Sharapova and Meldonium.

Topher

New Member
You're right Remy. I just read a similar article and did a Google search for the drug and CFS which led me to your post here. Unfortunately I don't see any info about CFSers that have tried it. So also interested to hear more about this!
 

Who Me?

Well-Known Member
@Remy. I've looked at Rupharma before. I think I ruled them out because they only use western union or bank transfer and that's such a hassle and $$$.

Look at www.pharmashipping.net. Or maybe it's dot com

I ordered from them when Sergey ran it and we used PayPal but I think it changed hands and they too are western union.
 

Who Me?

Well-Known Member
Nah, this time I actually meant her candy line...no candy for me but weird Russian drugs? Sign me up! Lol!
I was just hunting for my roxi. I know not weird enough. I thought I had a big box but only found 20. Who knows where I put it.

See if it'll knock back my mpn.
 
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Seanko

Well-Known Member
Some information from the Guardian newspaper in Britain
What is meldonium and why did Maria Sharapova take it?

  • Meldonium is used to treat ischaemia: a lack of blood flow to parts of the body, particularly in cases of angina or heart failure.
  • It is manufactured in Latvia and only distributed in Baltic countries and Russia. It is not approved by the Food and Drug Administration for use in the United States and is not authorised in the rest of Europe.
  • It increases blood flow, which improves exercise capacity in athletes.
  • Wada found “evidence of its use by athletes with the intention of enhancing performance” by virtue of carrying more oxygen to muscle tissue.
 
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Seanko

Well-Known Member
[bimg=500|no-lightbox]http://news.images.itv.com/image/file/920594/stream_img.jpg[/bimg]

Mechanism of Action from Wikipedia

The chemical name of meldonium is 3-(2,2,2-trimethylhydraziniumyl)propionate,[17][18] a structural analogue of γ-butyrobetaine, with a NH group replacing the CH2 at the C-4 position of γ-butyrobetaine. γ-Butyrobetaine is a precursor in the biosynthesis of carnitine.[19]

The mechanism of action of meldonium is to act as a fatty acid oxidation inhibitor, presumably by inhibiting enzymes in the carnitine biosynthesis pathway such as γ-butyrobetaine hydroxylase.[20] γ-Butyrobetaine hydroxylase is an enzyme that belongs to the 2-oxoglutarate (2OG) oxygenase superfamily and catalyses the formation of L-carnitine from γ-butyrobetaine.[21][22]

X-ray crystallographic and in vitro biochemical studies suggest meldonium binds to the substrate pocket of γ-butyrobetaine hydroxylase and acts as a competitive substrate/inhibitor to form malonic acid semialdehyde, dimethylamine, formaldehyde, 3-amino-4-(methyamino)butanoic acid and (1-methylimidazolidin-4-yl)acetic acid,[23][24] likely via a Steven's type rearrangement mechanism.[25]

Mildronate is a potent γ-butyrobetaine hydroxylase inhibitor, with a half maximal inhibitory concentration (IC50) value of 62 μM.[26] Meldonium is an example of a non-peptidyl substrate mimic inhibitor for human 2OG oxygenase.[27]

Meldonium has also been shown by NMR to bind to carnitine acetyltransferase.[28] Carnitine acetyltransferase belongs to a family of ubiquitous enzymes that play pivotal roles in cellular energy metabolism.[29] Meldonium therefore may act as a regulator of energy metabolism. Meldonium is a relatively weak inhibitor to carnitine acetyltransferase (when compared to γ-butyrobetaine hydroxylase), with an inhibition constant (KI) of 1.6 mM.
 

Remy

Administrator
Carnitine transport has already been shown to be deficient in CFS patients.
http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2796.2010.02341.x/full

I do not see a benefit in further limiting fatty acid metabolism.
I recommend steering clear of mildronate/meldonium, I strongly suspect it would make things worse.
Somehow inhibiting carnotine transport with Meldonium is producing almost exactly the opposite effects of whatever is inhibiting the carnotine transport in MECFS. I wonder if it's a different part of the pathway? It seems so from what I've read so far but I'm no expert. It just seems odd that inhibition on the one hand of MECFS causes extreme fatigue and neurological problems and inhibiting it on the Meldonium side causes an enhancement in athletic performance to the point where it has become a banned substance in sport.

From https://jakegshelley.wordpress.com/2016/03/03/what-is-melodoniummildronate/

literature review showed that Meldonium is an effective anti-ischemic drug with further applications in immunomodulation and in the treatment of neurodegenerative disorders and bronchopulmonary diseases.

Meldonium is a structural analogue of the carnitine precursor, gamma-butyrobetaine. Carnitine is a key regulator of fat metabolism, since it is required to transport fatty acids into the mitochondria for fatty acid breakdown via beta-oxidation. Meldonium affects carnitine metabolism by inhibiting its biosynthesis and transport and this protects mitochondria from an overload of Fatty Acid metabolites. Meldonium also increases gene expression related to glucose metabolism and thereby stimulates the aerobic oxidation of glucose (2).

Meldonium decreases the beta-oxidation of fatty acids and shifts cellular metabolism towards the oxidation of carbohydrates, which requires far less oxygen per ATP molecule than beta-oxidation of fatty acids. This sparing of oxygen could be of huge benefit under hypoxic conditions. The most obvious benefits have been seen in the treatment of ischemic heart disease, but there is evidence to suggest that Meldonium could be equally beneficial under the low oxygen conditions induced by intense endurance exercise (3).

One review (4) of the effects of Meldonium on exercise performance listed the following benefits:

  • Decreased levels of lactate and urea in blood
  • Improved economy of glycogen: level of glycogen increased in the cells during the long-lasting exercise
  • Increased endurance properties and aerobic capabilities of athletes
  • Improved functional parameters of heart activity
  • Increased physical work capabilities
  • Increased rate of recovery after maximal and sub-maximal loads
  • Activates CNS functions and protects against stress
 

Seanko

Well-Known Member
Latvian manufacturer issues statement on Meldonium
The Latvian company Grindeks, which manufactures meldonium, told the Associated Press that four to six weeks is a common course. “Depending on the patient’s health condition, treatment course of meldonium preparations may vary from four to six weeks. Treatment courses can be repeated twice or thrice a year,” the company said in an emailed statement.

“Only physicians can follow and evaluate patient’s health condition and state whether the patient should use meldonium for a longer period of time.”
While Grindeks has previously stated that the drug can provide an “improvement of work capacity of healthy people at physical and mental overloads and during rehabilitation period,” the company said that it believes the substance would not enhance athletes’ performance in competition and might even do the opposite.

“It would be reasonable to recommend them to use meldonium as a cell protector to avoid heart failure or muscle damage in case of unwanted overload,” the company said. Grindeks said that, in sports activity, the drug slows down how the body breaks down fatty acids to produce energy.

Source: Guardian via Associated Press
 

Remy

Administrator
that four to six weeks is a common course
Hmmm...and yet Sharapova has been using it for just shy of a decade.
I've also read it can be used because it somehow masks EPO use.
Really, can't we get some of these elite athlete's doctors and training coaches interested in MECFS? They must be light years ahead in terms of performance.
 

Remy

Administrator
Full text available...

CNS Drug Rev. 2005 Summer;11(2):151-68.
Mildronate: an antiischemic drug for neurological indications.

Sjakste N1, Gutcaits A, Kalvinsh I.

Abstract

Mildronate (3-(2,2,2-trimethylhydrazinium)propionate; MET-88; meldonium, quaterine) is an antiischemic drug developed at the Latvian Institute of Organic Synthesis. Mildronate was designed to inhibit carnitine biosynthesis in order to prevent accumulation of cytotoxic intermediate products of fatty acid beta-oxidation in ischemic tissues and to block this highly oxygen-consuming process.

Mildronate is efficient in the treatment of heart ischemia and its consequences. Extensive evaluation of pharmacological activities of mildronate revealed its beneficial effect on cerebral circulation disorders and central nervous system (CNS) functions. The drug is used in neurological clinics for the treatment of brain circulation disorders. It appears to improve patients' mood; they become more active, their motor dysfunction decreases, and asthenia, dizziness and nausea become less pronounced.

Since the brain does not utilize fatty acids as fuel other mechanisms of action of mildronate in CNS should be considered. Several reports indicate the possible existence of an alternative, non-carnitine dependent mechanism of action of mildronate. Our recent findings suggest that CNS effects of mildronate could be mediated by stimulation of the nitric oxide production in the vascular endothelium by modification of the gamma-butyrobetaine and its esters pools. It is hypothesized that mildronate may increase the formation of the gamma-butyrobetaine esters. The latter are potent cholinomimetics and may activate eNOS via acetylcholine receptors or specific gamma-butyrobetaine ester receptors.

This article summarizes known pharmacological effects of mildronate, its pharmacokinetics, toxicology, as well as the proposed mechanisms of action.
 

Merida

Well-Known Member
@ Remy
Like you idea about athletic experts having some knowledge beneficial to us. The very best surgeons, chiropractors, and physical therapists are often those who treat elite athletes.
 

Snow Leopard

Active Member
While Grindeks has previously stated that the drug can provide an “improvement of work capacity of healthy people at physical and mental overloads and during rehabilitation period,” the company said that it believes the substance would not enhance athletes’ performance in competition and might even do the opposite.
It would almost certainly reduce the performance of endurance athletes.

Such drugs are banned to protect the health of athletes just as much as any speculative performance advantage (or masking the effects of other drugs as mentioned already) - when athletes take a conucopia of speculative drugs and supplements that may or may not improve performance and may or may not have long term detrimental effects.

Somehow inhibiting carnotine transport with Meldonium is producing almost exactly the opposite effects of whatever is inhibiting the carnotine transport in MECFS.
I'm not sure this is true. The end result (reduced fatty acid metabolism) is the same. The speculated effects on performance have not been demonstrated in any randomised trial.
 

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