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

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Recently I've read some research related to this question.

@nanonug ,while there study above mentions interesting findings and concludes that some individuals metabolize DCA faster than others and thus doses should vary, there are some other examples of widely prescribed medications that also vary for each individual.

Take for example ACE inhibitors prescribed for people with chronic heart failure (about 6 million people have heart failure in USA and a large portion receives ACE inhibitors).

"As an example, up to one third of patients with congestive heart failure may not tolerate or respond to ACE inhibitor therapy [15,16]. In the late 1980s, researchers began investigating genetic factors to determine the origins of inter-individual variability in patients' responses to ACE inhibitor therapy."

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1283147/


ACE inhibitors are still prescribed for patents in all over the world.

Regarding the dosing and safety for Dichloroacetate - there has been a large and long study on this.

"Another recently completed randomized, controlled trial investigated the same dichloroacetate dose in 43 young children (mean age at entry: 5.6 years) with congenital lactic acidosis (CLA) because of defects in pyruvate dehydrogenase or in ≥1 complex of the respiratory chain or a mitochondrial DNA mutation.3 In contrast to the findings in older subjects with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes, this study demonstrated good tolerability of dichloroacetate, and there were no significant differences in the severity or frequency of adverse events between the drug and placebo groups after 6 months of treatment.

Here we report our experience with long-term administration of dichloroacetate in the 36 children on the trial who received dichloroacetate, from their starting times on the drug. Some of these patients have received treatment continuously for ~10 years."

So, young people received 12,5 mg/kg of DCA daily. Someone who weights 50 kg or 110 lbs took 625 mg of DCA daily for loooong periods of time (minimum of 2 years, some even 10 years).

Frank Comhaire suggests that a formula with 400 mg of DCA daily should be okay for people with ME/CFS in his study. As far as I get it, he decided to use a dose which is even below the minimal threshold for side effects to occur. 400 mg of DCA should be safe for most of the people, despite the fact if they have EGT (faster DCA metabolism) or they don't have EGT (slower DCA metabolism).

These are my thoughts, however, I could also be wrong.
 

nanonug

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So, young people received 12,5 mg/kg of DCA daily.
On weight alone, regardless of GSTZ1 status, one size doesn't fit all when it comes to DCA. Add GSTZ1 status and things become even more complex when it comes to dosing. As such 400mg of DCA may either be too little (no useful effect) or too much (serious side effects.) One should not be relying on a very simplistically designed pilot trial for dosing information.
 
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this is a topic that interests me a lot. Back when I first found out about PDH deficiency in people with cfs I looked at pyruvate dehydrogenase complex deficiency, which is a more severe but specific condition in which people have no pyruvate dehydrogenase activity, or less than cfs. they get lactic acidosis, and generally die young. but the available treatments are keto and DCA, sometimes thiamine megadoses. Keto wouldn't be good for CFS imo. DCA, of course, is pretty toxic.

but this recently got me down the rabbit hole of trying to understand glycolysis and cellular respiration in general. Ray peat is a somewhat kooky physiologist who has written about this stuff a lot. He has stated that both aerobic and anaerobic glycolysis produce lactate. At first that seems a little wild, but i've seen papers recently that have agreed with this... maybe Ray was prescient here
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4343186/

So onto DCA... DCA apparently blocks both aerobic and anaerobic glycolysis. and is toxic. Peat says that a more targeted therapeutic agent that only blocks aerobic glycolysis would be better.

Peat lists a number of things that are similar therapeutically to DCA but are less toxic. Some of these supplements seem to be already prescribed by CFS doctors.

"Therapeutically, even powerful toxins that block the glycolytic enzymes can improve functions in a variety of organic disturbances "associated with" (caused by) excessive production of lactic acid. Unfortunately, the toxin that has become standard treatment for lactic acidosis—dichloroacetic acid—is a carcinogen, and eventually produces liver damage and acidosis. But several nontoxic therapies can do the same things: Palmitate (formed from sugar under the influence of thyroid hormone, and found in coconut oil), vitamin Bl, biotin, lipoic acid, carbon dioxide, thyroid, naloxone, acetazolamide, for example. Progesterone, by blocking estrogen's disruptive effects on the mitochondria, ranks along with thyroid and a diet free of polyunsaturate fats, for importance in mitochondrial maintenance."

http://raypeat.com/articles/articles/mitochondria-mortality.shtml


The other article that discusses DCA is this one:
http://raypeat.com/articles/articles/lactate.shtml
 
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Now I still don't understand peat's model of cellular respiration totally, but I'm starting to think it's not as crazy as it seems on first glance. Peat is not an advocate of ketogenic diets, so I have a hard time understanding what he thinks is optimal if glycolysis is understood as a negative thing... I mean there's no other way to get glucose metabolized, right? /there's no other way to make pyruvate for the kreb's cycle
 

sb4

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so I have a hard time understanding what he thinks is optimal if glycolysis is understood as a negative thing
As far as I understand it, when he refers to glycolysis, he means glucose going down the lactic acid path, as opposed to going through PDH/PDC and to the mito to be oxidised.
 
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As far as I understand it, when he refers to glycolysis, he means glucose going down the lactic acid path, as opposed to going through PDH/PDC and to the mito to be oxidised.
okay, but it gets weird, because he also thinks aerobic glycolysis produces lactic acid and is bad, not just anaerobic glycolysis. so if aerobic glycolysis and anaerobic glycolysis are out, what form of glucose metabolism is there, and under which conditions does it occur? Since we're talking about glycolysis as something that occurs before the kreb's cycle... so is there a third option, glycolysis which produces pyruvate, not lactate, but it's not aerobic or anaerobic? Or when he says aerobic glycolysis, is he not referring to all oxidative metabolism of glucose, but rather only to the occasional aerobic production of lactate from glucose, which is disordered metabolism?
 

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@debored13 I think he will be referring to some glucose being shunted to anaerobic lactic acid even in the presence of aerobic glycolysis. I think although partial glycolysis occurs before pyruvate, they are referring to complete glycolysis as lactic acid production. Although I wish they would be clearer.
 
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@debored13 I think he will be referring to some glucose being shunted to anaerobic lactic acid even in the presence of aerobic glycolysis. I think although partial glycolysis occurs before pyruvate, they are referring to complete glycolysis as lactic acid production. Although I wish they would be clearer.
okay... so when ray is referring to proper oxidative metabolism he means "partial glycolysis" plus the krebs cycle and so on
 
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Could be something else, little doses like this rarely exhibit any effects in such short period of time.
Do you take Vitamin B1, Alpha Lipoic Acid, L-Carnitine and Q10 ?
 
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It's best to take Vitamin B1 before breakfast and lunch (afaik they don't recommend taking it before night because it could stimulate a little bit, wake you up and make falling asleep harder). Take 50 mg 2x daily.

Alpha Lipoic Acid potentiates the effect of DCA (so that even 500 mg DCA doses become more efficient) and it also prevents unwanted reactions. You can take it before breakfast, lunch, dinner. It's your choice. Frank recommended 50 mg of R+ Alpha lipoic acid (if you have the racetame variation which is R- and R+ - you've got to take 100mg minimum because R- is inactive). I would advice 100 mg of R+ but again, I've got no say in this. I've just seen that people are better of with slightly higher ALA doses.

L-Carnitine (if you don't get any funny feelings with it) is the third supplement that is great for DCA usage. I am not completely aware how it works. Afaik it helps with the fatty acid and other material transportation to the mitochondria from cytoplasm. If you choose to take this, take atleast one 500 mg capsule a day. You can take it twice if you're feeling that it's better.
 

nanonug

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Tried 1@ 500 mg per day for 2 days...made me even more tired....anyone else get this effect?
Did you take it with food, meaning, carbs? For my own protocol, have a look here, in case you haven't seen it yet: From brain fog to clarity in 30 minutes. A dosage of 500mg may be too little or too much, depending on how much you weight and how efficient you are at metabolizing DCA.
 
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I've heard that some of the DCA vendors get their powder from manufacturers in China. Maybe that could be the reason why those impurities cause fatigue ?

@debored13, I have read all the information you had posted regarding the physiology explained by Ray Peat and I'm sorry to say that I don't agree with some of the things he has in mind.
Firstly, basic biochemistry textbooks explain cellular respiratory mechanisms better than Ray does.
Secondly, when he mentions dichloroacetate he claims that it is toxic and is a cancerogen and fails to explain the subject further.

The reputation for Dichloroacetate being a cancerogen comes from a single report based of research with mice, when they were given about 200 - 300 mg/kg of DCA for continuous periods of time, hepatic tumors developed. It's not hard to say that many other substances that are metabolized in the liver could cause the same result.

Regarding the toxicity of DCA, let's mention the fact that the LD50 of DCA is somewhere between 1000 - 3000 mg/kg (based on this article). The LD50 of Table salt (NaCL) is 3000 mg/kg (link). This means that you have a similar probability to die from the huge amounts of table salt as you do with DCA. (it would take about 50 g for a person who weights 110 lb).

DCA doses of 6,25 mg/kg are atoxic (cause no side effects) with certainty (Stalpool et al. 1990).
However, with higher doses and GSZT1 variatons side effects can occur and this is usually when you're talking about prolonged use of 25 mg/kg of DCA per day with no breaks and no additional neuroprotective supplementation.

Ray is however right on one thing, Vitamin B1 can cause a similar effect like DCA.
Also, I agree on his perspective that high levels of prolactine could also be a major issue related to chronic fatigue.
 

Chris

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I have been using the stuff for a week now--333mg, once or twice a day. When I take two (in conjunction with Acetyl-l-carnitine, ALA, Q10, B1, as recommended--I had been taking all before I started DCA) I am able to be more active, physically and mentally, but am sometimes rather tired the next day. Overall I think it does improve my state, but not hugely so far. There are several private clinics that have been using the stuff for years and have useful info on their sites: Edmonton Integrative Cancer Treatment, OICC (Ottawa Integrative Cancer Centre). Since it is known to damp down its own metabolism, it is suggested to take breaks--two weeks on, one off, or whatever. I think that after one week I shall take 3 days off, and then start again at 333 twice a day--should keep me from getting the neuropathy that seems the commonest side-effect. Overall I feel positive about it, but no rapid magic ..yet. Thanks to all for the info above.
 
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I would like someone to pm me the contacts of Prof. Ronald Davis. Could someone pm me his email ?
I've tried his university e-mail and got no luck.

I've got a serious question regarding his previous findings with ME/CFS that could be important.

Thanks in advance.