jangle

Great job lemons, but be careful about thanking me. I'm a strict personal trainer, think Jilian Michaels without the compassion.

Christy, did your son improve in any of his POTS symptoms with vitamin D supplementation?

And just so we're clear are we talking about 25 -OH vitamin D3 levels or 1, 25( OH)2 vitamin D3 (calcitriol) levels

My vitamin d levels haven't come back yet. You guys might want to try calcitriol for vitamin d as it's the body's active form of vitamin d.

This is definitely Dr. Stewart's and Raj's idea. I'm just trying to take their idea and form a treatment on it.

Right now it seems like Vitamin D would be the best option, namely because it is safe. But obviously that hasn't helped many people on this forum.

Also exercise, which has shown to help some people.

There is a lot of guess work, I'm honestly at a point where I wouldn't mind trying things that haven't been proven yet.

No doubt. But Stewarts work demonstrated a subset of patients only with elevated angiotensin II levels and these were nearly exclusively females. The Vandy work suggests that they included 15 female patients who just happened to also have elevatede angiotensin II levels. They believe a larger portion do, but again you will notice that all the patients in that research were also female.

Email Dr stewart again - i think you'll find he thinks its about 20-25% ish.

This isnt criticising you, the idea or anything like that. Just applying some observations to the idea. I have often thought about whether inflammation could effect angiotensin II catabolism and I know that some studies suggest that C-reactive protein does as an example.

As for advocacy and sending stuff to doctors - the dangers of emailing and sending doctors volumes of research is that unless its relevant, demonstrates a basic understanding of physiology and is supported by actual peer-reviewed science relevant to POTS patients it probably just reinforces the belief that we are all obsessed with our symptoms and are crazy. The likelihood that a bunch of patients are going to solve the etiology of POTS based on random internet searches is probably pretty low simply because we cant test any of our hypothesis on patients and because we cant actually test any favourable results. But more often, it is because the theories are based on incomplete understanding of what has already been established about POTS or the physiology of the vascular / autonomic system.

It is a complex problem not just for us but for the researchers as well. But we shouldn't let that deter us from trying to see if we can find something that might be of use. Even if it isn't everything, making any little bit of progress down the right direction can shave years off of our suffering as well as future POTS sufferers.

The way to move forward from here is to see if we can get those ACE2 autoantibody/ACE2 tests. Without objective evidence as to the pathology we have nothing.

http://www.ncbi.nlm.nih.gov/pubmed/20093667

This is the study I think Dr. Stewart was referring to. I think everyone should at least read the abstract, it states that ACE2 levels definitely have an impact on autonomic activity.

Ya I just want to say that I'm not sure about spironolactone and I wouldn't want anyone getting hurt trying that medicine from my suggestion. But hopefully we can get something going here.

EDIT: Do you think we can get our angiotensin ii levels checked? I'll ask my doctor when I see him.

Double EDIT: Also Rama, the study I linked from Raj did show that POTS patients tended to have higher angiotensin ii levels. Also Stewart's research established this as well. It might not be universal in POTS patients, but for some it could be their major issue.

Florinef is artifical aldosterone. Don't know if spironalactone is????

In the email Dr. Stewart sent me he said that florinef is essentially artifical aldactone (spironolactone).

Looking at their chemical formulas, they do seem to have the same stereochemistry. They have some major electronegativity functional groups though and some consitutitional isomerism going on as well. I took two semesters of organic chemistry but I don't know anything about human metabolism of chemicals, so I wouldn't know what significance this would hold.

I'll take Dr. Stewart's word for it.

I can experiment on myself, I think I know a doctor who will give it to me for acne. I'll keep a chart of my vitals/dosage/electrolytes.

I don't know much about Florinef/angiotensin but I do know Dr. Stewart said Florinef is essentially artifical spironolactone. The difference though is probably the difference in a complete therapeutic response.

You actually got a dr to respond to you via email??? Well done!

I know right, I was shocked but glad

"

As perhaps you might know we published on increased ANF-II well before Satish and also established the role of ACE2 in certain forms of POTS.

Florinef is more or less artificial aldactone which had been shown to be decreased in Satish’s patients while ANG-II is increased.

Spironolactone is a diuretic and might have an adverse effect in patients, but it is a thought.

Recent work in animal; models of CHF and hypertension show that ACE2 is abnormal and

exercise makes it normal."

Exercise makes it normal.

Naomi, I can't explain why your vitamin D levels are low yet your angiotensin ii levels are normal. There can be many causes of POTS I guess, but from the study done by Raj, there was definitely a higher angiotensin ii in POTS patients than controls with subsequent lower ACE2 levels.

EDIT: also they don't have my bloodwork ready yet

Double EDIT: Apparently spironolactone is prescribed for acne. I have some acne, maybe I can get a doctor to prescribe it to me? Then I can report back the results.

Triple EDIT: Continuing with the ironic and confusing nature of POTS, spironolactone acts opposite of florinef's actions. Florinef is a MR agonist whereas spironolactone is a MR antagonist. Florinef helps POTS patients yet my theory would say that spironolactone should help POTS patients?

"???"

Thanks everyone for the support and replies!

lieze, julieph85 yes also I think that's why during pregnancy POTS symptoms will alleviate because the body naturally boosts ACE2 enzyme levels. Also julieph85 you're right it might be related to the heightened sensitivity for catecholamines rather than a primary connective tissue disorder we have. Either way, I'm sure it's tied to the high angiotensin ii levels. I hope your IVIG treatments help you a lot, I recall you saying that your mayo clinic doctor was very enthusiastic so I'm sure it will go well.

Rama I haven't looked at losartan yet, but yeah there's gotta be more ways other than spironolactone for upping ACE2 activity levels. I'm wondering if it might be possible to just inject the enzyme directly as some research I read did so with mice. Don't know how feasible that is with humans though.

Cfmartin, I think your best bet would be to go to Vanderbilt, Mayo Clinic, or Cleveland Clinic. It was at Vanderbilt that they did the study with POTS/angiotensin ii/ACE2 enzyme activity tests. As for the autoantibodies for ACE2 enzyme, that test might not be available anywhere, but if you got someone interested in one of those three clinics they might be able to carry it out for you.

For now I think we should all get our vitamin D levels checked and see if supplementing that can do it for us. Maybe if we got to a doctor in one of those three research clinics they might be willing to try a medicine to boost ACE2 levels, but I don't think any doctor off the street is going to do that.

Oh and Rama, I had my vitamin D levels tested, I'm going today to see the results.

It's 1 am right now, and I have a bunch of thoughts wizzing through my head and a large volume of information. Nothing concrete, everything based off of conjecture, but I'm going to try to present my argument in the most concise and coherent manner.

1.) Angiotensin ii is heavily involved in the inflammatory process.

http://www.ncbi.nlm.nih.gov/pubmed/12676174

http://www.jci.org/articles/view/41709

2.) People with rheumatic illnesses have increased levels of angiotensin ii, most likely due to a deficiency in ACE2 enzyme, which gets rid of angiotensin ii

Lupus

http://www.nature.com/gene/journal/v3/n1s/full/6363907a.html

Rheumatoid Arthritis

http://www.ncbi.nlm.nih.gov/pubmed/17265479

A study showing that patients with lupus and scleroderma had elevated levels of ACE2 enzyme autoantibodies (which would lead to higher angiotensin ii levels)

http://arthritis-research.com/content/12/3/R85

In that study, it showed that treatment with traditional immunosuppressive agents reduced the ACE2 enzyme autoantibody in one patient, which corresponded to a decrease in symptoms.

In POTS:

http://www.heartrhythmjournal.com/article/S1547-5271%2810%2901204-X/abstract

We have elevated angiotensin ii in our bodies. This circulating angiotensin ii, (from the 2nd study I posted) can result in inflammatory expression from virtually any cell in the body. My theory is, is that the only distinguishing characteristic between lupus, rheumatoid arthritis, POTS, and other connective tissue disorders is the type of cell that expresses an inflammatory reaction and the body's unique reaction to it.

Now, one emerging theme is that vitamin D deficiency is common amongst people with autoimmune illnesses.

Well it just so happens that vitamin D deficiency is correlated to increased angiotensin ii levels.

http://www.ncbi.nlm.nih.gov/pubmed/20351344

People with lower vitamin D levels have higher angiotensin ii levels. Which perhaps combined with other factors, predisposes them to autoimmune disease through the mechanism I explained earlier.

I.E. it's not necessarily the vitamin D deficiency directly that is causing the autoimmune disease, but it's the resulting increase in angiotensin ii levels coupled with a sensitive body to it.

Where's the proof??

Well, interestingly enough, there is a study done on a drug by the name of spironolactone in rheumatoid arthritis patients.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1808828/

Spironolactone increases ACE2 enzyme activity by 3 times (thus reducing circulating angiotensin ii levels by ~3 times)

http://circres.ahajournals.org/content/97/9/946.short

The results of the study showed that 76% of patients with rheumatoid arthritis responded favorably. "drug was also well tolerated."

My theory:

POTS is somehow tied to a connective tissue autoimmune disorder. It resembles in some way EDS, which is why EDS patients have an increased risk for POTS. According to the study that showed POTS patients have increased angiotensin ii levels, it is likely that that is causing our body to have a dysfunctional renin-angiotensin-aldesterone system which is causing our POTS directly.

Therefore, treatment would have to consist of increasing ACE2 activity

This can be accomplished in two ways.

The first, is by dramatically but safely increasing Vitamin D levels

The second is by using spironolactone to directly boost ACE2 activity.

now I can really only test one of those theories, however, according to this case study, supplementation with Vitamin D has been shown to treat POTS already.

http://www.mindcull.com/data/the-endocrine-society/endo-2009-the-endocrine-society/1-alpha-hydroxylation-defect-in-postural-orthostatic-tachycardia-syndrome-type2-remission-with-calcitriol-supplementation/#

This would be the point where I would experiment on myself with this medication: http://circres.ahajournals.org/content/97/9/946.short

That medicine seems to increase ACE2 enzyme activity twice its original level. Unfortunately, the day and age we live in, I don't think I'll get to be doing any experimenting on myself

Bingo: http://www.heartrhythmjournal.com/article/S1547-5271%2810%2901204-X/abstract

I'm referring to the enzyme ACE2 which I guess is involved in dealing with angiotensin 2. The paper is recent (2010) in their discovery of autoantibodies targeting ACE2 enzyme.

I wonder if there is a way we can get our ACE2 levels checked?

I found this article, about autoantibodies that can target the angiotensin II enzyme. http://arthritis-res...ontent/12/3/R85

It kind of all makes sense. Our symptoms have always mimicked connective tissue autoimmune disorders. Difficulty swallowing, Raynauds, Shortness of Breath, Nausea/Gastroparesis, also people with the connective tissue disease EDS have an increased risk of POTS.

This could be our autoimmune disorder. We have antibodies that target our ACE2 enzyme, thus limiting the conversion of angiotensin II to angiotensin (1-7). Thus making us have a blunted effect to angiotensin II infusion (as cited in the previous study). Also explains why people who are pregnant have reduced POTS symptoms (It increases their ACE2 enzyme levels).

PLEASE DON'T LET DOCTORS SEE THIS!!!!!!

Oh, I had a hypothesis that the thing causing our POTS was an ACE2 deficiency. ACE2 converts angiotensin II to angiotensin (1-7). In this study it was shown that POTS patients had an altered response to angiotensin II infusion

http://circep.ahajou...11.965343.short

and it was shown in this study that ACE2 is heavily involved in the renin-angiotensin system

http://www.sciencedi...043276004000566

And then it was shown in this study that people who had ACE2 deficiency had lower weight babies

http://hyper.ahajour...ontent/58/5/852

So I was making a pseudo test to see if it was low ACE2 levels we were suffering from.

HOWEVER!

In that last study I cited, it did show that mommies have an increase in ACE2 levels upon getting pregnant. So presumably, if we have low levels of ACE2, then upon getting pregnant, it should alleviate the symptoms of POTS somewhat. Depending on whether or not the ACE2 levels increased enough. I do remember some moms saying their POTS symptoms decreased upon getting pregnant, and some didn't. Now I'm wondering if for those whose symptoms did not decrease if they had lower than average weight babies.

Don't ask me why I'm asking this, but if you had POTS when you were giving birth, was your baby's weight lower than normal?

Here's another article related to exercise. http://www.ncbi.nlm....les/PMC2343225/

Since so many on here were very fit before they got sick, it's interesting that these articles note that there is evidence that some people could be TOO fit which they theorize can lead to OI.

Ya that is interesting to note, however I've since been deconditioned since my athletic time period and I haven't recovered at all. Also, this doesn't seem to be a common occurrence in high level athletes. It's possible I guess, but the results from the other studies seem to suggest that moderate exercise seems to help us.

It is true the study involved men in the army, but just last october before I knew I had pots I was jogging 3and miles a day and still had bad symptoms. So they could still have been badly off but nit severely disabled.

Ya I've done the epley manuever whenever I get vertigo. It usually takes it away in about 2 or so sessions of it. Does nothing for my lightheadedness

Before I even opened this thread I thought to myself, "Hawaii". You can get good vitamin D year round which seems to help pots symptoms for some people. Additionally its a tropical paradise and golf courses to boot! Enjoy yourself!