Is POIS a version of CFS?

[Journey]

My symptoms are quite similar to it

[Muon]

Brainstem Abnormalities in ME/CFS: A Scoping Review and Evaluation of Magnetic Resonance Imaging Findings

POIS/CFS/POTS could be brainstem pathologies as in overlap of affected areas within the brainstem.

https://poiscenter.com/forums/index.php?topic=2683.msg23766#msg23766

[Muon]

And now this amazing article that explains why amino acids, vasodilators, immune mediators help both POIS and CFS. It is an irrigation issue!

https://www.healthrising.org/blog/2021/12/08/energy-chronic-fatigue-syndrome-immunometabolic-disease/

Stellate Ganglion Block: Blood flow.
https://www.healthrising.org/blog/2021/12/28/stellate-ganglion-long-covid-fibromyalgia

Discussion thread:
https://poiscenter.com/forums/index.php?topic=4098.0

[Progecitor]

I still believe that cellular senescence is the most logically sound explanation to our ails. This also explains the similarity in the pharmacological approach in the treatment of both CFS and POIS and several other diseases as well (e.g. asthma, multiple sclerosis, postcovid, etc). The most notable difference is in the affected tissues that makes it seem like they are completely different illnesses when in truth they stem from the same problem. In the case of POIS these cells are evidently located in the tissues and organs involved in reproduction. In my particular case I believe the origin is the prostate and with the senescence induced inflammation it can be simply described as prostatitis. For me prostatitis is a chronic phenomenon as I had POIS-like symptoms even after half a year without any sexual activity, so this phase may be more aptly considered as CFS. As said before following stimulation or stress senescent cells become activated, thus releasing even more cytokines than usual for a few days and this leads to the emergence of more severe POIS symptoms compared to the CFS phase when symptoms are rather subdued. As these cells normally have a role in sexual activity they are most potently stimulated by related activities and especially ejaculation. Other sources of stimulation like dietary elements are only secondary, however due to their additive and/or synergistic effect they can induce extreme POIS in case of acute onset and can be major determinants of symptom severity in the chronic phase of the disease.

Senescence also affects us on a psychological level which is almost funny when one considers how much our behavior resembles these cells. As senescent cells function incompletely they can't behave as normal cells do, so when they are put under pressure and expected to do things that a normal, healthy cell would be able to do easily, they can only respond by a kind of back-lash aggression. This is so much like the irritability that many of us describe. Senescence is also a normal process in aging, however it happens prematurely in our case. Still this makes us resemble a fatigued old man who lacks the capacity to do excessive physical work or at least act poorly when forced anyway. Somewhere it is even mentioned that senescent cells are kind of like zombie cells and in truth we ourselves our just like that after acute disease onset. So what I mean is that senescence is not only a cellular event, but is also reflected in our whole personality given adequate scrutiny. If only psychologists were more educated they should be able to easily diagnose people with senescence just by evaluating their behavioral patterns and with appropriate medications many of these diseases could be properly treated and static lives turned into lively ones.

[Progecitor]

I find it really intriguing that so many aphrodisiacs are effective in my case. Mastic gum is no exception as it is a traditionally known aphrodisiac. It is however not clear if all of these supplements'  aphrodisiac properties are only due to an increase in testosterone. I can only guess there is a convergence between aphrodisiacs and the mechanisms of anti-inflammatory pathways. Of course I have no clear proof of this, but one still has to wonder about the coincidence.

A most likely explanation to this probable connection lies in the overexpression of the NRF2 pathway. Although in the past I thought that NRF2 may not play a significant role in my problems recently I had to realize that it must be one of the factors at its core. This is nothing new of course as NRF2 has a central role in the anti-oxidant response mechanism, however I feel its function lacks proper emphasis and discussion.

A guy who cured himself from CFS made a great article about NRF2.
https://mybiohack.com/blog/nrf2-cirs-sensitivities

A lot of the things he highlights about NRF2 reminds me of things what POISers were talking about on the site. Although he wanted to point out some of the drawbacks regarding NRF2 activation, most of the article describes its beneficial effects. He lists loads of NRF2 agonist supplements, most of which helped me, though with varying efficacy. Most importantly NRF2 activation can decrease pro-inflammatory cytokines, which must be an important aspect of its effects. It is also indicated that NRF2 activation can play a role in libido enhancement and sexual organ protection, however it is less clear if this can be generalized.

Although not in the list, but Giloy/Guduchi also potently activates NRF2 and acts as an aphrodisiac.
https://www.researchgate.net/publication/354468485_Tinospora_cordifolia_Willd_Miers_Protection_mechanisms_and_strategies_against_oxidative_stress-related_diseases

Mastic oil and its constituents all induce NRF2.
https://www.mdpi.com/2076-3921/10/1/127/htm

There is abundant evidence that saffron also activates the NRF2 pathway.
https://www.researchgate.net/profile/Arian-Khoshandam/publication/361822359_Interaction_of_saffron_and_its_constituents_with_Nrf2_signaling_pathway_A_review/links/62ebcdb80b37cc34476dd64b/Interaction-of-saffron-and-its-constituents-with-Nrf2-signaling-pathway-A-review.pdf

It may also explain why exercise intolerance develops as (premature-) aging turns NRF2 signaling defective which impairs proper responses to exercise.
https://www.frontiersin.org/articles/10.3389/fphys.2017.00268/full

It was a bit surprising to see Lansoprazole as an activator as it also helped me in the past. Well there are a number of other interesting inducers, but too many to list them here, so check at the link.
Some controversies do exist though. For one apigenin, quercetin and luteolin may work dose-dependently, so their effects are less predictable. Another one is that fenugreek was indicated as an inhibitor, but it is also a source of dioscin and diosgenin both of which clearly increase NRF2 expression. Needless to say this also makes maca an NRF2 inducer.
https://saudijournals.com/media/articles/SJBR_410_318-323.pdf

It also seems contradictory that testosterone is indicated to reduce NRF2 while a number of supplements that increase NRF2 are actually testosterone boosters like damiana, mangosteen, maca, tribulus, zinc, beta-ecdysterone, tongkat ali and probably more.

He also proposes a regime based on hormesis which means an intermittent intake of a combination of NRF2 inducers that may act in synergy for an increased benefit, however the episodic intake may help to avoid the potential pitfalls of prolonged NRF2 overexpression.

Another good deal of NRF2 inducers can be found at Table 1. in the following article. It is quite a good thing that it also details many trace elements, vitamins and amino acids.
https://www.mdpi.com/1422-0067/21/12/4484/htm

Well this latter review provides much more information than just about NRF2. It puts our whole problem in a context as I believe that premature aging (senescence) of sexual organs is the most likely cause of POIS.

It is common knowledge that covid-19 causes pro-inflammatory cytokine storm and it was discussed earlier that NRF2 agonist agents may serve to ameliorate this state.
https://poiscenter.com/forums/index.php?topic=3733.msg40429#msg40429

NRF2 signaling can be also connected to the earlier model of metabolic syndrome.
https://www.nature.com/articles/s41598-017-08899-7

Some additional information that could serve to complement this:
1. Prolonged endurance exercise can significantly reduce Serca2a expression if NRF2 is deficient.
https://www.frontiersin.org/articles/10.3389/fphys.2017.00268/full
2. Combined PPARA and NRF2 upregulation causes the downregulation of SREBP-1c and NF-kB.
https://onlinelibrary.wiley.com/doi/abs/10.1002/mnfr.201700479
3.  PGC-1alpha potentiates the function of NRF1 and NRF2.
https://www.sciencedirect.com/science/article/pii/S1550413111002117
4. NRF2 activation inhibits TGFbeta signaling.
https://openheart.bmj.com/content/8/1/e001663.full
5. AP-1 subunit c-Jun can activate NRF2-induced transcription, while c-Fos can suppress it.
PPARG and estrogen receptor alpha can directly bind to NRF2 and suppress its activity.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7369905/
6. Estrogen can cause oxidative stress. SULT1E1 inactivates 17beta-estradiol. Oxidative stress induces SULT1E1 through Nrf2 activation. Estrogen also activates Nrf2 as control.
https://cancerci.biomedcentral.com/articles/10.1186/s12935-019-0826-x

[Progecitor]

Severe anxiety may be treated with a combination of N-acetyl-glucosamine (NAG), flaxseed oil and turmeric. There are some additional possible anxiolytics recommendations by a CFS sufferer.
https://forums.phoenixrising.me/threads/completely-eliminated-my-severe-anxiety-symptoms-with-three-supplements.18369/

[Progecitor]

A new study suggests that the mere impairment of spermatogenesis, a process also involving meiosis, may itself lead to a significant deterioration of the individual’s overall health. Hopefully researchers will realize that POIS is most likely a human role model for this exact phenomenon.

New Study Reveals How the Reproductive System Can Accelerate Aging and Worsen Health
The new study, led by researchers from the University of Pittsburgh and UPMC and published in the journal Aging Cell, found that disrupting a process called meiosis in C. elegans reproductive cells caused a decline in the worms' health and triggered an accelerated aging gene signature similar to that of aging humans.
"This study is exciting because it’s the first direct evidence that manipulating the health of reproductive cells leads to premature aging and a decline in healthspan," "The implications of this finding are profound: It suggests that the status of the reproductive system is important not simply to produce children, but also for overall health."
While the consequences of aging on fertility are well known, research in the past two decades has started to show that reproductive fitness also has an impact on human aging and health.
They discovered that animals with mutations in meiosis genes had shorter lives than their non-mutated counterparts. The mutants also had worse overall health ratings, including premature reductions in mobility, muscular function, and memory.
"The exciting part of this healthspan work was that these animals also showed signs of disrupted protein homeostasis," said Ghazi. "Disruption to the balance of proteins inside cells is at the heart of age-related neurodegenerative diseases, like Alzheimer's disease."
When the researchers improved protein homeostasis in the worms, some loss of lifespan was prevented. These findings point to disrupted proteostasis as a key mechanism linking reproductive health and aging.
"In human terms, it's like someone in their early 20s having the physical appearance, physiology, and gene signatures of a 70-year-old," explained Ghazi. "Messing with meiosis has dramatic effects on healthspan and accelerates aging in C. elegans."
https://scitechdaily.com/new-study-reveals-how-the-reproductive-system-can-accelerate-aging-and-worsen-health/

[Muon]

Treatment survey for ME/CFS.
https://twitter.com/organichemusic/status/1614127798087565312

[b_jim]

Amazing Muon
You're still doing a fantastic job after so many years

[Muon]

Amazing Muon
You're still doing a fantastic job after so many years

It actually makes me sad when I think about how much time I have spent on this forum.

Here is a tweet from Michael VanElzakker:
https://twitter.com/MBVanElzakker/status/896841175973457922