Clinton's Stack

[Clinton]

I use the cronometer app to inform me which micronutrients I require to be topped-up to RDA-ish levels using supplements.  Based on this and having reviewed several others' stacks such as Michael Rae's & Gordos as well as lurking other 'anti-aging' websites I take the following supplements:

(The intent of this stack/regimen is to maximize healthspan & lifespan)

8 am AND 2pm (I take each item listed at both 8 and 2)

AOR Multi-Basics3  1 capsule (serving size is 3 per day)

AOR Ortho Minerals  1 capule (serving size is 7 per day)

45mcg of vitamin K2-MK7 1 capsule (Doctor's Best)

ZMA 1 capsule (NOW brand) (this is 5mg of B6 pyridoxine, 150mg Magnesium Aspartate and 10mg Zinc)

720mg Fish Oil 1 capsule (440 EPA 280 DHA) yeah it's Kirkland (kept in the freezer)

AOR Active green tea 1 capsule (contains 315mg of EGCg)

420mg of Phosphatidylcholine 1 capsule (provides 57mg choline)

750mg Glucosamine Sulfate 1 capsule (good ol' Kirkland again)

3 or 4 days per week I take 100mg of Ubiquinol (Kaneka QH)

Additonal vitamin D3 to bring the total including the vitamin & mineral capsuls to approx. 3000IU per day - fwiw I live in Canada and don't get allot of sun.

I drink 2-3 cups of black coffee per day

ALL of my vitamins & mineral intake are at or very near RDA levels

In my 8am AND 2pm smoothie I add the following:

1/4 cup of total nuts about 50/50 mix of almonds & walnuts

1/4 cup of rolled oats

2 tbspn of ground flaxseeds (webber from Costco - kept in the freezer) (total of 4 tablespoons per day)

1/4 cup frozen blueberries, 1/4 cup frozen raspberries

1/2 tsp ceylon cinnamon, 1/4 tsp creapure creatine (approx 1g), 1/4 tsp beta-alanine (approx 1g)

1/8 tsp taurine (approx 375mg) (750mg per day total), lithium orotate approx 0.5mg (approx 1mg per day total)

I eat all meals prior to 3pm and thus within about 7 hours per day; thus practicing 'Time Restricted Feeding' something like 17-7 daily

Maintain BMI of 22.5 with almost zero visceral fat; doing upper & lower body resistance training 6 days per week and very high level of strength.

I donate blood on the allowable schedule with the Red Cross and sleep well each night w some Melatonin, Sleep Mask & often use ear plugs ...

My meals between those smoothies are lots of beans & greens; lots of chickpeas, blackbeans, green peas, brocolli, carrots, kale, onions, avocado, sweet potatoe ... and typically 2 bananas and an apple or other fruit.  I end up eating a small amount of meat or an egg 3 or 4 x per week. 

I never eat less than 60g per day of fiber according to the Cronometer app; typically 65+g per day; My Omega 6:3 intake ratio is approx 2:1 or better, Cu:Zn intake ratio approx. 1:10

 

I'm interested on any feedback,

Thank you,

Clinton

 

Edited September 2, 2018 by Clinton
spelling & clarity

[Gordo]

Greetings Clinton.  Looks reasonable to me.  It seems we have a lot in common.

I've read mixed things on taking melatonin supplements - your description mentions melatonin, sleep mask, and ear plugs - to me this seems like a possible red flag - I mentioned this in another post, but going to bed so many hours after last food intake may be suboptimal (I believe Dr. Panda talked about this here).  Another thing you might want to give a try, is lowering your core body temperature about 30-60 minutes before you expect to fall asleep - I find that this helps produce deep, restorative sleep.

https://www.nytimes.com/2009/08/04/health/04real.html

One thing I do is apply ice bags like these: https://amzn.to/2MJZhn2

to my supraclavicular zones just before drifting off (dark room).  I love the way it makes me feel too (it also increases heart rate variability like deep breathing and meditation do).

 

Regards,

Gordo

Edited August 30, 2018 by Gordo

[mccoy]

Gordo, probably the optimum time interval from last meal to sleep depends on people. In my case I find that digestion impairs sleep and since I have  a long digestion sometimes my optimum time is more than 3 hours.

My sleep is anyway always desultory and of poor quality according to all the literature on sleep quality. I don't use sleep enhancing supplements nor contraptions and sleep with no window panes, so light from outside comes in (I cannot sleep in a very dark room).

Yet I survive, but this is probably a topic for another thread. My feeling is that the body adapts by triggering other mechanisms which I don't know. Otherwise I would be in a very poor health.

 

 

Edited August 30, 2018 by mccoy

[mccoy]

Clinton, the stack seems good but, since you are working out and I do the same (in a more moderate fashion), I'm interested in your macros and daily protein average. Can you pls also include the average daily amount of Leucine, arginine and methionine as per cronometer (amminos which stimulate the activity of mTOR and IGF-1)? Last week or month, or 3 months even better. Here or in another thread on cronometer results. Any protein powders or BCAAs?

 

[Clinton]

All,

Sincerely thank you for your replies.

I edited my original post to also include the “ZMA” capsule that I take with my 8am and 2pm supplements as well as the 100mg ubiquinol (Kaneka QH) that I take 3 or 4 times per week and the 2-3 cups of coffee that I drink; I consider a few cups of black coffee part of my stack.

 

@Gordo – this is the type of feedback I was hoping for is for a ‘cold-eyes’ review for any red flags.  I don’t believe that I have a true issue falling asleep however I can likely benefit by lowering body temp and really like your pointers on this; the melatonin certainly helps falling asleep but what I’m striving for is hopefully a deeper and unbroken sleep to hopefully achieve longer ‘deep sleep’ and REM periods.  With a crazy cat running around the house in the middle of the night, and 2 young kids that like a few lights on, blocking out some light and noise is helpful for unbroken sleep.  Another thing I try to do is stop drinking water after approx. 6 or 7pm to minimize waking to use the washroom in the middle of the night.  Regarding your comments on timing of eating & circadian rhythm; a paper that prompted me to eat more food earlier in the day rather than later is ‘Promoting Health and Longevity Through Diet: From Model Organisms to Humans’ by Luigi Fontana and Linda Partridge.  Some key take-aways from the article are the likely benefits of time restricted feeding and increase of fiber intake; they also discuss possible benefits of selective amino acid restriction.

 

@McCoy – I must admit my use of the cronometer has been to evaluate a few different scenarios of one of my ‘typical’ days which includes my 2 smoothies at 8 and 2pm and then various meals I’ll include between them; so my data does not precisely reflect all of the actual meals that I’ve eaten over a week or two or a month.  What I’ve done is input a few different typical days and play with the app adding/subtracting foods while examining macro's & micro’s. 

I’m a gym rat and so I should have been a little more transparent with my smoothie and admit that I typically add 1 TBSP of whey protein to each one and often times 2 TBSP to each. 

Through my ‘anti-aging’ quest as well as my interest in strength-training I’ve studied amino acids to some extent but no, I do not take BCAA’s as such.  However the whey protein I take includes imho enough BCAA’s for my goals wrt strength & muscle mass and probably more BCAA’s than I’d like for my goals wrt lifespan, and I often increase my creatine intake as well but no more than 5-6g per day.

At 140-142lbs I consume usually a minimum of 90g of protein per day but perhaps as high as 110g on some days when I eat a little extra food; my wife and children are not veg(etari)an and so I am often tempted with many additional tasty meals and leftovers in the evenings and on weekends.

According to the chronometer I intake a minimum of Leucine 5.9g, Methionine 1.15g; the app I have on my iPhone doesn’t seem to evaluate Arginine. 

My protein intake at approx. 0.7g per lb of bodyweight maybe one of the ‘worst’ aspects of my overall diet & regimen resulting from my (possibly conflicting) interests in physical strength (improving insulin sensitivity, bone density, delaying sarcopenia & cognitive decline) and maximum longevity.

Other Macros are minimum 220g of carbs and 55g of fats; these are low-end values; considered minimums.

Carbs breakdown to approx. 64.4g fiber, starch 64.9g, sugars 81.8g, Fructose 30.5g Glucose 23.4g, Sucrose 24.9g

Fats breakdown to approx. Monounsaturated 11.7g, Polyunsaturated 32.6g, Omega 3 10.9g, Omega 6 20.5g Saturated 5.4g, Cholesterol 18.3mg

Edited August 30, 2018 by Clinton
Micro and Macro breakdowns

[Clinton]

I realize based on many threads here and on other forums that with our current state of scientific research, even with all of our bright minds there is still not anything resembling a 'consensus' among us (people persuing health & longevity goals) on a diet + supplement stack.  I've made my choices on supplementing with K2, the qty of D3 and magnesium I take and the decision to take more than the 'likely' minimum required 0.3 to 0.36ish g of protein per lb of bodyweight.  I'm taking fish oil au contraire to many here but not what I consider to be large quantities, and I've read Michael's fish oil theory of aging.

I find myself constantly reviewing and challening myself on the supplements I take, how much especially wrt their long-term safety.  I want to ensure I 'do no harm'; consider vitamin K2 for example: the Rotterdam study showed that people that took 45mcg per day vs 12mcg lived 7 years longer and that sounds absolutely amazing.  So is the amount of K2 I take (90mcg) safe for daily long-term use starting at say age 40 in a 140lb guy?  The question of safety is always on my mind - the fish oil seems quite beneficial for omega 6:3 ratio and inflammation but are 2 capsules per day ok or way too much?  Are my B-vitamins included in the Multi-Basics3 'safe'??

I've decided against Nicotinamide Riboside supplementing at the moment largely due to cost, and I've also been tempted to consider some prescription drugs such as 2-3mg of Rapamycin (or generic) once per week along with some Metformin ... but have decided to stay 'natural' or at least 'over-the-counter' (OTC) wrt supplementation.

Glucosamine and EGCg might be somewhat (possibly to some extent) 'natural' metformin and rapamycin mimetics ... Another nutraceutical that had some overlapping mechanisms was good ol' ashwagandha.  The paper that discusses EGCg, glucosamine and ashwagandha as mimetics is entitled "Towards Natural Mimetics of Metformin and Rapamycin" in Aging 2017 Vol.9, No.11 (www.aging-us.com) authors Alexander Aliper, Leslie Jellen, et. al..

Regarding alcohol intake and the on-going discussions; I'm interested in possible benefits but have greatly simplified my approach to exclude even red wine due to my own personal issues with alcohol use; I consider myself an alcoholic and simply don't allow myself any. 

Edited August 30, 2018 by Clinton

[Gordo]

Hi Clinton, I also endorse the circadian rhythm science and do time restricted feeding, with the bulk of calories earlier rather than later in the day, but for me and others, sleep is negatively affected by going more than about 5 hours without food before bed.  For that reason (and other reasons) I eat my first meal of the day between noon and 1PM and finish eating before 7PM (6 hour window of eating each day, 18 hours fasting).  But I think everyone varies with these minor differences.

Like mccoy, I think another potential caution flag with what you are doing is the "amped up" growth factors.  This is still a controversial topic with differing opinions, but many years ago anti-aging gurus and practitioners thought taking growth hormone would help (with longevity), but its actually counterproductive.  You aren't taking growth hormone injections, but some of the things you mention (high protein intake including protein supplements, eating meat/eggs, doing extensive weight lifting) potentially increase your rate of aging (see the various research on mTOR/IGF-1).  The longest lived cohorts eat low protein, plant based diets.   That said, muscle mass IS important and associated with longevity

So its sort of anyone's guess as to what is too much and what is just right.  At the end of the day, all of these little tweaks we debate are probably only going to make at most, a cumulative difference of maybe 1-2 years of life.  Focusing on supporting and participating in research and development toward promising technology/discovery is probably a far better use of time when it comes an interest in longevity.  A little fringe mad science probably couldn't hurt either...

Regards,

Gordo

Edited September 1, 2018 by Gordo

[Clinton]

Thanks Gordo, and I agree on the protein and it's effects on mTOR and IGF-1; Fontana and Partridge also point out that in humans IGF-1 does not seem to reduced without a reduction in protein.  I've known for a while that my protein intake is something that wrt maximum health/longevity I should be getting exclusively from plant sources; I suppose I just need to hear it a few mores times ;-)

I try to take fairly responsible care of my 'meat-suit' and have my fingers crossed that there are technologies on the horizon (gene therapies such as CRISPR-Cas9, etc., 3D organ printing, medical nanotechnology, and SENS) that may be able to address aspects of our metabolism (the clocks) that allow or cause accelerated damage with age, as well as eliminate some of the of damage that have already accumulated.

Edited August 31, 2018 by Clinton

[mccoy]

Quote

...and the decision to take more than the 'likely' minimum required 0.3 to 0.36ish g of protein per lb of bodyweight.

The issue is very debated and unclear. 0.36 g/lb/d = 0.8 g/kg/d is the official RDA for protein. This ensues form the Randall et al. metanalysis based on nitrogen balance. There are some issues with that study, like the nitrogen to protein conversion (Jones' factor) and the actual presence of an equilibrium state.

But, even if the study is taken as very reliable, it is relevant to light physical exercise (daily activities) and a mixed plant-based+animal protein intake. 

Another indisputable fact is the very large statistical variability in the minimum daily requirement of protein. This may be  factored in by the RDA point estimate, which is a cautious value which represents 97.5% of all the minimum requirements.

The above being said, it seems reasonable to extend the RDA concept to a plant-based diet with resistance exercise by increasing the cautious value. Plant matrix makes the protein apparently less available. Also, resistance exercise implies destruction and reconstruction of muscle protein. 0.9-1.0 g/kg/d is the RDA suggested by Brenda Davis in his reference handbook for vegans. It becomes 1.6 to 1.9  g/kg/d for strenght athletes (0.6-0.7 g/lbs/d).

Another issue: IF mere mantainance of muscular mass is desired, the RDA is a value which should consider the destruction and replacement of muscle tissue ensuing resistance exercise.

IF synthesis of muscular mass (muscular growth) is desired, than an additional amount is needed for the synthesis itself. Raw material=protein must be provided for the building of muscle tissue.

I'm studying the case of 2 natural pro vegan bodybuilders, who do not take enhancement drugs so that there is a benchmark at least for a plant-based, natural, very active resistance exercise athlete. An upper bound from which we can extrapolate an initial estimate for our individual needs if working out.

Least, and NEVER EVER mentioned in publications (mentioned only by Dr Peter Attia AFAIK), since protein requirement is a random variable with significant variability, the RDA may constitute a large amount of protein for some people so, according to the principles of longevity and protein moderation, the RDA is detrimental to longevity for a group of people. Less is needed for these high absorbers of nitrogen. Uncomfortable truth in a world which likes certainties and loves abundance.

Bottom line, there is no way we can walk the edge of this razor if not by intuition and attentive observation of individual response. Alternative to extensive measurements of daily urinary nitrogen.

[Clinton]

McCoy - Thanks, you've made excellent points on protein consumption & summarized this in a clean & logical manner -

Based on this feedback (I've gotten from you and Gordo; and btw this information isn't foreign to me), I'm motivated to at least see the results on my body composition & strength levels as a result of changing protein sources to exclusively plant-based and strive for an upper-limit of 0.36g/lb/day.

I really appreciate these forums - I hope I can add some value to you as well,

Clinton

 

[mccoy]

Clinton, you are welcome, but I believe, if you  want to try the switch to exclusively plant-based protein, that you should start from an higher value than the omnivorous RDA, especially so if you are training.

I would start from at least 1 g/kg7d = 0.45 g/lbs/d, maybe something more like 0.5 g/lbs/d and see what happens, if muscle tissue is mantained then you can scale down the amounts. Otherwise you might loose muscle tissue at the beginning and at the same time loose motivation.

I also opened another thread which is in progress and I'm about to post some considerations on vegan protein intake and resistance exercise, based on two practical cases of vegan natural bodybuilders:

 

 

[Gordo]

The main problem I see with relying on intuition or how you feel or strength levels etc. is that those things likely associate with suboptimal longevity. I mean when taken to extremes you can see this all the time: pro American football players, body builders, and wrestlers are not known for their longevity.  Most men feel great when they are eating rare steak every night, pumping up their muscles and testosterone and having sex every day. I’m not going to judge anyone for choosing the lifestyle that makes them feel the best, but this probably won’t lead to optimal lifespan or healthspan.  There’s a saying “strong today, gone tomorrow”. I’m guessing the longest lived pro athletes are the ones that seriously cut back, lose weight, and lean out after their careers end.

[mccoy]

Gordo, I agree, let's say that we should use 'trained intuition' rather than purely subjective intuition.

For example, the average football player or bodybuilder thinks nothing about longevity. They are simply not interested (until often when they hit their fifties in a wrecked state). There can be no relevant intuition.

Whereas, in the case of a specific subset of the population concerned with health and longevity (for example, the members of this forum) intuition, guided by knowledge of scientific progress and by  longtime observation of the reactions of one's body  (and one's blood labs) and finally by objective reason and discrimination, can be a powerful tool.

In the case of Torre Washington, he was born in a family of 7th day adventists, so his diet has always been pretty good. His intuition is guided within certain constraints. And sure right now his intuition is more oriented toward competition than longevity. He's probably going to change his mind within the next decade, like many do.

Our case is very different I believe, since we let our tastes be shaped by the perceived healthyness of foods as shown by the current relevant literature in nutrition and biogeorntology (blue zones, VAlter Longo, Luigi Fontana and so on). I feel very good by eating vegetables and fruit in the right amounts and whatever  my trained intuition says  is good. I feel very awkward when I eat even a morsel of junk food, so much so that it happens only once or twice a year. 

[mccoy]

On 8/30/2018 at 3:23 PM, Clinton said:

All

@McCoy – I must admit my use of the cronometer has been to evaluate a few different scenarios of one of my ‘typical’ days which includes my 2 smoothies at 8 and 2pm and then various meals I’ll include between them; so my data does not precisely reflect all of the actual meals that I’ve eaten over a week or two or a month.  What I’ve done is input a few different typical days and play with the app adding/subtracting foods while examining macro's & micro’s. 

I’m a gym rat and so I should have been a little more transparent with my smoothie and admit that I typically add 1 TBSP of whey protein to each one and often times 2 TBSP to each. 

Through my ‘anti-aging’ quest as well as my interest in strength-training I’ve studied amino acids to some extent but no, I do not take BCAA’s as such.  However the whey protein I take includes imho enough BCAA’s for my goals wrt strength & muscle mass and probably more BCAA’s than I’d like for my goals wrt lifespan, and I often increase my creatine intake as well but no more than 5-6g per day.

At 140-142lbs I consume usually a minimum of 90g of protein per day but perhaps as high as 110g on some days when I eat a little extra food; my wife and children are not veg(etari)an and so I am often tempted with many additional tasty meals and leftovers in the evenings and on weekends.

According to the chronometer I intake a minimum of Leucine 5.9g, Methionine 1.15g; the app I have on my iPhone doesn’t seem to evaluate Arginine. 

My protein intake at approx. 0.7g per lb of bodyweight maybe one of the ‘worst’ aspects of my overall diet & regimen resulting from my (possibly conflicting) interests in physical strength (improving insulin sensitivity, bone density, delaying sarcopenia & cognitive decline) and maximum longevity.

Other Macros are minimum 220g of carbs and 55g of fats; these are low-end values; considered minimums.

Carbs breakdown to approx. 64.4g fiber, starch 64.9g, sugars 81.8g, Fructose 30.5g Glucose 23.4g, Sucrose 24.9g

Fats breakdown to approx. Monounsaturated 11.7g, Polyunsaturated 32.6g, Omega 3 10.9g, Omega 6 20.5g Saturated 5.4g, Cholesterol 18.3mg

Clinton, sorry I didn't see previously your detailed answer, but I use a black background (to minimize blue light radiation) and, for some reason, the characters were black instead of the usual white, so I only saw a black screen at the beginning, and just now I investigated further.

I'm interested in your data because your bodyweight (140 lbs) is not very far from mine (149) although you probably have less bodyfat right now (I am 5'7").

your protein data is also similar to mine. Last week I averaged 100 grams (180% RDA or  1.5 g/kg/d or  0.67 g/lbs/d), but that's because of the german volume training I'm practicing now.

My leucine averaged 6.8 grams, methionine 1.4;  it's interesting that my methionine is higher than yours, although I don't eat animal food (only occasionally). Mine is an experiment of mTOR activating cycle, which probably will not last long. My goal is to settle at an higher lean body mass than now, then go thru a mantainance phase.

As to the yours (and mine) quantities being favourable or not to longevity, that depends. A lot of those amminos are used to replace and syntehtize new muscle tissue, so they activate mTOR in skeletal muscle and hopefully not so much in the liver and other organs.

Serum IFG-1 might be a good reference to decide wether and in what measure to decrease protein, although IGF-1 is sensitive to the glucose signal besides protein. There is no blood parameter for systemic mTOR  status. 

Usually, an anabolic state means mTOR activation, but if bodyfat is not increasing then mTOR is activated locally and not systemically, probably.

Not so easy to decide, this is another one of those razor edges to walk along... The data I posted on the thread 'vegan specimens' may be of some help for those who do weight training.

A good strategy if you are OK with your muscle mass would be to decrease protein intake gradually and see what happens to muscle mass. If it does not decrease, then you can diminuish further your protein intake and so on, until you hit your zero nitrogen balance, at that point you are sure there is no amplilfied mTOR signaling (catabolism=anabolism). The above while continuing exercising of course, and with the same carbs ratios.

 

 

[Clinton]

I agree with your comments McCoy.  

I am 5’-6 1/2” and approx 141lbs atm = BMI of 22.5 with low body fat (always under 10%) probably 8% right now and 6or 7% in my profile picture. 

Sounds like we have similar goals and I’m intrigued about not raising mTOR if bf is not increasing.  I often use body fat as a fast/crude gauge as to if my total calories and macros are ‘in line’.

 

[Sibiriak]

Quote

Clinton:  I’m intrigued about not raising mTOR if bf is not increasing.

Is there any science backing that notion?   Can you cite any expert who argues that point?    

According to Valter Longo, "high consumption of protein before age sixty-five is associated with a 75 percent increase in risk of death and a fourfold increase in risk of death from cancer."  (The Longevity Diet).    But Mccoy has hypothesized that  " when there is a strong growth signal driven by the mechanoreceptors in the muscles and bones, by the virtue of adaptive response that becomes a priority with respect to the organs, it makes sense that the abundance in Leucine and other amino acids is sequestered by muscle and bones, not organs".    That is  pure speculation, though, as far as I can tell.   In contrast,  there is  massive scientific evidence of systemic effects of high protein/ leucine etc. intake.

Keep in mind also that dietary protein reduction isn't just about mTOR-- there are multiple  very complex nutrient sensing pathways involved. 

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

Luigi Fontana, et al.

Aging Cell. 2008 Oct; 7(5): 681–687.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2673798/

 

Quote

 

[...]we conducted additional studies to evaluate the importance of long-term protein intake in modulating serum IGF-1 concentration in humans. 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) (Table 3). Protein intake was significantly lower in the moderately PR group than in the CR group, while energy intake tended to be higher (Table 3). 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, whereas fasting insulin and C-reactive protein were similarly low in the moderately low-protein vegan and CR groups (Fig. 2), as previously reported in a smaller group of raw food vegans (Fontana et al., 2006a, 2007a). 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 (Table 4).

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.

 

 

Quote

...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., 1999; Flurkey et al., 2001; Holzenberger et al., 2003; Ikeno et al., 2003; Kenyon, 2005; Kurosu et al., 2005; Bonkowski et al., 2006; Russell & Kahn, 2007) and in the pathogenesis of many human tumors (Samani et al., 2007; Sachdev & Yee, 2007).

 

Yes, maintaining muscle mass is important as one grows older [but note:  maintaining or gaining muscle mass does not prevent aging-associated declines in muscle strength] , however  that issue can be addressed by modestly increasing protein intake (+continued resistance training) after approx. 65 yrs. of age.  I've seen no evidence that decades of  high protein intake+bodybuilding-style hypertrophy training have any sarcopenia-preventive effects that might possible justify exposing oneself to the  very serious pro-aging,  pro-cancer, anti-longevity risks involved.

 

 

 

Edited September 2, 2018 by Sibiriak

[Clinton]

Thank you for your post Sibiriak.

I appreciate the information you provided.  I should have said I’m intrigued to look into the possibility that mTOR may not be increasing as long as bodybfat is not increasing; not that it IS established that this is the case. I have no references- just the post above from McCoy that mentioned that possibility,

Regards,

Clinton

[Saul]

Hi Sibiriac!

Michael Rae has suggested that methionine restriction is most important to reduce IGF1/IGFBP3, and that protein restriction is of lesser importance.  Most non-cereal vegetable proteins have roughly half as much methionine per gram of protein than most animal proteins.

  --  Saul

[Sibiriak]

Thanks Saul for binging up methionine.  Michael Rae  expressed his views on the topic here:

Methionine Restriction is Not Viable in Humans

https://www.crsociety.org/topic/13120-methionine-restriction-is-not-viable-in-humans/

 

I won't attempt to summarize his many detailed arguments.   To cut to the chase:

Quote

....there certainly is some evidence that "moderate MetR" is healthy  — altho' this may simply amount to saying that plant-based sources of protein is good for you, potentially for reasons not related to Met.

 

Quote

Additionally, although plant-sourced protein is in general good for one, and although I emphasize again that MetR ≠ PR, still people on CR should also engage in protein moderation to avoid overriding the reduction of IGF-1 induced by CR — ie, on CR, your protein should be at or a little above the RDA . [emphasis in original]

 

That's essentially the position he arrived at back in 2010:

Quote

....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.  [emphasis in original]

https://www.longecity.org/forum/topic/41691-low-protein-the-real-way-to-go/

Edited September 2, 2018 by Sibiriak

[mccoy]

Re. mTOR and adipose tissue: my idea is that growth of adipose tissue, which strictly speaking si realted to stimulation of mTOR in adipose cells, may be a proxy suggesting systemic  stimulation of mTOR.

The idea sounds plausible: mTOR is a metabolic master switch,. maybe THE masterswitch, a sensor of all nutrients and of the energy state of cellular systems. The concept is simplified but, if we get fat, iit's sensible to infer that we are probably in an anabolic phase and viceversa. I repeat, in its simplification this idea is conceptually pretty reasonable.

The fact that adipose tissue loss and accretion is governed by mTOR is accepeted in the literature, for example:

 

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Trends Pharmacol Sci. 2016 Apr;37(4):303-317. doi: 10.1016/j.tips.2015.11.011. Epub 2015 Dec 14.

Recent Advances in Adipose mTOR Signaling and Function: Therapeutic Prospects.

Cai H¹, Dong LQ², Liu F³.

Author information

 

Abstract

The increasing epidemic of obesity and its comorbidities has spurred research interest in adipose biology and its regulatory functions. Recent studies have revealed that the mechanistic target of rapamycin (mTOR) signaling pathway has a critical role in the regulation of adipose tissue function, including adipogenesis, lipid metabolism, thermogenesis, and adipokine synthesis and/or secretion. Given the importance of mTOR signaling in controlling energy homeostasis, it is not unexpected that deregulated mTOR signaling is associated with obesity and related metabolic disorders. In this review, we highlight current advances in understanding the roles of the mTOR signaling pathway in adipose tissue. We also provide a more nuanced view of how the mTOR signaling pathway regulates adipose tissue biology and function. Finally, we describe approaches to modulate the activity and tissue-specific function of mTOR that may pave the way towards counteracting obesity and related metabolic diseases.

Of course, lean bodybuilders who ingest 300 g/kg/d protein, because of the huge leucine signal, may have disregulated mTOR in some specific organs like liver. We don't know everything of mTOR signalling in specific tissues. Interestingly enough David Sabatini, the one who discovered mTOR and has been allegedly shortlisted for the Nobel Prize together with Valter Longo, in his latest interview with Peter Attia makes reference to the empirical observations of bodybuilders and hints how he may sometimes use them as a working hypotheses for mTOR signalling (for example, bodybilders already knew that leucine rich compounds were highly anabolic. Arginine has been known for decades to be anabolic by bodybuilders and very recently Sabatini has mentioned such AA to be an active mTOR stimulant togehter with Leucine.

I'm citing this because it shows that empirical observations have their importance and are often used as a starting hypothesis even by the top researchers.

Bottom line, my chain of thought is the following:

1. mTOR is a nutrient sensor, master switch of the metabolic states
2. growth of adipose tissue is a positive indicator of general systemic abundance of nutrients
3. such an abundance of nutrients in the system is sensed by mTOR which is turned into its active state= anabolism.

There are sure specific exceptions to the above rule in specific states and tissues, but as an approximate conceptual reference it seems pretty sound to me.

 

 

[mccoy]

On the sequestering of Leucine into the muscle tissue because of resistance training:

Quote

Sports Med. 2014; 44(Suppl 2): 117–125.

Published online 2014 Oct 30. doi:  10.1007/s40279-014-0252-0

PMCID: PMC4213370

PMID: 25355186

Using Molecular Biology to Maximize Concurrent Training

Keith Baar

excerpt:

Quote

Contraction-induced dissociation of TSC2 from the lysosome is not the only thing that occurs following resistance exercise that leads to the prolonged activation of mTOR. In the hours after resistance exercise there is also an increase in the rate of amino acid uptake from the blood into the muscle. Specifically, leucine and glutamine are increased within the working muscle [9, 15]. This increase in leucine within the muscle is likely the result of an increase in the primary leucine transporter (LAT1) messenger RNA (mRNA) [16] and protein [17].

From the above, it makes sense to infer that a greater amount of protein ingested in cocomitance to resistance training does not necessarily means increased amminoacid signaling in the whole body. To the increased baseline dietary protein associated with moderation/restriction (the RDA for example) we must subtract the additional amount uptaken by muscle tissue. In a few words, increase in protein intake with resistance exercise means an increased AAs signal in muscle cells but not necessarily in other cells (unless the additional amount is greater than the amount uptaken by muscle+bone+connective tissues).

[mccoy]

From the same article by Keith Baar:

Quote

n many cells, mTOR is activated by growth factors as a way to stimulate protein synthesis [11]. However, resistance exercise activates mTOR in a growth factor-independent manner [12]. Unlike growth factors that use a receptor tyrosine kinase to signal through phosphoinositide 3-kinase (PI3K) to PKB, resistance exercise activates mTOR without activating PI3K [13]. Instead, resistance exercise activates an unidentified kinase (Fig. 2) that phosphorylates the potent mTOR inhibitor tuberin (TSC2) on RxRxx motifs [14]. When TSC2 is phosphorylated in this manner, it binds to 14-3-3 proteins and is moved away from mTOR and its activator Ras-homolog enriched in brain (Rheb). In this way, Rheb becomes activated and stimulates mTORC1 activity, leading to increased protein synthesis.

I'm not completely convinced that mTOR activation in muscles is independent of the growth factor, otherwise professional top bodybuilders would not be spending thousands of dollars on growth hormones.

However, key in the above citation is that growth hormones govern the PI3K→Akt signaling in many cells different from muscle tissue (for example liver).

So, in this conceptual framework, we get back to the IGF-1+Insulin axis, which rules the amount of growth factors.

But we know that:

• Insulin can be moderated by eating low-glycaemic load foods (can be checked by measuring blood glucose)
• Insulin can be moderated by avoiding an excess of dietary leucine
• IGF-1 can be moderated by moderating methionine (can be checked by blood analyses)

So the unknown factor to optimize would be the amount of Leucine. All other factors can be optimized. 

Valter Longo's affirmation that we should not ingest more than the RDA amount of protein is generic and probably valid for people not involved in work or exercise which employs muscular strength.

Muscle cells uptake Leucine for mTOR signalling after exercise and AAs in general to be used as building blocks for cellular growth and repair. So there is a need for increased protein intake.

 

 

[mccoy]

Last for now:

In ripped and muscular people like Clinton, who exercise regularly and eat a substantial amount of protein, I may envisage the followign conditions:

• Optimization of Leu and AAs intake such as to satisfy muscle/bone/connective tissue demands without overamplyfing mTOR in other cells
• Systemic increase of AMPK activity due to regular strenuos exercise (inhibits systemic mTOR activity)
• Balance in systemic IGF-1 and insulin due to glucose and AAs utilization by muscle tissue and by moderation of the caloric intake

The above is a possible explanation to be checked of course by measurement of blood glucose, insulin (glucose is a proxy also for insulin), IGF-1 and IGFBP-1.

Monitoring bodyfat and muscle mass also monitors the metabolic state of muscle and adipose cells.

 

Edited September 3, 2018 by mccoy

[mccoy]

The diagram explains how the mechanoreceptors by unidentified kinases (????) inhibit the TSC2 complex (allowing the transfer of mTOR to the lysosome surface and its activation).

Aminoacids and especially Leucine are uptaken by LAT1 receptors. Less leucine circulates in the blood so less is available for other bodycells.

Ingesting just enough Leucine that it feeds the muscle cells without a surplus to other body tissue would constitute a practical optimization in the art of bodybuilding+longevity.

The above would be aided by the optimization of growth factors thru the  optimization of systemic insulin and IGF-1 .

Edited September 3, 2018 by mccoy

[Clinton]

I recall a YouTube video by Rhonda Patrick (PhD) where she states something similar, McCoy.  I’m vague on her exact statement and will try to find the video- but it may take several days... sorry but I’m quite busy.  

She says (again this is my best attempt to recall her words) that essentially people that do resistance training can eat more protein without upregulating  mTOR or IGF-1 (not sure - or both?) due to the demands on protein for muscle tissue repair ... 

I will try to find this video to clarify the statement and reference time in the video she says this,

Clinton