The power and pitfalls of omics part 2: epigenomics, transcriptomics and ME/CFS
Simon McGrath concludes his blog about the remarkable Prof George Davey Smith's smart ideas for understanding diseases, which may soon be applied to ME/CFS.
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Tried dichloroacetate, Great energy return - But Chemical Taste to it

Discussion in 'General Treatment' started by XenForo, Oct 25, 2017.

  1. XenForo

    XenForo

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    Two times so far, I tried Tree of Life brand DCA: https://smile.amazon.com/gp/product/B06XQ5FRK4/ (from Amazon, USA and manufactured in China) It seems to give me much more energy, which is great obviously, but it has a strong chemical taste to it. All the descriptions of the supplement say it is tasteless and odorless. So I'm off it for now and ordered a different brand manufactured in the EU to compare. Maybe I'm just sensitive to the taste more than other people. Anyway, I wanted to ask if anyone else who has made the jump and tried this potentially dangerous supplement has noticed a chemical taste or not. I know there are quite a few DCA threads on PR, but I only see it described as tasteless / odorless. My concern is that this particular brand / batch etc is contaminated. I put a question Tree of Life, but haven't heard back. There doesn't seem to be a phone number to contact, just email. Thanks for any help
     
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  2. Hip

    Hip Senior Member

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    Very interesting. That's the first positive response from dichloroacetate (DCA) I have seen reported from an ME/CFS patient. Can I ask, what dose did you use, and after you took it, how long before its energy-boosting effects kicked in? Does the extra energy appear within a matter of hours after taking DCA? And how long would you say the energy boost from DCA lasts?

    Does the DCA seem to improve any other ME/CFS symptoms, such as the brain fog, or is it only the fatigue and lack of energy DCA addresses?


    I still have some DCA here which I have not yet tested properly. I can confirm that it is almost tasteless, but with just a slight chemically tang. I bought mine here.
     
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  3. XenForo

    XenForo

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    I took 580, I think that was milligrams; it wasn't much powder. I didn't have time to take a nap or break before I tried to go out at night to a late night concert - that's not something I can normally do, but I was fine. It "worked" from the afternoon to the next morning. I think it "worked" after maybe an hour or two; I can't remember how long it took.

    I kept going back and forth thinking I was thinking quick on my feet, then thinking I was still getting confused, so I'm not sure

    Ah, that's the EU product I ordered the second batch from. Good to know yours also had a chemical tang; I guess that's normal; thanks!
     
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  4. Hip

    Hip Senior Member

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    The product you bought looks to be in powder form, so presumably you would have had to measure out some powder?

    Myself I took 350 mg as a single dose, but did not notice much. But then 2 days later some significant depression hit me, which lasted for nearly a month (which is why I have not taken DCA again as yet, as I am concerned it might have been the cause of that bout of depression).
     
    Last edited: Oct 25, 2017
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  5. rodgergrummidge

    rodgergrummidge

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    Hi @XenForo
    I have also been interested in whether DCA may help in some CFS cases, although I wouldnt advocate using it because of the potential toxicities. I had been following a thread in which @Hip suggested he was going to use it, but he put it on delay.

    I think it is important to include a few cautionary notes. DCA is not simply a supplement. Its a drug that has pharmacological effects which means that you should carefully consider its pharmacokinetics, toxicities and adverse effects before and during use. In the interests of risk management for the development of treatment plans, I have listed a few considerations below.

    1) On what basis do you think DCA may be an effective treatment for you? Do your path tests point toward DCA being a potentially useful drug? Do you get lactic acidosis following a high carbohydrate meal or low-level exercise? Have you got elevated Pyruvate? Do any of your tests suggest a PDH deficiency? Have you been shown to have a mitochondrial defect in your TCA cycle or OXPHOS pathway? If your results for these metabolic tests are normal, why 'give DCA a try' given the potential risks and toxicities?

    2) Dose? You need to be absolutely clear on the dose you are using. 580 somethings? There are lots of DCA trials published. You should find those studies and calculate your dose in terms of mg/kg/day. Studies I have seen range around 10-50mg DCA/kg/day. But you should research drug dosing regimens carefully

    3) Because any drug can have toxicities, you should always start on a low dose and escalate slowly into a 'therapeutic range'. Dont start at a 580 something dose and then have a night out. Start slow and conservatively.

    2) How are you going to test efficacy? Clearly, taking DCA and having a good 1-2 days can be coincidence, particularly with CFS where symptoms can range widely from day-to-day. Ideally, if 1 or more of the tests under point 1 (above) are abnormal, you would simply test whether DCA improves those results.

    3) How are you going to test for toxicity? Very important. While DCA can be reasonably well-tolerated, clinical use of DCA has largely stalled due to toxicities found a couple of human trials. DCA has been shown to cause liver dysfunction, hypoglycemia and peripheral neuropathy. They appear to be reversible, but you should regularly test for each of these potential toxicities. Fairly easy to do.

    4) What are the chances that DCA manufactured in China and purchased from a 'faceless' company via Amazon is therapeutic grade and free of impurities and toxins? Low. I have seen the online reviews for some sources (eg there is a Lithuanian DCA that has good online reviews), but an online review for a Lithuanian drug is worthless unless it can be independently verified by some accredited tester)

    5) Consult your doctor before undergoing treatment.

    Hopefully you find these suggestions helpful and positive.

    Good luck

    Rodger
     
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  6. sinas

    sinas

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    hi All,

    I am glad somebody opened this topic.

    First of all: I am unsure if have CFS / ME (on top of my hopefully beaten cancer) but its very likely in my view. my story here:
    http://forums.phoenixrising.me/index.php?threads/cfs-me-in-addition-to-cancer.54331/

    Second: it is a toxic drug. Although the neuropathy caused is reversible. you need to be careful and start with a very low dose. Many people take 15mg per kg per day but i am not saying it is safe as it depends on the individual. Consult your doctor. It is a potentially DANGEROUS drug.....

    When I took DCA (against cancer...) i noticed that:
    - my back pain became milder in 3 days
    - the amount of fasciculations was drastically decreased (to appr 10% of the previous frequency) This decrease was permanent which makes me wonder....

    After like 3 months I did not notice any further improvement so I stopped to avoid the side effects. I am considering now again.

    I dont have major fatigue but I noticed I was more active during the weeks I took DCA. Maybe it was placebo though. The above impact was NOT for sure.

    DCA is known to restore the enzyme PDH which is required for the mitochondria to work. Although the PDH inhibition is a consequence in CFS and not a cause, seemingly restoring the PDH can actually help.

    sinas
     
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  7. pattismith

    pattismith Senior Member

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  8. pattismith

    pattismith Senior Member

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    That's very interesting.

    In fact I tryed DCA 250 mg twice a day (10mg/kg/day) for 4 days, but couldn't see any improvement so I stopped.

    I may start again once my state will be stabilized with my current supplement program. (I bought the one @Hip quoted)
     
  9. sinas

    sinas

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    hi @pattismith

    I would not be comfortable with encouraging people to take a toxic drug but I think that 4 days is too short to judge....

    or is it normal for supplements / drugs to work THAT quickly against CFS?
     
  10. XenForo

    XenForo

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    Urgh, I crashed pretty bad. I don't know if it was the DCA or just staying out late. I'm going to wait before trying DCA again.
     
  11. sinas

    sinas

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    hi @XenForo - did you make a pause? like 5 days on 2 days off? The absorption is kind of slow so what you take is somewhat cumulative. they recommend having breaks.
     
  12. pattismith

    pattismith Senior Member

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    I hope that nobody took it as encouragement to take it. I used a lower dose to avoid side effects anyway.

    At the time I tryed it, I had blood lactates issues, but I have managed to fix it with more natural treatements, so it may be that I don't really need this one, hopefully!
     
    Last edited: Oct 27, 2017
  13. rodgergrummidge

    rodgergrummidge

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    Absorption of DCA is not slow and doesnt accumulate. Most human trials I've seen dose with DCA daily. Only about 15% in the blood after 24h. Rapid clearance is perhaps not surprising given that its a relatively small salt. Half-life and and blood clearance below from trials.

    hopefully it helps

    Rodger
    upload_2017-10-27_21-44-53.png
    upload_2017-10-27_21-51-43.png
     
  14. sinas

    sinas

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    hi @rodgergrummidge

    Did these patients have breaks ? I dont think they were taking DCA for 60 months continuously.

    Also, in the cerebrospinal fluid the half -life is appr 5 days based on several reports, interesting case:

    "A 46-year old patient with melanoma which had metastasized to the lung and lymph nodes 2 years previ- ously, was admitted to the Antoni van Leeuwenhoek Hospital in The Netherlands because of confusion and gait disturbance. Four weeks before admission he had started taking capsules with identified DCA (400 mg, thrice daily, corresponding with 15 mg/kg/day) and vitamin A capsules (150,000 IU/day), prescribed by an alternative physician. On neurological examination he showed impaired mental processing, dysarthria and an unsteady gait. MRI of the brain and serum blood tests were normal. In the following days he became more confused, showed aggressive behaviour, had visual hallucinations and dysphasia. Cere- brospinal fluid (CSF) examination demonstrated normal biochemical parameters, no malignant cells and negative PCRs for neurotrophic viruses. Antineuronal antibody screening was negative. Both the DCA and vitamin A capsules were stopped on the day of admission. The DCA concentration in the CSF on day 2 after hospital admission was 78 lg/mL, as measured by liquid chromatography tandem mass-spectrometry. On day 16, the DCA CSF concentration decreased to 11 lg/mL, indicating an elim- ination half-life for DCA in the CSF of approximately 5 days. No serum samples for DCA measurement were available."


    I have read the half time of app 1-2 hours gets longer with time, although you are roight that there is a plateau after the initial cummulation:

    "Although the pharmacokinetics of DCA in healthy volunteers follow a simple one-compartment model, they are more complex in severely abnormal states like severe lactic acidosis or cirrhosis. Dichloroacetate inhibits its own metabolism by an unknown mechanism, and the clearance of DCA decreases after multiple doses (Stacpoole et al, 2003). Although the initial half-life with the first dose is less than one hour, this half-life increases to several hours with subsequent doses. However, there is a plateau of this effect and DCA serum levels do not continue to rise with chronic use. This is also true for DCA metabolites (which do not have any biologic effect, at least on PDH). For example, the serum DCA levels after 5 years of continued treatment with oral DCA at 25 mg kg−1 are only slightly increased compared with the levels after the first several doses (and remain in the range of approximately 100 μg ml−1) (Mori et al, 2004). The effects on lactate levels are sustained and persist after the DCA levels decrease, because the inhibition of PDK is not immediately reversible; DCA ‘locks' PDK in a sustained inactive state."
     
  15. XenForo

    XenForo

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    I just took it for 2 days, then stopped. I might try again and see if it seems like i respond positively or not a second time.
     
  16. rodgergrummidge

    rodgergrummidge

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    Hi @sinas

    The DCA story you quoted has been doing the rounds on the internet and has turned up on redditt etc generating alot of traffic. It describes a person who was medicating with DCA and Vitamin A through an 'alternative physician' and there was no indication how the 'alternative physician' was monitoring DCA and Vitamin A toxicities or adverse reactions (both of which are well known but easily monitored). But most importantly @sinas , when you pasted the story, you only included the 1st paragraph. The second paragraph (found widely on the internet) clearly indicates what was causing the issue. I pasted the whole story including the second paragraph below (in italics with second para bolded). The person had developed neuropathy which is a known and well described toxicity of DCA. Once the person was taken off DCA, the improved over 8 months.

    "A 46-year old patient with melanoma which had metastasized to the lung and lymph nodes 2 years previ- ously, was admitted to the Antoni van Leeuwenhoek Hospital in The Netherlands because of confusion and gait disturbance. Four weeks before admission he had started taking capsules with identified DCA (400 mg, thrice daily, corresponding with 15 mg/kg/day) and vitamin A capsules (150,000 IU/day), prescribed by an alternative physician. On neurological examination he showed impaired mental processing, dysarthria and an unsteady gait. MRI of the brain and serum blood tests were normal. In the following days he became more confused, showed aggressive behaviour, had visual hallucinations and dysphasia. Cere- brospinal fluid (CSF) examination demonstrated normal biochemical parameters, no malignant cells and negative PCRs for neurotrophic viruses. Antineuronal antibody screening was negative. Both the DCA and vitamin A capsules were stopped on the day of admission. The DCA concentration in the CSF on day 2 after hospital admission was 78 lg/mL, as measured by liquid chromatography tandem mass-spectrometry. On day 16, the DCA CSF concentration decreased to 11 lg/mL, indicating an elim- ination half-life for DCA in the CSF of approximately 5 days. No serum samples for DCA measurement were available.

    Meanwhile, the patient was treated with haloperidol and lorazepam. His confusional state improved within 2 weeks, but severe dysarthria remained. A bilateral facial nerve paresis (grade II), a profound sensory ataxia of arms and legs and a severe distal paresis of the legs were present on further neurological examination. He was unable to walk. Electromyography demonstrated a severe sensorimotor axonal polyneuropathy. In the following 8 months, all neurologic deficits gradually improved. Only a slight paresis of the foot extensors (MRC 5-) but no cognitive deficits remained."

    The story above (italics) illustrates my point perfectly. Taking DCA without carefully monitoring for side-effects and toxicities is, in my opinion, foolish. The 46 year old patient described above was let down by his 'alternative physician'. The patient suffered such serious neuropathy that they couldnt walk and were seriously mentally impaired. Upon admission, the doctors immediately ceased DCA and Vitamin A. The patient slowly recovered.

    Yes they did. Look at the x-axis of the graph. 60 months of daily DCA. This data actually comes from the Mori et al 2004 reference that you quoted. I pasted your quote with the reference to the Mori study below.
    (my bold) So the findings here are that patients take were able to take DCA for 5 years as long as they were closely monitored for toxicities and adverse effects.

    Should DCA be taken intermittently?: According to published clinical trials, No. If you read the DCA clinical trials, patients with mitochondrial disorders usually take DCA daily. This is an important point because someone with a mitochondrial disorder doesnt want to have peaks and troughs in mitochondrial energy production which could cause wild swings in their symptoms. Intermittent dosing of DCA may actually make symptoms worse as mitochondrial energy production goes up and down with the peaks and troughs of DCA.

    Does a drug half-life measured in hours means that it accumulates?: Not necessarily.
    It is well known from clinical trials that DCA at doses found to be clinically appropriate (10-50mg/kg/d) do not accumulate. Thats what both the table and the graph that I pasted earlier shows. The initial half life of DCA is short (~1.4h), but becomes longer with continual use (~9h). But even with a longer half life of 9h, only ~15% DCA would be left after 24h. So there is no accumulation of DCA which is what has been published in graph/table I pasted earlier.

    Lastly, as I mentioned in my earlier post, I dont advocate taking DCA unless it is under the supervision of a doctor.

    great discussion!

    Rodger
     
  17. XenForo

    XenForo

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    @rodgergrummidge Can you point me to a resource / webpage that explains the tests you refer to, so I can talk to my doc about it?
     
  18. rodgergrummidge

    rodgergrummidge

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    Hi @XenForo , some basic info below.

    A brief background on pyruvate metabolism, energy production and CFS: When energy demands are high (eg exercise) in a normal non-CFS person, carbohydrates are converted to pyruvate via glycolysis. The pyruvate then passes into the mitochondria where the pyruvate dehydrogenase enzyme converts it to acetyl-coenzyme A (acetyl CoA). Acetyl-CoA then enters the TCA cycle which is used to fuel energy production. A deficiency in any of these steps could result in reduced energy production and CFS-type symptoms. In fact, a number of studies have suggested that PDH activity is reduced in some CFS patients. Because impaired PDH activity results in the reduced conversion of pyruvate to Acetyl-CoA, pyruvate tends to 'pile up' in cells, particularly when energy demands are high (eg. during exercise). Under these conditions, pyruvate is converted to lactate. Excessive pyruvate accumulation and lactate production can lead to lactic acidosis, a condition that can lead to CFS-type symptoms.

    How can PDH deficiency be determined? PDH enzymatic activity can be measured directly in the test tube from a tissue/blood biopsy, but not many labs are able to perform such tests accurately. Initial investigations usually examine the blood/serum/plasma levels of both pyruvate and lactate. If both are elevated, PDH activity may be impaired (note however, that there are other conditions that can lead to lactic acidosis and so pyruvate/lactate measurements alone dont provide a definite diagnosis). Note that in some CFS patients, blood lactate and pyruvate can be normal, and increased levels are only found i) in the cerebral spinal fluid and/or ii) after exercise challenge. So an exercise challenge could be an important step in determining if a PDH deficiency exists.

    Lactate and pyruvate pathology tests: Lactic acidosis can be indirectly analysed by an increase in the anion gap (blood concentration of sodium minus those of chloride plus bicarbonate). Lactate can also be directly measured in the blood in most pathology labs. Blood pyruvate can also be directly measured in many path labs . Note that blood pyruvate levels are plagued by errors in collection and handling; furthermore, pyruvate is a very unstable compound. Pyruvate and lactate are often assessed by the Lactate:pyruvate ratio where ratios <10 or >20 would be considered abnormal and further testing would be required to determine if the cause is a PDH deficiency.

    DCA, a drug used for treating PDH deficiencies: Dichloroacetate (DCA) is a potent lactate-lowering drug that activates PDH activity. PDH activity is controlled by 2 enzyme 'switches': i) Pyruvate dehydrogenase phosphatase (PDP) that switches PDH on and ii) pyruvate dehydrogenase kinase (PDK) that switches PDH off. DCA works by 'jamming' the PDK 'off-switch', thus leaving PDH in the 'on-position'. Thus, some patients who i) have a PDH deficiency (which may include some CFS patients), ii) have decreased conversion of pyruvate to Acetyl-CoA and so decreased mitochondrial energy production and iii) lactic acidosis may benefit from the ability of DCA to activate PDH.

    DCA treatment and monitoring: At least one diagnostic criteria where DCA treatment could be considered would be in patients diagnosed with a PDH functional deficiency that also have increased levels of both pyruvate and lactate. Some CFS patients may fit this criteria with elevated pyruvate and lactate in the blood and/or cerebal spinal fluid. Daily treatment with DCA would normally commence with a 'low dose' and progress with a dose-escalation while monitoring symptoms. Response to DCA treatment (efficacy) would monitored by regular analysis of both pyruvate and lactate in the blood. A therapeutic effect would be measured as a return to normal levels of pyruvate and lactate in the blood or cerebral spinal fluid.

    Monitoring toxicities: Neuropathy is a potential toxicity described in a number of trials. I'm not sure how it would be tested, but your doctor should make sure to follow up with appropriate tests. Liver toxicities can be measured by examining liver enzymes in your blood tests. Similarly, kidney toxicities can be analysed by examining kidney enzymes/functions using standard pathology tests that your doctor will know. I would also monitor glucose levels as DCA may affect carbohydrate usage through the glycolytic pathway.

    That is a 'brief' overview, but there is probably much that I have either forgotten to include or just skimmed (getting tired), so please dont take my word as any ultimate authority.

    I'll try and find some info/webpages to post sometime later to point you in the right direction (starting to crash now). I'm sure others may also have some good suggestions/ideas. I hope it helps with some of your decisions in terms of diagnostics and treatments.



    best of luck

    Rodger
     
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  19. sinas

    sinas

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    hi @rodgergrummidge

    great discussion indeed, thanks for sharing your view. It is surprising to me that the overall level is only marginally increased after years. Also, what you shared resonated with my experience: even after I stopped DCA I noticed the improvements remained.

    With regards to the cancer patient: you are right, the doctors were careless and the fact that there were increasingly brutal side effects might not necessarily mean that DCA itself accumulates. I rather meant to say that the side effect themselves accumulate if that makes sense.

    I come from a different background (being a cancer patient and maybe.... a cfs patient) - the few oncologists in Canada and Us that are actually using DCA recommend breaks (for instance 5 days on, 2 days off) You must be right in pointing out the different use for mitochondrial disorder... which is closer to CFS than cancer.

    Have you tried DCA and if yes - did it help you?
     
    Last edited: Oct 30, 2017
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  20. XenForo

    XenForo

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    Argh, I tried DCA again today and I got back no energy from it. The thing I do, however, notice (or think I notice) is that when my chest hurts, it makes the pain / discomfort go away. Or maybe just coincidence.
     

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