Root Causes Of Postural Orthostatic Tachycardia Syndrome (POTS) And Ways To Reverse It

I usually look at a Total Toxicology Test for my POTS clients, as those are the most common issues to cause the dysautonomic biomarkers below.

Top Recommendations:

• Astragalus (↓ ANG-II, ↑ eNOS, ↑ ACh) R R R

• Butyrate (↑ NET) R

• CBD (↑ CB2, ↑ nNOS) R

• CDP-Choline (↑ mitochondrial CTL1/SLC44A1, ↑ ACh) R

• Low Lectin diet (to reduce symptoms of autoimmunity) - eat frequent, smaller meals (less high insulin spikes) and keep physically active/not sitting laying down all day, helps reduce symptoms

• Neo40 (↑ NO significantly) R

• Sunlight (↑ eNOS/nNOS significantly, ↑ GAL via MSH?) R

• Vitamin B1 (↑ ACh) R R

• Vitamin B12 R

• Vitamin C (↑ BH4, ↓ ROS) R

As POTS is multifactorial, this is not a one-size fits all – this order below is not definitive, but each section may be a contributing problem and must be addressed properly.

1. Deal With Underlying Infection, Toxin, Or Trauma

Infections can get into nervous tissue and cause dysautonomia, so they should be addressed first (posts pending):  R

• Candida

• EBV/Mono

• Herpes

• Lyme

• Mold

If you have a buildup of heavy metals they need to be removed as they can cause secondary POTS:

• Arsenic

• Cadmium

• Mercury

NRF2 activation also helps with some heavy metals as well as other oxidative factors contributing to secondary POTS.

If you have had trauma to the Dura Mater, then addressing that is very important to rule out CSF leak.

2. Increase Nitric Oxide

Typically you can get nitric oxide from eating leafy greens, but if you have dysbiosis in your mouth, this reaction of nitrates to nitrites will be blunted and you should supplement with nitrates until the oral dysbiosis is fixed. R

Also, depletion of BH4 will blunt the beneficial effects of NO, especially from an infection in the basal ganglia. R

Strong ways to increase nitric oxide (you want to increase nNOS, not iNOS): R

• Beetroot Juice

• Celery

• Exercise (gradual increase) R R R

• LLLT

• Nitrates (such as Neo40 -> increases BH4 and recouples eNOS) R

• Sun

See all ways to increase nitric oxide here.

3. Other

Lifestyle/Therapies:

• Avoid excessive heat, such as hot showers, sauna (sun may be an exception) R

• Cognitive behavioral therapy R

• CT-Guided, Percutaneous T2 Ethanol Ablation R

• IVIG R R

• IV Saline R

• Limit caffeine (↑ vasoconstriction, ↑ urination) unless you have CSF leak; alcohol; excessive carbs R R

• Liquid and electrolyte (salt) intake R

• Sleep elevated with pillows R

• Wear Compression stockings R

Supplements:

• Vitamin B1 R

• Vitamin B12 R R

Drugs/Hormones:

• Angiotensin II receptor blockers (ie Losartan) - ↑ NO R R R

• Antibiotics (if you have SIBO) R

• Beta-blockers R

• Desmopressin (DDAVP) R

• Droxidopa R

• Erythropoietin R

• Fludrocortisone R

• Ivabradine R

• Liraglutide R

• Methyldopa

• Methylphenidate R

• Midodrine (for neuropathic POTS) R

• Modafinil R

• Naltrexone (as Low-Dose Naltrexone) R

• Norepinephrine reuptake inhibitors R

• Octreotide R

• Physostigmine (strong for ACh inducing orthostatic tolerance) R

• Propranolol R

• Pyridostigmine R

• Serotonin reuptake inhibitors R

• Sertraline R

• Vasopressin R

Pathways:

• Increase α1-adrenergic receptor (for neuropathic POTS) R

• Increase acetylcholine (acetylcholinesterase inhibition leads to an increase in CBF without a change in metabolism while supine) R

• Increase GAL (via NPY) R

• Increase H2S (↑TRPV1) R R

• Increase RAAS (activating sodium retention to restore extracellular fluid volume) R

• Inhibit HDAC (shown to increase SLC6A2 via MeCP2) R

Simple:

• Nitric oxide becomes uncouple and depletes BH4 which causes high inflammatory nitric oxide, aka peroxynitrate (ONOO-), and thus nitric oxide is high, but less bioavailable.

• Also, see biomarkers above.

Advanced:

• Impaired vascular innervation, high plasma norepinephrine concentrations, mutation/reduced activity in the NE transporter (NET) SLC6A2 (A457P), α‐receptor sensitivity, β‐receptor hypersensitivity and baroreceptor dysfunction. R R

• A blunted ACE 2 pathway which results in increased serum levels of ANGII, decreased Ang-(l-7), and resultant scant nitrous oxide (NO). R

  • ↑ ANGII -> ↓NO by superoxide scavenging to create peroxynitrite R

  • ↑ ANGII via ROS ↑ central and peripheral sympathetic activity R R R

  • ↓ BH4 uncouples NOS, -> ↑superoxide and ↑ ROS -> positive feedback ↓ NO -> endothelial dysfunction R

• The deficit in NO (as well as down-regulation of NO receptor sites) has been associated with increased plasma levels of ANG II, attributed to a defect in angiotension-converting enzyme-2. R

• This is known to produce ROS via binding to ANG II type 1 receptors (AT1R) on NADPH oxidase and scavenging NO by superoxide. R

• Cutaenously, eNOS is normal or high, while nNOS is low. R

• Various autoantibodies, including those directed against cardiac proteins, β1/2-adrenergic, M2/3 muscarinic and N-type acetylcholine receptors, have been identified in POTS patients, strengthening the idea of POTS as member of the autoimmune autonomic neuropathies family. R

• In choline synthesis R

  • ↑ remethylate homocysteine (tHcy) + ↑ cystathione (tHcy metabolite) + ↓ cysteine (metabolite of cystathione)

  • The choline transporter is ↓ CTL1/SLC44A1 (~2.5x) in skin -> causing less cellular uptake (60%) and mitochonrdial (50%) uptake of choline

    • ↓ P-choline and ↓ CDP-choline

    • ↓ respiration capacity, ↓ glycolytic activity, and ↓ ATP synthesis

Primary actions of neuropeptides/peptide hormones: R

• Vasodilation

  • B-type natriuretic peptide

  • Atrial natriuretic peptide

  • Adrenomedullin

  • Galanin

  • Vasoactive intestinal peptide

• Vasoconstriction

  • Endothelin (1-3)

  • Vasopressin

• RAAS inhibition

  • Endothelin (1-3)

  • Galanin

• Diuresis

  • B-type natriuretic peptide (BNP)

  • Atrial natriuretic peptide (ANP)

  • Galanin

  • Vasoactive intestinal peptide (VIP)

ENOS

rs2070744 (T-786C)

• With E298D - experienced the largest changes in heart rate and plasma norepinephrine with standing R

• C allele of the T-786C polymorphism reduces eNOS activity as a result of suppressed NOS3 transcription R

E298D

• With Or without T-786C - experienced the largest changes in heart rate and plasma norepinephrine with standing R

• TT allele - increased myocardial infarction (MI) in smokers vs GG R

SLC6A2

rs5564 (I'm AA)

• significantly associated with the diagnosis of POTS R

rs7194256

• T allele - found higher in POTS, panic disorder, major depression and hypertension R

• Astronauts returning from space not yet re-adapted to gravity may demonstrate symptoms of POTS. R