Hypermobility Isn’t Just Flexibility: The Energy Cost of Unstable Joints
She looks healthy. She’s young, she’s slim, she can touch her palms to the floor without bending her knees. Doctors have called her “flexible” since childhood, and physiotherapists have admired her range of motion. Nobody told her that her flexibility is a structural deficit — that her ligaments are made of collagen that doesn’t hold joints together the way it should — and that this deficit costs her body three times the energy to do everything a normally-jointed person does without thinking.
Hypermobility spectrum disorder (HSD) and hypermobile Ehlers-Danlos syndrome (hEDS) are conditions of connective tissue — specifically, of collagen. The protein that forms the structural scaffold of ligaments, tendons, skin, blood vessels, and the extracellular matrix of essentially every organ in the body. When collagen is abnormally elastic, every structure it builds is abnormally elastic. Joints don’t hold position. Blood vessels don’t maintain tone. The gut doesn’t propel contents efficiently. The consequences cascade through every system, and the cumulative energy cost is a tax that the patient pays every minute of every day.
1 The invisible tax on every movement
In a normally-jointed person, ligaments provide passive stability. When you stand, your knee ligaments hold the joint in position without any muscular effort. The muscles are free to do other things — generate movement, respond to perturbation, carry loads. The ligaments are like guy-wires on a tent pole: they provide structural stability for free (Hakim and Grahame 2003).
In a hypermobile person, the ligaments are elastic enough that they don’t fully stabilise the joint. The muscles must compensate. Every joint, every moment, the postural muscles are doing the work that ligaments should handle passively. Standing still is not effortless — it requires continuous active muscle contraction to prevent the joint from subluxing, hyperextending, or drifting into an unstable position.
This has a direct metabolic cost. Skeletal muscle contraction requires ATP. Continuous low-level contraction — the kind needed to stabilise hypermobile joints during ordinary activities — requires sustained ATP expenditure that does not occur in normally-jointed individuals. A hypermobile person sitting in a chair is burning more energy than a normally-jointed person sitting in the same chair, because their muscles are actively stabilising their spine, hips, and shoulders against gravity in a way that ligaments should handle for free.
The proprioceptive system — the network of sensors in joints, tendons, and muscles that reports body position to the brain — is also working overtime. In a stable joint, proprioceptive input is straightforward: the joint is in position, the ligaments confirm it, the brain barely registers it. In a hypermobile joint, proprioceptive input is noisy and unreliable. The joint drifts. The brain receives constant correction signals. The computational load of processing position data from every unstable joint, continuously, is not trivial — and cognitive processing consumes glucose.
The result: a person with hypermobility expends significantly more energy on posture, movement, and body-position monitoring than a normally-jointed person performing identical activities. This is not documented in calorie-counting apps or exercise physiology textbooks. It is invisible to anyone who measures “activity” by steps taken or minutes exercised. But the mitochondria know.
2 The vascular cascade
Connective tissue isn’t only in joints. It forms the walls of blood vessels. In hypermobility, blood vessels are abnormally distensible — they stretch more easily under pressure. This has a specific and devastating consequence for blood pressure regulation.
When a person with hEDS stands up, blood pools in the distensible veins of the lower body. Normally, venous tone and the muscle pump return blood to the heart promptly. In hEDS, the veins stretch excessively, pooling is greater, and venous return drops. The heart receives less blood. Cardiac output falls. Blood pressure drops. The brain, sitting at the top of the circulatory system, gets perfused last and least (Roma et al. 2018; De Wandele et al. 2014).
This is the mechanism of POTS (postural orthostatic tachycardia syndrome) in hEDS patients: the heart rate surges to compensate for reduced stroke volume, producing tachycardia. The patient experiences palpitations, lightheadedness, and cognitive dysfunction on standing — not because the heart is diseased, but because the blood vessels are too stretchy to maintain adequate preload.
The energy cost of compensatory tachycardia is real. A resting heart rate of 100 bpm (common in hEDS/POTS) versus 65 bpm represents a 50% increase in cardiac work — every minute, every hour, every day. The heart is a muscle. Increased cardiac work means increased cardiac ATP consumption. In a patient whose energy budget is already strained, a 50% increase in cardiac workload is not a minor consideration.
3 The mast cell connection
The overlap between hEDS and mast cell activation syndrome (MCAS) is clinically striking and not fully explained. Estimates vary, but MCAS prevalence in hEDS cohorts is far above the general population (Seneviratne, Maitland, and Afrin 2017).
One hypothesis: defective connective tissue provides abnormal mechanical signalling to mast cells that reside within it. Mast cells are mechanosensitive — they respond to physical forces in their surrounding matrix. In abnormal extracellular matrix, the mechanical signals are abnormal, potentially leading to inappropriate mast cell activation.
When mast cells degranulate, they release histamine, prostaglandins, tryptase, and a cascade of inflammatory mediators — systemically. The resulting energy cost is substantial: immune activation consumes 20-25% of basal metabolic rate at peak. Post-degranulation fatigue in MCAS patients is profound and can last 24-72 hours, mimicking PEM.
For an hEDS patient who also has MCAS, the energy equation is devastating: structural instability tax + compensatory cardiovascular work + recurrent immune activation episodes = chronic energy deficit even before any additional ME/CFS pathology is added.
4 The full cascade
Start with defective collagen. Follow the consequences:
- Joint instability → continuous muscular compensation → increased ATP cost of all movement and posture
- Vascular laxity → blood pooling → POTS → compensatory tachycardia → increased cardiac energy cost
- Autonomic dysregulation → impaired vagal tone → reduced gut motility → SIBO → malabsorption → nutrient theft
- Mast cell dysfunction → recurrent immune activation → inflammatory energy cost + post-flare crashes
- Proprioceptive overload → increased CNS processing demand → cognitive fatigue
- Chronic pain → from subluxations, dislocations, neuropathy → pain processing is metabolically expensive + sleep disruption + psychological toll
- Sleep disruption → from pain, POTS (supine tachycardia), mast cell activation → impaired restoration → residual fatigue
Every step in this cascade has an energy cost. The costs are additive. A patient experiencing all seven is paying an energy tax that a normally-jointed person does not, before they get out of bed in the morning.
5 hEDS and ME/CFS: not coincidence but substrate
The prevalence of ME/CFS in hEDS populations — and vice versa — is too high to be coincidental. The cluster (hEDS + POTS + MCAS + ME/CFS) appears in clinical practice with a frequency that screams shared pathophysiology.
The framework this series has been developing suggests why: ME/CFS is a state of chronic energy failure maintained by multiple self-reinforcing mechanisms. Hypermobility provides the substrate — a body that was never structurally equipped for normal energy efficiency, running a permanent deficit that brings the patient closer to the threshold at which any additional hit (an infection, a period of stress, a surgical procedure) tips them into the ME/CFS attractor state.
On this model, a hypermobile person doesn’t develop ME/CFS because of bad luck. They develop it because their baseline energy margin was always smaller. The buffer between “managing” and “failing” was narrower. The cliff was closer.
This has a practical implication: in the hEDS subset of ME/CFS patients, treatment must address the structural energy drain alongside the metabolic and immune mechanisms. Compression garments (reducing venous pooling), joint bracing (reducing muscular compensation), POTS management (fludrocortisone, midodrine, increased sodium and fluids), and MCAS treatment (antihistamines, mast cell stabilisers) are not peripheral interventions. They are direct reductions in the energy tax that the connective tissue dysfunction imposes (Loth 2026).
6 The dismissal pattern
Hypermobile patients are dismissed with remarkable consistency. Their joint pain is attributed to “growing pains” in childhood and “overuse” in adulthood. Their fatigue is attributed to deconditioning. Their POTS is attributed to anxiety. Their MCAS symptoms are attributed to food sensitivities or psychosomatic reactions.
The pattern persists because no single complaint, in isolation, is dramatic enough to trigger investigation. Mild joint laxity. Slightly fast heart rate. Occasional flushing. Non-specific fatigue. Each piece is individually sub-diagnostic. The diagnosis requires recognising the pattern — the cluster of mild connective tissue laxity plus autonomic dysfunction plus immune hyperreactivity plus chronic fatigue — and understanding that the cluster is one disease process, not four unrelated symptoms in a patient who complains a lot.
The average time to hEDS diagnosis in the UK is 10 years. The average time to ME/CFS diagnosis is 4-7 years. A patient with both may spend 15 years being told that each individual symptom is not severe enough to warrant investigation, while the cumulative energy cost drives progressive disability.
The fix is pattern recognition. The Beighton score takes two minutes. The question “do your joints click, pop, or sublux?” takes ten seconds. The observation that a patient with unexplained fatigue also has stretchy skin, hyperextensible elbows, and a resting heart rate of 100 should trigger a cascade of investigation that changes everything about their management.