How can we "stimulate" mTOR?

[Sushi]

Hey, I don't want to be a pain in the a-- or anywhere else, especially since you're trying to stave off PEM right now, but my NOW BCAA powder came today and the usual dosage (on the label for 2 tsp) provides2,00mg leucine,1,100mg Isoleucine and 1,100 mg Valine which doesn't jive with your dosage of 600mg Leucine etc., etc. as in your post.

You're not a pain in the ass! Here is what is happening--they have changed their formula and my bottle (which is a few months old) as different amounts of the 3 ingredients. So, yes, I'm taking a quarter dose but it is different from your quarter dose--who knows why they changed.

Using your tip about starting at 1/4 of the recommended, I took 1/2 tsp of the stuff today.
You seem to strive for accuracy in your posts (which I find very helpful, btw) so I thought I'd let you know.

Thanks, it is good for all of us to know that they have changed their formulation. Hope it helps you. I am just guessing about doses though--what else can we do?

 

[energyoverload]

@nandixon Did anyone contemplate the potential capacity of or Insulin or IGF-1 to augment mTORC1 activation in parallel to high dose L-leucine + L-arginine (I take >6 grams of leucine three times/D) via the PI3K/AKT pathway. Of course with this I am making the assumption that PI3K/AKT signalling is unimpaired in ME/CFS. Obviously this would not be a good long term strategy. But rather an approach to elucidate role of mTOR in ME. I read of someone trying intranasal insulin on phoenix for ME - there are some research on applications of this in old age cognitive decline and on Alzheimers.

Also has anyone been on metformin? In theory if mTOR is under activated, metformin could further worsen this inactivity, interfacing via AMPK.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3709085/

Disclaimer: Do not take any of this as medical advice.

 

[ukxmrv]

Metformin gave me a terrible stomach ache, an all over malaise (sorry don't have better word), body felt like a dead weight and all my energy felt sucked out of me. A more extreme version of the everyday ME type muscle weakness I feel

 

[Tunguska]

Infrared light:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4408556/

For the record I ended up trying this with some 850nm LEDs on my neck/thyroid. I don't know if it was the pathway activation or thyroid itself acting up but it was strong enough that I had a mini crash for half a week from it. Maybe it hit lymph nodes or something I'm not aware of. It doesn't do anything for me unless it's on the neck.

I'm actually really impressed and plan on trying to use it in the winter (max 10min/day). The effect felt subjectively better than using two 100W red bulbs.

 

[frozenborderline]

Hey you guys have started some good lists. But could you tell me where you read that Uridine is an mTor promoter? I read a lot on this one and it seems to behave like a FoxO promoter (the opposite). The pyrimidines are more likely to be inhibitory substances in general (in ray peat's generalizations, seems to be true) and it's the purines - intracellular adenosine and ATP (but even also extracellular, apparently) - that would help mTor the most.

There could a dose-dependent and cell type-specific response I suppose.

Like other poster wrote I think rhodiola is bad here (see examine.com). Maybe there are exceptions but herbs are a bad bet.

hey can you show me where ray peat said this? not that i disbelieve you, just am curious. Like a lot of his work and correspond with him a little

 

[EtherSpin]

@nandixon Did anyone contemplate the potential capacity of or Insulin or IGF-1 to augment mTORC1 activation in parallel to high dose L-leucine + L-arginine (I take >6 grams of leucine three times/D) via the PI3K/AKT pathway. Of course with this I am making the assumption that PI3K/AKT signalling is unimpaired in ME/CFS. Obviously this would not be a good long term strategy. But rather an approach to elucidate role of mTOR in ME. I read of someone trying intranasal insulin on phoenix for ME - there are some research on applications of this in old age cognitive decline and on Alzheimers.

Also has anyone been on metformin? In theory if mTOR is under activated, metformin could further worsen this inactivity, interfacing via AMPK.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3709085/

Disclaimer: Do not take any of this as medical advice.

Been on Metformin for a year in an attempt to aid intermittent fasting and general low calorie stuff at dropping my weight. Nothing happened and 6 months in I took a 3 week hiatus and out weight on without markedly changing diet so went back on it. Zero obvious decline or improvement but that can be tricky to gauge as I fluctuate without apparent rhyme or reason e.g. last summer my gardening failed, this summer I have my bean trellis and tomatoes going all round the house even though I'm still under the air conditioning on a couch with stacks of ice 80% of the day and will get a little better as I adjust to this heat.

 

[aaron_c]

I don't have the focus to read through this whole thread so apologies if this has already been covered:

Losartan increases mTOR expression in mice: "we observed a significant increase in the expression of phospho-Akt (pAkt), phospho-FoxO3a (pFoxO3a), phospho-mTOR (p-mTOR), and phospho–4E-BP1 (p4E-BP1) in the losartan-treated animals as compared to the placebo-treated animals."

 

[Tunguska]

hey can you show me where ray peat said this? not that i disbelieve you, just am curious. Like a lot of his work and correspond with him a little

http://raypeat.com/articles/articles/caffeine.shtml

In general, substances related to purines are stimulants, and substances related to pyrimidines are sedatives.

The most important roles for uridine are only coming out recently (https://www.sciencedaily.com/releases/2017/03/170317131617.htm) so it's impossible that he knew very much about it, so I wouldn't hold him as an authority on it anyway.

 

[renski]

Bob Miller (Nutrigenetic research institute) has done a lot of work on mTOR and Autophagy (and a lot of other stuff too)

 

[wastwater]

Stimulate FOXC1 or FOXO1A maybe,can that be done,increase genetic expression, that would also boost FOXP3 increase tregs lowering activated T cells
EBV lowers FOXO1A expression
FOXO1 involved at pro B stage
Stimulating FOXC1 increases heat shock protein(HSPA6,mentioned also by dr Alan light) and FOXO1A
FOXC1 has association with breast cancer among others as it’s a tumour suppressor
https://www.ncbi.nlm.nih.gov/m/pubmed/29487724/

FOXC1 target genes

https://academic.oup.com/hmg/article/17/4/490/2355979
Mifepristone used to stimulate reaction

 

[renski]

Seems we want to inhibit mtor and encourage autophagy, but maybe this only applies to a subset of people? Maybe stimulating mtor is done later in healing stage (would make sense given things like methyl b12, phospholipids shouldn't be given until later in the healing process, at least for lyme type people?). Going by Bob Miller's work, there's a lot of bad stuff (peroxynitrites, glutamate, xenoestrogens etc) which stimulates mtor.

 

[XenForo]

Seems we want to inhibit mtor and encourage autophagy, but maybe this only applies to a subset of people? Maybe stimulating mtor is done later in healing stage (would make sense given things like methyl b12, phospholipids shouldn't be given until later in the healing process...

Ahhhhh, it's been seeming like one or so meds are not working for me. I had a feeling methylcobalamin or phospholipids was it - mtor inhibitors seem to help me and maybe mtor stimulators ( like methylcobalamin or phospholipids) are working against me. I'll have to try omitting one mtor inhibitor at a time and see if it has a positive effect or not.

 

[renski]

It's interesting a lot of the nutrients that inhibit mtor inhibit the neuroinflammation/microglial activation, improve Th1 response/immune system balance, reduces cytokines, improve Nrf2 etc.. seem to have overlapping actions

 

[XenForo]

Day one dropping the methylcobalamin, methylfolate and phosphatidylcholine lipids and I'm doing much much better. Wish everyday was like this. I wonder how many days it will last. I'll just have to see.

 

[Learner1]

Day one dropping the methylcobalamin, methylfolate and phosphatidylcholine lipids and I'm doing much much better. Wish everyday was like this. I wonder how many days it will last. I'll just have to see.

Er, they are needed by everyone at some level, patients with me/CFS have been found by researchers to need them, they are used to reduce peroxynitrite damage and have health mito and cell function. Not sure everyone should follow you here.

How did you decide you had too much? Did you stop all the vitamin mineral and amino acid cofactors too? When and how will you test to check progress?

 

[XenForo]

Day one dropping the methylcobalamin, methylfolate and phosphatidylcholine lipids and I'm doing much much better. Wish everyday was like this. I wonder how many days it will last. I'll just have to see.

Oh man that was a terrible idea. Won't be doing that for a while

 

[Learner1]

Glad you found out... hope you recover quickly...