Ideas on Endothelial Dysfunction

[FernandoPOIS]

Nas

I believe then that the stimulators of the central nervous system are capable of contracting the blood vessels. In this case we have several options that seem to help a lot as reported here in the forum: Caffeine, pseudoephedrine, green tea....

[swell]

I take Adderall one of most potent stimulators of CNS known.  It is also a vasoconstrictor.  Its a fact and not my opinion.  It lifts your mood like a rocket by increasing helpful neurotransmitters (dopamine, norepinephrine, serotonin).  Whether you are in POIS or not in POIS it will lift you up.  I consider it helping pois 0%.  I say because it only temporary camouflages  your mental fog with this alert feeling.  Its temporary and it follows with a crash.  These meds do nothing to therapeutically cure or help treat your POIS.  In fact it worsens your POIS.  It marshals blood flow and all your energies towards your brain so yes mental fog temporary is gone but at direct factual expense of your other vital organs and your peripherals like skin effect of POIS.  Most POIS sufferers I think have Raynauds syndrome too, and these CNS stimulators make you swell up due to less blood flow reaching furthest organs.  By the way I got Berberine I start eating it today will let all know.

[Muon]

I've uploaded my brother's data, check the second link: http://poiscenter.com/forums/index.php?topic=2545.0
Check the elevated Lp-PLA2 activity. I don't know how this is defined compared to Lp-PLA2 levels. The order form @ #73: https://www.imd-berlin.de/fileadmin/user_upload/Anforderungsscheine/SI_Anforderung_IGEL.pdf  emphasizes endothelial origin?

Check the discussion section: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5377521/
There are more references to other papers in the above article.

[Quantum]

Hi guys,
So I previously mentioned in this thread that Vasoconstrictor drugs could possibly decrease Endothelial permeability by increasing vascular walls' integrity.

So I did by the suggestion of Nanna on his thread: http://poiscenter.com/forums/index.php?topic=2502.msg24507#msg24507

Where he mentioned:
"Taken 45 minutes prior to sexual activity (prepack):
Vasoconstrictors:
---Excedrin (acetaminophen 250mg, aspirin 250mg, caffeine 65mg)"
"The below supplements were not taken in the above trial, but can be stacked. However, consult your doctor before stacking multiple vasoconstricting agents as they can increase the risk of heart attack or stroke.
Enhancements:
---Trimethylglycine/TMG (methyl-donor) (2g)
---Indomethacin (COX inhibitor/antioxidant) (75mg)
---propranolol (beta2-blocker, blocks PGE2 induced vasodilation) (see personal doctor for details)"

So I did try a vasoconstrictor based on his suggestion yesterday, and after consulting a doctor, he suggested taking: Propanolol 10mg, Indomethacin 25mg, Paracetamol 250mg and Aspirin 100mg, all before orgasm.

The results were positive, I noticed a clear reduction in many of the Cognitive POIS symptoms I usually suffered from; there were still some symptoms that I felt, like social anxiety, brain fog and fatigue. But overall dare I say that I had about 80% success rate?. I even masturbated two more times after the first session, after about an hour, and I still was able to talk to people after that! That's an insane result for some one who suffers from POIS.

So this trial and the Dexamethasone trial both gave good results, so I can not dismiss the effect these medications had on the Enndothlium and thus I can not disprove the role of the Endothelium and Epithelium on POIS.

I highly advise you people to try one of these suggested treatments after consulting a doctor to prove a consistency in results. And perhaps be able to look more accurately for suitable tests and predict more accurate theories for the future.

Hi Nas,

I am very happy for you, that you have finally found an effective method to relieve your POIS symptoms. You have been very patient, and tried many methods, and now it pays up for you. 

Please keep us updated in the coming months about how it goes for you.

[Nas]

Ok so I have tried a second round of Vasoconstrictor stack with an increase in some of the doses; I've taken 50mg Indomthacin, 20mg propanolol, 100mg Aspirin and 250 paracetamol, waited 45 minutes as usual and had an O. The result was different, in that while I believe there was a reduction, I'd say about 40%, I still suffered from usual symptoms like brain fog and speech issues. There were less fatigue and pain in the urethra and the genitals region and slightly clearer mind. Still, I was still annoyed from POIS symptoms so I decided to take another 25mg Indomethacin pill to see if it can clear my head a bit more, and it did, but at the same time it caused a huge decrease in blood pressure. I tested it and it was about 116/61 with a 55 heart beat rate, I took it on an empty stomach which is probably why there was a huge decrease in blood pressure. I stabilized my self later after breakfast and drinking salt water.
Overall I'd say that it still caused me POIS, with decreased symptoms.

[Nas]

Ok so I have tried a second round of Vasoconstrictor stack with an increase in some of the doses; I've taken 50mg Indomthacin, 20mg propanolol, 100mg Aspirin and 250 paracetamol, waited 45 minutes as usual and had an O. The result was different, in that while I believe there was a reduction, I'd say about 40%, I still suffered from usual symptoms like brain fog and speech issues. There were less fatigue and pain in the urethra and the genitals region and slightly clearer mind. Still, I was still annoyed from POIS symptoms so I decided to take another 25mg Indomethacin pill to see if it can clear my head a bit more, and it did, but at the same time it caused a huge decrease in blood pressure. I tested it and it was about 116/61 with a 55 heart beat rate, I took it on an empty stomach which is probably why there was a huge decrease in blood pressure. I stabilized my self later after breakfast and drinking salt water.
Overall I'd say that it still caused me POIS, with decreased symptoms.

I will try to give a more accurate prescription of symptoms using Muon's symptoms from his Muon's case post: http://poiscenter.com/forums/index.php?topic=2545.msg24545#msg24545

1= positive result ( had relief )
0= negative result ( did not have relief )
%= about 50% decrease
X= Do not suffer from this symptom

- Extreme fatigue = 1
- Muscle ache = 1
- Joint pain = X
- Exercise/motion intolerance = %
- Heavy body = 1
- Feeling cold/warm, feeling cold happens far more often than warm = 1
- Decreased endurance, especially with the duration of standing and sitting straight = 1
- Sensitive teeth = X
- Stinging pain at liver area = X
- Yellowing of facial skin = X
- Pale skin and facial skin becomes like a babyskin = X
- Decreased vocabulary = 0
- Articulation problems = %
- Poor concentration = %
- Grammar problems (constructing sentences suddenly becomes a puzzle) = 1
- Short term memory loss (temporary) = %
- Motivation in general is being lowered and often completely wiped out = %
- I become someone without personality = %
- Accelerated Bowel movement, loose stools and sometimes diarrhea = X
- It amplifies my food intolerance/sensitivity = X
- Decreased digestion = X
- A sense of being full (digestion) = X
- Fasciculations = X
- Itching = X
- Soar Throat = X
- Decreased accuracy of handwriting ,also problems with controlling videogames like aiming in FPS = 1
- Faster spreading of local fungal skin infection at feet in POIS = X

So there are two points that are interesting here:
1- It seems that I do not suffer from Physical symptoms, or let's say that they are not really that extreme, possible explanation? Perhaps endothelial leaks vary from person to person?
2- I still suffer from cognitive symptoms, which can mean that this treatment is not enough to reduce Endothelial permeability enough so that an inflammatory response doesn't happen in the brain. Any suggestions for better cognitive relief? Also what do you guys think of all of this?

[dizzy]

Do you have tension in the jaw (clenching/bruxism)? I'm getting some good results in the speech/articulation department by simply keeping my jaw relaxed during the day. (I say "simply", but it's not that simple actually, and really requires and effort. But for me the effect is remarkable.)

[Nas]

Do you have tension in the jaw (clenching/bruxism)? I'm getting some good results in the speech/articulation department by simply keeping my jaw relaxed during the day. (I say "simply", but it's not that simple actually, and really requires and effort. But for me the effect is remarkable.)

No, and probably it's not that simple in my case lol.

[swell]

What strategies you use dizzy?  I clench my teeth only when I am real angry so I say once every day I clench my teeth and fist, is that same as bruxism?

Do you have tension in the jaw (clenching/bruxism)? I'm getting some good results in the speech/articulation department by simply keeping my jaw relaxed during the day. (I say "simply", but it's not that simple actually, and really requires and effort. But for me the effect is remarkable.)

[FernandoPOIS]

Look at this:

Bioflavonoids, the diosmin with hesperidin, promote increased resistance of the vascular wall of the vein, with decreased capillary permeability. Clinical and experimental studies suggest that the association of diosmin with hesperidin potentiates the action of noradrenaline in the cellular receptors of the veins, potentiating vasoconstricting action (1), acting as a phlebotropic agent and vascular protector, improving venous tone and lymphatic drainage, reducing the capillary permeability and protecting the microcirculation of inflammatory processes (2,3,4). By reducing the expression of some molecules of endothelial adhesion (5), they inhibit the activation, migration and adhesion of leukocytes at the capillary level (6,7). This causes a reduction in the release of inflammatory mediators, such as free radicals of oxygen, prostaglandins and thromboxane, resulting in reduction in capillary permeability (6,8).

1. Araújo, M.:”Farmacoterapia das Doenças Vasculares Periféricas” Angiologia e Cirurgia Vascular: guia ilustrado pgs 1-13 2003 disponível em www.lava.med.br/livro .

2. Struckmann JR, Nicolaides AN. Flavonoids: a review of the pharmacology and therapeutic efficacy of MPFF 500 mg in patients with chronic venous insufficiency and related disorders. Angiology 1994 Jun 45 (6): 419-28.

3. Daftary SN, Irani JS, Tsouderos Y: “The Therapeutic Activity of Micronized Flavonoid Fraction in IUCD-induced bleeding” Drugs of Today vol 31 (suppl. E) 41-45 1995

4. Bouskela E, Cyrino FZGA, Lerond L. Leukocyte adhesion after oxidant challenge in the hamster cheek pouch microcirculation. J Vasc Res 1999 36 Suppl. 1: 11-4.

5. Korthuis RJ, Gute DC. Adhesion molecule expression in postischemic microvascular dysfunction: activity of a micronized purified flavonoid fraction. J Vasc Res 1999 36 Suppl. 1: 15-23.

6. Damon M, Flandre O, Michael F, et al. Effect of chronic treatment with a purified flavonoid fraction on inflammatory granuloma in the rat: study of prostaglandin E2 and F2a and thromboxane B2 release and histological changes, Arzneimittelforschung 1987 Oct 37 (10): 1149-53

7. Lonchampt M, Guardiola B, Sicot N, et al. Protective effect of a purified flavonoid fraction against-reactive oxygen radicals: in vivo and in vitro study. Arzneimittelforschung 1989 Aug 39 (: 882-5.

8. Boccalon, H., et al.: “Therapeutic Equivalence of Two Dosage Forms of a Micronized Flavonoid Fraction in Patients with Chronic Venous Insufficiency” Current Therapeutic Research vol 57 (10) 1996.

Jean T, Bodinier MC. Mediators involved in inflammation: effects of MPFF 500 mg on their release. Angiology 1994 Jun 45 (6 Pt 2): 554-9

[Quantum]

Ok so I have tried a second round of Vasoconstrictor stack with an increase in some of the doses; I've taken 50mg Indomthacin, 20mg propanolol, 100mg Aspirin and 250 paracetamol, waited 45 minutes as usual and had an O. The result was different, in that while I believe there was a reduction, I'd say about 40%, I still suffered from usual symptoms like brain fog and speech issues. There were less fatigue and pain in the urethra and the genitals region and slightly clearer mind. Still, I was still annoyed from POIS symptoms so I decided to take another 25mg Indomethacin pill to see if it can clear my head a bit more, and it did, but at the same time it caused a huge decrease in blood pressure. I tested it and it was about 116/61 with a 55 heart beat rate, I took it on an empty stomach which is probably why there was a huge decrease in blood pressure. I stabilized my self later after breakfast and drinking salt water.
Overall I'd say that it still caused me POIS, with decreased symptoms.

Hi Nas,

20mg of propranolol is a high a dose for someone who has a normal blood pressure and normal heart rate to begin with, and therefore, hypotension and bradychardia are quite possible outcome to watch for.  Two of the main effects of propranolol is that it lowers blood pressure, and, it slows down the heart rate  ( it his an antihypertensive drug, as well as a beta-blocker, which all slow down the heart rhythm in a very significant way).

With prescription drugs, more is not necessarily better.  The usual aim is to find the lower efficient dosage.

[Nas]

Thank you Fernando for this suggestion,
I don't think Hesperidin is available in my country and Diosmin is hard to find.
But overall that's exactly the drug I'm looking for; a drug that can in crease the resistance of the vascular wall and thus reduce permeability.
The thing is there is really isn't that many medications that are readily available for this job, I've searched many times but I still can't pin point one readily available drug. If you guys find any please share it with us.

[Nas]

Ok so I have tried a second round of Vasoconstrictor stack with an increase in some of the doses; I've taken 50mg Indomthacin, 20mg propanolol, 100mg Aspirin and 250 paracetamol, waited 45 minutes as usual and had an O. The result was different, in that while I believe there was a reduction, I'd say about 40%, I still suffered from usual symptoms like brain fog and speech issues. There were less fatigue and pain in the urethra and the genitals region and slightly clearer mind. Still, I was still annoyed from POIS symptoms so I decided to take another 25mg Indomethacin pill to see if it can clear my head a bit more, and it did, but at the same time it caused a huge decrease in blood pressure. I tested it and it was about 116/61 with a 55 heart beat rate, I took it on an empty stomach which is probably why there was a huge decrease in blood pressure. I stabilized my self later after breakfast and drinking salt water.
Overall I'd say that it still caused me POIS, with decreased symptoms.

Hi Nas,

20mg of propranolol is a high a dose for someone who has a normal blood pressure and normal heart rate to begin with, and therefore, hypotension and bradychardia are quite possible outcome to watch for.  Two of the main effects of propranolol is that it lowers blood pressure, and, it slows down the heart rate  ( it his an antihypertensive drug, as well as a beta-blocker, which all slow down the heart rhythm in a very significant way).

With prescription drugs, more is not necessarily better.  The usual aim is to find the lower efficient dosage.

Yes, that's where I messed up thank you for pointing it out Quantum.

[FernandoPOIS]

Nas

I do not believe that Hesperidin with Diosmin is such a powerful remedy. Here in Brazil it is sold under the names of Flavonid, Daflon and Diosmin. But it is also possible to get in pharmacy handling. It is a remedy used for varicose veins.
I believe that potent vasoconstriction we get with caffeine and pseudoephedrine.

[swell]

Fernando you have any solution for Voice fatigue?   I wake up in morning with a perfect crisp voice and people can hear me even at lower volume.  But then middle of day something happen and my voice gets muffled as if someone stuffed something in my mouth and people have hard time hearing me and I have to speak very loud and I feel if I am straining or shouting.   Sleep is very important and it does something because as experiment if I dont sleep my voice stays muffled through morning.

[FernandoPOIS]

I'm a physiotherapist and I do not have much knowledge about voice problems.

But we can imagine something related to the functioning of the vagus nerve and inflammation. It is known that singing stimulates the vagus nerve. You may have chronic inflammation of the vocal cords. I had a similar problem a few years ago and had to take antibiotics and anti inflammatory (corticoid).

The sure thing is you consult an otolaryngologist who is an ear, nose and throat specialist. This doctor will be able to tell you what happens to your voice.

[nanna1]

Ok so I have tried a second round of Vasoconstrictor stack with an increase in some of the doses; I've taken 50mg Indomthacin, 20mg propanolol, 100mg Aspirin and 250 paracetamol, waited 45 minutes as usual and had an O. The result was different, in that while I believe there was a reduction, I'd say about 40%, I still suffered from usual symptoms like brain fog and speech issues. There were less fatigue and pain in the urethra and the genitals region and slightly clearer mind. Still, I was still annoyed from POIS symptoms so I decided to take another 25mg Indomethacin pill to see if it can clear my head a bit more, and it did, but at the same time it caused a huge decrease in blood pressure. I tested it and it was about 116/61 with a 55 heart beat rate, I took it on an empty stomach which is probably why there was a huge decrease in blood pressure. I stabilized my self later after breakfast and drinking salt water.
Overall I'd say that it still caused me POIS, with decreased symptoms.

I will try to give a more accurate prescription of symptoms using Muon's symptoms from his Muon's case post: http://poiscenter.com/forums/index.php?topic=2545.msg24545#msg24545

1= positive result ( had relief )
0= negative result ( did not have relief )
%= about 50% decrease
X= Do not suffer from this symptom

- Extreme fatigue = 1
- Muscle ache = 1
- Joint pain = X
- Exercise/motion intolerance = %
- Heavy body = 1
- Feeling cold/warm, feeling cold happens far more often than warm = 1
- Decreased endurance, especially with the duration of standing and sitting straight = 1
- Sensitive teeth = X
- Stinging pain at liver area = X
- Yellowing of facial skin = X
- Pale skin and facial skin becomes like a babyskin = X
- Decreased vocabulary = 0
- Articulation problems = %
- Poor concentration = %
- Grammar problems (constructing sentences suddenly becomes a puzzle) = 1
- Short term memory loss (temporary) = %
- Motivation in general is being lowered and often completely wiped out = %
- I become someone without personality = %
- Accelerated Bowel movement, loose stools and sometimes diarrhea = X
- It amplifies my food intolerance/sensitivity = X
- Decreased digestion = X
- A sense of being full (digestion) = X
- Fasciculations = X
- Itching = X
- Soar Throat = X
- Decreased accuracy of handwriting ,also problems with controlling videogames like aiming in FPS = 1
- Faster spreading of local fungal skin infection at feet in POIS = X

So there are two points that are interesting here:
1- It seems that I do not suffer from Physical symptoms, or let's say that they are not really that extreme, possible explanation? Perhaps endothelial leaks vary from person to person?
2- I still suffer from cognitive symptoms, which can mean that this treatment is not enough to reduce Endothelial permeability enough so that an inflammatory response doesn't happen in the brain. Any suggestions for better cognitive relief? Also what do you guys think of all of this?

Hi Nas,
 You might be interested in this article on anti-oxidants.
Inositols prevent and reverse endothelial dysfunction in diabetic rat and rabbit vasculature metabolically and by scavenging superoxide

[swell]

nanna1, fernando or anyone on this forum, do you anyone here has a white film like thing in the inside of your mouth, inner part of the lips?.   This is rare, but I am thinking maybe we poisers have this white film called epithelial hyperplasia or hyperkeratosis?.  Background:  My vocal cords are always inflamed and red from time immemorial.  I also have had sore throat that gets worse during POIS since childhood.  I spent close to $15,000 with Gastro and Otolaryngologist they did some studies and procedures few years back and came to conclusions (no acid reflux, no GERD, no LPR, no H. Pylori, no barretts esophaegal cancer they initially all suspected) and lol referred me to psychiatrist for depression.   I dont have a good insurance at moment.  My dentist today is still concerned and points me to this white film I have.  She says it is epithelial hyperplasia and hyperkeratosis which could be due to a virus or some immune reaction.  My first inclination is its HPV since I do have 2-3 warts on my feet sole since last 10 yrs.

I looked up Wikepedia and it says:
The causative agent implicated is Epstein-Barr virus, the same virus that causes infectious mononucleosis (glandular fever). After the primary EBV infection has been overcome, the virus will persist for the rest of the host's life and "hides" from the immune system by latent infection of B lymphocytes.[5] The virus also causes lytic infection in the oropharynx, but is kept in check by a normal, functioning immune system. Uncontrolled lytic infection is manifested as Oral Hairy Leukoplakia (OHL) in immunocompromised hosts. OHL usually arises where the immunocompromise is secondary to HIV/AIDS.[4] Rarely are other causes of immunocompromise associated with OHL, but it has been reported in people who have received transplants and are taking immunosuppressive medication. OHL may also accompany chronic graft versus host disease.[6] Even more rare are reports of OHL in persons with competent immune systems

The white lesion cannot be wiped away,[6] unlike some other common oral white lesions, e.g. pseudomembranous candidiasis, and this may aid in the diagnosis. Diagnosis of OHL is mainly clinical, but can be supported by proof of EBV in the lesion (achieved by in situ hybridization, polymerase chain reaction, immunohistochemistry, Southern blotting, or electron microscopy) and HIV serotesting.[6] When clinical appearance alone is used to diagnose OHL, there is a false positive rate of 17% compared to more objective methods.[7] The appearance of OHL in a person who is known to be infected with HIV does not usually require further diagnostic tests as the association is well known. OHL in persons with no known cause of immunocompromise usually triggers investigations to look for an underlying cause. If tissue biopsy is carried out, the histopathologic appearance is of hyperplastic and parakeratinized epithelium, with "balloon cells" (lightly staining cells) in the upper stratum spinosum and "nuclear beading" in the superficial layers (scattered cells with peripheral margination of chromatin and clear nuclei, created by displacement of chromatin to the peripheral nucleus by EBV replication). Candida usually is seen growing in the parakeratin layer.   I dont have HIV, I was tested.

Another article points me to: "Focal epithelial hyperplasia is a rare contagious disease caused by human papilloma virus".  https://www.hindawi.com/journals/crid/2013/871306/

To simply postulate, I might have EBV, HPV and maybe also Candida in my throat despite fact Otolor.  didn't do anything about it and wrote biopsies are normal.   I suspect they didn't test for these viruses as they were focused on Barrets and GERD etc.  I am currently taking Berberine 1000mg daily since last 3 days and since this morning in POIS.   I dont believe Berberine has helped though I would continue it for 3-4 weeks.  I am in full-blown POIS currently minus some relief that I get from supplement protocol.  But my point is, wouldn't Berberine be taking care in the event this white film is indeed Candida?  What there be a supplement for this HPV, EBV and Candida in general or this requires Rx med?  I currently take daily:  Adderall, Multi-vitamin with Minerals, Liposomal Glutathione and Vitamin C.  And few days prior to POIS I start:  NAC, ALA, B-Vitamins, Vit-D3, Vit-E, Olive Leaf Extract (for Luteolin) and now Berberine.

Update: I was hopeful on Berberine, since Echinicea and Goldenseal do provide me some relief and Berberine is a constituent of Goldenseal.  The longest anything that has worked on me is Liposomol Glutathione and Vit C for 6-7 times with a 100% relief but then stopped working.  Mineral supplementation to 100% DV like Zn, Cu  has not changed much, maybe I need higher values?     

[dizzy]

@Swell,

I think I had the same problem as you, Swell, with the voice fatigue. I traced it back to a tight jaw. I'm using these techniques:

1. I relax the jaw as often as I can.

2. I'm doing the Wim Hof breathing exercise several times a day (lookup FloppyBanana's post about this on this forum).

3. When speaking, I'm making the upper back wider (this is a singing technique).

4. Magnesium glycinate and vitamin B2 help me with tension headache, and this also makes it easier for me to do the relaxation of the jaw.

5. While at it, I'm also relaxing the cranium, because this makes me feel overall more relaxed. Also helpful while speaking.

6. You may want to do sit-ups and look for exercises on youtube to strengthen the scalene and sternocleidomastoid muscles.

7. Watch out for forward-head posture, it kills the voice.

8. Don't overdo any strength-exercises, as they may create tension which you want to avoid for a good voice.

It takes a real effort, but in my case these rules have been very helpful so far.

By the way, also make sure you don't have (silent) stomach acid reflux, because it may cause vocal chord problems. An ENT doctor can tell easily by using a scope.

[Muon]

HPV replicates in the epithelium. Might be interesting to test these for the oral epithelium.