How can we "stimulate" mTOR?

[Tunguska]

CT has much more to do with increasing AMPK than mTor. In that respect, it's still very relevant.

The hormone question isn't that relevant. CT revolves around BAT. Estrogen increases BAT (this is 100% expected), DHT lowers it (likely 5-AR inhibited), testosterone appears neutral, so with CT you get roughly +/-/variable estrogen/DHT/test. Homeostatis over time (less related to acute exposure) might be something else. Estrogen can actually contribute to muscles too.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4392498/
https://www.ncbi.nlm.nih.gov/pubmed/1621488
http://www.endocrine-abstracts.org/ea/0037/ea0037gp.09.07.htm
https://www.hindawi.com/journals/ije/2012/789653/

 

[Sushi]

As mentioned above, keep your feet from hypothermia by wearing water shoes. And 5 mins has a notable effect on me. I wouldn't try 10-15 mins the first few times, it would crash most of us.

Please see this Note:

How about continuing this discussion in one of the existing threads on the subject unless it is directly related to mTOR?

 

[Gondwanaland]

need to increase it

Avoid excess aromatase inhibitors (paper enclosed)

 

[adreno]

You can add luteolin to the list:

Our findings showed that luteolin treatment significantly induced neurite outgrowth extension, enhanced acetylcholinesterase (AChE) activity, known as neuronal differentiation marker, and increased the level of total choline and acetylcholine in PC12 cells. In addition, luteolin persistently, activated extracellular signal-regulated kinase 1/2 (ERK1/2) and Akt

https://www.ncbi.nlm.nih.gov/pubmed/22226506

 

[Tunguska]

You can add luteolin to the list:

https://www.ncbi.nlm.nih.gov/pubmed/22226506

Good find but I think that's circumstial and the cell type thing again. Luteolin is anti-angiogenesis and anti-cancer (also stuff in liver - foxo1 issues): http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0052279 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4885545/ (the abstract sucks, the full paper is nice)
It's not without benefits but I definitely don't seek it out personally (seems too hard to avoid entirely).

Anyhow in that paper they're mostly interested in how it mimics NGF. So anything on this list is a possible alternative: https://selfhacked.com/2016/03/27/all-about-nerve-growth-factor-and-50-ways-to-increase-it/

Butyrate (R)
PQQ (R)
Lion’s Mane (R)
Lithium (R)
[...]
Estrogen
Progesterone
[...]

 

[adreno]

Good find but I think that's circumstial and the cell type thing again. Luteolin is anti-angiogenesis and anti-cancer

Yeah, you're probably right. On that note we can probably write off almost any flavonoid/antioxidant.

 

[eljefe19]

THC activates the PI3K/AKT/mTORC1/BDNF pathway
http://www.nature.com/cdd/journal/v22/n10/full/cdd201511a.html
We finally know why it's such good medicine for me!

 

[Tunguska]

Yeah, you're probably right. On that note we can probably write off almost any flavonoid/antioxidant.

Seems to work as a general rule for flavonoids. Problem is they're impossible to avoid.

 

[EtherSpin]

Theanine is also an mTOR activator. I bought some today and also ordered BCAAs.
@Sushi

I am so glad to hear you say that after virtually checking every damn box on the mTor inhibitors list for 3-5 years
(caffeinated drinks,metformin,curcumin,intermittent fasting etc) - I take L-theanine reasonably regularly and have a few tablespoons of powder form dissolved into a water bottle in the fridge for quick addition to any beverage.
- its the anxiety eradicator that got my eldest kid attending school every day last year after having panics most mornings and worked well for me in early days of CFS when POTS emerged and the anxiety wasn't stratospheric but I try to cycle it now as it has much diminished effects .

I'm considering dropping all those mtor inhibitors I'm on but am nervous as its a big change and so far seems like slim evidence that CFS people all have a problem

 

[XenForo]

...
I'm considering dropping all those mtor inhibitors I'm on but am nervous ...

Well if you do drop them, let us know your results!

 

[EtherSpin]

Well if you do drop them, let us know your results!

I am in that situation we all probably get to periodically - my fog is such that I am baffled and can't keep track but I am right now having fantasies about dropping the Metformin (1 year on it as attempt to lose weight after 4 years prior of different fasting methods with hardcore enthusiasm!) and making some easy to shake up morning drink powder that has theanine along with a protein powder and digestive enzymes

crowd funding development of CFS specific supplements is something I would be into because its too hard to keep track of the ratios of what would be useful to us but the science is so contentious I can't see it happening for another couple of years

I will definitely report any progress if i ditch the drugs that impact mtor but for now Im off to get the shaker bottle and my L-theanine water + amino mix !

 

[aquariusgirl]

http://blogs.discovermagazine.com/d...cise-hitting-the-wall-endurance/#.WQjEr7tOmEd

 

[eljefe19]

@aquariusgirl Wasn't PPAR delta found to be upregulated in ME/CFS by Fluge and Mella?

 

[ljimbo423]

It's well established in many studies that PDH kinases reduce the activity of PDH. The expression of the kinases is known to be promoted by PPAR-delta (particularly PDK4). The current study shows an increase in PPAR-delta expression.

http://forums.phoenixrising.me/inde...on-in-myalgic-encephalopathy-cfs.48446/page-5

Looks like it is.
http://forums.phoenixrising.me/inde...on-in-myalgic-encephalopathy-cfs.48446/page-5
http://forums.phoenixrising.me/inde...on-in-myalgic-encephalopathy-cfs.48446/page-5

 

[adreno]

Methylcobalamin:

Abstract
Methylcobalamin (MeCbl), a vitamin B12 analog, promotes neurite outgrowth by activating Akt in neurons. However, Akt is involved in many cellular functions, and the downstream signal of Akt that promotes neurite outgrowth in neurons in the presence of MeCbl remains obscure. Mammalian target of rapamycin (mTOR) is a serine/threonine protein kinase that regulates multiple cellular functions including neurite outgrowth. mTOR is regarded as important for the regeneration of injured nerves. In this study, we examined the relationship between MeCbl and mTOR activity and found that MeCbl increases mTOR activity via the activation of Akt and promotes neurite outgrowth in cerebellar granule neurons via the activation of mTOR.

https://www.ncbi.nlm.nih.gov/pubmed/21458538

 

[Tunguska]

Methylcobalamin:
https://www.ncbi.nlm.nih.gov/pubmed/21458538

It's very interesting - in the brain specifically. I read this similar one: https://www.ncbi.nlm.nih.gov/pubmed/20045411
and what jumped out was that in those conditions the effect lasted 72h as opposed to 1h for BDNF.

But they write as if straight out of Freddd's playbook (he must have read all these) that achieving high enough concentrations in CNS is extremely hard. They also wrote this:

In summary, we showed that MeCbl and SAM had similar effects on
neurite outgrowth but SAM did not increase the effect of MeCbl, and
Nbtd only inhibited the effect of MeCbl. These results led us to
consider that MeCbl promotes neurite outgrowth through the
methylation cycle, which is a metabolic pathway related to both
MeCbl and SAM.

For what it's worth I still take take subl. MB12 once or twice a week. But with or without folate+cofactors it didn't come close to the brain effects of other substances on me, so I'll never really know its full therapeutic use until I decide to try large injections someday. (SAMe petered out quickly and does nothing)

I still wonder a lot about the context and secondary effects of this though.

 

[adreno]

Infrared light:

The protein arrays (Figure 6D) showed an upregulation of Akt 1 and PP2a with infrared light exposure.
With IR wavelengths, the protein arrays also detected an increase in Akt 1 phosphorylated serine 124, serine 246 and threonine 450, phosphorylated mTOR threonine 2446. The predominant pathway at 633nm was the TGF beta 1 pathway whereas at 830nm, it was the Akt 1 pathway.

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

 

[Jill]

I used to find high dose b12 helpful but no more. It's now hydroxycoblamin rather than methyl - would that make a diffference ?

 

[Tunguska]

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

Good idea to look at that! I already do this with lights when I remember but I didn't think to look from this area. It tends to help but it can be draining. That it would increase PI3K/Akt makes a lot of sense.

It's worth pointing out the upregulation of c-Myc, this usually means enhanced mitochondrial activity, cell proliferation and/or protein synthesis. You can kind of look for this as a marker instead of mTor.

 

[Tunguska]

I used to find high dose b12 helpful but no more. It's now hydroxycoblamin rather than methyl - would that make a diffference ?

Methyl tends to be stronger, but the methyl effects lessened over time on me. I'm not convinced it's supposed to be sustainable. You'll find other opinions.