30 replies to this topic

[JustGetMeIntoSpace]

I had built my arms up to close to 15 inches and went on an AMPK activator or two (glucosamine for example) and - kaboom! - the muscle melted off down to 14 inches.  Now I know how to put on muscle in the gym, so I really don't think it was not getting enough calories or protein.  

 

So my question is this:  is there a way to put on muscle when taking some of these bigger gun anti-aging supplements?  Right now I think I am maintaining my muscle but that seems to be the best I can do.  Any tips out there?  Anyone else noted this issue?

[Darryl]

AMPK activation inhibits mTORC1 activity, and hence shifts the balance from anabolic to catabolic activity.

 

This mechanism is deeply rooted. We share it with yeast. 

 

Aerobic exercise is another effective AMPK activator. This doubtless contributes to the lithe figures of marathon runners.

 

In the future, it may become common knowledge that longevity optimisation is incompatible with strength optimisation. But experimental gerontologists have only suspected it for a decade, I've only known it for 3 years, and for the world at large more decades will pass.

[JustGetMeIntoSpace]

AMPK activation inhibits mTORC1 activity, and hence shifts the balance from anabolic to catabolic activity.

 

This mechanism is deeply rooted. We share it with yeast. 

 

Aerobic exercise is another effective AMPK activator. This doubtless contributes to the lithe figures of marathon runners.

 

In the future, it may become common knowledge that longevity optimisation is incompatible with strength optimisation. But experimental gerontologists have only suspected it for a decade, I've only known it for 3 years, and for the world at large more decades will pass.

Interesting on the aerobic analogy.  i never actually thought about that!  I didn't put two and two together but some of the ultra long-lived populations are incredibly "athletic" for lack of a better word.  They're climbing all over the mountains - tremendous distances and heights - and likely have very solid aerobic capacity as well.  

 

Anyway, I was afraid you were gonna say that.  Well, I am going to try to "hack" my way around it, but nothing has worked so far.  It's all I can do to just hold onto what muscle I have.  I have cut back a bit on protein, so maybe that's it, butI have my doubts.

[zorba990]

It may help to downregulate ampk with extra leucine post workout. Now whether that will be enough is the question

http://www.ncbi.nlm....pubmed/17178807

Leucine stimulates mammalian target of rapamycin signaling in C2C12 myoblasts in part through inhibition of adenosine monophosphate-activated protein kinase.
Du M1, Shen QW, Zhu MJ, Ford SP.
Author information
Abstract
Mammalian target of rapamycin (mTOR) signaling is one of the main signaling pathways controlling protein synthesis. Leucine treatment upregulates mTOR signaling, which enhances protein synthesis; however, the mechanisms are not well understood. Herein, treatment of C2C12 myoblast cells with leucine enhanced the phosphorylation of mTOR and ribosomal protein S6 kinase. Leucine treatment also decreased the adenosine monophosphate/ATP ratio in myoblasts by 36.4 +/- 9.1% (P < 0.05) and reduced the phosphorylation of adenosine monophosphate-activated protein kinase (AMPK) alpha subunit at Thr172 (28.6 +/- 4.9% reduction, P < 0.05) and inhibited AMPK activity (43.6 +/- 3.5% reduction, P < 0.05). In addition, leucine increased the phosphorylation of mTOR at Ser2448 by 63.5 +/- 10.0% (P < 0.05) and protein synthesis by 30.6 +/- 6.1% (P < 0.05). Applying 5-aminoimidazole-4-carbox-amide 1-beta-d-ribonucleoside, an activator of AMPK, abolished the stimulation of mTOR signaling by leucine, showing that AMPK negatively controls mTOR signaling. To further show the role of AMPK in mTOR signaling, myoblasts expressing a dominant negative AMPKalpha subunit were employed. Negative myoblasts had very low AMPK activity. The activation of mTOR induced by leucine in these cells was abated, showing that AMPK contributed to mTOR activation. In conclusion, leucine stimulates mTOR signaling in part through AMPK inhibition. This study implicates AMPK as an important target for nutritional management to enhance mTOR signaling and protein synthesis in muscle cells, thereby increasing muscle growth.

[JustGetMeIntoSpace]

Zorba:  I could do that.  However, I don't want think I want to activate mTOR any more anyway.  I'm already on TRT - reasonable levels btw - and that's enough activation right there to keep me happy.  My understanding is that if you are int'd in longevity, you need to go easy on mTOR.  (Can't beleive I'm saying that after all the bodybuilding mags I've read!)

 

Now I think I may have a better hack.  Check this out:

 

http://aups.org.au/P.../39/92P/92P.pdf

 

"Results. A 3-way ANOVA rev ealed a strong trend (p = 0.067) and a significant interaction (p = 0.023) between treatment (creatine vs placebo) x exercise x time for Akt and GSK3β phosphorylation levels, respectively. For Akt, further analyses demonstrated a trend (p = 0.076) for an interaction between treatment and time suggesting an increase in Akt phosphorylation levels at days 1 and 5 in the creatine group. Along similar lines, GSK3β phosphorylation levels were increased at days 1 and 5 in the creatine group. There was no interaction or main effects for mTOR, 4EBP1, Foxo1 and Foxo3a phosphorylation levels or IGF-1 mRNA. Conclusion. These observations suggest that creatine supplementation for 1 to 5 days may increase the activity of the Akt/ GSK-3β signalling pathway. Acute single leg endurance exercise does not appear to affect the phosphorylation level"

 

Creatine does not, apparently counterintuitely, active mTOR if I am reading that right but does activate another muscle buidling pathway.  Now, to be honest, I'm just now reading on Akt and GSK3β, so those may not be good activate either.  I'll let you know if I find anything out and, hopefully, if someone knows something, they'll post it as well.  A lot of these pathways are new to me.

[JustGetMeIntoSpace]

Okay, it looks like you don't want to inhibit GSK3β for survival and longevity if I am reading this right:

 

http://www.ncbi.nlm....les/PMC2253697/

 

"Furthermore, cellular survival in response to oxidative stress was diminished in the presence of GSK3β inhibitor (Fig. 3E)."

 

And check this out:

 

http://circ.ahajourn...A16161.abstract

 

"Abstract 16161: GSK-3β Activates Autophagy and Protects Against Cardiac Aging Through Ulk1"

"

[zorba990]

You may consider timing ampk activation coupled with aerobic exercise, since


Exercise-induced AMPK activation does not interfere with muscle hypertrophy in response to resistance training in men
http://www.ncbi.nlm....pubmed/24408998

Interesting to note from the above study:
"Myostatin gene expression was downregulated after acute AE + RE but not RE. Muscle size showed greater (P < 0.05) increase after AE + RE (6%) than RE (3%) training. "

Edited by zorba990, 09 March 2016 - 05:51 AM.

[JustGetMeIntoSpace]

Nice find!  Okay, that is super interesting from many standpoings.  First of all, I want to point out that the full study is avialable here: http://jap.physiolog.../116/6/611.long .

 

And now a few comments:

 

--There have been multiple studies recently on the pros and cons of doing cardio then weight or vice versa.  The findings are involved and Fitness Rx has done the best job of covering all the material:

 

http://fitnessrxform...-you-do-first/ 

 

My interpretation of the research is that you want to do aerobic/cardio last.  But read the above for yourself and see what you think.

 

--There is another critical reason to do cardio after weight for some men.  Weight lifting creates very high blood pressures.  Yes, they're transient, but there is evidence that they literally stun the arteries and, therefore, likely could cause issues for some men long term.  However, they have found that doing cardio afterwards restores the responsiveness of the arteries.

 

So imo one should not end with resistance exercise.  So I guess what I am saying is that I am still looking for a hack.  By the way, I think creatine may be it for me.  I'm seeing now if I can get my arms to grow.  Time will tell...

[Sith]

This is slightly confusing since mTOR activity is inhibited through AMPK activation yet metformin actives AMPK but also aids in muscle gain and is used as a 'supplement' by bodybuilders. 

[zorba990]

Nice find! Okay, that is super interesting from many standpoings. First of all, I want to point out that the full study is avialable here: http://jap.physiolog.../116/6/611.long .

And now a few comments:

--There have been multiple studies recently on the pros and cons of doing cardio then weight or vice versa. The findings are involved and Fitness Rx has done the best job of covering all the material:

http://fitnessrxform...-you-do-first/

My interpretation of the research is that you want to do aerobic/cardio last. But read the above for yourself and see what you think.

--There is another critical reason to do cardio after weight for some men. Weight lifting creates very high blood pressures. Yes, they're transient, but there is evidence that they literally stun the arteries and, therefore, likely could cause issues for some men long term. However, they have found that doing cardio afterwards restores the responsiveness of the arteries.

So imo one should not end with resistance exercise. So I guess what I am saying is that I am still looking for a hack. By the way, I think creatine may be it for me. I'm seeing now if I can get my arms to grow. Time will tell...

High dose ascorbic acid negates the stiffness issue afaik. There are other longecity threads on this. Stretching and foam rolling as well.
And then there is the anti-antioxidants with training crowd. Sorry, but I know too many over 50's for whom anti oxidants plus training is working well....

[zorba990]

This is slightly confusing since mTOR activity is inhibited through AMPK activation yet metformin actives AMPK but also aids in muscle gain and is used as a 'supplement' by bodybuilders.

There may be a window of mtor that is key, since
Normalizing a hyperactive mTOR initiates muscle growth during obesity
http://www.ncbi.nlm....les/PMC3082017/

[Sith]

 

This is slightly confusing since mTOR activity is inhibited through AMPK activation yet metformin actives AMPK but also aids in muscle gain and is used as a 'supplement' by bodybuilders.

There may be a window of mtor that is key, since
Normalizing a hyperactive mTOR initiates muscle growth during obesity
http://www.ncbi.nlm....les/PMC3082017/

 

 

Oh that's fascinating! So more is not always better I guess. 

[JustGetMeIntoSpace]

This is slightly confusing since mTOR activity is inhibited through AMPK activation yet metformin actives AMPK but also aids in muscle gain and is used as a 'supplement' by bodybuilders. 

Okay, that is counterintuitive - at least to me.  Doesn't Metformin lower insulin levels?  I've read a thousand threads all over claiming that insulin is highly anabolic.

[JustGetMeIntoSpace]

 

 

This is slightly confusing since mTOR activity is inhibited through AMPK activation yet metformin actives AMPK but also aids in muscle gain and is used as a 'supplement' by bodybuilders.

There may be a window of mtor that is key, since
Normalizing a hyperactive mTOR initiates muscle growth during obesity
http://www.ncbi.nlm....les/PMC3082017/

 

 

Oh that's fascinating! So more is not always better I guess. 

 

That makes a lot of sense.  I gotta read the whole study but I wonder if the inflammation/oxidation state leads to that hyperactivation of mTOR?  In any event, obesity leads to Opposite Land.  Example:  healthy man can cut calories and they will significantly lower their testosterone; an obese man will cut calories and they will raise testosterone.  (Of course, his testosterone is low already almost always.)

[JustGetMeIntoSpace]

I think the creatine is helping but haven't really proved it yet via measurements.

[Rocket]

AMPK activation inhibits mTORC1 activity, and hence shifts the balance from anabolic to catabolic activity.

This mechanism is deeply rooted. We share it with yeast.

Aerobic exercise is another effective AMPK activator. This doubtless contributes to the lithe figures of marathon runners.

In the future, it may become common knowledge that longevity optimisation is incompatible with strength optimisation. But experimental gerontologists have only suspected it for a decade, I've only known it for 3 years, and for the world at large more decades will pass.

The quality of life is so much better with muscle than without. Enjoy being 80 in a nursing home or unable to climb a simple 2 step staircase. That's not an exaggeration either! Enjoy living to 90 unable to take a shower.

I will gladly extend my healthy and vitality span with muscle at the expense of not being incapacitated by 82 and not living a pointless life to 100 simply breathing and waiting to be fed.

CR practitioners need to consider what their life will be like when they already lack muscle and for when sarcopenia is in full swing taking what's left.

Edited by Rocket, 09 May 2016 - 01:46 AM.

[sativa]

About AMPK and Natural AMPK Activators:

https://selfhacked.c...mpk-activators/

[JustGetMeIntoSpace]

Guys,

 

I kind of wimped out here.  I stopped taking the glucosamine, because I feel that we really don't have a good handle of dosage yet for anti-aging.  Can anyone give me another good AMPK activator where we know the dosage in humans fairly well?  Otherwise, I'll probably just go with exercise and CR Lite.  I've already started counting my calories and losing body fat.

[JustGetMeIntoSpace]

About AMPK and Natural AMPK Activators:

https://selfhacked.c...mpk-activators/

Nice summary but, again, we don't know dosage on any of these for anti-aging purposes.  I guess Metformin is probably the best known, but it has a couple of studies where it hasn't done really well.  If you have any insight there, I'd love to hear it.

[JustGetMeIntoSpace]

 

AMPK activation inhibits mTORC1 activity, and hence shifts the balance from anabolic to catabolic activity.

This mechanism is deeply rooted. We share it with yeast.

Aerobic exercise is another effective AMPK activator. This doubtless contributes to the lithe figures of marathon runners.

In the future, it may become common knowledge that longevity optimisation is incompatible with strength optimisation. But experimental gerontologists have only suspected it for a decade, I've only known it for 3 years, and for the world at large more decades will pass.

The quality of life is so much better with muscle than without. Enjoy being 80 in a nursing home or unable to climb a simple 2 step staircase. That's not an exaggeration either! Enjoy living to 90 unable to take a shower.

I will gladly extend my healthy and vitality span with muscle at the expense of not being incapacitated by 82 and not living a pointless life to 100 simply breathing and waiting to be fed.

CR practitioners need to consider what their life will be like when they already lack muscle and for when sarcopenia is in full swing taking what's left.

Couldn't agree more the gen'l sentiment you expressed.  I guess, though, that there is a midway point that probably yields nice results and is a good compromise.  Some of the supercultures ate quite low calories (~2200/day) in spite of prodigious amounts of activity and exercise.  My theory is that one can maintain good muscle if you go at that slowly.

 

And I believe - this is just belief admittedly - that 2200 calories with a lot of moderate exercise is probably dang near as good for longevity as CR of 30%.

 

I think a great (n=1) example of this is Jack LaLanne.  The guy ate only two meals per day and so he couldn't have had many calories.  But he exercised incredibly.  He lived to be 96 and had incredibly muscle all the way through his 80's.  He also had excellent energy and alertness into his 90's.  My guess is that overtrained and might have been able to live even longer with a few tweaks to his routine and with some of the supplements that we know today.

 

So his life is my ideal, although I'd like to extend it out another 10 years or so in the hopes that technology will have advanced sufficiently by then.

 

My two cents...

[zorba990]

Curious if anyone who noticed AMPK reduced mass -- did it also reduce strength as well?

Mass without strength seems rather useless.

 

Food for thought:

 

[JustGetMeIntoSpace]

Curious if anyone who noticed AMPK reduced mass -- did it also reduce strength as well?

Mass without strength seems rather useless.

 

Food for thought:

I lot an inch and a half off of my arms and strength as well.  Of course, I don't know whether it was all the glucosamine and turmeric.  I've definitely been getting stronger since quitting those even though I have been slowly dropping bodyfat.

[zorba990]

Glucosamine sulfate and hcl have long half lives so that may be the issue (15 hrs). One key may be to figure out the timing on various ampk activators versus short burst mtor activation with leucine. It may be better to have 1-3 days where longer half life ampk activators are avoided (glucosamine, quercetin (25 hours), rapamycin (60 hrs yikes)) In favor of others like salicylic acid (3 hours), sodium Butyrate (minutes), berberine(hours) etc. Someone can make a larger matrix of half lives of ampk activators / mtor blockers.
Google shows have lives of most of these....someone's thesis could be on such a strategy

e.g. https://www.google.c...amine half.life

The idea being to activate pituitary and ampk pre workout, with low levels of antioxidants in your system, but have that end by mid to post workout when, taking advantage of higher protein uptake, a short, strong, mtor activation burst with leucine, whey, phosphatidic acid, some carbs, healthy fats, etc for say a max of 4-6 hours add antioxidants at this point if over a certain age.

http://www.ergo-log....tioxidants.html

After that the ampk activation could be restarted or a second mtor activation later in the day if you have a more hardgainer metabolism or a competing athlete.

I've heard some info about melatonin being an mtor "regulator" but no hard data yet. Melatonin, niacinamide, glucosamine pm workout days might be preferred timing.

This assumes am muscle building workouts on an empty stomach...which itself takes a bit of getting used to. Cardio goes well with ampk activation (see aicar)

N acetyl Glucosamine does not activate ampk, btw.
https://www.ncbi.nlm...les/PMC3988823/


Sodium butyrates activates follistatin which can increase muscle mass through myostatin inhibition - short half life and intestine healing properties make it under utilized IMHO.

http://www.sciencedi...534580704001078

Edited by zorba990, 06 March 2017 - 04:56 AM.

[JustGetMeIntoSpace]

 

Curious if anyone who noticed AMPK reduced mass -- did it also reduce strength as well?

Mass without strength seems rather useless.

 

Food for thought:

I lot an inch and a half off of my arms and strength as well.  Of course, I don't know whether it was all the glucosamine and turmeric.  I've definitely been getting stronger since quitting those even though I have been slowly dropping bodyfat.

 

Thx Zorba - great info.  I heard Bill Andrews say, though, that human have a very powerful antioxidant system and we can, assuming we are healthy and not overtrained, flood our systems with antioxidants in response to the ROS from exercise.  In other words, we do not need megadosed antioxidants.  Research shows that that may be detrimental anyway.

[recon]

Here are some of my thoughts. I hope it’ll help the discussion:

1) Antioxidants should be avoided when training. It blunts the benefits from exercises. One of the benefits from exercises stem from the adaptation against oxidative eustresses. I believe that the natural antioxidant production in the body will be enhanced through exercises via these ROS during exercises and supplementation with antixoxidant just blunts them.

This has a collection of studies: http://www.longecity...ts/#entry296548

Watson T. A, MacDonald-Wicks L. K, Garg M. L. Oxidative stress and antioxidants in athletes undertaking regular exercise training. International Journal of Sport Nutrition and Exercise Metabolism. 2005;15:131–146. [PubMed]

Antioxidant supplementation preserves antioxidant response in physical training and low antioxidant intake.
Randomized controlled trial
Palazzetti S, et al. Br J Nutr. 2004.


2) Doing strength training and cardio in the same day impairs benefits compared to different days. They’re both essentially the opposite. One important benefit that you are impairing is the increase in VO2max. That is a very important benefit to exercise that will be impaired if you combine both exercises.

Appl Physiol Nutr Metab. 2016 Jul;41(7):767-74.

Edited by recon, 22 October 2017 - 04:44 PM.

[CWF1986]

 

Nice find! Okay, that is super interesting from many standpoings. First of all, I want to point out that the full study is avialable here: http://jap.physiolog.../116/6/611.long .

And now a few comments:

--There have been multiple studies recently on the pros and cons of doing cardio then weight or vice versa. The findings are involved and Fitness Rx has done the best job of covering all the material:

http://fitnessrxform...-you-do-first/

My interpretation of the research is that you want to do aerobic/cardio last. But read the above for yourself and see what you think.

--There is another critical reason to do cardio after weight for some men. Weight lifting creates very high blood pressures. Yes, they're transient, but there is evidence that they literally stun the arteries and, therefore, likely could cause issues for some men long term. However, they have found that doing cardio afterwards restores the responsiveness of the arteries.

So imo one should not end with resistance exercise. So I guess what I am saying is that I am still looking for a hack. By the way, I think creatine may be it for me. I'm seeing now if I can get my arms to grow. Time will tell...

High dose ascorbic acid negates the stiffness issue afaik. There are other longecity threads on this. Stretching and foam rolling as well.
And then there is the anti-antioxidants with training crowd. Sorry, but I know too many over 50's for whom anti oxidants plus training is working well....

 

A good counter-argument for megadosing antioxidants is provided in this article:

https://well.blogs.n...n-your-workout/

 

Basically, the article makes a case for how the free radicals are more like important messengers involved in the exercise response as opposed to just being the health boogey man.  

 

I wish we knew more about the magnitude of effect and effect overtime.  

[Captain Obvious]

This thread has been super informative! Has anyone gained any new information on the topic since? 

At the moment I'm training hard at the gym 3-4 days per week as well as supplementing with several AMPK activators (resveratrol, berberine, curcumin, gynostemma etc). After reading on muscle hypertrophy and how AMPK activators stimulate catabolism and inhibit anabolism, I started worrying about if to take them at all or when to take them.

It seems that AMPK activation is essential part of body's response to resistance training, but too much at the wrong time might switch body to a more anabolic state. 

 

I have been taking a lot of stuff in the evening before going to bed or first thing upon waking. I'm now wondering whether it would be better to take AMPK activators before exercise, since the body's natural AMPK activation happens in result of exercise anyway. On the other hand resveratrol supplementation has been shown to inhibit some beneficial effects of exercise.

 

Also, AMPK activators have been shown to have beneficial effects on exercise capacity. I'm unsure whether that's a good thing or not when it comes to muscle hypertrophy.

https://www.ncbi.nlm...pubmed/26186961
 

Edited by Captain Obvious, 17 July 2018 - 06:53 AM.

[John250]

If you want to increase mTOR for muscle gain take 3g Luecine every 3hrs. 20-40mcg Igf-Lr3 is great.

[Nate-2004]

I'm taking metformin on the reg but I'm wondering if I shouldn't cycle it with leucine for this very reason. I also fast 48 hrs a week while still taking metformin.

[John250]

I'm taking metformin on the reg but I'm wondering if I shouldn't cycle it with leucine for this very reason. I also fast 48 hrs a week while still taking metformin.

I don’t think Leucine will completely affect the inhibiting of mTOR from Metformin as Metformin is pretty powerful. Maybe limit Luecine to pre and post workout only.

Edited by John250, 17 July 2018 - 10:07 PM.