Post Orgasmic Illness Syndrome (P.O.I.S.)

POIS Cause/Treatment Discussions => Auto-Immune Causes and Treatments => Topic started by: trusttheprocess on April 09, 2017, 09:16:13 AM

Title: New ideas about POIS and review of excitotoxicity
Post by: trusttheprocess on April 09, 2017, 09:16:13 AM
I know everyone has been a little depressed lately about the POIS study, so I would like to share some progress I made recently reading some very interesting medical articles that have made me rethink the role of histamine and genetic factors in POIS.  If these factors are implicated in POIS like I believe, then this will explains the symptoms pretty well and even points to some possible treaments.  But it will also mean POIS is still very complicated, which it why this post is long.  Also what I've read lately changes my opinion on the promise of VNS stimulation as a cure, and shows why there might be some possible underlying medical issues in POIS.

Overview
I think POIS is caused by genetic factors, and the complex immune reaction in POIS involves systemic inflammation due to dysfunctional immune cells and environmental facotrs, mast cell activation and neuroinflammation from microglia activation (which causes a breakdown of the blood brain barrier), and production of the enzyme Indoleamine 2,3- Dioxygenase (or IDO).  IDO also depletes Tryptophan (which is eventually converted to Serotonin and Melatonin) and causes dysfunctions in the Kynurenine Pathway (KP), which seems to cause a large portion of POIS symptoms.  This is induced by IDO for two reasons.  First, to produce Kynurenine, as it is strongly neuroprotective and immunosupressive (although later on it leads to neurotoxicity and vagus nerve-blocking inflammation).  Second, IDO causes Tryptophan depletion to prevent T cell responses against your body.  This suggests POIS triggers some strong neurotoxic and autoimmune response, and the IDO and Kynurenine helps in the short run buts leads to many days of recovery.  Furthermore, the IDO depletion of Tryptophan leads to a temporary state of Pellegra, and at the same time the Kynurenine Pathway shifts from NAD+ to Kynurenine.  This is important because niacin is rapidly converted to NAD+.  NAD+ declines with aging and is associated with mitochrondrial dysfunction.  This can lead to free radical production and excitotoxicity, as energy is needed to pump Calcium ions out of neurons to prevent excitotoxic damage.  The neural tissue is the main energy consumer of the human body, and imbalance in energy homeostasis can lead to neuronal deficit and, eventually, to neuronal death.  The very same immune dysfunctions that caused the autoimmune reaction leads to various antibodies being produced in a desperate attempt by the body to restore homeostasis. 

This final stage of POIS would be much like lupus (with the production of multiple antibodies), with the main difference being that POIS flares are triggered by orgasm instead of sunlight, infections, or stress like in lupus.  Anything the body could possibly interpret as causing this cascade could be targeted, especially sperm cells (antibody causes IBS symptoms), tryptase (and possibly even histamine as both chemicals activate microglia causing brain fog and neuroinflammation), chymase, CRH and other mast cell products, glutamate and glutamate receptors, acetylcholine receptors, calcium and potassium channels, anti-basal ganglia antibodies, anti-nuclear antibodies, and possibly even mitochondrial antibodies (is a target in Sj?gren's syndrome, because mitochrondria produce many damaging free radicals).
Title: Re: New ideas about POIS and review of excitotoxicity
Post by: trusttheprocess on April 09, 2017, 09:20:22 AM
Causes of POIS

I. Lack of Immune Tolerance:  Immune Tolerance is a complex series of mechanisms that impairs the immune systems ability to mount responses against self antigens.  Failure or breakdown of immunological tolerance leads to autoimmune disease, while high tolerance can lead to cancers and infections that avoid elimnation.  Certain parts of the body such as the brain and testes have evolved immune priveledge, meaning they are able to tolerate the introuduction of antigens without an inflammatory immune response. (Wikipedia)

2. Molecular Mimicry: "Molecular mimicry can be a mechanism for instigating an autoimmune disease.  Certain antibodies and T cells can interact with dissimilar antigens found in microbes and in host cells. More than 5% of over 800 monoclonal antibodies derived from multiple RNA and DNA viruses, as well as from a large number of T cell clones, engage in such interactions.  Molecular mimicry provides an explanation for the genetic observation that identical twins rarely manifest the same autoimmune disease and the documented epidemiologic evidence that microbial and/or viral infections often precede autoimmune disorders." (Check out this article for a good description and pictures explaining this.  Pubmed ID: 24694269)

While there are many factors that can lead to failed immune tolerance and the body being fooled by molecuar mimicry, I'd like to focus on the dsyfunction of Regulatory T Cells and Dendritic Cells, as they've been implicated in systemic inflammation.

"While systemic inflammation may be induced by multiple external factors, research suggests that a lack of control by tolerogenic dendritic cells and T-regulatory cells (Treg) is possibly the primary risk factor for the development of system inflammation. In functioning immune responses, T-helper and T-cytotoxic cells are activated by presentation of antigens by antigen-presenting cells (APCs). Chief among these are dendritic cells (DCs).  When a DC presents an antigen to a Treg cell, a signal is then sent to the nucleus of the DC, resulting in the production of IDO. IDO inhibits T cell responses by depleting tryptophan and producing kynurenine.  Individuals susceptible to developing chronic systemic inflammation appear to lack proper functioning of Treg cells and TDCs. In these individuals, a lack of control of inflammatory processes results in multiple chemical and food intolerances, autoimmune diseases and many other symptoms and diseases." (Wikipedia)

In an attempt to try and confirm the involvement of DC's, T reg cells and the possibility of immune priveledge-related disease, I used three genome analysis tools (23andMe, Promethease, and LiveWello) to check my results for all DC's and Treg associated genes.  Results are attached, gene frequency is listed, and statistically significant genes are colored. I had one rare mutation in the gene Foxp3, considered to be the master regulator of the regulatory T cells, and could cause a disease called IPEX syndrome.  All of my TNF receptor-associated factor 1 genes (TRAF1) were yellow.  For my Dendritic cells, I had 4 red SNPs and 3 yellow SNPs which could I'd imagine could lead to molecular mimicry. There's a lot more info in two images I've attached to this post, including the 23andMe data, population data and an explanation of what DC and Treg Cells do and what each gene is responsible for.

Often times genes need to be triggered by environmental factors, and the same is true for autoimmune diseases.  One bacteria that could activate microglia (cause neuroinflammation) and fool the body with Molecular Mimicry at the same time is  Streptococcus pneumoniae.  Streptococcus pneumoniae is both a frequent colonizer of the upper respiratory tract and a leading cause of life-threatening infections such as pneumonia, meningitis and sepsis.  It is commonly found in the nasopharynx of asymptomatic carriers, and, under certain still unknown conditions, can invade the brain.  The organism also causes many types of pneumococcal infections other than pneumonia. These invasive pneumococcal diseases include bronchitis, rhinitis, acute sinusitis, otitis media, conjunctivitis, meningitis, sepsis, osteomyelitis, septic arthritis, endocarditis, peritonitis, pericarditis, cellulitis, and brain abscess.  It is toxic to microglia and astrocytes and may be in part responsible for brain injury during meningitis.  One study investigated it's effect on brain injury:

"S. pneumoniae infection triggered atherogenesis, led to systemic induction of interleukin (IL) 1, and profoundly exacerbated (50-90%) ischemic brain injury in rats and mice, a response that was more severe in combination with old age and atherosclerosis. Systemic blockade of IL-1 with IL-1 receptor antagonist (IL-1Ra) fully reversed infection-induced exacerbation of brain injury and functional impairment caused by cerebral ischemia."

One signifcant way that it does this is by blocking phagocytosis in the brain, preventing the clearing of dead cell debris and possibly triggering the production of anti nuclear antigens.  Along with Streptococcus pneumoniaes toxicity to microglia and astrocytes, histamine induced neuroinflammation could combine to break down the blood brain barrier and expose the brain to this bacteria.  This could be happening in the 20% of POIS sufferers who suffer from fever, a sign of meningitis, as they exhibit worse symptoms than most POIS sufferers.  I think this is the environmental factor that led to my POIS because I had many strep infections as a kid, which led to the movement disorders tics and chorea, and Tourette's and psychiatric disturbance starting right after one of the strep infections.  These are all symptoms of an Anti-basal ganglia antibody, suggesting that the strep had invaded my brain and I was fighting it.  It eventually went away, but I've had a history of chronic bronchitis so it might have just moved to my lungs, and if it can get in my brain once I don't see why it can't again.

This is not the only environmental factor that could trigger POIS though.  Herpes simplex virus (HSV) can cause herpes encephalitis, and studies have shown that long-term neuroimmune activation persists after the herpes infection in patients.  I believe these factors could explain a lot about why we are vulnerable to autoimmune diseases, why strict diets are necessary with POIS (due to the huge number of inflammatory additives in foods), and could even relate POIS to dysfunctions of immune priveledge. This also sets up the body for Kynurenine pathway dysfunction with IDO activation, and this is bad as Kynurenine is found in aging and in neurodegenerative diseases (ex. Physchiatric disorders and Encephalopathies).
Title: Re: New ideas about POIS and review of excitotoxicity
Post by: trusttheprocess on April 09, 2017, 09:24:26 AM
Review of Kynurenine Pathway shift in POIS
Kynurenine is useful as an emergency neuroprotective molecule (through it's NMDA, AMPA and kainate receptor antagonism it strongly prevents excitotoxicity) and it scavenges reactive oxygen species.  This is  just my theory but I think it's used by the body to raise the tolerance to increased intracranial pressure and excess Glutamate and Quinolinic acid activity.  I think this because AMPA is used for fast synaptic transition and NMDA is used for learning and memory.  Both seem to be inhibited during POIS, both are activated by Glutamate and Quinolinic acid, and both targeted by Epsilepsy drugs.  If glutamate excitotoxicty (which also happens in encephalitis) is so great to reach levels close to cause a seizure or a Cushing response, I'd imagine the body would release a lot of IDO, which leads to the production of Kynurenine that will counteract the over excitement and slow your brain down.  The release of IDO must be triggered by a serious immune event though, as this will lower tryptophan, serotonin, and melatonin levels, will lead to the prodution of the potent neurotoxin Quinolinic acid, impairs learning and memory, and leads to slower synaptic transmission.

Kynurenine also has significant immunosuppressant effects such as, "Inhibition of T cell functions, activation of the regulatory T cells, and the inhibition of Natural Killer cells are among the important factors in the immunosuppressive effects of IDO and kynurenines. There is a close connection between cytokines (IFN-α, IFN-γ, TNF-α, TGF-β, IL-4 and IL-23) and the kynurenine system, and an imbalance in the TH1/TH2 cytokine profile may possibly lead to neurologic or psychiatric disorders. As the tryptophan metabolic pathway is activated by pro-inflammatory stimuli, the anti-inflammatory effect of kynurenic acid provides a further feedback mechanism in modulating the immune responses." (https://link.springer.com/article/10.1007%2Fs00702-011-0681-y)

Although Kynurenine seems to have many upsides, it has equally as many downsides, making it only useful as an emergency measure.  The first downside is that it blocks α7-nicotinic acetylcholine receptors (non-competitive antagonistic effect).  What this does is block an incredibly important process from performing it's anti-inflammatory effects. This response to excess inflammation is known as the Cholinergic Anti-Inflammatory Pathway (CAP), and it is how the Vagus Nerve is able to reduce inflammation.  It does this specifically by activating the efferent (from the CNS) portion of the Vagus Nerve, causing the release and the binding of acetycholine to the α7-nACh receptors.  This blocking of the CAP by Kynurenine explains the prolonged inflammatory response in POIS, as the bond between Kynurenine and the α7-nAChr is non-competitive, meaning it completely blocks many receptor sites that acetycholine should be activating.  The body produces more acetycholine to compensate for this, explaining lowered heart rate in POIS.  Even VNS devices will probably have some but limited effect (reported by Colm_2), as VNS stimulation releases serotonin and acetylcholine by firing the same nerve as the CAP (Although there is the possiblity that this just means we need a stronger or higher frequency VNS device).

At the same time as IDO is triggering the shift to the KP, it has also been shown to cause temporary pellegra (studies find N1-methylnicotinamide in blood, a marker for pellegra) because it oxidizes tryptophan molecules to impair T cell responses against your body (Pubmed ID: 25933499).  This makes sense, as a deficiency in either niacin or tryptophan can lead to pellegra.  The shift from Tryptophan to Kynurenine is so important that it is commonly used as an indicator for IDO actvity, as the ratio of Kynurenine/Tryptophan in the body, some disorders with changes to this ratio include inflammation, stress, release of gluocorticoids, arthritis, HIV/AIDS, pyschiatric disorders, and cancer. 

The problem of excessive IDO enzyme activity and depleted tryptophan becomes a very serious when you consider that mast activation can also deplete serotonin.

"It is known that mast cells can synthesize and store serotonin...The specific mediator content of mast cell granules however, depends on the local microenvironment in which they reside...As much as 20-40% of serotonin may originate from mast cells. Determination of the role of this immune cell in hippocampal physiology and function is especially interesting given evidence for other immune system effects on an array of hippocampal functions.  The hippocampus is important in the regulation of anxiety and depressive behaviors as well as in spatial learning and memory (PMC ID: PMC3721752)."

Mast cells are located in many areas between the outside world and the body such as connective tissues, skin, lungs, digestive tract, mouth, nose, conjunctiva or lining of the eyelid, and the brain in areas such as the pituitary stalk, the pineal gland, the area postrema, the choroid plexus, thalamus, hypothalamus, hippocampus and the median eminence.  These tissues are the most directly affected due to the inflammatory effects of mast cell activation as well as the release of dozens of other chemicals.  Mast cell activation and depletion of serotonin in the GI tract is unhealthy and underlies many disorders.

This systemic depletion of serotonin and tryptophan is an immunosuppressive mechanism used by the body in order to prevent autoimmune damage, as a tryptophan defiency prevents damaging T cell responses.  Although combined with the depletion of serotonin by mast cells, it leads to anxiety, depression and insomnia.  This is because instead of producing neurotransmitters that it needs to prevent these changes, the body produces Kynurenine.  This is good in the short term, but in the long run it leads to toxic byproducts.

The first notable toxic byproduct of Kynurenine is anthranilic acid (AA).  "AA has been shown to inhibit citric acid cycle and the respiratory chain complexes I?III [46], interfering with mitochondrial function. It may have an anti-inflammatory effect by forming a complex with copper."  This will worsen excitotoxicity and energy levels.  Another neurotoxic byproduct of Kynurenine is "3-hydroxykynurenin (3-HK), which is generally considered as a neurotoxic agent in vivo, causing convulsive attacks when administered intraventricularly [54] or leading to tissue damage when administered intrastriatally [55]. 3-HK is also present in eye lens, and it has been connected with cataract formation [56].  The toxicity of 3-HK can be attributable to its capability to produce free radicals during its auto-oxidation. The next step in the metabolism of Kynurenine is the generation of 3-HA from either 3-HK  or from AA. 3-HA is also prone to auto-oxidation, generating superoxide radicals, H2O2, and cinnabarinic acid [59]. Cinnabarinic acid is a ligand for the type 4 metabotropic glutamate receptor and also for AHR [60,61]. 3-HA can induce apoptosis in monocytes/macrophages [62], and it can inhibit the mitochondrial respiratory chain [46,63]. Furthermore, it has important immunoregulatory functions by interfering with T-cell survival.

Next, Quinolinic acid, under normal conditions is present in the brain in nanomolar concentrations and metabolized for the synthesis of NAD+. In vitro, QUIN is toxic for brain cells from above 150 nM [73]. QUIN is a weak endogenous agonist on NMDA receptors [74], the action of which is selective, involving the receptor subtypes containing the NR2A and NR2B subunits [75]. QUIN causes the greatest excitotoxic damage in brain areas rich in NMDA receptors containing NR2A and NR2B subunits, mainly in the striatum and in the hippocampus [76]. Furthermore, it can increase glutamate release by neurons and inhibit glutamate uptake by astrocytes, maintaining an elevated level to constantly stimulate NMDA receptors, resulting in excitotoxicity [77]. Lipid peroxidation also contributes to QUIN toxicity [78]; results suggest that QUIN forms a complex with iron, and this complex can contribute to the formation of ROS [79,80]. The toxicity of QUIN on brain cells is exerted mainly through NMDA-mediated excitotoxicity [73,81].  Quinolinic acid phosphoribosyltransferase converts QUIN to NAD+, finishing the metabolic process. NAD+ is thereafter utilized by different intracellular processes, serving as an electron transfer molecule" (PMC ID: PMC4463617).

The shift towards Kynurenine production also causes a shift away from the end product of the pathway, Nicotinamide adenine dinucleotide (NAD).  If NAD sounds a little familiar, it's because its health benefits have been in the news lately as having an even more direct anti-aging supplement than resveratrol, and thats what niacin is turned into when it enters the body (this happens very rapidly, with a half life of 20-60 minutes).  Although something about the flushing response does help greatly, I think a large part of niacins benefit may come from the microchrondrial effects of NAD.

"NAD has emerged as a vital cofactor that can rewire metabolism, activate sirtuins, and maintain mitochondrial fitness through mechanisms such as the mitochondrial unfolded protein response (Pubmed ID: 26118927).  NAD, as well as its phosphorylated form, NADP, are best known as electron carriers and co-substrates of various redox reactions. As such they participate in approximately one quarter of all reactions listed in the reaction database KEGG" (Pubmed ID: 26614649).

I believe NAD plays a large part of the benefits of niacin because it maintains the microchrondria, an absolutely critical benefit.  This is critical because the mitochrondrial theory of aging states that mitochondria are the chief targets of free radical damage, since it is known that they can produce reactive oxygen species.  Also, Mitochrondrial DNA demonstrates higher levels of free radical damage than nuclear DNA.  Electrons might be able to escape from mitochrondrial processes and react with water to form reactive oxyen species (ROS).  NAD works as an electron transfer molecule, so its possible this is what NAD prevents.  These free radicals can then damage the DNA, damaging mitochondrial components and leading to impaired mitochrondrial function.

"Impaired mitochondrial function causes the uncontrolled generation of ROS and nitrogen species (RNS) which can attack macromolecules, resulting in misfolded proteins, lipid peroxidation or nitrosylation and nucleic acid damage. The excess amount of reactive species, i.e., oxidative stress, is closely related to neurodegenerative diseases.   The theory proposes that a positive feedback loop of this process leads to deteoriation of the cells in the entire body and this is why aging occurs."

Temporary Mitochondrial dysfunction is incredibly releveant to POIS for the following reason, "The neural tissue is the main energy consumer of the human body, and imbalance in energy homeostasis can lead to neuronal deficit and, eventually, to neuronal death. The energy, in the form of ATP, is provided by the mitochondria. These organelles are the scenes of the citric acid cycle, fatty acid oxidation, the urea cycle and oxidative phosphorylation. Impaired mitochondrial function leads to energy deficit (lack of ATP), which, in turn, leads to the disruption of Na+/K+-ATP-ase, Ca2+/H+-ATP-ase and the reversion of the Na+/Ca2+ transporter [5]. Under these circumstances, the cells are not able to maintain their normal membrane potential, resulting in depolarization. Cells with disrupted membrane potential are more prone to excitotoxic and oxidative damage. 

Excitotoxicity is the neuronal death caused by excessive or prolonged activation of excitatory amino acid receptors. The main participant in this process is glutamate, acting on ionotropic N-methyl-d-aspartate (NMDA), α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) and kainate receptors and on metabotropic glutamate receptors [3]. An excessive amount of glutamate in the synaptic cleft can result in the dysregulation of Ca2+ homeostasis, mitochondrial dysfunction and the generation of ROS and RNS. Under normal conditions, the presence and amount of glutamate is highly regulated, but in neurodegenerative diseases, this regulation is often disrupted, contributing to neuronal damage" (PMC ID: PMC4463617).

Glutamate is not the only cause of excitotoxicity in POIS though, so is something called Ischemia, which is a restriction in blood supply to tissues causing a shortage of oxygen and glucose needed for cellular metabolism (to keep tissue alive).  This is caused by lowered heart rate due to excess acetylcholine production, along with inflammation (especially in the brain), and could be made worse by iron deficiency.  This combined with NAD depletion leads to serious mitochrondrial dysfunction and results in excitotoxicity.

I think POIS is also related to lupus because lupus is associated with defects in clearing dead cells, which can be very damaging if not cleared.  This is because when they are not removed by phagocytes they are captured instead by antigen presenting cells, which leads to the production of antinuclear antibodies.  I think this aspect of lupus links it to POIS, as someone a few months back had a positive ANA result.  Furthermore, the primary reason the body has immune priveledged sites is because of physical structures that cause a lack of lymphatic drainage and limit the immune system's ability to enter the site.  This explains why POIS manifests strongly for days, as what is supposed to prevent this autoimmune reaction is instead now a roadblock in clearing antigens.

When POIS does not start at puberty, I think defects in the blood-testes barrier (caused by injury or surgery) along with reduced immune tolerance leads to POIS in this subgroup.  I think these POIS sufferers will have antisperm antibodies more often than the rest of POIS sufferers and will tend to exhibit worse IBS symptoms as a result of the antibody.  Effects not explained by the cascade above can be explained by neurotransmitter disruption inherent with an orgasm (called the honeymoon effect), as well as abnormally high levels of glutmate and histamine present in POIS sufferers after orgasm (and these chemical's whole brain modulating effects).

Going forward I'm going to focus on researching which antibodies are present in POIS, the overlap between POIS and lupus, and what this could mean for treating POIS with the variety of lupus treatments.  I'm also going to start taking Hydrangea root to support regulatory T cell production, Neuroproteck to prevent mast cell activation, Zyrtec and Benedryl to prevent the immune response, Basis by Elysium Health to support mitochrondria function and prevent pellegra, supplements that support lymphatic drainage, and some IDO and TDO inhibitors.

note: any PubMed ID references an article on the joint National Center for Bioinformatics-US National Library of Medicine-National Institudes of Health website, which can be accessed by appending the ID to the end of the following URLS:
Pubmed: https://www.ncbi.nlm.nih.gov/pubmed/
PMC: https://www.ncbi.nlm.nih.gov/pmc/articles/
Title: Re: New ideas about POIS and review of excitotoxicity
Post by: Quantum on April 09, 2017, 06:44:36 PM
Hi TTP,

You have worked a lot on these posts, thanks for sharing your hypothesis on the forum.

I have came to very similar conclusions, in particular about the kynurenine pathways "hacking" the tryptophan metabolism through immune upregulation of the IDO enzyme, and TDO enzyme too in the liver, this ultimately producing toxic metabolites that causes excitotoxicity in the brain ( I have written a lot about this on the forum 2 years ago, for example here: http://poiscenter.com/forums/index.php?topic=1988.msg15559#msg15559 and here: http://poiscenter.com/forums/index.php?topic=2078.msg16431#msg16431 .

If you have never seen any of my posts about this, it means that we independently came to the same kind of conclusions, which is very interesting :-)

The most part of my current relief method is largely based on those hypothesis I made then, and has been efficient since that time.  I have included in my pre-pack some IDO inhibitor ( for example, turmeric, and also sources of rosmarinic acid, like rosemary essential oil, Holy Basil, ....) and TDO inhibitors ( my favorite is quercetin, because it is also a mast cell stabilizer)), to lower the effect of upregulated IDO and TDO,  and also including in this pack NMDAr inhibitors, to protect neurons form excitotoxicity ( neuroprotective substances), like magnesium, flaxseed ( the lignan in it) and L-theanine. ( See complete composition of my pre-pack at http://poiscenter.com/forums/index.php?topic=2090.msg16604#msg16604 )

I think you may enjoy looking at this diagram, too:  http://fr.slideshare.net/adonissfera/tryptophan-and-madness/17-Cytokines_Come_in_Two_FlavorsProInflammatory .  It helped me understand how it could be possible that a POIS sufferer can have some clusters of symptoms and not others  ( I don't have any cognitive symptoms, no memory or speech or concentration problems, but much emotional problems... and most have a mix of both, more or less severe on one side or the other.... not to mention other clusters, like the pellagra-like symptoms ).

Keep on diggin, TTP,, and don't hesitate to post about your hypothesis and what you will come up with, in continuing your huge research effort.  :)




Title: Re: New ideas about POIS and review of excitotoxicity
Post by: certainlypois2 on April 09, 2017, 08:43:59 PM
good stuff from both you.
Title: Re: New ideas about POIS and review of excitotoxicity
Post by: Spartak on April 09, 2017, 08:58:39 PM
Agree with certainlypois2.
But I am not afraid to say that I can not understand many things.
Title: Re: New ideas about POIS and review of excitotoxicity
Post by: trusttheprocess on April 09, 2017, 11:41:18 PM
Thanks guys, and Quantum I've read almost all of your posts, I've only been around POIS center for around 3 years but I've learned more about POIS from you and kurtosis more than anyone else.  Over the past year or so I've been reading up on inflammation, ischemia, excitotoxicity, histamine, and countless other topics I learned were important in POIS thanks to you guys.  No matter how mysterious POIS is, much can be learned from related diseases.  I think it's important we know everything we can about excitotoxicity to understand POIS, so I reviewed your theory of its involvement in POIS and included everything I think is relevant from what I've learned about it.  Its unfortunately a little long and I realize its going to be hard to understand, but everything I included underlies some important process or symptom in POIS, and I think its important to see the causes of these in order to more effectively treat them.  I've also tried to make it clear that POIS is not some random psychosomatic disorder, it is a serious medical condition that requires a scientific perspective to see how one process leads to another, and the calculated responses the body makes in order to prevent damage.  I also tried to explain why symptoms vary among POIS sufferers, and how this can lead to unrelated clusters of symptoms, the understanding of which can be incredibly useful in finding treatments and treating POIS.  I wish I had more time right now to investigate the newly released POIS survey, as it is very detailed and in combination with my posts above and some more research could give us answers as to what causes each of the different POIS types and some methods of treatment.  I really have to focus on exams for the next month so take a look yourself, I might not be able to investigate this for a little while.

Edit: Forgot to mention that I'm starting to think tryptophan depletion and IDO production is a good thing in POIS, as it prevents harmful T cell responses and produces Kynurenine which is strongly neuroprotective.   The article i read describe this process as "tryptophan utilization" and not depletion, as it shows how the immune system can use IDO as an useful tool.  I think NAD+  depletion causes the majority of KP related symptoms such as quinolinic acid production (needed to produce NAD+), mitochondrial dysfunction (which makes this quinolinic acid toxicity worse), and combines with tryptophan depletion to lead to Pellagra.  So I think NAD+ is a much more useful supplement than IDO/TDO inhibitors.
Title: Re: New ideas about POIS and review of excitotoxicity
Post by: trusttheprocess on April 10, 2017, 12:48:34 AM
Since I've come up with my theory that my POIS may be related to meningitis, I've done a little research and have found a new supplement that seems to have many benefits that could help POIS.  I'm ordering it right now, I'll let everyone know how it works.

IL-1 is produced by Streptococcus pneumoniae, bacteria I think I have, and seems to correlate with a lot of POIS symptoms.
(https://selfhacked.com/2014/09/23/interleukin-1/)
I'm going to try a supplement called Andrographis Paniculata, which should have extremely beneficial effects if my recent POIS theories are right.  (https://selfhacked.com/2016/03/25/top-12-scientific-benefits-of-andrographis-paniculata-including-dosage-safety-and-side-effects/#1_Andrographis_is_a_PotentAnti-Microbial)
Title: Re: New ideas about POIS and review of excitotoxicity
Post by: Quantum on April 10, 2017, 09:28:03 AM
Since I've come up with my theory that my POIS may be related to meningitis, I've done a little research and have found a new supplement that seems to have many benefits that could help POIS.  I'm ordering it right now, I'll let everyone know how it works.

IL-1 is produced by Streptococcus pneumoniae, bacteria I think I have, and seems to correlate with a lot of POIS symptoms.
(https://selfhacked.com/2014/09/23/interleukin-1/)
I'm going to try a supplement called Andrographis Paniculata, which should have extremely beneficial effects if my recent POIS theories are right.  (https://selfhacked.com/2016/03/25/top-12-scientific-benefits-of-andrographis-paniculata-including-dosage-safety-and-side-effects/#1_Andrographis_is_a_PotentAnti-Microbial)

Hi TTP,

LEt us know the results you get.

This supplement reminds me of Olive Lefa Extract, which is efficient against many pathogens.

I am not sure I understand when you say the Interleukin-I is produced by Streptococcus pneumoniae.  To my knowledge, Interleukin-1 is a pro-inflammatory cytokin produced by the immune system, more precisely by tissue macrophages, monocytes, fibroblasts, and dendritic cells, but is also expressed by B lymphocytes, NK cells and epithelial cells ( see https://en.wikipedia.org/wiki/Interleukin-1_family#Biological_activity ) 

Maybe you mean that the Strep infections induce a greater production of IL-1 in the body and worsens inflammation ?   Like mentioned here: "S. pneumoniae infection triggered atherogenesis, led to systemic induction of interleukin (IL) 1" - http://onlinelibrary.wiley.com/doi/10.1002/ana.24146/abstract .  Otherwise, I need some more information on your hypothesis.

Any infections will affect the immune overall response, so may affect POIS as well ( I do think there is definitively a auto-immune component in POIS )

Title: Re: New ideas about POIS and review of excitotoxicity
Post by: Quantum on April 10, 2017, 11:05:55 AM
Thanks guys, and Quantum I've read almost all of your posts, I've only been around POIS center for around 3 years but I've learned more about POIS from you and kurtosis more than anyone else.  Over the past year or so I've been reading up on inflammation, ischemia, excitotoxicity, histamine, and countless other topics I learned were important in POIS thanks to you guys.  No matter how mysterious POIS is, much can be learned from related diseases.  I think it's important we know everything we can about excitotoxicity to understand POIS, so I reviewed your theory of its involvement in POIS and included everything I think is relevant from what I've learned about it.  Its unfortunately a little long and I realize its going to be hard to understand, but everything I included underlies some important process or symptom in POIS, and I think its important to see the causes of these in order to more effectively treat them.  I've also tried to make it clear that POIS is not some random psychosomatic disorder, it is a serious medical condition that requires a scientific perspective to see how one process leads to another, and the calculated responses the body makes in order to prevent damage.  I also tried to explain why symptoms vary among POIS sufferers, and how this can lead to unrelated clusters of symptoms, the understanding of which can be incredibly useful in finding treatments and treating POIS.  I wish I had more time right now to investigate the newly released POIS survey, as it is very detailed and in combination with my posts above and some more research could give us answers as to what causes each of the different POIS types and some methods of treatment.  I really have to focus on exams for the next month so take a look yourself, I might not be able to investigate this for a little while.

Edit: Forgot to mention that I'm starting to think tryptophan depletion and IDO production is a good thing in POIS, as it prevents harmful T cell responses and produces Kynurenine which is strongly neuroprotective.   The article i read describe this process as "tryptophan utilization" and not depletion, as it shows how the immune system can use IDO as an useful tool.  I think NAD+  depletion causes the majority of KP related symptoms such as quinolinic acid production (needed to produce NAD+), mitochondrial dysfunction (which makes this quinolinic acid toxicity worse), and combines with tryptophan depletion to lead to Pellagra.  So I think NAD+ is a much more useful supplement than IDO/TDO inhibitors.

Thanks, TTP. for your good words about my post on the forum.

It is very impressive how much time you have devoted in understanding all the physiologic details that can help shed some light on the physiopathology of POIS.  Thanks for having doing it.


I understand your interesting point on the last "edit" part of your post, but we lack data in order to conclude about what's really happening in real time.  Is it a lack of NAD+ production, or symply an overflow of kynurenine and its toxic metabolites?   Hard to say.   Quinolinic acid have positive role to play in the cerebral physiology, because it is present in every human's brain.   Same thing for the IDO enzyme - we all have it in our cerebral tissues.  But too much a something can become harmful.  Kynurenine itself do not have a clear, blank slate, and kynurenine accumulation is associated with depressive symptoms, psychotic symptoms, and cognitive problems ( https://en.wikipedia.org/wiki/Kynurenine ), and kynurenic acid is known to cause same king of problems ( https://en.wikipedia.org/wiki/Kynurenic_acid#Role_in_disease ) .    So, it all depends on the timing and extent of a reaction.  Maybe it is beneficial, for a short, initial period, to use the kynurenine pathways as a protection against a strong auto-immune reaction ( equivalent of a shutdown in order to avoid an electrical surge), but maintaining the shutdown for too long becomes more a solution than a problem.  I think in POIS, there is a dysfunction in either the way the protective reaction is trigered, its intensity, and also a problem in the way it goes off or do not goes off.

Quinolinic acid is present, in physiologic conditions, in very tiny amounts in cerebral tissues.  If the normal metabolic ways that uses it are overloaded, and this may not imply a large additional production of quinolinic acid, toxic effects appears in the microglia from this "unattended" quinolinic acid, rather than from a lack of NAD production, that may work at full capacity but cannot handle more quinolinic acid. The transformation of quinolinic acid into NAD+ would be the rate limited process. Just an hypothesis, here.   


I remember that Kurtosis had been using NAD supplements, and had reported positive effects.  In his way od seeing things, he said he used NADH in order to recycle BH4, if L- Methylfolate does not work or is not well tolerated.  I never tried NADH myself, because I have found something that works before going there ( some other members did not have good results with NADH, though).   However, it is interesting to note that niacin also help recycle BH4, as well as vitamin C and resveratrol.  ( Vitamin C is clearly a winner in POIS:  recycles BH4, promotes oxytocin production, good antioxidant, and clears excess histamine :)  ...  and it is cheap and readily available.  I often use it for any residual symptoms of POIS, in small but frequent doses, like 125mg every 2 to 4 hours, never exceeding 1000mg a day... I prefer to complete with other things, like resveratrol or other antioxidants or anything on my "preferred" list )

Your hypothesis is interesting, though, and I really enjoy discussing this with you.  If you try NADH supplements, let me know of the results.   If it's essentially a NAD+ depletion, NAD+ supplement would make the emotional and cognitive symptoms disappears.  If it is an accumulation of kynurenine and its toxic metabolites, blocking the KP through inhibiting both IDO and TDO should be more effective. 

In both cases, eating pumpkin seeds or other sources of tryptophan is beneficial :)

Let me know what you think, TTP, when your exam will be over and you 'll have time to work on this.








Title: Re: New ideas about POIS and review of excitotoxicity
Post by: trusttheprocess on April 10, 2017, 03:03:26 PM
Quantum,

I have spent a ridiculous amount of time on studying POIS, but if I'm right it will all be worth it, and since I'm hopefully going to be starting a career in medical research soon it will be a worthy investment.  No need to thank me, you have done so much in advancing POIS knowledge that I figured you had to be getting a little tired of it, and someone else needed to step up.  It was one of your posts that inspired me to do this, so I'm the one that should be thanking you.

You are 100% right about not having enough data to support the "edit" portion of my post, which is why I ordered NAD+ last night, and plan on testing it Thursday or Friday.  Although its a little dangerous, I've made significant progress in understanding POIS this way, by forming a theory, determining a treatment based on that theory, and testing it to verify the theory.

I've also reached the same conclusions about vitamin C and olive leaf extract being among the top POIS treatments.  Also, you are right in that I meant Strep infections induce a greater production of IL-1 in the body.  As you can tell by my edits and frequent posts in this topic, this latest theory I've had is evolving rapidly and I may have overlooked some things, but I think I finally get the big picture and understand it enough to explain it simply.

According to my new theory, POIS is essentially an orgasm induced state of sepsis.  Sexual activity causes a natural release of histamine, which is "one of the few central nervous system neurotransmitters found to cause consistent blood-brain barrier opening".  This exposes the brain to pathogens that remain undetected in the body (and which could vary greatly among POIS sufferers), causing a strong septic response and in some an autoimmune response against the brain to root out the pathogen.  Elimination of the pathogen should get rid of POIS for good (but will require close work with a doctor I'm meeting later this month) so in the meantime I will focus on preventing the opening of the blood-brain barrier and limiting of effects of the orgasm induced sepsis.
Title: Re: New ideas about POIS and review of excitotoxicity
Post by: Quantum on April 10, 2017, 09:25:37 PM
Hi TTP,

About NAD+, to be safer while trying it, you must know that it has a long half-live, meaning it is eliminated very slowly from the human body.  So, like other substances with a long half-life, it may accumulate and blood level will slowly raise if taken every day for a long time.   So, you can choose strategies like taking it every other day, or 5 days than stop for 2 to 3 days, or taking it only the day of release, and the day after.   At any rate, avoid taking it daily for a prolonged period.

Also, never exceed 10mg in a day.  Better to start at 2,5mg a day, go to 5mg maybe, but never more than 10mg a day, again because of the long half-life.   High dosage will multiply this building-up effect.

Watch for side effects as signs that concentration is getting too high in your body:  insomnia, upset stmach, anxiety, mood swings, high blood pressure.  If you experiment any of these, both lower the dose and increase time between doses.   

Title: Re: New ideas about POIS and review of excitotoxicity
Post by: Nas on April 11, 2017, 04:45:11 PM
Hi TTP,
You mentioned that the release of histamine in the brain causes the blood-brain barrier to open, wouldn't ant-histamines help with this issue ? I've personally even tried anti-histamines that cross the BBB but they didn't work, any reason for that ? I also tried Niacin but it also doesn't work. And btw from what I could understand from your theory, is that pois is triggered by Orgasm and not by ejaculation, which for me I always assumed that we have an auto-immune response to our seminal fluid, mostly due to my inflation in my urethra that doesn't seem to get better only if I abstain from orgasm for a long time.
Title: Re: New ideas about POIS and review of excitotoxicity
Post by: trusttheprocess on April 12, 2017, 09:00:52 AM
Nas,
Good point that anti-histamines don't seem to be as effective as they should.  It seems like the breakdown of the BBB is triggered by both H1 and H2 receptors.
H1: http://www.pnas.org/content/107/44/18967.full.pdf
H2: https://www.ncbi.nlm.nih.gov/pubmed/11450085
I'm glad you asked this question though because it seems like the most important change (depolarization/permeability of the BBB) is activated by H2 receptors.  I was going to use Zyrtec and Benedryl before, both H1 blockers, but I think I'm going to look into getting an H2 blocker like ranitidine (most H2 blockers end in -idine).  Histamine is very important in sexual activity regardless of whether there is an orgasm or not, I think the amount of histamine released correlates with severity of symptoms, and since this shows up as flush (without niacin) then I think histamine probably spikes after orgasm.

I'm with you on Niacin not helping too much as well, but it takes at least an hour for niacin to turn into NAD+.  If the body senses NAD+ depletion it might cause more production of Quinolinic acid than Kynurenine, in an attempt to make the NAD+ itself.  I think niacin is just an indirect way of treating an NAD+ depletion and that NAD+ will be more effective, but I'll see if I'm right in the next few days, whenever NAD+ comes in the mail.  Thanks Quantum for the advice, I think I'm going to limit it at night and the morning after O twice a week.  This stuff is very strong and there's a lot of promise but not much research so I'm gonna start with the smallest dosage I can take and work my way up.  The andrographis came yesterday, I started with one and worked up to two, no side effects.  Hopefully the NAD+ will come in today and I can test that out too.
Title: Re: New ideas about POIS and review of excitotoxicity
Post by: Nas on April 12, 2017, 05:07:07 PM
I mean, I tried H2 blockers, they pretty much don't work. You can try if you want but I personally had nothing out of them.
Title: Re: New ideas about POIS and review of excitotoxicity
Post by: trusttheprocess on April 13, 2017, 01:21:14 AM
I'll probably read more into how pathogens break down the BBB soon, but from what I've read so far about mine it sounds like it activates microglia and astrocytes causing neuroinflammation (by stimulating production of IL-1).  This is what I'm trying to treat with Andrographis.  Tried it last night alone and didn't seem to help with POIS symptoms much, but I was mainly just testing to see if it had any side effects, I didn't think it would do much on its own.  Took two and didn't notice any side effects, I think that and antihistamines would help my form of POIS a lot.

I have an MTHFR gene, which leads to higher levels of histamine than normal, so B vitamins, Vitamin C, Olive Leaf Extract, Mast Cell Stabilizers and Anti-Histamines help greatly in lowering those levels and preventing histamine from breaking down the BBB even more. 

I did have one great find today.  I was feeling awful with POIS symptoms all day, had an exam at night and didn't even start studying for the night exam until 4pm because I felt extremely tired, but I couldn't really sleep.  Around 6pm I tried my NAD+ that came in the mail (along with the other supplements I usually take during POIS), and I went to workout for half an hour, and that got rid of almost all of my symptoms.  Worked out, studied, went to 70 person meeting, took an exam, and went to a party for two hours all on day one symptoms of POIS. 

I still felt a little brain fog and inflammation though, so now it just comes down to combining these new supplements with my old ones (which stabilized mast cells, lowered histamine levels, prevented microglia activation, protected the brain from excitoxicity and prevented autoimmune T cell responses).
Title: Re: New ideas about POIS and review of excitotoxicity
Post by: Nas on April 13, 2017, 07:29:43 AM
Well for me personally I completly shut down when I'm on day one of POIS so I avoid anything that involves talking with people. If I gone out on day one I'd behave like a complete retard socially and I'd probably make people either super weird or super bored.
It seems like your POIS symptoms are not as much extreeme and that's why these supplement probably work for you. Just talking out of experiance.
Title: Re: New ideas about POIS and review of excitotoxicity
Post by: trusttheprocess on April 13, 2017, 09:46:54 AM
Same for me, my POIS symptoms are very extreme.  I felt full POIS symptoms, wanted to skip everything last night, kept trying to fall back asleep until 4.  I still was a little out of it but the fact that I even went when I didn't have to go shows how effective the NAD+ is. 
Title: Re: New ideas about POIS and review of excitotoxicity
Post by: Quantum on April 13, 2017, 10:22:06 PM
I have an MTHFR gene, which leads to higher levels of histamine than normal, so B vitamins, Vitamin C, Olive Leaf Extract, Mast Cell Stabilizers and Anti-Histamines help greatly in lowering those levels and preventing histamine from breaking down the BBB even more. 

I did have one great find today.  I was feeling awful with POIS symptoms all day, had an exam at night and didn't even start studying for the night exam until 4pm because I felt extremely tired, but I couldn't really sleep.  Around 6pm I tried my NAD+ that came in the mail (along with the other supplements I usually take during POIS), and I went to workout for half an hour, and that got rid of almost all of my symptoms.  Worked out, studied, went to 70 person meeting, took an exam, and went to a party for two hours all on day one symptoms of POIS. 

I still felt a little brain fog and inflammation though, so now it just comes down to combining these new supplements with my old ones (which stabilized mast cells, lowered histamine levels, prevented microglia activation, protected the brain from excitoxicity and prevented autoimmune T cell responses).

Great, TTP,  I am happy for you that you have found some effective relief.   Keep us updated on NAD+, and on your overall method of relief.
Title: Re: New ideas about POIS and review of excitotoxicity
Post by: trusttheprocess on April 17, 2017, 09:45:40 PM
First Update

This weekend I tested out some new supplements, they showed great promise but I can't say anything conclusive yet because I kind of ruined the experiment.  Started POIS around 4am last Friday, and woke up Saturday and felt fantastic, a first for me.  I didn't feel like a truck hit me the previous night, had some energy, was in a pretty good mood, although I could still feel brain fog and inflammation.  Unfortunately I was very hungry after waking up, and immediately ate a huge plate of leftover spaghetti and meatballs with piles of Parmesan cheese.  This ruined the experiment because immediately after I went into full blown POIS for two days. 

This happened because Parmesan cheese contains a huge amount of glutamate, which worsened the POIS excitotoxicity from almost undetectable to normal POIS levels.  Usually I have such bad POIS that I can't even notice the effect Parmesan cheese has on my symptoms, so I regularly use it during POIS anyway.  I'm aware of the strongly negative effect MSG and aspartame has on my POIS, but I'm a huge fan of Parmesan cheese and pasta and had not noticed the effect it was having on me until these new supplements.  This makes me think these supplements have great promise, because it takes a big improvement in symptoms to notice things that have subtle effects on POIS, like the recent discussion on how exercise can have both a positive and negative effect on POIS symptoms.

This becomes even more true when you considered that I only took 1 pill of everything and cut a few supplements out.  Although I'm disappointed I ruined my test with the Parmesan cheese, the main purpose of this test was to make sure I could take every supplement listed below together with no side effects, and I did that.  I will likely test the supplements again later this week when this round of POIS is cleared, and try to find ideal dosages and hopefully eliminate all symptoms.  In the meantime, the list of supplements in this test is below.

Edit:  This group of supplements helped quite a bit, but still not as much as I hoped so I'm moving on to testing anti-fungal supplements.  Don't try these, I just wanted to test these out.  Hydrangea root is probably not good for POIS sufferers, because even though it prevents suppresses IL-17 (and the resulting autoimmune response) this cytokine is what kills Candida, the fungus I think most POIS sufferers have.

Vitamins
B complex (MTHFR gene)
Vitamin B12
Vitamin C
Vitamin D3 (VDR gene)
Vitamin E

Antihistamines (DAO and HMNT genes)
H1 blocker Benedryl
H2 blocker Pepcid

Antimicrobials (Suspected Strep. Pnuemonae infection)
Andrographis
Resveratrol
Olive Leaf Extract
Hydrangea root

Mast Cell Stabilizers
EGCG
Luteolin
Fisetin

Extra Strength NIAGEN NAD+ amplifier
Nicotamide riboside
Astragalus extract
Bilberry extract
Title: Re: New ideas about POIS and review of excitotoxicity
Post by: Quantum on April 18, 2017, 07:34:43 AM
Hi TTP,

It sounds promising for you.

Your story with Parmesan reminded me of a "recipe" I had written about how to have a severe POIS cycle ( I have found it back at the bottom of this post: http://poiscenter.com/forums/index.php?topic=1235.msg15572#msg15572 ):

"So, a good recipe for a hellish POIS cycle would be to take, at least 2 hours before O, a lot of sodas and junk sweets ( as HFCS sources), along with aspartame and MSG, and also some BCAA supplement as well if you are really masochist.  Add some lactose or gluten, if your digestive tract is irritated by them, or anything else that will help produce pro-inflammatory cytokines in the guts - this will increase the madness of your POIS. And, of course, avoid anything beneficial, including niacin, tryptophan sources, 5-HTP, curcumin, or any antioxidant.  Be sure to be stressed and worried, so your cortisol is high and turns your TDO liver enzyme in overactive mode, depleting your Trp still more. Anybody want to try this recipe for the worst POIS ever ?   O_o    Sincerely, I hope not ! ! !

A healthy diet is obviously leading to.....  a better health :)"


It is surprising how much what we eat can influence our immune reactions.   


Keep us updated on your experiments. 



I have a question about one of your supplement,  What source of luteolin are you using ?   It is not easy to find a good sources of it.  I am using artichoke and rosemary as luteolin source, currently.
Title: Re: New ideas about POIS and review of excitotoxicity
Post by: trusttheprocess on April 18, 2017, 10:55:32 PM
Quantum,

Yeah the gluten in the pasta and glutamate in Parmesan cheese is one of the worst things you could eat during POIS, I just love it so much I've kind of ignored it until now, now that I've really seen the effect it has on me I'm not going near it during POIS.

For Luteolin it is hard to find, which is unfortunate because it might be even better than Quercetin.  I used to order Luteolin, Quercetin, Bromelain and Olive Leaf Extract from Swanson vitamins, but I just ordered NeuroProtek because it essentially combines all of these into a few pills. 
Title: Re: New ideas about POIS and review of excitotoxicity
Post by: Spartak on April 20, 2017, 10:58:35 AM
Hi Trust,

Interesting to see that you mentioned parmessan, I can say that cheese is pois safe food for me, same as milk,
I saw that some POIS-ers can't handle them, but judging by verious relief treatments which work on various members and fact that there are various types of POIS, it seems that every intolerance or relief method are pretty subjective.
I can't handle magnesium suplementation, while some have relief with it. Seems the same with gluten, I can eat gluten as much as I want, no effect on my POIS, but I can't handle sugars.

Take care,
Spartak
Title: Re: New ideas about POIS and review of excitotoxicity
Post by: Quantum on April 21, 2017, 12:36:43 PM
Quantum,

Yeah the gluten in the pasta and glutamate in Parmesan cheese is one of the worst things you could eat during POIS, I just love it so much I've kind of ignored it until now, now that I've really seen the effect it has on me I'm not going near it during POIS.

For Luteolin it is hard to find, which is unfortunate because it might be even better than Quercetin.  I used to order Luteolin, Quercetin, Bromelain and Olive Leaf Extract from Swanson vitamins, but I just ordered NeuroProtek because it essentially combines all of these into a few pills.

Thanks TTP for the information about the Swanson preparation of luteolin.   Luteolin is contained in parsley, artichoke leaves, celery, peppers, olive oil, rosemary, olive leaf extract, lemons, peppermint, sage, thyme and other foods, but it is harder to know how much you get through these sources, exactly.

At least a couple of member reported they had used NeuroProtek ( I think Kurtosis did, and had positive results with it). Let us know what it will do for you.

Title: Re: New ideas about POIS and review of excitotoxicity
Post by: VSmasher on April 23, 2017, 07:49:40 PM
Maybe we have candida.

Check this out...

https://www.ncbi.nlm.nih.gov/pubmed/20624941
Title: Re: New ideas about POIS and review of excitotoxicity
Post by: trusttheprocess on April 24, 2017, 01:19:59 AM
Maybe we have candida.

Check this out...

https://www.ncbi.nlm.nih.gov/pubmed/20624941

Interesting.  I think a weakened immune system is a necessary requirement for POIS, and Candida is not only caused by a weak immune system but it can also worsen the immune system by causing leaky gut syndrome, imbalanced gut flora, and adrenal fatigue/HPA dysfunction.  I always knew Candida affected many POIS sufferers, caused by lowered immunity, but I've looked into it more and I learned it can be caused by taking antibiotics or eating a high sugar diet as well.  I believe this article does support us having Candida, so I've read through that article and a few others about Candida.  I found a Candida quiz that seemed reliable (http://bodyecology.com/quiz.php), and it said I almost certainly have Candida.  After a lot of reading up on Candida I think it might be behind gut problems, along with many other symptoms of POIS, for the following reasons.

Research from Rice university shows that 70% of all people have Candida infections, and this is rising due to factors like lowered gut diversity, poor food quality, poor diets, widespread use of antibiotics, and other drugs that create an acidic environment which weakens our immunity.  Candida can cause dozens of symptoms, because it produces toxins and causes inflammatory and autoimmune reactions (which can lead to autoimmune disease).  Candida also lowers nutrient absorption, and can produce a neurotoxin named acetaldehyde (the same chemical that causes hangovers).  High levels of acetaldehyde taxes the liver, which reduces its ability to store and use the essential vitamin B12, this along with other factors puts excess stress on others organs like the brain (which uses lots of energy to pump calcium out of neurons, preventing excitotoxicity).  Acetaldehyde also can cause a deficiency in B1 (crucial for good brain health), binds with dopamine (why alcoholics are usually depressed), can damage nerve cells in a similar way to chronic alcoholism or Alzheimer's, and makes red blood cells less effective at carrying oxygen to the brain.  All this damage from one toxin, and Candida produces around a hundred toxins, including other serious ones like ammonia and uric acid. 

While the body is processing Candida toxins it also must fight Candida and maintain energy levels so neuronal death doesn't occur.  This can deplete hormones like pregnenolone, cortisol, and DHEA, which are also being used by the body to counter inflammation.  Candida can also suppress the production of serotonin, crucial in depression.  Candida also down regulates IL-17, perhaps as a defense mechanism, as IL-17 is very important in removing Candida.  Recent research suggests that it might directly bind to Candida and induce nutrient starvation conditions in the organism.  Candida down regulates IL-17 by shifting the Kynurenine pathway the opposite direction that POIS does, which may support its proliferation in our bodies as a way to counter this effect.  Coincidentally, Staph. A infections counter the inflammatory effects of Candida, and a few years ago I had a antibiotic resistant Staph A. infection (MRSA).

Throughout my life I've also had chronic bronchitis, colds, enteroviruses, and as a kid I had asthma, Tourette's syndrome, and Sydenham's chorea.  This makes me think that I either have a bacterial infection or are very vulnerable to them.  Candida causes physical damage to endothelial cell walls, making them vulnerable to bacteria.  As a result, 1 in 4 patients with Candida also have a bacterial infection. (https://www.ncbi.nlm.nih.gov/pubmed/17888612)

Now how could we treat Candida and possible polymicrobrial infections?  I need to look more into this but it seems like I've already figured most of it out by cutting sugar, milk, and recently gluten from my diet, taking antimicrobial supplements like Resveratrol, Olive Leaf Extract, and Andrographis, and IL-1 antagonists like Luteolin for the following reason:  "'Interleukin 1b is now turning out to be a decisive molecular switch, which the microbes use to dictate between healthy or sick,' says Dr. Christina Zielinski. She sees great potential in the therapy of inflammatory diseases by blocking this messenger substance. In contrast to other immune therapies this does not lead to a weakening of the immune system, but rather enables the cells instead to be anti-inflammatory if needed, without losing the ability to fight dangerous pathogens."
(https://www.candidaplan.com/620/candida-linked-to-arthritis-multiple-sclerosis-psoriasis-and-other-autoimmune-conditions/)
Title: Re: New ideas about POIS and review of excitotoxicity
Post by: notmythirdaccount on April 24, 2017, 11:36:51 AM
Hey guys,

I wanted to throw my experience into the mix.

TLDR: I think POIS has an immune, microbial, viral infection link, and Olive Leaf Extract seems to have helped. I have been taking most of the other vitamins for months without much change, however OLA seems to have improved my overall symptoms.

I have begun taking multivitamins and supplements diligently over the past three weeks. I can safely say that my symptoms have improved. My symptoms basically last only 1 day, following ejaculation. Day 2 and onwards is solid.

I've noticed no negative change by doing this (although you should take my and anyone else's information with a grain of salt and caution.) My libido is the same if not higher, my mood is more stabilized (day 1 is still rough, albeit better.)

The best part is not having muscular contractions or aches following an O. They're virtually non-existent. I can work-out like normal. On day 1 of POIS, I managed to run a total of 2 miles at a pace I've never ran before. I'd say that's an improvement.

So, on to the good stuff. Going off the first post in this thread, I do feel that POIS has an immune link, and also a bacterial, infectious or viral sickness link. I've had a couple of bouts of Staph infection in the past, one of which caused me to miss 3 weeks of work a few years back. I was on anti-biotics, but to be perfectly honest I may not have used all of the pills.

Additionally, as a child I was constantly sick with diarrhea or rashes. Growing up, I had a feeling that my immune system was crappy. But it's taken me a while to connect the dots.

I feel like I'm rambling, but will get to the point. Out of all the supplements that I have been using, like others in this thread, I feel that Olive Leaf Extract has been the most potent.

Unfortunately, I don't have a way of narrowing it down to OLA, but I feel that it plays an important role in my recovery and well-being.

My total regimen includes:
B-Complex (100mg?)
Quercetin Complex (with Vitamin C.) (500mg)
Vitamin D (5,000 IU)
Basic multivitamin (with Vitamin E, and other needed traces.)
Niacin (500mg)
Iron (60mg)
Ashwagandha
Olive Leaf Extract

I take all of these once a day, in the morning. I don't like using percentages because it's subjective, but I feel...at least at 70% on day 1, and 90%+ on day 2 and onwards. Before, my symptoms would last 2-3 days, and they were more severe.

I'd also like anyone else's bowel experience following an O, and the day after. When I release, it's as if my bowel movements entirely shut down. I can eat tons of food that day, and it seems like nothing is processed. I've also experienced this while taking Niacin, for example. Sometimes the Niacin will not work. I take 500mg and can feel the flush every time, so it baffles me why I can't feel it some days after an O. It's like my system goes on pause-mode on day 1. Once day 2 starts, I can use the restroom normally.

The gut has got to be important in this as well. I will try to get my hands on a high-quality probiotic to add to my stack.

Hope this helps.
Title: Re: New ideas about POIS and review of excitotoxicity
Post by: trusttheprocess on April 24, 2017, 10:45:51 PM
Hey notmythirdaccount,

Thanks for sharing your experience, I agree with your views on POIS and I'm going to start taking Olive Leaf Extract and other antimicrobrials on a daily basis. 

I originally thought just taking them before O would be enough, but my last two tests with these supplements have convinced me otherwise.  Both times I was missing a few supplements (neuroprotek, h2 blocker, b complex), and although they still gave me like 70% POIS relief, I was disappointed because I was still tired, unmotivated, out of it, and a little depressed.  Because I've done just about everything else I can try, I'm seeing my endocrinologist Wednesday and telling him I think I have candida, and that is has either made my immune system very vulnerable or it has allowed bacteria to colonize somewhere in my body.
Title: Re: New ideas about POIS and review of excitotoxicity
Post by: trusttheprocess on April 26, 2017, 04:17:03 AM
Maybe we have candida.

Check this out...

https://www.ncbi.nlm.nih.gov/pubmed/20624941

The more I read about Candida, the more convinced I am that it is causing POIS.

VagSmasher, I'm really glad you started a discussion about Candida in this thread, because it fits like a puzzle piece with everything I've described in the first page.  I thought the fact that I tended towards certain bacterial illnesses meant I had a bacterial infection, but that doesn't really make sense because I've had a wide range of both viruses and bacterial infections at a rate that just about everyone in my life has noticed and commented on how often I get sick.

Candida could not only make the body vulnerable to these illnesses, but it could do this consistently because it can evade detection.  How does it do this?  In the same way that I proposed the bacterial infection could, through molecular mimicry.  This leads to systemic auto immunity, as candida has been proven to cause fibromyalgia, something that runs in my family along with many other Candida/POIS related issues.  The genetic components that allow this are described in the first page of this thread, and has evolved because once we treat the Candida infection, these genes should give us an above average resistance to cancer.
(Read this article, much more info about this: http://nutritioninstitute.com/fibromyalgia/)

Now I know what your thinking, POIS isn't like fibromyalgia, but that's because there is a rather rare occurrence in POIS sufferers, which is the breakdown of the Blood Brain Barrier (BBB) during sex.  Rather than Candida's toxins just attacking nerves, it attacks the central nervous system.  Many factors can lead to the breakdown of the BBB, but during sex there is only one, the natural release of histamine which reliably opens the BBB.  This exposes the brain to around 100 extremely poisonous toxins like Acetaldehyde and Ammonia, which not only taxes your liver and kidneys, but triggers IDO activation and Kynurenine production to protect the brain at the cost of significant excitotocitiy.  This requires every ounce of energy in your body to protect you from stroke or seizure, which puts significant strain on the HPA (Hypothalamus-Pituitary-Adrenal) axis and depletes your body of hormones.  Dietary factors, particularly alcohol, sugar, and antibiotic consumption will feed the Candida and result in worse symptoms.  Even a comprehensive strategies to eliminate POIS will never completely work until Candida is removed from our bodies, so I'm going to ask my doctor to prescribe me a special antibiotic for fungal infections called nystatin later on today and see what he says.
Title: Re: New ideas about POIS and review of excitotoxicity
Post by: VSmasher on April 27, 2017, 07:08:26 PM
Yes. I think candida affects alot of people without them knowing it. There's even an Italian MD that says candida is the cause of cancer. Now, I just saw on the news that there's a new form of candida from China called Candida Auris that can KILL you! Shits crazy. I ate a ton of sugar all my life. My intestines are probably loaded with fungus. Also, I get POIS symptoms when I take herbs and supplements that kill candida. Maybe POIS is actually candida die off.

Things I take to kill candida...

raw garlic
Niacinamide
Raw coconut oil
Olive leaf xtrct
Grapefruit seed xtrct
Eat no sugar diet.

Title: Re: New ideas about POIS and review of excitotoxicity
Post by: trusttheprocess on April 28, 2017, 10:44:17 PM
Yes. I think candida affects alot of people without them knowing it. There's even an Italian MD that says candida is the cause of cancer. Now, I just saw on the news that there's a new form of candida from China called Candida Auris that can KILL you! Shits crazy. I ate a ton of sugar all my life. My intestines are probably loaded with fungus. Also, I get POIS symptoms when I take herbs and supplements that kill candida. Maybe POIS is actually candida die off.

Things I take to kill candida...

raw garlic
Niacinamide
Raw coconut oil
Olive leaf xtrct
Grapefruit seed xtrct
Eat no sugar diet.

Everyone on here should try it and see if it affects POIS in any way and report back here.
Thanks!!!!

Yeah I agree with that you it's crazy, that most doctors around the world ignore a fungus that can cause autoimmune disease, cancer, and even kill you is absolutely insane.

When I was at my endocrinologist on Wednesday, I brought that candida quiz that I linked to (in this thread), which said I almost certainly had it.  I told him that, and said the quiz had just about every single serious health symptom I was experiencing, and tried to hand the list to him.  As I held the papers out, he said he didn't want to look at them because as far as he was concerned, it was "bogus".

Then he went on and tried convince me I wasn't there for the symptoms I had repeatedly told him about, but had actually come to him for frequent urination, something which I never even wanted him to treat.  He just forced that upon me because he thought that was the most serious symptom, even though I listed at least five other more serious symptoms.

Needless to say, I was out of that office in five minutes and will never be going back to that guy.  This was my first time trying to seek professional help for POIS, and 6 months, 2 appointments, and a few hundred dollars thrown out the window later, I probably will never be trying that again.  Glad I listened to everyone's advice on this forum and tried to figure out POIS myself, trying to get help for POIS from that guy probably would've required dozens of tests and thousands of dollars.

I'd much rather try to treat Candida naturally anyway, so I just ordered three new supplements, and plan on trying these.  I have no clue what effects these will have, and ever since I started taking OLE andrographis and resveratrol my symptoms have gotten worse, not sure if I'm just stressed out about finals or if they're giving me side effects, so don't take any of these but I'll let you guys know how much they help.

http://www.iherb.com/Wakunaga-Kyolic-Kyolic-Formula-102-Candida-Cleanse-Digestion-100-Veggie-Tablets/56189
(Kyolic Formula 102 herb & enzyme blend, contains a unique, natural and synergistic combination of Aged Garlic Extract, Ginger, Glucanase, Lipase and Protease)

http://www.iherb.com/Now-Foods-Candida-Support-90-Veggie-Caps/462
(Candida Support is a combination of traditional herbal ingredients (Pau D'Arco, Black Walnut and Oregano Oil), Biotin (a B-complex vitamin) and Caprylic Acid (a naturally occurring fatty acid derived from plant oils)

http://www.iherb.com/Nature-s-Sources-Kolorex-Advanced-Candida-Care-60-Softgels/6634
(Kolorex Advanced Candida Care helps maintain balanced intestinal micro-flora, using a patented extract of New Zealand RedLeaf Horopito.)

Along with VagSmashers suggestions
Raw Coconut oil
Olive Leaf Extract
No sugar diet

And a few of mine
Andrographis
Resveratrol
Probiotics
Title: Re: New ideas about POIS and review of excitotoxicity
Post by: trusttheprocess on May 04, 2017, 01:32:04 AM
Found a better quiz for diagnosing Candida:  http://www.wholeapproach.com/candida/questionnaire.php

This link was in an article about histamine intolerance, the author of the article said they "scored a whopping 200 points!"

I scored 395.

This is very troubling as the author was a woman, and I should be less susceptible to Candidiasis for the following reasons:
(from http://thehistamineintolerantchick.blogspot.com/2013/08/coulld-candida-albicans-be-causing-your.html)
Why did I score so highly on the quiz then?  Without getting into the genetic factors behind this, I can think of two reasons.
Below is a good explanation of the link between histamine and candida, and some effective ways to treat Candida.
Quote
"Research shows that Candida triggers histamine release, but did you know you can be allergic to candida, causing repeated, longer lasting or more intense infections? Or that those with chronic candida are 70% more likely to have a history of family allergies and allergic rhinitis? There?s really exciting news though ? Tufts researchers have made a discovery that will rock our world!

Will treating Candida help resolve histamine intolerance/excess histamine/mast cell activation?

Possibly.

Are there natural treatments available?

Yes! A recent study by researchers at Tufts has found that a coconut oil rich diet reduces the amount of Candida albicans in the gut by more than 90% in mice [1].

More on that below.

Before proceeding, I?m just adding a quick update on a new review published in the European Journal of Pharmacology which discusses the findings that curcumin, extracted from turmeric, may be an appropriate treatment for invasive fungal infections like candida in cancer patients [1a].

We?ll have to wait for convulsive results but I thought it worthy of a mention given the study I read in Critical Reviews in Microbiology which shared something new to me: not only does candida take advantage of the immunocompromised by increasing the risk of carcinogenesis and metastasis in those undergoing chemotherapy, but that new research indicates candida may cause cancer progression by triggering inflammation [1b].

Back to the histamine connection.

Most, if not all, bacterial, viral and fungal infections cause an immune system response which comprises the release of histamine and many other inflammatory molecules [2].

A number of studies, including one published this year (2015) in the Nature Journal show that candida infection triggers mast cells to release inflammatory mediators to try and kill off the fungus [3].

As you?ll remember, histamine is found outside of the body in foods but it?s also present in our body, where it lives in mast cells, which are a key component of our immune system. When mast cells freak out for no reason (like in mast cell activation disorder/syndrome) or need to get in there and fight a pathogen, they do their degranulation boogaloo, shaking loose a ton of inflammatory cytokines to get the healing process going.

In 2012 authors of a study published in Frontiers in Immunology concluded that mast cells could be involved in the defence against Candida albicans by releasing histamine [4]."  (https://healinghistamine.com/are-you-allergic-to-candida/)

Candida, Histamine, and Leaky gut all seemed to be linked, probably because Candida can put holes in cell walls, damaging and destroying them.  This will lead to an immune response, allergies, and mast cell activation.

"Studies show that if your gut is colonised with the fungus Candida you are likely to become sensitive against food antigens (food allergy), because of the increased number of mast cells, and the hyper permeability of the gastrointestinal mucosa (which is caused by histamine release).  If you have histamine intolerances and food allergies it is very important to test for pathogens. As a minimum they can be contributing to the histamine load if you have a histamine related disease. They could also just be the cause." (http://alisonvickery.com.au/fungal-infections-histamine-intolerance-and-mast-cells/)

These gut issues can also lead to low levels of DAO, the main factor in histamine intolerance.  A list of conditions that cause DAO deficiency is listed below:
Or taking any of the following medications: (from (http://www.amymyersmd.com/2016/02/everything-you-need-to-know-about-histamine-intolerance/)
Note: Don't know if this entire list is accurate.  Tagamet did inhibit DAO by 25%, but Benedryl increased DAO by 20%, and Zyrtec and Zantac had no effect (from (http://www.ncbi.nlm.nih.gov/pubmed/9831324?dopt=Abstract).

Other factors can raise histamine levels even more such as allergies, histamine-rich foods, and HNMT, MAO, NAT2, or MTHFR deficiency.  This explains why B vitamins help POIS, as they are required for these histamine clearing enzymes. (http://mthfr.net/histamine-intolerance-mthfr-and-methylation/2015/06/11/)
I want to talk about why Candida/Histamine are so imporant now, so if you want to know more about treating histamine intolerance, read this website (https://selfhacked.com/2014/08/01/deal-histamine/).
Title: Re: New ideas about POIS and review of excitotoxicity
Post by: trusttheprocess on May 04, 2017, 05:49:54 AM
Importance of Candida related Histamine release

High levels of histamine are not healthy, one reason for this is because it opens the blood brain barrier.  This can allow Candida, or at least the toxins it produces, into the brain.  Although the causes behind it aren't clear, Candida can cause meningitis, something that is recognized by the Meningitis Research Foundation (http://www.meningitis.org/disease-info/types-causes/fungal).  Due to the link between Candida overgrowth and Histamine intolerance, and the interaction between them just worsens symptoms until a diet that doesn't feed Candida is adopted.

Overview of Fungal Meningitis (Gottfredsson, Magn?s, and John Perfect. "Fungal Meningitis.")

"Fungal infections have increased in incidence. This increase is attributed to an enlarging population of high-risk immunosuppressed patients, which is due in part to more successful pharmacological immunosuppression and chemotherapies and the frequent use of antibacterial and antiviral therapies. In addition, large numbers of patients living with human immunodeficiency virus (HIV) infection and the acquired immunodeficiency syndrome (AIDS) develop life-threatening fungal infections during the course of their illness. As a result of these trends, central nervous system (CNS) infections caused by opportunistic fungal pathogens are becoming increasingly relevant. In addition, seemingly immunocompetent individuals can acquire these CNS infections with fungi.

In the majority of cases the fungus appears to seed the CNS hematogeneously, usually from a pulmonary focus of infection but occasionally from extracranial sites such as infective endocarditis. Direct extension of fungal infections involving the cranial bones or sinuses into the subarachnoid space has also been described, usually causing basal meningitis or mass lesions. For clinicians, the varied clinical presentations of fungal meningitis and its possible concomitant brain parenchymal involvement constitute a major diagnostic challenge, because the yield of traditional diagnostic methods, such as culture, may not routinely be positive. Moreover, as more potential treatment options for these CNS infections become available, a timely and accurate diagnosis is crucial to improve prognosis for these seriously ill patients. In this review, we examine the topic of fungal infections of the meninges in both a general and a fungus-specific format...

The brain and the subarachnoid space are considered immunologically sequestered sites. The subarachnoid space has anatomic and functional barriers that exclude or modify immune responses. Except for the apparent neurotropism of C. neoformans, it remains unclear why this fungus uniquely invades this privileged sanctuary and what factors possessed by the fungus allow it to do so. On the other hand, although some patients with fungal meningitis have no overt immune defect or underlying disease, most patients with this infection have some predisposing factors or immune abnormalities that allow invasion by these low-virulent pathogens.

Certain clinical conditions have been identified that lead to failure of these host defenses. For example, direct inoculation of fungi into the brain following head injuries or neurosurgical procedures is an easily defined pathological mechanism. However, there can be subtle local immune cell dysregulation that allows establishment of meningitis; for instance, development of suppressor T cells in cerebrospinal fluid (CSF) has been observed in a case of Histoplasma meningitis.   Even potent antibacterial regimens may be a contributing factor to Candida meningitis. Corticosteroid treatment is a risk factor for fungal meningitis, and C. neoformans is the most prominent fungus complicating corticosteroid use.  The host immune responses and underlying disease are not only the major factors in the pathogenesis of these infections but also the most significant determinants of outcome in the patients.

All types of invasive infections with C. albicans and other Candida species are increasing in prevalence. The clinical symptoms of Candida meningitis are highly variable and can range from acute to chronic in nature, with headache and fever the most common clinical manifestations. In patients with Candida meningitis without concomitant HIV infection, [neck] rigidity is also commonly detected.  Almost all of these patients have also received broad-spectrum antibacterial agents and in some reports have had an antecedent bacterial meningitis.  In rare circumstances, Candida species can invade the subarachnoid spaces from the sinuses and the adjacent bone.  This is generally associated with an anatomic defect. Intracranial extension of the Candida infection can lead to arteritis within the CNS and subarachnoidal hemorrhage.

All Candida meningitis cases should be aggressively treated. The mortality for Candida meningitis with treatment has been reduced to 10 to 20%. The combination of amphotericin B and flucytosine is attractive as the regimen of choice because this combination has synergistic activity against Candida in vitro and flucytosine immediately reaches high concentrations in the CSF. Clinical experience suggests that this combination provides an excellent cure rate."

Pathology of fungal meningitis (S?nchez?Portocarrero, Jorge, et al. "The Central Nervous System and Infection by Candida Species.")

"When the CNS is involved in patients with systemic candidiasis, several clinical manifestations can be overlooked due to the severity of the patient?s situation. The decrease in the level of consciousness is the most frequent manifestation of CNS candidiasis. Often, not much attention is given to this manifestation when we come across septic patients suffering from severe illnesses in intensive care units, patients undergoing invasive procedures or sedated on drugs. Studies of the brain of patients who died from systemic candidiasis have concluded that up to 50% had CNS invasion by Candida species.  However, these patients were rarely diagnosed when alive because of the lack of clinical manifestations.

Recently, Candida species have been considered to be responsible for other neurologic clinical manifestations besides decreasing the level of consciousness. We therefore think that it is necessary to review the full and constantly changing spectrum of neurologic pathology caused by this microorganism.  The physiopathology of Candida CNS involvement varies according to the clinical setting. When systemic candidiasis is prolonged, it can affect the CNS and induce diffuse encephalopathy with diminished consciousness in which the predominant lesions are microabscesses. These have been reproduced experimentally by introducing C. albicans into the internal carotid of rats, thus simulating candidemia.

Pathologic findings are many. Microabscesses are usually found in the joint between the gray and white matters and they are widely spread in the CNS, being the basal ganglia and the cerebellum the sites more frequently involved.  Other findings are macroabscesses and lesions of vascular origin such as cerebral infarcts by vasculitis or mycotic aneurysms.  Up to 23% of patients with CNS candidiasis in necropsy studies may have evidence of vascular invasion, either in the vascular wall itself or with invasion of the arterial lumen. When cerebral ischemic damage exists, the infarcts are usually found in the basal ganglia. Old vascular lesions such as operated subdural hematoma can be infected by Candida species (Lipton et al., 1984). In general, these vascular complications seem to have a less important clinical role, although invasion of the arteries at the base of the brain by the fungus can produce transitory or permanent neurologic deficits.  Microabscesses cannot generally be seen on the cranial CT scan. They can be observed using magnetic resonance (MR) imaging, where they are seen as small enhanced ring lesions with a hemorrhagic component and widely spread in the brain."


Title: Re: New ideas about POIS and review of excitotoxicity
Post by: Quantum on May 04, 2017, 06:53:23 AM
Hi TTP,

Have added yet coconut oil and curcumin to your diet, the proposed natural cure for candida proposed in one of your references ?

I note that having a healthy diet and incorporating healthy food has many advantages, beyond what we may be aware of.   I say that because I already have turmeric/curcumin incorporated in my daily diet for at least 2 years, and in January, I have started to add organic coconut oil to my green smoothies ( I like its smell and its taste !   Be aware that if the coconut oil you use do not have a coconut smell, it has been tempered with and is not as healthy).

DAO has been discussed as a solution.  A member seemed to have some good initial results, but we did not have any news after.  One other member reported no effect with DAO.  But we already no that no one product works for every POIS sufferer.
Title: Re: New ideas about POIS and review of excitotoxicity
Post by: trusttheprocess on May 04, 2017, 12:13:20 PM
Quantum,

I haven't added coconut oil to my diet yet, although I plan on doing that sometime this weekend. 

Curcumin I have been using for a long time as the main anti-inflammatory for me during POIS.  I used to use Aspirin, but I have always mixed many different supplements and I didn't want to risk stomach or liver damage.  The health benefits of curcumin are staggering, I think it belongs in the "elite" tier of supplements with the most benefits, along with green tea and fish oil.  Check out these 37 proven health benefits if you don't believe me: https://selfhacked.com/2016/03/14/curcumin-cures-top-15-scientifically-proven-health-benefits-with-references/

I agree with you that healthy diets are very important, cutting out dairy, MSG, aspartame and most gluten and sugar has helped me tremendously.  I'm not an expert on healthy foods so I've mainly just tried to start eating organic salads with vegetables mixed in.  Also was eating blueberries for a while, they are excellent at reducing neuro-inflammation. 

I've never tried DAO but have always wanted to.  As I mentioned in my post, low DAO it is the main risk factor in elevated histamine but many other things can cause it including candida.  I would think a healthy diet would work better than DAO because it treats the cause of the elevated histamine, the candida, and not just the body's response to it.
Title: Re: New ideas about POIS and review of excitotoxicity
Post by: Mr Raba on May 04, 2017, 02:24:36 PM
TTP,

I have both CFS and POIS.  Latest studies have found a state of induced hypometabolic state such as in sepsis with CFS. Also remarkable findings in the pathways you describe.

I do not know if you are aware of the latest CFS research which is now a breakthrough after a breakthrough.

I strongly encourage you to look at several excellent articles regarding energy impairment and compensations ocurring to bring homeostasis in this excellent blog site:  Health Rising.  Here is one such article that discusses calcium channels involvement. Look at older posts in same blog  for a literal gold mine of info on inflammation and energy pathways.

https://www.healthrising.org/blog/2017/02/28/biomarker-aussies-chronic-fatigue-syndrome/

Title: Re: New ideas about POIS and review of excitotoxicity
Post by: VSmasher on May 06, 2017, 11:43:12 AM
Yes. I've long believed that POIS is caused by High brain histamine. Histamine is the neurotransmitter that makes you orgasm. The higher your brain histamine, the quicker you orgasm. That's why so many of us have Nocturnal emissions and Premature ejaculations.

Candida increases histamine which can increase POIS. Intense exercise also increases histamine. So does STRESS and ANXIETY. (Corticotropin-Releasing Hormone and Brain Mast Cells Regulate Blood-Brain-Barrier Permeability Induced by Acute Stress causing even more histamine to get into the brain!!!)

Not only does high histamine increase orgasm, but orgasm increases histamine. It's a never ending cycle. Maybe our H3 receptors aren't working? ( they work to control histamine like an automatic feedback loop)

The Diencephalon part of the brain is our emotional center. It is surrounded by mast cell. The mast cell release histamine into Diencephalon causing emotional sensitivity, anxiety, autism, brain fog, and Pois??...
Title: Re: New ideas about POIS and review of excitotoxicity
Post by: ThisType on May 07, 2017, 07:56:02 AM
VagSmasher, that's an interesting theory.  I have a benign pineal cyst seen via MRI.  The Diencephalon (https://en.wikipedia.org/wiki/Diencephalon) includes the pineal gland (https://en.wikipedia.org/wiki/Pineal_gland).  I see the cluster 1 symptoms of POIS (speech, brain fog, etc) per (http://tau.amegroups.com/article/view/11107/11778).
Title: Re: New ideas about POIS and review of excitotoxicity
Post by: demografx on May 07, 2017, 02:36:13 PM
Interesting, TT.
Title: Re: New ideas about POIS and review of excitotoxicity
Post by: Going less Crazy on May 08, 2017, 05:05:03 AM
Hmm maybe that's why vitamin c has helped me, antihistamine?

I didn't read too much but candida could be a possibility by paving the way for food sensitivities, Intolerance/auto immune issues causing high histamine and other inflammatory issues.  Im not sure if "curing candida" would resolve this issue once your immune system has tagged food a foreign invader.
Title: Re: New ideas about POIS and review of excitotoxicity
Post by: Pois 2011 on May 08, 2017, 10:17:10 AM
I dont believe in the Candia theorie. I made the candida test as well and scored like 265 or something. But then again I dont have any lose stool problems, constipation, white coating on tongue , bowel movement, which should be the main symptoms for candida. I asked 2 doctors about it and both reacted pretty much the same. They said candida is something almost esoteric like. If you go to to a nutritionist and you make a candida test they will always tell you that you have overgrowth. Candida would be all around us and there are people with a very bad immune system who have problems with it but you would see that directly on skin etc that they have problems with it.  At least I dont think i have such a problem. I was on a Candida diet and was very strict and later I ate a lot of sugar - it didnt change a thing. What had an influence on me as far as I believe was when I started eating prossessed sweets again - but here I blame the other ingriedients. White sugar seems to be fine to me...

Regarding Vitamin C I tried the vitamin C Flush a couple of times and felt very good affterwards. Read about it here: http://www.beyondhealthnews.com/wpnews/index.php/2012/08/the-vitamin-c-flush-a-critical-weapon-in-the-fight-for-health/
but it wont heal Pois. Maybe it could give you some further relieve.
Title: Re: New ideas about POIS and review of excitotoxicity
Post by: VSmasher on May 09, 2017, 05:51:37 PM
I dont believe in the Candia theorie. I made the candida test as well and scored like 265 or something. But then again I dont have any lose stool problems, constipation, white coating on tongue , bowel movement, which should be the main symptoms for candida. I asked 2 doctors about it and both reacted pretty much the same. They said candida is something almost esoteric like. If you go to to a nutritionist and you make a candida test they will always tell you that you have overgrowth. Candida would be all around us and there are people with a very bad immune system who have problems with it but you would see that directly on skin etc that they have problems with it.  At least I dont think i have such a problem. I was on a Candida diet and was very strict and later I ate a lot of sugar - it didnt change a thing. What had an influence on me as far as I believe was when I started eating prossessed sweets again - but here I blame the other ingriedients. White sugar seems to be fine to me...

Regarding Vitamin C I tried the vitamin C Flush a couple of times and felt very good affterwards. Read about it here: http://www.beyondhealthnews.com/wpnews/index.php/2012/08/the-vitamin-c-flush-a-critical-weapon-in-the-fight-for-health/
but it wont heal Pois. Maybe it could give you some further relieve.

That's because most Medical Doctors aren't taught in medical school about candida.

Below is a link to more than 61,000 scientific studies about candida...

https://www.ncbi.nlm.nih.gov/pubmed/?term=candida

And if you have candida in your blood stream, it doesn't always cause gut issues.

Trust me. Candida is very very real.

Just because a doctor doesn't know about something doesn't mean it doesn't exist..
Title: Re: New ideas about POIS and review of excitotoxicity
Post by: caveeater on May 10, 2017, 05:49:40 AM
Candida makes sense. I certainly have it to some extent (it almost always co-incides with mercury poisoning, which I suspect I have due to having had amalgam fillings for years).

When I did a ketogenic diet, my candida was fairly under control and POIS didn't affect me as badly.
Title: Re: New ideas about POIS and review of excitotoxicity
Post by: paradoxx on May 20, 2017, 05:00:06 PM
Hi trusttheprocess, you raise some concepts about candida which seem plausible. While I find it easy to believe that candida is a common problem and involved in at least some cases of POIS, I remain sceptical about it. Earlier in my life I was really polarized towards 'natural' health practicioners while condemning academic medicine (now I guess i believe its much more complex). It was during that time (2008) when I saw an alternative practicioner for my digestive issues. His diagnosis was candida based on viewing a blood sample in a dark field microscope (http://tarahealthcentre.com.au/Services/Ev-methods/Darkfield.htm). He let me take a look through the microscope and it all seemed very plausible. As a treatment he prescribed me an antifungal rectal suppository plus a skin cream and told me to avoid certain foods for a while. As far as i can remember, my problems didn't really disappear during the next months and I stopped pursing the candida topic. Over the years, i kept stumbling over the topic every now and again like here in this thread. Until now I don't know what to think of it (the previous two posts here pretty much sum up the conflict I have in my mind) and didn't take enough time yet to understand all of what was posted about it here, but still I wanted to share these things.

Did anyone else ever get a candida diagnosis and what's your opinion on dark field microscopy (if you have one)?
Title: Re: New ideas about POIS and review of excitotoxicity
Post by: trusttheprocess on June 07, 2017, 02:35:10 PM
Hey fellow POISers,

Sorry I haven't updated you guys sooner on my results with candida supplements, I was hoping to report almost complete reduction of symptoms with it, but unfortunately it is a very slow process.  It's similar to when I took my 23andme test, discovered I had issues processing vitamins B & D, and started taking those.  Great improvement of symptoms at first, but mixed results since then. 

I'm not going to change anything, however.  Candida is a notoriously tough pathogen to get rid of, almost all cases I've read about needed multiple strong antibiotics to cure it, and the only way to convince a doctor that it could get in the nervous system is to get a cereberospinal fluid sample and do extensive tests on it.  This is because every case of candida that's been studied has varied, with some only harmlessly colonizing and others being life threatening.  This is why doctors believe it is so rare, they only consider it if someone is having life threatening encephalitis, and they must do tests are far from the normal standard of care.

There are numerous reasons why my improvement in symptoms have diminished.  I had gastrointestinal problems the first week of the supplements, but felt absolutely great.  Then, I was sick for two weeks.  The supplements definitely did not start my illness, that happened after a late night out.  When I was sick I had thrush on my tongue which is rare for me and is a sign of candida overgrowth, but I also used asthma medicine which can cause that.  I haven't been strict at all with my diet, which is slowing my recovery as sugar and alcohol feed candida.  I have also gone into POIS a few times and did not take any supplements before, which probably played a part in getting me sick and why I didn't recover sooner.  I was hoping the candida supplements would work right away, but for the reasons described above I have a feeling it will take a while.

I was hoping to get more concrete results, but I still believe those will come with time.  Also I've been very busy starting an internship doing medical research, first week I filled out a proposal to our IRB for a study.  We are doing an ex vivo study on human tissue samples, and even though there was no chance of adverse effects for the participants, there were dozens of questions asking us to anticipate the effects it could have on them and how we would handle it.  There is no way Dr. K did not foresee the potential problems with the study, but now that I have a little experience with research I think VNS provided little benefit and he didn't see any point in continuing to subject participants to POIS and publish a paper if there weren't significant results to justify continuing it.

TTP 
Title: Re: New ideas about POIS and review of excitotoxicity
Post by: Mr Raba on June 11, 2017, 09:47:17 AM
It is very common for me to get great initial results that eventually dissipate when tryng supplements.

My body brings everything back to  the lower state of homeostasis.

Very common also on CFS.


Look at blog I mentioned earlier. Healthrising.org.   Many good articles as to why may happen.

For example. Body is or enters into a very high level of oxidative stress. Which causes drastic ireduction in energy generation. Body resorts to anabolic energy production. Which causes a builld up of lactic acid in the brain and body. This alternative energy production pathway being  on causes the CNS and emotional  Symptoms. The diets you mentioned help energy production in that anaerobic pathway.   This discovered and evidenced by recent top researchers in field of CFS. See site history for wealth of info.

CFS is the closest illnesd to POIS I kmow. The overlap is amazing. The main symptom difference is that ejaculation triggers temporary episodes in POIS.  But in CFS  is energy use. Several of us have a clear case of BOTH CFS AND POIS. Others in varying degrees.



Title: Re: New ideas about POIS and review of excitotoxicity
Post by: demografx on June 11, 2017, 10:46:23 PM
Interesting how many parallels you see between
CFS & (http://i858.photobucket.com/albums/ab143/demografx/562B1190-80C7-4AC5-B5FC-94C034B424F6.jpg), Mr Raba.


Title: Re: New ideas about POIS and review of excitotoxicity
Post by: Mr Raba on June 13, 2017, 04:32:13 PM
TT, Demo and all.

Several have mentioned that they benefit from ketogenic diet.

Here is a recovery story and lots if info on it.

https://www.healthrising.org/blog/2017/06/13/loris-chronic-fatigue-syndrome-fibromyalgia-ketogenic-success-story/

Again look at this site for lots of good info the biology of inflammation, vagus nerve, microglia, brain inflammation, autoimmunity, brain fog, energy production issues, oxidative stress, etc.
Title: Re: New ideas about POIS and review of excitotoxicity
Post by: trusttheprocess on June 18, 2017, 10:22:10 AM
It is very common for me to get great initial results that eventually dissipate when tryng supplements.

My body brings everything back to  the lower state of homeostasis.

Very common also on CFS.


Look at blog I mentioned earlier. Healthrising.org.   Many good articles as to why may happen.

For example. Body is or enters into a very high level of oxidative stress. Which causes drastic ireduction in energy generation. Body resorts to anabolic energy production. Which causes a builld up of lactic acid in the brain and body. This alternative energy production pathway being  on causes the CNS and emotional  Symptoms. The diets you mentioned help energy production in that anaerobic pathway.   This discovered and evidenced by recent top researchers in field of CFS. See site history for wealth of info.

CFS is the closest illnesd to POIS I kmow. The overlap is amazing. The main symptom difference is that ejaculation triggers temporary episodes in POIS.  But in CFS  is energy use. Several of us have a clear case of BOTH CFS AND POIS. Others in varying degrees.

I seem to be getting better, slowly but surely, have only seen a slight decrease in POIS symptoms but let me explain why this is still very good news.

First off I agree that CFS and POIS have great parallels, as I think the drastic reduction in energy generation is not why we have POIS, but is why our bodies take several days to recover from the factors that cause POIS.

I think high levels of histamine lets candida into the brain, and as a result the brain produces IDO, which depletes tryptophan to signal to T-cells that they need to kill the candida.  This unfortunately leads to a temporary state of pellegra, the first factor in decreased energy production.  It also mounts a highly cytotoxic and damaging immune response which uses a great amount of energy, factor two.  Finally the killing of the candida triggers a herxheimer reaction (a normal - and even healthy - detoxification reaction that indicates that parasites, fungus, viruses, bacteria or other pathogens are being effectively killed off).  This releases 79 toxins, causing the high level of oxidative stress, factor three.

Then as you have said the body resorts to anabolic energy production, causing a build up of lactic acid.  This causes a state known as acidosis in the body, which is why we have such sore muscles and foamy urine, and also contributes to many other POIS symptoms.

The reason my recovery from candida overgrowth has been a slow and unpleasant experience is because killing the candida releases these toxins and causes oxidative stress.  Just google candida die off or candida herxheimer reaction, there are dozens of pages on how to get through it as easily as possible.  Although I've been very lax with the diet, I'm taking the best supplements I could, and after a month of this I feel I've reached a turning point in this treatment.
Title: Re: New ideas about POIS and review of excitotoxicity
Post by: VSmasher on July 11, 2017, 09:32:20 AM
TrustTheProccess,

      Me to brother. I have been on a candida killing diet for almost 8 months now and I am finally turning the corner and having great results. I have 1 or 2 orgasms a week now and my POIS is almost completely gone.

 I cut about 85% of the sugar out of my diet. I also take anti-candida supplements daily. The first 5 months of the candida cleanse were hell. I was iching all over, sneezing, flakey rash on my face and scalp, bad anxiety and stress, bad vivid nightmares, and so on. It was well worth it though because now I have almost no die off symptoms. And my POIS is only about 15% of what it once was.

Keep me updated on your progress!!

Good luck!!
Title: Re: New ideas about POIS and review of excitotoxicity
Post by: paradoxx on July 14, 2017, 07:21:01 PM
Wanted to drop a link to a good article I found, reading it and carefully rereading the information in this thread cleared up a lot of my confusion on candida. The article made me aware of the many studies on candida I didn't know existed: https://www.jeremyrhammond.com/2014/09/17/intestinal-candida-overgrowth-real-condition/

@trusttheprocess/VagSmasher: From what I understood killing the candida releases toxins which the body needs to get rid off causing the intense reactions you describe. Maybe this explains the heavy reactions I get from coconut oil. Are you adding additional supplements for supporting the liver during this process? A doctor once told me I have a weak liver so I want to be careful in my next attempt.
Title: Re: New ideas about POIS and review of excitotoxicity
Post by: Quantum on July 15, 2017, 09:45:01 AM
Wanted to drop a link to a good article I found, reading it and carefully rereading the information in this thread cleared up a lot of my confusion on candida. The article made me aware of the many studies on candida I didn't know existed: https://www.jeremyrhammond.com/2014/09/17/intestinal-candida-overgrowth-real-condition/

@trusttheprocess/VagSmasher: From what I understood killing the candida releases toxins which the body needs to get rid off causing the intense reactions you describe. Maybe this explains the heavy reactions I get from coconut oil. Are you adding additional supplements for supporting the liver during this process? A doctor once told me I have a weak liver so I want to be careful in my next attempt.


Interesting article, paradoxx, thanks.  This article could explain, at least in part, why taking probiotics and reducing sugar have been beneficial for many POIS sufferers

Interestingly, I have integrated organic coconut oil in my smoothies, a few months ago.  I didn't know it could be beneficial for the guts, I added it for its nutritional qualities.  But, good and healthy foods have many positive properties, and even if we don't know all the specifics, changing for a completely healthy diet bring many benefits, even when we are not aware of many of them :)

Title: Re: New ideas about POIS and review of excitotoxicity
Post by: notmythirdaccount on July 15, 2017, 01:26:24 PM
TrustTheProccess,

      Me to brother. I have been on a candida killing diet for almost 8 months now and I am finally turning the corner and having great results. I have 1 or 2 orgasms a week now and my POIS is almost completely gone.

 I cut about 85% of the sugar out of my diet. I also take anti-candida supplements daily. The first 5 months of the candida cleanse were hell. I was iching all over, sneezing, flakey rash on my face and scalp, bad anxiety and stress, bad vivid nightmares, and so on. It was well worth it though because now I have almost no die off symptoms. And my POIS is only about 15% of what it once was.

Keep me updated on your progress!!

Good luck!!

Hey VM,

Can you elaborate on your die-off symptoms? I've noticed a horrible itch that happens after I take probiotics (1 month in now). I keep reading that this is a die-off symptom but want to make sure it's not an adverse effect of taking them.

Thanks/
Title: Re: New ideas about POIS and review of excitotoxicity
Post by: paradoxx on July 16, 2017, 09:01:33 AM
Interesting article, paradoxx, thanks.  This article could explain, at least in part, why taking probiotics and reducing sugar have been beneficial for many POIS sufferers

Interestingly, I have integrated organic coconut oil in my smoothies, a few months ago.  I didn't know it could be beneficial for the guts, I added it for its nutritional qualities.  But, good and healthy foods have many positive properties, and even if we don't know all the specifics, changing for a completely healthy diet bring many benefits, even when we are not aware of many of them :)

It seems that many of the things that have been reported to help POIS directly or indirectly influence the gut flora in a positive way (ginger, garlic, niacin, olive leaf extract etc) and a disrupted flora / dysbiosis could be one of the underlying factors in POIS. If that is true, it makes sense that a healthy diet is a reasonable way to address this. Though I agree there might be other benefits we are not aware of (yet). I'm interested in the smoothies you prepare, did you already write about them somewhere?
Title: Re: New ideas about POIS and review of excitotoxicity
Post by: Quantum on July 16, 2017, 01:38:55 PM

I'm interested in the smoothies you prepare, did you already write about them somewhere?


Hi paradoxx,

I have mentioned them, didn't write about them.  So here is some information and a typical recipe I prepare.

I have started green smoothies because it is a great way to consume a large volume of healthy veggies, and fruits, and other healthy food, in a tasty and easy way.  I had difficulty in particular with eating some kind of green veggies, even in salad.  For example, kale is one of the best greeny leafs there is from a nutritional point of view, but I don't enjoy at all eating raw kale, and not even in a salad.  But they easily blend in my green smoothies !

Here is a typical recipe of my green smoothies: 

Organic kale    2/3 to 1 cup   ( always included !)

Organic broccoli   2/3 to 1 cup   ( Always included too! I use the stem, the leafs too when some left, not only the flower tops)

Source water   100ml / 4 oz    ( to ease the mix in the blender)

1 organic banana  ( always included, great for the taste)

1/2 organic apple

1/2 organic tomato

Organic virgin, cold pressed coconut oil   2 to 4 tablespoon, depending on your taste, but I really like it  ( to know if your oil is a good brand and has not been tempered with, it has to smell coconut - if no smell, it has been processed )

Grapefruit juice 100ml/4 oz   (  good for the liver, but caution, grapefruit juice is a potent CYP3A4 inhibitor, an important enzyme in the liver, so it interacts significantly with many prescribed and OTC drugs, and those interactions can be severe, so check out with your pharmacist or physician if you can take grapefuit or grapefruit juice, or just use another fruit juice , since this is quite specific to grapefruit juice and some rare citrus like Pomelo and Seville oranges - see https://en.wikipedia.org/wiki/Grapefruit%E2%80%93drug_interactions for more details.  Of course, the safest alternative is to skip the juice, or replace it with source water or coconut water to work the smoothie to the desired consistency ) )

Frozen mango chunks      1/2 cup   ( this with banana add up to a great taste ) ( I use the no pesticides-no gmo Nature's Touch brand from Costco - there are virtually no organic mangos available around here)

Organic basilic    one or two leaves

Organic parsley     a little bit

Organic chia or kemp      1 or 2 oz  ( source of complete proteins, and lots of vitamins and minerals, and omega-3 too)

2 times a week, I add organic red beets, that are good for the liver... turn my green smoothie to a red smoothie, of course !


 I can also add some of what I have on hand:  some organic spinach, or some red berries, or some blueberries, or some organic green peas, or some organic carrot, or organic psweet pepper bell, and so on.

I add sometime some organic ginger, or organic cinnamon, or organic cacao powder, or else.  But never again I will add spiruline in my smoothies, for me it totally spoils the taste !  ( I take spirulina powder apart, in water ).


After nearly six months, I got used to get a result that suits my taste.  But at the start, it happened I had to adjust the final result by adding some maple syrup or organic vanilla soya drink, to make it more tasty and more enjoyable.

The taste I get has nothing to do with high sugar commercial preparations, but since I had cut refined sugar for a long time now this is very tasty to me and sweet enough.

I mix everything in the blender and usually consume half the quantity right after making it, and put the other half in a mason jar, in the fridge, for later in the day.


I do not always have the 30 mins or so to mix all the ingredients and clean the blender and everything after.  So, I have two back ups in the form of healthy organic juices:  either the Biotta Breuss ( http://biotta.ch/en/products/biotta-classic/breuss/ ), or the Suja Mighty Dozen organic greens, that I buy at Costco ( see https://www.burpy.com/costco/suja-essentials-organic-mighty-greens-juice/product-detail/1146247 ).    This way, I can have my daily dose of organic veggies and fruits, even if I have much work to do, or a family event, or anything else.

After six months, I had great benefits from this new addition to my diet.  I am not a total vegan, I eat eggs, meat, some cheese, but adding this much fruits and high quality veggies on a daily basis have been good for my health.  For example, I did not have a single cold or flu this last winter despite the harsh cold of Canada, a first in many years, and my green smoothies may be one of the reason why.

Let me know if you have any questions. Of course, anyone interested should start slowly, with only a few ingredients - my recipes have grown to  become quite elaborate, after all these months.  just 4 to 5 ingredients can do for a starter, and I use to go for half fruits-half veggies in volume, in the beginning, but I am now more leaning toward 2/3 veggies - 1/3 fruits.  Experiment !

Cheers !


( p.s.  I may re-post this on a separate thread, I think it is a good thing to promote healthy diet among the POIS sufferers community )

Title: Re: New ideas about POIS and review of excitotoxicity
Post by: trusttheprocess on July 20, 2017, 03:54:59 AM
Hey guys, been a while since I posted last, I've been very busy at my internship as a researcher this summer along with continuing the candida diet (seeing slowly improving symptoms). 

Paradoxx, supporting the liver during candida cleanse is a good idea, candida die-off produces acetyaldehyde, the by product of alcohol that damages your liver.  I've heard many people recommend NAC, as it has been proven to kill candida and produces glutathione which protects the liver.

Quantum, I'm not much of a chef or smoothie person, but I like your diet as I've adapted something very similar.  I've seen it referred to as the MEVY diet, where I'm just eating Meat, Eggs, Vegetables, and Yogurt (with live cultures).  Cheese is prohibited on a Candida diet, as is sugar, although candida can also feed on ketones from if you consume too little sugar so fruits are an ideal source of this sugar. 

VS, Great news! Very glad to hear the candida diet is working so well!  The die off symptoms can be harsh at times, and progress very slow, I realized it would take a very long time but I was hoping it would be less than 8 months.  I'm starting a new semester of college soon and I will do just about anything to shorten that, so I'm trying to get a prescription for an anti-fungal.  Thanks for letting me know it would take this long, this has made me do a lot of research (posted below), which has made me think anti-fungals would be much more useful than a candida diet for POIS.  This is because I think we have more systemic, deep seated infections of candida than just the gastrointestinal tract.

Before I get to that information I just wanted to say I recently ordered urine test strips to finally find out why my urine gets cloudy during POIS.  I'm two days into POIS now and have come up with some good results from this.  Day one of the urine test read that I had a pH of 5, which is a sign the body is trying to fight an infection.  This tests also revealed a small to moderate amount of white blood cells in my urine, which is commonly found with urinary tract infections, both fungal and bacterial.  By day two of the urine tests the pH remained the same, but the white blood cells had almost disappeared and yet there were still white cloudy particles in my urine. I read that if you notice white specks in your urine, this may be yeast (from Candidahub).  I went to the doctor to see if they could get a urine culture for fungi, they did confirm an abnormally low pH but they normally only culture urine for bacteria, and the doctor wasn't sure if the lab would culture for fungi but is going to ask.  In the meantime I have done some research on the presence of candida in the urine, and the possible link this has to prostate inflammation.
Title: Re: New ideas about POIS and review of excitotoxicity
Post by: trusttheprocess on July 20, 2017, 04:00:00 AM
Overview on Candidal Urinary Tract Infection

In the last decades, fungal urinary tract infections (UTI) due to candida yeasts have increased significantly. Recently, Behzadi et al. reported the incidence of UTI associated with Candida albicans to be 6.8% of all microbial UTIs. Fisher et al. have recently published a review article on Candida infection of the urinary tract. They could conclude that Candida organisms are very well equipped for colonization and invasion of the urinary tract, and little is currently known about the regulating factors for Candida virulence. (Chronic prostatitis/chronic pelvic pain syndrome: the role of an antifungal regimen. Central European Journal of Urology. 2013)

Candida Albicans, a commensal yeast that inhabits human skin and mucosa and thrives on sugars and carbohydrates.  Candida can be isolated from up to 70% of the general population at any given moment, and it is believed that all individuals have been colonized with Candida at a some point (Functional genomics identifies type I interferon pathway as central for host defense against Candida albicans. Nature Communcations. 2013).  Although it is a commensal organism, C. albicans can also cause mucosal and systemic infections, and is the most common cause of fungal infection in immunocompromised persons.  Despite the advances in diagnostic mycology, candiduria (candida found in urine) definition and management remains a controversial subject.  Most research on candidal infection (invasive candidiasis) is done on immunocompromised patients (with HIV, Cancer, etc.) or on hospital patients, and most doctors do not consider it outside of these patients.  Here are some good reasons why they should.

1) Some individuals are genetically predisposed to fungal infection.  When persistent or recurrent invasive fungal infections develop in a "normal" host, they are indicative of genetic defects causing innate or adaptive immune dysfunction.  These seem to be mainly caused by a shift from IL17 immunity (important for the clearance of fungal infections) to a type I interferon response that is broadly implicated in autoimmune disease, caused by mutations in STAT1 and other immune system related genes.  Below are two studies that implicated a few gene families in invasive candidiasis, along with my genetic report for these genes.

(Genetic Susceptibility to Fungal Infections in Humans. Current Fungal Infection Reports. 2012)
AIRE - 5 normal - 5 heterozygous mutations
MPO - 2 normal - 1 homozygous mutation
CARD9 - 1 normal - 2 heterozygous mutations

(Functional genomics identifies type I interferon pathway as central for host defense against Candida albicans. Nature Communcations. 2013)
STAT1 - 16 normal - 3 homozygous mutations
SP110 - 1 heterozygous mutation
PSMB8 - 3 heterozygous mutations
CCL8 - 1 normal

2) Most incidence of candiduria is likely to be underestimated, mainly because the use of standard urine culture is not very sensitive.  Colony counts is considered the corner stone in the diagnosis of bacterial urinary tract infection however, it was not proven to be diagnostically useful in candiduria. In addition, most urine cultures only test for bacterial infection, and throw the urine specimen out before fungus has a chance to grow, so the diagnosis of candiduria may be overlooked. (Epidemiological Study on Species Identification and Susceptibility Profile of Candida in Urine. Fungal Genomics & Biology. 2015 )

3) Candiduria is a common finding, but is often asymptomatic and dismissed by doctors.  They do this because the serious finding of canidida in the blood (candidemia) does not result from the colonization of a single body site, but from multiple sites.  This is becoming increasingly common however, as oropharyngeal (upper respiratory) colonization is found in 30%-55% of healthy young adults, and Candida species may be detected in 40%-65% of normal fecal flora (Medscape. Infectious Diseases. Candidiasis).

4) Candiduria is becoming an increasingly important source of infections in hospitals. People speculate that this is due to the change in our diets away from meats and fats to carbohydrate-rich convenience foods, combined with heavy use of antibiotics in the last 20 years, as there is compelling evidence linking antibiotic usage to the increased incidence of candiduria, or the presence of candida in the urine (Epidemiological Study on Species Identification and Susceptibility Profile of Candida in Urine. Fungal Genomics & Biology. 2015).  92% of Candida bloodstream infections are preceded by a course of broad-spectrum antibiotics (Epidemiology, clinical characteristics, and outcome of candidemia: experience in a tertiary referral center in the UK. International Journal of Infectious Disease. 2011)  Oral or inhaled corticosteroids, as well as TNF inhibitors, can also increase one's risk of fungal infection (from the CDC).

5) There is a large range of reported rates for the complication of candiduria (candida in the urine) turning into the candidemia (candida in the blood stream).  For example, in one study urinary colonization had the highest positive predictive value of candidemia, with 20% of colonized patients subsequently being diagnosed with candidemia (The association between anatomic site of Candida colonization, invasive candidiasis, and mortality in critically ill surgical patients. Mycology. 2006).  In another study of patients with persistent candiduria, 41% developed candidemia, as evidenced by polymerase chain reaction (a highly accurate method).  Most candidemia studies use blood cultures (the current gold standard for candidemia) although the sensitivity of this method is only 50%, and blood cultures become positive late in the disease course (The End of an Era in Defining the Optimal Treatment of Invasive Candidiasis. Oxford Clinical Infectious Diseases. 2012).

If enough sites are colonized by candida then invasive candidiasis can develop, encompassing candidemia and deep-seated candidiasis, infections of tissue sites beneath mucosal surfaces.  Deep-seated infections may remain localized, spread to contiguous sites, or lead to secondary candidemia. Animal models show that deep-seated infections generally persist after clearance of candidemia.  Candida has been shown to infect the bladder, prostate, epididymis, urethra, and kidneys.  Several of these spots are immune privileged, which could explain why the Candida can evade the immune system, and only reach the blood stream on occasion.  Personally I believe POIS to be a candidal infection of the prostate, causing an illness known as prostatitis.


Title: Re: New ideas about POIS and review of excitotoxicity
Post by: trusttheprocess on July 20, 2017, 04:09:43 AM
Overview on Prostatitis

Prostatitis is inflammation of the prostate gland and there are four categories.  90-95% of prostatitis diagnoses fit into category three, known as chronic nonbacterial prostatitis.  The symptoms of prostatitis include painful and frequent urination and post ejaculatory pain, mediated by nerves and muscles, and is a hallmark of the condition.  This serves to distinguish chronic prostatitis from men with BPH or normal men.  The Prostatitis Foundation's list of symptoms get even closer to describing POIS (figure 1).  Also, men with chronic prostatitis are more likely than the general population to suffer from Chronic Fatigue Syndrome (CFS), and Irritable Bowel Syndrome (IBS).  Due to the concomitant presence of bladder disorders, gastrointestinal disorders, and mood disorders, research has been conducted to understand whether chronic prostatitis might be caused by problems with the hypothetical bladder-gut-brain axis. Anecdotal evidence suggests that food allergies and intolerances may have a role in exacerbating chronic prostatitis, perhaps through mast cell mediated mechanisms. There is also some evidence of an association between chronic prostatitis with non-celiac gluten sensitivity in some patients (from Wikipedia).

There are also a few more links between prostatitis and POIS.  First, autoimmunity is present in prostatitis, as the CD4 T cell proliferative response to seminal plasma was statistically significant in men with prostatitis compared with healthy men (Autoimmune prostatitis: Evidence of T cell reactivity with normal prostatic proteins. Urology. 1997).  Second, prostatitis likely plays a role in premature ejaculation, the number one symptom of POIS.  Prostatitis was found in almost half of subjects with premature ejaculation in one study, which was significant compared to controls and suggests a role for chronic prostate inflammation in the pathogenesis of some cases of premature ejaculation (Prevalence of chronic prostatitis in men with premature ejaculation. Urology. 2001).  Third, the symptoms of prostatitis confuse doctors.  38% of primary care providers, when presented with a vignette of a man with chronic prostatitis, indicate that they have never seen such a patient. However, the overall prevalence of symptoms suggestive of chronic prostatitis is 6.3%.  Also new evidence suggests that the prevalence of chronic prostatitis is much higher in teenage males than once suspected (all from Wikipedia).  I'm sure there are other links between prostatitis and POIS, as these are just ones I came across as I was researching prostatitis.

In 2003 it was shown that bacteria do not have a significant role in the development of prostatitis, and it has since been studied as a systemic disorder.  The evidence supporting a viral cause of prostatitis and chronic pelvic pain syndrome is weak, and many researchers believe it is caused by a micro-organism (from the NIH).  The symptoms of chronic prostatitis appear to result from an interplay between psychological factors and dysfunction in the immune, neurological, and endocrine systems.  Theories behind the disease include stress-driven hypothalamic-pituitary-adrenal axis dysfunction and adrenocortical hormone (endocrine) abnormalities, neurogenic inflammation, and myofascial pain syndrome.  In the latter two categories, dysregulation of the local nervous system due to past trauma, infection or an anxious disposition and chronic albeit unconscious pelvic tensing lead to inflammation that is mediated by substances released by nerve cells (from Wikipedia).

The prostate (and other areas of the genitourinary tract: bladder, urethra, testicles) can become inflamed by the action of the chronically activated pelvic nerves on the mast cells at the end of the nerve pathways. Similar stress-induced genitourinary inflammation has been shown experimentally in other mammals.  Chronic nonbacterial prostatitis is furthered classified into inflammatory or noninflammatory based on the levels of white blood cells in expressed prostatic secretions (EPS), although both show subtle signs of inflammation like cytokines.  In 2006, Chinese researchers found that men with categories three prostatitis both had significantly and similarly raised levels of anti-inflammatory cytokine TGFβ1 and pro-inflammatory cytokine IFN-γ in their EPS when compared with controls.  Interferon gamma limits IL-17 production, which plays an important role in anti fungal immunity. (Cutting edge: IFN-gamma regulates the induction and expansion of IL-17-producing CD4 T cells during mycobacterial infection. Journal of Immunology. 2006)

A significant number of men with chronic prostatitis have found relief ranging from a cure to welcome diminution of symptom severity after following an anti-candida regimen. The full science behind this phenomenon is incomplete at this time. It is uncertain whether a yeast overgrowth in the gut lowers general body resistance by attacking the immune system, thereby allowing dormant bacteria in the prostate to re-activate (proven science: Candida Albicans toxins disarm elements of the immune system), or whether the effects on the immune system result in non-bacterial inflammation to the prostate tissue (and often the sinuses as well - another poorly perfused part of the body), or indeed whether the organism actually infects the prostate tissue directly. (from The Prostatitis Foundation) 

A systematic review and meta?analysis of literatures on management of chronic prostatitis in 2011 concluded that although chronic prostatitis had to represent a spectrum of cases that are free of microbial infection, antibiotics administered alone or in combination with alpha?blockers represent the best current modality of treatment for such cases. One study in 2013 tried this on around 70 patients with two weeks of the common antifungal flucanazole daily, and although there was lack of a urine culture documenting fungal infection, 80% of the cases showed significant improvement of their prostatitis symptoms.  Also study patients who received multiple previous courses of antibiotics showed a better response to the antifungal regimen.  Recurrent antibiotic courses block the local immune mechanisms, facilitating the invasion and virulent behavior of the colonized Candida infection.  Patients that showed a response to the antifungal regimen had significantly lower serum total PSA (0.5 ng/ml), so it seems that fungal prostatitis may be associated with lower PSA values (Chronic prostatitis/chronic pelvic pain syndrome: the role of an antifungal regimen. Central European Journal of Urology. 2013).  I would like to note that PSA was below 0.5 in one POIS forum member, and another reported in the normal range of 0.5 - 2.0 when you search PSA on this forum.  Other types of fungus have also been investigated as the cause of prostatitis (How to Diagnose and Treat Fungal Infections in Chronic Prostatitis. Current Fungal Infection Reports. 2007).
Title: Re: New ideas about POIS and review of excitotoxicity
Post by: paradoxx on July 20, 2017, 04:51:36 PM
Paradoxx, supporting the liver during candida cleanse is a good idea, candida die-off produces acetyaldehyde, the by product of alcohol that damages your liver.  I've heard many people recommend NAC, as it has been proven to kill candida and produces glutathione which protects the liver.

Thanks for the tip, NAC seems to have benefits for many conditions.

A Review on Various Uses of N-Acetyl Cysteine:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5241507/

Before I get to that information I just wanted to say I recently ordered urine test strips to finally find out why my urine gets cloudy during POIS.  I'm two days into POIS now and have come up with some good results from this.  Day one of the urine test read that I had a pH of 5, which is a sign the body is trying to fight an infection.  This tests also revealed a small to moderate amount of white blood cells in my urine, which is commonly found with urinary tract infections, both fungal and bacterial.  By day two of the urine tests the pH remained the same, but the white blood cells had almost disappeared and yet there were still white cloudy particles in my urine. I read that if you notice white specks in your urine, this may be yeast (from Candidahub).  I went to the doctor to see if they could get a urine culture for fungi, they did confirm an abnormally low pH but they normally only culture urine for bacteria, and the doctor wasn't sure if the lab would culture for fungi but is going to ask.  In the meantime I have done some research on the presence of candida in the urine, and the possible link this has to prostate inflammation.

I'm also doing urine tests since yesterday. I ordered them to check for bilirubin and urobilinogen (indicating liver issues). Results of the first 2 tests were identical, showing a ph of 5 and a specific gravity of 1.030, other indicators are negative/normal. I want to see if the results change during the POIS cycle. I also have foamy urine sometimes.

Interesting stuff about candiduria and prostatitis. Thanks for your research efforts.
Title: Re: New ideas about POIS and review of excitotoxicity
Post by: certainlypois2 on July 20, 2017, 06:21:13 PM

I'm interested in the smoothies you prepare, did you already write about them somewhere?


Hi paradoxx,

I have mentioned them, didn't write about them.  So here is some information and a typical recipe I prepare.

I have started green smoothies because it is a great way to consume a large volume of healthy veggies, and fruits, and other healthy food, in a tasty and easy way.  I had difficulty in particular with eating some kind of green veggies, even in salad.  For example, kale is one of the best greeny leafs there is from a nutritional point of view, but I don't enjoy at all eating raw kale, and not even in a salad.  But they easily blend in my green smoothies !

Here is a typical recipe of my green smoothies: 

Organic kale    2/3 to 1 cup   ( always included !)

Organic broccoli   2/3 to 1 cup   ( Always included too! I use the stem, the leafs too when some left, not only the flower tops)

Source water   100ml / 4 oz    ( to ease the mix in the blender)

1 organic banana  ( always included, great for the taste)

1/2 organic apple

1/2 organic tomato

Organic virgin, cold pressed coconut oil   2 to 4 tablespoon, depending on your taste, but I really like it  ( to know if your oil is a good brand and has not been tempered with, it has to smell coconut - if no smell, it has been processed )

Grapefruit juice 100ml/4 oz   (  good for the liver, but caution, grapefruit juice is a potent CYP3A4 inhibitor, an important enzyme in the liver, so it interacts significantly with many prescribed and OTC drugs, and those interactions can be severe, so check out with your pharmacist or physician if you can take grapefuit or grapefruit juice, or just use another fruit juice , since this is quite specific to grapefruit juice and some rare citrus like Pomelo and Seville oranges - see https://en.wikipedia.org/wiki/Grapefruit%E2%80%93drug_interactions for more details.  Of course, the safest alternative is to skip the juice, or replace it with source water or coconut water to work the smoothie to the desired consistency ) )

Frozen mango chunks      1/2 cup   ( this with banana add up to a great taste ) ( I use the no pesticides-no gmo Nature's Touch brand from Costco - there are virtually no organic mangos available around here)

Organic basilic    one or two leaves

Organic parsley     a little bit

Organic chia or kemp      1 or 2 oz  ( source of complete proteins, and lots of vitamins and minerals, and omega-3 too)

2 times a week, I add organic red beets, that are good for the liver... turn my green smoothie to a red smoothie, of course !


 I can also add some of what I have on hand:  some organic spinach, or some red berries, or some blueberries, or some organic green peas, or some organic carrot, or organic psweet pepper bell, and so on.

I add sometime some organic ginger, or organic cinnamon, or organic cacao powder, or else.  But never again I will add spiruline in my smoothies, for me it totally spoils the taste !  ( I take spirulina powder apart, in water ).


After nearly six months, I got used to get a result that suits my taste.  But at the start, it happened I had to adjust the final result by adding some maple syrup or organic vanilla soya drink, to make it more tasty and more enjoyable.

The taste I get has nothing to do with high sugar commercial preparations, but since I had cut refined sugar for a long time now this is very tasty to me and sweet enough.

I mix everything in the blender and usually consume half the quantity right after making it, and put the other half in a mason jar, in the fridge, for later in the day.


I do not always have the 30 mins or so to mix all the ingredients and clean the blender and everything after.  So, I have two back ups in the form of healthy organic juices:  either the Biotta Breuss ( http://biotta.ch/en/products/biotta-classic/breuss/ ), or the Suja Mighty Dozen organic greens, that I buy at Costco ( see https://www.burpy.com/costco/suja-essentials-organic-mighty-greens-juice/product-detail/1146247 ).    This way, I can have my daily dose of organic veggies and fruits, even if I have much work to do, or a family event, or anything else.

After six months, I had great benefits from this new addition to my diet.  I am not a total vegan, I eat eggs, meat, some cheese, but adding this much fruits and high quality veggies on a daily basis have been good for my health.  For example, I did not have a single cold or flu this last winter despite the harsh cold of Canada, a first in many years, and my green smoothies may be one of the reason why.

Let me know if you have any questions. Of course, anyone interested should start slowly, with only a few ingredients - my recipes have grown to  become quite elaborate, after all these months.  just 4 to 5 ingredients can do for a starter, and I use to go for half fruits-half veggies in volume, in the beginning, but I am now more leaning toward 2/3 veggies - 1/3 fruits.  Experiment !

Cheers !


( p.s.  I may re-post this on a separate thread, I think it is a good thing to promote healthy diet among the POIS sufferers community )

Do you know a non organic substitute to the juices you recommend.
Title: Re: New ideas about POIS and review of excitotoxicity
Post by: Quantum on July 20, 2017, 09:56:32 PM
Hi CP2,

I do not search for any, so I didn't notice.  But from what I know, mainstream commercial vegetable juices rely strongly on tomato juices base, like V8 and Garden Cocktail for example, and they have been shown to be far too acid for my stomach, back when I tried them, before I had started to look for organic food.

But I definitively think that organic veggies are way better.   Chemical like pesticides cannot be of any positive value, and I am not found of GMO neither.
Title: Re: New ideas about POIS and review of excitotoxicity
Post by: certainlypois2 on July 21, 2017, 05:38:26 PM
Hi CP2,

I do not search for any, so I didn't notice.  But from what I know, mainstream commercial vegetable juices rely strongly on tomato juices base, like V8 and Garden Cocktail for example, and they have been shown to be far too acid for my stomach, back when I tried them, before I had started to look for organic food.

But I definitively think that organic veggies are way better.   Chemical like pesticides cannot be of any positive value, and I am not found of GMO neither.
Thanks, I will see if i can find one. I am interested in trying an organic diet for pois but cant afford it right now. Right now I just need the juice to increase veggie and fruit intake, my intake is to low. I  prefer drinking them to eating them.
Isn't scientific consensus on gmo is that they are okay.
Title: Re: New ideas about POIS and review of excitotoxicity
Post by: Quantum on July 21, 2017, 09:54:38 PM
Isn't scientific consensus on gmo is that they are okay.

http://www.davidsuzuki.org/blogs/science-matters/2009/09/more-science-needed-on-effects-of-genetically-modifying-food-crops/

Title: Re: New ideas about POIS and review of excitotoxicity
Post by: romies on July 25, 2017, 12:59:42 PM
I remember that Kurtosis had been using NAD supplements, and had reported positive effects.  In his way od seeing things, he said he used NADH in order to recycle BH4, if L- Methylfolate does not work or is not well tolerated.  I never tried NADH myself, because I have found something that works before going there ( some other members did not have good results with NADH, though).   However, it is interesting to note that niacin also help recycle BH4, as well as vitamin C and resveratrol.  ( Vitamin C is clearly a winner in POIS:  recycles BH4, promotes oxytocin production, good antioxidant, and clears excess histamine :)  ...  and it is cheap and readily available.  I often use it for any residual symptoms of POIS, in small but frequent doses, like 125mg every 2 to 4 hours, never exceeding 1000mg a day... I prefer to complete with other things, like resveratrol or other antioxidants or anything on my "preferred" list )

Your hypothesis is interesting, though, and I really enjoy discussing this with you.  If you try NADH supplements, let me know of the results.   If it's essentially a NAD+ depletion, NAD+ supplement would make the emotional and cognitive symptoms disappears.  If it is an accumulation of kynurenine and its toxic metabolites, blocking the KP through inhibiting both IDO and TDO should be more effective. 

I have tried NADH, NAD+, NR supplements in the past.

NADH 20mg (Now foods) was and still is amazing. Very stimulating, so I only take it in the morning, when I need it (probably once a month or less). And most of its effect seems to derive from elevating BH4 levels:
1. feeling of more dopamine, serotonin in brain
2. peripheral NO synthesis : my hands/feet would get very warm from improved circulation.

NAD+ (sublingual), and NR do not have any effect on me.

NAD+ only has a 2hr half life: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2852209/ So I consider it low-risk supplement.

Title: Re: New ideas about POIS and review of excitotoxicity
Post by: romies on July 25, 2017, 01:11:50 PM
  • HNMT ? which requires SAMe as a cofactor (and this requires an effective MTHFR enzyme to help produce SAMe)
  • DAO ? which requires vitamin B6 and copper
  • MAO ? which requires vitamin B2 and iron
  • NAT2 ? which requires CoA which stems from vitamin B5

DAO metabolizes histamine outside of cells, and exists only in small intestine and colon, placenta and kidney
DAO does not consume VB6 when breaking down histamine

HNMT is metabolizes histamine mostly within a cell, and exists in most tissues
HNMT does consume 1 molecule of SAM-e when breaking down 1 molecule of histamine.

Since you have C677T heterozygous, you will need some methylfolate or SAM-e supplement to help HNMT to break down histamine.

Details: http://ajcn.nutrition.org/content/85/5/1185
Title: Re: New ideas about POIS and review of excitotoxicity
Post by: trusttheprocess on July 26, 2017, 01:08:30 AM
Romies, thanks for your suggestions, I never tried DAO or NADH but both should help POIS sufferers.  I have been taking SAM-e and methylfolate for a long time, I agree they are essential for someone with an MTHFR mutation (30-40% of people).   

I wanted to let everyone know that I will be testing an antifungal drug against POIS in the next few days.  I'm still in shock I got a doctor to let me try this, I haven't even gotten my urine culture back yet, and I didn't even have to go to the doctor to get him to agree to this. I cancelled my appointment because I was in the middle of POIS, he asked how I was and if there was anything he could do to help, so I sent him this message:

"Thanks for checking in with me!  I'm alright, just having a flare up of a chronic condition, nothing I haven't dealt with before.  If you would like to help I'd greatly appreciate your opinion on something.  My condition (chronic prostatitis) is notoriously hard to treat, as it's a syndrome with many forms, and the first line of treatment is antibiotics even though this only helps a small portion of patients.  It is also known that bacteria are not involved in its pathogenesis.  This disease has a great number of systemic effects and lowers quality of life significantly, so I've been doing a lot of research on it.  I heard many reports of low carb diets helping, and this is helping me, but I'm still having serious symptoms.  Many people believe that low carb diets treat prostatitis by starving out fungal species, which are normally present in the body as commensal organisms, but can also lead to serious infection.  There was a study that treated 1000 prostatitis patients with a low carb diet and a common anti fungal drug flucanazole, and there was a significant improvement in 80% of patients.  It is a rather unorthodox treatment, but one I'd like to try, as I have been given many rounds of simultaneous antibiotics and corticosteroids for chronic bronchitis.  This not only suppresses the antifungal immune response, but also eliminate the bacteria that compete with it.  During flare ups of my condition my urine becomes cloudy, so I went to the doctor a few days ago to get a urine culture, but they said the lab ordinarily only tests for bacteria, and cultures for fungi are unreliable (they didn't even test for it in the study I mentioned).  I'm starting a new semester of college soon and I really want to try this treatment, I missed more than a quarter of my classes last semester dealing with flare ups of this condition, do you know any doctors that might be open to me trying this?"

To my surprise he got back and said he had read about this, agreed with all that I had researched, and would be glad to write me a prescription for an anti fungal.  The antifungal I mentioned, flucanazole, is a highly bio-available and effective anti fungal that is excreted through the urine.  Some candida species are resistant to it however, so hopefully the lab is testing for this if my urine cultures grew candida.

I hope I can report positive results very soon, but in the meantime for everyone else I have done a few days of research into what I think the best natural treatments for candida induced POIS.  My theory is that some candida has colonized some immune privileged or "sanctuary sites", a term that describes sites with a significant reduction or complete lack in immune system activity, such as the brain, spinal cord, eyes, testes, prostate, or epididymis.  I believe POIS is simply the leaking of candida into the bloodstream, a very serious finding as candida can get into the brain and cause death pretty quickly in immune compromised patients (or in our case, with flawed but intact immune systems, it will just make you feel like you're dying).  The barriers that prevent the immune system from reaching immune privileged sites can be passed by lipids that are small and nonpolar, properties that can be found in essential oils.  After looking over a few dozen scientific papers regarding anti-candida essential oils, I believe the following are the most promising for the treatment of POIS in order of most effective.  Do not take any of these without researching them yourself first, to make this easier I've put the active ingredient in parenthesis for most of these, which also helps with comparing them:

Sandalwood Oil
Lemongrass Oil (citral)
Coconut Oil (caprylic acid)
Winter Savory Oil/Oregano Oil (carvacrol)
Clove oil/Cinnamon Oil (eugenol)
Cinnamon Bark oil (trans-cinnamaldehyde)
Thyme oil/Black Cumin Seed Oil (thymol)
Black Walnut Oil (juglone)
Pau D'Arco Bark Oil (lapachol)
Olive Oil (hydroxytyrosol)
Eucalyptus Oil
Peppermint Oil
Tea Tree Oil
Garlic Oil (allicin)
Goldenseal Oil (berberine)
Ginger Oil (gingerol)
North American Ginseng Oil
Wormwood Oil
Grapefruit Seed Oil

Title: Re: New ideas about POIS and review of excitotoxicity
Post by: Quantum on July 26, 2017, 09:32:42 PM
HI TTP,

I will be very interested to follow the results of your fluconazole treatment and your overall approach of POIS treatment.  Thanks for sharing your hypothesis and all the steps you make.
Title: Re: New ideas about POIS and review of excitotoxicity
Post by: romies on July 27, 2017, 12:11:55 PM
Hi TTP,

Thank you for sharing your thoughts and experiences in dealing with Candidas and prostatitis.

1. Have you found a reliable way of testing your candida load? I understand it is normal for everyone to have a little bit of candidas in their guts. You just don't want to have an overgrowth. So I think it would be useful to quantify how much one has in his system.

For example, is urine D-Arabinitol test reliable in your experience?

2. What essential oil can get to those immune-privilege sites? Any thoughts?

Thanks and recover soon.
Title: Re: New ideas about POIS and review of excitotoxicity
Post by: certainlypois2 on August 01, 2017, 12:35:30 PM
can a fungal culture be done on semen
Title: Re: New ideas about POIS and review of excitotoxicity
Post by: Vandemolen on November 01, 2018, 10:38:34 PM
Romies, thanks for your suggestions, I never tried DAO or NADH but both should help POIS sufferers.  I have been taking SAM-e and methylfolate for a long time, I agree they are essential for someone with an MTHFR mutation (30-40% of people).   

I wanted to let everyone know that I will be testing an antifungal drug against POIS in the next few days.  I'm still in shock I got a doctor to let me try this, I haven't even gotten my urine culture back yet, and I didn't even have to go to the doctor to get him to agree to this. I cancelled my appointment because I was in the middle of POIS, he asked how I was and if there was anything he could do to help, so I sent him this message:

"Thanks for checking in with me!  I'm alright, just having a flare up of a chronic condition, nothing I haven't dealt with before.  If you would like to help I'd greatly appreciate your opinion on something.  My condition (chronic prostatitis) is notoriously hard to treat, as it's a syndrome with many forms, and the first line of treatment is antibiotics even though this only helps a small portion of patients.  It is also known that bacteria are not involved in its pathogenesis.  This disease has a great number of systemic effects and lowers quality of life significantly, so I've been doing a lot of research on it.  I heard many reports of low carb diets helping, and this is helping me, but I'm still having serious symptoms.  Many people believe that low carb diets treat prostatitis by starving out fungal species, which are normally present in the body as commensal organisms, but can also lead to serious infection.  There was a study that treated 1000 prostatitis patients with a low carb diet and a common anti fungal drug flucanazole, and there was a significant improvement in 80% of patients.  It is a rather unorthodox treatment, but one I'd like to try, as I have been given many rounds of simultaneous antibiotics and corticosteroids for chronic bronchitis.  This not only suppresses the antifungal immune response, but also eliminate the bacteria that compete with it.  During flare ups of my condition my urine becomes cloudy, so I went to the doctor a few days ago to get a urine culture, but they said the lab ordinarily only tests for bacteria, and cultures for fungi are unreliable (they didn't even test for it in the study I mentioned).  I'm starting a new semester of college soon and I really want to try this treatment, I missed more than a quarter of my classes last semester dealing with flare ups of this condition, do you know any doctors that might be open to me trying this?"

To my surprise he got back and said he had read about this, agreed with all that I had researched, and would be glad to write me a prescription for an anti fungal.  The antifungal I mentioned, flucanazole, is a highly bio-available and effective anti fungal that is excreted through the urine.  Some candida species are resistant to it however, so hopefully the lab is testing for this if my urine cultures grew candida.

I hope I can report positive results very soon, but in the meantime for everyone else I have done a few days of research into what I think the best natural treatments for candida induced POIS.  My theory is that some candida has colonized some immune privileged or "sanctuary sites", a term that describes sites with a significant reduction or complete lack in immune system activity, such as the brain, spinal cord, eyes, testes, prostate, or epididymis.  I believe POIS is simply the leaking of candida into the bloodstream, a very serious finding as candida can get into the brain and cause death pretty quickly in immune compromised patients (or in our case, with flawed but intact immune systems, it will just make you feel like you're dying).  The barriers that prevent the immune system from reaching immune privileged sites can be passed by lipids that are small and nonpolar, properties that can be found in essential oils.  After looking over a few dozen scientific papers regarding anti-candida essential oils, I believe the following are the most promising for the treatment of POIS in order of most effective.  Do not take any of these without researching them yourself first, to make this easier I've put the active ingredient in parenthesis for most of these, which also helps with comparing them:

Sandalwood Oil
Lemongrass Oil (citral)
Coconut Oil (caprylic acid)
Winter Savory Oil/Oregano Oil (carvacrol)
Clove oil/Cinnamon Oil (eugenol)
Cinnamon Bark oil (trans-cinnamaldehyde)
Thyme oil/Black Cumin Seed Oil (thymol)
Black Walnut Oil (juglone)
Pau D'Arco Bark Oil (lapachol)
Olive Oil (hydroxytyrosol)
Eucalyptus Oil
Peppermint Oil
Tea Tree Oil
Garlic Oil (allicin)
Goldenseal Oil (berberine)
Ginger Oil (gingerol)
North American Ginseng Oil
Wormwood Oil
Grapefruit Seed Oil
Can you report back if the flucanazole helped you? I asked my doctor to give this medicine because I have candida because of antibiotics. I take those antibiotics against prostitis. After every O. my prostate gets infected. Then I take antibiotics. After two weeks the prostate infection is gone, but in the 3th week I get candida. And because of the candida I get another prostate infection. So I am in vicious circle. So now I want to abstain for a few weeks and stop antibiotics, then I hope the flucanazole will help. I also take VSL#3 and drink kefir and eat yoghurt and garlic.
Title: Re: New ideas about POIS and review of excitotoxicity
Post by: b_jim on November 07, 2018, 04:13:56 AM
I don't want to create a new topic so I post this here.
The article is in french.
https://www.7sur7.be/7s7/fr/1523/Famille/article/detail/1628417/2013/05/07/Allergique-a-son-propre-sperme-il-a-eu-du-mal-a-etre-pere.dhtml

This man is allergic to his own semen.
But the CAUSE seems clear : when he was 11 years old he get a severe pain in pelvic region with testicular infection.
The contact between blood and sperm creates antibody.
According to this article : 5 to 10% of men create antibodies against semen !

The negative point : the article don't talk about symptoms.

Title: Re: New ideas about POIS and review of excitotoxicity
Post by: Vandemolen on November 07, 2018, 08:20:43 AM
I don't want to create a new topic so I post this here.
The article is in french.
https://www.7sur7.be/7s7/fr/1523/Famille/article/detail/1628417/2013/05/07/Allergique-a-son-propre-sperme-il-a-eu-du-mal-a-etre-pere.dhtml

This man is allergic to his own semen.
But the CAUSE seems clear : when he was 11 years old he get a severe pain in pelvic region with testicular infection.
The contact between blood and sperm creates antibody.
According to this article : 5 to 10% of men create antibodies against semen !

The negative point : the article don't talk about symptoms.
I think my Pois started when I over masturbated and have a bit flood on my p.
Title: Re: New ideas about POIS and review of excitotoxicity
Post by: Muon on January 12, 2019, 05:41:25 PM
I'm surprised Treg cells haven't been explored yet because they play a huge role in self tolerance. If allergies, auto-antibodies and MCAD have been explored then the next logical step would be investigation of Treg cells. About IL-17, my brother and I have low levels. People with local fungal outbreaks, should in my opinion, check their IL-17 level.
Title: Re: New ideas about POIS and review of excitotoxicity
Post by: Nas on January 12, 2019, 07:05:02 PM
I'm surprised Treg cells haven't been explored yet because they play a huge role in self tolerance. If allergies, auto-antibodies and MCAD have been explored then the next logical step would be investigation of Treg cells. About IL-17, my brother and I have low levels. People with local fungal outbreaks, should in my opinion, check their IL-17 level.
I do have a fungal issue in my skin, I do not know what to call it but it's been since forever. All the doctor told me is that it is fungal. It doesn't cause me any issues other than pimples.
Title: Re: New ideas about POIS and review of excitotoxicity
Post by: Vandemolen on January 12, 2019, 08:09:37 PM
I'm surprised Treg cells haven't been explored yet because they play a huge role in self tolerance. If allergies, auto-antibodies and MCAD have been explored then the next logical step would be investigation of Treg cells. About IL-17, my brother and I have low levels. People with local fungal outbreaks, should in my opinion, check their IL-17 level.
I do have a fungal issue in my skin, I do not know what to call it but it's been since forever. All the doctor told me is that it is fungal. It doesn't cause me any issues other than pimples.
Pityrosporum folliculitis is a fungal ‘acne’. Could it be PF? My doctor said that I have it. Ketonazole cream helps me.
Title: Re: New ideas about POIS and review of excitotoxicity
Post by: Nas on January 12, 2019, 08:27:44 PM
I'm surprised Treg cells haven't been explored yet because they play a huge role in self tolerance. If allergies, auto-antibodies and MCAD have been explored then the next logical step would be investigation of Treg cells. About IL-17, my brother and I have low levels. People with local fungal outbreaks, should in my opinion, check their IL-17 level.
I do have a fungal issue in my skin, I do not know what to call it but it's been since forever. All the doctor told me is that it is fungal. It doesn't cause me any issues other than pimples.
Pityrosporum folliculitis is a fungal ‘acne’. Could it be PF? My doctor said that I have it. Ketonazole cream helps me.
I just looked up PF and I think I have it. But what I mostly have are patchy brown stains that keep growing in my chest and back region.
Title: Re: New ideas about POIS and review of excitotoxicity
Post by: Vandemolen on January 12, 2019, 08:57:57 PM
I have PF in back region, chest and upper arms. POIS and antibtioics my PF worse. Daktarin (ketonazole creme) helps me a bit.

https://poiscenter.com/forums/index.php?topic=2612.msg22753#msg22753
Title: Re: New ideas about POIS and review of excitotoxicity
Post by: Muon on January 12, 2019, 09:11:46 PM
Pityrosporum folliculitis is a fungal ‘acne’. Could it be PF? My doctor said that I have it. Ketonazole cream helps me.
You mentioned Daktarin earlier. That one in gel form got me rid of oral fungal outbreak (there were literally fungal wires appearing in my mouth). There was a problem. Normally you would swallow the substance. When I did that I got literally flattened by it, my legs got weak and I collapsed to the ground and my immune system felt extremely weak, never experienced something like this. So I called the doc and she said it never happened before, she contacted the producer and they told her I was the first case that experienced something like this. They advised me not to swallow it just flush the mouth. I still don't know why I reacted so extreme to it (herxheimer?). If that was a herxheimer reaction then perhaps I should take it again.
Title: Re: New ideas about POIS and review of excitotoxicity
Post by: Vandemolen on January 12, 2019, 09:27:41 PM
Pityrosporum folliculitis is a fungal ‘acne’. Could it be PF? My doctor said that I have it. Ketonazole cream helps me.
You mentioned Daktarin earlier. That one in gel form got me rid of oral fungal outbreak (there were literally fungal wires appearing in my mouth). There was a problem. Normally you would swallow the substance. When I did that I got literally flattened by it, my legs got weak and I collapsed to the ground and my immune system felt extremely weak, never experienced something like this. So I called the doc and she said it never happened before, she contacted the producer and they told her I was the first case that experienced something like this. They advised me not to swallow it just flush the mouth. I still don't know why I reacted so extreme to it (herxheimer?). If that was a herxheimer reaction then perhaps I should take it again.
Wow that must be frightening. The oral gel of Daktarin did not help me much. But Daktarin for the skin helped me a bit againgt PF. But it also helped that the 3 weeks of antibiotics were passed. I had no side effects from both Daktarin’s.
Title: Re: New ideas about POIS and review of excitotoxicity
Post by: Nagisa on March 09, 2019, 11:46:39 PM
Wow, I?m so glad to find this forum. I came here while researching kynurenine pathway.

My story:

One year ago, I used fluoxetine for my generalized anxiety. I started with 10 mg and I continued it for 20 days.

Even at early days, it gave me some symptoms like hypersomnia. I couldn?t stand it and stopped it cold turkey.

But symptoms remained. Progressively worsened to this day and still worsening day by day. There is not any window or something like that.

My symptoms are:

-Excessive sleepiness
-Cognitive impairment (Very, very much)
-İmpairment on visuoperception (I can barely see what I?m looking. I stopped to read some forums as I can?t read any text)
-İmpairment on fine motor skills. (I was able to type 10 finger before. Now I?m can barely type one word.)
- All of the issues of estrogen doninance (joint pain, muscle weakness, body shape chances, fat on belly, low libido, men boobs?!)
- Inability to taste
- Random tremors (my muscles twitching at random times.)
- Gut problems. (These are very bad when I?m at a silent room)
- Additionaly to these bad side effects, my excessive anxiety completely gone.


I have read tons of things since that day. My final theory is that fluoxetine disrupted my kynurenine pathway. Studies shows that these antidepressants increases KAT and decreases KMO. Excess kynurenic acid blocks most of the excitatory receptors.


So why I don?t try a KAT inhibitor? I don?t know if there is an inflammation or not. I can fry my brain if I do something wrong. You guys seemed very informed to me. Also I think I have POIS too. Because the biggest thing that make me worse is masturbation. I?m permanently crashing after every orgasm.

My cognitive side effects are gone so bad that I?m not able to research anymore. I?m wanting help at this point. What should I do now?