Understanding POTS and Its Autoimmune Connection
Written by: the Editors of goop
Updated: February 20, 2020
Photo courtesy of David Cohen de Lara/The Licensing Project
Thirty years ago, Dr. Blair Grubb began studying a group of people who would faint for no apparent reason, often upon standing up. Some doctors originally believed that reaction might be caused by triggers like seeing blood or extreme distress. But further research determined that this was its own distinct condition called postural orthostatic tachycardia syndrome.
POTS is an autonomic disorder: It affects the autonomic nervous system, which controls involuntary bodily functions such as breathing, digestion, and heartbeat. It’s diagnosed predominantly among women—and its symptoms are broad and often include anxiety, which doctors may mischaracterize as a purely mental affliction. We talked to Dr. Grubb, the program director of the Clinical Autonomic Disorders Center at the University of Toledo Medical Center, to understand more about what POTS is and how it manifests. Raising awareness about the condition, he believes, is the key to getting patients proper care and adequate tools for recovery.
A Q&A with Blair P. Grubb, MD
When a person stands up, gravity immediately attempts to displace roughly one third of the body’s blood volume downward. The body has to compensate for that immediately, or everybody would pass out once they stood up.
The reason most of us don’t pass out is because the brain senses the fall in pressure and sends out instructions to make the heart beat faster and more forcibly and tells all the blood vessels in the lower half of the body to become three times tighter. This pushes blood toward the brain to compensate for the amount of blood that gravity is pulling downward. This process happens automatically, which allows us to jump out of bed or do double back flips while maintaining our blood pressure.
Some people can’t maintain their blood pressure because their blood vessels fail to tighten. The brain senses this and asks the heart to beat harder and faster to pump more blood upward. But because the blood vessels in the lower half of the body haven’t tightened, all of this is to no avail: Gravity wins, and blood moves downward and away from the brain, causing the brain to receive less oxygen. This condition is called postural orthostatic tachycardia syndrome. Postural orthostatic means standing, and tachycardia means fast heart rate.
The lack of oxygen to the brain results in symptoms such as fatigue, trouble thinking, lightheadedness, tunnel vision, and sometimes fainting. When patients are lying down, their heart rate is relatively normal, but when they stand up, they feel extreme fatigue, weakness, shortness of breath, and as if their heart is pounding out of their chest. This makes it difficult to exercise and can also cause anxiety. As with any disease, there are varying degrees of severity.
There are many different pathways that point to POTS. If you’re a long-term diabetic, you may have damage to the nerves that cause your blood vessels to tighten, which can result in POTS. There’s a congenital condition called Ehlers-Danlos syndrome (joint hypermobility syndrome), which results in greater elasticity of the blood vessels and allows blood pooling to occur.
“Five times as many women as men have POTS.”
The majority of people with POTS appear to be autoimmune. Often their issues started after an infection or a pregnancy, when there were changes in the immune environment. There are several nonspecific blood markers—such as antimitochondrial antibodies, sedimentation rates, and C-reactive protein—that are elevated in people with POTS, suggesting that the disease is autoimmune.
In 2019, my team and I published a paper where we isolated a previously unknown autoantibody in blood vessels that affects alpha-one receptors. Alpha-one receptors are important because if you simulate them, they cause blood vessels to tighten. And if they’re blocked by these autoantibodies, the blood vessels are unable to tighten.
“We found that 90 percent of the patients with POTS whom we tested had very high levels of these autoantibodies in their blood.”
We found that 90 percent of the patients with POTS whom we tested had very high levels of these autoantibodies in their blood. Of those individuals, 50 percent also had high levels of a different autoantibody that affects a type of acetylcholine receptor called M4, which are found in the gastrointestinal tract and the brain. This evidence strongly suggested that many people have POTS due to an autoimmune issue. We hope to eventually make these biomarkers available as a diagnostic commercial test so that you could send out your blood for testing and see if you have these autoantibodies. There also may be other autoantibodies that we didn’t test for, which future research with a larger study could help determine.
Five times as many women as men have POTS. This is likely due to hormones: Estrogen is a vasodilator, meaning it relaxes blood vessels and encourages blood pooling. Testosterone is a vasoconstrictor and does the opposite.
Women are also three to five times more likely to develop autoimmune diseases than men. Women’s immune systems are much more complicated than men’s because women have to deal with pregnancy, when a foreign body that has only half of your genetic material lives inside you for nine months. Even beginning with conception, a woman’s body has to try not to destroy the sperm or the fertilized egg, which both have different genetic material than her own body.
The biggest determining factor is heart rate response. If someone with POTS stands up, they will have a greater than 30 beat per minute increase in their heart rate compared to when they’re sitting down. Alternatively, their heart rate may exceed 120 beats per minute within the first ten minutes of standing.
The tilt table test, the most common way to make a diagnosis of POTS, was developed in England by Dr. Richard Sutton. He put people on a tilt table with a footboard meant for weight-bearing and tilted them at sixty degrees to measure how their blood pressure and heart rate responded. The idea is that this method inhibits the skeletal muscle pump and isolates the autonomic system. (The skeletal muscle pump contracts the leg and abdominal muscles when standing, which compresses the veins and propels blood back to the heart. This system allows humans to walk around on two legs unlike all of the other animals in the world, which have to crawl on four legs in order to maintain adequate blood supply.) For humans, a strong set of legs can raise blood pressure to a point, via the skeletal muscle pump, but the tilt table test removes that advantage to see how the autonomic system functions alone.
It depends on the severity of the person’s condition. People who have a milder form of POTS may be able to manage it with hydration and increasing their salt intake, which help their bodies to retain more fluid and increase their total blood volume. However, you will end up peeing it out eventually, so this may be effective only to a certain extent.
The other thing people can do is recondition and strengthen their leg muscles to be a better backup pump and increase their blood flow upward. Physical therapy or graded exercise programs are used to build lower leg strength and improve patients’ functionality.
Regular exercise and eating a healthy diet can also help. There are some people who are sensitive to certain foods, such as gluten, which may exacerbate their POTS symptoms. If you suspect you are gluten intolerant, you may try avoiding it for a month or two and see if you feel better. If you don’t notice a difference, then eat it all you want.
If conservative measures are not effective and patients remain heavily symptomatic, they may try a number of different medications that work to compensate for what the body is not doing. One such medication is called fludrocortisone, which promotes sodium retention and allows you to keep more fluid in your body. Desmopressin is another medication that does something similar. Another medication that can be used is called midodrine, which tightens blood vessels to minimize blood pooling in the lower extremities.
One of the medications that we often use now is called ivabradine, which slows down the heart rate without affecting blood pressure. Studies have shown that if a patient has an excessively high heart rate (above 160 beats per minute), they do much better if you slow the heart rate down. My team at the University of Toledo published a study showing that 76 percent of the POTS patients we studied improved when taking ivabradine. There’s another medication called pyridostigmine that was originally developed for the treatment of an autoimmune disorder called myasthenia gravis, which damages acetylcholine receptors. We studied pyridostigmine and found that it was effective in roughly 50 percent of the POTS patients.
In the future, we will start treating the most severely affected patients with immunomodulatory medications. The University of Texas Southwestern Medical Center in Dallas has started a clinical trial of a type of intravenous immunoglobulin called Gammunex-C for treating POTS. IVIG is used in the treatment of many autoimmune disorders, so researchers are trying to see if it will help with POTS as well. IVIG works by flooding the patient’s system with other people’s antibodies to stop their body from making their own.
There’s a nonprofit patient support group called Dysautonomia International that’s a great source of information. It advocates for patients with autonomic disorders and collects data on their overall frequency. At least a million people are diagnosed with POTS, but some probably would argue the number is even higher, like 2 or 3 million.
Blair P. Grubb, MD, is the director of clinical cardiac electrophysiology and the program director of the Clinical Autonomic Disorders Center at the University of Toledo Medical Center. He is one of the leading experts in the treatment of autonomic disorders.
This article is for informational purposes only, even if and regardless of whether it features the advice of physicians and medical practitioners. This article is not, nor is it intended to be, a substitute for professional medical advice, diagnosis, or treatment and should never be relied upon for specific medical advice. The views expressed in this article are the views of the expert and do not necessarily represent the views of goop.