EDS & Hypermobility: The Functional Medicine Approach

When Flexibility Becomes the Problem

In a culture that prizes flexibility — yoga classes celebrate the contortionist, dance rewards the bendy, gymnastics selects for hypermobility — the person whose joints move beyond normal range is often admired. Until they start dislocating. Until their joints ache constantly. Until standing up makes their heart race to 140. Until they react to every food, every medication, every environmental stimulus. Until the thing that looked like a gift reveals itself as a systemic connective tissue disorder affecting every organ, every tissue, every structure that depends on collagen for its integrity.

Ehlers-Danlos Syndrome (EDS) is not a joint condition. It is a collagen condition. And since collagen is the most abundant protein in the human body — providing structural scaffolding for skin, joints, blood vessels, organs, the gut wall, the blood-brain barrier, the heart valves, the pelvic floor — a defect in collagen synthesis or structure produces a multi-system disorder that touches everything.

The Types

There are 13 recognized subtypes of EDS, each involving mutations in different genes coding for collagen or collagen-processing enzymes:

Hypermobile EDS (hEDS): The most common type (estimated 1 in 3,500 to 1 in 5,000, though likely underdiagnosed). The genetic basis has not yet been identified — hEDS is the only type without a confirmable genetic test. Diagnosis is clinical, using the 2017 International Classification criteria. Characterized by generalized joint hypermobility, musculoskeletal complications, and systemic features.

Classical EDS (cEDS): Mutations in COL5A1 or COL5A2. Skin hyperextensibility, atrophic scarring, generalized hypermobility. Skin is markedly fragile — wounds gape, heal slowly, and leave widened scars.

Vascular EDS (vEDS): Mutations in COL3A1. The dangerous type. Type III collagen is predominant in blood vessels, hollow organs, and the uterus. vEDS carries risk of spontaneous arterial dissection/rupture, bowel perforation, and uterine rupture during pregnancy. Median lifespan historically ~50 years (improving with surveillance). Thin, translucent skin through which veins are visible. Easy bruising disproportionate to trauma. Characteristic facial features (thin nose, thin lips, prominent eyes). Any suspicion of vEDS demands urgent genetic testing and vascular surveillance. Avoid invasive procedures (colonoscopy, arteriography) unless absolutely necessary.

Other types: Kyphoscoliotic, arthrochalasia, dermatosparaxis, cardiac-valvular, myopathic, periodontal, musculocontractural, spondylodysplastic, classic-like — each rare, each with distinct genetic and clinical features.

The Beighton Score and 2017 Criteria

The Beighton score quantifies generalized joint hypermobility on a 9-point scale:

• Passive dorsiflexion of 5th MCP (pinky finger) beyond 90 degrees: 1 point per side (2)
• Passive apposition of thumb to forearm: 1 point per side (2)
• Hyperextension of elbow beyond 10 degrees: 1 point per side (2)
• Hyperextension of knee beyond 10 degrees: 1 point per side (2)
• Forward flexion of trunk with palms flat on the floor, knees straight: 1 point

Score interpretation: adults >5/9 indicates generalized hypermobility (cutoff of >4 for those over 50, as hypermobility naturally decreases with age).

The 2017 international criteria for hEDS diagnosis require all three:

1. Generalized joint hypermobility (Beighton score meeting age-adjusted cutoff)
2. Two or more of: systemic features (skin hyperextensibility, piezogenic papules, dental crowding, arachnodactyly, MVP, tissue fragility), positive family history, musculoskeletal complications (chronic pain, dislocations/subluxations, atraumatic joint instability)
3. Exclusion of other heritable connective tissue disorders (Marfan, Loeys-Dietz, other EDS subtypes) and alternative diagnoses

The Terrible Triad: EDS + POTS + MCAS

Hakim (2017) and Seneviratne (2017) documented what patients had been experiencing for years: hypermobile EDS, postural orthostatic tachycardia syndrome (POTS), and mast cell activation syndrome (MCAS) co-occur at rates far exceeding chance. The triad is so common that finding one should prompt screening for the other two.

The proposed mechanisms connecting them:

EDS to POTS: Lax connective tissue in blood vessel walls allows excessive venous pooling upon standing. The autonomic nervous system compensates with excessive heart rate increase (tachycardia). Collagen defects in the autonomic nerve sheaths may also directly impair autonomic function. Cervical instability (CCI/AAI) can compress the brainstem and vagus nerve, further disrupting autonomic regulation.

EDS to MCAS: Defective collagen in the extracellular matrix surrounding mast cells may destabilize them, lowering the degranulation threshold. The chronic inflammation from joint instability and tissue damage also activates mast cells. Once MCAS is established, mast cell mediators (histamine, prostaglandins, leukotrienes) further destabilize connective tissue, impair autonomic function, and create a self-amplifying cycle.

POTS to MCAS: Mast cell mediators cause vasodilation (worsening pooling) and directly stimulate the autonomic nervous system. Conversely, autonomic dysregulation triggers mast cell degranulation — adrenaline surges activate mast cells through beta-2 receptors.

Joint Management: Stability Over Flexibility

The central principle of EDS physical management contradicts everything the patient has been told by well-meaning yoga teachers and physical therapists: stop stretching. Hypermobile joints do not need more range of motion. They need stability.

What Works

• Proprioceptive training: The body’s position-sensing system (proprioception) is impaired in EDS — joint position sense is less accurate. Training exercises: balance boards, single-leg standing, eyes-closed balance challenges, tai chi, Pilates (with EDS-aware modifications)
• Progressive resistance training: Slow, controlled, through mid-range (avoid end-range where subluxation risk is highest). Eccentric and isometric exercises build tendon strength. Start with low weight, high repetition, and increase gradually. The muscles must compensate for what the ligaments cannot do
• Physical therapy: With a therapist knowledgeable in EDS. The wrong PT — one who pushes range of motion — worsens the condition. The right PT focuses on stabilization, proprioception, and compensatory muscle strengthening. Mulvey protocol, physiotherapy specific to EDS
• Bracing and taping: Kinesiology tape, ring splints (for finger hyperextension), SI belts, knee braces — external stabilization that the ligaments cannot provide. Use strategically for high-risk activities, not continuously (to avoid muscle atrophy from over-reliance)
• Avoid: Yoga (traditional — especially Bikram/hot yoga), aggressive chiropractic manipulation, high-impact sports, end-range stretching, passive stretching by another person. The bendy person does not need to bend more

What Hurts

• Sustained static positions (standing, sitting in one position for hours)
• High-impact loading (running on hard surfaces, jumping)
• Heavy lifting without adequate stabilization training
• Repetitive motions (occupational injury risk is high)
• Contact sports (subluxation/dislocation risk)

Pain Management

Chronic pain in EDS is constant, pervasive, and poorly responsive to conventional analgesics. It arises from: joint instability (mechanical), chronic muscle guarding (compensatory), neuropathic pain (nerve compression from subluxing joints), central sensitization (the nervous system amplifies pain signals after chronic input), and often comorbid fibromyalgia.

Low-Dose Naltrexone (LDN)

1.5-4.5mg at bedtime. Naltrexone at sub-therapeutic doses (standard dose for opioid addiction is 50mg) modulates the immune system by transiently blocking opioid receptors, causing a rebound upregulation of endorphin production and opioid receptor sensitivity. It also modulates microglial activation in the central nervous system — reducing neuroinflammation. Clinical experience in EDS is strongly positive. Start at 0.5-1mg and titrate slowly over weeks. Compounded preparation (not available at this dose commercially). Vivid dreams common initially.

Palmitoylethanolamide (PEA)

600mg 2-3 times daily. An endogenous fatty acid amide that modulates mast cell activation (MCAS benefit), reduces glial activation, and has analgesic properties without addiction potential. Works through PPAR-alpha receptor activation. Onset is gradual (2-4 weeks for full effect). Micronized or ultramicronized forms have better bioavailability.

Supplemental Pain Support

Supplement	Dose	Mechanism
Magnesium glycinate	400-800mg	Muscle relaxation, NMDA receptor modulation
Curcumin (bioavailable)	1000-2000mg	Anti-inflammatory (NF-kB, COX-2)
Omega-3 (EPA focus)	3-4g EPA+DHA	Anti-inflammatory (resolvin/protectin production)
CBD oil	25-50mg	Endocannabinoid modulation, pain, sleep

Other Modalities

• Frequency-Specific Microcurrent (FSM): Specific frequencies for connective tissue, inflammation, and nerve pain. Particularly useful in EDS where systemic anti-inflammatory strategies are needed
• Pelvic floor physical therapy: Pelvic floor dysfunction is extremely common in EDS (lax connective tissue + poor proprioception). Contributes to incontinence, pelvic pain, dyspareunia, and organ prolapse. Specialized PT is essential
• Aquatic therapy: Water provides joint support, resistance without impact, and warmth. Often the best-tolerated exercise modality for EDS patients

POTS Management in EDS

Non-Pharmacological (First Line)

• Salt loading: 10-12g sodium daily (3-4 teaspoons of salt). Expands blood volume. Use quality salt (sea salt, Himalayan). Salt tablets, electrolyte mixes (LMNT, Normalyte, Trioral), or adding salt to food and water. This is not the same as a high-salt junk food diet — it is therapeutic sodium supplementation
• Compression garments: Waist-high 30-40 mmHg compression stockings or abdominal compression binder. Reduces venous pooling. Knee-high stockings are insufficient — the largest venous capacitance is in the abdomen and thighs
• Fluid intake: 2.5-3 liters daily minimum. IV saline (1-2 liters) for acute decompensation
• Levine/CHOP protocol: Graduated exercise program designed specifically for POTS. Begins with recumbent exercise (recumbent bike, swimming, rowing) — no upright exercise initially. Gradually progresses to semi-recumbent, then upright over 3-6 months. Published improvement rates: 71% no longer met POTS criteria after training

Pharmacological

• Fludrocortisone 0.1-0.2mg daily: Mineralocorticoid that increases sodium retention and blood volume
• Midodrine 2.5-10mg three times daily: Alpha-1 agonist that causes vasoconstriction. Take sitting/standing; avoid supine (causes supine hypertension). Last dose by 4 PM
• Ivabradine 2.5-7.5mg twice daily: Selective funny channel (If) inhibitor that reduces heart rate without lowering blood pressure. Often preferred over beta-blockers in EDS-POTS because beta-blockers worsen fatigue and exercise intolerance
• Pyridostigmine 30-60mg three times daily: Acetylcholinesterase inhibitor that enhances ganglionic neurotransmission. Improves upright heart rate and blood pressure without supine hypertension

MCAS Management in EDS

Detailed in the MCAS article, but key points specific to the EDS overlap:

• H1 blocker: Cetirizine 10mg or fexofenadine 180mg daily
• H2 blocker: Famotidine 20-40mg twice daily
• Mast cell stabilizer: Quercetin 500-1000mg twice daily (natural), cromolyn sodium 200mg four times daily (pharmaceutical)
• DAO enzyme: 1-2 capsules before meals containing histamine-rich foods
• Low-histamine diet: Reduce but do not obsess — the goal is reducing mast cell burden, not creating orthorexia
• Avoid known mast cell triggers: Heat, alcohol, NSAIDs, opioids, stress, hormonal fluctuations

GI Manifestations

The GI tract is a collagen-rich organ. EDS GI dysfunction is common and under-recognized:

• Gastroparesis: Delayed gastric emptying (the stomach is a muscular organ wrapped in connective tissue — lax connective tissue impairs motility). Treat with small meals, prokinetics (low-dose erythromycin 50-100mg, ginger, domperidone where available)
• Functional dysmotility: Slow transit throughout the GI tract. Constipation predominant. Magnesium, adequate hydration, motility support
• Visceroptosis: Organs (stomach, kidneys, colon) prolapse due to lax suspensory ligaments. Can cause positional abdominal pain, vascular compression
• IBS overlap: Highly prevalent. Address with standard IFM gut protocol (5R framework) — but recognize that the underlying connective tissue dysfunction will not be fully “healed”
• Rectal prolapse: Pelvic floor laxity. Pelvic floor PT is first-line

Cervical Instability

Craniocervical instability (CCI) and atlantoaxial instability (AAI) deserve special attention. The upper cervical spine (C0-C2) is held in place primarily by ligaments — the alar ligaments, transverse ligament, and tectorial membrane. In EDS, these ligaments are lax, allowing excessive motion between the skull and the first two vertebrae.

This matters because the brainstem, vertebral arteries, and upper spinal cord pass through this region. Instability can compress these structures, producing:

• Severe headaches (especially occipital, worse with upright posture)
• Brain fog and cognitive impairment
• Dysautonomia (POTS, blood pressure instability)
• Swallowing difficulty
• Vision changes
• Nausea, vertigo
• Sensation of head being “too heavy”
• Symptoms that worsen with neck flexion, rotation, or sustained upright posture

Diagnosis: Upright MRI (standard supine MRI may show normal anatomy because gravity is not loading the joint). Dynamic digital motion X-ray. Measurement of clivo-axial angle, Grabb-Oakes measurement, and dens-basion interval.

Treatment: Conservative first — cervical stabilization exercises, custom cervical collar, prolotherapy, PRP to cervical ligaments. If severe and refractory: occipitocervical fusion surgery (major procedure, specialized neurosurgeons — Henderson, Bolognese). Not to be undertaken lightly, but can be life-changing for patients with confirmed severe CCI.

Nutritional Support

Collagen synthesis requires specific nutrient cofactors. In EDS, the collagen produced is genetically altered — you cannot fix the genetic code — but you can optimize the raw materials and cofactors to support the best possible collagen quality from the existing genetic template.

Nutrient	Dose	Role in Collagen
Vitamin C	1-3g daily	Absolutely required — cofactor for prolyl and lysyl hydroxylase (collagen cross-linking enzymes)
Collagen peptides	10-15g daily	Provides amino acid building blocks (glycine, proline, hydroxyproline)
Glycine	5g daily	Most abundant amino acid in collagen, supports sleep and joint repair
Lysine + Proline	500mg each, 1-2x daily	Essential collagen amino acids
Magnesium glycinate	400-800mg	Cofactor for collagen synthesis enzymes, muscle relaxation
Zinc picolinate	30mg	Required for collagen synthesis and wound healing
Copper	1-2mg (only if supplementing zinc)	Required for lysyl oxidase — the enzyme that cross-links collagen fibers. Without copper, collagen cannot be properly cross-linked
Vitamin D3	Target 50-70 ng/mL	Connective tissue maintenance, bone density, immune regulation
MSM	1-3g	Sulfur for connective tissue
Silica	10-20mg	Structural support for connective tissue

The Vascular Type Red Flags

Every practitioner working with EDS patients must know the vascular type red flags — because vEDS can present initially as “just hypermobility” and the consequences of missing it are catastrophic:

• Easy bruising out of proportion to trauma, especially in unusual locations
• Thin, translucent skin (veins visible through skin on chest, abdomen)
• Characteristic facial appearance: thin nose and lips, prominent eyes, small chin
• Family history of early death from vascular events, organ rupture, or aneurysm
• Spontaneous arterial dissection (carotid, vertebral, iliac, renal)
• Spontaneous bowel perforation (particularly sigmoid colon)
• History of uterine rupture or severe obstetric complications

If vEDS is suspected: Urgent genetic testing for COL3A1 mutations. Avoid unnecessary colonoscopy, arteriography, and invasive procedures. Avoid contact sports, heavy lifting, and Valsalva maneuvers. Vascular surveillance protocol with a geneticist familiar with vEDS.

Living With EDS

EDS is a lifelong condition without a cure. Functional medicine cannot fix the genetic code. But it can optimize every variable within the patient’s control — nutrient status, inflammation, gut function, immune regulation, autonomic balance, muscular stability, pain management, and nervous system resilience. The difference between a well-managed EDS patient and a poorly-managed one is enormous.

The patient who learns to stabilize rather than stretch, to support their collagen synthesis, to manage their POTS and MCAS, to protect their cervical spine, and to build a medical team that understands the condition — that patient can live a full, active, meaningful life within the boundaries their connective tissue sets.

If your body’s structural blueprint is different from what the textbook expects, what would it mean to build a life that works with that blueprint instead of against it?