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Meldonium - would this drug help ME/CFS patients ?

Discussion in 'General Treatment' started by sue la-la, Mar 7, 2016.

  1. sue la-la

    sue la-la

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    What is Meldonium, and what does it do to your body?

    http://mobile.abc.net.au/news/2016-...does-it-do-to-your-body/7228670?section=sport

    Brain Performance:
    • Meldonium is associated with improved blood flow, including to the brain. At least three studies have shown mood-improving effects as well as increased learning and memory performance.
    Central Nervous System:
    • At least two studies have shown enhanced activation of central nervous system (CNS) functions. One review also found it protects against stress.
    Effects on Oxygen Use:
    • Meldonium has been found to improve endurance properties and aerobic capabilities of athletes.
    • It helps stop mitochondria ("powerhouses" of cells) from being overloaded by fatty acid breakdown, by stopping carnitine activites. It instead shifts focus towards the breakdown of carbohydrates, which requires less oxygen.
    • One review also found increased glycogen in the cells during exercise.
    Heart Performance:
    • Meldonium has anti-ishemic properties, meaning it can prevent strokes caused by lack of blood flow. It is used clinically to treat angina, myocardial infarction and chronic heart failure.
    Kidneys:
    • One review of the effects of meldonium found lower levels of lactate and urea in blood
     
    Last edited: Mar 7, 2016
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  2. Snow Leopard

    Snow Leopard Hibernating

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  3. alicec

    alicec Senior Member

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    I agree. Unless I supplement carnitine, my fatty acid oxidation markers on an OAT test are appalling.
     
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  4. Abha

    Abha Abha

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    Hi sue-la-la
    This is the drug that Sharapova has admitted to taking(in the news today)I have copied this from a website...Sharapova had partnered with the brand since 2004.

    Meldonium is manufactured in Latvia. It is used in Lithuania and the Russian Federation but is not approved by the U.S. Food and Drug Administration. A number of athletes have tested positive for the drug since Jan. 1: Abeba Aregawi (Ethiopian-born, Swedish nationality, 1,500-meter world champion), Eduard Vorganov (Russian cyclist), EndeShaw Negesse (Ethiopian marathoner), Ekaterina Bobrova (Russian ice dancer) and Olga Abramova (Ukranian biathlete).
     
  5. Scarecrow

    Scarecrow Revolting Peasant

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    The Sharapova story got me mulling about this yesterday, too.

    Interestingly, the paper that @Snow Leopard linked to hypothesises that reduced formation of carnitine palmitoyltransferase-I is responsible for the deficiency in long-chain acylcarnitines measured.

    Paradoxically, this review (http://onlinelibrary.wiley.com/doi/10.1111/j.1527-3458.2005.tb00267.x/epdf) states that:

    yet mildronate (meldonium) also seems to reduce long-chain acylcarnitines.

    Meldonium may be worth a closer look. My metabolic knowledge is woeful and I don't have time to search further just now but this looks intriguing.
     
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  6. Snow Leopard

    Snow Leopard Hibernating

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    Cartinine deficiency leads to chronic muscle weakness and muscle pain:
    https://en.wikipedia.org/wiki/Systemic_primary_carnitine_deficiency

    Carnitine palmitoyltransferase I deficiency leads to hypoketotic hypoglycemia.
    https://en.wikipedia.org/wiki/Carnitine_palmitoyltransferase_I_deficiency
    Carnitine palmitoyltransferase II deficiency is interesting in that the effects are transient -
    https://en.wikipedia.org/wiki/Carnitine_palmitoyltransferase_II_deficiency

     
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  7. Scarecrow

    Scarecrow Revolting Peasant

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    The paper you linked didn't show reduced CPT-I but proposed that it could be responsible for reduced levels of long-chain acylcarnitines, if I interpreted it correctly. There is some evidence that meldonium increases levels of CPT-I.
     
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  8. Deltrus

    Deltrus Senior Member

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    I'd be scared to take it because if your problem is due to b vitamins etc then your body would be struggling to metabolize energy as it is. Limitting strategies for your body to make energy might completely fuck you over. This drug lowers carnitine in cells so that your body is forced to rely on glycolysis. I believe pyruvate, the product of glycolysis, is also a fatty acid, but is very short, and it goes through different pathways. I tried to learn further today but got much too tired.

    All I know for sure is that getting you b vitamins right is essential before even thinking about trying out this drug. B1 and I think a few more are extremely important for these pathways and they wont function properly at all if you are deficient.
     
    Last edited: Mar 10, 2016
  9. Scarecrow

    Scarecrow Revolting Peasant

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    Regardless to what's is or isn't going on with carnitine and fatty acid metabolism (ok, that's a big 'regardless'), meldonium's useful mechanism of action seems to be to shift to an alternative energy pathway, particularly in conditions of hypoxia, which may be another of our problems.
     
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  10. Snow Leopard

    Snow Leopard Hibernating

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    Yes, there are other possibilities to explain the paper I linked, something else effecting the carnitine levels in the cytosol for example.


    Yes, it is a dynamic system - if you suppress one thing, the cell tries to compensate another way. The end result of meldonium is still a suppression of fatty acid metabolism. Boosting levels of CPT-I is not desirable in itself if fatty acid metabolism is suppressed overall.

    Another example:
    http://cpt.sagepub.com/content/17/2/215.short

    Also note that much of the literature talks about meldonium having benefits in the context of hypertension-related heart disease. The hypoxia case they are talking about is post-ischemia.

    Another study:
    Potential Therapeutic Role of L-Carnitine in Skeletal Muscle Oxidative Stress and Atrophy Conditions
    http://www.hindawi.com/journals/omcl/2015/646171/

    There are plenty more along those lines. All this suggests to me is that taking Moldronate/Meldonium is likely to harm more than help us.
     
    Last edited: Mar 8, 2016
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  11. Christopher

    Christopher Senior Member

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  12. anciendaze

    anciendaze Senior Member

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    @Christopher

    Haven't gone very deep into the subject. At the moment I'm trying to find ways of avoiding the reduced perfusion and hypoxia in the first place. Reperfusion injury is not at all trivial, and seems to have deep evolutionary roots, which implies it would not be easy to deal with. This may be a personal idiosyncrasy caused by my own serious trouble with delayed orthostatic hypotension. At the moment I'm looking more at autonomic problems. It looks easier to modify control than to directly intervene in fundamental metabolic processes.

    Have to run now to make a doctor's appointment, which you will understand consumes most of my activity for the day.
     
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  13. hvac14400

    hvac14400 fatty & acid : )

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    taking high dose of l-carnitine (approx more than 2-3g a day) also shifts your metabolism into glycolisis - don't you know that? so what - it feels just great, don't be scared and try this - you'll not die.

    mildronat helps too, in the same way, but gives less pronounced effect - i've tried them both in very high doses.
     
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  14. Deltrus

    Deltrus Senior Member

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    By what mechanism? Carnitine isn't used in glycolysis, it is used in the branched amino acid catabolism pathway, it should do the opposite of what meldonium does. Supplementing alcar would make your BCAA catabolism pathway more effective and add more options while meldonium removes options and makes the BCAA catabolism pathway weaker.

    Here's the only study I got searching "l carnitine glycolysis": http://www.ncbi.nlm.nih.gov/pubmed/11099658

    Edit this study says it increased glycolysis but only in diabetic rats which is weird. http://www.ncbi.nlm.nih.gov/pubmed/7781011

    Edit apparently it boosts glycolysis through donating acetyl groups and NOT from the carnitine. http://www.ncbi.nlm.nih.gov/pubmed/1740427

    At any rate alcar adds while meldonium takes away. Safety cannot be correlated.
     
    Last edited: Mar 10, 2016
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  15. hvac14400

    hvac14400 fatty & acid : )

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    i can't post links till 5 posts so sorry, and that article in russian anyway : )
    but you need pure carnitine - not acyl one.
     
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  16. charles shepherd

    charles shepherd Senior Member

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    From the discussion about this drug on the MEA Facebook page:

    THE MARIA SHAROPOVA EFFECT – COULD THAT BANNED DRUG BE ANY USE TO M.E. OR POTS SUFFERERS?

    Anonymous writes:

    I would be interested to hear Dr Shepherd's take on the drug meldonium which has been in the press recently due to a certain tennis player.

    The reason I ask is that the press reports are stating that it increases blood volume which made me wonder if it could be of some use to me / pots suffers? Has this drug ever been prescribed, tested in this manner?

    Please can you make my question anonymous

    Thanks

    Write a comment...

    Anon - We have had quite a few queries about this drug today - so I have prepared a reply that covers the main queries. This is it:

    I have followed the media story you refer to today and read up the pharmacology of this drug

    From the information available it appears to increase tissue oxygenation and may be of benefit in the treatment of angina and heart failure. But it does't increase blood volume.

    Meldonium is made in Latvia and seems to be used in Eastern Europe and Russia

    It is not used here in the UK or in the USA and does not have FDA approval in the USA

    So I think there may be some doubts over the actual efficacy (and possibly safety) in relation to heart disease

    And I think there are far better drugs available here in the UK for heart disease than this one

    As with any heart drug that acts in this way, it may have an effect on exercise tolerance and increase excerise capacity - but there are other drugs and foods (good scientific evidence here for beetroot juice:http://www.ncbi.nlm.nih.gov/pubmed/24089377) and supplements that have similar properties

    So I don't think this particular drug could be regarded as a high priority item for a clinical trial in relation to ME/CFS

    Good summary of key points here:

    http://www.theguardian.com/.../meldonium-maria-sharapova...

    Dr Charles Shepherd
    Hon Medical Adviser, MEA
     
  17. Deltrus

    Deltrus Senior Member

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    Hmm alright I'l have to take your word on it.
     
  18. hvac14400

    hvac14400 fatty & acid : )

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    by this one

    terapy6_ris2.gif
     
  19. hvac14400

    hvac14400 fatty & acid : )

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    merylg likes this.
  20. helen1

    helen1 Senior Member

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    I found this about meldonium:

    The action of the drug is to prevent accumulation of cytotoxic intermediate products of fatty acid beta-oxidation in ischemic tissues and to block this highly oxygen-consuming process. Mildronate has a beneficial effect on cerebral circulation disorders and central nervous system functions. Mildronate is prescribed for patients with decreased working efficiency.

    It sounds good to me, written that way. Is anyone else apart from hvac going to try it? Has anyone tried beetroot juice as Dr Shepherd linked?

    @hvac14400 Could you give us more details of the effects you had with meldonium? And how long did you use it for?
     
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