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Low Protein the real way to go?


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#1 captainbeefheart

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Posted 15 June 2010 - 07:43 PM


Not sure if anyone saw the article in the New Scientist I think it would have been last month (don;t subscribe, a friend showed it to me). But basically it rubbished CR and said low protein was in fact the key to longevity. Can't find the article on their site, but anyone know what I'm talking about!? At any rate it;s nice to see arctles whatever they say on longevity. Not that I partake in CR I'm rather skeptical, or don't see enough of a reason to put myself through it anyway... Nor do I probably have much of a low protein diet however!

#2 TheFountain

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Posted 16 June 2010 - 10:25 AM

The problem with very low protein diets is that you can't really go low carb on them because having a high fat, low carb diet without protein will leave you emaciated. Plus it will make you skinny-fat. Protein is necessary to burn the fat we consume. Now maybe something like 120 grams a day is adequate for this. This would be more moderate than the usual 1 pound of protein per pound of body weight. I do not know how far this level of protein would get a body builder. Probably not very far.

Edited by TheFountain, 16 June 2010 - 10:26 AM.

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#3 Blue

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Posted 16 June 2010 - 12:05 PM

The problem with very low protein diets is that you can't really go low carb on them because having a high fat, low carb diet without protein will leave you emaciated. Plus it will make you skinny-fat. Protein is necessary to burn the fat we consume. Now maybe something like 120 grams a day is adequate for this. This would be more moderate than the usual 1 pound of protein per pound of body weight. I do not know how far this level of protein would get a body builder. Probably not very far.

Sources are greatly needed for all of these dubious statements. The RDA for protein is only 0.8g / kg body weight which is adequate for 97.5% of the population (obviously not bodybuilders).

Edited by Blue, 16 June 2010 - 12:07 PM.


#4 e Volution

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Posted 16 June 2010 - 04:31 PM

Full article: NewScientist: Eat less, live longer?

edit: Just read the comments (I buys the magazine), we need a couple of these guys on the forum!

Snippet with main point of the article (IGF-1):

But Fontana has found a notable difference in the way people and animals respond to calorie restriction, and it is not great news. It involves a hormone made by the liver called insulin-like growth factor 1.

IGF-1 has emerged as an important promoter of ageing. IGF-1 levels are lower than normal in worms, flies and mice on a restricted diet, and this is thought to be at least partly responsible for their longer lifespan. When it comes to people, however, CRONies have the same IGF-1 levels as the rest of us.

The explanation for this anomaly may lie in a new theory about how diet affects ageing. This says that it may not only be the drop in calories that is responsible for lifespan extension - in some species at least, perhaps it is also the accompanying drop in dietary protein.

One piece of evidence for this idea comes from studies in fruit flies and rodents. If these animals are fed special diets with less amino acids - the building blocks of proteins - they can eat as many calories as they want and still live longer. "These results clearly show that you don't need to restrict calories as a whole to get lifespan extension," says Piper, an author of the study on flies (Nature, vol 462, p 1061).

Further support for this idea comes from studying the molecular pathways inside cells that affect lifespan. A molecule called TOR has been found to set off a chain of reactions that boost cell growth at the expense of longevity. Blocking TOR increases lifespan in all organisms studied to date, including yeast and mice (Aging Cell, vol 9, p 105). Crucially, the most potent activators of TOR are amino acids.

Where does the protein theory leave the CRONies? Fontana noticed that the people in his study group were eating high levels of protein, about 1.7 grams per kilogram of body weight per day. This is more than the US government-recommended intake of 0.8 g/kg/day, and higher than that in a typical American's diet, about 1.2 g/kg/day.

So Fontana asked six CRONies to cut their protein intake to 0.95 g/kg/day while maintaining their usual calorie intake. After only three weeks on the low-protein diet, the CRONies showed a 25 per cent drop in their levels of IGF-1 (Aging Cell, vol 7, p 681). "Even if the CRONies are restricting their calories severely, if they're eating a high-protein diet, they're probably negating some of the most important beneficial effects," says Fontana.

If the new theory is right, then the whole concept of calorie restriction needs to be rethought. The very term would be misleading; Fontana and others have started referring to dietary restriction instead. As news of the study has spread, some CRONies have already reduced their protein intake.


Overall a great article on CR by NewScientist. I don't believe they rubbished CR/CRONies at all. Everything seemed aligned and in accordance with discussions on this forum, even went into methionine, TOR, rapamycin, metformin, and obligatory resveratrol ("Resveratrol still has supporters, but inconsistent animal data have since dampened much of the enthusiasm" lol).

Edited by icantgoforthat, 16 June 2010 - 04:51 PM.


#5 Blue

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Posted 16 June 2010 - 04:59 PM

Full article: NewScientist: Eat less, live longer?

edit: Just read the comments (I buys the magazine), we need a couple of these guys on the forum!

Snippet with main point of the article (IGF-1):

But Fontana has found a notable difference in the way people and animals respond to calorie restriction, and it is not great news. It involves a hormone made by the liver called insulin-like growth factor 1.

There are lots of discussions of protein restriction and this not all that new study by Fontana in other threads.

They mention possible side effects of metformin but miss the most worrying which is a possible promotion of Alzheimers.

Edited by Blue, 16 June 2010 - 05:03 PM.


#6 Skötkonung

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Posted 17 June 2010 - 12:10 AM

The problem with very low protein diets is that you can't really go low carb on them because having a high fat, low carb diet without protein will leave you emaciated. Plus it will make you skinny-fat. Protein is necessary to burn the fat we consume. Now maybe something like 120 grams a day is adequate for this. This would be more moderate than the usual 1 pound of protein per pound of body weight. I do not know how far this level of protein would get a body builder. Probably not very far.

Sources are greatly needed for all of these dubious statements. The RDA for protein is only 0.8g / kg body weight which is adequate for 97.5% of the population (obviously not bodybuilders).

Yes, but that protein requirement is likely given in the context of a "normal" diet, no one that is carbohydrate restricted (characteristically high in fat). The body requires amino acids (whether from diet or its own tissues) as a necessary substrate for gluconeogenesis. At a certain point, when dietary protein is sufficiently restricted, the body will begin catabolizing its own tissues to power gluconeogenesis. This is essentially the same process that occurs during starvation -- the difference being the body is wasting the muscle without using the fat (the bloated look mentioned by TheFountain).

It is worth noting, however, that ketogenic diets for epileptic children (very low protein) do not cause wasting but often stunt growth. I'm not sure about the protein restricted ketogenic cancer protocols, though. There is some evidence that once the body is "fully adapted" to using ketones the protein requirement will become lower.
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#7 Sillewater

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Posted 17 June 2010 - 01:43 AM

Curr Opin Clin Nutr Metab Care. 2010 Jan;13(1):52-7.
Evidence that protein requirements have been significantly underestimated.
Elango R, Humayun MA, Ball RO, Pencharz PB.

The Research Institute, The Hospital for Sick Children, Toronto, Canada.
Abstract
PURPOSE OF REVIEW: This review discusses recent evidence that suggests a significant underestimation of protein requirements in adult humans. RECENT FINDINGS: Traditionally, total protein requirements for humans have been determined using nitrogen balance. The recent Dietary Reference Intake recommendations for mean and population-safe intakes of 0.66 and 0.8 g/kg/day, respectively, of high-quality protein in adult humans are based on a meta-analysis of nitrogen balance studies using single linear regression analysis. We reanalyzed existing nitrogen balance studies using two-phase linear regression analysis and obtained mean and safe protein requirements of 0.91 and 0.99 g/kg/day, respectively. The two-phase linear regression analysis is considered more appropriate for biological analysis of dose-response curves. Considering the inherent problems associated with the nitrogen balance method, we developed an alternative method, the indicator amino acid oxidation technique, to determine protein requirements The mean and population-safe requirements in adult men were determined to be 0.93 and 1.2 g/kg/day and are 41 and 50%, respectively, higher than the current Dietary Reference Intakes recommendations. SUMMARY: The indicator amino acid oxidation-based requirement values of 0.93 and 1.2 g protein/kg/day and the reanalysis of existing nitrogen balance studies are significantly higher than current recommendations. Therefore, there is an urgent need to reassess recommendations for protein intake in adult humans.

PMID: 19841581 [PubMed - indexed for MEDLINE]


I keep my protein intake around 1g/kg/day to 1.2g/kg/day. I find that if I get it lower I become ravenously hungry (I also like having some muscle).

Edited by Sillewater, 17 June 2010 - 01:47 AM.

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#8 hypnotoad

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Posted 17 June 2010 - 02:36 AM

Ok so my take-away from this is that like everything else with diet you have a trade off - more muscle and strength vs a potentially longer life. But longer by how much? We have no idea how the protein intake vs lifespan curve might work out in humans (nor with normal CR as well)

I guess people have to ask themselves how much longer they really think they are likely to live by cutting their protein way down. Going through life under-muscled and suffering sarcopenia in the hopes that you are going to squeeze out a few more years is a guessing game I'm not willing to make.

I can see not going nuts on protein intake (200 grams per day etc), but neither will I be cutting it back despite my general interest in longevity. My wild hunch is that 1 - 1.5g/kg body weight puts people right in the sweet spot of the risk-reward ratio and dropping it lower will give minimal returns for the deprivation required. 15 extra lbs of muscle has benefits in and of itself in terms of metabolic rate, physical robustness, appearance, injury resistance etc.

Edited by hypnotoad, 17 June 2010 - 02:38 AM.


#9 niner

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Posted 17 June 2010 - 02:44 AM

Ok so my take-away from this is that like everything else with diet you have a trade off - more muscle and strength vs a potentially longer life. But longer by how much? We have no idea how the protein intake vs lifespan curve might work out in humans (nor with normal CR as well)

I guess people have to ask themselves how much longer they really think they are likely to live by cutting their protein way down. Going through life under-muscled and suffering sarcopenia in the hopes that you are going to squeeze out a few more years is a guessing game I'm not willing to make.

There hasn't been any mention of autophagy here, but as protein consumption goes down, autophagy goes up. This will make it less likely that you will suffer from neurological disease later in life. Having good musculature but a bad brain is not a good outcome. This is a good argument for intermittent fasting.
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#10 hypnotoad

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Posted 17 June 2010 - 02:52 AM

Ok so my take-away from this is that like everything else with diet you have a trade off - more muscle and strength vs a potentially longer life. But longer by how much? We have no idea how the protein intake vs lifespan curve might work out in humans (nor with normal CR as well)

I guess people have to ask themselves how much longer they really think they are likely to live by cutting their protein way down. Going through life under-muscled and suffering sarcopenia in the hopes that you are going to squeeze out a few more years is a guessing game I'm not willing to make.

There hasn't been any mention of autophagy here, but as protein consumption goes down, autophagy goes up. This will make it less likely that you will suffer from neurological disease later in life. Having good musculature but a bad brain is not a good outcome. This is a good argument for intermittent fasting.



Totally agree - The great thing about IFing is that you can get some beneficial autophagy and metabolic improvements without wasting away ala a chronic standard (or even protein targeted) CR lifestyle. And rest assured, if you cut out too much protein you WILL waste away your muscle. I know that its open to debate whether or not IFing enhances total lifespan, but even if it doesn't, it has certainly enhanced the quality of my life in the meantime. It's the old quality vs quantity dilemma and normal protein but lowish carbs, low-insulin, and IFing seem to be a great way (for me at least) to balance conflicting demands.

FYI I go through the same dilemma in regards to numerous LEF topics - nuts and omega 6, the ratio of Sat vs Poly vs Mono oils, how much starch is healthy, how much fructose is safe, how much to supplement etc. Sunlight damage vs vitamin D etc. So many grey areas in this whole thing.

Edited by hypnotoad, 17 June 2010 - 02:57 AM.


#11 TheFountain

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Posted 17 June 2010 - 08:46 AM

The problem with very low protein diets is that you can't really go low carb on them because having a high fat, low carb diet without protein will leave you emaciated. Plus it will make you skinny-fat. Protein is necessary to burn the fat we consume. Now maybe something like 120 grams a day is adequate for this. This would be more moderate than the usual 1 pound of protein per pound of body weight. I do not know how far this level of protein would get a body builder. Probably not very far.

Sources are greatly needed for all of these dubious statements. The RDA for protein is only 0.8g / kg body weight which is adequate for 97.5% of the population (obviously not bodybuilders).



I am not saying it isn't adequate but I am sure it is not adequate for a low carb diet. I tried it and was emaciated and left with more body fat than I wanted. Increasing portein made it easier for me to burn the body fat off.
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#12 Blue

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Posted 17 June 2010 - 09:34 AM

Curr Opin Clin Nutr Metab Care. 2010 Jan;13(1):52-7.
Evidence that protein requirements have been significantly underestimated.
Elango R, Humayun MA, Ball RO, Pencharz PB.

The Research Institute, The Hospital for Sick Children, Toronto, Canada.
Abstract
PURPOSE OF REVIEW: This review discusses recent evidence that suggests a significant underestimation of protein requirements in adult humans. RECENT FINDINGS: Traditionally, total protein requirements for humans have been determined using nitrogen balance. The recent Dietary Reference Intake recommendations for mean and population-safe intakes of 0.66 and 0.8 g/kg/day, respectively, of high-quality protein in adult humans are based on a meta-analysis of nitrogen balance studies using single linear regression analysis. We reanalyzed existing nitrogen balance studies using two-phase linear regression analysis and obtained mean and safe protein requirements of 0.91 and 0.99 g/kg/day, respectively. The two-phase linear regression analysis is considered more appropriate for biological analysis of dose-response curves. Considering the inherent problems associated with the nitrogen balance method, we developed an alternative method, the indicator amino acid oxidation technique, to determine protein requirements The mean and population-safe requirements in adult men were determined to be 0.93 and 1.2 g/kg/day and are 41 and 50%, respectively, higher than the current Dietary Reference Intakes recommendations. SUMMARY: The indicator amino acid oxidation-based requirement values of 0.93 and 1.2 g protein/kg/day and the reanalysis of existing nitrogen balance studies are significantly higher than current recommendations. Therefore, there is an urgent need to reassess recommendations for protein intake in adult humans.

PMID: 19841581 [PubMed - indexed for MEDLINE]


I keep my protein intake around 1g/kg/day to 1.2g/kg/day. I find that if I get it lower I become ravenously hungry (I also like having some muscle).

Very interesting. Will see what follow from that study. But for now its one against many others which have found support for a lower requirement. Regarding ravenously hungry, well, that may well be exactly how you should feel under a working CR since a common baseline for CR is unrestricted intake which presumable means that the animals select the most enjoyable level of intake.

Edited by Blue, 17 June 2010 - 09:36 AM.


#13 Sillewater

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Posted 21 June 2010 - 07:01 AM



J Clin Invest. 1983 Feb;71(2):175-82.


Dietary components that regulate serum somatomedin-C concentrations in humans.
Isley WL, Underwood LE, Clemmons DR.


Abstract
Dietary components responsible for the regulation of somatomedin-C in humans were assessed in five adult volunteers of normal weight who were fasted for 5 d on three occasions, then refed three diets of differing composition. The serum somatomedin-C decreased from a mean prefasting value of 1.85 +/- 0.39 U/ml (+/- 1 SD) to 0.67 +/- 0.16 U/ml at the end of fasting (P less than 0.005). After refeeding for 5 d with a normal diet, the mean serum somatomedin-C increased to 1.26 +/- 0.20 U/ml. A protein-deficient (32% of control), isocaloric diet resulted in a significantly smaller increase, to a mean value of 0.90 +/- 0.24 U/ml (P less than 0.05). A diet deficient in both protein and energy led to a further fall 0.31 +/- 0.06 U/ml. The changes in somatomedin-C during fasting and refeeding correlated significantly with mean daily nitrogen balance (r = 0.90). We conclude that both protein and energy intake are regulators of serum somatomedin-C concentrations in adult humans, and energy intake may be of greater importance. The correlation between changes in somatomedin-C and nitrogen balance suggests that the former are directly related to changes in protein synthesis and may be helpful in assessing the response to nutritional therapy.

PMID: 6681614 [PubMed - indexed for MEDLINE]PMCID: PMC436855Free PMC Article



It seems IGF1 increased up to when the subjects consume 1g/kg/day/

Edited by Sillewater, 21 June 2010 - 07:06 AM.

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#14 PWAIN

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Posted 21 June 2010 - 11:44 PM

What is the carbs/fat/protein ratio being used on the test monkeys?

They seem to be responding to CR so it may be worth observing them, since they are closer to us than flies.
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#15 captainbeefheart

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Posted 04 July 2010 - 04:45 PM

Overall a great article on CR by NewScientist. I don't believe they rubbished CR/CRONies at all. Everything seemed aligned and in accordance with discussions on this forum, even went into methionine, TOR, rapamycin, metformin, and obligatory resveratrol ("Resveratrol still has supporters, but inconsistent animal data have since dampened much of the enthusiasm" lol).


do';t think that's the article I was referring to. The article I was referring to very much said CR was pointless and a low protein diet was key to longevity.

#16 Saintor

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Posted 04 July 2010 - 09:30 PM

The explanation for this anomaly may lie in a new theory about how diet affects ageing. This says that it may not only be the drop in calories that is responsible for lifespan extension - in some species at least, perhaps it is also the accompanying drop in dietary protein.

...
Where does the protein theory leave the CRONies? Fontana noticed that the people in his study group were eating high levels of protein, about 1.7 grams per kilogram of body weight per day. This is more than the US government-recommended intake of 0.8 g/kg/day, and higher than that in a typical American's diet, about 1.2 g/kg/day.

So Fontana asked six CRONies to cut their protein intake to 0.95 g/kg/day while maintaining their usual calorie intake. After only three weeks on the low-protein diet, the CRONies showed a 25 per cent drop in their levels of IGF-1 (Aging Cell, vol 7, p 681). "Even if the CRONies are restricting their calories severely, if they're eating a high-protein diet, they're probably negating some of the most important beneficial effects," says Fontana.



This is a direct hit in my balls. :wacko:

I find it easy to have a low calories 'diet' in good part because of the proteins. For some meals, I'll just eat a 300g chicken or beef tournedos steak with vegetables - and love it.

Some don't agree (but we don't see evidences)
http://www.ironmanma...aging-research/

Preliminary studies of IGF-1 with human subjects have shown beneficial effects. For example, researchers recently examined the effects of IGF-1 on human mortality.2 Critics of IGF-1 and GH therapy often say that rather than offering a fountain of youth, the hormones may hasten death, citing the longevity of some animals that are hormone deficient. In the eight-year human mortality investigation of IGF-1, which involved 376 healthy subjects aged 73 to 94, higher amounts of IGF-1 were associated with longer life and reduced cardiovascular risk. Those with the least IGF-1 in their bodies showed nearly twice the risk of death of those who had more.


Edited by Saintor, 04 July 2010 - 09:52 PM.


#17 Sillewater

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Posted 05 July 2010 - 04:18 AM

Well as long as your IGF-1 is lower (due to CR) then it shouldn't be a problem. MR used to promote a higher protein diet for CR-folks but recently in a post he says his opinion is more "nuanced." From a lot of experiments manipulating the GH/IGF1 signalling/pathway it sure seems IGF1 is important.

Reading MR's Albatross post over at CRSociety he uses a lot of data from adlib-folk and says the benefits should transfer over to CR-folk but in my mind higher protein = higher IGF1, if CR lowers IGF1 maybe protein may not be that beneficial. But based on Fontana's statement above there was a 25% decrease in IGF1 at 1g/kg/day (which is my around my limit).

Anyways I'm interested to see where the research goes.

I fast 2-3 times a week and intermittent fasting has been shown to raise IGF1 (this explains my ability to retain muscle mass, and I definitely eat less calories then when I didn't fast). I was wondering if a lower protein intake would lower IGF1 in those who fast.

#18 Sillewater

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Posted 05 July 2010 - 06:43 AM

Just out of interest:



J Clin Endocrinol Metab. 2005 Jan;90(1):366-71. Epub 2004 Oct 27.


Free rather than total circulating insulin-like growth factor-I determines the feedback on growth hormone release in normal subjects.
Chen JW, Højlund K, Beck-Nielsen H, Sandahl Christiansen J, Orskov H, Frystyk J.

Medical Research Laboratories and Medical Department M, Aarhus University Hospital, Norrebrogade 44, DK-8000 Aarhus C, Denmark.


Abstract
Pituitary GH secretion is feedback regulated by circulating IGF-I. However, it remains to be determined whether the feedback control is mediated through circulating free or total IGF-I. To study this, we compared the temporal changes in circulating levels of GH vs. free and total IGF-I during fasting. Seventeen healthy normal-weight subjects (body mass index 23.4 +/- 0.6 kg/m(2)) were studied during 80 h of fasting. Serum was assayed for GH every 3 h; total, free, and bioactive IGF-I, IGF binding protein (IGFBP)-1, -2, and -3 as well as IGFBP-1 bound IGF-I were assayed every morning. During fasting, mean 24-h GH levels increased from 1.41 +/- 0.20 to 3.01 +/- 0.46 and 2.09 +/- 0.30 microg/liter (d 1 vs. d 2 and 3; P < 0.03). After 24 h of fasting, free and bioactive IGF-I had decreased by 40 +/- 5 and 17 +/- 5%, respectively (P < 0.02), and both concentrations remained suppressed for the rest of the study. In contrast, total IGF-I remained unchanged until the end of d 3, at which levels were slightly reduced (P < 0.007). IGFBP-1 increased from 38 +/- 2 to 137 +/- 24, 212 +/- 32, and 214 +/- 22 microg/liter (d 1 vs. d 2, d 3, and end of d 3; P < 0.0001), and these changes closely paralleled those of IGFBP-1-bound IGF-I (P < 0.0001). IGFBP-2 increased only transiently at d 2 (P < 0.05), and IGFBP-3 remained unchanged. The increase in mean 24-h GH levels from d 1 to d 2 correlated inversely with the relative reduction in free IGF-I from d 1 to d 2 (r = -0.51; P = 0.04), i.e. the larger the reduction in free IGF-I, the larger the increase in GH. None of the other IGF-related parameters correlated with GH. In conclusion, the temporal relationship between the increase in GH and the reduction in free IGF-I supports the hypothesis that circulating free IGF-I mediates the feedback regulation of GH secretion.

PMID: 15509643 [PubMed - indexed for MEDLINE]Free Article





#19 Michael

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Posted 05 July 2010 - 06:42 PM

The explanation for this anomaly may lie in a new theory about how diet affects ageing. This says that it may not only be the drop in calories that is responsible for lifespan extension - in some species at least, perhaps it is also the accompanying drop in dietary protein. ... "Even if the CRONies are restricting their calories severely, if they're eating a high-protein diet, they're probably negating some of the most important beneficial effects," says Fontana.


Some don't agree (but we don't see evidences)
http://www.ironmanma...aging-research/

Preliminary studies of IGF-1 with human subjects have shown beneficial effects. For example, researchers recently examined the effects of IGF-1 on human mortality.2 Critics of IGF-1 and GH therapy often say that rather than offering a fountain of youth, the hormones may hasten death, citing the longevity of some animals that are hormone deficient. In the eight-year human mortality investigation of IGF-1, which involved 376 healthy subjects aged 73 to 94, higher amounts of IGF-1 were associated with longer life and reduced cardiovascular risk. Those with the least IGF-1 in their bodies showed nearly twice the risk of death of those who had more.

As with testosterone,(1) this is likely reverse causation: aging and ill-health leads to degeneration of homeostasis, and so IGF-1 falls with biological aging and disease. Cf. firemen at a fire not being arsonists.

CR lowers IGF-1 levels in youth, but keeps them steady, while "normal" aging has them high in youth but progressively declining. The New Scientist piece is quite correct in saying here's all kinds of evidence suggesting that IGF-1 contributes to aging and age-related disease, and that CR's lowering of same is very reasonably thought to be at least in part due to lowering its level. Contrary to what the NS piece says, in most CR rodent studies protein is NOT lowered, and it's clear that higher protein level is no worse for, and may well be better for, CR in rodents. The problem in interpretation is that in nearly all of the few studies that have looked at the question, CR in rodents lowers IGF-1 no matter what the protein level, whereas it seems that humans can't get much more than RDA levels without boosting it. And contrasting with the human epidemiological data on level of IGF1 vs health outcomes, is the evidence of low IGF-1 signaling and activity, independent of its level (due to genetic variations in the signaling system) in human exceptional longevity.(2-4)


References
1: Yeap BB. Are declining testosterone levels a major risk factor for ill-health in aging men? Int J Impot Res. 2009 Jan-Feb;21(1):24-36. Epub 2008 Nov 27. Review. PubMed PMID: 19037223.

2: Pawlikowska L, Hu D, Huntsman S, Sung A, Chu C, Chen J, Joyner AH, Schork NJ, Hsueh WC, Reiner AP, Psaty BM, Atzmon G, Barzilai N, Cummings SR, Browner WS, Kwok PY, Ziv E; Study of Osteoporotic Fractures. Association of common genetic variation in the insulin/IGF1 signaling pathway with human longevity. Aging Cell. 2009 Aug;8(4):460-72. Epub 2009 May 31. PubMed PMID: 19489743.

3: Suh Y, Atzmon G, Cho MO, Hwang D, Liu B, Leahy DJ, Barzilai N, Cohen P. Functionally significant insulin-like growth factor I receptor mutations in centenarians. Proc Natl Acad Sci U S A. 2008 Mar 4;105(9):3438-42. Epub 2008 Mar 3. PubMed PMID: 18316725; PubMed Central PMCID: PMC2265137.

4: van Heemst D, Beekman M, Mooijaart SP, Heijmans BT, Brandt BW, Zwaan BJ, Slagboom PE, Westendorp RG. Reduced insulin/IGF-1 signalling and human longevity. Aging Cell. 2005 Apr;4(2):79-85. PubMed PMID: 15771611.

Edited by Michael, 05 July 2010 - 06:46 PM.

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#20 Sillewater

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Posted 05 July 2010 - 09:45 PM

So if we increase IGFBP, would that be similiar to lower IGF1?

#21 Michael

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Posted 07 July 2010 - 02:49 PM

I guess people have to ask themselves how much longer they really think they are likely to live by cutting their protein way down. Going through life under-muscled and suffering sarcopenia in the hopes that you are going to squeeze out a few more years is a guessing game I'm not willing to make.

First, sarcopenia is not a simple problem of loss of muscle mass, but of muscle structure and function as well. CR, in mice, rats, and nonhuman primates, preserves that low level of mass steadily with age, whereas in AL it goes down; and, CR preserves the structure (fiber breakage, mitochondrial deletions, neuromuscular junctions) and function (strength output per unit mass) of that muscle, whereas aging causes a steady erosion, even in master athletes.

If you want to gain muscle mass in advanced age, you can always exercise, eat more, and up your protein then, but there's no way (yet) to get back the lost structure and function: you can (as yet, and only if translatable, blah blah blah) only reduce its deterioration in the first place it with CR.

There hasn't been any mention of autophagy here, but as protein consumption goes down, autophagy goes up. This will make it less likely that you will suffer from neurological disease later in life. Having good musculature but a bad brain is not a good outcome. This is a good argument for intermittent fasting.

First, IF/EOD does not actually increase the full range of autophagy, and in particular not the part most likely important in aging (unpublished, Cuervo; travel back in time and see her UABBA presentation ;) ). More broadly:

Totally agree - The great thing about IFing is that you can get some beneficial autophagy and metabolic improvements without wasting away ala a chronic standard (or even protein targeted) CR lifestyle.

Again (and perhaps this incomplete effect on autophagy is one of the reasons why): contrary to what is often said or implied, there is no specific effect of alternate-day fasting (ADF)/every-other day feeding (EOD) on long-term health or aging: the limited effect on lifespan boils down entirely to the small Caloric difference (which, of course, is associated with a parallel loss of weight). Feeding the same number of Calories once, twice, or several times/day, or on alternate days, at the same Calorie intake yields the same retardation of the aging process, and therefore lifespan benefit. See, on these issues:

http://www.imminst.o...indpost&p=29979
http://www.imminst.o...ndpost&p=300366
http://www.imminst.o...showtopic=23010
http://www.imminst.o...showtopic=27757

Moreover, most of the apparently beneficial metabolic changes in EOD mice (which, again, don't actually result in any functional or lifespan benefit in the end, except against acute neurological insults of questionable real-world relevance) don't translate to humans. On that:

http://www.imminst.o...ndpost&p=299810
http://www.imminst.o...ndpost&p=350036

Some day, I pray, this will become widely-enough known that I can stop repeating myself, barring dramatic new evidence...

Edited by Michael, 02 March 2011 - 08:12 PM.


#22 Sillewater

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Posted 21 July 2010 - 01:31 AM

MR,

Do you think IGF1 is still a "minor" contributor?

CR Does Not Work thru' GH/IGF-1 (Primarily) More Evidence

I'm also curious as to this paper:




J Clin Endocrinol Metab. 2005 Sep;90(9):5175-81. Epub 2005 Jun 21.


Effects of dietary carbohydrate restriction with high protein intake on protein metabolism and the somatotropic axis.
Harber MP, Schenk S, Barkan AL, Horowitz JF.

University of Michigan, Division of Kinesiology, 401 Washtenaw Avenue, Ann Arbor, Michigan 48109-2208, USA.


Abstract
CONTEXT: Alterations in dietary macronutrient intake can influence protein turnover. OBJECTIVE: The purpose of this study was to assess the influence of a low-carbohydrate/high-protein diet (LC/HP) on skeletal muscle protein synthesis and whole-body proteolysis, without the confounding influence of a negative energy balance. DESIGN: Nine-day dietary intervention was applied. SETTING: Subjects remained in the General Clinical Research Center throughout the 9-d study. PARTICIPANTS: Eight young, healthy volunteers participated. INTERVENTION: Subjects ate a typical Western diet (60% carbohydrate, 30% fat, 10% protein) for 2 d, followed immediately by 7 d of an isocaloric LC/HP (5% carbohydrate, 60% fat, 35% protein). MAIN OUTCOME MEASURES: Skeletal muscle fractional synthetic rate and whole-body proteolysis [leucine rate of appearance in plasma (Ra)] were measured after an overnight fast before and after 2 and 7 d of LC/HP. We also measured plasma concentrations of insulin, GH, and IGF-I. RESULTS: Leucine Ra was increased (P = 0.03) after 2 and 7 d of LC/HP, and muscle fractional synthetic rate was approximately 2-fold higher (P < 0.01) after 7 d of LC/HP. Fat free mass was not altered by LC/HP. Average 24-h plasma insulin concentration was 50% lower (P < 0.001) after 2 and 7 d of LC/HP, whereas GH secretion and total plasma IGF-I concentrations were unchanged with LC/HP. However, plasma free IGF-I decreased by approximately 30% after 7 d of LC/HP (P = 0.002), whereas muscle IGF-I mRNA increased about 2-fold (P = 0.05). CONCLUSIONS: Increasing dietary protein content during a 7-d carbohydrate restricted diet stimulated muscle protein synthesis and whole-body proteolysis without a measurable change in fat free mass.

PMID: 15972575 [PubMed - indexed for MEDLINE]Free Article






Its only 8 subjects, but a low-carb high protein diet resulted in lower total and free IGF-1.

Edited by Sillewater, 21 July 2010 - 02:11 AM.


#23 bodyhacker_com

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Posted 21 July 2010 - 03:50 PM

The China Study: The Most Comprehensive Study of Nutrition Ever Conducted and the Startling Implications for Diet, Weight Loss and Long-term Health by T. Colin Campbell,

It might not just be the amount of protein in your diet, but the type of protein. The focus of this book isn't necessarily on nutrition and extending maximum life span, but nutrition's role in cancer. The quality, depth, and number of peer reviewed papers that stem from the China Study are immense. It's a must read for anyone serious about maximizing their healthy lifespan and looking for quantified research to make their decisions.

Edited by Michael, 23 August 2010 - 07:20 AM.
Trim quote; improve book URL

  • Agree x 1

#24 Forever21

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Posted 15 August 2010 - 06:58 PM

Is it time to go Vegan yet?
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#25 JLL

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Posted 16 August 2010 - 08:04 AM

How is soy superior to meat protein in terms of IGF-1?

#26 mikeinnaples

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Posted 18 August 2010 - 07:34 PM

They mention possible side effects of metformin but miss the most worrying which is a possible promotion of Alzheimers.


Couple with inadequate insulin ...as far as I can tell from the specific paper, normal insulin levels combined with metformin may actually reduce risk.

#27 hivemind

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Posted 23 August 2010 - 05:45 AM

I have heard that low IGF-1 makes you look and feel older. Your skin, muscles, bone... everything. Maybe it's a tradeoff between living longer and being more youthful?

This guy recommends drugs for old people to rise their IGF-1:

http://video.google....59810828270231#

Edited by Trip, 23 August 2010 - 05:46 AM.


#28 Michael

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Posted 07 September 2010 - 12:48 AM

All:

A few snippets from some recent CR Society posts, jammed together, should give a feel for my views on the protein subject, which have changed substantially in the last year:

I should finally elaborate a bit on the fact (which I've mentioned a couple of times in recent months) that, for reasons that are very complex and require a lot of exposition and documentation to explain (and no, I'm sorry, I will not be providing full details in the near future) recent findings have substantially brought me 'round to something much closer to Dr. Luigi Fontana's (and Paul McG's) position: that while the case remains uncertain, and by far the most important issue is 'Calories, Calories, Calories' as it has always been, the best bet, for long-term Calorie restriction practice, is probably to limit oneself to not much more than RDA levels of protein, and to monitor IGF1 as a likely mediator of the effects of CR — if CR is initiated in middle age or before, and if a lower-protein diet and lower-IGF1 metabolic state is sustainable by the individual without substantial decrements in quality of life or health risks.

I realize that this change in my position sounds earth-shattering to some; I apologize if it takes me quite some time until I have time to fully explain and document the nuances and basis of my new, revised view, which is certainly not just "protein bad."

To start with: the typical IGF-1 of a person on CR who has bumped hir protein down from the Zonish high-protein levels typical of long-term CR people, to RDAish levels are in the data from Luigi's report on our group:
 

In one study, we evaluated serum IGF-1 and IGFBP-3 concentrations, and IGF-1 : IGFBP-3 ratio in 28 vegans who had been consuming a moderately protein-restricted (PR) diet (0.76 g kg−1 per day; ~10% of intake from protein) for ~5 years age-matched with 28 members of the Calorie Restriction Society who consume a high-protein diet (1.73 g kg−1 per day; ~24% of energy intake from protein) " vs. a conventional Western diet; "Both serum IGF-1 concentration and IGF-1 : IGFBP-3 ratio were significantly lower in the moderately PR diet group than in the severe CR diet group ... This effect of a moderate protein restriction is independent of body weight and body fat content, as serum total and free IGF-1 concentrations were lower in the moderately PR group than in the severe CR high-protein diet group, despite the PR groups’ higher body weight, BMI and body fat content.(1)

".

From visual inspection of their Figure 2, these appear to be IGF-1 of <150, ~190, and >200 ng/mL, and IGF-1:IGFBP-3 ("free" IGF-1 ratio) of ~.14, ~.17, and ~.17, repectively.
 

It also seemed possible that the CR groups’ rather high protein intake (~24% of the calories from protein; 1.73 g kg−1 per day of protein) may have prevented a reduction in IGF-1 level. As a first step in evaluating this possibility we were able to arrange for six of the CR volunteers to reduce their protein intake from 1.67 ± 0.1 g kg−1 of body weight per day to a protein intake of 0.95 ± 0.1 g kg−1 of body weight per day for 3 weeks. This short-term isocaloric reduction of protein intake resulted in a 25% reduction in serum IGF-1 concentration (from 194 ± 34 ng mL−1 to 152 ± 41 ng mL−1; p = 0.01) in the six CR individuals, suggesting that the high protein intake was preventing a reduction in IGF-1 levels in response to CR.(1)


Unfortunately, they don't give the post-protein-reduction free IGF-1 ratio.

Do note the standard deviation (± 41 ng/mL), the very small number of subjects (6), and the short duration of the experimental study (3 weeks).

[A CR Society poster wrote:]
> On the one hand, MR has shown that higher protein consumption
> enhances longevity. On the other hand, you keep bringing up the
> relationship of IGF-1 and cancer. Since cancer is the second most
> common cause of death after cardiovascular disease, it makes sense to
> try to avoid it.

The connection of IGF1 seems to extend not just to cancer, but to aging itself, in rodent longevity mutants and in (female) human familial centenarians. I had noted this many years before the protein issue became contentious, but pointed (wrongly, I now believe, on the balance of evidence) to the studies that do indeed find that CR rodents live longer when given on higher-protein diets.

> However, I don't think that the case for a low-protein diet for
> longevity has been unequivocally demonstrated. As a matter of fact,
> just yesterday, [another interlocutor] posted a note that TWICE THE RDA OF
> PROTEIN was necessary to maintain nitrogen balance for humans on a
> 20%CR diet (PMID: 20164371):

... as had many previous studies, as had been summarized in the graph from _Modern Nutrition in Health and Disease_ discussed in The Albatross. But note that this is for maintaining nitrogen *balance* , and balance /during/ energy restriction. I think it's prudent to go high-protein during teh *weight loss* phase of CR for this reason, but once weight is stable, the best lifespan bet for humans is to slowly transition to not much more than RDA for protein, unless your IGF1 levels are low even at a higher intake.

> To maintain the body at equilibrium, the anabolic functions that are
> stimulated by eating have to balance the catabolic functions that are
> the result of energy expenditure and autophagy.

Yes -- exactly smile.gif .

> [Another poster's] quote from the Stephen Hursting paper [2] that "IGF-1's involvement
> in cancer was first suspected when *in vitro* studies consistently
> showed that supplementation of culture media with IGF-1 enhances the
> growth of a variety of cancer cell lines." seems somewhat alarmist
> since IGF-1 is produced as a normal reaction to exercise and
> ingestion of protein, but it is not necessarily the causative agent
> of cancer.

I agree that there is far, far too much focus and speculation on the List (and on many other life-extension oriented discussioin groups) on "make-the-case" arguments based on cell signaling and to in vitro studies, rather than in vivo studies in normal, healthy organisms -- and especially lifespan studies, and studies directly manipulating the relevant independent variables. In this case, however, if you look at the paper, it gives many stuies linking low IGF1 in vivo, in rodents and humans, to lower cancer risk and longer lifespan. In the context of our current discussion, Hurstig also notes:

"In fact, *restoration* of IGF-1 levels in CR mice has been shown to *abolish* the antitumor effects of CR in multiple preclinical models (43,46,47). Conversely, we have shown that diet-induced obesity can lead to insulin resistance, with increased IGF-1 and decreased IGF binding protein-1, all of which can result in enhanced IGF-1 signaling (48)."

See also the rest of his discussion in the section on "Selected potential mechanisms" of the anti-cancer effect of lowered IGF-1.

Many other papers have reviewed the connection between IGF-1 and lifespan in rodent models and the available parallels to humans.

 

In addition to moderating protein intake, I also moderate my intake of methionine + cysteine and of BCAAs, particularly leucine (see this and this for more recent studies on health effects of high intake of leucine; we were discussing this study and this one). (Please, please, please, people, stop muddying the water by referring to limiting one's intake of some nutrient to RDAish levels as "restriction" of that nutrient! Biogerontological studies of protein, Met + Cys, Leu, Trp, or Calorie restriction involve restricting consumption of these nutrients to levels far below the animals' "RDA" intake; I don't practice or endorse that, and neither does anyone I know of (including a few folks who do, unfortunately, refer to what they do as "restriction" of that nutrient)).

 

You can selectively reduce your Met+Cys out crazy micro-management of protein sources if you minimize meat, dairy, and especially eggs, and focus on plant-derived protein other than grains (and particularly rice), preferably consuming said protein in its original matrix rather than as powders. Not only are plant-derived proteins generally lower in the op cit amino acids, but there is also evidence that vegetal protein is much less IGF-1-inducing than animal protein, and epidemiological evidence that vegetable-based proteins are associated with lower risk of CVD mortality (covered in the methionine + cysteine post linked above).

 

Long after the original posting of this post (2013), Fontana, Valter Longo, and colleagues published a remarkable study (14) in which they showed that protein restriction (per se: 7% protein diet, vs. 21% normal rodent chow) or simple replacement of animal protein (lactalbumin, with or without casein) with the same amount of vegetal protein (wheat and corn gluten plus isolated soy protein) substantially inhibited the growth of a variety of implanted cancers in vivo, ostensibly independently of Calorie intake. However, it doesn't appear from reading the paper that they actually measured how much food the animals ate, or how much the animals weighed: the chow was isocaloric, but without measuring food intake you can't rule out crypto-CR. And, implanted cancer cells aren't as good a model as actual "spontaneous" (age-related) cancer incidence and mortality over a lifetime of feeding one diet vs. another.

 

In response to some standard objections raised on the CR Society email discussion list (predecessor of today's CR Forums):

> Cancer occurs when the cells are damaged and lose the capability to
> react to the signals of apoptosis mediated by genes such as P53. If
> the damaged cells cannot self-destruct, they can grow into a tumor. ...

> High levels of IGF-1 can enhance that growth, but IGF-1 is not the
> reason why the cells become damaged in the first place.

This is "It's OK if you don't ALREADY have cancer" idea is an appealing but very misleading line of reasoning.

> The scientific studies on IGF-1, mTOR and other polypeptides can help
> to elucidate the biochemical pathways of the cells. Some of this
> information can be useful to hypothesize strategies for longevity,
> but what we really want to know is:
>
> What is the optimal percentage of protein to achieve the maximum
> lifespan?
>
> This cannot be resolved from biochemical studies that focus on
> mechanistic aspects of part of the picture. What we need is
> experimental data from longevity studies.

Yes, I agree (I've emphasized the same points myself), and again it is a source of great frustration to me that people are so willing to extrapolate from signaling models and in vitro studies.

> If the animal models are
> not available or are not applicable to humans, then, we, the members
> of the CR Society are the real Guinea pigs.

To some extent, of course, we are anyway, and we have to get used to that and remind ourselves of it constantly: human CR is a goddamned EXPERIMENT. But in this case, the balance of evidence has in my judgement turned, and if maintaining low IGF-1 levels requires lowering protein intake to levels not much higher than the RDA, then in my view that is the strategy most likely to help assure that the promise of CR in the animal models may be realized in its human practitioners.

[A CRS interlocutor asked]:
>>> Is there a source for the long lived Okinawans [eating] 9% calories from
>>> protein or am I mis-reading that? According to the book "The
>>> Okinawan Program" it was 15-20% calories from protien.

[MR replies:]
>> That's old, rough data; the best available data on the diet of
>> today's Okinawan centenarians is (3), whose Table 1 indicates that
>> their 1949 diet (before they began eating more and different food
>> in ~1960) was indeed ~9% protein.

[Interlocutor asks]:
>> Wow, that is a bit surprising and very informative! Disconcerting is the see-saw, back and forth kind of
>> information Nutrition Science provides. Nurses Health study reccomends 25% P etc etc.

[MR replies]: "And in AL people, all the evidence still suggests that. [On this front: the China Study is scum-sucking cross-population/"ecological" comparison, not proper prospective epidemiology, and the popular book based on it is worse; both should be ignored]. The question is what's good for CR people, granted that higher protein intake blocks the CR-induced IGF-1 reduction in humans. There's no reason to think that bumping down protein intake would significantly lower IGF-1 in the populatioin at large, or that such reductioins would be beneficial, especially in older people. "

Another CRS Interlocutor asked:

> Michael, at what decade do you think we should consider ourselves
> "older people" and therefore should perhaps be cautious about
> lowering our protein intake if we are on CR? I have very
> successfully practiced CR for many years with a Zoneish protein
> intake and I do wonder about the wisdom of lowering it now that I am
> over 70. My BMI has been 18.2 for years and I'm in excellent health.
> My fasting glucose is 77, blood lipids and CRP are perfect.
> My latest IGF-1 test result was 138. Most of my protein is plant based
> except for salmon. I work out at the gym five times a week which obviously
> requires protein also.

That's somewhat of a different question. For reasons based on reflection on Fontana's discussion of the issue at the last CR Conference and later digging (and I'm sorry to be recalcitrant about elucidating same), it would depend on when one started CR and how severe it had been. My caution about older folks and protein really applies to folks who were STARTING CR as older (≥60), normally-aging people; if you've ALREADY been on CR for years, have had good bloodwork, have low inflammation, been are working out (and I take it that includes resistance training), and ALREADY have low-normal IGF-1, I would simply congratulate you and tell you to go about your business smile.gif . I would EXPECT you would be fine to lower your protein further, and also fine to keep doing exactly what you're doing.

Another interlocutor wrote:

> At what point in a persons BMI would they make that change?
>
> If a woman is at the low end of normal BMI - say 18.5 or 18.2, is
> that considered ad-lib?

As I'm sure you know, my position is that unfortunately, it's quite impossible to judge when one is on CR, let alone determining exactly a given person's "% CR" as a translation of the equivalent rodent phenomenon, in free-living, genetically unique humans based on an arbitrary BMI, body fat, or Caloric intake standard.

In mice, it's easy: you take a few hundred mice from a genetically-homogeneous strain, watch what they eat when given unlimited access to lab chow, and then cut back about 10-15% from that to keep them from getting overweight, and there's your AL baseline Calorie intake. For humans, however, we don't have anything like this level of precision, unless you've got a colony of a hundred or so identical twins that you can lock up and force to eat the same ad libitum diet and get the same amount of exercise for a decade or so.

If you are lucky enough to have had a clear, healthy 'setpoint' in your youth -- a weight to which you tended to remain stably when you were in your early twenties, and that was within the healthy BMI range -- take that as your baseline, and restrict Calories down to a level that keeps you at least 15% below that. Unfortunately, of course, fewer and fewer people were in the healthy range, or had a stable weight rather than a slow upward creep -- and once a higher weight is established, the body resets its setpoint to the new, abnormal fat mass. If that's you, you're stuck with a somewhat more arbitrary starting point, somewhere around the middle of the 'healthy' 18-25 BMI range, but taking some account of your build: if you're extremely lean and muscular at BMI 25 and only moderately active, that should work fine; if you can still "pinch an inch" and can't count your ribs at BMI 22, you probably need to start from a lower baseline. But CR is not about your weight or body fat, as recently re-posted for the umpteenth time: the effect comes from Calories, Calories, Calories, and pays no heed eg to leanness achieved by exercising a lot.

But you do need to keep Calories lower than your physiology 'thinks' it needs, and a level of Calorie intake that only normalizes an overweight body will simply return you to the historical norm for our species, not induce the anti-aging metabolic shift that characterizes CR.

SIGNPOSTS that a *given* person should consider hirself to be on CR: at a minimum, human CR should operationally be defined as restricting down from the level of intake that supports the lower of (a) your early-adult "setpoint" weight, and (if that 'setpoint' was already overweight) (b) a 'healthy' anthropometry, based on % body fat, waist-to-hip ratio, and (ideally) visceral adiposity.

Wherever you start from, you need to cut Calories. That's probably a big part of the reason why the epidemiology fails to find a longevity benefit to low BMI: people with low BMI aren't on CR. If you're already skinny, you just need to get skinnier. ...Some skinnier people are eating tons but getting exercise, or have pre-existing illnesses or malabsorption issues (Crohn's disease), hyperthyroidism (associated with high cardiovascular and other risks), high Non-Exercise Activity Thermogenesis (NEAT), or what have you. ...

You should also look for the endocrinological (TSH, T4, and T3; IGF-1 if possible) and risk factor (blood glucose, fasting insulin, cholesterol profile, etc) signs discussed in Walford's Beyond the 120 Year Diet.

> Would a female need to have a lower BMI than 18.5 to be CR? At what
> point would a person make the decision to lower protein from
> ad-lib?

When one has *stably* reached a BMI that is as low as one intends to go. Folks should, in my view, actively maintain a high protein intake during the initial period of active weight loss, to help minimize the inevitable loss of muscle, bone, and possibly internal organ mass.

[My original interlocutor above wrote]:
> I think that the minimum RDA protein consumption might be appropriate
> for fairly sedentary people, but not necessarily for people who
> exercise.

The IOM DRI report (4) found that while there is evidence that protein requirements may be /temporarily/ increased when *starting* resistance training, it normalizes within a few weeks; this makes sense, because in the early days (a) you're actively BUILDING new muscle mass, rather than just maintaining what you've got, and (b) your body has likely beeen being a bit 'lazy' about protein use as a sedentary person who really doesn't even need the RDA of protein.

As to the RDA being a 'minimum:' the RDA isn't a minimum requirement for any nutrient, including protein, for most people. Temember that the RDA is set to meet 97.5th percentile requirements; the *median* protein requirement for healthy adults is 0.65 g/kg.

> Paul has has scared everybody by pointing out the increased
> association of cancer with higher IGF-1 levels, but IGF-1 is not the
> *causative* agent for cancer. Cancer is the result of mutations that
> make the cells unresponsive to apoptosis so that they cannot be
> killed and re-absorbed through the normal processes. Cancer cells
> require protein to grow, and once you have cancer, you should
> probably limit protein consumption.

Again, I've pointed out the dangerous mistake involved in the above reasoning before.

> Cancer prevention is something that we should practice in addition to
> CR. We should avoid ionizing radiation, carcinogenic chemicals in
> tobacco and household products, asbestos dust, HPV, organic solvents,
> raw mushrooms, etc.

Agreed, of course.

> Protein is only part of the IGF-1 story. The other part is exercise.
> The following article[5] shows how IGF-1 decreases with exercise.

The studies on this are inconsistent. The explanation seems to be that diabetics, obese folks, and even typical Americans are overweight and hyperinsulinemic, leading to a perverse rise in IGF-1, which is then lowered as tehy become leaner. Exercise in people who are already lean raises it. And, the original group of CR folk from our cohort had normal IGF-1 levels, and almost all of them exercise.

IAC, the study that originally got Luigi interested in protein and IGF-1 found that "Plasma insulin-like growth factor I (IGF-I) and the concentration ratio of IGF-I to IGF binding protein 3 were lower in the low-protein, low-calorie diet [raw food vegan] group (139 ± 37 ng/mL and 0.033 ± 0.01, respectively) than in the runner (177 ± 37 ng/mL and 0.044 ± 0.01, respectively) and sedentary Western (201 ± 42 ng/mL and 0.046 ± 0.01, respectively) diet groups (P < 0.005)."(6) Population reference range for IGF-1 is ~150 ng/mL.

In any case, the 2 strategies aren't mutually exclusive. Everyone in this discussioin agrees that CR people should also exercise, as do nearly all of the people in our cohort in Luigi's study.

> If
> you are not currently exercising, you will lose mobility and muscle
> tone as you get older. It is well known that lower protein
> consumption and lack of exercise lead to sarcopenia[7]. Exercise is
> a natural way of reducing IGF-1 levels while maintaining an adequate
> level of dietary protein.

Everyone agrees that we should maintain an ADEQUATE intake of protein: despite the misleading use of the term 'protein restriction' in these discussions, neither Paul nor I nor IIRC anyone else is recommending sub-RDA protein intake, and as I poionted out earlier in the thread, Luigi's study corrected the blunting effect of protein on CR-induced IGF-1 reductions with 0.95 g/kg, which is ~18% higher than the RDA.

Again, remember that even the RDA is set to meet 97.5th percentile requirements for protein; the *median* protein requirement for healthy adults is 0.65 g/kg.

And, again: I wouldn't recommend that older (≥60) AL adults -- including older AL adults making a late-life swithc to CR -- cut their protein intake.

> I think that the key to longevity is optimum nutrition, sanitation,
> and physical activity, even if some studies show that burning
> calories by exercise does not have the same effect on longevity as
> restricting dietary calories.

... and so does everyone else in this discussion smile.gif .

[Someone else again:]

>
> Well, there is NO significant association of serum IGF-Iwith either fatal cancer or with non-fatal cancer. [in (8)]
>
> This was the conclusion of a high quality longitudinal study lasting 11.6 years duration, performed in the general
> Dutch population of older persons (65 yrs old) with a total of (n=1273) subjects. [8] ...

> So forget cancer (either fatal cancer or non-fatal) being related to IGF-1.

... in lifelong AL people 65 years and older at baseline. As I've said several times on related subjects, that is an entirely different question vs. the long-term preventive effects of CR, and the related but much more torturous question to the effects of CR, protein, and IGF-1 in long-term CR people who are NOW chronologically-advanced.

Lifelong AL people 65 years and older are a population who (a) have a range of IGF-1 levels that are lower than that of cohorts of young or middle-aged individuals, due to the biological aging of the endocrine system; (b) responsiveness to IGF-1 at the cellular level is blunted for the same reason; © have already undergone many years of cell proliferation 'baked in the cake,' and have now if anything got a problem of too many growth-arrested cells due to cellular senescence and systemic aging factors repressing stem cell proliferation, and (a) substantial existing lean body mass loss and systemic inflammation, giving a relative survival advantage for higher levels just to hold on to what little they have.

That is quite different from the queston of the long-term risks of high IGF-1 in younger people, even if those people are consuming an AL diet and thus aging normally, let alone if they are trying to reap the benefits of CR.

Similarly, there are animal studies (eg, (10-13)) where aged animals given IGF-1 show short-term rejuvenative effects in some of their systems, for these same kinds of reasons; that doesn't refute the fact that lifelong low IGF-1 levels due to CR or mutation retard the global biological aging process and keeps organisms young, healthy, vigorous, and alive long after their AL cohorts are moribund or dead.

> PS: Why worry about risks unless you have high-quality
> studies [with adjusted data to avoid phantom confounding]?

Because we DO have high-quality studies -- on CR animals. The AL epidemiology is in this case tautologically uninformative, I'm afraid.

References
1. Fontana L, Weiss EP, Villareal DT, Klein S, Holloszy JO. Long-term effects of calorie or protein restriction on serum IGF-1 and IGFBP-3 concentration in humans.
Aging Cell. 2008 Oct;7(5):681-7. PubMed PMID: 18843793;

2. Hursting SD, Smith SM, Lashinger LM, Harvey AE, Perkins SN. Calories and carcinogenesis: lessons learned from 30 years of calorie restriction research.
Carcinogenesis. 2010 Jan;31(1):83-9. Epub 2009 Dec 7. Review. PubMed PMID: 19969554.

3. Willcox BJ, Willcox DC, Todoriki H, Fujiyoshi A, Yano K, He Q, Curb JD, Suzuki M.
Caloric restriction, the traditional Okinawan diet, and healthy aging: the diet of the world's longest-lived people and its potential impact on morbidity and life span.
Ann N Y Acad Sci. 2007 Oct;1114:434-55.
PMID: 17986602 [PubMed - indexed for MEDLINE]

4. Food and Nutrition Board, INSTITUTE OF MEDICINE OF THE NATIONAL ACADEMIES.
Dietary Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids (Macronutrients)
2005; THE NATIONAL ACADEMIES PRESS: Washington, D.C. Pp.660-661.
http://www.nap.edu/o...=10490&page=661

> [5] IGF-1 gene expression in rat colonic mucosa after different
> exercise volumes.
> Katja Buehlmeyer
> Journal of Sports Science and Medicine (2007) 6, 434-440
> http://www.jssm.org/...8/v6n4-8pdf.pdf

6. Fontana L, Klein S, Holloszy JO. Long-term low-protein, low-calorie diet and endurance exercise modulate metabolic factors associated with cancer risk. Am J
Clin Nutr. 2006 Dec;84(6):1456-62. PubMed PMID: 17158430.

> [7] Am J Clin Nutr. 2008 May;87(5):1562S-1566S.
> Role of dietary protein in the sarcopenia of aging.
> Paddon-Jones D, Short KR, Campbell WW, Volpi E, Wolfe RR.
> PMID: 18469288

8. The Association of Serum Insulin-Like Growth Factor-I with Mortality, Cardiovascular Disease, and Cancer in the Elderly: A Population-Based Study.
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9: Ramsey MM, Weiner JL, Moore TP, Carter CS, Sonntag WE. Growth hormone treatment attenuates age-related changes in hippocampal short-term plasticity and spatial learning. Neuroscience. 2004;129(1):119-27. PubMed PMID: 15489035.

10: Wannenburg T, Khan AS, Sane DC, Willingham MC, Faucette T, Sonntag WE. Growth hormone reverses age-related cardiac myofilament dysfunction in rats. Am J Physiol Heart Circ Physiol. 2001 Aug;281(2):H915-22. PubMed PMID: 11454598.

11: Khan AS, Lynch CD, Sane DC, Willingham MC, Sonntag WE. Growth hormone increases regional coronary blood flow and capillary density in aged rats. J Gerontol A Biol Sci Med Sci. 2001 Aug;56(8):B364-71. PubMed PMID: 11487595.

12: Strömer H, Cittadini A, Douglas PS, Morgan JP. Exogenously administered growth hormone and insulin-like growth factor-I alter intracellular Ca2+ handling and enhance cardiac performance. In vitro evaluation in the isolated isovolumic buffer-perfused rat heart. Circ Res. 1996 Aug;79(2):227-36. PubMed PMID: 8755999.

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14. Fontana L, Adelaiye RM, Rastelli AL, Miles KM, Ciamporcero E, Longo VD, Nguyen H, Vessella R, Pili R. Dietary protein restriction inhibits tumor growth in human xenograft models. Oncotarget. 2013 Dec;4(12):2451-61. PubMed PMID: 24353195; PubMed Central PMCID: PMC3926840.

[Edited to include focus on plant-based protein and moderation of certain amino acids, and Fontana  - 2015-02-06]


Edited by Michael, 11 September 2017 - 07:11 PM.
Updating dead links, and adding weaknesses of (14)

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#29 Michael

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Posted 28 December 2012 - 04:46 PM

How is soy superior to meat protein in terms of IGF-1?

There is both human and animal evidence that vegetable proteins increase IGF-1 levels less than animal proteins. This is also consistent with the anecdotal experience of Dean P, myself, and at least one other CR person, who all have very low IGF-1 when consuming very substantially more protein from largely vegetal sources than the RDAish level that seems to be a threshold for carnivo-centric protein regimens.

This is likely in part due to the differing levels of amino acids in vegetal proteins, particularly of methionine and possibly of leucine. Some of the effect with vegetal proteins is also caused by the food matrix itself, with much of the protein bound to fiber; this may explain why The effect seems inconsistent in studies dealing with soy protein powder (tho' some of those studies don't actually keep the total protein levels in the soy vs. control groups equal).

Dean P found a video series on IGF-1, Cancer and Diet, including one that "discusses how a plant-based vegan diet dramatically lowers IGF-1 and raised IGF-1 binding protein, relative to people eating a meat-based diet or lacto-ovo-vegetarianians (which didn't differ from each other:":
http://nutritionfact...to-lower-igf-1/

Edited by Michael, 28 December 2012 - 05:19 PM.

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#30 scottknl

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Posted 29 December 2012 - 05:17 AM

In the data referred to in the IGF-1 video, it's interesting that women have a greater drop in IGF-1 levels when they switch from a meat-eating diet to a vegan diet than men do. Women drop 12.7% and men drop only 7.8%. Also men's testosterone gains 15.5% with the same diet change.




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