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

[Chris]

Have now read two papers on diispropylene dichloroacetate, which seem to suggest that it is a superior version of our DCA--more potent, maybe less neurotoxic--but all the suppliers seem to be in Japan or China. Does anyone know more about this stuff, and have clues about availability? It sees to get all mixed up with the vitamin B15 and "pangamic acid" disputes, but as far as I can tell is a legitimate and used therapy over in the East. Any ideas?
The papers are-names in PubMed format- Yamane K, "Diispropylamine Dichloroacetate, a Novel Pyruvate Dehydrogenase Kinase 4 Inhibitor...", and Su L, "Superior anti-tumor efficacy of diispropylamine dichloroacetate compared with dichloroacetate..".

 

[tiredowl]

Sodium dichloroacetate sadly gave me severe neuropathy, even with B1.
Unsure whether to try again as it seemed to make me able to excercise better, I could go for a walk and not feel completely brain fogged/heavy in legs, but had to stop it because of that side effect.


Found this interesting;
'' Dichloroacetate causes toxic neuropathy in MELAS''

''Inhibition of glutathione S-transferase zeta and tyrosine metabolism by dichloroacetate: a potential unifying mechanism for its altered biotransformation and toxicity''

 

[Moof]

I've never heard of diispropylene dichloroacetate, but the work sounds really promising. Hopefully some research will be done on it in the west, too.

I benefit from sodium DCA, but only use it to get over humps that might otherwise make me crash, e.g. my house removal a few months ago. I did the move more-or-less-single handed over a couple of months, and although I obviously got extremely fatigued, there was no significant crash or major immune flare-up. I had some repairs done to the old house in the two years before my DCA trial; that did cause crashes and and an immune response, so I really think the DCA is what made the difference.

I'm about to have most of my new place tiled with industrial porcelain floor tiles, which are pretty much indestructible and don't mind powered wheelchairs being rolled over them. It will mean moving everything (including kitchen appliances) and emptying two walk-in cupboards, so although the tiler will help me with the heavy stuff, I'll need to go back on the DCA for a couple of weeks!

 

[Daniel E.]

Regarding the question regarding diispropylene dichloroacetate, it seems it was the older version of DCA?
40 or 50 years ago they used diispropylene dichloroacetate for all the research.
20 or 10 years ago they moved to Sodium dichloroacetate for some reasons.

I am not sure why but I believe that it was due the overall advantages that Sodium DCA had over Diispropylene.

Currently Sodium DCA is in a couple of clinical trials. Sadly, none of them are for people with CFS.
It looks like this either needs more support or some new researchers to get involved.
Dr. Frank is a little bit too elderly or busy with his other work, I guess.

However, I've recently read some papers with hints that DCA could be helpful for CFS that go far back to 2010.
I wonder why someone got interested just in 2017.

Regarding the side effects that some are experiencing here due to DCA, please read my past posts or pages such as DCAGuide.org for correct dosing and supplement info. The cycles (for eg. 5 days on, 2 days off / 2 weeks on, 1 week off) tend to help also.

 

[Chris]

FWIW, I am still using DCA at around 350-400mg for 5days, then 2 off; it seems to be doing a bit of good--less intense and lower duration of the mild PEM I get after my short morning walk, and a bit greater readiness to sit at my PC and write something or research an issue. No major change, but no problems either. I do take the recommended supplements. I am also expanding my use of Red/Near Infra Red light--after reading Ari Whitten's "Ultimate Guide" I have bought a Platinum BIO 300, and so far am pleased--have only had it about 10 days--again, no sudden or major change, but overall I do seem on a gentle upwards slope.

 

[msf]

Sodium dichloroacetate sadly gave me severe neuropathy, even with B1.
Unsure whether to try again as it seemed to make me able to excercise better, I could go for a walk and not feel completely brain fogged/heavy in legs, but had to stop it because of that side effect.


Found this interesting;
'' Dichloroacetate causes toxic neuropathy in MELAS''

''Inhibition of glutathione S-transferase zeta and tyrosine metabolism by dichloroacetate: a potential unifying mechanism for its altered biotransformation and toxicity''

Yup, me too. On this subject, I have found a partial solution, one that has allowed me to complete 6 weeks of full time work without major problems (I was already able to work a bit without DCA, as I only have moderate ME these days): I use 1 to 1 and a half grams of resveratrol daily (an ampk activator rather than dca inhibitor, thereby coming at the problem from a different angle), and when this is not enough add a small amount of ALA, which seems very similar to dca in its effects, worsening my peripheral neuropathy and really helping with lactic acid. As soon as I am back to lactic acid `baseline` (usually in no more than 1 day) I stop taking the ala and hopefully let my feet recover a bit.

Alternatively you could be more careful with the dca and avoid this problem, but needs must when the devil drives...

 

[msf]

Finally, I think I understand why ala seems to be neurotoxic not neuroprotective in our case (please note it may still be less neurotoxic than DCA, and therefore substituting or adding it to dca may mean you can reduce the amount of DCA and thereby reduce overall neurotoxicity, or maybe it really does have a neuroprotective effect when dca is present).

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4786733/

So it seems that pdk activation in diabetic neuropathy (where ala is neuroprotective) results in neuropathy, whereas in me (and I assume others here), pdk inhibition results in neuropathy. This I suggest explains the paradoxical effects of ala. I will let someone more biochemically minded than me spell this out in proper science speak.

 

[msf]

You might be able to tell that I'm kinda proud of this deduction of mine, or at least of the reading it took to get there. I think this Coleridge couplet is particularly apt for ME patients:

`And haply by abstruse research to steal/ From my own nature all the natural man`

 

[sb4]

@msf Good Sir, please put this in terms my dumb dumb brain can understand.

So you are saying inhibiting the PDKs, enzymes that add phosphate to PDH and thus inactivating it, in the Dorsal Root ganglion causes increased neuropathy. In other words, activating PDH in the DRG causes neuropathy, wheras actiivating PDH in other cells relieves lactic acid build up and improves glucose tolerance?

 

[msf]

@msf Good Sir, please put this in terms my dumb dumb brain can understand.

So you are saying inhibiting the PDKs, enzymes that add phosphate to PDH and thus inactivating it, in the Dorsal Root ganglion causes increased neuropathy. In other words, activating PDH in the DRG causes neuropathy, wheras actiivating PDH in other cells relieves lactic acid build up and improves glucose tolerance?

No, I wasn't suggesting that the drg is different. I was suggesting that the opposite process is at work in diabetic peripheral neuropathy to the one at work in peripheral neuropathy I got about I took RCA, even though the symptoms are the same, and this is why ALA (which is a PDK inhibitor) helps on the first and harms in the second.

 

[msf]

When I say the opposite process is at work I mean that the two way process (the one controlled by pdc) is tilted in one direction in the first, and the other direction in the second.

 

[sb4]

@msf So in peripheral neuropathy the DRG is getting too much activation of PDH via DCA/ALA inhibiting PDK and worsening neuropathy; and in diabetic peripheral neuropathy PDH is underactive and thus DCA/ALA improve PDH to normal levels and improve neuropathy?

 

[msf]

That's my best guess!

 

[Xisso]

Im planning to try this. But I wanted to ask for advice on what doses and suppliments I should take.

Im a guy, 27 years having me/cfs and I just came along this thread looking for something to possible change my life for the better.

What do you think about this:

Sodium Dichloroacetate 500mg / single dose / day
B1(thiamin HCL) 500mg / single dose / day || I already have 500mg tables of this at home.
Alpha Lipoic Acid 200 mg / single dose / day
Q10 powder 125~mg / singel dose / day || I have this home aswell
Acetyl-l-carnitine 500mg / single dose / day || I have this home aswell

Should I try this setup or adjust doses?

 

[gregh286]

Im planning to try this. But I wanted to ask for advice on what doses and suppliments I should take.

Im a guy, 27 years having me/cfs and I just came along this thread looking for something to possible change my life for the better.

What do you think about this:

Sodium Dichloroacetate 500mg / single dose / day
B1(thiamin HCL) 500mg / single dose / day || I already have 500mg tables of this at home.
Alpha Lipoic Acid 200 mg / single dose / day
Q10 powder 125~mg / singel dose / day || I have this home aswell
Acetyl-l-carnitine 500mg / single dose / day || I have this home aswell

Should I try this setup or adjust doses?

Personally I think your ala is too low. 2g I take daily. I had dca but made me nauseous.
Thiamine very marginal or unnoticeable benefits..same with others. Just in my experience however.
Citrus fruits in high doses work well with me. Something is wrong with my uric acid cycle that makes it jump to 15.0 in morning. Working on a solution to that.
Uric acid is inhibitor of phosphofructinose pathway that is one of lead enzyme control hibernation and dauer states in mammal.

 

[Daniel E.]

Im planning to try this. But I wanted to ask for advice on what doses and suppliments I should take.

Im a guy, 27 years having me/cfs and I just came along this thread looking for something to possible change my life for the better.

What do you think about this:

Sodium Dichloroacetate 500mg / single dose / day
B1(thiamin HCL) 500mg / single dose / day || I already have 500mg tables of this at home.
Alpha Lipoic Acid 200 mg / single dose / day
Q10 powder 125~mg / singel dose / day || I have this home aswell
Acetyl-l-carnitine 500mg / single dose / day || I have this home aswell

Should I try this setup or adjust doses?

I believe that everything is alright with the dosing. Keep those proportions.
They could serve as an example for some people willing to try this out.

You can up the ALA a bit (to 500 mg), not to 2000 mg (ALA potentiates DCA, so you can get some side effects if you overdo it).

 

[ljimbo423]

Citrus fruits in high doses work well with me. Something is wrong with my uric acid cycle that makes it jump to 15.0 in morning. Working on a solution to that.

Do you think the citric acid in the citrus fruits are helping in some way? Maybe by adding citric acid to the Krebs cycle?

 

[gregh286]

Do you think the citric acid in the citrus fruits are helping in some way? Maybe by adding citric acid to the Krebs cycle?

Yea....for.sure I have response to lime lemon and grapefruit for the good. I eat around 10 a day.
I think its lowering my uric acid then phosophofrucktinose enzyme is less inhibited and glycosis kicks in. HR drops and metabolism jumps....aerobic respiration. Surprised I dont have gout tbh with these levels.

I can feel myself "switching" metabolically if that makes sense into glycosis.
Waiting for new test strips so can measure uric properly and accurately and/or if their is direct relationship to uric acid and citrus and/or energy.

I think also my daily dose of ala at 2g is dropping uric....time will tell. Without it I lose lots of functionality.

 

[gregh286]

I added DCA to my regime and It has been exceptional since. At start i tried powder with nausea. In capsule form, no issues.
My regime now ended up like the nutricel that combaire tested.
I take 1500Mg DCA
1200 Mg ALA
500mg Thiamine.

I eat low carbs now, and CFS is very stable, for sure the DCA made very good addition. ITs only been a week but very noticeable to date.
Certainly, there is marked "lightness" about my body, less lactic in muscles I would safely assume.

Regarding the citrus fruits, I think the high doses of lemons only alleviate the serum lactate caused by poor functioning PDH, and that highly alkaline solution reduce some of the lactate.
I understand neuropathy can become a problem, but against fatigue, i'll take tingling any day.

Its possibe the PDH pathway is overacting at night, why we feel poisoned wakening up, then as day goes on, PDH maybe improve marginally. I would imagine our serum lactate peak in morning.

2 weeks ago I went back to work full time as project manager. First job since 2012.

 

[knackers323]

@gregh286 are you still back at work and getting the same benefits from the DCA?