Treating patients suffering from ME/CFS with sodium dichloroacetate (pilot trial)

[msf]

I quite clearly wasn't suggesting that peripheral neuropathy is just numbness (although this is the first symptom in DCA-induced peripheral neuropathy, and if DCA is discontinued at this point often is the only one). I believe you asked a question and I answered it to the best of my knowledge, probably having read more papers on DCA and peripheral neuropathy than most people on here. The paper I read did not specify that it was the mitochondria that were affected - oxidative stress can damage other parts of cells as well, such as through the peroxidation of lipids that you seemed to refer to yourself.

 

[Learner1]

Apparently it does act upon mitochondria, which can be a good thing for some, but perhaps not for others. As a patient who has accrued mitochondrial damage causing a huge amount of ROS that has further damaged mitochondria from substances others did fine with, it seems prudent going forward to question everything.

I found this:

Reversal of Cancer Cell Metabolism

DCA acts on the mitochondrial matrix of cancer cells, diverting metabolism from fermentative glycolysis back to oxidative phosphorylation (13, 14). DCA does this by activating the pyruvate dehydrogenase complex, inhibiting pyruvate dehydrogenase kinase. The shift from cytosolic
metabolism of pyruvate to mitochondrial metabolism effectively reduces lactate levels by promoting the conversion of lactate into pyruvate (14, 15).

Decreased Mitochondrial Membrane Potential

DCA administration results in the reopening of voltage and redox sensitive mitochondrial transition pores (16). This allows for the pro-apoptotic mediators, cytochrome c and apoptosis-inducing-factor,to be released into the cytoplasm, resulting in an apoptotic cascade selective to cancer cells which
were previously operating under anaerobic glycolysis (3).

ROS Production

By relying heavily upon cytoplasmic aerobic glycolysis for energy, cancer cells are able to avoid the production of reactive oxygen species (ROS) via mitochondrial oxidative phosphorylation (14, 17, 18). DCA triggers the remodeling of mitochondrial metabolism, opening transition pores and increasing the levels of pro-apoptotic ROS through the activation of caspases (14, 15, 17).

 

[msf]

Apparently it does act upon mitochondria, which can be a good thing for some, but perhaps not for others. As a patient who has accrued mitochondrial damage causing a huge amount of ROS that has further damaged mitochondria from substances others did fine with, it seems prudent going forward to question everything.

I found this:

Of course it works on the mitochondria, it affects the production of energy, which happens within the mitochondria. I was saying I don't know whether the producton of free radicals affects the mitochondria or whether, for example, it affects the fatty sheath of neurons through peroxidation of lipids, which given the diameter of neurons is reduced in DCA induced peripheral neuropathy, would seem to be a possibility to this layman.

 

[Daniel E.]

@Learner1 has a good reason to worry about DCA acting on mitochondria health, however, this is unavoidable. Cancer and ME/CFS (according to Naviaux) are very closely related to mitochondrial mechanisms.

We must keep in mind that alcohol, cigs, sunlight, antiviral medications (such as Aciclovir), cancer medications (such as Cicloplatin), maybe even stress etc. all cause mitochondrial damage (isn't i reversible since all the cells duplicate and replace themselves?).
In order to revive mitochondria and the energy production (fire) there has to be some side production - ROS (smoke). Regarding the mechanism of neuropathy, I believe that @msf explained it briefly and accurately. It's more related to the neurons than to mitochondria.

Let's remember some important things - if you follow the rules, don't rush it (etc. take 4 doses daily when you should take 1 dose) and you take the protective supplements like Vit B1, ALA - it all should be well.

I mean, look at some of the double blinded studies or long-term safety studies - some people have taken it for 6 months and experienced no side effects (I believe they were children and were closely monitored by the doctors).

The other study mentions: "We followed 8 patients <...> received oral dichloroacetate (DCA; 12.5 mg/kg/12 h) for 9.7 to 16.5 years."(link)

Some people have taken far larger doses for decades and are still taking it. What I want to once again outline is that with the correct dosing, correct supplementation and schedules you can have a relatively safe experience. The substance has been reviewed and studied for 40+ years. However, we need more attention and further studies to be sure about all of this.

A new, more broad article from the same researcher should be available openly till September if I remember right. Who knows, maybe other guys will be interested in all of this and answer more important questions in the near future.

I'm far more interested how's it going for the guys in the forum who were taking it ? Maybe we can make a pool or something.

 

[Learner1]

You are right. It is not for everyone. In the recently published paper, it only helped half of the patients.

It is wise to be concerned about mitochondrial health. Many of us have many factors which cause mitochondrial damage, prescription drugs, heavy metals, inadequate SOD production or BH4 leading to peroxynitrite damage and infections can all damage membranes or impair function.

One more thing can be the proverbial straw that breaks the camel's back

 

[Moof]

I'm far more interested how's it going for the guys in the forum who were taking it ? Maybe we can make a pool or something.

I'm taking a small dose of 350g, five days on/two days off, and still doing very well on it. Don't get PEM nearly as much as I used to, and no side effects at all. I need to see several more months through to be sure there won't be any crashes or an increase in my existing peripheral neuropathy (which is secondary to spinal inflammatory arthritis), but so far, so good.

 

[Chris]

I have been taking it on and off for maybe 6 weeks or so, alternating between 333 and 500 (I weigh around 62 k, so that represents a pretty low dose), and taking irregular short breaks of 2-3 days here and there. I took a 3 day break recently, and then resumed at 500; after two good (for me, now) days I had a disturbing moment on my usual morning walk ( about 1/2 mile out, lie down rest for maybe 15-20mins, then return). I now wear a Garmin Vivosport band, which records my HR full-time. Usually the rate while walking is 95-110. This time I was feeling not good, low energy level, and it showed 84--and then switched to showing just a row of dots. I stopped and took my rest; a quick finger on my carotid artery showed I was not having PVCs, which I have occasionally had, though not for several years now, but the pulses were very strong. I took my early rest, then walked home slowly and carefully. I figured that maybe the DCA had had some effect on my autonomic nervous system, and did find one reference to that possibility. This was 3 days ago, and I have taken none since and am feeling better.

We know (thanks to smart people who posted earlier) that both Kudzu and Sytrinol have some effect on those receptors, and luckily the two split their focus between the two main groups. I tried the two together a while back, before ordering DCA, and they did not seem to be having any noticeable effect. But I now realize that Sytrinol has a tested lowering effect on blood lipids, and so I am going to try, after taking a few more days off, taking some of both of them in conjunction with a low dose (maybe ca 250) of DCA, and maybe even taking the DCA on alternate days, and using it on a rotating base, not sure just what as of now. It seems clear that it can boost our mito energy production, but it is also clear that people vary in the speed with which they metabolize and clear the stuff, with oldies like me (85) having more trouble than those young kids who seem to have had no trouble at all taking it for years on end. The story obviously holds real promise, but also pitfalls.

@Moof--thanks for posting--are you using the powder form together with a sensitive weighing scale? How is that going--any problems?

 

[Moof]

...are you using the powder form together with a sensitive weighing scale? How is that going--any problems?

Yes, I'm using the powder form, weighed out and dissolved in a drink. My first dose woke me from my brain fog so violently that I got a thumping headache! – but I've had no side effects at all since. I seem to be doing pretty well on it, with more function and much less PEM than usual (in particular, I rarely get swollen glands in my throat the day after activity now). It's not a cure by any means, but it's really helped me go up a couple of notches on the function side.

I hope you continue to have success with it too, once you've sorted out how it works with other supplements.

 

[Chris]

Just for interest--found interviews with the parents of the five kids who improved on Surinam in the Naviaux trial--impressive, though of course not directly relevant to DCA--but I assume we are all taking it as an available substitute.

www.sandiegouniontribune.com/business/biotech/sd-me-autism-parents-20170525-story.html

 

[ljimbo423]

I don't know if this has been mentioned in this thread yet. It looks like alpha lipoic acid (ALA) also inhibits pyruvate dehydrogenase kinases (PDK's).

If you look to the left on the diagram, you see it shows DCA and ALA inhibiting the pyruvate dehydrogenase kinases-

LINK

This paper also talks about ALA inhibiting PDK's

An inhibitory effect of lipoic acid on PDKs would result in less phosphorylation of E1 and hence increased PDC activity.

This finding provides a possible mechanism for a glucose (and lactate) lowering effect of R-lipoic acid in diabetic subjects.

LINK

Jim

 

[Daniel E.]

I don't know if this has been mentioned in this thread yet. It looks like alpha lipoic acid (ALA) also inhibits pyruvate dehydrogenase kinases (PDK's).

If you look to the left on the diagram, you see it shows DCA and ALA inhibiting the pyruvate dehydrogenase kinases-

LINK

This paper also talks about ALA inhibiting PDK's

LINK

Jim

Thanks for posting this scheme.

When they were researching Dichloroacetate for Congenital lactic acidosis, PW Stacpoole has performed a study which stated that 6,5 mg/kg of DCA is atoxic on daily use. However, such a dose is so small, you might risk experiencing no swift benefit at all and it might take longer time periods for good things to happen.

On the other hand,I think I might finally get it why there was some information on the statement that ALA potentiates the effect of DCA. Maybe that's why when they're used together, you need lower doses of DCA.

"<...>the formulation was extended by adding alfa-lipoic acid (ALA)<...>" - that might explain why the doctor from Belgium got away with small DCA doses and still managed to receive noticeable results.

 

[Learner1]

My old doctor used a protocol with DCA and PolyMVA, an alpha lipoic acid polymer, on cancer patients with some success.

 

[msf]

Thanks for posting this scheme.

When they were researching Dichloroacetate for Congenital lactic acidosis, PW Stacpoole has performed a study which stated that 6,5 mg/kg of DCA is atoxic on daily use. However, such a dose is so small, you might risk experiencing no swift benefit at all and it might take longer time periods for good things to happen.

On the other hand,I think I might finally get it why there was some information on the statement that ALA potentiates the effect of DCA. Maybe that's why when they're used together, you need lower doses of DCA.

"<...>the formulation was extended by adding alfa-lipoic acid (ALA)<...>" - that might explain why the doctor from Belgium got away with small DCA doses and still managed to receive noticeable results.

The study I linked to before stated that ala worsened DCA induced peripheral neuropathy, through (they suggested) it having a similar mechanism.

 

[Learner1]

ALA is capable of pulling toxic stuff (for example, arsenic) out of the mitochondria. It would depend on how toxic one is, but could be responsible for various results.

After chelating for a few years and thinking I was pretty clean, beginning ALA pulled enough arsenic into my blood that was measured at CDC recognized toxic level.

 

[Moof]

Just a quick update: I'm still doing really well on this. Worth saying that I may have started at a high baseline compared to some folk, as my ME is only moderate and I've been really well since I retired four years ago (I loved my job, but it was flippin' killing me).

The main benefit has been a notable reduction in PEM after doing a bit of activity. I was worried I could crash after a while because I was using borrowed energy, but any relapse would have started by now if it was going to happen. I can only usually sustain a few days at even slightly too high an energy expenditure.

I've probably only increased my activity by about 20% – slowly does it, specially now the hinges are getting a bit creaky! – but I'm really pleased so far.

 

[msf]

The lactic acid lowering effect continued to increase over YEARS in one study, so hopefully you will continue to see benefits.

I experimented with larger doses of ALA last week, as I needed to get over PEM without using DCA. There was a very noticeable positive effect, of the same order of magnitude as DCA. I was taking 600mg a day, in two divided doses. My peripheral neuropathy did not seem to worsen. I found one study where they showed that about half the participants got some benefit from such a dose.

 

[msf]

Here it is.

 

[Moof]

Fascinating stuff – thank you for posting. I'll struggle to understand it, but I'll give it a good go!

 

[Chris]

@msf--looks like the real thing, but having trouble downloading it--E declined, asked it to show it, but it refused, and after 5 mins I quite--and was told off "hey, its still downloading..." Firefox more or less managed, but every second page seems a blank, and I am not going to try to print it... Will struggle on with my very limited understanding. But thanks anyway!

 

[msf]

I managed it on my phone, as it's a bit speedier, but it still took a while to load each page.