2 replies to this topic

[medicineman]

Mildronate is an anti-ischemic drug with good evidence. It reduces infarct size in MIs, improves anginal symptoms, and also has positive characteristics regarding neurological function.

How does it work? It inhibits buterobetaine synthase, and hence carnitine synthesis. As a matter of fact, administration of carnitine with mildronate in rat models of ischemia completely abolishes the benefits of mildronate. This favors the new evidence linking carnitine to atherosclerosis and vascular disease. IMHO, this is enough for me to forego carnitine supplementation until evidence disproves what seems like to me, the new prevailing theory of carnitines role in vascular disease.

Nonetheless, I'd appreciate some input on this issue.

sorry, I just realized I posted in the wrong subforum.

Edited by medicineman, 02 June 2014 - 04:46 PM.

[Metagene]

Seems like a good place to me. We can kill two birds with one stone.

TMA/TMAO

Intestinal microbiota metabolism of L-carnitine, a nutrient in red meat, promotes atherosclerosis.

http://www.ncbi.nlm....5301199/related

Suppression of intestinal microbiota-dependent production of pro-atherogenic trimethylamine N-oxide by shifting L-carnitine microbial degradation.

AIMS: Trimethylamine-N-oxide (TMAO) is produced in host liver from trimethylamine (TMA). TMAO and TMA share common dietary quaternary amine precursors, carnitine and choline, which are metabolized by the intestinal microbiota. TMAO recently has been linked to the pathogenesis of atherosclerosis and severity of cardiovascular diseases. We examined the effects of anti-atherosclerotic compound meldonium, an aza-analogue of carnitine bioprecursor gamma-butyrobetaine (GBB), on the availability of TMA and TMAO.

MAIN METHODS: Wistar rats received L-carnitine, GBB or choline alone or in combination with meldonium. Plasma, urine and rat small intestine perfusate samples were assayed for L-carnitine, GBB, choline and TMAO using UPLC-MS/MS. Meldonium effects on TMA production by intestinal bacteria from L-carnitine and choline were tested.

KEY FINDINGS: Treatment with meldonium significantly decreased intestinal microbiota-dependent production of TMA/TMAO from L-carnitine, but not from choline. 24hours after the administration of meldonium, the urinary excretion of TMAO was 3.6 times lower in the combination group than in the L-carnitine-alone group. In addition, the administration of meldonium together with L-carnitine significantly increased GBB concentration in blood plasma and in isolated rat small intestine perfusate. Meldonium did not influence bacterial growth and bacterial uptake of L-carnitine, but TMA production by the intestinal microbiota bacteria K. pneumoniae was significantly decreased.

SIGNIFICANCE: We have shown for the first time that TMA/TMAO production from quaternary amines could be decreased by targeting bacterial TMA-production. In addition, the production of pro-atherogenic TMAO can be suppressed by shifting the microbial degradation pattern of supplemental/dietary quaternary amines.

http://www.ncbi.nlm....3563705/related

This is my biggest reservation when it come to using mildronate as a nootropic. Any thoughts?

Degenerative events in retina and optic nerve induced by inhibition of carnitine transport.

http://www.ncbi.nlm....ubmed/25001658/

Interaction of mildronate with the mitochondrial carnitine/acylcarnitine transport protein.

http://www.ncbi.nlm....ubmed/18273902/

Edited by Metagene, 26 March 2015 - 08:43 PM.

[VerdeGo]

Have you taken mildronate before? If not, I wouldn't risk it. From my standpoint, you don't f*ck with the eyes, or with entire systems in your body that synthesize certain amino acids. I've taken acetyl-l-carnitine on many occasion, and it increased my energy and my focus. It eliminated the brain fog I didn't even know I had. It was as if I "woke up" after using carnitine for the first time. I haven't used it in awhile because you can build tolerance to the effects, and sometimes it affects sleep. 

 

There seems to be overwhelming evidence of the many benefits of carnitine (and acetyl-l-carnitine in particular) that far outnumber these newer studies. But it's still a major concern, and that is why I have completely stopped for now. Amino acids are like drugs themselves, and they can throw your brain off balance. It's best not to mess around with our own biological processes to break down carnitine. I also haven't seen any studies on long term effects.

 

Is it reversible if the drug is stopped?