There are an estimated one to three million Americans and millions more around the world, who struggle with POTS (Postural Orthostatic Tachycardia Syndrome). POTS is a disorder that affects the autonomic nervous system, heart and blood pressure, with rapid heart rate, dizziness, and several other symptoms upon standing. It can lead to mild problems or can be severely disabling. Several autoimmune disorders, including Chronic Fatigue Syndrome, and MS, are known to cause or be associated with POTS. The recent information may help many of these individuals better manage this often disabling disorder.
What is POTS?

The main feature of POTS is a form of orthostatic intolerance, wherein symptoms occur upon standing and are often relieved by lying down. There may be symptoms of tachycardia or elevated heart rate upon standing with other symptoms of palpitations, fatigue, exercise intolerance, light headedness, nausea, trouble concentrating, near fainting, and feelings of trembling. Depending on the subset of POTS, blood pressure may drop, remain normal, or elevate in response to standing. There may be difficulties or disturbances in sweating, temperature regulation and even bowel and bladder function (motility, irritation, etc). It may make individuals unable to exercise because the activity brings on fainting spells or dizziness.
Anyone at any age can develop POTS, but the majority of individuals affected (between 75 and 80 percent) are women between the ages of 15 to 50 years of age. Some women report an increase in episodes of POTS right before their menstrual periods. POTS often begins after a pregnancy, major surgery, trauma, or a viral illness. Daily life activities are often a struggle for many of these individuals. The amount of functional impairment can be similar to that of persons struggling with congestive heart failure or COPD. Often these individuals are dismissed or misdiagnosed with anxiety or panic disorder as the diagnosis is easily missed. The gold standard in diagnosis is a tilt table test to observe heart rate, skin changes, blood pressure, and blood levels of various neurotransmitter levels.
POTS and Autoimmune Inflammation

A recent study in Journal of the American Heart Association found that patients with POTS had elevated antibodies to adrenergic receptors. This isn’t completely new information as previous findings identified problems with receptors sites and imbalanced norepinephrine. The new discoveries, however, show that it is an autoimmune attack on the receptor sites. Adrenergic receptors are receptors sites for catecholamines (norepinephrine and epinephrine) that are involved with the tone and regulation of the sympathetic autonomic nervous system. This antibody activity is thought to change the receptor site function that mediates the actions of adrenaline type compounds. This change leads to a build-up of norepinephrine in the blood stream and results in tachycardia and other symptoms of POTS. They did not identify the specific trigger, but as we know with autoimmune concerns, often there are numerous possibilities. These findings provide strong evidence that POTS is by itself an autoimmune disorder.
A study published in Neurology April 2015 by Mayo Clinic also identified changes in antibody levels in patients with POTS. The researchers found that at least one-third of the patients with POTS had evidence of antibodies attacking other specific organs. Most of the patients with POTS had IgG antibodies specific to the thyroid or to gastric parietal cells. Gastric parietal cells are needed for stomach acid production and to help with the absorption of vitamin B12. Most of the patients in the study were female.
Further information released June 2015 showed other autoimmune markers and disorders in patients with POTS. Just like the Mayo Clinic study, they found that Hashimoto’s autoimmune thyroid disorder was the most prevalent. This was followed by rheumatoid arthritis, and SLE (systemic lupus erythematosus). Ninety percent of the patients with POTS in this study were female. In this patient population, 25 percent had positive ANA antibodies, 7 percent had positive anti-phospholipid antibody (aPL antibody) and 20 percent had some other current autoimmune disorder.
There are several other autoimmune disorders that are known to be associated with POTS. Some of these other disorders include amyloidosis, chiari malformation, Chronic Fatigue Syndrome, deconditioning, diabetes and prediabetes, Ehlers-Danlos Syndrome, infections with mononucleosis, Epstein Barr virus, Lyme’s disease, mycoplasma pneumonia and hepatitis C, multiple sclerosis, mitochondrial disorders, mast cell activation disorders, paraneoplastic syndrome, toxicity from alcohol, chemotherapy, or heavy metal poisoning, and vaccinations.
Choline and POTS

Back in 2005, researchers identified that a type of medication called acetylcholinesterase inhibitors could positively improve POTS symptoms. When patients were give medications that blocked the breakdown of choline, the symptoms markedly improved within just a few hours. They didn’t know exactly why, they just knew it helped. Acetylcholinesterase inhibitors are a chemical that blocks the enzyme – acetylcholinesterase from breaking down acetylcholine. This allows the neurotransmitter acetylcholine levels and activity to remain intact. Acetylcholine is the activated form of choline.
Ten years later in May 2015, researchers found further information that expands this information into a whole new world of understanding. While it is an isolated very small study, the information is fantastic and promising. Researchers took a sample of connective tissue (fibroblast sample) from a patient who had POTS. The patient had low blood levels of choline and betaine. They compared choline transport, lipid homeostasis or fat balance in cells, and mitochondria function in the cells from the POTS patient and compared it to healthy cells. The choline transporter-like protein carrier (CTL1/SLC44A1) and messenger RNA (mRNA) was 2-3 times lower in the POTS cells and choline uptake was reduced by 60 percent. This resulted in deficient choline for cell membranes disrupting the structural make-up of the cell membrane. In addition, the lack of choline impaired mitochondria function. This was seen as a reduction in the ability to use oxygen, impairments in burning blood sugar and reduced electrical activity in the mitochondria. When the POTS cells were treated with choline, the entire disabled pathway of function reversed. This study was the first if its kind in demonstrating this disrupted pathway of poor choline transport, altered cell membrane functions and impaired mitochondria. The researchers recommended that choline be an option for patients who struggle with POTS.
What is Choline?

Choline is a vitamin-like essential nutrient. It is a methyl donor essential for many different functions in the body including normal metabolism, transport of lipids, homocysteine metabolism and methylation, and making the neurotransmitter acetylcholine. Acetylcholine is a neurotransmitter that is our memory neurotransmitter. It also plays a major role in regulating skeletal muscle movement, smooth muscle (intestines, bladder function, etc.), peripheral nerves, and cardiac muscle. Insufficient choline can lead to an increasingly common disorder of non-alcoholic fatty liver disease associated with inactivity and high carbohydrate diets. The medications used in the study listed above for choline support was acetylcholinesterase inhibitors. These meds are typically used for helping patients with Alzheimer’s disease for memory problems.
Betaine or trimethylglycine is a metabolite of choline that works together with methylation and homocysteine metabolism. Choline and betaine are both beneficial in reducing systemic inflammation which may be related with the autoimmune inflammation and receptor site breakdown. Research published a few years ago in the American Journal of Clinical Nutrition found reduction of systemic inflammation with increased choline and betaine consumption from foods. The inflammatory markers, C-reactive protein, IL-6, TNF-a, and homocysteine were all reduced in diets rich in choline and betaine.
Chronic Fatigue Syndrome and Choline Receptor Antibodies

As we saw earlier, there are many autoimmune disorders that are associated with POTS, including patients Chronic Fatigue Syndrome/Mylagic Encephalomyelitis (CFS/ME). Interestingly, back in 2003, researchers identified that certain groups of patients with CFS/ME had autoimmune antibodies to a specific type of cholinergic receptors, CHRM1. The study identified only this aspect and did not look further into treatment options. In this particular study, the patients who had the auto-antibodies to the CHRM1 choline receptors had symptoms of muscle weakness, forgetfulness, and difficulty thinking. If you take this finding and think about these CFS/ME symptoms in context of choline, it is striking that these symptoms are often seen with choline deficiency within the brain and seen much later in life with various dementias including Alzheimer’s. This makes me wonder, is there a correlation with poor choline function earlier in life with CFS/ME affecting methylation, mitochondria, oxygenation, and brain inflammation that causes perhaps similar symptoms to later life issues of Alzheimer’s?
Multiple Sclerosis and Choline

Multiple sclerosis (MS) patients also have trouble with POTS. In fact, CFS/ME and MS research shows many remarkable overlapping neurological and immunological symptoms and metabolic dysfunction including POTS. The findings with choline and POTS may be applicable for MS patients, but it is even more important for healthy myelination. Choline is crucial for keeping the fatty myelin sheath intact around nerve fibers. This is critical information as choline function and activity was found to be altered in MS patients. Just a few months ago, researchers identified a new mechanism to enhance central nervous system remyelination via the choline pathway. They found that CDP-choline could become a promising substance for patients with multiple sclerosis as an add-on therapy and had an excellent safety profile.
Summary

The expanded findings of autoimmune antibodies present with POTS and that POTS is often found in other neuro-immune disorders opens the door for exploration, understanding, and new options of support. The additional discovery that choline defects and deficits lead to loss of cell membrane integrity, mitochondrial dysfunction, and impaired oxygen use are an exciting find that may help patients with POTS and CFS/ME, MS and many other autoimmune sufferers with POTS. It should also raise questions for those with other concerns related to choline insufficiency with family history of Alzheimer’s disease. Others may have problems with non-alcoholic fatty liver disease, (NAFLD) methylation defects, elevated homocysteine levels, or problems with PEMT enzyme and gene as seen with your commercial genetic profile, may need much higher intake of choline in your diet or as a supplement. This may especially be the case if you have been of the mindset that eggs, especially egg yolks are bad for heart health.
Given the decades long fear of egg yolks as being bad for you or the Standard American Diet, it is not surprising to see choline deficiency present in the population. Beef liver and egg yolks have some of the highest amounts of choline in foods. Other foods that contain choline include cod, chicken breast, wheat germ, cauliflower, broccoli, amaranth, spinach, quinoa and others. Incorporating these foods into your diet on a regular basis can help support fundamental needs, but if you have one of these concerns, then consider supplementation for additional fortification. This powerful essential nutrient just might help turn your life around and improve your tolerance for gravity and being upright!


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