Carnitine Is A Glucocorticoid Agonist, Acts Like Cortisol

haidut

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Most people on the forum know of Ray's views on carnitine due to the fact that it stimulates fat oxidation. The drug mildronate, which Ray has written about, is a carnitine antagonist and is used as a performance enhancing drug by many athletes.
This study shows that there is another good reason to avoid carnitine. It binds to and activates the glucocorticoid receptor similar to cortisol.

http://www.ncbi.nlm.nih.gov/pubmed/12824292

"...Millimolar concentrations of L-carnitine, which were not cytotoxic in vitro, significantly reduced the whole cell binding of [3H]dexamethasone to GRalpha by decreasing the affinity of this receptor for its steroid ligand. At the same concentrations, L-carnitine was able to trigger nuclear translocation of green fluorescent protein (GFP)-fused human GRalpha and transactivate the glucocorticoid-responsive mouse mammary tumor virus (MMTV) and TAT3 promoters in a dose-dependent fashion. This effect was solely dependent on the presence of glucocorticoid-responsive elements on the promoter and on the expression of functional GRalpha by the cell. Finally, similarly to glucocorticoids, L-carnitine suppressed tumor necrosis factor-alpha (TNFalpha) and interleukin-12 release by human primary monocytes stimulated with lipopolysaccharide ex vivo. Both GRalpha transactivation and cytokine suppression by L-carnitine were abrogated by the GRalpha-antagonist RU 486. Taken together, our results suggest that pharmacological doses of L-carnitine can activate GRalpha and, through this mechanism, regulate glucocorticoid-responsive genes, potentially sharing some of the biological and therapeutic properties of glucocorticoids."
 

jb116

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I wonder then, would common cortisol antagonists also work against carnitine as well?
 

haidut

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haidut

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I wonder then, would common cortisol antagonists also work against carnitine as well?

I posted a study on niacnamide lowering cortisol, and niacinamide is a known functional carnitine antagonist. So, the direct (receptor) opposition is unlikely but functionally drugs that promote and oppose fatty acid oxidation will probably be antagonists of each other. Good point btw.
 

jb116

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I posted a study on niacnamide lowering cortisol, and niacinamide is a known functional carnitine antagonist. So, the direct (receptor) opposition is unlikely but functionally drugs that promote and oppose fatty acid oxidation will probably be antagonists of each other. Good point btw.
Nice, it is indeed two birds with one stone as they say. Niacinamide is great, and that study you posted confirmed that after couple of years of personal experimentation.
 

NathanK

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Yep, and it's not just her. Pretty much every athlete from Eastern Europe knows about mildronate and a few other performance enhancing drugs like some serotonin antagonists for which there is no doping test yet:)
I just thought of my next idealabs supplement recommendation :). Mix it with acetazolamide and MB (in DMSO of course) and call it Oximax
 

haidut

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I just thought of my next idealabs supplement recommendation :). Mix it with acetazolamide and MB (in DMSO of course) and call it Oximax

That's a pretty good idea, but acetazolamide is a controlled drug in the USA. I have to find some research chemical that inhibits carbonic anhydrase is not labelled as a drug yet.
 

NathanK

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That's a pretty good idea, but acetazolamide is a controlled drug in the USA. I have to find some research chemical that inhibits carbonic anhydrase is not labelled as a drug yet.
Not going to get my hopes up too high, but this sounds pretty exciting.

CA Inhibitors and Activators book: Carbonic Anhydrase

These might help you find leads.
CAI Natural sources: Carbonic anhydrase inhibitors from the pericarps of Punica granatum L. - PubMed - NCBI

CAI Research: The development of topically acting carbonic anhydrase inhibitors as anti-glaucoma agents. - PubMed - NCBI
 

haidut

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Not going to get my hopes up too high, but this sounds pretty exciting.

CA Inhibitors and Activators book: Carbonic Anhydrase

These might help you find leads.
CAI Natural sources: Carbonic anhydrase inhibitors from the pericarps of Punica granatum L. - PubMed - NCBI

CAI Research: The development of topically acting carbonic anhydrase inhibitors as anti-glaucoma agents. - PubMed - NCBI

Thanks, I will look into some of the synthetic ones that are not drugs yet. But in the meantime, famotidine and thiamine are both pretty effective as carbonic anhydrase inhibitors.
Famotidine inhibits carbonic anhydrase (CA)
Thiamine is a carbonic anhydrase inhibitor as effective as acetazolamide
 

Stryker

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i have been experimenting with 2x1000mg of mildronate daily the last week, very smooth lasting energy as long as you are consuming ample carbs.

it takes away the muscular soreness and fatigue after a days work thats for sure
 

Dhair

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Isn't there evidence that carnitine can repair lipid metabolism?
Or would lipid metabolism be repaired just by increasing the metabolism in general/repairing mitochondria?
 

DaveFoster

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@haidut You ever try mildronate (meldonium)? What do you think of it?
 

haidut

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@haidut You ever try mildronate (meldonium)? What do you think of it?

Haven't tried that one but I don't see anything in its effects that could not be achieved with niacinamide. In higher doses, niacinamide suppresses fatty oxidation directly by antagonizing SIRT1.
 

DaveFoster

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Haven't tried that one but I don't see anything in its effects that could not be achieved with niacinamide. In higher doses, niacinamide suppresses fatty oxidation directly by antagonizing SIRT1.
Niacinamide came to mind. +1 for longevity, thanks.
 
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