Transiently Induced Immune Deficiency and Therapy

[quikot]

I. prevent transient immune suppression (prepack, 90min prior)
caffeine (150mg)
citrulline malate or citrulline nitrate (3g)
N-acetyl-tyrosine (200mg)
theanine (300mg)

Indomethacin is know to increase NK cell number and activity by inhibiting prostaglandin induced immune suppression. Indomethacin has antiviral, antibacterial and anticancer properties due to this increase in NK cells. indomethacin (with prepack) can be used as a quick immune stimulant to speed up results.

So if I understand correctly, COX-2 inhibition isn't necessary to include in a prepack as long as immune competence is being constantly established via pathogen removal, daily immune boosting stack and epithelial barrier repair.

Although, at the same time it seems like COX-2 inhibition by Indomethacin is greatly advantageous to establishing immune competence faster? But since I'm already taking 12 supplements a day, I'm a bit uncomfortable with adding NSAIDs as well (even though ibuprofen did help me a lot) as I don't want any stomach or liver problems.

Btw, what function does N-Acetyl-Tyrosine have? Does it inhibit Adenylyl Cyclase?

[nanna1]

Hi quikot,

Thanks for the good questions and comments!

So if I understand correctly, COX-2 inhibition isn't necessary to include in a prepack as long as immune competence is being constantly established via pathogen removal, daily immune boosting stack and epithelial barrier repair.

Although, at the same time it seems like COX-2 inhibition by Indomethacin is greatly advantageous to establishing immune competence faster? But since I'm already taking 12 supplements a day, I'm a bit uncomfortable with adding NSAIDs as well (even though ibuprofen did help me a lot) as I don't want any stomach or liver problems.

  I think you are correct. But there were a few times during my early experimentation that I took indomethacin for an immune boost. I assume the immune boost only last for 4 hours, so I am not sure how much impact it had on the results. But the most effective time for that immune boost is before and during ejaculation.

  Whenever you take indomethacin, you should always take the antioxidants selenium and vitamin C (i.e. selenmethionine - 200 micrograms and ascobate-vitC - 500mg). The toxicity of indomethacin comes from free radicals (ROS) and a slow depletion of glutathione over time (when taken daily over weeks). This is because the concentration of oral drugs is always highest in the stomach and liver. Antioxidants detoxify indomethacin:

  About Vasoconstrictors:..
... The research indicates that selenomethionine detoxifies indomethacin (Ref1, Ref2, Ref3, Ref4)...

For example:
"Oral administration of indomethacin clearly increased the gastric ulcer area in the stomach, whereas selenium applied for 3 days significantly decreased the gastric ulcer area in a dose-dependent manner. In addition, selenium markedly reduced the increase of lipid peroxidation induced by indomethacin in the gastric mucosa and increased activities of radical scavenging enzymes such as superoxide dismutase, catalase, and glutathione peroxidase in a dose-dependent manner. These results reveal that selenium can heal indomethacin-induced gastric ulcers through elimination of the lipid peroxides and activation of radical scavenging enzymes."
-Curative effect of selenium against indomethacin-induced gastric ulcers in rats (2011)

  But indomethacin is an FDA approved drug that is one of the most effective and common treatments for coital(sex)-headaches, trigeminal hemicrania, cluster headaches, migraines and many other neuroimmune diseases. Since it is taken with the pre-pack only (not daily), I don't see any problems with safety even in the long term. However, people who have allergic reactions to medications should definitely share this with your doctor before trying any drug.

Btw, what function does N-Acetyl-Tyrosine have? Does it inhibit Adenylyl Cyclase?

N-Acetyl-Tyrosine (NAT) converts to dopamine, and dopamine prevents caffeine jitters. But too much dopamine can interfere with the immune stimulation of the stack. AlphaGPC works better than NAT, but AlphaGPC is more expensive. If you have the money, I would prefer AlphaGPC.

-------------------------------------------

Hi slon_ik,
Thanks for the interesting comments.

...We tried to find at least something that, according to the analyzes, all people with POIS would have. We did a lot of tests on the endocrine system. The closest disorder was an increase in morning blood cortisol (80% of patients). The remaining 20% ​​had other adrenal disorders. Therefore, it can be concluded that the endocrine glands are very close to the first cause of POIS, but are not this cause. The closest are the hypothalamus and pituitary gland.

Everyone (including non-POIS) has an early morning increase in cortisol. So this is perfectly normal. When trying to determine if some result is related to POIS, I like to use a control group. You can use the "Neuroendocrine responses to arousal and orgasm" thread as a source for your control group.

White circles: 24 hour sleep deprivation, Black circles: 24 hour normal sleep. Gray region (23:00 - 7:30): sleeping period
-Number and Function of Circulating Human Antigen Presenting Cells Regulated by Sleep

... And then you very accurately said that D3 stimulates the response to infections. But the problem is that this answer is almost always the same - it is inflammation, local or general, but inflammation. And if the inflammation system is knocked down, then even from the slightest increase in the response to infections (from D3), the inflammation will increase greatly. That is, it is impossible to understand the root cause without additional research)) It may be an immune response to infections, and a failure of the inflammation system))

  Immune responses to infection are not always inflammatory. Fever, rhinitis, diarrhea, fatigue, etc... usually do not involve inflammation. Symptoms from the immune system can make you feel bad without causing inflammation. A small part of immune reactions involve inflammation, but most immune reactions are hormone/cytokine/neurotransmitter signaling that creates a hostile environment for infections, poisons and cancers. The good news is that there is already a lot of POIS research published in journals and POIS data hosted on this forum. If we do not ignore the research/data, then I think we will be encouraged by the wealth of knowledge that currently exist for POIS. With that said, new data and test can lead to new hypotheses that are useful. It would be a great benefit to the POIS community if you would be willing to share any medical test here: Gather and Post Here Your Medical Tests Results

[quikot]

Very informative response nanna1, thank you. As per your recommendation, I've ordered Alpha GPC. And perhaps I could give Indomethacin a shot too, though here in the UK it's a prescription-only drug. I guess I could try to persuade my GP to prescribe it...

I'm seeing various improvements from this therapy and I'll post a detailed review eventually. I think the longer I am on this therapy, the more positive results I get. Thank you for sharing it!

[slon_ik]

But perhaps this is a failure of the inflammation system. And the inflammation is exacerbated even by weak immune rises.

Immune activated state making you weak as in Th1 polarization (good against viral infection, not so good when it's not needed anymore and you keep getting stuck in that same state). Immune stimulants may skew it further towards Th1 activation. Steroids could have a positive effect.

Я много раз пытался принимать стероиды. Это были аналоги кортизола и некоторых его предшественников. Во всех случаях мне становилось хуже, иногда сразу, а иногда через несколько дней. Так же знаю других больных POIS, которым стероиды тоже не помогали. Поэтому я сделал вывод, что причина POIS точно не в эндокринной системе. А когда мы пытаемся компенсировать наши проблемы с помощью стероидов, то результаты будут непредсказуемыми, так как мы не попадаем точно в цель.

Проблема поиска причины POIS в иммунной системе в том, что иммунная система намного больше, чем мы о ней знаем, и имеет множество регуляторов ))


I have tried steroids many times. These were analogs of cortisol and some of its predecessors. In all cases, I got worse, sometimes immediately, and sometimes after a few days. I also know of other POIS patients who were not helped by steroids either. Therefore, I concluded that the cause of POIS is definitely not in the endocrine system. And when we try to compensate for our problems with steroids, the results will be unpredictable, since we don't hit the target.

The problem of finding the cause of POIS in the immune system is that the immune system is much more than we know about it, and has many regulators))

[slon_ik]

So if I understand correctly, COX-2 inhibition isn't necessary to include in a prepack as long as immune competence is being constantly established via pathogen removal, daily immune boosting stack and epithelial barrier repair.

Although, at the same time it seems like COX-2 inhibition by Indomethacin is greatly advantageous to establishing immune competence faster? But since I'm already taking 12 supplements a day, I'm a bit uncomfortable with adding NSAIDs as well (even though ibuprofen did help me a lot) as I don't want any stomach or liver problems.

Btw, what function does N-Acetyl-Tyrosine have? Does it inhibit Adenylyl Cyclase?

Возможно вам будет полезна информация ))

Я принимаю ингибиторы ЦОГ-2 уже 25 лет. У меня во время POIS всегда болит голова. Так же  у меня головные боли и в другое время. Я принимаю цитрамон, это русский препарат, который содержит аспирин и кофеин. За 25 лет никаких побочных эффектов не заметил ) Принимаю где то 1 - 2 раза в неделю. Но у меня понижена кислотность желудка, поэтому язва мне не грозит.

Но последние несколько лет мне ингибиторы ЦОГ-2 уже не помогают. Это значит, что понижая ЦОГ-2 мы лишь компенсируем другую проблему, но не уменьшаем истинную причину POIS.


Perhaps the information will be useful to you))

I have been taking COX-2 inhibitors for 25 years. I always have a headache during POIS. I also have headaches at other times. I am taking citramone, a Russian drug that contains aspirin and caffeine. For 25 years I have not noticed any side effects) I take it somewhere 1 - 2 times a week. But my stomach is acidic, so I don't have an ulcer.

But over the past few years, COX-2 inhibitors are no longer helping me. This means that by lowering COX-2, we only compensate for another problem, but do not reduce the true cause of POIS.

[slon_ik]

Everyone (including non-POIS) has an early morning increase in cortisol. So this is perfectly normal. When trying to determine if some result is related to POIS, I like to use a control group. You can use the "Neuroendocrine responses to arousal and orgasm" thread as a source for your control group.
...
It would be a great benefit to the POIS community if you would be willing to share any medical test here: Gather and Post Here Your Medical Tests Results

В качестве контрольной группы у нас были здоровые люди ))
Когда я говорю про увеличение кортизола утром, то имею в виду, что увеличение было выше нормы для здоровых людей.
12 человек с POIS сдали анализы кортизола , и у 10 из них кортизол был выше, чем норма! Статистически это серьезный результат.
Кроме кортизола были и другие анализы, но там все было разное  у всех.

Проблемы в том, что я пользуюсь автоматическим переводчиком, и название анализов может быть переведено некорректно. Поэтому я ещё и не выложил все результаты. А переводить вручную у меня сейчас нет времени, очень много работы ))

Попробую сейчас тут сделать автоматический перевод, может будет понятно ))

Всего сдавали анализы 17 человек с POIS, но многие сдали только некоторые анализы.

Про кортизол я уже сказал.
Список анализов, по которым у всех были разные результаты (норма, выше или ниже нормы):

лг, тестостерон, дегидротестостерон

ттг, т3, т4

актг, кортизол по суточной моче, альдостерон, ренин, 17-кетостероиды по суточной моче, ДГЭА

Норадреналин, Адреналин, Дофамин

пролактин, прогестерон, эстрадиол

PH, PO2, PCO2, K+, Na+, Cl-

Понятны ли названия?

Ещё следует отметить, что есть подозрение, что PH, PO2, PCO2 будут в сторону гипоксии, но у нас мало этих анализов (только 4 человека)
 поэтому статистически это не подтверждено.



We had healthy people as a control group))
When I talk about the increase in cortisol in the morning, I mean that the increase was higher than normal for healthy people.
12 people with POIS had their cortisol tested, and 10 of them had higher than normal cortisol levels! Statistically, this is a serious result.
In addition to cortisol, there were other tests, but everything was different for everyone.

The problem is that I use an automatic translator, and the name of the tests may be translated incorrectly. Therefore, I have not yet posted all the results. And now I don't have time to translate manually, there is a lot of work))

Now I will try to make an automatic translation here, it may be clear))

In total, 17 people with POIS were tested, but many were only tested.

I've already mentioned cortisol.
List of tests for which everyone had different results (normal, above or below normal):

lh, testosterone, dehydrotestosterone

ttg, t3, t4

actg, daily urine cortisol, aldosterone, renin, 17-ketosteroids daily urine, DHEA

Norepinephrine, Adrenaline, Dopamine

prolactin, progesterone, estradiol

PH, PO2, PCO2, K +, Na +, Cl-

Are the names clear?

It should also be noted that there is a suspicion that PH, PO2, PCO2 will be in the direction of hypoxia, but we have few of these analyzes (only 4 people)
 therefore, it is not statistically confirmed.

[Monte]

I have the same as sun_ik. I can take vitamin C and vitamin D only in very small doses, because higher doses cause me symptoms as in POIS. But now it's getting better, perhaps because I take prepacks and a lot of anti-inflammatory and antiviral drugs, so my vitamin C and vitamin D tolerance has increased.

[nanna1]

...Do you now rule out the possibility of a glutamate-mediated triggering of POIS ? How would it fit in the theory ? I've done a (very) quick research on the web and glutamate / NMDAr activation seems rather to *inhibit* adenylyl cyclase, but it's really a bit too complicated for me.

Hi Prospero,

  Great question! POIS treatment: Theory and supplement stack focuses narrowly on the trigger of POIS symptoms. The therapy in the original post focuses more generally on a potential cause of the disease that causes POIS. But the trigger of symptoms is the same in both cases.
  Glutamate turns neurons on (excitation) so that they can receive signals from other neurotransmitters like acetylcholine, dopamine and adrenaline. GABA turns neurons off (sedation) so that those neurons become unresponsive to other neurotransmitters like acetylcholine, dopamine and adrenaline. Glutamate is required for any kind of arousal, including orgasm. It is not possible to completely inhibit NMDA and have an orgasm at the same time. Both adrenaline and glutamate are required to orgasm, and both noradrenaline (norepinephrine) and glutamate are required for ejaculation. So I don't really know how to distinguish between a glutaminergic triggered POIS and an adrenergic triggered POIS. They should happen together.

"...different neuropharmacological factors impact thresholds for seizures and sexual climax in similar ways, likely reflecting overall propensity for activation cascades to spread through neuronal networks: thresholds increase with elevated GABA receptor stimulation, but decrease with elevated glutamate receptor stimulation, dopamine agonists, and dopamine/norepinephrine reuptake inhibitors" -What is orgasm? A model of sexual trance and climax via rhythmic entrainment

  This probably deserves some background information: Neurons have on and off states. When a neuron is on, neurotransmitters like catecholamines (dopamine, adrenaline, etc...) and acetylcholine can send signals by binding to their receptors. But when a neuron is turned off, the neuron becomes unresponsive to neurotransmitters even when those neurotransmitters bind to the receptor.

  The on state of a neuron is controlled by the NMDA and other glutamate receptors. When glutamate and glycine stimulate the NMDA receptor, then a neurotransmitter like dopamine can stimulate the D2-dopamine receptor (signaling sexual pleasure). Or a neurotransmitter like norepinephrine can stimulate the alpha1-adrenergic receptor (signaling ejaculation).

  The off state of a neuron is controlled by the glycine and GABA receptors. When GABA stimulates the GABA receptors, then a neurotransmitter like dopamine cannot stimulate the D2-dopamine receptor and norepinephrine is prevented from stimulating the alpha1-adrenergic receptor. So GABA prevents the signals of sexual pleasure and ejaculation.

So this means that anytime norepinephrine is involved, glutamate is also involved.
NMDAr stimulates an increase in adenylyl cyclase activity (nMDA receptor activation increases cyclic AMP in area CA1 of the hippocampus via calcium/calmodulin stimulation of adenylyl cyclase (1993)). But beta-alanine is a much stronger NMDAr inhibitor than theanine. I chose theanine (instead of beta-alanine) in the pre-pack because it is an immune stimulant that can also balance the jitter effects of caffeine.

[nanna1]

I have the same as sun_ik. I can take vitamin C and vitamin D only in very small doses, because higher doses cause me symptoms as in POIS. But now it's getting better, perhaps because I take prepacks and a lot of anti-inflammatory and antiviral drugs, so my vitamin C and vitamin D tolerance has increased.

Hi Monte,
  That is awesome that you are able to increase your tolerance to vitamin C and D. I would like to point out that with the therapy described in this thread is supposed to stimulate an immune response to pathogens in your body. If you are successful at stimulating your immunity, this will likely cause symptoms at some point. When I did this therapy for myself, I tried to maximize the symptoms as much as possible by increasing the dose. Vitamin C is an antioxidant, anti-inflammatory, anti-histamine nutrient with no known oral toxicity. So I was able to use the symptoms as an indirect indicator of its immune boost and the attempt by my immune cells to remove pathogens.

  My symptoms increased in the beginning, but these were not typical POIS symptoms. For example, I had a lot of face-muscle twitching on AHCC the first week, but this was s minor symptom that I sometimes experienced with POIS. I don't remember having an orgasm the first few weeks when I was trying AHCC (or I don't remember the symptoms). Eventually, I did experience more POIS like symptoms from taking AHCC, but it was never as bad as real POIS. I think that the path to symptom reduction will look a little different for each person. People who also take andrographis may not experience increased symptoms with AHCC. I read that andrographis speeds up the adaptive immunity, but initially I was not taking andrographis.

  In my case, it was a detox reaction. At high concentration, copper is toxic to certain bacteria and virus. Good bacteria in the microbiome have mostly adjusted to be compatible with the nutrients and minerals in the human diet. But foreign (harmful) bacteria die quickly in the presence of copper. When these bacteria die they burst open and release toxins/debris. If the toxins reach a high enough concentration in the digestive tract, our immune system will try to remove the toxins from the body as fast as possible. Sometimes this means vomiting.
  Drinking more water and/or food can dilute the copper and slow down how fast the bacteria die. But too much food could eliminate the die-off effect from copper. I preferred to just drinking water when I felt sick or like I might vomit. Eventually, I got to the point where I could take copper on an empty stomach and not feel anything. But, not everyone has to do what I did. Experiment with whatever method you feel comfortable with.

  I found out early on that AHCC cause (short duration) random localized nerve pain and muscle twitches. Mega-dose-vitamin C cause rhinitis. High-dose melatonin caused itching. I interpreted these symptoms as the supplements activating different parts of my immune system. These symptoms were mind enough to tolerate and did not cause fatigue or cognitive issues. So I started trying to maximize the symptoms with different supplement combinations. As the (non-POIS) symptoms started to disappear, I increased the dose to restore maximal immune activation and symptoms. Sometimes I cycled off-on the supplements to restore and increase flu-like symptoms. The side-effects of melatonin cause me to stop taking it...

...These experiments occurred mostly outside of POIS. But I notice something weird around April/May 2019. When the vitamin C "wore off" (I could no longer produce rhinitis by increasing the dose), the rhinitis that I used to experience during POIS disappeared. I never experience rhinitis during POIS again.
  The same effect happen with AHCC and the nerve-pain/muscle-twitch. Once increasing my AHCC dose could no longer produce nerve pain, the pains and muscle-twitch that I used to experience during POIS also disappeared.
  The same effect happened with copper. Copper initially caused diarrhea and stomach pain in the area where I would normally get IBS, with a little nausea. But after a while of cycling copper on-and-off and gradually taking it more often throughout the day, the stomach problems caused by copper went away. And the IBS from POIS also went away at the same time.
  These effects were permanent (or at least still effective) and continue to last several months after I no longer take these supplements. The time frame for remission of POIS symptoms varied for each combo of supplements and symptoms. For example, it took about 2 month for AHCC to cause symptom remission, but during that time the (non-POIS) symptoms increased before they decreased. For copper, it took a little over two weeks, but I started experiencing a reduction in stomach problems after 1 week. The immune therapy reflects more so the lessons learned rather than a exact description of all the things that I experimented with. I hope that clarifies things a bit

[berlin1984]

Huge Wikipedia article about Copper in health.
https://en.wikipedia.org/wiki/Copper_in_health

"Studies have shown that elevated concentrations of copper can be found near the sites of infection.
Other studies have shown that copper deficiency in the host can be linked to increased susceptibility to infection (and improved immune response when the host is provided with a copper supplement)."
http://blog.eoscu.com/blog/copper-and-our-innate-immune-system

 "The immune system requires copper to perform several functions, of which little is known about the direct mechanism of action. [...] Some of the recent research showed that interleukin 2 is reduced in copper deficiency and is likely the mechanism by which T cell proliferation is reduced. These results were extended to show that even in marginal deficiency, when common indexes of copper are not affected by the diet, the proliferative response and interleukin concentrations are reduced. The number of neutrophils in human peripheral blood is reduced in cases of severe copper deficiency. "
https://pubmed.ncbi.nlm.nih.gov/9587153/

Some old forum links that we could go through:
https://www.thenakedscientists.com/forum/index.php?topic=6576.19040
https://www.thenakedscientists.com/forum/index.php?topic=6576.18800
https://www.thenakedscientists.com/forum/index.php?topic=6576.17480 <- something about elevated levels though (not deficiency..)
https://www.thenakedscientists.com/forum/index.php?topic=6576.18540
There used to be a ton of discussion about copper.

[Monte]

I've been feeling very good for a long time lately, the pre-orgasm prepacks have worked beautifully. But yesterday I ate 2 sour mandarins. This was followed by symptoms such as tetany (jumping muscles, body pain) and POIS (brain fog, mood drop, anxiety). It was not so bad for a long time. I had to take prepack and calcium several times (50% improvement). Only today taking a multivitamin helped so much that now (after 30 hours) I'm 98% ok. Do you think that vitamin C in mandarins caused these symptoms? I had long suspected citrus as a symptom trigger as with POIS, but now I'm pretty sure. In addition to mandarins, I also had tofu in a sprout salad, but I suspect mandarins are the cause.

[Clues]

I suspect mandarins are the cause.

Citrus fruits can trigger mast cell mediator release IIRC.

[nanna1]

Do you think that vitamin C in mandarins caused these symptoms?

Hi Monte, mandarins don't contain enough vitamin C to cause any near-term immune stimulation. The highest vitamin C foods (by weight) are:
guavas > bell peppers > kiwi > broccoli > papaya > snow peas > oranges > green leaf vegetables (spinach, kale).

If mandarins are causing problems, it is probably either the citric acid or the malic acid. I haven't had that reaction from mandarins, but lemons (high citric acid) used to give me a sore throat.

[...] Some of the recent research showed that interleukin 2 is reduced in copper deficiency and is likely the mechanism by which T cell proliferation is reduced. These results were extended to show that even in marginal deficiency, when common indexes of copper are not affected by the diet, the proliferative response and interleukin concentrations are reduced. The number of neutrophils in human peripheral blood is reduced in cases of severe copper deficiency. "
https://pubmed.ncbi.nlm.nih.gov/9587153/

Good finds berlin1984!

[berlin1984]

There used to be a ton of discussion about copper.

I did a hair mineral test and I'm now very confused about taking copper or not.
Maybe I should not have done the test while supplementing with copper though. 

https://poiscenter.com/forums/index.php?topic=2684.msg37430#msg37430

[Prospero]

Hi nanna1,

I saw a doctor today who already knew POIS (which is quite rare for a non-specialist), and at the end of the meeting I succinctly summarized your theory. He thought it was complete bullshit and that you were a charlatan, sorry Nanna ^^ He was also very skeptical about the benefits of IV Vitamin C generally speaking, and seems to believe quite strongly in the thesis of a temporary dysautonomia (or this kind of neurological disorder). I'm French and the neurological cause is favored by the French researchers who have studied POIS, so this is not really surprising.

Though I don't make a big deal about his strong reject of your hypotheses (I probably explained it badly and, be that as it may, it was too quick for him to really think about it), he pointed out the efficacy of benzodiazepines, neuroleptics, SSRIs, beta-blockers, etc., at least in a reasonable number of cases, as a sign that the cause of the problem was neurological. I thought that it was indeed a kind of blind spot of what I understand about your theory.

What would be the link between the transient immune deficiency (and the possible viral infection leading to an impaired endorphin signalling), and the success of "neurological" treatments ? I can see that the serotonin depletion arguably provoked by IDO activation may provoke troubles that might be countered by serotonergics/SSRIs, but apart from that it's quite obscure to me. (Maybe the treatments are calming down some of the "opioid withdrawal-like" symptoms ?)

[Muon]

I saw a doctor today who already knew POIS (which is quite rare for a non-specialist)

Could you ask your doctor if we can add him to this list?
https://poiscenter.com/forums/index.php?topic=2575.0

[Prospero]

I'll see but basically for POIS he will send me to prof. Amarenco of Hospital Tenon, who studies it and is already in the list. (Before that he wants to make some check-ups because he believes, as I do, that I have a prostatitis, and it would be better to know exactly what is caused by POIS and what is caused by prostatitis.)

[Muon]

Before that he wants to make some check-ups because he believes, as I do, that I have a prostatitis.

Show him this paper: https://sci-hub.se/10.1016/j.jri.2013.02.004

[Prospero]

Well, I'm sorry but I can't open it.

[Muon]

What about these? Same paper different URL.
https://sci-hub.tw/10.1016/j.jri.2013.02.004
https://sci-hub.do/10.1016/j.jri.2013.02.004