Meldonium - would this drug help ME/CFS patients ?

[hvac14400]

@helen1
that was like 3 years ago, so i don't quite remember anything now. but my goal (as always) was to increase energy level and this drug wasn't effective for my biochemistry - that's all i can tell.
i used up to 2g per day for about month or two.
and i think it raised my (already increased) intracranial pressure.

 

[Snow Leopard]

Google translate of the above Russian quote:

Physiological concentrations of carnitine have saturating effect on carnitine-palmitoyl transferase I, and the increase in the dose does not increase the transport of acyl groups of fatty acids into mitochondria involving the enzyme. However, this leads to the activation of carnitine-acylcarnitine translocase (which is not saturated with physiological concentrations of carnitine) and fall intramitochondrial acetyl CoA concentration, which is transported to the cytosol (acetylcarnitine through the formation). In excess of cytosolic acetyl-CoA is subjected to acetyl-CoA carboxylase to form malonyl-CoA, which has the properties of indirect inhibitor of carnitine-palmitoyl transferase I. Reduction intramitohondrialnogo the acetyl-CoA is correlated with increased levels of pyruvate dehydrogenase, pyruvate which allows and restricts oxidation products lactate. Thus, carnitine antihypoxia action due to blockage of the transport of fatty acids into mitochondria is dose-dependent and appears at higher doses, whereas lower doses have a specific vitamin activity.

This reasoning seems a bit sloppy. The saturation effect simply means that further fatty acid metabolism (from an already elevated level) is limited. Any subsequent inhibition of CPT-1 is just normal part of the feedback system and does not suggest that fatty acid metabolism will be reduced beyond that which results from normal oscillations of biochemical activity.

In any event, the description above also suggest that high doses of carnitine has the opposite (biological) effects as taking Mildronate.

 

[hvac14400]

@Snow Leopard

so you saying that

>blockage of the transport of fatty acids into mitochondria

>>does not suggest that fatty acid metabolism will be reduced beyond normal oscillations

right?

 

[Scarecrow]

Is anyone else apart from hvac going to try it?

I'm thinking about it.

Has anyone tried beetroot juice as Dr Shepherd linked?

Love beetroot juice. I make it fresh and drink it once or twice a week. Haven't notice any effect.

 

[Snow Leopard]

@Snow Leopard

so you saying that

>blockage of the transport of fatty acids into mitochondria

>>does not suggest that fatty acid metabolism will be reduced beyond normal oscillations

right?

No, I'm not saying that at all.

 

[hvac14400]

Love beetroot juice. I make it fresh and drink it once or twice a week. Haven't notice any effect.

i don't know why, but any NOx stimulator like arginine, citrulline or beet juice makes me weaker in the gym - am dropping reps left and right : \
and at the same time i feel myself pretty normal in ordinary life, any attempt to measure blood pressure always fails with normal readings, like 118/75 or 125/80.
no positive effect on cfs.

 

[hvac14400]

@Snow Leopard

ok, your translation of my quote contains this part

Thus, carnitine antihypoxia action due to blockage of the transport of fatty acids into mitochondria is dose-dependent and appears at higher doses, whereas lower doses have a specific vitamin activity.

i know that not all acids are blocked - long or short/middle chains only (i forgot which), but isn't it sufficient reduction of normal fat metabolism?

 

[hvac14400]

Google translate of the above Russian quote:

In any event, the description above also suggest that high doses of carnitine has the opposite (biological) effects as taking Mildronate.

no, coz mildronat does the same thing:

Милдронат обратимо ограничивает скорость биосинтеза карнитина из его предшественника - гамма-бутиробетаина. Вследствие этого нарушается карнитин-опосредованный транспорт длинноцепочечных жирных кислот через мембраны митохондрий без воздействия на метаболизм короткоцепочечных жирных кислот. Это означает, что милдронат практически не способен оказывать токсического действия на дыхание митохондрий, так как не может полностью блокировать окисления всех жирных кислот. Частичная блокада окисления жирных кислот включает альтернативную систему производства энергии - окисление глюкозы, которая значительно эффективнее (на 12%) использует кислород для синтеза АТФ.

it blocks transport of long chain fatty acids into mitos, thus activating glycolysis.
and this quote explains and supports may previous saying, that high doses of carnitine shifts your metabolism towards glycolysis.

 

[Deltrus]

I'm learning that carnitine shuttles fatty acids into the mitochondria for the Kreb cycle, but mitochondria also use these fatty acids to make up all sorts of things such as lipid membranes. Thus, it is essential for healing. Mildronate might prevent healing to some extent.

 

[tinlizzy]

Meldonium is just a drug that prevents the heart from damage in case of overload:

Meldonium (INN), trade-named as Mildronate among others, is a limited-market pharmaceutical, developed in 1970 by Ivars Kalviņš, Latvian Institute of Organic Synthesis (USSR), and manufactured primarily by Grindeks of Latvia and several generic manufacturers. It is distributed in Eastern European countries as an anti-ischemia medication.

 

[JHF1]

Sorry for digging this old thread out...
I wonder if it couldn't also make sense (in some cases) of combining Meldonium with Carnitine supplementation,
as it seems it's positive effects (if it really has) are also related to other targets and also to a build up of Carnitine's direct precursor. So maybe one could have both if used in combination.