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 
.
> [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 . 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 .
[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.
> van Bunderen CC, van Nieuwpoort IC, van Schoor NM, Deeg DJ,
> Lips P, Drent ML.
> J Clin Endocrinol Metab. 2010 Jul 7. [Epub ahead of print]
> PMID: 20610588
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.
13. Groban L, Pailes NA, Bennett CD, Carter CS, Chappell MC, Kitzman DW, Sonntag WE. Growth hormone replacement attenuates diastolic dysfunction and cardiac angiotensin II expression in senescent rats. J Gerontol A Biol Sci Med Sci. 2006 Jan;61(1):28-35. PubMed PMID: 16456192.
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)
LongeCity
