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Dichloroacetate appears to inhibit mTOR

nanonug

Senior Member
Messages
1,709
Location
Virginia, USA
The prototypical inhibitor of mTOR is rapamycin. This drug has been touted by Life Extension's Bill Falloon as a way to extend healthy lifespan. mTOR inhibition leads to, among other things, an increase in autophagy. Rapamycin has also been used with apparent success in a handful of SEID patients.

Dichloroacetate is an inhibitor of pyruvate dehydrogenase kinase. It promotes the conversion of pyruvate to acetyl-CoA and, as such, appears to be an important drug in the treatment of the hypometabolic state observed by Naviaux et al in SEID patients.

What is amazing, from my point of view, is that dichloroacetate also appears to inhibit mTOR as suggested in the following four studies:

Overexpression of pyruvate dehydrogenase kinase supports dichloroacetate as a candidate for cutaneous melanoma therapy.
Melanoma cell lines treated with DCA showed a shift in metabolism, that is, a decrease in glucose consumption and lactate production, downregulation of proliferation, an increase of apoptosis and a decrease in mTOR pathway activation.
Dichloroacetate induces protective autophagy in esophageal squamous carcinoma cells
Notably, the protein kinase B (Akt)-mechanistic target of rapamycin (mTOR) signaling pathway, an important negative regulator of autophagy, was demonstrated to be suppressed by DCA treatment.

Dichloroacetate induces autophagy in colorectal cancer cells and tumours
DCA induces autophagy in cancer cells accompanied by ROS production and mTOR inhibition, reduced lactate excretion, reduced k(PL) and increased NAD(+)/NADH ratio.

Dichloroacetate induces protective autophagy in LoVo cells: involvement of cathepsin D/thioredoxin-like protein 1 and Akt-mTOR-mediated signaling

Finally, we demonstrated that the Akt-mTOR signaling pathway, a major negative regulator of autophagy, was suppressed by DCA treatment.
 

Wayne

Senior Member
Messages
4,267
Location
Ashland, Oregon
Thanks @nanonug for starting this thread on dichloroacetate (DCA), a compound I've had a long-standing interest in. My understanding is it's a drug that's been around since about the 1950's, and has been used primarily for the treatment of mitochondrial diseases. More recently it was studied fairly extensively at a University in Canada (Edmonton?), and was looking very promising for treating various kinds of cancer. I think DCA is even sold on Amazon as a cancer treatment for animals. I always had the concern that since DCA is cheap and the patent had run out on it, that the prospects for this research continuing were not all that good.

I'm not a scientist, chemist or physicist, but I've wondered if the "chloro" part of DCA makes it some kind of "chlorine compound" which may give it any number of similarities to chlorine dioxide. If so, it might explain why there's so many reports online of chlorine dioxide being helpful for a variety of heath conditions, including those that overlap with ME/CFS. If it does affect the mitochondria in any way similar to DCA, then perhaps that would be an explanation for the increased energy people have often reported with chlorine dioxine (also known as MMS or CDS).
 

nanonug

Senior Member
Messages
1,709
Location
Virginia, USA
I always had the concern that since DCA is cheap and the patent had run out on it, that the prospects for this research continuing were not all that good.

If you search on Pubmed, there are plenty of studies on the use of DCA for cancer treatment.

I've wondered if the "chloro" part of DCA makes it some kind of "chlorine compound" which may give it any number of similarities to chlorine dioxide.

Unlike DCA, there is no evidence that chlorine dioxine is an inhibitor of pyruvate dehydrogenase kinase.

If so, it might explain why there's so many reports online of chlorine dioxide being helpful for a variety of heath conditions, including those that overlap with ME/CFS.

I'm not aware of any evidence to suggest that chlorine dioxine is beneficial in the treatment of SEID. There is plenty of evidence, however, that this substance is both quite toxic and the subject of many deceitful health claims.
 

JES

Senior Member
Messages
1,318
DCA is sold as a dietary supplement on Amazon (at least on Amazon US), so it's as simple as clicking and ordering to test. Supplements like DCA will probably never get any drug status or approval, so waiting for evidence is probably useless when the product is already available.

DCA can also cause toxic neuropathy according to at least this study, but then again most medications are toxic once you exceed a certain dosage. But it's good to keep in mind this issue.
 

msf

Senior Member
Messages
3,650
Hmm, I'm using DCA, and I've been prescribed Azithro for sinusitis, anyone got any suggestions for what I can expect?
 

Jackb23

Senior Member
Messages
293
Location
Columbus, Ohio
Found that dichloroacetate cleared up my brain fog a bit, but it also made me quite depressed. I receive ketamine infusions and one of its metabolites, esketamine works through mTOR, while arketamine works through other mechanisms.
 

Jackb23

Senior Member
Messages
293
Location
Columbus, Ohio
@jaybee00

Hello, ketamine has a very short half life, but I find the effects vary over time. I normally have a course of 12 infusions over two months and during this time they make me more lethargic and tired the more I do them. However, after my infusions the antidepressant effect tends to last and I slowly gain a bit of energy that I hadnt had before the infusions.