ME/CFS and DCA/Meldonium Study (Glucose/Insuline, Brainblood flow)

[Hd-x]

I am not sure if it is the right subforum (or if "general treatments") for this ME/CFS study.
There was last year some rumor around Fibromyalgia + Metformin treatment and its Insuline crosslink (see "Fibromyalgia subforum")
Meanwhile there was also a small ME/CFS study around this topic as well: https://www.sciencedirect.com/science/article/pii/S0306987719309831

Some remarkable quotes from the study:
Sixteen ME/CFS patients, who did not benefit from treatment with DCA, were given Meldonium in increasing dose from 500 mg to 1000 mg per day. One patient interrupted treatment because of a feeling of agitation, and 7 patients (44%) reported a positive effect varying form moderate increase of energy and of physical capacity, to almost complete recovery of wellbeing. In one patient a NeuroSPECT examination was performed before and after treatment, which confirmed the enhanced blood supply to the prefrontal region, and the brainstem corresponding to the pons Varolii
Fig. 2. This patient presented decreased blood supply to the prefrontal brain cortex (Brodmann area 10) and the brainstem (pons Varolii) before treatment (orange-yellow colour on NeurosSPECT image, left panel). After 6 weeks of Meldonium treatment the blood supply to these regions was significantly increased

Six out of 13 patients (46%), who did not respond to DCA, reported subjective improvement of their health status and fatigue when using Meldonium. This may be related to the metabolic action of this medication on intracellular glucose transportation, and with its positive effect on cerebral blood circulation. In fact, blood supply to the prefrontal region was found to be significantly decreased in all ME/CFS cases, whereas some also presented decreased blood supply to the brain stem. Additional investigation is needed to confirm the improvement of blood supply to the prefrontal cortex, as observed in the example of one patient.


There was in past a Meldonium Tread@PR:
https://forums.phoenixrising.me/threads/meldonium-would-this-drug-help-me-cfs-patients.43518/
Some speculations, but seems noone (or not much) ever tried the drug.

I currently have some trouble with heart arrythmia that have to investigated closer and treated first,
so I am currently not the "best test candidate" for DCA or Meldonium. I am also not sure about DCA as CFS treatment, because I read somewhere concerns it could be cancerous.
So, I decided to try only Meldonium (in small dosages first) and what I can say about that the drug didnt fix my arrythmia problems, but even from the small dosage I notice an overall energy increasement (with less "sore" muscles), less brain fogging and surprisingly side effect: I can better breathing

Well, certainly I need now first to care about my arrythmia problems (they have nothing to do with Meldonium, I had this before trying the drug) and once the arryhtmia are somedays fixed, I will try Meldonium on other dosages to check out if it gives further improvements.
How the drug works:

 

[Diwi9]

Never heard of Meldonium before this post. I found this news clip on it.

 

[MonkeyMan]

Meldonium is available on Amazon.

https://www.amazon.com/Grindex-Mildronate-Meldoium-500mg-N60/dp/B07KMHWHXC

 

[Hd-x]

Yes, it is availible online from some sellers,
but the drug is since 2016 on the WADA list - so depending on the country it would be very wise to have a legal prescription (for medical use) from yours Doctor, because importing illegally such drugs could be expensive depending on the country if the customs office stops the parcel. Another thing to consider: You will never know if drugs offered somewhere in the web is really Meldonium or just fake products.

I got my Meldonium legally prescribed and ordered from the offical phamacy drugstore.

Never heard of Meldonium before this post.

This may have something to do that Meldonium is only approved for medical use in Latvia/Russia for treating stable angina pectoris, chronic heart failure (NYHA I-III functional class), chronic ischemic brain blood circulation and so on.
That heart drugs like many other medical drug classes e.g. diuretika, Glucocorticoide (Cortisone), strong pain drugs (Oxycodone), Insuline and so on, have been abused in sports and are prohibited during competitions isnt any news. ß-blockers are also on the WADA prohibeted competition list, noone would draw in such a case similar assocations like with Scharapowa.
If any (not so well known) athletes (mis)used Bisoprolol, Cortisone or any strong pain drugs and get disq. from sports it would not be worth any press note nor Youtube clip, but she is a popular tennis star, so the boulevard press maked some big noise & headlines around it.
That´s all.

Attached the original packed leaf sheet,
this should clarify things.

 

[Mary]

I currently have some trouble with heart arrythmia that have to investigated closer and treated first,

@Hd-x - have you looked into potassium? Persons with ME/CFS can have low intracellular potassium (which can cause arrhythmia) despite normal blood work. This post explains why.

A safe simple thing to do which can help determine if low potassium is a problem, is to drink 2 or 3 or even 4 glasses of low-sodium V8 or comparable vegetable juice, which is high in potassium. The low-sodium vegetable juices have more potassium than regular vegetable juices. Many people here have had low potassium symptoms relieved when they did this.

 

[Hd-x]

@Hd-x - have you looked into potassium? Persons with ME/CFS can have low intracellular potassium (which can cause arrhythmia) despite normal blood work. This post explains why.

Thx. for the link, Mary.
There were some circumstandings that may "perhaps" triggered the arrythmia and unbalanced electrolytes was also one off them that was coming in my mind. Well, first I dropped each drug/Sups to rule out few things, but doing so didnt help anything and was as next doing the following:
3g potassium (was too much, had to go down to 1.5g)
1g Magnesium (Mg)
+ COP (https://examine.com/supplements/creatinol-o-phosphate/ )
+ 125mg Meldonium
+ 3x daily Motherwort tincture (can help by thyroid triggered heartburn)
+ tapering the whole day with Xanax (to rule out CNS + mastcell (MCAS) triggered SVTs)
+ lots off pacing
I had much SVTs/VPB arrythmia over 1week, but today first time noticable less heart problems and the ECG looks imo better ( I buyed a mobile Pulox ECG from Amazon)
Well, I am carefully with any prognosis, but certainly I hope the arrythmia may perhaps during the next days with some luck "fade away".

 

[ljimbo423]

3g potassium (was too much, had to go down to 1.5g)

I was taking 3 grams of potassium a day and it gave me anxiety, insomnia and heart palpitations (arrhythmia). I completely stopped it for about 3 days before my symptoms completely went away.

I tried to take just 1.5 grams a few days ago and my symptoms can back but were milder. Again they stopped, within a day or so, after I stopped the potassium. Just sharing my experience.

 

[Mary]

@ljimbo423 - we are all so different! I take about 1000 mg a day of potassium gluconate in divided doses (including 200 mg. middle of the night) - without it I get symptoms of hypokalemia - muscle twitching/spasms, fatigue. I started taking potassium after starting methylfolate some 10 years ago (can't believe it's been that long!) initially boosted my energy, which was quickly followed by severe fatigue as my potassium tanked.

 

[ljimbo423]

@ljimbo423 - we are all so different! I take about 1000 mg a day of potassium gluconate in divided doses (including 200 mg. middle of the night) - without it I get symptoms of hypokalemia - muscle twitching/spasms, fatigue. I started taking potassium after starting methylfolate some 10 years ago (can't believe it's been that long!) initially boosted my energy, which was quickly followed by severe fatigue as my potassium tanked.

I use to take about 1,200 mg a day for the last couple of years, now I get heart palps at 1,500. Maybe it's because my diet is so high in potassium now. I eat a lot of bananas, avocados and some other high potassium foods.

Potassium does give me a lot of energy. I might just need to keep it at or below 1,000mg a day now.

 

[sb4]

@Hd-x I skimmed the paper but couldn't find out how long they took it for. How long have you been taking Meldonium? I believe @ShepherdK took it and felt better for 3 or so days before feeling worse.

 

[ShepherdK]

@Hd-x I skimmed the paper but couldn't find out how long they took it for. How long have you been taking Meldonium? I believe @ShepherdK took it and felt better for 3 or so days before feeling worse.

Yep! Here are my notes on Meldonium:

I ran Meldonium for five days total, 500mg twice a day. The second and third days were pretty great - tons of energy - however it made me eat quite a bit of carby/sugary foods. This makes sense, since it forces your body to favor glycolysis, which requires sugars to break down. Days 4 and 5 is where things went south - super fatigued, physically very cold, started developing liver pains. My guess is that an increase in glycolysis (and thus, an increase in pyruvate production, which wound up as lactic acid due to PDH issues) led to increased liver stress since the liver metabolizes lactic acid. I would put Meldonium into the "moderately dangerous" category of drugs for ME/CFS patients based on my own experiences + what we know about ME/CFS metabolic disturbances.

It wound up being pancreas pain, not liver pain, which is one of my typical ME/CFS symptoms. Also it appears that Meldonium is an immunomodulator, which isn't surprising given how it drastically changes underlying metabolic function. My Meldonium experiment led to a weird month-long ME/CFS crash where I experienced only some of my typical symptoms - largely just the physical ones - while preserving my mental function. It also messed my microbiome up quite a bit - finally got that back under control after a round of antibiotics and probiotics back-to-back.

Since then I have stopped trying to re-program my broken metabolism / immune function, and instead have embraced the broken components + added supplements to try and duct tape the holes. High dose ubiquinol (1200mg/day, broken into two doses) over the last 60 days seems to be making a major difference - it has restored my energy, mental function, gut health, and seems to be blocking PEM. I've been able to do housework without crashing (yay!), go to work, deal with stressful events, and largely live a normal sedentary lifestyle. I'm going to see if I can start a low-intensity workout plan in April or May - I've tried doing this before and have crashed out - but it's the only way to really test whether my condition really is improving.

The theory around high dose ubiquinol: 1) reduce oxidative stress, 2) boost underlying antioxidant enzyme function, and 3) decrease inflammation caused by 1&2. This study found benefits for ME/CFS symptoms at low doses (150mg/day), and this study found that doses of 1200mg/day have no adverse effects (but did find ubiquinol - improved cerebral mitochondrial oxidative metabolism). There seems to be a treasure-trove of tangential studies that investigate the importance of ubiquinol on immune system function, but haven't had the time to comb through them yet.

 

[Hd-x]

@Hd-x I skimmed the paper but couldn't find out how long they took it for. How long have you been taking Meldonium?

I am taking it since few days and not long enough to say something about long term effect,
my 125mg dosage is also much lower then @ShepherdK 1000mg total dosage regime.
Even if I wouldnt have those arrythmia problems, I usually start with (new) drugs @the lowest possible dosage and watch how it works, then I usually decide after a while if any further dosage increasing would make any sense or if it is better to go off.

About dosage lenght:
Usually Meldonium will be taken 4-6weeks and then you have to pause for some months.
A course off 2-3x times a year is recommended.

My Meldonium experiment led to a weird month-long ME/CFS crash where I experienced only some of my typical symptoms

I am really sorry to hear this - how long have you taken it at 2x500mg?
Certainly I was curious about this 4-6weeks only dosing regime and was researching some WADA documents.
It seems the drug is even if you dont take it for some time with doping tests detectable, so it seems the metabolides from the drugs stay for some time in the body and this may explain why it led unfortunaly in yours case to a long crash even after going off the drug.
The study itself, showed 44% improved from Meldonium and this means in return 56% did not improve ,
that it can obvisously in some cases worsen the condition.

I personally think, it is somewhat similar like with many drugs we try "offlabel" to fix ME/CFS,
there have been for example few cases getting well from Rituximab whereas other ME/CFS cases like Olaf Bodden (professional football player) got bedridden from the same drug.
Since there is unfortunatly very little ME/CFS research,
it is always a difficult decision if we should try or better avoid trying this or that drugs.
It is a decision that each one can at last only decide for itself.

 

[pattismith]

Very interesting thank you. I do have Ventricular Extrasystoles too, and I wish I could try it, but it's not available in my country.
i do think my VES (VPB) is related to my SFN, Do you know if you have small fiber neuropathy?

 

[Hd-x]

@pattismith
Besides postviral CFS, I was diagnosed FMS + MCAS ---> small fiber neuropathy is very common in both diseases.
I was never undergoing a small fiber biopsy, but I am convinced that I have it because I had lots off trouble with my lower body and exspecially my legs, feeds feel often like "burning" - even few stairs are enough to trigger this strange pain syndrom.
Sometimes I also have tingle like hundret ants are walking over my whole body.

I wish I could try it, but it's not available in my country.

The drug is also not availible in my country and I dont know the laws in yours country, so
I can still tell you how such things are regulated in my country:
If a drug with similar ingredient isnt availible and if there are reasons for medical use --> a doctor can prescribe such drugs and the local phamacy drugstore will in such case import the drug from the offical Latvia/RU phamacy drugstore.
Unfortunatly importing legally any drugs from country A to B for medical use isnt that cheap,
Meldonium costs in Russia still 5bucks, --> I paid 43Euro.
Certainly thats a huge price difference, but I think it is "ok" to be sure getting original medical drugs and not any fake products. I never tried SARMs or Peptides, but I had read some analysis from Sarms/Peptides that you can buy "here & there" online and many off this stuff was stretched (some products even contained pollutants)

 

[pattismith]

@pattismith
Besides postviral CFS, I was diagnosed FMS + MCAS ---> small fiber neuropathy is very common in both diseases.
I was never undergoing a small fiber biopsy, but I am convinced that I have it because I had lots off trouble with my upper body and exspecially my legs, feeds feel often like "burning" - even few stairs are enough to trigger this strange pain syndrom.
Sometimes I also have tingle like hundret ants are walking over my whole body.

yes I bet you have SFN. I didn't have the skin biopsy, but I have CFS/Fibro and the wrinkling finger test at zero (showing dysautonomia with peripheral nerve involvement most of the time).
I tried pulsed high dose of methylprednisolone with some good results but had to stop it because of the covid epidemic. I plan to try Agmatine or hydroxychloroquine (but feel concerned about it's cardiac toxicity!).
My country doesn't allow any drug import...

 

[Hd-x]

I am sorry that yours country didnt allow it.

I tried pulsed high dose of methylprednisolone with some good results but had to stop it because of the covid epidemic.

I have not tried it, but in the MCAS guidlines is a-lipoic acid(?) listed as treatment for neuropathic pain and paresthesia. Have you tried a-lipoic acid?
As secound line treatment* for neuropathic MCAS pain:
Benzos, Cannaboide, Omalizumab, Minozyklin. (*I dont know if this stuff also works if SFN is FMS triggered)

I do have Ventricular Extrasystoles too

What have you tried to get it fixed and were you able to get ridd off it?

 

[pattismith]

I am sorry that yours country didnt allow it.


I have not tried it, but in the MCAS guidlines is a-lipoic acid(?) listed as treatment for neuropathic pain and paresthesia. Have you tried a-lipoic acid?
As secound line treatment* for neuropathic MCAS pain:
Benzos, Cannaboide, Omalizumab, Minozyklin. (*I dont know if this stuff also works if SFN is FMS triggered)
What have you tried to get it fixed and were you able to get ridd off it?

-Dr T. Levine and Dr A.L Oaklander who are great neurologists think that SFN is the trigger of Fibro and ME/CFS, and so do I. I believe that from my own experience (from the inside) of a progressive illness lasting for 35 years.
-I take high dose of Lipoic acid since last august, but got no improvement in my arrhythmia;
-no way for me to take the drugs you quoted. Methylprednisolone was very effective to remove my pain syndrome.

 

[Hd-x]

i do think my VES (VPB) is related to my SFN,

Methylprednisolone was very effective to remove my pain syndrome.

If you guess there is a crosslink betwenn VES + SFN, so did Methylprednisolone also reduce yours VES/arrythmia?

 

[pattismith]

If you guess there is a crosslink betwenn VES + SFN, so did Methylprednisolone also reduce yours VES/arrythmia?

I couldn't say, because I don't have any machine that could register my VES frequency. I just have a classical ECG machine (so I need someone to help me for pushing buttons when I am supine, and I can't print too much or I will miss paper!). Can your mobile Pulox ECG tell you how many VES you have per hour?

 

[Hd-x]

@pattismith
Pulox is this ECG:
https://www.amazon.de/PM10-Mobiles-Einkanal-EKG-Gerät-Software/dp/B0123ZKICO/ref=sr_1_12?__mk_de_DE=ÅMÅŽÕÑ&dchild=1&keywords=mobiles+ekg&qid=1585411881&sr=8-12
It is in US/amazon.com avaiblibe as "Newgen" and some other brands, but it can still do 30sec ECG.
= so it is not the right ECG for yours porpuses.

The Healforce PC-80B ECG would be for you a better choice, it can measure up to 10h:
https://www.amazon.de/Healforce-PC-80B-EKG-Monitor-Datenrekorder-Software/dp/B016HYUO2G/ref=sr_1_11?__mk_de_DE=ÅMÅŽÕÑ&dchild=1&keywords=mobiles+ekg&qid=1585411881&sr=8-11