be achieved in a rat prone to nephropathy by lowering calories without lowering protein and even that this was very slightly better than also lowering protein as the same time as calories? This study does not say that a high-protein diet in general without CR is good. Or that CR with higher than normal protein is good even for these nephropathic rats. Or that normal protein for laboratory rats is equivalent to the very high average protein intake for Americans. Or that protein restriction alone cannot achieve life extension. Or that CR + normal protein is better than PR or MR.

More importantly, humans are not rats prone to nephropathy. A human study is more important that a rat study. The human CR + PR study I cited showed that human react differently to CR as compared to rats.

Regarding your claim "We should keep in mind that PR (or low IGF-1) is not necessary for the CR effect." Some very, very selective citations in your first link which rely on this table: http://www.pnas.org/....expansion.html For Growth hormone receptor (GHR)/GH-binding protein knockout (GHRKO) mice CR has an insignificant effect on median or average lifespan. Yes, CR had some small effect on maximal longevity for GHRKO mice (maximal longevity is the mean age at death of the oldest 10% in each group). But median and average lifespan increase is the most important for the majority. It seems clear from that study that almost all of the CR effect can be prevented by inactivating the GH receptor (which in turn strongly affects IGF-1).

Or to quote a more recent study: "The authors concluded that the findings more likely indicate the requirement of GHR signaling for lifespan extension by calorie restriction".
http://www.gghjourna...me22/3/ab15.cfm

Edited by Blue, 19 July 2009 - 01:38 PM.

[kismet]

It's so tedious to argue with you, but I'm way too bored to just give up.

You claim (I do not "claim", but the data I presented definitely shows that those) "animals fed a high protein diet live the same or longer than their counterparts // and that a restriction too severe results in a shortened lifespan"? Are you again talking about the the 1989 study that do find that life extension could be achieved in a rat prone to nephropathy by lowering calories without lowering protein and even that this was very slightly better than also lowering protein as the same time as calories? Yes, and all the other studies demonstrating that high protein CR is similar or better than low P CR. What's the problem with this study anyway? Those rats were pushing pretty solid life spans, so it's a valid observation. What's the problem with nephrophaty? If anything, I'd expect those rats to benefit less from protein if they have kidney issues.If your theory of low P/M being necessary applied to those animals, they'd show a shorter lifespan, but they don't.

This study does not say that a high-protein diet in general without CR is good. It doesn't. Neither did I in my recent posts (although, I think that to be the case if you want to practise an ad lib diet, as I do not consider CR, PR or MR to be ad lib. While CR is best supported by the evidence). Or that CR with higher than normal protein is good even for these nephropathic rats. Actually, I believe their diet was "higher" in protein on a protein/weight basis. Or that normal protein for laboratory rats is equivalent to the very high average protein intake for Americans.

Or that protein restriction alone cannot achieve life extension. Or that CR + normal protein is better than PR or MR. It doesn't. Neither do I.
Let me reiterate for the umpteenth time, it shows: CR with "high" protein still works perfectly well in those animals. Considering that there is a lot of evidence in favour of CR and PR/MR used to have "experimental" status (sure, that may have changed), it's not very prudent to do either. Heavy MR found to extend life span in lab animals is still not feasible in humans BTW. We're left with CR, PR or slight MR as an addition...

More importantly, humans are not rats prone to nephropathy. A human study is more important that a rat study. Yeah, but we have no human studies. The human CR + PR study I cited showed that human react differently to CR as compared to rats. So what? The data definitely shows that lowered IGF-1 is not necessary for CR. What is your point?

Regarding your claim "We should keep in mind that PR (or low IGF-1) is not necessary for the CR effect." Some very, very selective citations in your first link which rely on this table: http://www.pnas.org/....expansion.html For Growth hormone receptor (GHR)/GH-binding protein knockout (GHRKO) mice CR has an insignificant effect on median or average lifespan. Yes, CR had some small effect on maximal longevity for GHRKO mice (maximal longevity is the mean age at death of the oldest 10% in each group - thank you, I didn't know!). But median and average lifespan increase is the most important for the majority. No it is not! This statement is just wrong*. It seems clear from that study that almost all of the CR effect can be prevented by inactivating the GH receptor (which in turn strongly affects IGF-1).

*look at the human survival curves: They are almost square and advances in medicine will further contribute to increased average life span. Average life span is irrelevant, we're already pushing the boundaries. It is accepted by gerontologists that max life span is a very good marker of rate of aging and only slowing the latter is really benefical. http://sorrytoconfus...c...w=423&h=309

Or to quote a more recent study: "The authors concluded that the findings more likely indicate the requirement of GHR signaling for lifespan extension by calorie restriction". "GHR signalling likely to be involved to some degree", yes, that would be more accurate, because the data shows a trend towards increased average life span and improved max life span. We shouldn't discount small increases in maximal life span, as the authors state: "Possible explanations include a “ceiling effect” in maximal life extension that was already achieved by GHRKO" (=the law of diminishing returns)
Assuming IGF is involved (which no one denies), it doesn't change the fact that PR is not backed up by as much data as CR.
http://www.gghjourna...me22/3/ab15.cfm

What do you want to discuss? What do you suggest?
Currently you are talking about a million things at one time and putting words in my mouth I didn't say. Do you want to know whether PR or MR or CR is superior in humans? We just don't know. Dr Fontana's objection is certainly valid (based on the biomarker study), but it's nothing but a hypothesis at this time. I've already mentioned that CR + slight MR seems like a good bet and possibly CR + slight PR.

But forgoing CR in favour of MR or PR, while the CR experiment in primates is nearing its end and showing benefits, would be crazy from a risk:benefit ratio and not because MR or PR does not "work" (that is assuming the primate CR did not involve PR or lowered IGF-1, which is the reason why I'd like to see the data if it exists...)

Edited by kismet, 19 July 2009 - 05:39 PM.

[Blue]

Let's discuss one central thing of importance and confusion. You state "look at the human survival curves: They are almost square and advances in medicine will further contribute to increased average life span. Average life span is irrelevant, we're already pushing the boundaries. It is accepted by gerontologists that max life span is a very good marker of rate of aging and only slowing the latter is really benefical"

There are two sorts of "maximum life span". One is rather inexactly the life span of the longest lived members of a species under certain conditions. More exactly it can also mean the mean age at death of the oldest 10% in each group.The curves are not square. There is a huge difference between the average for all and the average for the 10% who live the longest.

So look again at the poorly cited table:
http://www.pnas.org/....expansion.html

Normal, none-GHRKO mice had an average lifespan of 887 and a "maximal life span" of 1163. GHRKO mice on non-CR diet had an average lifespan of 1139. That is, almost the same as the "maximal life span" for ordinary mice. Putting the GHRKO mice on CR changed this very little. What is the equivalent among human? From you graph it looks like 10% lives to at least 90-95 years.

Why should we only look at the average mean age of death of oldest 10% in each group? That is the extraordinary minority, not the normal majority.

Edited by Blue, 19 July 2009 - 06:00 PM.

[JLL]

What are the other studies showing high-protein CR is better than medium/low-protein CR?

[kismet]

 Why should we only look at the average mean age of death of oldest 10% in each group? That is the extraordinary minority, not the normal majority.

Because it is a better measure of aging than average life span.

The curves are not square.

I give up. Apparently we do not speak the same language (maybe I'll get back to some of the more interesting points during the week). But see for yourself...
Kismet said: "look at the human survival curves: They are almost square and advances in medicine will further contribute to increased average life span. [i.e. in the future they will be much more square than that] Average life span is irrelevant, we're already pushing the boundaries [and we shouldn't forget that life style choices influence avg life span more than anything else, without affecting the rate of aging]. It is accepted by gerontologists that max life span is a very good marker of rate of aging and only slowing the latter is really benefical"

@JLL Although, I still haven't read his old Albatross/Zone megapost. We can find some references there, e.g. another pro-protein study (I skimmed the text to find the info, but I think it shows high and moderate protein CR superior to low protein CR).  

Let me quote the relevant part, but you can (and actually should, as it is more complicated than my quote makes it seem) read the rest & incl. the table for yourself: http://health.groups...ty/message/4224
"But that isn't what Ross' data shows. In fact, to my surprise, it shows what we are constantly told that the data DON'T show: that MACRONUTRIENT COMPOSITION CAN INFLUENCE MAX LS, and that the higher the protein, the longer the LS...Turning to their [77] table 2, we find that there is improved max LS in BOTH the Cr AND the ad lib groups, correlated postiively with protein intake...."
Ref. 77. Ross MH, Bras G.
Influence of protein under- and overnutrition on spontaneous tumor prevalence in the rat. J Nutr. 1973 Jul;103(7):944-63. No abstract available.
PMID: 4351915; UI: 73211348

EDIT:
Disregarding Fontana's hypothesis, here's some more on the situation in rodents:
http://www.mfoundati...mp;postcount=14
And Ross' paper seems to be available for free: http://jn.nutrition....t/103/7/944.pdf

Edited by kismet, 19 July 2009 - 08:34 PM.