Fatigue and hEDS
Fatigue in someone with hypermobile Ehlers-Danlos syndrome (hEDS) is extremely common and often debilitating. While it’s not fully understood, there are several theoretical mechanisms that may explain it, many of which likely overlap and compound one another:
Autonomic Nervous System Dysfunction (e.g., POTS)
One of the most common coexisting conditions with hEDS is dysautonomia, especially Postural Orthostatic Tachycardia Syndrome (POTS).
Leads to poor blood flow regulation, resulting in inadequate oxygen delivery to the brain and muscles
Causes lightheadedness, brain fog, and profound fatigue, especially after standing or minimal exertion
This is one of the leading known contributors to fatigue in hEDS.
Mitochondrial Dysfunction (Theoretical)
Emerging hypotheses suggest that chronic stress on connective tissue and cells may cause mitochondrial stress or inefficiency, reducing the body’s ability to produce energy. Mitochondria are the "powerhouses" of the cell, responsible for generating ATP, the energy currency used for nearly all cellular functions.
This isn’t yet well-studied in hEDS but is suspected in some connective tissue disorders.
If true, it could result in fatigue that feels cellular, like chronic fatigue syndrome.
Microcirculation Issues and Tissue Hypoxia
Abnormal collagen may affect the structure of small blood vessels, leading to
Poor tissue perfusion, especially in muscles
Lactic acid buildup and pain or fatigue with mild exertion
This would make even mild activity lead to muscle fatigue due to limited oxygen delivery.
Musculoskeletal Instability and Compensatory Effort
In hEDS, joints are unstable and muscles must compensate constantly to hold the body together.
This requires extra muscle activation even during rest or light activity.
Over time, this leads to muscle fatigue, tension, and exhaustion.
Chronic Pain and Poor Sleep Quality
Chronic pain is extremely common in hEDS and leads to
Poor sleep quality, even when sleep duration is normal
Non-restorative sleep, increasing both mental and physical fatigue
Neurological or Central Sensitization
Fatigue may also stem from central nervous system dysregulation, sometimes described in the context of
Central sensitization (also tied to chronic pain)
Neuroinflammation theories (still early-stage research)
This can make normal sensory input feel overwhelming or tiring
Cognitive Load from Self-Regulation
Living with hEDS requires constant body awareness, planning, avoidance of triggers, and management of symptoms.
This chronic vigilance, both physical and emotional, may lead to mental fatigue.
It is especially common in people managing multiple comorbidities (pain, GI, fatigue, anxiety, etc.).
Immune System Dysregulation (Theoretical)
Some researchers suspect a low-grade chronic inflammatory state or immune dysregulation in hEDS or related conditions.
This could potentially contribute to fatigue and flu-like malaise
Mast Cell Activation Syndrome
Mast Cell Activation Syndrome (MCAS) is known to cause fatigue in several ways.
Mast cells release a variety of chemical mediators (like histamine, prostaglandins, cytokines) that trigger inflammation and allergic-type symptoms. When these mediators are released excessively or inappropriately, they can cause systemic symptoms, including fatigue.
Fatigue in MCAS may result from chronic low-grade inflammation, immune activation, and the body’s ongoing effort to deal with these mediators.
Additionally, MCAS can cause sleep disturbances, pain, gastrointestinal symptoms, and autonomic dysfunction, all of which contribute to feeling tired or exhausted.
Summary
Fatigue in hEDS is multifactorial and not just "tiredness" — it’s often a combination of
Autonomic dysfunction (especially POTS)
Poor oxygen delivery and circulation
Chemicals, such as histamine, or inflammation
Muscle overuse to stabilize joints
Poor sleep and chronic pain
Possible mitochondrial or immune factors
Managing it typically requires a multi-pronged approach: physical therapy, treating dysautonomia, pacing activities, improving sleep, and possibly medication or nutritional support.
