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

POIS Cause/Treatment Discussions => Auto-Immune Causes and Treatments => Topic started by: Quantum on December 08, 2014, 12:26:48 AM

Title: Prevention and relief with plant sterols and sterolins (Moducare)
Post by: Quantum on December 08, 2014, 12:26:48 AM
Hi everyone,
In the last 2 weeks, since i have discovered this forum, my understanding of POIS has made a quantum leap ( pun intended! :) ).    One of the great revelation for me about POIS have been its relation to allergy and auto-immunity.  For the last 36 years, it never came to me that an allergic or immune reaction could be at the base of my symptoms, because I never had any of the allergy-like cluster of symptoms (runny nose, itchy eyes, local swelling, and so on), corresponding to a type I hypersensitivity reaction.  I did not have symptoms neither from the flu-like cluster of symptoms ( fever, muscle aches, joint pains,...) related to a type IV hypersensitivity reaction.  My symptoms are more related to the metabolic consequences of those immune imbalance due to overproduction of cytokines and other immune inflammatory messengers.    My extreme fatigue, hypotension, exercise intolerance, emotional liability, irritability, anxiety, and so on, are not what one expect from an allergic reaction, so I never ever considered this possibility.  I had very severe allergy symptoms as a child, I had a very, very bad case of hay fever  (sneezing, eye irritation, itching, redness of the skin, hives within 5 minutes of being in or near a hay field,....). I had desensitization injections for grasses and weeds, when I was 8 to 10 years old, and knowing that cross-desensitization is possible, that is maybe why, a few years later, when I first had an O, I didn't have any allergy symptoms. 

Thanks to this forum, I can now make new links.  I see that the allergic and so-called delayed immune response are responsible for two other clusters of symptoms that I suffer from, but that do not look like allergy symptoms.  They are rather consequences of the complex mechanic of the immune system, and in POIS case, of its somehow inappropriate response.  So, the third cluster I see is the pellagra-like cluster of symptoms (cognitive, dermatological, gastrointestinal), related to niacin deficiency, and the hypotension and dysphoria (bad mood) cluster of symptoms, related to serotonine deficiency in the brain, both of which are linked, it seems, to immune-triggered disorder of tryptophan metabolism, tryptophan being the precursor of both niacin and serotonin  ( I will for sure clarify and share my hypotheses as I will have time to continue working on this, and to test a bit more and verify with data and case reports if my hypothesis on the physiopathology of POIS makes sense.  I use my spare time doing this, but I am still working full time as a pharmacist, have managing duties as co-owner of the business, I play badminton two times a week, and above all the rest, I have a wonderful wife and two children I love spending time with )

Once I understood that too much IL-6 or TNF-alpha or other pro-inflammatory cytokines could be at the root of POIS, and that T-cell and auto-immunity could be at work in POIS, I've decided to try the natural product I suggest the most to my patients having auto-immune disorders like Rheumatoid arthritis and allergies. In the past 20 years, i have seen very good results with this product.  In fact, i have been using it myself, whenever I have a cold or flu.  It is a proprietary blend of plants sterols and sterolins in  specific ratio  (the brand name is Moducare ).  It is safe, and present no interactions with prescribed drugs or with supplements and OTC drugs.   It reduces IL-6 And TNF-alpha productions, regulates many others cytokines, lower cortisol, balance the TH1:TH2 ratio, among other things.  Many scientific studies have been made with this product. See for example,  https://duckduckgo.com/l/?kh=-1&uddg=http%3A%2F%2Fwww.rheumatology.org.tw%2Fmagazine%2FFolder%2F23_2%2F23_2_072.pdf  - interesting information in the introduction about how it works.   Search the net and see for yourself, lots of info available.

So, 2 days ago, I tried 2 capsules  40 minutes pre-O, along with some other things in my ?pre-O pack? like omega-3 and 200mg of Ibuprofen, and I had a POIS-free O , which has been very, very rare for me in the last 36 years.  I monitored my blood pressure, as usual, and other signs, and saw that another capsule very 4 to 6 hours for the next 24 hours was ok to stay POIS-free.  However,  this was not a stand-alone, magic bullet type of thing , I use a multiple approach to POIS (very healthy diet, Omega-3, exercise, curcuma, rosemary, increased Tryptophan in diet, probiotics, total avoidance of aspartame,and so on... ).  But Moducare do help to complete my strategy in a very effective way.  I suppose the results won't be as dramatic with someone that has not optimized his diet and lifestyle, and has not started yet some useful supplementations like omega-3 and vitamin D ( I have been taking those daily for a long time, having noticed it helped me a lot.... and now, I have been able to understand why ).  In other cases than mine, it may take a few weeks of Moducare before it starts being effective.

I did not have time yet to try Moducare as a daily supplement ( I have been trying some other products I read about in here, like fenugreek, niacin, olive leaf extract, and will eventually share about those too).  But I do wanted to share my success with it, because it targets the very root of the POIS acute phase, so in theory, it should be beneficial, at least in part, for the four clusters of symptoms (allergy-like, flu-like, niacin related and serotonine related).

Some caution applies to Moducare.  If you are pregnant, nursing, a diabetic, an organ transplant recipient or have multiple sclerosis, do not use unless on the advice of and under the direct supervision of a health care professional.

Like with any treatment, take the time to read about this product before trying it.  You are fully responsible if you decide to give it a try -  I am just sharing what works for me, and cannot be liable for what it will do or not do for you.  It is however a rather safe product, with no known side effects if you take as directed.  I use it myself on many occasions in the last 15 years, and have suggested it to many of my patients, some still taking it daily after 10 years, for RA.

I am quite sure that it is available in Europe, and in most part of the world as well.

I think it will make a perfect complement to any POIS-relieving strategy.

Hoping it will be of help,

Quantum
Title: Re: Prevention and relief with plant sterols and sterolins (Moducare)
Post by: Colm on December 08, 2014, 04:15:05 AM
Hi Quantum,

Thanks for sharing all of this.

Like you, I am 4 decades with POIS. Unlike you, I haven't a scientific or medical understanding for a lot of the terms you and others use.

However, like many other posters, I read all this with much interest and hope to try the moducare Etc.

I have been on a nutritional and dietary approach for six months with some encouraging signs,working with a nutritionist,  trying various things, and am about to embark on a new phase on this, which I hope to report on in a few weeks.
Title: Re: Prevention and relief with plant sterols and sterolins (Moducare)
Post by: Macster on December 08, 2014, 05:25:59 PM
Hi Quantum,

Thanks a lot for sharing what you have found out about this syndrome. Its nice to have someone with some knowledge on pharmacology on this forum. I think it will make pinpointing the actual roots of the "illness" much easier and more exact.

I find it interesting how you grouped the different symptoms into clusters. These seem to work with what I have read online although I would not have been able to link them up like this (my background is not so close to that of biochemistry). I know that you said you will give us more info on all this later, but I'm trying to understand the relationship between the sterols medication and the metabolism of tryptophan. Feel free to take your time to answer. I'm guessing that as a pharmacist you must have a busy schedule.

Thanks

Macster
Title: Re: Prevention and relief with plant sterols and sterolins (Moducare)
Post by: Quantum on December 10, 2014, 12:06:31 AM
Hi Quantum,

Thanks for sharing all of this.

Like you, I am 4 decades with POIS. Unlike you, I haven't a scientific or medical understanding for a lot of the terms you and others use.

However, like many other posters, I read all this with much interest and hope to try the moducare Etc.

I have been on a nutritional and dietary approach for six months with some encouraging signs,working with a nutritionist,  trying various things, and am about to embark on a new phase on this, which I hope to report on in a few weeks.

Hi Colm,

Thanks for your interest.

About the scientific aspect, you could just start slowly, and learn bit by bit, each day, and first thing you know, you will understand many new biology-related concepts. 

I agree with you that nutition is very important in POIS, because it has a direct impact on what I have tagged cluster of symptoms #3 (niacin related) and cluster of symptoms #4 (serotonine related).  In a simplified version, it is very important to increase your dietary intake of tryptophan, an amino-acid ( http://en.wikipedia.org/wiki/Tryptophan ) .  Tryptophan is the base material that the our body uses to build serotonin and niacin.  From what I understand of POIS, the metabolism of tryptophan is deeply affected by the immune messengers that are produced following the allergy/immune over-response that occurs just after O. I will spare you all the details for now, as I know you are not at ease with all that biochemistry stuff, but the final consequence is that in POIS, those two clusters of symptoms are consistent with a tryptophan shortage in the brain.  That means lack of niacine in the brain (cognitive problems, memory loss, brain fog, slow thinking, ....)  and lack of serotonine in the brain ( social phobia, irritability, anxiety, mood swings, low self esteem, lack of joy ....). 

I will come up with a more complete description in another post.  But for now, as I have seen for myself, and as I think would be of help for any POIS sufferer, a good nutrional approach is to increase tryptophan (Trp) intake, so I encourage you to discuss about it with your nutriyionist.  My personnal favorite sources are pumpkin seeds and sunflower seeds, but there are others: https://en.wikipedia.org/wiki/Tryptophan#Dietary_sources . 

Once Trp is in your blood flow, it has to pass through the blood brain barrier (BBB) in order to get to into your brain.  You have to stop it from being metabolized too much before reaching the brain (take curcumin with black pepper, for example, to help wiht that). Also,  if you eat some glucose sources with your Trp source, like a slice of white bread, it will help the process ( I will spare you the details for now, but you can read about the BBB, it is a very important concept in human physiology and in pharmacology - see http://en.wikipedia.org/wiki/Blood%E2%80%93brain_barrier ). But as a source of sugar, avoid fructose, and also sucrose (table sugar) and HFCS, which are half fructose - go for glucose, as in starch, as in corn syrup also.

Also about nutrition, all POISers should avoid aspartame (nutrasweet) at all costs. Aspartame is an artificial sweetener that is found in diet soda pop, in sugarless chewing gum (if you like chewing, find some xylitol chewing gum!), O calorie yogourt, and on, and on...read the labels.   Aspartame worsen POIS !  I had already noticed, through my (too many) POIS years that aspartame was like a poison for me, and now, since last week, I know why.  It is a source of phenylalanine, another amino acid, and phenylalanine competes with Trp to get in the brain. So when you flood your blood with aspartame, you worsen the Trp supply problem to the Central Nervous System (CNS, which includes the brain).  For those interested for a detailed explanation of the mechanism, see http://www.nature.com/ejcn/journal/v62/n4/full/1602866a.html , excellent article, you won't take any aspartame after reading and understanding this. Just remember that for POIS, niacin is also relevant, but that they only mention serotonine in the article as being affected by decrease of Trp in the CNS.  But niacin is decreased as well, so not only one cluster of symptoms for us, but two, and one may be more present in some poisers than the others, depending on your particular "metabolic settings".  For me, cluster 4 (emotional unbalance due to low serotonine) is far, far more present than cluster 3.  I see that it is the opposite for other POISers, and some have even both at a severe level.

Aspartame stick  long time in the body.  You will have to wait about 4 weeks after the complete avoidance of aspartame before seeing the results of your wise decision.

Since about three weeks, I have implanted the Trp increase in my diet, among other things, and results are great.  I realized that I always had a kind of low-noise, chronic POIS , every day of my life, related to that Trp problem, because now, i need like 1 hour to 1 hour and a half less sleep per day (no kidding!).  It make me think that, apart from the immune reaction I believe is really occurring at O, we may also share a kind of enzyme defect in the Trp metabolism, like am enzyme (the IDO) too sensitive to immune messengers, and naturally too active, hence explaining that low-noise POIS, even when no O for a month.  Having those two conditions would be a very rare "chance", and that would explain why our syndrome is so rare.

Well, sorry for the long post, here is a TLTR version:  increase tryptophan sources in your diet, eat them with some starch/glucose source for a glycemic load that will help get the Trp into your brain, and add in a little curcuma with a little black pepper, or add some rosemary, or some marjoram.  Also, completely eliminate aspartame, and see improvements after 4 weeks of having totally stopped it

Hoping that will help some others as much as it helped me!

Quantum



Title: Re: Prevention and relief with plant sterols and sterolins (Moducare)
Post by: Quantum on December 10, 2014, 12:46:43 AM
Hi Quantum,

Thanks a lot for sharing what you have found out about this syndrome. Its nice to have someone with some knowledge on pharmacology on this forum. I think it will make pinpointing the actual roots of the "illness" much easier and more exact.

I find it interesting how you grouped the different symptoms into clusters. These seem to work with what I have read online although I would not have been able to link them up like this (my background is not so close to that of biochemistry). I know that you said you will give us more info on all this later, but I'm trying to understand the relationship between the sterols medication and the metabolism of tryptophan. Feel free to take your time to answer. I'm guessing that as a pharmacist you must have a busy schedule.

Thanks

Macster

Hi Macster,

Thanks for your comments :)

About your question, the relationship sterols and Tryptophane metabolism is found in the fact that some of the immune messengers produced following O, like interferon-gamma and TNF-alpha, are activating/upregulating an enzyme that metabolise (break up) tryptophan, the IDO enzyme ( see http://en.wikipedia.org/wiki/Indoleamine_2,3-dioxygenase ).  This is a strategy of the immune system to try to kill tumor cells by depriving them of tryptophane, an essential and rare amino-acid, that is as much a need for cancer cell than for our normal, healthy cells.  The role of sterols in all this is at the beginning of the sequence, by reducing the production of pro-inflammatory cytokines and of other immune messengers that also promotes inflammation. In clear, the sterols and sterolines help reduce the frenzy of the hypersensitivity reactions that occur at O .  Less interferon-gamma and the like are produces, and this means less upregulating of IDO, so less Trp is metabolized, leading to less depletion of Trp in the body and brain. 

As you may have read on my previous answer to Colm, the more I understand POIS, the more I see that, after the first 2 clusters of symptoms related to allergy (cluster 1) and cellular immunity reaction (cluster 2, flu-like symtoms), there are two other possible clusters, related to lack of niacin (cluster 3) and lack of serotonine (cluster 4), the 2 being based on a tryptophane shortage ( I intend to make a more detailed post about this hypothesis, in a near futur, as it tends to help me explain my own POIS, and also explain what I read on the forum from other POISers experiences).

You can find much information on IDO on the internet. There are already plenty of scientific references on IDO on the wikipage I gave the link for, just above.  You my find along the way why I have became very found of curcuma and rosemary, among other things ;)

I think that we are very lucky that the IDO enzyme have been targeted as a study subject in cancer therapy.  I just had to search on the web, and found numerous useful studies on this enzyme.  We indirectly benefits from hundred of thousands of dollars of cancer research funding.  I am quite grateful for this unexpected help for me, and for all POISers as well.

I know that some of what I talk about is not a confirmed pathophysiology for POIS, so everybody may not agree with my view, and It'S OK.  At least, I hope to have expressed part of my hypothesis with enough clarity.  If not, do not hesitate to ask about any detail.

Quantum

Title: Re: Prevention and relief with plant sterols and sterolins (Moducare)
Post by: Quantum on December 10, 2014, 01:04:29 AM
Thanks Quantum! That's super interesting stuff to read, and I appreciate you sharing that info with us. Thinking back, I had a cat fur allergy before developing POIS (I would sneeze a lot and my eyes would get red/itchy when I visited someone with a kitty). Now though, I've been around cats several times, and I don't seem to have the allergy anymore since POIS...weird. I see that you had a similar experience, but with hay. I've tried a lot of difference supplements, and I won't mind trying out the supplement you mentioned. Thanks, and let us know if you have any updates.

Prancer

Hi Prancer,

It is fascinating to see how complex the immune system is, and how some part of it may activate itself and replace the provious response pattern.  That is the aim, in fact, of the injections I had for my hay fever.  tHe goal was to slowly activate the IgM response, to the point that it eventually have replaced the previous IgE repsonse, the one leading to tons of histamine being released in my body, causing sneezing, iching, runny nose, hives, and ichy eyes.

It seems that, in your case, some metabolic change or some epigenetic change as turned off the IgE response to cat, and have unfortunately turned on what another type of immune response that triggered POIS.  As I see, judging form what is written in your signature, your POIS do not seem to include what I call symptoms of cluster 1 ( hay fever-like) and cluster 2 (flu-like - muscle and joints ache, fever,...), but cluster 3, cognitive/niacin depletion, and cluster 4, emotionnal/serotonine depletion.

I would be curious to know, as you have CNS niacin depletion symptoms, if you also have peripheral niacin depletion symptoms, like gastro-intesinal problems/diarrhea, and some dermatologic problems, like redness, sensitivity to sun, canker sores in the mouth, gingivitis, and the like. 

I will eventually post the chart I have developed for symptoms of all those four clusters... as time allow me to do so.....

Quantum
Title: Re: Prevention and relief with plant sterols and sterolins (Moducare)
Post by: Prancer on December 10, 2014, 01:59:37 AM
I would be curious to know, as you have CNS niacin depletion symptoms, if you also have peripheral niacin depletion symptoms, like gastro-intesinal problems/diarrhea, and some dermatologic problems, like redness, sensitivity to sun, canker sores in the mouth, gingivitis, and the like. 

Nope, I don't experience any redness, gastro-intestinal problems, gingivitis, canker sores, and not I'm sensitive to the sun, except my eyes maybe, if it's very bright out. Overall, my symptoms are limited to what's in my signature. My biggest problem is cognitive symptoms.

Prancer
Title: Re: Prevention and relief with plant sterols and sterolins (Moducare)
Post by: nathan123 on December 10, 2014, 04:14:53 AM
Hi guys,,

Pls see the my new post in POIS naked scientists forum.... Pls come there......Finally, I got the breakthroug...
Title: Re: Prevention and relief with plant sterols and sterolins (Moducare)
Post by: Colm on December 10, 2014, 10:55:30 AM
Hi Quantum,

Thanks for sharing all of this.

Like you, I am 4 decades with POIS. Unlike you, I haven't a scientific or medical understanding for a lot of the terms you and others use.

However, like many other posters, I read all this with much interest and hope to try the moducare Etc.

I have been on a nutritional and dietary approach for six months with some encouraging signs,working with a nutritionist,  trying various things, and am about to embark on a new phase on this, which I hope to report on in a few weeks.

Hi Colm,

Thanks for your interest.

About the scientific aspect, you could just start slowly, and learn bit by bit, each day, and first thing you know, you will understand many new biology-related concepts. 

I agree with you that nutition is very important in POIS, because it has a direct impact on what I have tagged cluster of symptoms #3 (niacin related) and cluster of symptoms #4 (serotonine related).  In a simplified version, it is very important to increase your dietary intake of tryptophan, an amino-acid ( http://en.wikipedia.org/wiki/Tryptophan ) .  Tryptophan is the base material that the our body uses to build serotonin and niacin.  From what I understand of POIS, the metabolism of tryptophan is deeply affected by the immune messengers that are produced following the allergy/immune over-response that occurs just after O. I will spare you all the details for now, as I know you are not at ease with all that biochemistry stuff, but the final consequence is that in POIS, those two clusters of symptoms are consistent with a tryptophan shortage in the brain.  That means lack of niacine in the brain (cognitive problems, memory loss, brain fog, slow thinking, ....)  and lack of serotonine in the brain ( social phobia, irritability, anxiety, mood swings, low self esteem, lack of joy ....). 

I will come up with a more complete description in another post.  But for now, as I have seen for myself, and as I think would be of help for any POIS sufferer, a good nutrional approach is to increase tryptophan (Trp) intake, so I encourage you to discuss about it with your nutriyionist.  My personnal favorite sources are pumpkin seeds and sunflower seeds, but there are others: https://en.wikipedia.org/wiki/Tryptophan#Dietary_sources . 

Once Trp is in your blood flow, it has to pass through the blood brain barrier (BBB) in order to get to into your brain.  You have to stop it from being metabolized too much before reaching the brain (take curcumin with black pepper, for example, to help wiht that). Also,  if you eat some glucose sources with your Trp source, like a slice of white bread, it will help the process ( I will spare you the details for now, but you can read about the BBB, it is a very important concept in human physiology and in pharmacology - see http://en.wikipedia.org/wiki/Blood%E2%80%93brain_barrier ). But as a source of sugar, avoid fructose, and also sucrose (table sugar) and HFCS, which are half fructose - go for glucose, as in starch, as in corn syrup also.

Also about nutrition, all POISers should avoid aspartame (nutrasweet) at all costs. Aspartame is an artificial sweetener that is found in diet soda pop, in sugarless chewing gum (if you like chewing, find some xylitol chewing gum!), O calorie yogourt, and on, and on...read the labels.   Aspartame worsen POIS !  I had already noticed, through my (too many) POIS years that aspartame was like a poison for me, and now, since last week, I know why.  It is a source of phenylalanine, another amino acid, and phenylalanine competes with Trp to get in the brain. So when you flood your blood with aspartame, you worsen the Trp supply problem to the Central Nervous System (CNS, which includes the brain).  For those interested for a detailed explanation of the mechanism, see http://www.nature.com/ejcn/journal/v62/n4/full/1602866a.html , excellent article, you won't take any aspartame after reading and understanding this. Just remember that for POIS, niacin is also relevant, but that they only mention serotonine in the article as being affected by decrease of Trp in the CNS.  But niacin is decreased as well, so not only one cluster of symptoms for us, but two, and one may be more present in some poisers than the others, depending on your particular "metabolic settings".  For me, cluster 4 (emotional unbalance due to low serotonine) is far, far more present than cluster 3.  I see that it is the opposite for other POISers, and some have even both at a severe level.

Aspartame stick  long time in the body.  You will have to wait about 4 weeks after the complete avoidance of aspartame before seeing the results of your wise decision.

Since about three weeks, I have implanted the Trp increase in my diet, among other things, and results are great.  I realized that I always had a kind of low-noise, chronic POIS , every day of my life, related to that Trp problem, because now, i need like 1 hour to 1 hour and a half less sleep per day (no kidding!).  It make me think that, apart from the immune reaction I believe is really occurring at O, we may also share a kind of enzyme defect in the Trp metabolism, like am enzyme (the IDO) too sensitive to immune messengers, and naturally too active, hence explaining that low-noise POIS, even when no O for a month.  Having those two conditions would be a very rare "chance", and that would explain why our syndrome is so rare.

Well, sorry for the long post, here is a TLTR version:  increase tryptophan sources in your diet, eat them with some starch/glucose source for a glycemic load that will help get the Trp into your brain, and add in a little curcuma with a little black pepper, or add some rosemary, or some marjoram.  Also, completely eliminate aspartame, and see improvements after 4 weeks of having totally stopped it

Hoping that will help some others as much as it helped me!

Quantum
Hi Quantum,

Thank you for taking the time to share what you have learned, with your deep knowledge of anatomy & physiology, and also about various minerals & nutritional approaches.

Like others, I will study this further and look into a greater understanding here with much interest, over the next few days and update anything of use I can contribute. Much appreciated !

There is such a wealth of experience and knowledge now among the forums. Such a shame a lot of it is buried so deep, for instance, some of the great posts we have had in the last few months are really gone/buried with no connection to other theories. I am certain we can crack a lot of this POIS mystery before 2016, when hopefully we can also raise funds for a qualified physician to mine all this valuable research & data and merge it with Dr K's outputs - who knows.

Blinded by naked science !
Title: Re: Prevention and relief with plant sterols and sterolins (Moducare)
Post by: Quantum on December 10, 2014, 08:43:22 PM
*******
I would be curious to know, as you have CNS niacin depletion symptoms, if you also have peripheral niacin depletion symptoms, like gastro-intesinal problems/diarrhea, and some dermatologic problems, like redness, sensitivity to sun, canker sores in the mouth, gingivitis, and the like. 

Nope, I don't experience any redness, gastro-intestinal problems, gingivitis, canker sores, and not I'm sensitive to the sun, except my eyes maybe, if it's very bright out. Overall, my symptoms are limited to what's in my signature. My biggest problem is cognitive symptoms.

Prancer
*******


Hi Prancer,

Thanks for your feedback!

It is very interesting to note that almost all of your symptoms affect your Brain/ Central Nervous System (CNS), and that you have almost no peripheral symptoms, that is, in the peripheral blood flow, that goes everywhere else in the body except the CNS.  I have this with serotonin-related symptoms (mainly central symptoms like anxiety, mood swings, emotional instability, irritability, ...), but, regarding niacin, I have the exact opposite of what you have.  I have no CNS symptoms that would be related to lack of niacin in the brain (no brain fog, no difficulty finding words, no memory problems, no slow impaired capacity at problem resolution), but I have some peripheral symptoms (canker sores ++++, gingivitis, eyes redness occurs easily).  The more I read about other members symptoms, the more I feel that the large range of POIS effects on the metabolism will manifest in different forms for each one, because of our physiological specificities.  For example, in my case, there is a process that recycle niacin in my brain that must be faster than the rate at which it is depleted, so I do not have any cognitive problems ( I have no idea for now what this process is).  On the other hand, my serotonin level was already impaired ( I was very anxious have social phobia as a child, way before any POIS), so when POIS sets in and deplete my serotonin level further, I am in for a very depressed mood, extreme fatigue, hypotension, irritability, emotional instability.... unless, like in the past 3 weeks, I learn how to control this, by protecting my precious serotonin form POIS-produced consequences, and by having a regular routine ( nutrition, lifestyle, ....) to increase and maintain my serotonin "assets".  Results are very good so far, got a 100% POIS-free O, and have more stamina on a daily basis, less anxiety too, maybe because my CNS serotonin level is more normal now.

If I look at your list of symptoms from my current hypothesis about POIS, I would say that the lack of niacin in CNS explains brain fog/difficulty thinking and trouble finding the right words, and the lack of serotonin would explain anxiety,racing thoughts,  social withdrawal, fatigue, extreme frustration and irritability,  lack of motivation, and possible OCD.  If you raise tryptophan intake, and help it pass through the BBB ( using some glycemic load with your Trp source, and using rosemary or curcuma with black pepper), that should help, if my hypothesis is correct, because you will raise both niacin and serotonin levels, both being build by the brain from tryptophan.

I think you, and other forum members, would be interested in taking a look at the list of symptoms of a niacin deficiency ( http://en.wikipedia.org/wiki/Niacin#Deficiency ) and also at the list of symptoms of the disease called pellagra ( http://en.wikipedia.org/wiki/Pellagra ) , which is due to a lack of tryptophan and niacin in the diet.  The similarity with many of POIS symptoms is striking.  That is why I came to think that POIS is, at its base, an hypersensitivity reaction of type I and/or IV causing clusters of symptoms on their own (allergy and flu-like), but moreover, this inappropriate and massive production of pro-inflammatory immune messengers is also responsible for the upregulation of an enzyme (IDO), causing a major disturbance in tryptophan metabolism, causing the niacin and serotonin problems.  Other aggravating factors come in play as well, like impaired absorption in the guts ( IBS, SIBO, etc.. further limiting available Trp ), high vagal tone (intensifying some POIS symptoms), low testosterone and/or progesterone levels (they both inhibits prostaglandins and refrain the over-reaction of the immune system), and some other co-morbidity as well, and other factors worsening POIS like aspartame intake  ( I am in the process of collecting all of them in a chart).

It is very valuable for me to be able to hear about other POISers symptoms, it gives me hints to better get a glimpse of the bigger picture. So, thanks to everyone for sharing how your POIS manifest

Quantum



Title: Re: Prevention and relief with plant sterols and sterolins (Moducare)
Post by: poisioq on December 11, 2014, 12:49:36 PM
Hi Quantum,

thank you for this.

Do you think that taking tryptophan supplements together with glicemic food would help?

thanks
Title: Re: Prevention and relief with plant sterols and sterolins (Moducare)
Post by: staypositive on December 11, 2014, 05:12:37 PM
Hi everyone,
I thought it might be helpful if I contribute something to this forum. Since this illness affects my life also pretty much. I just got home from my work out, so I will make this short.
It all started when I was 11-12yrs old, I?m now 18 yrs old.
Symptoms
?   Right after ?O?: I feel pure emptiness, I don?t even know how to explain it. It?s like everything stopped working.
?   My eyes are red after O and I see worse in this state. (Blurry etc.)
?   I?m sensitive to the sun, and loud noise
?   Endurance literally non existent, I feel exhausted even after the easist task
o   I sweat very fast and this leads then to a blackout most of the time
?   Can?t concentrate in school
?   I feel weak, tired and exhausted
?   I feel dehydrated, can barley open my eyes, it feels dried up.
o   Same with my mouth and inner body
?   I get aggressive very fast
?   Have troubles finding words, talking in generall
?   Knee and back pain

These are not the only symptoms I have, these only occur when I ?O? once every 3-4 days. If I ?O? more, the symptoms gets way worse and I have to deal with more symptoms.

Now most important part
I don?t know why but MOST of the symptoms ALWAYS occur after I wake up. Even if I take a nap for 1 or 2min. I sometimes feel totally destroyed after I wake up.

Things I do or avoid to help my POIS
Drinking a lot of water (9-12l a day)
Doing sports (endurance sports > bodybuilding, endurance )
Avoiding food or drinks in which I think contains sugar
Shower cold
Avoiding extreme heat
I?m taking niacin (but not entirely sure if it really helps)
I rarely drink alcohol
I don?t smoke or take drugs.

I would write more but my english is not that good to express all the things I know 
Title: Re: Prevention and relief with plant sterols and sterolins (Moducare)
Post by: FloppyBanana on December 11, 2014, 06:08:38 PM
Quantum,

I had given up taking Niacin because sometimes it worked and other times not. Today after reading your post I decided to pop a couple of Niacins. I forgot about it and made a quick dinner as soon as I finished I started to get a light pain in my stomach (it was the Niacin I believe) so I went a lay on the couch....

It started to get hotter.........and hotter........and hotter. It was like the scene in the film "train spotting" where he takes the heroin and sinks into the floor. NO JOKE I could hardly move for 15 mins.....it was bliss....my body was like a shimmering light. All my stresses of the last two weeks disappeared and I started to giggle to myself after the 15 mins. I could feel the blood rushing around deep inside of my ears and supplying blood to my brain. It was most striking. I'm going to sleep well tonight I think. My stomach now feels very relaxed.

I have had positive effects with Niacin a handful of time but this was remarkable. Two hours later now I feel really relaxed. I have not O'd in quite a few weeks so I didn't think the Niacin would do anything. When I say I have been stressed I really have been, I have finding quotes to get my prostate removed and speaking to different people in different countries and it's sh*t scary. I don't mind sharing this. Perhaps this is the wrong phrase but I don't know if I got the balls to do it.

So in summary what I learnt is that Niacin has a benefit in getting a flush outside of POIS (for me at least). I can actual choose to think of "nothing" now, instead of a highway of speedy thoughts I can't stop.

On a side note I once took progesterone and some Niacin together. I didn't get the flush until after O'ing but when I did it came on so strong. Through taking my normal progesterone regime then I experienced the least POIS symptoms ever. I would say about 90% reduced.

On there side note, progesterone makes me feel really cold in the afternoons, so I wondering if I can have a blast of Niacin to warm me up. I shall try it!

FloppyB
Title: Re: Prevention and relief with plant sterols and sterolins (Moducare)
Post by: FloppyBanana on December 11, 2014, 06:27:05 PM
Hey staypositive,

Welcome. Check out the remedies page if you have not done yet. I hope something there helps you.
FloppyB
Title: Re: Prevention and relief with plant sterols and sterolins (Moducare)
Post by: G-man on December 11, 2014, 08:19:02 PM
I found evidence to support a possible link between the immunological ideas in this thread and Quantum's thoughts on the autonomic nervous system in the slow heart beat thread here:

http://poiscenter.com/forums/index.php?topic=1566.0

The link being that a weak sympathetic nervous system could result in underproduction of antiinflammatory mediators.

"Significance

Hitherto, both the autonomic nervous system and innate immune system were regarded as systems that cannot be voluntarily influenced. The present study demonstrates that, through practicing techniques learned in a short-term training program, the sympathetic nervous system and immune system can indeed be voluntarily influenced. Healthy volunteers practicing the learned techniques exhibited profound increases in the release of epinephrine, which in turn led to increased production of anti-inflammatory mediators and subsequent dampening of the proinflammatory cytokine response elicited by intravenous administration of bacterial endotoxin. This study could have important implications for the treatment of a variety of conditions associated with excessive or persistent inflammation, especially autoimmune diseases in which therapies that antagonize proinflammatory cytokines have shown great benefit.

Abstract

Excessive or persistent proinflammatory cytokine production plays a central role in autoimmune diseases. Acute activation of the sympathetic nervous system attenuates the innate immune response. However, both the autonomic nervous system and innate immune system are regarded as systems that cannot be voluntarily influenced. Herein, we evaluated the effects of a training program on the autonomic nervous system and innate immune response. Healthy volunteers were randomized to either the intervention (n = 12) or control group (n = 12). Subjects in the intervention group were trained for 10 d in meditation (third eye meditation), breathing techniques (i.a., cyclic hyperventilation followed by breath retention), and exposure to cold (i.a., immersions in ice cold water). The control group was not trained. Subsequently, all subjects underwent experimental endotoxemia (i.v. administration of 2 ng/kgEscherichia coli endotoxin). In the intervention group, practicing the learned techniques resulted in intermittent respiratory alkalosis and hypoxia resulting in profoundly increased plasma epinephrine levels. In the intervention group, plasma levels of the anti-inflammatory cytokine IL-10 increased more rapidly after endotoxin administration, correlated strongly with preceding epinephrine levels, and were higher. Levels of proinflammatory mediators TNF-?, IL-6, and IL-8 were lower in the intervention group and correlated negatively with IL-10 levels. Finally, flu-like symptoms were lower in the intervention group. In conclusion, we demonstrate that voluntary activation of the sympathetic nervous system results in epinephrine release and subsequent suppression of the innate immune response in humans in vivo. These results could have important implications for the treatment of conditions associated with excessive or persistent inflammation, such as autoimmune diseases."

http://m.pnas.org/content/111/20/7379.abstract
Title: Re: Prevention and relief with plant sterols and sterolins (Moducare)
Post by: Nightingale on December 12, 2014, 07:01:30 PM
My mind is not so sharp today, but I've gleaned a good bit from this conversation. Very glad to see the quality of discussion going on here
Title: Re: Prevention and relief with plant sterols and sterolins (Moducare)
Post by: Quantum on December 12, 2014, 11:40:52 PM
Hi Quantum,

thank you for this.

Do you think that taking tryptophan supplements together with glicemic food would help?

thanks

Hi Poisioq,

Thanks for your interest.

A load of glucose (not frustose or HFGS), definitively helps to get more tryptophan (Trp) through the blood brain barrier.  The glucose will cause a production of insulin, which in turn will stimulate the metabolic use of  Leucine, Isoleucine and Valine (the BCAA, branched-chain amino acids ), and their concentration will drop in the blood.  That is good news for Trp, because the BCAA compete for the same channel as tryptophan to enter in the brain, that is called the large neutral amino acid transporter (LAT1, or NAAT, or CD98...many names, same thing, see http://en.wikipedia.org/wiki/CD98 to learn more about it ).  Getting more Trp in the brain is, in my opinion, the main goal in order to reduce the cognitive and the emotional clusters of symptoms (but won't help much with allergy and flu-like symptoms). So getting the BCAA out of the way is a good thing.  Eliminate all intake of aspartame is important for the same reason - the phenylalanine it produces is also competing with Trp for the LAT1 channels.  For a more detailed explanation about the LAT1/NAAT bridge and Trp, BCAA and other competing amino-acids, see the excellent article at http://www.nature.com/ejcn/journal/v62/n4/full/1602866a.html .

I prefer to raise my dietary intake of Trp instead of taking Trp supplements, because "pure" Trp is too much for the guts to handle.  A part of it is transformed directly in the guts into serotonin, which then act as a stimulant for the smooth muscles of the guts.  You then get cramps, nausea, diarrhea,... .  You do not get that from eating food having Trp in them. As sources of Trp, I like sunflowers seeds, and pumpkin seeds too, but for me, I must be cautious with pumpkin seeds, they are diuretic, and I am prone to hypotension.  For a list of food with Trp, see https://en.wikipedia.org/wiki/Tryptophan#Dietary_sources . In Canada, we can also buy 5-HTP supplements (5-hydroxytryptophan), which is the compound that Trp is transformed to before finally be transformed in serotonin.  I take 25mg, no more, of it in the morning, with peppered curcuma or rosemary, and have no gastrointestinal problems.

But eating Trp is only one step, it has to make its way into the brain before it is transfomed by body enzymes ( IDO and TDO).  So, take some peppered curcumin or rosemary along with your Trp source or supplement, so it will be less metabolized in your body before getting to the blood brain barrier.  Avoid too much stress as well - the stress hormone cortisol stimulates the TDO enzyme.

According to my current view of POIS, and the results i get for myself, if enough Trp finally reaches the brain, the emotional symptoms are reduced and eventually eliminated (anxiety, irritability, mood swings, social phobia,...) and the cognitive symptoms should also diminished - but I can't verify since I do not get them (brain fog, lack of concentration, memory problem, searching for words, ...). 

I hope that will help

Quantum
Title: Re: Prevention and relief with plant sterols and sterolins (Moducare)
Post by: Quantum on December 13, 2014, 12:21:39 AM
Quantum,

I had given up taking Niacin because sometimes it worked and other times not. Today after reading your post I decided to pop a couple of Niacins. I forgot about it and made a quick dinner as soon as I finished I started to get a light pain in my stomach (it was the Niacin I believe) so I went a lay on the couch....

It started to get hotter.........and hotter........and hotter. It was like the scene in the film "train spotting" where he takes the heroin and sinks into the floor. NO JOKE I could hardly move for 15 mins.....it was bliss....my body was like a shimmering light. All my stresses of the last two weeks disappeared and I started to giggle to myself after the 15 mins. I could feel the blood rushing around deep inside of my ears and supplying blood to my brain. It was most striking. I'm going to sleep well tonight I think. My stomach now feels very relaxed.

I have had positive effects with Niacin a handful of time but this was remarkable. Two hours later now I feel really relaxed. I have not O'd in quite a few weeks so I didn't think the Niacin would do anything. When I say I have been stressed I really have been, I have finding quotes to get my prostate removed and speaking to different people in different countries and it's sh*t scary. I don't mind sharing this. Perhaps this is the wrong phrase but I don't know if I got the balls to do it.

So in summary what I learnt is that Niacin has a benefit in getting a flush outside of POIS (for me at least). I can actual choose to think of "nothing" now, instead of a highway of speedy thoughts I can't stop.

On a side note I once took progesterone and some Niacin together. I didn't get the flush until after O'ing but when I did it came on so strong. Through taking my normal progesterone regime then I experienced the least POIS symptoms ever. I would say about 90% reduced.

On there side note, progesterone makes me feel really cold in the afternoons, so I wondering if I can have a blast of Niacin to warm me up. I shall try it!

FloppyB

Hi FloppyB,

I am glad you had some symptoms reliefs by taking niacin. You experience is in agreement with my hypothesis on how the different clusters of POIS symptoms are caused.  Thanks for having shared t.

 I take some niacine too, every morning (125mg), and it helps me too as a daily supplementation along with other supplements, to eliminate my chronic- low-noise every day POIS, but which is not related to any sexual activity, but, I think, to a metabolic defect that is awfully amplified by O, through immune activation of the defective component.

As a side note, it is still soon for any conclusion, but i think the flush is not important for the daily supplement, not like when niacin is taken pre-O.  I take it at breakfast, have sometime no noticeable flush, but still help.  for the 1 or 2 times I used it Pre-O, I took it on empty stomach and waited for the flush.  With 125 mg niacin, and also 2 caps of Moducare, 200mg of Ibuprofen, along with Omega-3 and acetaminophene/paracetamol, I had last week a Pois-free O :)

My main symptoms are not cognitive, but emotional, so for me, tryptophan/5-HTP bring me a more dramatic improvement of my daily, chronic POIS (POIS name doesn't fit for this, as it is not related to O in this chronic form...but anyway.... )  I have no concentration issue, no brain fog, no memory problems so my brain does not crave for niacin. But it craves sooooooo much for serotonin!  Anxiety, mood swings, irritability, .......   I take niacin mostly for peripheral symptoms (canker sores ++++, intolerance to cold, ....), Trp and 5-HTP for serotonin, Along with peppered curcuma or rosemary as an IDO, that's a great synergistic combo for me. 

Keep me update about your results!

Quantum
Title: Re: Prevention and relief with plant sterols and sterolins (Moducare)
Post by: Quantum on December 13, 2014, 12:55:01 AM
I found evidence to support a possible link between the immunological ideas in this thread and Quantum's thoughts on the autonomic nervous system in the slow heart beat thread here:

http://poiscenter.com/forums/index.php?topic=1566.0

The link being that a weak sympathetic nervous system could result in underproduction of antiinflammatory mediators.

"Significance

Hitherto, both the autonomic nervous system and innate immune system were regarded as systems that cannot be voluntarily influenced. The present study demonstrates that, through practicing techniques learned in a short-term training program, the sympathetic nervous system and immune system can indeed be voluntarily influenced. Healthy volunteers practicing the learned techniques exhibited profound increases in the release of epinephrine, which in turn led to increased production of anti-inflammatory mediators and subsequent dampening of the proinflammatory cytokine response elicited by intravenous administration of bacterial endotoxin. This study could have important implications for the treatment of a variety of conditions associated with excessive or persistent inflammation, especially autoimmune diseases in which therapies that antagonize proinflammatory cytokines have shown great benefit.

Abstract

Excessive or persistent proinflammatory cytokine production plays a central role in autoimmune diseases. Acute activation of the sympathetic nervous system attenuates the innate immune response. However, both the autonomic nervous system and innate immune system are regarded as systems that cannot be voluntarily influenced. Herein, we evaluated the effects of a training program on the autonomic nervous system and innate immune response. Healthy volunteers were randomized to either the intervention (n = 12) or control group (n = 12). Subjects in the intervention group were trained for 10 d in meditation (third eye meditation), breathing techniques (i.a., cyclic hyperventilation followed by breath retention), and exposure to cold (i.a., immersions in ice cold water). The control group was not trained. Subsequently, all subjects underwent experimental endotoxemia (i.v. administration of 2 ng/kgEscherichia coli endotoxin). In the intervention group, practicing the learned techniques resulted in intermittent respiratory alkalosis and hypoxia resulting in profoundly increased plasma epinephrine levels. In the intervention group, plasma levels of the anti-inflammatory cytokine IL-10 increased more rapidly after endotoxin administration, correlated strongly with preceding epinephrine levels, and were higher. Levels of proinflammatory mediators TNF-?, IL-6, and IL-8 were lower in the intervention group and correlated negatively with IL-10 levels. Finally, flu-like symptoms were lower in the intervention group. In conclusion, we demonstrate that voluntary activation of the sympathetic nervous system results in epinephrine release and subsequent suppression of the innate immune response in humans in vivo. These results could have important implications for the treatment of conditions associated with excessive or persistent inflammation, such as autoimmune diseases."

http://m.pnas.org/content/111/20/7379.abstract

Thanks for the link, G-man. I will try to dig about their breathing technique when i will have time.

Regarding meditation, It is the one technique that help me the most with my POIS emotional symptoms.  It is maybe what have saved my relationship and family life.  I practice it each and every day. 

Title: Re: Prevention and relief with plant sterols and sterolins (Moducare)
Post by: G-man on December 13, 2014, 04:31:24 AM
I stumbled upon a very informative article:

The Cholinergic Anti-inflammatory Pathway: A Missing Link in Neuroimmunomodulation
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1430829/

"The SNS plays a dual role in the regulation of inflammation, because it mediates both pro- and anti-inflammatory activities; it is thus an integral component of the host defense system against injury and infection (15,51). The locus coeruleus (LC) and RVM, brain functional components of the SNS, project to sympathetic preganglionic cholinergic neurons in the spinal cord. Sympathetic innervation of primary (thymus and bone marrow) and secondary (spleen, lymph nodes, and tissues) lymphoid organs is the anatomic basis for modulation of immune function by the SNS (15,51,52). Sympathetic postganglionic norepinephrine (NE)-ergic and neuropeptide Y-ergic neurons also innervate blood vessels, the heart, the liver, and the gastrointestinal tract (15,52). NE, released from sympathetic postganglionic nerve endings, exerts anti-inflammatory effects by interacting with adrenoceptors expressed on lymphocytes and macrophages. Adrenoceptors belong to the G-protein coupled receptor superfamily and are divided into alpha and beta subtypes, which can be further subdivided. Sympathetic control on cytokine production is achieved by 2 mechanisms: (1) synaptic-like junctions with corresponding adrenoceptors (as in the spleen) and (2) nonsynaptic, distant mechanisms, such as NE diffusion through the parenchyma before interaction with the receptor. The nonsynaptic mechanism plays a dominant physiological role (15). The release of NE is subject to complex presynaptic regulation, involving the effects of neuropeptide Y, acetylcholine, dopamine, prostaglandins, and other micro-environmental factors. Sympathetic immunomodulation also is mediated via epinephrine, and to a lesser extent, by NE released from the chromaffin cells of the adrenal medulla. The chromaffin cells represent homologs of the sympathetic ganglia. Activation of the preganglionic sympathetic neurons innervating these cells leads to an increase in the release of catecholamines in the bloodstream, which can act systematically as hormones. Thus, sympathetic neural regulation is converted into “hormonal regulation” within the adrenal glands. The adrenals are therefore an important peripheral component of the CNS-controlled immunoregulation responsible for the synthesis of glucocorticoids (from the cortical cells) and catecholamines (from the medullar chromaffin cells).

SNS activation protects the organism from the effects of pro-inflammatory cytokines. Activation of beta-adrenoceptors leads to marked inhibition of endotoxin induced serum TNF, IL-1, IL-12, interferon-gamma, and nitric oxide production, and elevation of IL-6 and IL-10. Stimulation of beta-adrenoceptors also is accompanied by suppression of the TNF and IL-1 expression caused by hemorrhagic shock. NE and epinephrine inhibit production of pro-inflammatory cytokines through stimulation of beta2-adrenoceptor-cAMP-protein kinase A pathway, and they stimulate the synthesis of anti-inflammatory cytokines. Healthy volunteers receiving epinephrine and subsequent endotoxin treatment developed significantly decreased TNF levels and elevated IL-10 levels, as compared with controls exposed to endotoxin alone (53), raising the possibility that pharmacological control of cytokine production in septic patients could be achieved by selective adrenoceptor agonists and antagonists. A catecholamine-based strategy for treating sepsis and its complications is difficult, however, because of the broad effects of these agents and the need to balance the cardiovascular and immunomodulatory drug effects (15)."

"Many current approaches for treatment of unrestrained inflammation are based on direct suppression of pro-inflammatory cytokines or cytokine activity. The identification of the cholinergic anti-inflammatory pathway now suggests several new approaches to modulate cytokines and inflammatory responses to therapeutic advantage. For example, stimulation of the vagus nerve may represent a novel approach to inhibit TNF production and protect against pathological inflammation. Permanently implanted vagus nerve stimulators are clinically approved devices for treatment of epilepsy and depression (113–115). Vagus nerve stimulation prevents seizures by stimulating sensory vagal afferents associated with limbic and cortical function. Although vagal efferents also may be activated as a result of vagus nerve stimulation, no cardiac, gastric, or pulmonary complications have been observed (116). In animals, vagus nerve stimulation causes neural activation (assessed by c-Fos technique) in NTS, LC, DMN, and hypothalamic nuclei, including PVN (117,118). Vagus nerve stimulation enhances the activity of key components of the brain-derived anti-inflammatory response. In addition to the vagal efferents, the HPA axis and the SNS may also be activated as a “side effect” of vagus nerve stimulation. The occurrence of such activation remains to be evaluated by testing the fluctuations in serum glucocorticoid levels in patients with vagus nerve stimulators. If so, it may be possible to use currently existing, approved devices to control inflammatory responses.

The discovery of the cholinergic anti-inflammatory pathway identifies at least 1 receptor type that may be pharmacologically targeted to modulate cytokine activity. The nicotinic acetylcholine receptor alpha7 subunit is essential for regulation of peripheral inflammatory responses; activation of this receptor via vagus nerve stimulation (105) or cholinergic agonists (119,120) suppresses cytokine release and protects against lethal murine endotoxemia and sepsis. CNI-1493, the tetravalent guanylhydrazone that was instrumental in the discovery of the cholinergic anti-inflammatory pathway, exerts its anti-inflammatory effects in vivo by a central mechanism involving activation of the vagus nerve (69,80). It is possible that other experimental and clinically approved therapeutics function through the unanticipated mechanism of activating neural pathways. For example, low doses of centrally administered alpha-MSH or salicylates elicit specific peripheral anti-inflammatory responses. Likewise, the cardiac anti-arrhythmic drug amiodarone, as well as aspirin, indomethacin, and ibuprofen substantially increase vagus nerve activity (reviewed in 18). The precise identification of the brain receptor(s) that mediate these effects will facilitate the development of effective, specific receptor agonists to pharmacologically activate the cholinergic anti-inflammatory pathway.

It also is interesting to reconsider alternative therapeutic approaches in light of the cholinergic anti-inflammatory pathway. For instance, hypnosis, meditation, prayer, biofeedback, acupuncture, and even Pavlovian conditioning of immunological responses are believed to involve central mechanisms that modulate experimental systemic or peripheral inflammatory responses. Moreover, autonomic dysfunction occurs not only in association with lethal critical illness and sepsis but also is considered a complication of diabetes, rheumatoid arthritis, and other autoimmune diseases (reviewed in 18). Whether physiological augmentation of vagus nerve activity through any of these methods can modulate disease activity remains an open question."
Title: Re: Prevention and relief with plant sterols and sterolins (Moducare)
Post by: FloppyBanana on December 13, 2014, 05:29:58 PM
Hi G-Man,

Interesing;"Likewise, the cardiac anti-arrhythmic drug amiodarone, as well as aspirin, indomethacin, and ibuprofen substantially increase vagus nerve activity"

Dr S Dexter suggested I try ibuprofen for POIS a while back. He never explained why though.

FB
Title: Re: Prevention and relief with plant sterols and sterolins (Moducare)
Post by: G-man on December 14, 2014, 07:58:15 AM
Also from that article:

"Female sex hormones and estrogens, in particular, also exert immunomodulatory and anti-inflammatory effects. Because their synthesis and blood concentrations are under control of hypothalamo-pituitary hormones, estrogen-affected immune functions can be imputed to the brain. Female sex hormones play immunoregulatory roles during pregnancy and in diseases like rheumatoid arthritis and osteoporosis (60). The classic mechanism of steroid hormone action (as described above for glucocorticoids) may contribute to estrogen immunomodulating activity. Estrogens are neuroprotectors (61); they prevent cartilage degradation during inflammation associated with increased production of IL-1 (62); and they inhibit the production of pro-inflammatory cytokines at different stages of their synthesis (63,64)."
Title: Re: Prevention and relief with plant sterols and sterolins (Moducare)
Post by: Nightingale on December 27, 2014, 02:44:15 PM
I wanted to say I got my Moducare in the mail earlier this week. I have tried it out twice, once to make sure I tolerated it well and now to recover from a 2 orgasm night. I'm impressed, more to feedback to come.

Thanks Quantum!
Title: Re: Prevention and relief with plant sterols and sterolins (Moducare)
Post by: G-man on December 27, 2014, 09:14:36 PM
I have been taking moducare daily for the last two weeks. Also I have been doing a water fast for 1-2 days a week, and my POIS symptoms now last 4-5 days instead of the usual 6. More expiramentation is needed, but the results so far are promising.
Title: Re: Prevention and relief with plant sterols and sterolins (Moducare)
Post by: Quantum on December 27, 2014, 09:37:10 PM
I wanted to say I got my Moducare in the mail earlier this week. I have tried it out twice, once to make sure I tolerated it well and now to recover from a 2 orgasm night. I'm impressed, more to feedback to come.

Thanks Quantum!

Hi Nightingale,

I am glad you find it of help for your recovering phase. It has been of help for me, and thought it would also be for someone else on the forum.  Let's just hope this beneficial effect will be repeatable for you !

I totally agree with your safe approach when starting a new supplement  (first tie I took niacin, I went with only 60mg ).


I think that POIS sufferers that would benefit the most from Moducare are those with allergy-like symptoms (runny nose watery eyes, itching, asthma, ....), and maybe also those with flu-like symptoms, especially joints pain.  However, the immune system is complex.  I do not have allergy-like symptoms, and have slight flu-like symptoms, including some muscle tension, some general aching (hyperalgesia), and Moducare helps me with those, as it does with fatigue, too.  Its action on the inflammation process is broad, so, if my views on POIS are correct, it helps temper the pro-inflammatory cytokines release at the onset of POIS.  Theoretically, then, it would help any POISer, but real life does not always agree with theory...hehe....

However, I do know for a long time the beneficial effects of Moducare when I take it for a cold or flu, as well as in prevention of infections when too much people sick around me and at work.  It has been a safe supplement for me, and its effects did not wear off through the years (but i never used it on a regular basis, though, mostly for cold and flu treatment or preventions, and, more recently, during the last year, 1 capsule before sports to help with the post-sport inflammation and immune system backlash ).

I would be interested in knowing what POIS symptoms have been relieved for you, when taking Moducare, and if you took it before O, or only after.

Have a great day!

 
Title: Re: Prevention and relief with plant sterols and sterolins (Moducare)
Post by: Quantum on December 28, 2014, 10:06:41 AM
I have been taking moducare daily for the last two weeks. Also I have been doing a water fast for 1-2 days a week, and my POIS symptoms now last 4-5 days instead of the usual 6. More expiramentation is needed, but the results so far are promising.


Hi G-man,

Great to hear that you've had a measurable improvement with Moducare, reducing your POIS duration.

Since this product has not been tried a lot so far in POIS, I would for sure be interested to know if, apart from shorter duration of your acute POIS phase, any specific symptoms have been significantly reduced by Moducare, and if other symptoms less relieved or not at all.  In particular, since I do not have any cognitive symptoms myself and couldn't auto-test about these, I am curious to see if Moducare helps with this type of symptoms.

Thanks, and have a great day!
Title: Re: Prevention and relief with plant sterols and sterolins (Moducare)
Post by: Nightingale on December 28, 2014, 08:57:28 PM
Quantum, you and I are similar in our symptoms of POIS, I don't really get obvious allergic ones and only slightly flu like with the muscle soreness. Mine is highly energy related and highly cognitive.

On the Moducare: I found it to be very effective in reducing symptoms! I already get about 80% reduction with my previous routine (curcumin pills and olive leaf extract), and I would say the Moducare bumped it up to 90%.

There is a caveat. I began taking Moducare every 4-6 hours the day after, and by the evening dose I started to have trouble cognitively. I would describe it like writer's block, or just a blockage of thought. This has happened before when I have taken too many antihistamines.

So I think there may be a sweet spot for me to find. I definitely will be trying Moducare for my next orgasm, but I will only take a few doses the next day. My immune system is very funky. There was a point where I had to take 2x the recommended dosage of antihistamines to be able to function at work. Then, after my stomach issues improved, I began to get foggy headed again and tried backing off to 1x a day and that helped my mind function better. I then started allergy shots, and ended up stopping the antihistamines completely.

I'll have a chance to try again this weekend.
Title: Re: Prevention and relief with plant sterols and sterolins (Moducare)
Post by: G-man on December 29, 2014, 10:40:52 PM
My first impression was that it made my symptoms worse because my eyes felt more irritated after taking it. However I noticed that it was only the eye irritation that was worse and not my symptoms as a whole. At the moment I can say that I have less brain fog and muscle pain as a result of taking Moducare. I don't know for sure yet, but I believe that I benefit more from taking it on the days leading up to O, than from taking it post O.
Title: Re: Prevention and relief with plant sterols and sterolins (Moducare)
Post by: Quantum on December 31, 2014, 09:47:36 AM
My first impression was that it made my symptoms worse because my eyes felt more irritated after taking it. However I noticed that it was only the eye irritation that was worse and not my symptoms as a whole. At the moment I can say that I have less brain fog and muscle pain as a result of taking Moducare. I don't know for sure yet, but I believe that I benefit more from taking it on the days leading up to O, than from taking it post O.

Hi G-man,

I am amazed at how much human biology and immune system can be unpredictable at time.  Moducare is usually effective against allergy symptoms, and your eyes irritation is worsen by it....interesting, to say the least!....   

However, it is great to see that brain fog and muscle ache is relieved a bit.   This may partly confirm that there is in fact an immune reaction at the core of POIS.  One may say that muscle ache is relieved in a more direct way by the anti-inflammatory properties of Moducare.  But again, it is hard to talk about inflammation without referring to the immune system.  It is however clearer still that Moducare has nothing to do with cognitive faculties, unless that cognitive impairment would be mediated by an inappropriate immune reaction, as it seems to be in POIS.  And that is what I think - POIS cognitive symptoms are, in my humble opinion, caused at least in part by the immune upregulation of one or two specific enzymes (IDO, and TDO ) creating an unbalance in tryptophan, and thus niacin and also seroton metabolism, leading to cognitive symptoms (brain fog, memory problems,...) because of niacin lack in CNS, and also emotional symptoms (anxiety, mood swings, lack of motivation, extreme fatigue, social avoidance,....) due to central serotonin depletion.
Title: Re: Prevention and relief with plant sterols and sterolins (Moducare)
Post by: Nightingale on December 31, 2014, 03:08:25 PM
I just tried again, and didn't do the same protocol with my turmeric (used a different, more expensive supplement and was hesitant to take a higher dose $$). My soreness was definitely palpable, but my cognitive  function seems to be quite good. I went to work and had a good time juggling tasks.

Perhaps that's where Moducare can give me improvement!
Title: Re: Prevention and relief with plant sterols and sterolins (Moducare)
Post by: Quantum on January 01, 2015, 04:34:22 PM
I just tried again, and didn't do the same protocol with my turmeric (used a different, more expensive supplement and was hesitant to take a higher dose $$). My soreness was definitely palpable, but my cognitive  function seems to be quite good. I went to work and had a good time juggling tasks.

Perhaps that's where Moducare can give me improvement!

So, if I hear you correctly, you had less brain fog and cognitive symptoms, but as much muscle pain as usual?  As with many supplements, response with Moducare seems to vary from one individual to another, as G-man seems to have less cognitive AND less muscle pain with Moducare.

I can't comment myself on either cognitive symptoms or muscle pain form my Moducare usage - I don't have those symptoms.

Title: Re: Prevention and relief with plant sterols and sterolins (Moducare)
Post by: Colm on January 02, 2015, 04:56:22 AM
Is ibuprofen also a key to anti-ageing?
=======================

An interesting study (with animals) using Ibuprofen, and with reference to Tryptophan also. Not sure what it all means, but perhaps a positive side effect of using Ibuprofen in a safe manner periodically.

Overview of the interesting study...
http://www.independent.co.uk/life-style/health-and-families/health-news/could-ibuprofen-be-key-to-antiageing-study-finds-painkiller-extends-life-of-flies-and-worms-by-equivalent-of-12-human-years-9935169.html

About this study, for anyone scientifically minded or researchers ..
http://www.plosgenetics.org/article/info%3Adoi%2F10.1371%2Fjournal.pgen.1004860

Maybe all you guys taking Ibuprofen look a lot younger for your age than the rest of us !!!

Obviously all meds in moderation, or under the care of your Doctor !

Title: Re: Prevention and relief with plant sterols and sterolins (Moducare)
Post by: Nightingale on January 02, 2015, 01:50:19 PM
I just tried again, and didn't do the same protocol with my turmeric (used a different, more expensive supplement and was hesitant to take a higher dose $$). My soreness was definitely palpable, but my cognitive  function seems to be quite good. I went to work and had a good time juggling tasks.

Perhaps that's where Moducare can give me improvement!

So, if I hear you correctly, you had less brain fog and cognitive symptoms, but as much muscle pain as usual?  As with many supplements, response with Moducare seems to vary from one individual to another, as G-man seems to have less cognitive AND less muscle pain with Moducare.

I can't comment myself on either cognitive symptoms or muscle pain form my Moducare usage - I don't have those symptoms.

I should probably retract my observations, I began to become manic after switching to a new brand of curcumin, Theracuramin by Natural Factors. I switched because the extraction process reduces the curcumin to nano-size, and purports to increase absorption and to stay in the blood stream longer. I think it must be crossing the blood/brain barrier, too, so I felt very uncomfortable for about 2 days. The dilemma of trying to help oneself too fast and changing two things at once makes me doubt my conclusions.

I've returned to my old brand, back to testing Moducare more!
Title: Re: Prevention and relief with plant sterols and sterolins (Moducare)
Post by: Stef on January 02, 2015, 05:24:07 PM
"I should probably retract my observations, I began to become manic after switching to a new brand of curcumin, Theracuramin by Natural Factors. I switched because the extraction process reduces the curcumin to nano-size, and purports to increase absorption and to stay in the blood stream longer. I think it must be crossing the blood/brain barrier, too, so I felt very uncomfortable for about 2 days. The dilemma of trying to help oneself too fast and changing two things at once makes me doubt my conclusions.

I've returned to my old brand, back to testing Moducare more!"
[/quote]

Nightingale --

I so admire your candor and your willingness to always share your experiences with honesty.

Best wishes,
Stef

 
Title: Re: Prevention and relief with plant sterols and sterolins (Moducare)
Post by: Nightingale on January 03, 2015, 11:24:01 AM
"I should probably retract my observations, I began to become manic after switching to a new brand of curcumin, Theracuramin by Natural Factors. I switched because the extraction process reduces the curcumin to nano-size, and purports to increase absorption and to stay in the blood stream longer. I think it must be crossing the blood/brain barrier, too, so I felt very uncomfortable for about 2 days. The dilemma of trying to help oneself too fast and changing two things at once makes me doubt my conclusions.

I've returned to my old brand, back to testing Moducare more!"

Nightingale --

I so admire your candor and your willingness to always share your experiences with honesty.

Best wishes,
Stef
[/quote]

Thank you Stef!

There's nothing more valuable than sharing our experiences with each other here, it creates the kind of culture that is necessary for us to improve our lives. You play a part in that too! :)
Title: Re: Prevention and relief with plant sterols and sterolins (Moducare)
Post by: FloppyBanana on January 03, 2015, 11:56:24 AM
I then started allergy shots, and ended up stopping the antihistamines completely.


Hi Nightingale,
Can ask you how the allergy shots went?
Thanks FB
Title: Re: Prevention and relief with plant sterols and sterolins (Moducare)
Post by: Nightingale on January 03, 2015, 08:59:32 PM
To be clear, I'm taking allergy shots for pollen, dust mites, and dog hair.  I have not had shots for semen allergy, and I have never had a semen allergy test.

I have just reached maintenance dose for the allergy shots, and I have 2-3 years more
Title: Re: Prevention and relief with plant sterols and sterolins (Moducare)
Post by: Ccconfucius on January 19, 2015, 11:25:26 PM
do you think using pure tryptophan during pois episode can make symptoms worse. I have used this batch of tryptophan before without any problems. But when i used it during a strong pois episode caused by to much orgasm, the next day i woke up with strong fever and headache that only stopped in three days  because i used ibuprofen and tylenol.
Title: Re: Prevention and relief with plant sterols and sterolins (Moducare)
Post by: Quantum on January 20, 2015, 08:52:03 AM
do you think using pure tryptophan during pois episode can make symptoms worse. I have used this batch of tryptophan before without any problems. But when i used it during a strong pois episode caused by to much orgasm, the next day i woke up with strong fever and headache that only stopped in three days  because i used ibuprofen and tylenol.

Hi CertainlyPOIS,

How many milligrams or tryptophan were you taking per dose, and how many dose per day?

More or less side effects depends on how many mg of tryptophan you were taking.  Too much at once or too much daily will cause side effects and is not any better than the lack of tryptophan.

I am a big fan of "the smallest efficient dose" approach, and of synergy between small doses of substance helping each other.  For tryptophan, I wouldn't take more than 300mg, and not much than every 8 to 12 hours.  This is already much higher than what can be absorbed through diet. But the important part is to make sure that this new supply of tryptophan will not be metabolized by over-activated enzymes  ( IDO and TDO) as it get to the blood stream and before being able to get to the brain, unless it is like trying filling up a pail that has a hole in the bottom. 

Take a look at the little diagram I have attached, and you will see at the left that an inflammatory reaction (like I think there is in POIS), or simply stress ( cortisol activates TDO ), is activating the transformation of tryptophan in kynurenine. So, if you are in POIS, you may consider blocking those two enzymes together with your tryptophan intake. You will need far less tryptophan to get relief, and avoid side effects of large doses.  In my case, I take only 25mg to 50 mg of 5-HTP, 1 or 2 times a day  (even if recommended dosage is 100 mg 2 times a day), because I take along IDO inhibitors ( like peppered curcumin or rosemary) and TDO inhibitor (like quercetin, or Milk Thistle, which contains dihydroquercetin).

My experience, however, is that blocking the enzymes pre-O is more effective (taking IDO and TDO inhibitors 1 hour before O is more effective than after O).





Title: Re: Prevention and relief with plant sterols and sterolins (Moducare)
Post by: Ccconfucius on January 20, 2015, 07:30:26 PM
do you think using pure tryptophan during pois episode can make symptoms worse. I have used this batch of tryptophan before without any problems. But when i used it during a strong pois episode caused by to much orgasm, the next day i woke up with strong fever and headache that only stopped in three days  because i used ibuprofen and tylenol.

Hi CertainlyPOIS,

How many milligrams or tryptophan were you taking per dose, and how many dose per day?

More or less side effects depends on how many mg of tryptophan you were taking.  Too much at once or too much daily will cause side effects and is not any better than the lack of tryptophan.

I am a big fan of "the smallest efficient dose" approach, and of synergy between small doses of substance helping each other.  For tryptophan, I wouldn't take more than 300mg, and not much than every 8 to 12 hours.  This is already much higher than what can be absorbed through diet. But the important part is to make sure that this new supply of tryptophan will not be metabolized by over-activated enzymes  ( IDO and TDO) as it get to the blood stream and before being able to get to the brain, unless it is like trying filling up a pail that has a hole in the bottom. 

Take a look at the little diagram I have attached, and you will see at the left that an inflammatory reaction (like I think there is in POIS), or simply stress ( cortisol activates TDO ), is activating the transformation of tryptophan in kynurenine. So, if you are in POIS, you may consider blocking those two enzymes together with your tryptophan intake. You will need far less tryptophan to get relief, and avoid side effects of large doses.  In my case, I take only 25mg to 50 mg of 5-HTP, 1 or 2 times a day  (even if recommended dosage is 100 mg 2 times a day), because I take along IDO inhibitors ( like peppered curcumin or rosemary) and TDO inhibitor (like quercetin, or Milk Thistle, which contains dihydroquercetin).

My experience, however, is that blocking the enzymes pre-O is more effective (taking IDO and TDO inhibitors 1 hour before O is more effective than after O).


I only took a 500mg pill right before bed that day but before then i had not taken any for months. I will try it the way you described, i figured 500mg is to much anyways.
I see you mention rosemary, a poiser mentioned it helped them recover faster.
Title: Re: Prevention and relief with plant sterols and sterolins (Moducare)
Post by: Quantum on January 20, 2015, 11:12:57 PM
I only took a 500mg pill right before bed that day but before then i had not taken any for months. I will try it the way you described, i figured 500mg is to much anyways.
I see you mention rosemary, a poiser mentioned it helped them recover faster.

Rosemary is one of my best POIS-relieving supplement.  The rosmarinic acid in it is an excellent IDO inhibitor ( http://en.wikipedia.org/wiki/Rosmarinic_acid#Clinical_importance) , so it is good for blocking the transformation of tryptophan in kynurenine.  It is one of the best also as prevention, when I take it in my pre-O pack, one hour before O.  Rosemary is also a very good antioxidants source.  I have noticed years ago that rosemary was good for me, way before knowing about the role of IDO and tryptophan in my POIS. 

if you go to the link I gave above, you will also read that rosmarinic acid has anxiolytic properties, via the inhibition of the GABA transaminase enzyme.  No surprise it helps me a lot against POIS, my main symptoms being emotional symptoms, including anxiety.

My favorite and most effective way to take rosemary, and also very low cost, is to use rosemary essential oil.  I put 1 drop in a glass of water, mix it, and drink as needed (never put more than 1 or 2 drops in a glass of water, essential oils are highly  concentrated).  If you can bare the camphor-like taste of the rosemary essential oil,which is not that bad, that's much more efficient and faster than eating rosemary.  My "rosemary water" is good for all POIS symptoms, and the one most effective way to correct my POIS-induced hypotension (if I didn't take my pre-O pack and get symptoms ). Furthermore, 25mg of 5-HTP taken with rosemary water is very, very effective for me.

Other spices/herbs also contains rosmarinic acid, and are good for POISers as well: curcumin, oregano, sage, marjoram, peppermint oil, lemon balm, basil.  They are all anti-inflammatory and anxiolytic, some more than others ( rosemary and curcumin are my favorites).  I started to put more spices in what I eat, last year, after reading about the benefits of peppered curcumin and other spices as well.  I didn't know that would help me eventually with POIS :)

You are totally right, go slowly with your tryptophan dose.  It is better to take less, like 200mg. and take more a few hours later, than take too much and being stuck with side effects.
Title: Re: Prevention and relief with plant sterols and sterolins (Moducare)
Post by: G-man on February 05, 2015, 11:35:43 PM
The concept of depression as a dysfunction of the immune system

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3002174/?report=classic

"Chronic stress, by initiating changes in the hypothalamic-pituitary-adrenal axis and the immune system, acts as a trigger for anxiety and depression. Both experimental and clinical evidence shows that a rise in the concentrations of proinflammatory cytokines and glucocorticoids, as occurs in chronically stressful situations and in depression, contribute to the behavioural changes associated with depression.

A defect in serotonergic function is associated with hypercortisolaemia and the increase in proinflammatory cytokines that accompany depression. Glucocorticoids and proinflammatory cytokines enhance the conversion of tryptophan to kynurenine. In addition to the resulting decrease in the synthesis of brain serotonin, this leads to the formation of neurotoxins such as the glutamate agonist quinolinic acid and contributes to the increase in apoptosis of astrocytes, oligodendroglia and neurons.

The importance of the inflammation hypothesis of depression lies in raising the possibility that psychotropic drugs that have a central anti-inflammatory action might provide a new generation of antidepressants."

...

"Until recently, the brain was considered to be an immunologically privileged organ that was protected from the peripheral immune system by the blood-brain-barrier. It is now apparent that this view is incorrect and that the brain is directly influenced by peripherally derived cytokines, chemokines, prostenoids and glucocorticoids, as well as some immune cells, that can access the brain and thereby influence those neuronal networks that appear to be malfunctioning in depression [9]. The influence of large molecules from the periphery on the brain is somewhat surprising as specific transporters for peptides such as the interleukins do not appear to be present at the blood-brain-barrier. Nevertheless, there is now experimental evidence to indicate that such molecules could access the brain a) via a leaky blood-brain-barrier that occurs in major depression, b)by activation of endothelial cells that line the cerebral vasculature and produce inflammatory mediators inside the barrier c)by binding to cytokine receptors associated with the vagus nerve and thereby signalling inflammatory changes in the brain via the nucleus tractus solitarius and hypothalamus [10,11]. Once in the brain, the proinflammatory cytokines activated both neuronal and non-neuronal (for example, the microglia, astrocytes and oligodendroglia) cells via the nuclear factor-kappa-beta (NF-kB) cascade in a similar manner to that occurring in the peripheral inflammatory response [12].

There is also evidence from clinical studies that peripherally administered cytokines can enter the brain. Thus the therapeutic administration of IFN to patients with hepatitis results in an increase in the cerebrospinal fluid (CSF) not only of IFN but also IL-6 and monocyte chemoattractant protein (MCP-1) [13]. In experimental studies it has been shown that MCP-1 activates microglia to release IL-1 and TNF [14] and as the microglia are the primary source of proinflammmatory cytokines in the brain this could be an important means whereby peripheral inflammatory mediators activate the inflammatory response in the brain. In addition, the proinflammatory cytokines modulate the release of biogenic amine neurotransmitters [15]. Recently much attention has been paid to the activation of the tryptophan-kynurenine pathway by these cytokines whereby tryptophan is shunted from the synthesis of serotonin to that of kynurenine. The importance of this pathway will be discussed in more detail later and clearly this is an important mechanism whereby serotonergic function is decreased in depression. The activity of the dopaminergic system is also reduced in response to inflammation. For example, IFN reduces the synthesis of dopamine by decreasing the concentration of the co-factor tetrahydrobiopterin (BH4), thereby reducing the synthesis of dihydroxyphenylalanine (DOPA), the immediate precursor of dopamine, from tyrosine [16]. As IFN increases the synthesis of nitric oxide by activating the BH4 dependent enzyme nitric oxide synthase in the microglia it seems likely that the reduction in dopaminergic function is linked to the increase in nitric oxide. This gaseous neurotransmitter is known to activate the glutamatergic system which, when this exceeds physiologically limits, enhances apoptosis and neurodegeneration [15,16].

Cytokines, and their signalling pathways, have been shown to enhance the re-uptake of monoamine neurotransmitters and thereby reduce their functionally important inter-synaptic concentrations in the brain [16,17]. For example,IL-1 and TNF have been shown to activate the serotonin transporter on neurons by stimulating the p38 mitogen activated protein kinase pathway [17]

In addition to the modulation of neurotransmitter function, proinflammatory cytokines contribute to the major symptoms of depression by activating the HPA axis by increasing the release of CRF, thereby contributing to hypercortisolaemia, a feature of major depression [18,19,20]. The mechanism whereby the cytokines induce hypercortisolaemia involves a decreased sensitivity of the glucocorticoid receptors thereby leading to glucocorticoid resistance; both the brain and the peripheral receptors become insensitive to glucocorticoid activation. The precise mechanism whereby the proinflammatory cytokines cause glucocorticoid receptor insensitivity is uncertain but it is known that the cytokines activate the inflammatory cascade. Thus the NF-kB, p38MAPK and the 5-STATS (signal transducer and activator of transcription 5) pathway is activated and leads to a disruption of the translocation of glucocorticoid receptors from the cytoplasm to the nucleus (21), thereby decreasing the active form of the receptor. While it would appear that glucocorticoid receptor resistance is correlated with the increase in the serum concentration of the proinflammatory cytokines, it seems unlikely that glucocorticoid resistance is directly related to the psychopathology of depression. Thus an increase in proinflammatory cytokines leading to glucocorticoid resistance also occurs in nondepressed individuals without any major change in the mood state [22]. However, such observations do throw light on the fact that many aspects of cellular and humoral immunity are not suppressed in patients with major depression despite the elevation of the plasma glucocorticoid concentration that is a common feature of the disorder."

"An important conceptual shift in the possible cause of depression has occurred recently with the discovery that inflammation plays a crucial role in the psychopathology of the disorder. However, as major depression is often accompanied by inflammatory diseases (such as irritable bowel syndrome, type 2 diabetes, arthritis and autoimmune disorders) that can activate the peripheral and central inflammatory response, it is possible that such inflammatory disorders initiate the inflammatory changes that precipitate depression. Although this is plausible, it is evident that inflammation also occurs in depressed patients who are not suffering from concurrent inflammatory disorders. Thus the increased vulnerability of depressed patients to psychosocial stress is probably the key factor that leads to the activation of the immune and endocrine axes in depression. It is known, for example, that even the relatively mild acute stress of public speaking causes an increase in NF-kB activity, a key element in the induction of the inflammatory cascade [23]. In this regard, it is also known that patients with major depression frequently show an enhanced responsiveness of IL-6 and NF-kB to an antigen challenge [24]. However, chronic stress, as experienced by caregivers or individual subject to marital discord but who are not suffering from depression also show an increase in plasma C-reactive protein, IL-6 and other inflammatory mediators [24,25]. Whatever the cause, such changes appear to be associated with activation of the microglia thereby suggestion that the inflammatory changes are also occurring in the brain [26].

The mechanism whereby psychological stress influences both the peripheral and central inflammatory cascade is co-ordinated by the autonomic nervous system. Thus the release of noradrenaline and adrenaline following the activation of the sympathetic system results in the activation of both alpha and beta adrenoceptors on immune cells thereby initiating the release of proinflammatory cytokines, via the activation of the NF-kB cascade, particularly on macrophages and monocytes in peripheral blood; antagonists of these adrenoceptors block the stress induced rise in these cytokines [27]. Conversely stimulation of the parasympathetic system has the opposite effect on the stress induced inflammatory response. Thus stimulation of the vagus nerve results in release of acetylcholine that activates the alpha-7 sub-unit on nicotinic receptors thereby reduces the activation of NF-kB [28]. It is possible that the anti-depressant-like action of vagal nerve stimulation, occasionally used to treat resistant depression, is associated with such an anti-inflammatory action.

The question arises why should inflammation occur in depressed patients despite the frequently observed increase in glucocortioids? The most parsimonious explanation is that glucocorticoid receptor resistance in the brain and periphery contribute to the lack of suppression of most types of immune cells with the possible exception of the natural killer cells. One possible explanation is that the stress induced increase in the sympathetic nervous system, combined with steroid resistance, leads to the activation of the microglia in the brain, and macrophages and monocytes in the periphery, thereby leading to the inflammatory state."
Title: Re: Prevention and relief with plant sterols and sterolins (Moducare)
Post by: G-man on February 05, 2015, 11:39:09 PM
Continued from the previous post

"Of the numerous neurotransmitters that have been postulated to be dysfunctional in major depression, serotonin has been widely implicated for its contributory role in the symptoms of the disorder (sleep disturbance, depressed mood, anorexia, loss of libido and anxiety). Serotonin modulates the stress axis by activating the corticotrophin releasing factor pathways in the para ventricular nucleus thereby increasing the release of adrenocorticotrophic hormone from the anterior pituitary gland [29] There is a close relationship between the plasma cortisol concentration and the serotonergic system. Thus the stress induced rise in cortical is associated with an increased turnover of serotonin, a change that is linked to the stimulation of the rate limiting enzyme, tryptophan hydroxylase, in the pathway leading to the synthesis of serotonin from tryptophan [30]. Chronic stress that results in a sustained rise in cortisol has the opposite effect and sertotonin release is decreased. This is associated with the glucocorticoid activation of tryptophan dioxygenase in the liver whereby tryptophan is diverted from serotonin synthesis down the tryptophan-kynurenine pathway [31].

The increase in anxiety, and the impairment if adaptation to chronic stress that has been observed in both animals and man can be explained by the changes in the functional activity of the somatodendritic 5HT 1A receptors located on the median raphe nucleus and the hippocampus [32]. Experimental studies have shown that rats raised in a stressful, overcrowded environment show an increase in anxiety which is correlated with a decrease in the functional activity of the 5HT1A receptors. These receptors are influenced by the mineralocorticoid receptors that inhibit the 5HT1A receptor activity under conditions of chronic stress [33] In contrast to the 5HT1A receptors, the 5HT2 receptors are activated by chronic stress [34] while the 5HT1B receptors, that act as autoreceptors and thereby control the release of the transmitter, are activated by chronic stress [35]. Thus the stress induced changes in the circulating glucocorticoids can help to explain the decrease in the functional activity of the serotonergic system in depression."

...

"The emphasis in this review is on the adverse effects of the proinflammatory cytokines that, in pathological concentrations in the brain and periphery, are likely to cause cellular injury. However, it must be remembered that at physiological concentrations, these same cytokines provide trophic support for neurons, enhance neurogenesis and contribute to normal cognitive function [39]. Such effects are severely compromised when the cytokines are present in pathological concentrations and result in changes that are important in the psychopathology of depression. Thus in major depression, the prolonged activation of the inflammatory network in the brain results in a decrease in neurotrophins, leading to reduced neuronal repair, a decrease in neurogenesis, and an increased activation of the glutamatergic pathway that contributes to neuronal apoptosis, oxidative stress and the induction of apoptosis in astrocytes and oligodendrocytes [40,41,42,43].

In addition to the proinflammatory cytokines, nitric oxide and the glucocorticoids, glutamate plays a crucial role in the pathological processes that are associated with depression. The proinflammatory cytokines, and inflammatory mediators such as nitric oxide, increase glutamate release and decrease the expression of glutamate transporters on astrocytes and oligodendroglia thereby decreasing glutamate reuptake and enhancing the inter-synaptic concentration [44].

Stimulation of the extra-synaptic N-methyl-D-aspartate (NMDA) glutamate receptor not only causes excitotoxic damage to the neurons and astrocytes but also results in a decrease in synthesis of brain derived neurotrophic factor (BDNF), a key neurotrophic factor governing neuronal repair [45]. To add to the potential neurotoxic changes, IL-1 and TNF, that are generally raised in depression, trigger the release of reactive oxygen and nitrogen species from activated microglia and astrocytes; these are toxic to both neurons and oligodendroglia [46,47]. The net result of these changes is a loss of astrocytes and oligodendroglia, and neuronal apoptosis particularly in the subgenual prefrontal cortex, the amygdala and the hippocampus, brain regions that are thought to be crucially involved in the genesis of the symptoms of depression.[48].

The question now arises regarding the possible link between the neurotoxic effects of the proinflammatory cytokines, excess glutamate and the tryptophan-kynurenine pathway that, in depression, produces neurotoxic end-products that contribute to neurodegeneration in depression. Tryptophan is metabolised through two main pathways, one of which leads to the synthesis of serotonin and the other to kynurenine and kynurenic acid. In the latter pathway, tryptophan is metabolised by indoleamine 2,3 dioxygenase (IDO), an enzyme that is quite widely distributed in peripheral tissues and the brain, and by tryptophan 2,3 dioxygenase (TDO) that is primarily located in the liver [49]. IDO is activated by proinflammatory cytokines while TDO is activated by glucocorticoids. As both the cytokines and cortisol are raised in major depression, it is not surprising to find that the tryptophan-kynurenine pathway is increased [49,50]. Anti-inflammatory cytokines reduce the activity of this pathway [51]. There are two main pathways that lead to the metabolism of tryptophan following the formation of kynurenine. Kynurenine hydroxylase metabolises kynurenine first to 3-hydroxykynurenine and then to 3-hydroxyanthranilic acid and quinolinic acid. This pathway is increased in depression and dementia [49,50]. In glia and neurons 3-hydroxykynurenine increases the formation of reactive oxygen species while quinolinic acid activates NMDA glutamate receptors and thereby enhances apoptosis. By contrast kynurenine can be metabolised by kynurenine aminotransferase to for the neuroprotective end product, kynurenic acid, an antagonist of NMDA receptors [51]. In the brain,the metabolism of tryptophan by IDO occurs both in the microglia and astrocytes [52]. The microglia synthesise both 3-hydroxyanthranilic acid and quinolinic acid while the astrocytes produce mainly kynurenic acid. Astrocytes also metabolise quinolinic acid and therefore under physiological conditions can reduce the impact of the neurotoxins [53]. In chronic depression however, the activated microglia produce an excess of the neurotoxin that cannot be adequately metabolised by the astrocytes. Furthermore quinolinic acid can cause apoptosis of the astrocytes. This results in a reduction in the metabolic and physical buffer to the neurons that is usually provided by the astrocytes and thereby further exposes the neurons to the neurodegenerative actions of quinolinic acid [54].

The clinical evidence supporting the hypothesis that the tryptophan-kynurenine pathway is activated comes from two major studies. Wichers and coworkers [55] showed that the concentration of kynurenic acid was reduced in patients being treated with IFN for the treatment of hepatitis while Myint and colleagues [56] reported evidence that components of the neurodegerative pathway was increased in the blood of depressed patients before antidepressant treatment. Effective treatment for 8 weeks only partially reversed these changes in patients being treated for their first major episode of depression but had no effect in those patients who had suffered several episodes. This suggests that more permanent changes may occur in the brain of those with a chronic depression.

The structural changes observed in the brain of patients with chronic depression lends support to the neurodegenerative hypothesis of depression [57]. It is known that there is a shrinkage of the hippocampus in patients with major depression [58] and a decrease in the number of astrocytes and a neuronal loss in the prefrontal cortex [59] and in the striatum. Such changes could be the consequence of chronic low grade inflammation in which the proinflammatory cytokines, nitric oxide, prostaglandin E2 and other inflammatory mediators play key roles; the cytokines are known to induce the cyclo-oxygenase and nitric oxide sythase pathways in the brain and thereby increase the inflammatory insult [60]. The inhibition of neurotrophin synthesis in the brain by glucocorticoids [61], and the neurotoxic action of quinolinic acid, add further to the impact of the inflammatory changes."
Title: Re: Prevention and relief with plant sterols and sterolins (Moducare)
Post by: Quantum on March 06, 2021, 06:10:20 PM
I am posting a follow up on my Moducare use in POIS.  This thread dates back to the first months I had found poiscenter.   You can read my update in its context at https://poiscenter.com/forums/index.php?topic=3717.msg39648#msg39648 (https://poiscenter.com/forums/index.php?topic=3717.msg39648#msg39648) .

here is a copy and paste of it:
"Hi Journey,  here is some info about this Th1 and Th2 balance:
"Too little TH1 activity and the immune system can not fight off virus or cancer, whilst too much TH2 activity and the immune system will stop recognising self tissue as self and damage its own body (an auto immune reaction). A balanced T helper cell activity is essential for optimum health." ( from https://dennisthechemist.blogspot.com/2011/11/moducare-and-me.html (https://dennisthechemist.blogspot.com/2011/11/moducare-and-me.html)  , interesting and simple article to understand the basics of the Th1 - Th2 system)


Interestingly enough, Moducare will help either way.  It helps raise Th1 when too low and helps lower Th2 when too high.

Recently, I have used Moducare in the context of a couple of unexpected NE.  2 Capsules right after, when I woke up, and again the following day, a few other doses.  I was amazed at how well it works for me.  Back in 2014, when I developed my pre-pack composition, I remember I put it aside because of its rather higher cost than other supplements, but I already knew it was very effective for me.  Through the years, I kept it for treating cold and flu, and allergy symptoms.  Now I probably have developed more kindness for myself than back then (https://poiscenter.com/forums/Smileys/classic/smiley.gif)   I remembered having tested it positively in POIS, and now I "allow" myself to use Moducare more often, including when I have some POIS residual symptoms.  By not using it fo POIS for about 6 years now, I had forgotten how much it is effective to get rid of any residual fatigue and any other residual POIS symptoms, including emotional ones ( irritability, mood swings, ...).   "