TLDR version : I think POIS primary cause is immune, and can cause allergy-like and flu-like symptoms. In addition to that, i believe that the pro-inflammatory immune messengers produced can cause neurological, cognitive and emotional symptoms. Also, other conditions can worsen some or all of POIS symptoms.
Hi Labyrinth and everyone else,
In order to answer your poll question, that is "Do You think POIS is an immune disease or neurological illness", I would need another option in the poll to reflect my view: for me, it is both immune and neurological, WITH a relation to each other.
Here is why I think POIS is both an immune and a neurological disorder, that can also be worsen by other conditions as well. (note: my hypothesis on the physiopathology is a bit complex, but isn't POIS a complex disorder ? )
I will use my clusters of symptoms to help explain my view, so those who wants a more detailed description of each clusters and a list of symptoms by clusters can go to
http://poiscenter.com/forums/index.php?topic=2027.0 . Links are also given if you want to read more about certain key points.
Cluster 1, allergy-like symptoms, are clearly immunological in nature to me ( Type I hypersensitivity reaction ,
http://en.wikipedia.org/wiki/Type_I_hypersensitivity ) Sneezing and itching, for example, are allergy symptoms.
Cluster 2, Flu-like symptoms, are also of immunological symptoms in my hypothesis of POIS physiopathology ( Type IV hypersensitivity reaction,
https://en.wikipedia.org/wiki/Type_IV_hypersensitivity ). Muscle aches and sore throat, for example, are of the same immune origin than in an actual flu.
Dr Waldinger has proposed in his papers, as a matter of fact, that POIS implied both a Type I and a Type IV hypersensitivity reaction, so I didn't come up with this by myself.
In these hypersensitivity reactions, a massive amount of pro-inflammatory immune messengers are produced, like cytokines, TNF-alpha, and so on, and this will produce other reactions in the body and brain. That leads, in my view, to the two other clusters of symptoms.
Cluster 3, containing both cognitive symptoms / encephalopathy-like symptoms and other, peripherical, pellagra-like symptoms, are of neurological origin, in my opinion. However, in my hypothesis, those symptoms are a secondary effect of the hypersensitivity reaction mentioned above. For example, the pro-inflammatory messengers will produce inflammation in many part of the body, including in the brain. Inflammation in the brain is called "encephalitis". POIS cognitive symptoms like brain fog, memory problems, speech impairment, lack of mental focus, as well as others, can all be symptoms of encephalitis ( see
http://answers.webmd.com/answers/1173257/what-are-encephalitis-symptoms-and-signs ). Those symptoms are of neurological nature. I think it is also clear that the majority of the peripheral symptoms of cluster 3, like muscle twitch, muscle weakness, tingling in the extremities, photophobia, are of neurological nature.
Cluster 4, emotional/psychological symptoms, are, to me, also caused by the effects of the pro-inflammatory immune messengers in the brain. I have already talked a lot about this on the forum, and this aspect has also been studied and researched, as numerous papers have been published about the effect of immunological messengers as a cause of depression and anxiety. To simplify the explanation, those immune messengers can upregulate certain enzymes - which means they will raise the degree of activity of certain key molecules in specific metabolic pathways. The net results will be that the usual molecular activity of the brain will be changed, and some substances, like some neurotransmitters, will be less produced, and some other substances, like toxic products, will be produced in larger than normal quantities, all this causing imbalance and altered functioning of the brain. In all those papers, 2 enzymes are always referred to, the IDO and TDO enzymes, affecting the metabolic usage of tryptophan ( I have already written on the forum about that, in more details, like at
http://poiscenter.com/forums/index.php?topic=1988.msg15559#msg15559 , so you can go there for a more complete explanation) These changes are of enough large scale to produce major changes in mood and personality. The chemistry of the brain seems to be so affected in POIS acute phase that for a few days, depression, anxiety, mood instability and the like are full blown, and then slowly goes back to baseline, whatever your "normal" state is. So, even if underlying cause is immunological ( cytokines and other immune messengers massive production), some end effects are clearly neurological, and some would say "mental" symptoms - I prefer to say emotional and psychological symptoms.
To further clarify my position concerning cluster 3 and cluster 4 symptoms origin, I want to say that for me, ejaculation, not orgasm, is the trigger of the immune reaction. I believe that the neurological/brain imbalance in the brain in POIS has nothing to do with the neurotransmitters frenzy of orgasm itself, and has everything to do with ejaculation, has a trigger of the hypersensitivity reactions. Those hypersensitivity reactions will not only produce allergy and flu-like symptoms, but also cause some specific changes in the body functioning at the metabolic level, leading to cognitive and emotional symptoms. I have at least 2 arguments for this. First, many POIS sufferers will get some POIS symptoms after a semen leak caused by a bowel movement, or also by pre-ejaculation emissions, as in edging. You will agree that no O has occurred in those situations, but POIS did. Also, you can have POIS even in the case of ejaculatory anhedonia, that means an ejaculation with no pleasure felt or anything happening in the brain during ejaculation - again, no O, but POIS symptoms. Also, POIS symptoms seems minimal in case of a "dry orgasm", that is, an O without ejaculation ( although in this last case, this is not a common occurrence, so data are few).
For those wondering about how all this would tie with the vagus nerve hypothesis, just remember that the vagus is a cranial nerve, taking input directly from the brain, and, the other way around, bringing inputs in the brain about the state of the body, in order to keep things stable. If the brain has lost its balance, no wonder that the vagus nerve signals will be impaired and cause abnormal symptoms in the body.
Finally, by reading what all the members have shared over the years on this forum, I came up with a list of conditions and situation ( co-morbidity factors) that can worsen some or all of POIS symptoms:
- Inflammatory issues in the gut, which causes both a stronger/worst immune reaction, and also impair absorption of much needed substances for maintaining balance ( like tryptophan, for example). So, as I understand it, any IBS, leaky gut syndrome, SIBO, name it, will worsen POIS.
- Methylation cycle issues and Nitric oxyde/peroxynitrite cycle issues: having many MTHFR mutations, lower BH4, or anything related, can account for many if not the majority of POIS symptoms ( for example, see
http://www.methyl-life.com/symptoms-of-mthfr.html ). Some members, like Kurtosis, have achieved a very high level of control over their POIS symptoms by using supplementation that help restore normal balance in methylation and NO cycles, along with implementing healthy diet and other healthy habits ( you can read the interesting posts of Kurtosis about that, on this forum). Many multi-symptoms disorders, similar to POIS, like CFS, ME, fibromyalgia, autism, and others, are suspected of being linked to methylation issues and NO cycle issues, too.
- Low testosterone or progesterone levels. Those two hormones promote immune tolerance, so I think their lack will worsen the hypersensitivity reaction I see at the base of POIS. Some members have achieved high level of control with testosterone (Demografx ! ) or progesterone replacement therapy
- Atopy will worsen any dermatological issues ( Waldinger has noted in his first paper on POIS that the majority of POIS sufferers were also atopic). More on atopy at
http://en.wikipedia.org/wiki/Atopy - Secondary, POIS-induced anxiety, depression and psychological problems. After some years with POIS, having realized that one of the most pleasurable and gratifying experience as a human being has become the source of major debilitating symptoms that transform your life in a nightmare for a few days to a few weeks, this will cause, for the POIS sufferer, anxiety, depression and other psychological issues on its own, independant of any O and any POIS symptoms themselves. So, when the metabolic effect of actual POIS kicks in, it is added to the chronic state of depression and anxiety that having this condition is causing to us. In clear, the added impairment on mood and anxiety, after ejaculation, piles up with what already remains as a constant level of anxiety and depression. Obviously, any pre-existing conditions, independent of POIS, like anxiety, social problems, depression issues, will add up as well with what POIS causes on its own.
- Unhealthy diet: speaks for itself. Intakes of MSG, aspartame, preservative agents, and other chemicals do no good for a healthy balance. HFGS, fructose, and the like either. Gluten, milk protein, and other products can be bad too, if they trigger an immune response, adding to the POIS-induced immune reaction ( hypersensitivity reactions add one to another and pile up). Other unhealthy habits, like a bad omega-3 to omega-6 ratio, will increase inflammation. Many POISers have reported improvement when adopting a healthy diet
- Increased or low vagal tone: if you already have an unsteady autonomic nervous system, POIS won't fix that...on the opposite, you will experiment worsened symptoms
I have listed other comorbidity factors as well, like weak hepatic function, low dopamine, stress/chronic high levels of cortisol, intake of statins or beta-blockers ( increasing muscle pain), and so on. I will stop at that, I have mentioned the most frequent I have read about on the forum.
Sorry for this long post. I came with that since last November, so it is hard to sum up many months of analysis in just a few lines. If you are currently experimenting a brain fog, I have put a TLDR version at the beginning :-)
You are all welcomed to comment on my hypotheses. I have no proof that this is correct, or not. However, adding TDO inhibitors ( like quercetine and milk thistle) along with IDO inhibitors ( like rosmarinic acid and turmeric) to my POIS relief method has been highly beneficial for my emotional symptoms, and others as well. Is it just plain luck, or is there anything true about my hypothesis? I cannot tell for now.
Anyway, I hope my comments will be of help in resolving the POIS puzzle.
Quantum
Poll