EDS and POTS: Why These Two Conditions Often Overlap

Two Conditions, One Pattern

If you’ve been diagnosed with Ehlers-Danlos syndrome and you feel dizzy every time you stand up, your heart races when you take a shower, and you can barely get through a grocery store trip without feeling like you need to sit down, you’re not imagining things. You’re likely dealing with POTS on top of EDS.

POTS (postural orthostatic tachycardia syndrome) is defined as a sustained heart rate increase of 30 beats per minute or more (40 bpm for ages 12-19) within 10 minutes of standing, without a significant drop in blood pressure, accompanied by symptoms of orthostatic intolerance [1]. In the general population, POTS affects roughly 1-3 million Americans. In the hypermobile EDS population, the prevalence is strikingly higher.

Studies consistently show that 50-80% of patients with hypermobile EDS (hEDS) meet criteria for POTS or another form of dysautonomia [2]. That’s not a coincidence. These conditions share a biological link rooted in what collagen does in the cardiovascular system.

The Connective Tissue Hypothesis

Your blood vessels aren’t just hollow tubes. Their walls are composed of layers of connective tissue, including collagen and elastin, that give them the ability to actively constrict and relax. When you stand up from a lying or sitting position, gravity pulls about 500-700 mL of blood into your legs and abdomen. Your autonomic nervous system detects this shift and triggers blood vessels in the lower body to constrict, pushing blood back toward the heart and brain.

In EDS, the collagen in blood vessel walls is structurally different. Vessel walls are more compliant, meaning they stretch more easily than they should. When they’re supposed to constrict in response to standing, they don’t tighten sufficiently. The result: excessive blood pooling in the lower body, reduced blood return to the heart, and a compensatory spike in heart rate as the heart tries to maintain adequate cardiac output [3].

This isn’t just theory. Researchers have measured increased venous distensibility (stretchiness) in EDS patients compared to controls. Echocardiographic studies show smaller cardiac chamber sizes in standing EDS-POTS patients, consistent with reduced blood return to the heart [4].

Think of it this way: a normal blood vessel is like a garden hose that maintains its shape and pressure. An EDS blood vessel is more like a thin plastic bag that expands under pressure instead of maintaining tension. The pump (heart) is fine. The plumbing is just too stretchy.

The EDS-POTS-MCAS Triad

Over the past decade, clinicians working with EDS patients have identified a pattern that appears frequently enough to be recognized as a clinical entity: the triad of hypermobile EDS, POTS, and mast cell activation syndrome (MCAS).

MCAS is a condition where mast cells (immune cells found throughout connective tissue) release their chemical mediators inappropriately. Symptoms include flushing, hives, abdominal cramping, diarrhea, brain fog, headaches, and episodes of anaphylaxis-like reactions. When all three conditions are present, they create a feedback loop [5]:

• EDS provides the structural abnormality: Lax connective tissue throughout the body, including blood vessel walls and the tissue surrounding mast cells.
• POTS creates the hemodynamic instability: Blood pooling, tachycardia, and poor perfusion of the brain and other organs.
• MCAS drives inflammation and reactivity: Mast cell mediators like histamine cause vasodilation (which worsens POTS), increase GI motility (contributing to EDS-related GI symptoms), and can directly trigger tachycardia.

Each condition makes the others worse. Histamine from MCAS causes blood vessels to dilate, worsening POTS. POTS-related physiologic stress can trigger mast cell degranulation. And the structural laxity of EDS provides the tissue environment where both POTS and MCAS thrive.

Not every EDS patient has all three conditions. But if you have one, it’s worth screening for the others. The treatment approach changes significantly when multiple conditions are at play.

Shared Symptoms and Diagnostic Confusion

One reason EDS and POTS go undiagnosed for so long is that their symptoms overlap heavily, and both can mimic other conditions:

Many patients are told they have anxiety, panic disorder, chronic fatigue syndrome, fibromyalgia, or conversion disorder before either EDS or POTS is identified. One study found that POTS patients see an average of seven physicians over four years before receiving a correct diagnosis [6]. Add EDS to the mix, and the timeline stretches even longer.

How to Get Properly Evaluated

POTS Testing

The gold standard for POTS diagnosis is a tilt table test. You lie flat on a motorized table that tilts you to a 70-degree angle while your heart rate and blood pressure are continuously monitored. The test lasts 10-45 minutes and captures the hemodynamic response to positional change in a controlled setting.

If a tilt table test isn’t accessible, an active standing test can provide the same information with lower cost and complexity:

1. Lie flat for 5-10 minutes. Record resting heart rate and blood pressure.
2. Stand up and remain still (no walking or fidgeting).
3. Record heart rate and blood pressure at 2, 5, and 10 minutes.
4. A sustained heart rate increase of 30+ bpm (or absolute heart rate above 120 bpm) with orthostatic symptoms meets POTS criteria.

Important note: hydration status significantly affects results. Being dehydrated can produce a false positive. Being over-hydrated can produce a false negative. Test under normal conditions and avoid caffeine beforehand [1].

EDS Evaluation

If you already have a POTS diagnosis, screening for hypermobile EDS involves the 2017 diagnostic criteria, which include:

• Criterion 1: Generalized joint hypermobility (Beighton score of 5+ for adults, with age-adjusted thresholds)
• Criterion 2: Two or more of three features: systemic manifestations of connective tissue disorder, positive family history, and musculoskeletal complications
• Criterion 3: Exclusion of other diagnoses that could explain the findings

A geneticist or rheumatologist experienced with connective tissue disorders is the best person to perform this evaluation. For a detailed breakdown of symptoms to watch for, see our EDS symptoms guide.

MCAS Screening

If you have both EDS and POTS, ask your doctor about MCAS if you experience:

• Flushing episodes (face, chest, or neck turning red)
• Hives or skin reactions without clear allergic triggers
• GI symptoms that fluctuate unpredictably
• Reactions to medications, foods, fragrances, or temperature changes that seem out of proportion
• Episodes resembling allergic reactions without identifiable allergens

MCAS testing involves measuring serum tryptase, 24-hour urine for N-methylhistamine and prostaglandin D2 metabolites, ideally collected during or shortly after a symptomatic episode [5].

Treatment Strategies That Address Both Conditions

The most effective approach treats EDS and POTS as an integrated problem rather than managing each one in isolation. Many interventions help both conditions simultaneously.

Salt and Fluid Loading

This is the simplest and most immediately effective strategy for POTS symptoms. Increasing blood volume compensates for the excessive blood pooling caused by lax vessels.

• Fluid intake: 2-3 liters of water per day, spread throughout the day. Front-loading fluids in the morning is particularly helpful since POTS symptoms tend to be worst in the first few hours after waking.
• Sodium intake: 3-5 grams of supplemental sodium per day (in addition to dietary sodium). Salt tablets, electrolyte drinks, or adding salt to food can all contribute. Some patients use oral rehydration solutions (like WHO rehydration formula) for more efficient absorption [7].
• Avoid alcohol and large meals: Both cause peripheral vasodilation and worsen blood pooling. Smaller, more frequent meals reduce the postprandial blood pressure drop that’s common in POTS.

Compression Garments

Compression works by externally supporting the lax blood vessels that can’t constrict effectively on their own. This reduces blood pooling and improves venous return to the heart.

For maximum benefit:

• Waist-high compression stockings (20-30 mmHg or higher): Thigh-high or knee-high stockings are less effective because a significant amount of blood pools in the abdominal and pelvic vasculature, not just the legs [8].
• Abdominal binders: An abdominal compression garment (or even a firm waistband) can be as effective as lower extremity compression because the splanchnic (abdominal organ) blood vessels are a major pooling site.
• Put them on before standing: Compression works best when applied before blood has already pooled. Put stockings on while still lying in bed in the morning.

Compression also provides the proprioceptive input that EDS joints benefit from. Compression sleeves on knees and ankles can simultaneously stabilize joints and improve blood flow.

Exercise Reconditioning

This is where EDS and POTS treatment overlap most productively. Exercise improves POTS by increasing blood volume, improving cardiac stroke volume, and enhancing autonomic function. It improves EDS by building the muscular support system around unstable joints.

The Levine Protocol (also called the CHOP modified Dallas protocol) is the most studied exercise program for POTS. It was originally designed for deconditioned POTS patients and happens to work well for EDS-POTS patients with modifications [9]:

Month 1-2: Base building (recumbent only)

• Recumbent bike, swimming, or rowing (exercises where you’re not upright)
• Start with 15-20 minutes, 3-4 times per week
• Keep heart rate at a comfortable conversational pace
• For EDS: focus on controlled form; avoid locking joints on the bike or rower

Month 3-4: Introduce upright exercise

• Gradually add short periods of upright exercise (walking, elliptical)
• Continue recumbent exercise as the primary modality
• Begin adding lower extremity strengthening (leg press, wall sits, calf raises)
• For EDS: mid-range motion only; avoid full knee lockout

Month 5-6: Progress intensity

• Increase upright exercise duration
• Add interval training if tolerated
• Expand strength training to include upper body and core
• For EDS: higher reps, controlled tempo, avoid end-range positions

The key principle: progress slowly and don’t push through crashes. A day or two of increased symptoms after exercise means you did too much. Scale back and progress more gradually. Some patients take 6-12 months to work through the full protocol, and that’s completely fine.

Medications

When lifestyle measures aren’t sufficient, several medications can help:

• Fludrocortisone (0.1-0.2 mg daily): A mineralocorticoid that promotes sodium and water retention, increasing blood volume. Particularly useful for patients who can’t consume enough salt orally. Monitor potassium levels.
• Midodrine (2.5-10 mg, 3 times daily): An alpha-1 agonist that directly constricts blood vessels. Helpful for the lax vasculature in EDS-related POTS. Don’t take within 4 hours of bedtime (can cause supine hypertension).
• Ivabradine (2.5-7.5 mg, twice daily): Selectively slows heart rate without affecting blood pressure. Particularly useful when the primary complaint is tachycardia and palpitations. Does not cause the fatigue that beta-blockers often do [10].
• Beta-blockers (low-dose propranolol 10-20 mg): Can reduce heart rate and tremor. Start at very low doses since EDS-POTS patients often have lower baseline blood pressure and are sensitive to hypotensive effects. Some patients find beta-blockers worsen fatigue.
• Pyridostigmine (30-60 mg, 2-3 times daily): An acetylcholinesterase inhibitor that enhances autonomic ganglionic transmission. Can improve both heart rate control and GI motility, making it useful when both POTS and gastroparesis are present.

If MCAS is also present, adding H1 and H2 antihistamines (cetirizine and famotidine) and potentially a mast cell stabilizer (cromolyn sodium) should be considered. Controlling mast cell mediator release can independently improve both POTS and GI symptoms.

Day-to-Day Management Tips

Beyond formal treatment, small daily habits can make a meaningful difference:

• Stand up slowly: Sit on the edge of the bed for 30-60 seconds before standing. Flex your calf muscles and cross your legs before going fully upright.
• Counter-maneuvers: When you feel symptomatic while standing, crossing your legs, tensing your thigh muscles, or shifting your weight from foot to foot can push blood back toward the heart.
• Shower modifications: Use a shower chair. Keep water temperature lukewarm (heat causes vasodilation). If showers are a major trigger, try bathing instead.
• Timing matters: Symptoms are often worst in the morning and after meals. Schedule demanding activities for your best time of day.
• Portable salt: Keep salt packets, electrolyte tablets, or a water bottle with electrolytes with you at all times. If you start feeling symptomatic, drinking a salty fluid while sitting or lying down can help within 15-20 minutes.
• Cooling strategies: Cooling vests, handheld fans, and cold water can help when heat triggers POTS flares.

When to See a Specialist

Primary care can manage mild EDS-POTS with salt, fluids, compression, and exercise guidance. But consider referral to a specialist if:

• Symptoms are severe enough to limit daily function (unable to work, attend school, or maintain basic activities)
• You’re fainting regularly
• First-line treatments haven’t produced meaningful improvement after 3-6 months
• You suspect the MCAS triad is at play
• You need help differentiating EDS subtypes (especially ruling out vascular EDS)

Specialists to consider: autonomic neurologists, cardiologists with dysautonomia expertise, geneticists with connective tissue disorder experience, or multidisciplinary clinics that specialize in EDS-POTS-MCAS. The Dysautonomia International and Ehlers-Danlos Society websites maintain provider directories.

The good news: most EDS-POTS patients improve significantly with proper, targeted treatment. It takes patience and often some trial-and-error with medications and exercise programs, but the trajectory for most people is upward once they’re on the right path.

Related Reading

• Ehlers-Danlos Syndrome: The Complete Guide
• EDS Symptoms: What to Watch For
• EDS Treatment: Managing Hypermobility and Pain
• POTS Treatment: Managing Postural Orthostatic Tachycardia Syndrome
• Dysautonomia Symptoms: Recognizing Autonomic Dysfunction

References

1. Sheldon RS, Grubb BP 2nd, Olshansky B, et al. 2015 Heart Rhythm Society expert consensus statement on the diagnosis and treatment of postural tachycardia syndrome, inappropriate sinus tachycardia, and vasovagal syncope. Heart Rhythm. 2015;12(6):e41-e63. doi:10.1016/j.hrthm.2015.03.029
2. De Wandele I, Rombaut L, Ber Lennart, et al. Dysautonomia and its underlying mechanisms in the hypermobility type of Ehlers-Danlos syndrome. Semin Arthritis Rheum. 2014;44(1):93-100. doi:10.1016/j.semarthrit.2013.12.006
3. Gazit Y, Nahir AM, Grahame R, Jacob G. Dysautonomia in the joint hypermobility syndrome. Am J Med. 2003;115(1):33-40. doi:10.1016/S0002-9343(03)00235-3
4. Tat J, Engel L, King J, Gown J, Guz G. Reduced cardiac chamber sizes, impaired cardiac reserve, and diastolic dysfunction in hypermobile Ehlers-Danlos syndrome: an echocardiographic study. J Am Soc Echocardiogr. 2022;35(1):88-96. doi:10.1016/j.echo.2021.08.014
5. Seneviratne SL, Maitland A, Afrin L. Mast cell disorders in Ehlers-Danlos syndrome. Am J Med Genet C Semin Med Genet. 2017;175(1):226-236. doi:10.1002/ajmg.c.31555
6. Vernino S, Bourne KM, Stiles LE, et al. Postural orthostatic tachycardia syndrome (POTS): state of the science and clinical care from a 2019 National Institutes of Health Expert Consensus Meeting. Auton Neurosci. 2021;235:102828. doi:10.1016/j.autneu.2021.102828
7. Garland EM, Celedonio JE, Raj SR. Postural tachycardia syndrome: beyond orthostatic intolerance. Curr Neurol Neurosci Rep. 2015;15(9):60. doi:10.1007/s11910-015-0583-8
8. Bourne KM, Sheldon RS, Hall J, et al. Compression garment reduces orthostatic tachycardia and symptoms in patients with postural orthostatic tachycardia syndrome. J Am Coll Cardiol. 2021;77(3):285-296. doi:10.1016/j.jacc.2020.11.040
9. Fu Q, Vangundy TB, Galbreath MM, et al. Cardiac origins of the postural orthostatic tachycardia syndrome. J Am Coll Cardiol. 2010;55(25):2858-2868. doi:10.1016/j.jacc.2010.02.043
10. Taub PR, Zadourian A, Lo HC, et al. Randomized trial of ivabradine in patients with hyperadrenergic postural orthostatic tachycardia syndrome. J Am Coll Cardiol. 2021;77(7):861-871. doi:10.1016/j.jacc.2020.12.029