Direct inhibition of retinoic acid catabolism by SSRIs

General Discussion
#1

I have to admit this was kind of a no shit moment seeing this.
So now you have all three drugs (anti-androgens, Accutane,SSRIs) interacting with retinoid homeostasis or metabolism.

Direct inhibition of retinoic acid catabolism by fluoxetine

Recent evidence from animal and human studies suggests neuroprotective effects of the SSRI fluoxetine, e.g., in the aftermath of stroke. The underlying molecular mechanisms remain to be fully defined. Because of its effects on the cytochrome P450 system (CYP450), we hypothesized that neuroprotection by fluoxetine is related to altered metabolism of retinoic acid (RA), whose CYP450-mediated degradation in brain tissue constitutes an important step in the regulation of its site-specific auto- and paracrine actions. Using traditional pharmacological in vitro assays, the effects of fluoxetine on RA degradation were probed in crude synaptosomes from rat brain and human-derived SH-SY5Y cells, and in cultures of neuron-like SH-SY5Y cells. Furthermore, retinoid-dependent effects of fluoxetine on neuronal survival following glutamate exposure were investigated in rat primary neurons cells using specific retinoid receptor antagonists. Experiments revealed dose-dependent inhibition of synaptosomal RA degradation by fluoxetine along with dose-dependent increases in RA levels in cell cultures. Furthermore, fluoxetine’s neuroprotective effects against glutamate excitotoxicity in rat primary neurons were demonstrated to partially depend on RA signaling. Taken together, these findings demonstrate for the first time that the potent, pleiotropic antidepressant fluoxetine directly interacts with RA homeostasis in brain tissue, thereby exerting its neuroprotective effects.

#2

That’s why I take it daily.

#3

Here’s the full study.

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A simplified schematic depicting links between retinoic acid (RA) signaling, which has recently been suggested to be involved in the modulation of affective behavior and possibly even the pathogenesis of depression ( A ), and central neurobiological processes (cytokine, monoaminergic, glucocorticoid and neurotrophin signaling) involved in the pathogenesis of major depressive disorder that are equally targets of RA signaling ( B ). Fluoxetine, which has also been demonstrated to alter cytokine, monoaminergic, glucocorticoid and neurotrophin signaling, is suggested to directly interact with RA homeostasis and RA signaling ( C ), constituting a novel mechanism of action potentially involved in fluoxetine’s neurotrophic actions

1 Like
#4

I have had very mixed reactions supplementing high dose vitamin a in the past.
Multiple times it made me feel like the life of the party, I mean literally being at parties and being the life of. I can recall these moments specifically. It put color in my skin, in my face, helped with night vision.
I think this is what will generate heat in some.

It also gave me eye floaters.
I also had a crash as some would call it, like what goes up must come down.
From absolutely elated and mentally quick to depressed.

It might not be as simple as taking vitamin a supplements.
If serum retinol was in range that would indicate lack of intake or storage of vitamin a isnt the issue.
There is a 3 step conversion process that ends in Retinoic acid.
From Retinol to Retinal to Retinoic Acid.
I’ll get tested tomorrow for serum retinol.

#5

Yeah its seems thermogenic, seems to raise my testosterone. Have had eyefloaters but it was after sneezing, which may be normal.

There’s a MS study where retinyl palmitate reduced fatigue at 25,000iu.

But It could be dangerous at high levels like most antioxidants.

I do believe my RA is too low in me, but I also think retinol is broken. I sometimes wonder if I changed to low RA and retinol, as accutane took over.

#6

Enhancement of Local Retionic Acid Signaling: A Pivotal Mechanism in Fluoxetine’s Pleiotropic Actions


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Taken together, numerous depression-related processes that are altered through fluoxetine treatment are equally classical targets of RA-signaling, strongly supporting a RA-dependent mechanism in fluoxetine’s pleiotropic mode of action

Pleiotropic : Producing or having multiple effects from a single gene

#7

I’m just so confused with all the information out there on vitamin A and retinoic acid

#8

A thought from that study,

chronic treatment with isoretinoin, the 13-cis-isomer and prodrug of retinoic acid that is used in acne therapy, is well known to cause severe depressive symptoms including suicide18. Given the tight regulation of RA homeostasis by local synthesis and differential local degradation via fine-tuned feedback mechanisms, it is not surprising that opposite effects can be observed for chronic, high-dose treatment with retinoids (inducing depressive-like behavior) and for acute, short-term treatment, which was reported to have antidepressive effects similar to those observed for fluoxetine17.

#9

Up-regulation of steroid biosynthesis by retinoid signaling: Implications for aging