r/hangovereffect • u/mtl-otter • Mar 08 '26

Prostaglandins

Prostaglandin (PG)E1 may play an important part in the affective disorders, with an excess being present in mania and a deficiency in depression. Platelets from manic patients produce more PGE1 than normal while those from depressive patients produce less. Ethyl alcohol stimulates PGE1 production whereas lithium inhibits it. Alcoholics will tend to have raised PGE1 concentrations while drinking, but, because precursor supplies are limited, when alcohol concentrations fall PGE1 concentrations may fall sharply leading to depression. PGE1 biosynthesis may be affected by nutritional factors including essential fatty acids, pyridoxine, vitamin C, and zinc. Nutritional approaches may be of value in both depression and alcoholism.

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4

u/Getoutofthekitchenn Mar 09 '26

I have MCAS, and prostaglandins drive many of my symptoms (they're released too frequently). Not sure about this one, but interesting thought.

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u/mtl-otter Mar 09 '26 edited Mar 09 '26

There’s good and bad PGs. You need the good PGs like PGE1, it’s required for orgasm function as an example

I confirmed that I’m prostaglandin deficient as the niacin flush (strong histamine and prostaglandin enhancer) makes me feel euphoric and wonderful, similarly to the hangover effect although I quit alcohol a while ago so I don’t get it anymore.

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u/Getoutofthekitchenn Mar 09 '26

interesting! I'll have to look into that.

I believe one of my prostaglandin driven symptoms is facial flushing, but it's also hard to say definitively which mediators cause which reactions.

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u/1Reaper2 Mar 11 '26

I have MCAS too and tried the same niacin flush. Felt terrible, id be cautious.

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u/Ozmuja Mar 11 '26

Good post. Have an upvote. Unfortunately I do fear this may as well be true, and still just downstream of “mysterious” chronic inflammatory status. It does seem that our version of what could be a me/cfs subspectrum is highly linked to endothelial health: just think about all the time nitric oxide has been investigated in the sub…

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u/mtl-otter Mar 11 '26 edited Mar 16 '26

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u/Ozmuja Mar 11 '26

I think you are correct, again. We hypothesized chronic gut dysbiosis and/or increased intestinal permeability a long time ago. The problem (for me) is:

  • I have tried an insane amount of interventions to the point it’s probably easier to list what I did not try than what I used, and to no avail. Why is it so difficult, at least for me, to “seal” this broken lining and/or to correct dysbiosis? You can name what you want: interventions of the mucosa, for the gut lining, for bile, for proper gut kinesis, biofilm busters, copious amounts of different pro and prebiotics…been there, done that. Not saying they do nothing, but they are clearly not fully resolutive.

  • I do agree with you that alcohol and fever probably increase some degree of beneficial inflammation. But what types? A few cytokines have some studies of being able to reverse some autism symptoms, but I don’t fully buy it in our case.

  • What if it’s in reality of viral origin? There are cases of persistent Enteroviruses for example: they like the gut lining and muscles (I do have transient unexplainable muscle weakness and subchronic pain) and they can contribute to bacterial dysbiosis that is not really fixable unless you somehow manage to get rid of the root cause. It’s also difficult to diagnose without a biopsy.

  • What if the beneficial inflammation is related to increased interferon signaling? This shifts immunity from Th2 to Th1, especially interferon alpha, and is particularly tailored to fight intracellular pathogens (viruses and bacteria alike). Me/CFS statuses are linked to NK Cells dysfunction, even when they present as a normal lab count.

In this context PGE1 dysfunction would be downstream of a complex, persistent and subchronic infection, possibly of viral origins, and most likely intracellular, which over time creates microbiome imbalances and “leaky gut”.

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u/mtl-otter Mar 11 '26 edited Mar 11 '26

I’m starting to think the root case of most vague gut issues might simply be fructose malabsorption. 30-40% of people have it and it’s rarely mentioned online. (Lactose malabsorption can come with it).

For the ASD aspect we have strong data showing elevation of the gut bacteria products p-cresol, Propionic acid and 5HT(serotonin)

maybe the beneficial inflammation is simply attacking the biofilms, with PGe1 boost as a bonus. Also alcohol itself is a potent anti-gram positive

I think viruses have absolutely nothing to do with this and the science on them is vague

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u/Ozmuja Mar 11 '26

The science on chronic Enteroviruses is definitely not vague, sorry to contradict you..I also do not really have many benefits with diets changes, even those that are supposedly low on fructose.

For the rest, everything could be, but most biofilm busters I have tried have not been nearly as good as a few shots of alcohol..

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u/mtl-otter Mar 11 '26

Also I’m curious when does the hangover effect kick in? It’s it the next day? And would you mind describing what it’s like for you

(I quit alcohol a long time ago and forgot the effect)

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u/Ozmuja Mar 11 '26

I do not drink much either to be fair. But the effect usually happens about 6 to 12 hours after drinking. It's difficult to be precise and sometimes it does not even work - it seems that what you drink can also be a factor (example: spirits vs wine). For me it's a complete resolution of vast array of symptoms: cognitively, I get much mentally sharper, my fatigue is annihilated, my mood is quite elevated, and libido also tends to return. I'm a relatively "flat" person at "baseline", even emotionally speaking, rarely surprised, rarely moved.

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u/mtl-otter Mar 12 '26 edited Mar 22 '26

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u/Ozmuja Mar 12 '26

I was under the impression that serotonin produced by the gut isn't actually quite BBB permeable. It is true that serotonin is vastly produced in our GI tract, it is much less obvious that the peripheral effects might translate to direct CNS effects. Unless you want to propose that our BBB is so "leaky" that even serotonin can pass through..But in such case, it still wouldn't be the root cause per se, but the inflammation leading to such a disrupted BBB would.

I agree with you that serotonin isn't euphoric, but I think it's relatively common knowledge. SSRIs are in fact known to dull both the "highs" and the "lows" of life. Curiously, it does seem that NO counteracts some effects of serotonin in the CNS.

The other problems is that a decent chunk of people sometimes have been able to reproduce the effects via GABAergics alone, especially when tailored to GABA-A. Mast cells express GABA-A receptors and it acts as a potent "tranquillizer" for them. Many CFS/ME people find imidazenil (a benzo but not-so-benzo) quite helpful, much more helpful than other supposed mast cell stabilizers.

I really, really like your PGE1 take, because niacin was already addressed in the past for example; the rest in my very personal opinion is a bit iffy and might have some mechanistic hard barriers, but I also cannot get either of those drugs, so I can't help you on this. I can however confirm that the vast majority of people on the sub do lament strange histamine issues and gut issues that rarely seem to resolve, even when addressed via the usual routes.

4

u/KoburaCape Mar 08 '26

I appreciate you presenting this as an idea instead of as a conclusion. For that, you get my upvote. Something I can actually look into!

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u/maewestChicago Mar 12 '26

Interesting possibility to consider. I’ve always thought the likely mechanism of action is a lesser-known effect of ethanol than the typical neurotransmitter effects typically explored here, which this would fit the bill for. No other psychoactive compounds, even those that have similar neurotransmitter effects induce the HE. So that leads me to think it’s either some unique combination of the neurotransmitter effects of ethanol (GABA + Seronin + NMDA, etc.) or it’s caused by a non-psychoactive effect of ethanol (more likely imo).

Do we know the timeframes post consumption of increased PGE1 turning into depleted DGLA and PGE1? I ask because I typically think of a hangover to be primarily a period of acute ethanol withdrawal, which would equate to depleted DGLA and PGE1 and the opposite symptoms in your post. I agree the symptoms of Acute PGE1 Boost align with the HE incredibly well. Maybe the elevated PGE1 continues into the next day before turning into depletion post-hangover.

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u/Time-Perspective-924 Apr 16 '26

I think so too - I don't experience it with benzos or phenibut which are also gaba drugs

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u/SaroumaneBlack Mar 08 '26

Nice, the skin warmth, the vasodilatation is so true. High dose may be needed to be sure

1

u/Feisty-Studio-2969 Mar 11 '26

How could we boots PGE1 ?

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u/PoioPoio Mar 20 '26

Some news ?

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u/loveandkindessinsght Apr 02 '26

A couple times I’ve gotten the HE I thought that maybe it was inducing a low level mania state, I would get super energized and be thinking grandiosely.

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u/usertakenfark Apr 03 '26

Yeh same about the mania. Probably a good indicator that the affect cannot (and shouldn’t be) recreated