Author Topic: Desensitization, Fact or Fiction?  (Read 44794 times)

kurtosis

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Re: Desensitization, Fact or Fiction?
« Reply #60 on: November 06, 2012, 06:18:46 PM »
You may have to take the h3 blocker for more than 1 day but, I believe, that our histamine levels are just too high in general and we can't effectively clear it when it's released. In that case, the h3 blocker taken for a day or so would get over the worst effects.

The other alternative is to reduce histamine production using mast cell stabilisers. Histamine can also be produced by gut bacteria. If that's the problem then treating the bacteria may be the solution. Histamine can be overproduced by the body in conditions such as mastocytosis that I described earlier.

Methionine is one mechanism to help reduce histamine. Another mechanism is increasing DAO levels (as B_Daniel pointed out to me in an email).
There are supplements that can help you do this. B6 and vitamin C help increase it. Synthetic DAO can be taken in products such as DAOSIN / histame which may provide some release.

demografx

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Re: Desensitization, Fact or Fiction?
« Reply #61 on: November 06, 2012, 07:15:09 PM »
10 years of significant POIS-reduction, treatment consisting of daily (365 days/year) testosterone patches.

TRT must be checked out carefully with your doctor due to fertility, cardiac and other risks.

40+ years of severe 4-days-POIS, married, raised a family, started/ran a business

demografx

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Re: Desensitization, Fact or Fiction?
« Reply #62 on: November 06, 2012, 07:16:19 PM »

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10 years of significant POIS-reduction, treatment consisting of daily (365 days/year) testosterone patches.

TRT must be checked out carefully with your doctor due to fertility, cardiac and other risks.

40+ years of severe 4-days-POIS, married, raised a family, started/ran a business

kurtosis

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Re: Desensitization, Fact or Fiction?
« Reply #63 on: November 07, 2012, 07:17:10 AM »
Interesting. It seems that progesterone may increase the release of diamine oxidase in pregnant women. Why is this interesting?
Diamine oxidase is also known as histaminase and deactivates histamine in the intestines and kidneys.
In one of Dr Selwyn Dexter's cases, the patient was spontaneously cured during his wife's pregnancy with symptoms worsening after she gave birth. Dexter thought progesterone may be the reason and he gave the patient a small amount of progesterone. He was unsure why it worked however.

I have an idea. Perhaps the progesterone stimulated an increase in the levels of DAO in the patients intestines, thus reducing histamine levels.
Women with DAO synthesis deficits may have problems during pregnancy and it may lead to miscarriage, from the papers I've read. While DAO imbalance may be due to bacterial infection, it may also be due to a genetic problems in synthesising DAO or its consituents. THerefore, it's possible that POIS suffers may have an above average number of miscarriages in their extended family.

High histamine, increases estadiol levels and, therefore, may create hormone imbalance in males.

Increasing methylation may still solve the problem but it could be part of a joint approach involving increasing DAO or taking synthetic DAO to reduce gastric histamine levels.
Why do I favour methylation? Because histamine in the brain isn't cleared by DAO and because (from http://ajcn.nutrition.org/content/85/5/1185.full)
Quote
HNMT has a slightly higher affinity for histamine [Michaelis-Menten constant (kM): 6?13 μmol/L] than does DAO (kM: 20 μmol/L)

Also from the same paper
Quote
In migraine patients, plasma histamine concentrations have been shown to be elevated both during headache attacks and during symptom-free periods. An increase in the number of brain mast cells is associated with pathologic conditions such as migraine, cluster headache, and multiple sclerosis (64).

However, if your POIS symptoms involve irritable bowel syndrome then supplementary DAO may bring some relief. Olive oil also promotes DAO synthesis apparently.

So, I think that I understand why the b complex doesn't work for everybody. I took it either with ginkgo (which contains a mast cell stabiliser) or methionine (which assists histamine methylation). Taken by itself without either of these some of the b vitamins may increase DAO (and reduce histamine) and others (like folic acid) may actually increase histamine levels.

If you're taking methionine with the b complex and it's still not improving things, I'm not sure what's happening.

Starsky

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Re: Desensitization, Fact or Fiction?
« Reply #64 on: November 07, 2012, 08:25:21 AM »
B6 and Vit C increase DAO, do you think this combo would be worth testing:

For histamine breakdown in the intestines:
-DAOsin
-Vit C
-B6


For methyletion:
-NADH
-l-methionine
« Last Edit: November 07, 2012, 08:30:32 AM by Starsky »

demografx

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Re: Desensitization, Fact or Fiction?
« Reply #65 on: November 07, 2012, 08:32:08 AM »
kurtosis, based on Dexter's paper, and enthusiasm at the forum for T/P experiments at the time (other papers suggested benefits), I became a forum guinea pig and tried progesterone. After 4 days, I quit, adverse side effects. But the "T/P" theory is still 'out there', perhaps in Pyropeach's compendium at mat780's POIS Info website.

Also, previous progesterone/POIS posts:
https://www.google.com/search?q=progesterone+pois+site:http://thenakedscientists.com&ie=UTF-8&oe=UTF-8&hl=en&client=safari

« Last Edit: November 07, 2012, 08:46:17 AM by demografx »
10 years of significant POIS-reduction, treatment consisting of daily (365 days/year) testosterone patches.

TRT must be checked out carefully with your doctor due to fertility, cardiac and other risks.

40+ years of severe 4-days-POIS, married, raised a family, started/ran a business

LAPOISSE

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Re: Desensitization, Fact or Fiction?
« Reply #66 on: November 07, 2012, 10:31:54 AM »
Interesting theory about H3 receptors ; if POIS is an allergy, it's definitely involves H3

How do we confirm that ? I've just read there is no anti H3 commercialized in my country..what about the vertigo drug ? Better than nothing ?

It might be but you'd have to take it under medical supervision. It agonises h1 receptors. Most anti-histamines are h1 inverse agonists so I'd be worried that taking an agonist before an O would make POIS symptoms worse. A possibility is taking betahistine after a h1 antagonist but that sounds risky also.

Other possibilities are mast cell stabilisers. These may reduce the overall levels of histamine and are used to treat some high histamine conditions. This could be a safer option for the moment.
I'm taking methionine to reduce histamine. It's not perfect but I sure feel a lot better. Oddly methionine and D-Ribose seems to work a bit better for me than SAMe. SAMe is good though but it kicks in fast and I feel my allergies returning in a few hours. I've also noticed that the now b vitamins I take has TMG / Betaine which is also used in methylation reactions.

Until h3 inverse agonists with either no or inverse agonistic effects on h1 and h2 are available then there's no "silver bullet" and this assumes that this theory is correct. I have a hunch that h3 inverse agonists will prove to be successful ADHD medications as I've heard some people say SAMe and methionine helped with their ADHD, implying there may be a common histamine connection to our problem and some sufferers of attention disorders. Pitolisant (another H3 inverse agonist) has shown some efficacy in studies to treat schizophrenia. Similarly with http://en.wikipedia.org/wiki/ABT-239
this class of drugs appears to have a nootropic affect, stimulating memory, learning, concentration and increasing intelligence.

This is an emerging area in neuroscience research. This overview paper is as recent as 2004 http://learnmem.cshlp.org/content/11/1/1.full
Remember that drugs can have a very long gestation period. Pharmaceutical companies don't rush them out on the market.

Clinical trials are showing that dosages are very important. In our brains, the h3 receptor triggered reduction of neurotransmitter production is being done by the body for safety reasons.  Accepting that some people (POIS sufferers perhaps) could have a malfunction, most people would not want their h3 receptors antagonised on a permeant basis. It could prove overstimulating, affect cardiac rhythms etc. It may be safer than amphetamines but these will still be powerful drugs.

Anyway, it's a research area for NORD to consider.

It seems there is some H3 antagonist only :

Ciproxifan
Conessine
Impentamine
Iodophenpropit

There is something I dont understand : apparently H3 antagonist help release of histamine :

Ciproxifan is an extremely potent histamine H3 inverse agonist/antagonist.
The histamine H3 receptor is an inhibitory autoreceptor located on histaminergic nerve terminals, and is believed to be involved in modulating the release of histamine in the brain. Histamine has an excitatory effect in the brain via H1 receptors in the cerebral cortex, and so drugs such as ciproxifan which block the H3 receptor and consequently allow more histamine to be released have an alertness-promoting effect.[1][2][3]

Hi though we were trying to lower the level of histamine release.I probably missed something

kurtosis

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Re: Desensitization, Fact or Fiction?
« Reply #67 on: November 07, 2012, 11:09:14 AM »
Interesting theory about H3 receptors ; if POIS is an allergy, it's definitely involves H3

How do we confirm that ? I've just read there is no anti H3 commercialized in my country..what about the vertigo drug ? Better than nothing ?

It might be but you'd have to take it under medical supervision. It agonises h1 receptors. Most anti-histamines are h1 inverse agonists so I'd be worried that taking an agonist before an O would make POIS symptoms worse. A possibility is taking betahistine after a h1 antagonist but that sounds risky also.

Other possibilities are mast cell stabilisers. These may reduce the overall levels of histamine and are used to treat some high histamine conditions. This could be a safer option for the moment.
I'm taking methionine to reduce histamine. It's not perfect but I sure feel a lot better. Oddly methionine and D-Ribose seems to work a bit better for me than SAMe. SAMe is good though but it kicks in fast and I feel my allergies returning in a few hours. I've also noticed that the now b vitamins I take has TMG / Betaine which is also used in methylation reactions.

Until h3 inverse agonists with either no or inverse agonistic effects on h1 and h2 are available then there's no "silver bullet" and this assumes that this theory is correct. I have a hunch that h3 inverse agonists will prove to be successful ADHD medications as I've heard some people say SAMe and methionine helped with their ADHD, implying there may be a common histamine connection to our problem and some sufferers of attention disorders. Pitolisant (another H3 inverse agonist) has shown some efficacy in studies to treat schizophrenia. Similarly with http://en.wikipedia.org/wiki/ABT-239
this class of drugs appears to have a nootropic affect, stimulating memory, learning, concentration and increasing intelligence.

This is an emerging area in neuroscience research. This overview paper is as recent as 2004 http://learnmem.cshlp.org/content/11/1/1.full
Remember that drugs can have a very long gestation period. Pharmaceutical companies don't rush them out on the market.

Clinical trials are showing that dosages are very important. In our brains, the h3 receptor triggered reduction of neurotransmitter production is being done by the body for safety reasons.  Accepting that some people (POIS sufferers perhaps) could have a malfunction, most people would not want their h3 receptors antagonised on a permeant basis. It could prove overstimulating, affect cardiac rhythms etc. It may be safer than amphetamines but these will still be powerful drugs.

Anyway, it's a research area for NORD to consider.

It seems there is some H3 antagonist only :

Ciproxifan
Conessine
Impentamine
Iodophenpropit

There is something I dont understand : apparently H3 antagonist help release of histamine :

Ciproxifan is an extremely potent histamine H3 inverse agonist/antagonist.
The histamine H3 receptor is an inhibitory autoreceptor located on histaminergic nerve terminals, and is believed to be involved in modulating the release of histamine in the brain. Histamine has an excitatory effect in the brain via H1 receptors in the cerebral cortex, and so drugs such as ciproxifan which block the H3 receptor and consequently allow more histamine to be released have an alertness-promoting effect.[1][2][3]

Hi though we were trying to lower the level of histamine release.I probably missed something

Yes, my understanding is it isn't as simple as that. H3 uptakes histamine (good) but they are also inhibitory hetero-receptors for other neurotransmitters including dopamine.So I think that providing a histamine antagonist may stop them (just by physically blocking the receptors) from reducing levels of dopamine and serotonin in the brain. This seems to be what happen's in trials of the drug. However, even the drug companies developing these drugs don't seem 100% sure how they work.

kurtosis

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Re: Desensitization, Fact or Fiction?
« Reply #68 on: November 07, 2012, 11:24:28 AM »
I'd say that's an excellent idea.
It might be a good idea to read about histamine intolerance, the special diets people follow and note if you have similar reactions.
I have reactions to cheese, wine, chocolate & pretty much all the high histamine foods. I get the same odd throbbing feeling in my head and stomach upsets I get with POIS.

See this http://www.allergyuk.org/common-food-intolerances/histamine-intolerance

They're not saying that eating any of these foods will make you sick immediately but if foods make you feel unwell, give you what you believe to be indigestion, nausea, dizziness, upset your sinuses or give you a headache then make a note of them and check if they're high in histamine.

Snowblind

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Re: Desensitization, Fact or Fiction?
« Reply #69 on: November 07, 2012, 01:01:33 PM »
This all makes so much sens to me and I really do think this could be it. I'm so exited about these findings!

I searched around a bit on the internet about histamine and i read that for instance red wine is especially complicated to intake for people who are sensitive to histamine because it not only contains histamine, as do a lot of things (cheese etc.), but also the alcohol inhibits the bodys ability to break down the histamine. I cant drink red wine at all, i get a terrible headache and get very hot and red in the skin, i even get skin reaches from it. This is probably because i am sensitive to/have a high amount of histamine.

As for my own cure with Phosphatidylserine I found this:

Phosphatidylserine, in contrast with other phospholipids, markedly enhanced histamine release from rat peritoneal mast cells induced by dextran or protein antigens. This enhancing effect was selective for dextran and protein antigens and did not extend to the action of compound 48/80 or chymotrypsin. These findings suggest a role for phosphatidylserine in the response of mast cells to antigens.

So it might be a connection there to. But I will definitely try the DAO:s and the methionine and i think they will be more effective. I stated earlier that i was about 80% Pois free with the PS, but it acctually varies a bit, sometimes its 50% and at best 80%. I will stop taking folic acid as well if it makes things worse, I take a combined b6/folic acid tablet in the morning but will switch to only b6 instead.

 




demografx

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Re: Desensitization, Fact or Fiction?
« Reply #70 on: November 08, 2012, 12:41:22 PM »
WHICH specific component of semen does the desens theory claim is the allergen(s)?  Sperm? Fructose? Proteolytic enzymes? ALL semen components??

Does a SPECIFIC allergy to one or more of seminal components below need to be tested?


The components and contributions of semen are as follows:


Gland
 
Approximate %
 
Description
 


testes
 
2–5%
 
Approximately 200- to 500-million spermatozoa (also called sperm or spermatozoans), produced in the testes, are released per ejaculation. If a man has undergone a vasectomy, he will have no sperm in the ejaculation.
 


seminal vesicle

65–75%
 
amino acids, citrate, enzymes, flavins, fructose (2–5 mg per mL semen,[3] the main energy source of sperm cells, which rely entirely on sugars from the seminal plasma for energy), phosphorylcholine, prostaglandins (involved in suppressing an immune response by the female against the foreign semen), proteins, vitamin C
 


prostate

25–30%
 
acid phosphatase, citric acid, fibrinolysin, prostate specific antigen, proteolytic enzymes, zinc (the zinc level is about 135±40 micrograms/ml for healthy men.[4] Zinc serves to help to stabilize the DNA-containing chromatin in the sperm cells. A zinc deficiency may result in lowered fertility because of increased sperm fragility. Zinc deficiency can also adversely affect spermatogenesis.)
 


bulbourethral glands

< 1%
 
galactose, mucus (serve to increase the mobility of sperm cells in the vagina and cervix by creating a less viscous channel for the sperm cells to swim through, and preventing their diffusion out of the semen. Contributes to the cohesive jelly-like texture of semen.), pre-ejaculate, sialic acid

From http://en.wikipedia.org/wiki/Semen#Composition_of_human_semen
« Last Edit: November 08, 2012, 12:46:20 PM by demografx »
10 years of significant POIS-reduction, treatment consisting of daily (365 days/year) testosterone patches.

TRT must be checked out carefully with your doctor due to fertility, cardiac and other risks.

40+ years of severe 4-days-POIS, married, raised a family, started/ran a business

Vincent M

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Re: Desensitization, Fact or Fiction?
« Reply #71 on: November 09, 2012, 10:24:42 AM »
Yesterday was weird. I was on the border of an anxiety attack all day. It was day 5, however after a reasonable niacin session. I had to take 400mg to get a flush which was light. Day 1 was fairly rough, but strangely I did a lot of heavy work that day and it seemed to actually lessen the POIS. I don't know, it was as though the work seemed to activate something from the niacin effect. Normally exercise makes my POIS worse and I can't even do the amount that I did that day.

But getting back. The rest of the session has been good, little to no POIS after a good sleep the night of day 1.

Except for this day 5 anxiety. To make things worse, I didn't have my Xanax with me, that I usually have around "just in case". I tried to calm myself, and never really entered "an attack", but was feeling quite uncomfortable.

I started thinking about anti-histamines. Perhaps I was having a histamine surge or something. So I went to look for the equivalent of Benadryl (here in Chile) HA. Couldn't find it, but found loratadina. I am very cautious, certainly didn't want to make things worse, so just took a half dose.

It worked! Didn't feel any other effects, drowsiness, nothing, but the anxiety just went away within about half an hour.

Who knows, maybe even placebo!

Loratadina works on the H1. Who knows. I know anti-histamines have never worked for me with the more physical symptoms, but somehow something worked here.


Two things I noticed about your post here, Daveman. The first is about niacin. When I take niacin and "o" before a night's sleep the next day I've noticed I get increased physical strength and endurance, but I have to warm up before I'll notice that effect from the niacin kick in. So perhaps that is why the heavy work you did seemed to lessen your POIS.

The other thing is about Loratadina. I believe here in the states the equivalent is Loratadine, which is the generic version of Claritin. I've noticed that more of our POIS members have reported POIS symptom reduction with the use of Claritin than they have with Benadryl. Theoretically this doesn't make much sense seeing that Benadryl is able to cross the blood-brain barrier and is said to be a stronger anti-histamine than Claritin, but it seems that for some unknown reason Claritin just works better for POIS. You may want to try taking your Loratadina about an hour before having an "o" seeing as that's about how long before it's fully absorbed into the blood stream and that seems to be the most effective way of using it for POIS. I have noticed that it tends to stay in my system about 3 days, will make me slightly sleepier the following day of dosage, and if I take a second 10mg tablet within the 3 day period I'll get a minor headache.
Taking ginger tea, no wheat, fenugreek+green tea/garlic, saw palmetto, niacin, boswellia, huperzine, B complex and nutmeg. See my treatment summary post for more info: http://poiscenter.com/forums/index.php?topic=81.msg3513#msg3513

kurtosis

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Re: Desensitization, Fact or Fiction?
« Reply #72 on: November 09, 2012, 10:29:46 AM »
Try clarityn D with pseudo-ephedrine. You don't feel sleepy and it's effective in terms of reducing histamine levels. It's a smaller dose of the PE in an epi-pen.

Vincent M

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Re: Desensitization, Fact or Fiction?
« Reply #73 on: November 09, 2012, 01:03:03 PM »
Good suggestion on claritin D, kurtosis. I'll have to try it.
Taking ginger tea, no wheat, fenugreek+green tea/garlic, saw palmetto, niacin, boswellia, huperzine, B complex and nutmeg. See my treatment summary post for more info: http://poiscenter.com/forums/index.php?topic=81.msg3513#msg3513

Daveman

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Re: Desensitization, Fact or Fiction?
« Reply #74 on: November 12, 2012, 12:15:50 PM »
Try clarityn D with pseudo-ephedrine. You don't feel sleepy and it's effective in terms of reducing histamine levels. It's a smaller dose of the PE in an epi-pen.

As far as the work and niacin, I think you are right on. That was my feeling anyways, that it helped the niacin do it's thing.

I don't know if the day 5 kickback had anything to do with that..... that's kind of why I told the whole story!
WITHOUT RESEARCH THERE WILL BE NO CURE!
Sessions 5 to 9 days, mostly Flu-like, joints, digestion problems, light cognitive.
Niacin has changed my lif though, now 1 day MAX.
Somewhere in this interaction with Niacin is the answer!