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

Dan_USAAZ

Senior Member
Messages
174
Location
Phoenix, AZ
In regard to DCA treatment, has anyone experienced or heard reports of it causing abnormal blood test(CBC) results. After decades of relatively normal CBC results, my last test had what my PCP referred to as significant changes.

Macrocytosis - macrocytic erythrocytes
Absolute Immature Granulocytes – High​

I am scheduled for additional and confirmatory blood tests. There are numerous causes for the above abnormalities (Hypothyroidism, B12 deficiency, medications, infections, etc) that we are looking into.

Adding DCA (2 months) is the only major change I have made in recent months, so I am curious if anyone had heard of a connection. Also would be open to any hypotheses.

Thanks,
Dan
 
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Moof

Senior Member
Messages
778
Location
UK
I can't seem to find any links by Googling this...but as you say, there are so many other possible causes that it's difficult to know. I guess it could be some kind of secondary reaction, such as increasing your body's demand for B vitamins? It is just a wild guess, though.

You might have heard me banging on about it before (sorry if so!), but don't rely on serum B12 tests to pick up a deficiency. My GP did, and I could have ended up with irreversible dementia as a result. I had a severe, symptomatic deficiency that should have been recognised for what it was, and I only came out of it relatively unscathed by buying my own hydroxocobalamin and having a diabetic friend teach me to do subcutaneous injections! Cellular B12 deficiency can be hard to detect, but MMA and homocysteine tests are more reliable than serum B12.
 
Messages
41
Dan, I have read a lot of literature related to possible DCA adverse reactions, but, unfortunately, I have never seen any reports that DCA could cause blood changes in animals or in humans besides slight liver enzyme elavation (which is rare and could happen if one takes high doses of DCA for a prolonged time).

Macrocytosis can can be two types - either normoblastic or megaloblastic (correct me if I'm wrong).
The latter is much more frequent and is mainly due B12 or B9 deficiency (maybe you avoid animal foods lately?). Sometimes it can be due other ilnesses, etc. some types of stomach patologies etc.,etc. Your doctor should tell you the possible cause when more blood tests are performed. It's more likely that it is caused by loads of other reasons.
A friend who is vegan once and had megaloblastic macrocytosis for having insufficient B12 intake.

The other blood test.. well. Can't comment a lot about that situation. I bet the doctor could answer it better.
 

Chris

Senior Member
Messages
845
Location
Victoria, BC
Found an interesting paper (unable to get full text) on dosing DCA for use in cancer-
A phase I open-labeled, single-arm, dose-escalation, study of dichloroacetate (DCA) in patients with advanced solid tumors.
Chu QS1, Sangha R, Spratlin J, Vos LJ, Mackey JR, McEwan AJ, Venner P, Michelakis ED.

This comes from Michelakis, at Alberta, who is really the founder of the recent use of DCA for cancers. The dosing suggests (but does not state) that taking a low dose twice a day may be better, and repeats warnings about the variability with which different people metabolize the stuff. Has anyone tried cutting the daily dose into two halves? I shall give it a shot.

Does anyone have access to the full text, and if so, could you give us any info about what, if anything, is written about the advantages of twice daily dosing?
 
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Dan_USAAZ

Senior Member
Messages
174
Location
Phoenix, AZ
@Moof & @Daniel E. ,
Thank you for the review and input. I also have not found anything that might suggest the changes are DCA related. I go back in on Tuesday for blood draw, which will include a confirmatory CBC and additional blood work. My current theory is that the enlarged RBC result may have been caused by sample processing errors. This is listed as a possible cause. There were a couple abnormalities with the way the sample was processed and I have pointed that out to my doctor this morning. Have not heard back yet.
Thanks again.
Dan
 

Chris

Senior Member
Messages
845
Location
Victoria, BC
Have found an interesting paper, with Stacpoole as one author,
Model Informed Dose Optimization of Dichloroacetate for the Treatment of Congenital Lactic Acidosis in Children.
Mangal N1, James MO2, Stacpoole PW3, Schmidt S1.

Without explaining exactly why, they have chosen twice daily dosing. Makes clear the major differences between the young and the adult in clearing the stuff--unfortunately nothing about the aged! Thnking about the implications of this, I am inclined to consider a kind of 10-11 days set, alternate days, starting highish (say, for me, 2 x 333mg, then two days later 1x500, maybe again after two days, then 333 and again, and then one dose of 165; then 5 day break. Reasoning--the rate of clearance will slow over the doses, so a decreasing dose might keep the blood level closer to steady? Comments welcome.
 
Messages
41
@Chris. All I understand so far is that DCA metabolism is dependent on two things - age (the younger, the faster the clearence - as with a wast majority of the drugs) and the genotype (it appears that there are 3 or 4 variatons of the enzyme GST). DCA metabolism happens in the liver where gama S transferase does its job and breaks the molecule down in other simple compounds. Naturally, with age, the function of the liver gets "slower" or less active, that's why the clearence slows down a bit.

Till this moment, I have read a lot of papers that discuss the dosing and toxicity of DCA. What I can say - there are a lot of other toxic substances used as drugs these days. It's almost impossible to find new stuff which is 100% safe.
Take for example Rituximab, while it had promise and maybe even HAS promise for further studies on ME/CFS, it's worth noting that even substance affects the immunity, makes you more prone to infections, can cause liver,renal,cardiac,allergic reactions etc. However, with proper care and scheduling this all can be controlled to some levels.

Back to DCA. Okay, let's talk about what makes dosing a little bit difficult:

- AFAIK, the safe dose of DCA is something between 12,5 mg/kg - 6,5 mg/kg. This is confirmed by dozens toxicology studies done in the previous decades. This substance has been observed from all sides. Stacpoole has researched its safety for like 30 years, I believe. He has a study in which children took DCA for years and nothing bad happened to them (one kid had mild peripheral neuropathy which went off and never came back after a break).
The doses were 25 mg/kg daily. I don't recall if a specific dosing schedule was used. Keep in mind, these were children, so the safe dose for adults is probably lower due to slower clearence.

-Many people tend to take the recommended amount so far (400 - 500 mg daily). Doses like this are considered low and the effect is really slow if you take it like this. However, keep in mind that if you take DCA with Alpha-lipoic acid - the effects are combined and potentiated, so you don't really need to overdo the intake. Give it time. No one knows why some experience DCA's effect on their ME/CFS in a couple of days and why some experience it in a couple of weeks. Heck, there are people who don't experience any improvement at all. Their disease could be an other subtype of ME/CFS which is not mainly related to metabolism/mitochondrial "ice age - low ATP production".
You can take a larger dose than 400-500 mg daily, this is your risk, DCA is not an official supplement or drug yet. Who know's if it will be - this would need more studies targeted towards its safety. If you decide to do more than half a gram to see if it's for you, if it helps you achieve the effects faster - consider doing schedules. So far there are two ways to schedule:
A) 5 days on DCA, 2 days off DCA. Repeat. This is an old way which IMHO is more suitable for someone with ME/CFS.
B) 14 days on DCA, 7 days off DCA. Repeat. I imagine if one with ME/CFS takes a break for a week, this could provide a bounce-back to previous symptoms. However, who knows how it could really be ?

- Take Vitamin B1! This is a must, people. There have been some guesses that the main reason why DCA could cause adverse reactions is the fact that somehow thiamine is depleted faster when someone takes DCA. So take additional thiamine / benfotiamine (you need less of the latter, but more expensive).
Idk what the doses should be - maybe somewhat between 100 - 250 mg of thiamine.

-Some people say that L-Carnitine could help. I don't know a lot about it. My guess is that Carnitine helps transform DCA or energy substrate to the mitochondria and hence it could reduce the needed intake of DCA/ALA as well as adverse reactions.

-Finally, some people get adverse reactions, some don't. If you've got some kind of nerve damage from MS, if you've got a nutritional deficiency or other more serious underlying untreated diseases - the numbing of the tongue etc. is much likely to happen.

Who knows. Maybe careful intake of 400 - 500 mg DCA daily, 5 days on, 2 days off, with Alpha-lipoic and B1 could be all it takes to avoid anything unpleasant at all. That's a big question. That's why this deserves more attention and discussion in the future.
 
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Chris

Senior Member
Messages
845
Location
Victoria, BC
@Daniel E; many thanks for putting all this together, and finding the new Comhaire paper, with its new list of possibly helpful supplements--the guy is obviously exploring actively to try to find things that may help, and deserves our thanks. I have two comments--I shall assume that other intermediate dosing schedules are also possible while respecting the basic intent of having "off" periods to limit the build up of unmetabolized DCA--say 8 days on, 4 off, etc. And several papers by Stacpoole and others have divided the daily dose into two, presumably morning and evening. My feeling is that taking some in the evening may worsen sleep problems, though with a condition that is as variable as ours I find it difficult to be certain. Do you or others have thoughts/experience relevant to this?
 
Messages
41
@Chris, yes, other intermediate dosing schedules are also fully available and acceptable, I believe they chose 5 days on, 2 days off as a main way to take DCA because it's easier to remember that you take this on Monday - Friday and have a break on Saturday and Sunday. This is crucial and this is why I encourage people to take capsules to avoid things like overdosing etc.
So 8 days on, 4 days off is perfectly acceptable. The main point is that it should be advisable to have some days off DCA since it has a tendency to accumulate in people at different speeds.

There were even some experiments with mice and the results were that for example:
if you give the mice 5 mmol/l (228 mg/kg) of DCA daily for 60 weeks, it has a higher probability to have a negative impact than if you give 20 mmol of DCA (912 mg/kg) with a schedule (let's say 5 on, 2 off) for 60 weeks! Wow. This itself is explanatory.

However, let's remember - this was performed with much higher doses than 6,25 - 12,5 mg/kg daily. AFAIK, Frank Comhaire (the prof. who published these two articles on DCA for ME/CFS) gave the DCA in 400 mg in one capsule with other supplements at one serving - before / during breakfast. Also, they took it for months daily with no breaks and no one experienced neuropathy.

So summa summarum, yes, you can adjust the schedule the way you like. It can be 10 days on, 5 days off, 5 days on, 2 days off, 8 days on, 4 days off etc. It's your choice.
This whole perspective of DCA for ME/CFS is still in a "Beta version" and no one has made a clear statement on what intervals should used for taking Sodium dichloroacetate. As many of you have already heard, some people tried taking DCA for solid tumors, as far as I remember, the doctors, researchers and the patients adapted most of the dosing information from previous Stacpoole articles and decades of research on dealing with Congenital lactic acidosis in children.

If we talk about the current info on ME/CFS - DCA was used daily with no breaks at 400 mg in the present Belgium research.
---------------------------------

Now about sleep and DCA at evenings... well.. Tbh, I have never hear and read any info on the internet, nor I have heard it from other people who have taken DCA that it could disrupt sleep if taken at evenings. My guess would be that it could disrupt sleep if you take it before sleep on an empty stomach in a powder form. It's still a weak mucosa irritant and stomach aches don't go well with a good nights sleep. :D

It's the first time I have heard such a speculation. However, I have read some anecdotal reports that Vitamin B1 can stimulate the body in some people, so if one has sleep problems, it could be helpful to research this and maybe trying to take Thiamine at the first part of the day.
 

leokitten

Senior Member
Messages
1,542
Location
U.S.
Butyrate, an HDAC inhibitor and produced by microbes in your colon from fiber, is also known to activate PDH https://www.nature.com/articles/sigtrans201635.

Though If you’ve had high herpes virus titers, make sure you take antivirals because butyrate causes viral reactivation (which is not a bad thing if you are taking the right antivirals along with it since it works in synergy).

Researchers have investigated combining it with antivirals to get herpes viruses to come out of dormancy so that they can be killed https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1852196/.

Sodium butyrate is available as a supplement.
 

mariovitali

Senior Member
Messages
1,214
Butyrate, an HDAC inhibitor and produced by microbes in your colon from fiber, is also known to activate PDH https://www.nature.com/articles/sigtrans201635.

Though If you’ve had high herpes virus titers, make sure you take antivirals because butyrate causes viral reactivation (which is not a bad thing if you are taking the right antivirals along with it since it works in synergy).

Researchers have investigated combining it with antivirals to get herpes viruses to come out of dormancy so that they can be killed https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1852196/.

Sodium butyrate is available as a supplement.

Butyric acid may be a better idea :

http://algogenomics.blogspot.com/2018/07/gut-microbiome-bile-acids-and-butyric.html
 

Cheesus

Senior Member
Messages
1,292
Location
UK
New study:

Why do some ME/CFS patients benefit from treatment with sodium dichloroacetate, but others do not?

Abstract
Myalgic Encephalopathy/Chronic Fatigue Syndrome (ME/CFS) is an enigmatic disease the pathogenesis of which remains elusive. Pragmatic proof-of-principle of the hypothetical mechanisms causing the clinical symptoms has been delivered, but it is hard to explain why some patients do respond favourably to treatment with sodium dichloroacetate (DCA), which enhances the activity of the mitochondrial enzyme pyruvate dehydrogenase, but other patients experience no benefit from this substance. In a prospective trial including 35 ME/CFS patients, logistic regression analysis with stepwise elimination has identified 6 pre-treatment characteristics allowing for the differentiation between responders (n = 13) and non-reponders (n = 22) with high accuracy (P < 0.0001; area under the ROC-curve = 0.92). A formula was derived generating the probability of belonging to the group of responders. This finding may assist in selecting ME/CFS patients suitable for treatment with DCA, but requires further studies as to the predictive capacity of the derived formula.

https://www.ncbi.nlm.nih.gov/pubmed/30220343
 

Murph

:)
Messages
1,799
New study:

Why do some ME/CFS patients benefit from treatment with sodium dichloroacetate, but others do not?

Abstract
Myalgic Encephalopathy/Chronic Fatigue Syndrome (ME/CFS) is an enigmatic disease the pathogenesis of which remains elusive. Pragmatic proof-of-principle of the hypothetical mechanisms causing the clinical symptoms has been delivered, but it is hard to explain why some patients do respond favourably to treatment with sodium dichloroacetate (DCA), which enhances the activity of the mitochondrial enzyme pyruvate dehydrogenase, but other patients experience no benefit from this substance. In a prospective trial including 35 ME/CFS patients, logistic regression analysis with stepwise elimination has identified 6 pre-treatment characteristics allowing for the differentiation between responders (n = 13) and non-reponders (n = 22) with high accuracy (P < 0.0001; area under the ROC-curve = 0.92). A formula was derived generating the probability of belonging to the group of responders. This finding may assist in selecting ME/CFS patients suitable for treatment with DCA, but requires further studies as to the predictive capacity of the derived formula.

https://www.ncbi.nlm.nih.gov/pubmed/30220343

I read the whole paper (attached) and came out none the wiser. Seems like there's not much there.
 

Attachments

  • 10.1016@j.mehy.2018.08.014.pdf
    332.6 KB · Views: 29

Moof

Senior Member
Messages
778
Location
UK
I think he's suggesting that the most important discriminant in this very small study is the patient's perception of the level of disabling fatigue; those who feel the most disabled by it are less likely to respond. That concerns me, as it lacks scientific rigour and has echoes of BPS approaches.

Another factor is that people with autoimmune antibodies are less likely to respond (25% response in this group vs 41% response in the group without auto-antibodies). That's a bit more interesting and worthy of follow-up.

So as you say, @Murph, there's not much here yet – it has to be repeated as a double-blinded study before anyone will take any notice. However, all researchers have to do these small trials as part of the process of showing there's a case for a better-funded, more rigorous study, so we can't complain!
 

Hip

Senior Member
Messages
17,824
Why do some ME/CFS patients benefit from treatment with sodium dichloroacetate, but others do not?

Perhaps the answer lies in the Myhill, Booth and McLaren-Howard studies on energy metabolism dysfunction in ME/CFS: these studies found that there are various different types of blockages in energy metabolism in ME/CFS, and that not all patients had the same blockages (see Fig 2 in that post). Not all patients had blockages in oxidative phosphorylation, for example.
 
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junkcrap50

Senior Member
Messages
1,330
I guess I should report my experience taking DCA. I started it 5 weeks ago, taking 333mg AM and PM. I noticed no benefit or change taking it. And I have fairly bad lactic acid problem and easily get burning muscles very quickly, which all started when I was messing with methylation. For example, I get burning from brushing my teeth, scratching my head, walking up stairs, squatting down to pet a dog, etc.
 

Chris

Senior Member
Messages
845
Location
Victoria, BC
Thanks guys for finding and posting this new short paper from Comhaire. I think it makes some sense--if you put together two statements "pre-treatment items 3 and 4 of the FSS questionnaire, which were associated with higher probability of improving by DCA intake" and "items 3 and 4 relate to the limitation of physical performance caused by the disease, which probably result from mitochondrial metabolic insufficiency,"--one gets the picture that if your version of ME is rooted in problems of energy production DCA may very likely be helpful; but if it is rooted in immune/autoimmune problems, it likely will not. In spite of the fact that the two cannot be totally separated (presumably NK cells need energy to do their job efficiently), DCA is directly aimed at improving energy production by reducing hindrances to directing it towards the mitochondria (phosphorylation) rather than to within the body of the cell (glycolosis). This may be a small step in the slow process of discriminating between groups within ME.
 

S-VV

Senior Member
Messages
310
I tried DCA @ 1g per day with no noticeable benefits. To the contrary, my already swollen lymph nodes got worse. I'm going to try LDN next.

If the two major subgroups of CFS are inmune and energy production deficit, maybe a trial of LDN and DCA could be a front line treatment to trial for new patients.
 

Chris

Senior Member
Messages
845
Location
Victoria, BC
@S-VV, sorry it was of no help, though not sure why you started at the rather high dose of Ig. In my last post I did not mean to imply that it was now understood that there are two main sub-groups, rooted in energy metabolics (Naviaux and others) and immune/autoimmune problems --I just picked two directions which have been producing interesting research results recently, into one of which DCA would fit more obviously.