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"40% MetR does not Decrease Growth Rate and Body Size of Rats"

methionine restriction oxidative stress mitochondrial free radical aging

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#1 LexLux

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Posted 10 April 2014 - 09:12 PM


The purpose of this thread is to discuss the compatibility of MetR with body building. It would also be good to gather some information on how 40% translates into the RDA of protein and what protein sources work best. 

 

Regulation of longevity and oxidative stress by nutritional interventions: Role of methionine restriction

 

Ines Sanchez-RomanGustavo Barja

 

Abstract

 

"Comparative studies indicate that long-lived mammals have low rates of mitochondrial reactive oxygen species production (mtROSp) and oxidative damage in their mitochondrial DNA (mtDNA). Dietary restriction (DR), around 40%, extends the mean and maximum life span of a wide range of species and lowers mtROSp and oxidative damage to mtDNA, which supports the mitochondrial free radical theory of aging (MFRTA). Regarding the dietary factor responsible for the life extension effect of DR, neither carbohydrate nor lipid restriction seems to modify maximum longevity. However protein restriction (PR) and methionine restriction (at least 80% MetR) increase maximum lifespan in rats and mice. Interestingly, only 7 weeks of 40% PR (at least in liver) or 40% MetR (in all the studied organs, heart, brain, liver or kidney) is enough to decrease mtROSp and oxidative damage to mtDNA in rats, whereas neither carbohydrate nor lipid restriction changes these parameters. In addition, old rats also conserve the capacity to respond to 7 weeks of 40% MetR with these beneficial changes. Most importantly, 40% MetR, differing from what happens during both 40% DR and 80% MetR, does not decrease growth rate and body size of rats. All the available studies suggest that the decrease in methionine ingestion that occurs during DR is responsible for part of the aging-delaying effect of this intervention likely through the decrease of mtROSp and ensuing DNA damage that it exerts. We conclude that lowering mtROS generation is a conserved mechanism, shared by long-lived species and dietary, protein, and methionine restricted animals, that decreases damage to macromolecules situated near the complex I mtROS generator, especially mtDNA. This would decrease the accumulation rate of somatic mutations in mtDNA and maybe finally also in nuclear DNA."


Edited by LexLux, 10 April 2014 - 09:20 PM.

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#2 LexLux

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Posted 11 April 2014 - 12:36 AM

So I am aware that rat studies do not translate well into human models, for academic purposes I wanted to ask how one might convert that 40% reduction into a mg/kg amount for humans. Would one base such calculation on the RDA or the average intake of adults 19 and older? 

 

I've seen another study that reported decreased IGF-1 via protein restriction which was in the order of 760 mg/kg (total protein) per day, the decrease was more pronounced than that for severe CR. They stated that this amount was very close to the median protein requirement in a healthy adult. Mitochondrial reactive oxygen species were not reported unfortunately. See free full text:

 

Long-term effects of calorie or protein restriction on serum IGF-1 and IGFBP-3 concentration in humans

"In conclusion, our findings demonstrate that, unlike in rodents, long-term severe CR does not reduce total and free IGF-1 levels in healthy humans if protein intake is high. In addition, our data suggest that chronic protein intake is more powerful than calorie intake in modulating circulating IGF-1 concentration in humans. This is important because the median protein requirement of the healthy adult population is 0.65 g kg−1 per day and the reference daily intake (97.5th percentile) is 0.83 g kg−1 of body weight per day (Rand et al., 2003) that is close to the protein intake of our vegan group in this study. In contrast, half of the US males are eating 40% or more protein (≥ 1.34 g kg−1 per day) than the reference daily intake (Moshfegh et al., 2005), which is presently considered to be harmless and, according to public opinion and advocators of ‘low-carb’ diets, may even be beneficial. More studies are necessary to understand the biological and clinical implications of a chronic high protein intake, especially in sedentary people with a positive family history for cancer. In addition, more studies are needed to understand the effects of PR and methionine restriction on metabolism, disease prevention and longevity in humans, because several studies in rodents have shown major beneficial effects (Richie et al., 1994Miller et al., 2005;Pamplona & Barja, 2006Sanz et al., 2006). Finally, these findings underscore the importance of dietary macronutrient intake in regulating metabolic events, and suggest that reduced protein intake may become an important component of anti-aging and anticancer dietary interventions, due to the importance of IGF-1 in the biology of aging (Sonntag et al., 1999Flurkey et al., 2001Holzenberger et al., 2003;Ikeno et al., 2003Kenyon, 2005Kurosu et al., 2005Bonkowski et al., 2006Russell & Kahn, 2007) and in the pathogenesis of many human tumors (Samani et al., 2007Sachdev & Yee, 2007)."

 

It seems clear that methionine control can be achieved using a diet very low in animal proteins, which on a methionine/cal basis far exceed plant sources of protein. Of the plant sources lentils have notably little methionine when compared with soy beans which are still considered to be 'poor' sources of methionine.(1) Plant sources of protein are also not as easily absorbed as animal protein (80% vs. 90% respectively) (2). As seems logical, vegan diets are considered to be poor sources of methionine as well (3). Vegans are also noted as having lower IGF-1 levels than omnivores or ovo-lacto-vegetarians. (4)

(1) http://0-www.sciencedirect.com.wam.city.ac.uk/science/article/pii/S0306987708003836?np=y

(2) Ibid

(3) Ibid

(4) Ibid

 

From the full text article on vegan diets:

 

The low-methionine content of vegan diets may make methionine restriction feasible as a life extension strategy

Mark F. McCartJorge Barroso-ArandaFrancisco Contreras  http://dx.doi.org/10...ehy.2008.07.044      

 

http://www.ncbi.nlm....pubmed/18789600

   

"Vegans can keep their Met intakes relatively low by moderating their intakes of soy products and legumes, while diluting their total protein intake by ingesting ample amounts of fruit, wine, and/or beer. (Note however the comparatively low-Met density of lentils – on a mg per kcal basis, marginally higher than that of wheat or brown rice – and lower than that of oatmeal!) Protein dilution could also be achieved by including more plant oils in the diet; whether this would be advisable may hinge on the long-term impact of increased oil intake on insulin sensitivity. Very-low-fat diets coupled with exercise training can have a rapid insulin-sensitizing impact and in the longer term promote leanness [52][53] and [54] – effects that down-regulate insulin secretion, which should be favorable from a longevity standpoint [1]. However, it is conceivable that some lean, well-exercised individuals could increase their dietary intake of unsaturated oils without notably impairing their insulin sensitivity or leanness – studies have not yet assessed the impact of dietary fat modulation within the context of a vegan diet and regular exercise.

Theoretically, effective Met availability might be further reduced by ingesting supplemental glycine, which is inexpensive, delicious, and has anti-inflammatory effects which are potentially protective [55]. However, since dietary Met has an inductive impact on expression of glycine N-methyltransferase [56] and [57], dietary glycine may be less effective as a functional Met antagonist in the context of a low-Met diet.

Whether a feasible strategy of Met restriction, implemented consistently over most of a lifetime, could have a sufficient impact on Met availability to achieve a meaningful delay in the human aging process, remains a matter of speculation. To date, we still await confirmation that caloric restriction can increase maximal lifespan in primates to a worthwhile extent. Perhaps one way to assess the likely impact of a Met-restricted diet on human longevity would be to examine the long-term impact of such a diet on oxidation of mitochondrial DNA in leukocytes – though whether Met restriction influences this particular parameter in rodents is not yet known, as the relevant studies have targeted mitochondria obtained from liver or heart.

In any case, regular consumption of a low-fat, whole-food vegan diet, coupled with exercise training, is likely to have a favorable impact on mean longevity by reducing risk for cancers, coronary disease, and diabetes[45][58][59] and [60]. However, low systemic IGF-I activity seems likely to increase risk for hemorrhagic stroke, and possibly ischemic stroke as well, and is associated with poor prognosis following an ischemic stroke [61][62][63][64] and [65]. Furthermore, in Asian cultures, increasing intakes of animal products and total protein have been associated with declining stroke risk [66][67][68][69] and [70]. Since stroke is an uncommon cause of death in most strains of rodents, calorie/protein restriction studies in rodents can cast little light on the impact of such measures on stroke risk in humans. Vegans would thus be well advised to keep their blood pressures in the low-normal range throughout life, by employing a potassium-rich, low-salt diet, exercising, and staying lean [61].

Met plays a role in the endogenous synthesis of various “carninutrients”, including l-carnitine, creatine, and taurine, that are not supplied by vegan diets, and that may play important roles in health promotion [71]. Thus, supplementation with these agents may be warranted in vegans practicing a Met-restricted diet. Furthermore, since selenium occurs naturally in foods primarily as protein-bound selenomethionine – substituted for Met in proteins – it follows that a low-Met diet is prone to be a low-selenium diet; selenium supplementation may be prudent for vegans who are trying to keep their Met intakes low [72]. Unsupplemented vegan diets are devoid of vitamin D, so vegans who lack access to year-round uv light should be sure to include this in their supplementation regimens [73]. And it should go without saying that supplementation with vitamin B12 is mandatory for vegans [74]."

 

 

 


Edited by LexLux, 11 April 2014 - 01:06 AM.


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#3 LaViidaLocaa

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Posted 11 April 2014 - 09:07 AM

Nice thread!
It's strange though: I know that veganists might live longer than if they would eat animal protein (hard to prove though), but it is remarkable that none of the supercentenarians were vegan.

#4 LaViidaLocaa

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Posted 11 April 2014 - 11:10 AM

Here is an interesting video on the topic of IGF-1: http://nutritionfact...d-bodybuilding/

They do not mention methionine specifically though.



#5 LexLux

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Posted 11 April 2014 - 09:02 PM

I think the reason that most super-centenarians weren't vegan may have a lot to do with the times they grew up in. Vegan diets require b12 supplementation at the very least, however this was not accepted by many vegans for a long time.

 

One reason why may be that there are different 'camps' of vegans and vegetarians - some people are in it for ethical reasons and may not be in favour of unnatural supplements, while others are using it for the health benefits, or for treating a disease and are not afraid of sensible supplementation. This might include b12, d3, algae EDA/DHA and creatine. B12 deficiency can really ruin the fun by causing blood vessel stiffening and damage to the central nervous system, but with adequate supplementation you should actually be better off than some omnivores.

 

Another point that needs attention is the recent study showing lower all cause mortality in individuals under 65 consuming little protein, but the opposite trend was observed in over 65s. So, maybe if (fingers crossed) we make it to 65, we can then enjoy protein without the risk? What remains unclear is the exact role that methionine and IGF-1 play in this and that's why we need more data.

 

SJ Simpson, D Raubenheimer. Macronutrient balance and lifespan. Aging (Albany NY). 2009 1(10):875 - 880.:

 

"Dietary restriction (DR) without malnutrition is widely regarded to be a universal mechanism for prolonging lifespan. It is generally believed that the benefits of DR arise from eating fewer calories (termed caloric restriction, CR). Here we argue that, rather than calories, the key determinant of the relationship between diet and longevity is the balance of protein to non-protein energy ingested. This ratio affects not only lifespan, but also total energy intake, metabolism, immunity and the likelihood of developing obesity and associated metabolic disorders. Among various possible mechanisms linking macro nutrient balance to lifespan, the nexus between the TOR and AMPK signalling pathways is emerging as a central coordinator."

 

I think the point is that without malnutrition, we are free to reap the benefits of low rates of mitochondrial reactive oxygen species production. These benefits become important for cancer prevention (one of the leading causes of mortality):

 

M F McCarty. mTORC1 activity as a determinant of cancer risk--rationalizing the cancer-preventive effects of adiponectin, metformin, rapamycin, and low-protein vegan diets. Med Hypotheses 2011 77(4):642 - 648

 

Abstract

"Increased plasma levels of adiponectin, metformin therapy of diabetes, rapamycin administration in transplant patients, and lifelong consumption of low-protein plant-based diets have all been linked to decreased risk for various cancers. These benefits may be mediated, at least in part, by down-regulated activity of the mTORC1 complex, a key regulator of protein translation. By boosting the effective availability of the translation initiator eIF4E, mTORC1 activity promotes the translation of a number of "weak" mRNAs that code for proteins, often up-regulated in cancer, that promote cellular proliferation, invasiveness, and angiogenesis, and that abet cancer promotion and chemoresistance by opposing apoptosis. Measures which inhibit eIF4E activity, either directly or indirectly, may have utility not only for cancer prevention, but also for the treatment of many cancers in which eIF4E drives malignancy. Since eIF4E is overexpressed in many cancers, strategies which target eIF4E directly--some of which are now being assessed clinically--may have the broadest efficacy in this regard. Many of the "weak" mRNAs coding for proteins that promote malignant behavior or chemoresistance are regulated transcriptionally by NF-kappaB and/or Stat3, which are active in a high proportion of cancers; thus, regimens concurrently targeting eIF4E, NF-kappaB, and Stat3 may suppress these proteins at both the transcriptional and translational levels, potentially achieving a very marked reduction in their expression."

 

You can find many studies showing lower all cause mortality as well cause specific mortality for vegetarian diets but the relationship is not well established. The problem is that the camp of vegetarians/vegans eating only plant based for ethical reasons may not be supplementing b12 (malnutrition) and this throws off the figures.(1)(2)(3)

 

Many studies also show vegetarian diets as being similar or comparable to those of health conscious individuals in terms of mortality (4)(5)(6).

 

One thing that is becoming clear is that protein intake needs to be kept down. Most western men and woman eat more that the RDA and even just keeping to RDA can help as shown the study linked in my second post. There are many studies demonstrating increased mortality with increased protein intake (even high meat low calorie style)(7)(8)(9)(10)(11)(12)(13).

 

Also, to quote Darryl in another thread "We've known for 15 years that high methionine and lysine proteins stimulate IGF-1 signalling and cancer proliferation."

 

Personally, I think that a vegan diet (without malnutrition) has great potential as a life extension strategy, if done right.

------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------

(1) http://www.sciencedi...30698770091315X

(2) N. D. Barnard, J. Cohen, D. J. A. Jenkins, G. Turner-McGrievy, L. Gloede, A. Green, and H. Fer-dowsian. A low-fat vegan diet and a conventional diabetes diet in the treatment of type 2 diabetes: A randomized, controlled, 74-wk clinical trial. Am. J. Clin. Nutr., 89(5):1588-1596, 2009.

(3) http://www.karger.co...Abstract/337301

 

(4) http://journals.camb...line&aid=814540

(5) http://ajcn.nutritio...9/5/1613S.short

(6) http://0-journals.ca...line&aid=565040

 

(7) Low-carbohydrate–high-protein diet and long-term survival in a general population cohort
(8) Low carbohydrate–high protein diet and mortality in a cohort of Swedish women
(9) Low-carbohydrate diets and all-cause and cause-specific mortality: Two cohort Studies

(10) R. Sinha, A. J. Cross, B. I. Graubard, M. F. Leitzmann, and A. Schatzkin. Meat intake and mortality: a prospective study of over half a million people. Arch Intern Med. 2009 March 23; 169(6): 562–571.

(11) B. M. Popkin. Reducing meat consumption has multiple benefits for the world's health. Archives of internal medicine, 169(6):543, 2009.

(12) Fung TT, van Dam RM, Hankinson SE, Stampfer M, Willett WC, Hu FB. Low-carbohydrate diets and all-cause and cause-specific mortality: two cohort studies. Ann Intern Med. 2010 Sep 7;153(5):289-98.

(13) H. Noto, A. Goto, T. Tsujimoto, M. Noda. Low-carbohydrate diets and all-cause mortality: A systematic review and meta-analysis of observational studies. PLoS ONE 2013 8(1):e55030.

 

 

 

 


Edited by LexLux, 11 April 2014 - 09:23 PM.


#6 LexLux

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Posted 11 April 2014 - 10:35 PM

Here is an interesting video on the topic of IGF-1: http://nutritionfact...d-bodybuilding/

They do not mention methionine specifically though.

Nice find, I think IGF-1 can to some extent be controlled via methionine restriction and most certainly with branched-chain/general protein restriction.  Here are the studies he cited:

Friedlander AL, Butterfield GE, Moynihan S, Grillo J, Pollack M, Holloway L, Friedman L, Yesavage J, Matthias D, Lee S, Marcus R, Hoffman AR. One year of insulin-like growth factor I treatment does not affect bone density, body composition, or psychological measures in postmenopausal women. J Clin Endocrinol Metab. 2001 Apr;86(4):1496-503.

Phillips SM. Comments on Point:Counterpoint: IGF is/is not the major physiological regulator of muscle mass. In search of the skeletal muscle growth potential of

West DW, Burd NA, Tang JE, Moore DR, Staples AW, Holwerda AM, Baker SK, Phillips SM. Elevations in ostensibly anabolic hormones with resistance exercise enhance neither training-induced muscle hypertrophy nor strength of the elbow flexors. J Appl Physiol. 2010 Jan;108(1):60-7.

Sutter NB, Bustamante CD, Chase K, Gray MM, Zhao K, Zhu L, Padhukasahasram B, Karlins E, Davis S, Jones PG, Quignon P, Johnson GS, Parker HG, Fretwell N, Mosher DS, Lawler DF, Satyaraj E, Nordborg M, Lark KG, Wayne RK, Ostrander EA. Science. 2007 Apr 6;316(5821):112-5. A single IGF1 allele is a major determinant of small size in dogs.

Freda PU, Shen W, Reyes-Vidal CM, Geer EB, Arias-Mendoza F, Gallagher D, Heymsfield SB. Skeletal muscle mass in acromegaly assessed by magnetic resonance imaging and dual-photon x-ray absorptiometry. J Clin Endocrinol Metab. 2009 Aug;94(8):2880-6.

Rowlands MA, Gunnell D, Harris R, Vatten LJ, Holly JM, Martin RM. Circulating insulin-like growth factor peptides and prostate cancer risk: a systematic review and meta-analysis. Int J Cancer. 2009 May 15;124(10):2416-29.

de Herder WW. Acromegaly and gigantism in the medical literature. Case descriptions in the era before and the early years after the initial publication of Pierre Marie (1886). Pituitary. 2009;12(3):236-44.

Yang SY, Miah A, Pabari A, Winslet M. Growth Factors and their receptors in cancer metastases. Front Biosci. 2011 Jan 1;16:531-8.

Zhang Y, Ma B, Fan Q. Mechanisms of breast cancer bone metastasis. Cancer Lett. 2010 Jun 1;292(1):1-7.

Kleinberg DL, Wood TL, Furth PA, Lee AV. Growth hormone and insulin-like growth factor-I in the transition from normal mammary development to preneoplastic mammary lesions. Endocr Rev. 2009 Feb;30(1):51-74.


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#7 LaViidaLocaa

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Posted 12 April 2014 - 10:31 AM

Another point that needs attention is the recent study showing lower all cause mortality in individuals under 65 consuming little protein, but the opposite trend was observed in over 65s. So, maybe if (fingers crossed) we make it to 65, we can then enjoy protein without the risk? What remains unclear is the exact role that methionine and IGF-1 play in this and that's why we need more data.
 
SJ Simpson, D Raubenheimer. Macronutrient balance and lifespan. Aging (Albany NY). 2009 1(10):875 - 880.:
 
"Dietary restriction (DR) without malnutrition is widely regarded to be a universal mechanism for prolonging lifespan. It is generally believed that the benefits of DR arise from eating fewer calories (termed caloric restriction, CR). Here we argue that, rather than calories, the key determinant of the relationship between diet and longevity is the balance of protein to non-protein energy ingested. This ratio affects not only lifespan, but also total energy intake, metabolism, immunity and the likelihood of developing obesity and associated metabolic disorders. Among various possible mechanisms linking macro nutrient balance to lifespan, the nexus between the TOR and AMPK signalling pathways is emerging as a central coordinator."
 
I think the point is that without malnutrition, we are free to reap the benefits of low rates of mitochondrial reactive oxygen species production. These benefits become important for cancer prevention (one of the leading causes of mortality):

 
I wonder though if eating high protein, but low Met would lower all-cause mortality as well. Since this thread was mainly supposed to be about the effects on bodybuilding, eating low protein isn't very effective for this.
Also, lowering protein very much comes with increasing carbs, which might have its own implications (AGE's, insulin spikes, …) even when the sources are 'clean'.

Edited by Michael, 30 May 2015 - 11:06 PM.


#8 Jeoshua

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Posted 12 April 2014 - 11:24 AM

Also, lowering protein very much comes with increasing carbs, which might have its own implications (AGE's, insulin spikes, ) even when the sources are 'clean'.


Maybe percentage wise, but nobody said that you have to eat the same amount of calories. Lowering just Methionine intake without replacement of the lost calories is also fully possible, and actually is how I eat (restricted calorie, low meat). My weight has hovered around the same number for years.

#9 LaViidaLocaa

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Posted 12 April 2014 - 11:28 AM

 

Also, lowering protein very much comes with increasing carbs, which might have its own implications (AGE's, insulin spikes, ) even when the sources are 'clean'.


Maybe percentage wise, but nobody said that you have to eat the same amount of calories. Lowering just Methionine intake without replacement of the lost calories is also fully possible, and actually is how I eat (restricted calorie, low meat). My weight has hovered around the same number for years.

 

 

I understand, but I follow a caloric surplus as I lift weights 5-6 times per week in order to build muscle. Being in a deficit does not allow people to build muscle, unfortunately.



#10 Jeoshua

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Posted 12 April 2014 - 11:47 AM

Right, but the main thrust of this study is that lowering your Methionine intake without replacing the calories, up to a certain point, does not affect growth rate. I've been on the same diet while working out, and noted increased muscle gains, just as expected when working out, without having to give myself a caloric surplus. The key there was timing and supplementation, with 5g of Creatine pre-workout, and eating what food I do eat directly after working out when the insulin is most sensitive. In that sense, liquid calories are the best, since they are absorbed quickly, and blood levels will spike while your body is still sensitized to their effects. Strike while the iron is hot, so to speak.

Edited by Jeoshua, 12 April 2014 - 11:49 AM.


#11 LexLux

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Posted 12 April 2014 - 12:03 PM

Also just spotted that in post 5 Darryl meant 'leucine' not 'lysine'!



#12 Mind

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Posted 12 April 2014 - 01:01 PM

Nice thread!
It's strange though: I know that veganists might live longer than if they would eat animal protein (hard to prove though), but it is remarkable that none of the supercentenarians were vegan.

 

Win the genetic lottery and live to 110 - hardly matters what diet or bad habits you have. Jean Clement smoked until 106.

 

For the rest of us, more exercise, less calories, and more vegetables is probably your best bet for squeezing out a couple extra years of life.

 

Debating other finer points of diet and supplementation is fun, but not as productive as contributing money to research, such as the projects that LongeCity, SENS, and Methusleah support.


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#13 LaViidaLocaa

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Posted 12 April 2014 - 01:26 PM

Right, but the main thrust of this study is that lowering your Methionine intake without replacing the calories, up to a certain point, does not affect growth rate. I've been on the same diet while working out, and noted increased muscle gains, just as expected when working out, without having to give myself a caloric surplus. The key there was timing and supplementation, with 5g of Creatine pre-workout, and eating what food I do eat directly after working out when the insulin is most sensitive. In that sense, liquid calories are the best, since they are absorbed quickly, and blood levels will spike while your body is still sensitized to their effects. Strike while the iron is hot, so to speak.

 

Your post has some flaws, if I may:

1) even though lifting weights while taking in enough protein (especially around the workout) might maintain lean body mass (i.e. muscle) during CR, it is not possible to build muscle during a deficit (unless you are a beginner, but even then you would plateau quickly).

2) creatine timing does not matter, as it is merely filling stores.

3) liquid, 'fast' calories post-workout aren't necessary, as the so-called anabolic window lasts for hours (some studies show up to 24 hours). Unless you train fasted, post-workout meal isn't necessary immediately after training, though it doesn't hurt (I do take a post-workout shake or homemade kefir after training, but that's because I like it and it's convenient)



#14 Jeoshua

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Posted 12 April 2014 - 01:39 PM

Well, I never claimed to be a professional body builder. Points taken.

With a restricted diet, Creatine is extremely useful, not for gains, but rather to reduce the stress on the body as it scrambles to synthesize enough Creatine. The body will produce enough no matter what, but as noted above it is extremely important to supplement when you aren't eating a lot of meat. It frees up the rest of the methylation processes for more productive work, instead of burning it all just to keep your Creatine levels at normal. You're right in that the timing doesn't matter a bit, I take it all day, and only mentioned taking it before working out because that's what I do, rather than the best timing possible.

I was a hard gainer (hit a plateau, as you would say) for many years, until I started drinking smoothies or protein powder immediately after a workout. Maybe eating a box of Cheerios or something would have worked just as good, but as mentioned I try to stick with my diet as much as possible, albeit not religiously, and that helped immensely without having to resort to eating huge quantities of food.

So, without increasing my caloric intake at all, I was able to add a good 10 pounds of just muscle. Even with working out an hour a day, every day, I was never able to get above 130lbs (58 kg), and am now sitting on a much healthier 145 lbs (66 kg). If that seems low, you gotta realize that I am also short.

#15 LaViidaLocaa

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Posted 12 April 2014 - 02:12 PM

Well, I never claimed to be a professional body builder. Points taken.

With a restricted diet, Creatine is extremely useful, not for gains, but rather to reduce the stress on the body as it scrambles to synthesize enough Creatine. The body will produce enough no matter what, but as noted above it is extremely important to supplement when you aren't eating a lot of meat. It frees up the rest of the methylation processes for more productive work, instead of burning it all just to keep your Creatine levels at normal. You're right in that the timing doesn't matter a bit, I take it all day, and only mentioned taking it before working out because that's what I do, rather than the best timing possible.

I was a hard gainer (hit a plateau, as you would say) for many years, until I started drinking smoothies or protein powder immediately after a workout. Maybe eating a box of Cheerios or something would have worked just as good, but as mentioned I try to stick with my diet as much as possible, albeit not religiously, and that helped immensely without having to resort to eating huge quantities of food.

So, without increasing my caloric intake at all, I was able to add a good 10 pounds of just muscle. Even with working out an hour a day, every day, I was never able to get above 130lbs (58 kg), and am now sitting on a much healthier 145 lbs (66 kg). If that seems low, you gotta realize that I am also short.

 

I'm short as well, I feel you! I'm 5 ft 8 with 59 kg (132 lbs) so not spectacular, but I came from 48 kg in just over a year ago. I was very underweight for about 6 months, during which I also lifted weights. Granted, I didn't get sick or anything, slept well, learned well, etc. yet I was extremely skinny and barely had any muscles. Now, after eating in a surplus and following macros, I gained a decent amount of muscle and strength without much fat.

Like I said, I also take a post-workout shake or kefir, as it is very convenient (just not necessary). So keep doing what works for you!



#16 Darryl

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Posted 12 April 2014 - 07:24 PM

We're probably looking at at least two largely distinct lifespan extension pathways in protein restriction. Leucine moderation (and perhaps moderation of other BCAAS, as well as aromatic AAs) functions through the insulin/IGF-1/mTOR pathway. Methionine restriction, while reducing DNA methylation, and IIS/mTOR growth signalling as with other essential amino acids, may function uniquely through reductions in mitochondrial oxidative stress (much as mitochondrially targetted SOD expression, MitoQ, or membrane decoupling by DNP or C60 would).

 

Ruiz, Maria Cristina, et al. "Protein methionine content and MDA-lysine adducts are inversely related to maximum life span in the heart of mammals." Mechanisms of ageing and development 126.10 (2005): 1106-1114.
 
In this study, steady-state levels of markers of different kinds of protein damage – oxidation (glutamic and aminoadipic semialdehydes), mixed glyco- and lipoxidation (carboxymethyl- and carboxyethyllysine), lipoxidation (malondialdehydelysine) and amino acid composition – were measured in the heart of eight mammalian species ranging in maximum life span (MLSP) from 3.5 to 46 years. Oxidation markers were directly correlated with MLSP across species. Mixed glyco- and lipoxidation markers did not correlate with MLSP. However, the lipoxidation marker malondialdehydelysine was inversely correlated with MLSP (r2 = 0.85; P < 0.001). The amino acid compositional analysis revealed that methionine is the only amino acid strongly correlated maximum life span and that such correlation is negative (r2 = 0.93; P < 0.001). 
 
Sanz, Alberto, et al. "Methionine restriction decreases mitochondrial oxygen radical generation and leak as well as oxidative damage to mitochondrial DNA and proteins." The FASEB journal 20.8 (2006): 1064-1073.
 
We have found, for the first time, that MetR profoundly decreases mitROS production, decreases oxidative damage to mtDNA, lowers membrane unsaturation, and decreases all five markers of protein oxidation measured in rat heart and liver mitochondria. The concentration of complexes I and IV also decreases in MetR. The decrease in mitROS generation occurs in complexes I and III in liver and in complex I in heart mitochondria, and is due to an increase in efficiency of the respiratory chain in avoiding electron leak to oxygen. These changes are strikingly similar to those observed in CR and PR, suggesting that the decrease in methionine ingestion is responsible for the decrease in mitochondrial ROS production and oxidative stress
 
Caro, Pilar, et al. "Forty percent methionine restriction decreases mitochondrial oxygen radical production and leak at complex I during forward electron flow and lowers oxidative damage to proteins and mitochondrial DNA in rat kidney and brain mitochondria." Rejuvenation research 12.6 (2009): 421-434.
 
40% MetR decreases mitochondrial ROS production and percent free radical leak (by 62–71%) at complex I during forward (but not during reverse) electron flow in both brain and kidney mitochondria, increases the oxidative phosphorylation capacity of brain mitochondria, lowers oxidative damage to kidney mitochondrial DNA, and decreases specific markers of mitochondrial protein oxidation, lipoxidation, and glycoxidation in both tissues. Forty percent MetR also decreased the amount of respiratory complexes I, III, and IV and apoptosis-inducing factor (AIF) in brain mitochondria and complex IV in kidney mitochondria
 
Caro, Pilar, et al. "Effect of 40% restriction of dietary amino acids (except methionine) on mitochondrial oxidative stress and biogenesis, AIF and SIRT1 in rat liver." Biogerontology 10.5 (2009): 579-592.
 
All the dietary amino acids, except methionine, were restricted by 40% in male Wistar rats (RESTAAS group). After 6–7 weeks, experimental parameters were measured in the liver. Amino acid restriction did not change the levels of the methionine metabolites S-adenosylmethionine and S-adenosylhomocysteine, mitochondrial oxygen consumption and ROS generation, oxidative damage to mtDNA, amounts of the respiratory complexes I–IV, and the mitochondrial biogenesis factors PGC-1α and NRF-2. On the other hand, adenylate energy charge, mitochondrial protein oxidation, lipooxidation and glycooxidation, the degree of mitochondrial fatty acid unsaturation, and the amount of the apoptosis inducing factor (AIF) were decreased in the RESTAAS group. Amino acid restriction also increased SIRT1 protein. These results, together with previous ones, strongly suggest that the decrease in mitROS generation and oxidative damage to mtDNA that occurs during dietary restriction is due to restriction of a single amino acid: methionine.

 

 

 
As not everyone is willing to adopt methionine restricted diets, I think this paper is of significant interest:

Brind, Joel, et al. "Dietary glycine supplementation mimics lifespan extension by dietary methionine restriction in Fisher 344 rats." FASEB Journal. Vol. 25. 2011.
 
Dietary methionine (Met) restriction (MR) extends lifespan in rodents by 30–40% and inhibits growth. Since glycine is the vehicle for hepatic clearance of excess Met via glycine N-methyltransferase (GNMT), we hypothesized that dietary glycine supplementation (GS) might produce biochemical and endocrine changes similar to MR and also extend lifespan. Seven-week-old male Fisher 344 rats were fed diets containing 0.43% Met/2.3% glycine (control fed; CF) or 0.43% Met/4%, 8% or 12% glycine until natural death. In 8% or 12% GS rats, median lifespan increased from 88 weeks (w) to 113 w, and maximum lifespan increased from 91 w to 119 w v CF. Body growth reduction was less dramatic, and not even significant in the 8% GS group. Dose-dependent reductions in several serum markers were also observed. Long-term (50 w) 12% GS resulted in reductions in mean (±SD) fasting glucose (158 ± 13 v 179 ± 46 mg/dL), insulin (0.7 ± 0.4 v 0.8 ± 0.3 ng/mL), IGF-1 (1082 ± 128 v 1407 ± 142 ng/mL) and triglyceride (113 ± 31 v 221 ± 56 mg/dL) levels compared to CF. Adiponectin, which increases with MR, did not change in GS after 12 w on diet. We propose that more efficient Met clearance via GNMT with GS could be reducing chronic Met toxicity due to rogue methylations from chronic excess methylation capacity or oxidative stress from generation of toxic by-products such as formaldehyde.

 

 

 


Edited by Darryl, 12 April 2014 - 07:27 PM.

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#17 LaViidaLocaa

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Posted 12 April 2014 - 07:31 PM

The latter study sounds very pleasing indeed. I hope this correlation has similar effects in primates and humans.
What is interesting, though, is the contradiction with the original topic of this thread: here they DO suggest MetR limits growth.

#18 LexLux

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Posted 12 April 2014 - 07:36 PM

The latter study sounds very pleasing indeed. I hope this correlation has similar effects in primates and humans.
What is interesting, though, is the contradiction with the original topic of this thread: here they DO suggest MetR limits growth.

 yeah 80% MetR would inhibit growth, but not 40%. I think that's the jist of it. So that means we should figure out how many mg/kg that translates into for both restriction and glycine supplementation. 


Edited by LexLux, 12 April 2014 - 07:40 PM.


#19 LaViidaLocaa

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Posted 12 April 2014 - 08:53 PM

 

The latter study sounds very pleasing indeed. I hope this correlation has similar effects in primates and humans.
What is interesting, though, is the contradiction with the original topic of this thread: here they DO suggest MetR limits growth.

 yeah 80% MetR would inhibit growth, but not 40%. I think that's the jist of it. So that means we should figure out how many mg/kg that translates into for both restriction and glycine supplementation. 

 

 

Yeah, I hope someone more experienced in these kind of conversions could help us on this.

This might make MetR not necessary, which would be very convenient, since MetR pretty much means going all-vegan.



#20 Jeoshua

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Posted 12 April 2014 - 09:43 PM

Methionine Elimination would require going Vegan, but reduction of 40% would mean eating only a few less servings of meat, per day. You could replace the calories with pretty much anything plant-based. I use fruit.

That's right, I'm an omnivore who has practiced a Methionine Restricted diet for years, without even really knowing it. Even before I decided to eat less meat, fruits and vegetables were always more affordable, and so I've eaten them more than steak or chicken... plus, I hate cooking.
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#21 LaViidaLocaa

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Posted 13 April 2014 - 10:52 AM

Methionine Elimination would require going Vegan, but reduction of 40% would mean eating only a few less servings of meat, per day. You could replace the calories with pretty much anything plant-based. I use fruit.

That's right, I'm an omnivore who has practiced a Methionine Restricted diet for years, without even really knowing it. Even before I decided to eat less meat, fruits and vegetables were always more affordable, and so I've eaten them more than steak or chicken... plus, I hate cooking.

 

I do not eat much meat, except for chicken/turkey. I do eat a lot of dairy, though, which is still high in Met.

Would this 40% reduction considered as 60% of the RDA or 60% of your normal intake?







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