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Problems Standing? Studies Suggest Autoimmunity Causes Orthostatic Intolerance: Implications For Chronic Fatigue Syndrome

  [ 21 votes ]   [ 1 Comment ]
By Cort Johnson • www.ProHealth.com • April 29, 2014


Problems Standing? Studies Suggest Autoimmunity Causes Orthostatic Intolerance: Implications For Chronic Fatigue Syndrome
Reprinted with the kind permission of Cort Johnson and Health Rising

By Cort Johnson

The Rituximab findings, the female predominance, the increasing evidence of heritability, the inflammatory component, and the common infectious trigger all suggest that at least some people with Chronic Fatigue Syndrome (ME/CFS) may have an autoimmune/autoinflammatory disorder.

While these findings point to an autoimmune basis for ME/CFS, no studies have incontrovertibly demonstrated that ME/CFS or some subset of ME/CFS is an ‘autoimmune’ disorder. A new study on a closely allied illness, postural orthostatic tachycardia syndrome (POTS), however, strongly suggests that POTS is a autoimmune disorder and points to possibilities that could apply to ME/CFS.

If you have POTS, the findings of this study – if validated – could open exciting new treatment possibilities for you. If you ME/CFS and don’t have POTS, I believe this line of inquiry could ultimately provide some answers as well.

Postural Orthostatic Tachycardia Syndrome (POTS)

J Am Heart Assoc. 2014 Feb 26;3(1):e000755. doi: 10.1161/JAHA.113.000755. Autoimmune basis for postural tachycardia syndrome. Li H1, Yu X, Liles C, Khan M, Vanderlinde-Wood M, Galloway A, Zillner C, Benbrook A, Reim S, Collier D, Hill MA, Raj SR, Okamoto LE,Cunningham MW, Aston CE, Kem DC.

People with POTS experience high heart rates, fatigue, dizziness, and light-headedness while standing or even at times while sitting. One of the striking things about POTS is how commonly, like Chronic Fatigue Syndrome, infections precede it.

This study looked at autoantibodies to adrenergic (autonomic nervous system) receptors found on the blood vessels and in the heart which control heart rate and blood flow across the body. Two main types of adrenergic receptors, alpha-adrenergic receptors and beta-adrenergic receptors, exist and many subtypes are present (alpha-1, alpha-2A, alpha-2B, alpha-2C, beta-1, beta-2, etc.).

The researchers believed that autoantibodies to the a1 adrenergic receptors (AR-1) responsible for vasoconstriction would prevent blood vessels from squeezing tightly enough to prevent blood from pooling in the legs when POTS patients stood. Other autoantibodies would be implicated in the unusually high heart rates. They took sera from the patients and controls and then added it to various preparations to see if it triggered cAMP activity, that is, to see if it vasodilated or constricted arterioles.

They found greatly increased levels of autoantibodies to AR-1 receptors in ALL the POTS patients they studied. The consistent findings were remarkable given the heterogeneity believed present in POTS. With the autoantibodies putting those receptors out of commission, their blood vessels weren’t tightening as they should.

As their blood began pooling in their legs, their sympathetic nervous system kicked into gear and produced the racing heart rates characteristic of POTS.

A second type of autoantibody appears to produce this result in some patients. Treatment Implications The great thing about these findings is that if they’re validated there is the potential of a clear fix: develop a drug to latch onto and block the autoantibodies. In fact, such drugs are under development now.

We hope to eventually develop treatments to block these autoantibodies, without blocking the target receptor proteins at the cell surface at the same time. Such agents are in development and within a few years may be applicable in POTS.

This approach may prove useful in several other diseases which are caused by similar autoantibodies.

Chronic Fatigue Syndrome Connection?

It’s exciting to see a potentially clear pathway emerge for some people with POTS, but my guess is that these results and these types of studies will also ultimately pay dividends for people with ME/CFS. The disorders may be closer cousins than we think.

An identical pattern of altered pH and cerebral blood flow showed up in two separate studies on POTS and ME/CFS patients. When I pressed the ME/CFS researcher on whether she was inadvertently studying people with POTS, she made it clear that she was not. However, the two groups of patients appear to share some striking physiological abnormalities.

Orthostatic intolerance comes in all forms in Chronic Fatigue Syndrome

An abstract presented at an 2014 autonomic disorders conference indicating that a second tilt table test greatly increases the number of people who meet the criteria for POTS suggests many people are unaware that they have POTS. My guess is that many people with ME/CFS who don’t meet the criteria for POTS or other forms of orthostatic intolerance still have an undiagnosed form of orthostatic intolerance. These are people who have trouble standing up for long periods, who tolerate exercise much better if it’s done while lying down, who generally think and talk better while sitting or lying down, and who don’t tolerate repeated up and down movements well.

This is still a new field and there’s a lot to learn. One example of that are two studies that found autoantibodies to different adrenergic receptors in another form of orthostatic intolerance.

Orthostatic Hypotension Also Associated with Increased Levels of Autoantibodies

The POTS study was not the first to look for autoantibodies in orthostatic intolerance. Two earlier studies found autoantibodies to adrenergic blood vessel receptors (B2AR and M3R) in orthostatic hypotension.

Your blood vessels should tighten when you stand to counter gravitational blood flow to your legs. In people with orthostatic hypotension, however, inappropriately dilated blood vessels cause their blood pressure to drop when they stand. (The good part of this is that it’s a simple, non-invasive way to diagnose POTS.)

Different patterns of auto-antibodies surely remain to be unveiled

The earlier autoantibody study of orthostatic hypotension found three different patterns of autoantibody activity in six patients, and these three patterns produced three different clinical outcomes.

All patients, for instance, demonstrated problems with tightening their blood vessels when they stood, but some also had a blunted cardiac response. This simply suggests that very complex patterns of autoantibodies and functioning are present in these disorders. It bears noting that increased levels of autoantibodies to autonomic receptors are now associated with a variety of cardiovascular disorders which cause problems with standing, such as hypertension, heart rhythm problems, and heart disease.

The big question now is how much of orthostatic intolerance is autoimmune mediated? That’s why, even though this research is on POTS patients, I think of it as ME/CFS research; the more attention drawn to the blood vessels and cardiovascular system in POTS and ME/CFS and other orthostatically challenging disorders the better.

Crowdfunding Effort Underway

Dysautonomia International (DI) has launched a crowdfunding effort to take this research to the next level. Their ambitious research agenda includes examining autoantibodies in more POTS patients, developing a commercially available blood test, and, if the findings are validated, they’ll be working to develop new drugs to suppress those autoantibodies that are knocking the blood vessels for a loop.

The DI crowdfunding effort (which was inspired by the Rituximab effort in ME/CFS) is about halfway to its goal of $50,000. Donate during April and your contribution will be doubled due to a matching grant (up to $10,000) from an anonymous donor. DI is over half-way there, and you can make a difference with your donation!

Help Dysautonomia International crack cause and provide tests and treatments for POTS and other forms of orthostatic intolerance

Your donation will be matched during the month of April, so donate now!

About the Author: Cort Johnson has had ME/CFS for over 30 years. The founder of Phoenix Rising and Health Rising, Cort has contributed hundreds of blogs on chronic fatigue syndrome, fibromyalgia and their allied disorders over the past 10 years. Find more of Cort's and other bloggers' work at Health Rising.


Please Discuss This Article:   Post a Comment 

Interesting POTS finding!
Posted by: minivette
Dec 3, 2014
Thanks for reporting on this, Cort! I JUST heard a bit about this research in Dr. Lucinda Bateman's live talk on OFFER Utah's Youtube channel today and Googled it to find the source. I was recently diagnosed w/ POTS after I've probably had it for 8 yrs. I'm 22 and a couple of yrs ago I ended up in the ER w/ POTS symptoms/tachycardia and then had a subsequent referral to a cardiologist. Didn't find out then. They said it must've been caused by dehydration...I tote a water bottle and had been drinking water. At 14 I was hit w/ ME/CFS after what seemed like a flu that hung on. That was about 1.5-2 yrs down and much in bed even though I am one that can't stand to do nothing or just sit around usually. Of course I had to make some peace w/ it, try to learn all I could, and for a good portion of the time it was many Dr. appts to figure out what I was struck with. Around that time I saw a cardiologist at a large local children's hosp to check my heart since I had been so weak and experiencing heart racing w/ standing, palpitations etc. He said to eat more salt but gave me no name or clue as to what I was experiencing. A few mos ago I came to the unfortunate realization that I was headed into a major flare/recurrence of ME/CFS...I had endured repeated odd infections and episodes where I had to rest extra but been able to attend college from 17-22 until...bam...repeated throat infections, major fatigue that worsened along w/ the other odd symtoms that go w/ ME/CFS. This after 2 yrs of many stressful events and the rigors of college at 2 locations and a part time job, fathers open heart surg and 6 subsequent hospitalizations for complications w/ med, false alarm, and an unrelated infection. He has CFS too and has experienced terrible episodes of fatigue over his life but then times of unstoppable energy. EBV reactivation and stress are some of his triggers. He experienced many episodes as a kid of dizziness ad nearly passing out. His mom would say "sit down and put your head between your legs!" He most certainly had/has POTS too and I have read there is a strong genetic component. I am hopeful for treatments! When I am not experiencing ME/CFS acute trouble I don't notice much POTS trouble but when ME/CFS is in major play it really does affect me and adds to the debilitation. I am trying Florinef w/ good results so far! Salt was only a very temp fix and I'd have to load up on it all day. Also doing adrenal gladular support after results of an adrenal rhythm test by my Dr. Thanks for all you do! It is my goal to do all I can to also contribute to the ME/CFS community in the area of education and advocacy. There are sooo few Drs in the Central Valley of CA that know ANYTHING about ME/CFS...there is little to no help to patients that I know of. It's unacceptable. I recently found the only board cert Integrative and Holistic MD Physician in the whole Central Valley who has helped some and knows a decent amount...however she admits many others know more about it than her. And I am lucky enough to have 1 of the only 2 insurances she accepts.
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