Do hypermobile Ehlers-Danlos Syndrome (hEDS) and Mast Cell Activation Syndrome (MCAS) predispose patients to obesity due to their impact on adipose tissue?

Relationship Between hEDS, MCAS, and Obesity

There is currently no strong evidence supporting that hypermobile Ehlers-Danlos Syndrome (hEDS) and Mast Cell Activation Syndrome (MCAS) directly predispose patients to obesity through their effects on adipose tissue. 1

Pathophysiological Considerations

• hEDS is characterized by connective tissue abnormalities with softer, less stiff connective tissue than in control subjects, which affects collagen fibril structure and triggers fibroblast dysfunction 1
• MCAS involves abnormal mast cell activation causing release of histamine, heparin, and various cytokines into surrounding tissues, affecting multiple body systems including skin, soft tissue, gastrointestinal tract, respiratory tract, and cardiovascular system 1
• While these conditions affect various tissues throughout the body, current clinical guidelines do not identify a direct mechanistic link between these conditions and predisposition to obesity 1

Associated Conditions That May Indirectly Affect Weight

Gastrointestinal Manifestations

• Patients with hEDS/HSDs frequently report gastrointestinal symptoms (98% meet criteria for disorders of gut-brain interaction in one cross-sectional study), which may affect nutritional status and eating patterns 1
• Common GI manifestations include:
  • Gastroesophageal reflux disease 1
  • Delayed gastric emptying 1
  • Irritable bowel syndrome 1
  • Abdominal pain 2

Autonomic Dysfunction

• Postural Orthostatic Tachycardia Syndrome (POTS) is commonly associated with hEDS and may affect activity levels and energy expenditure 3
• Management of POTS often includes increasing fluid and salt intake, which could potentially affect weight management 1, 3

Medication Effects

• Many medications used to manage symptoms in hEDS and MCAS may have weight-related side effects:
  • Antihistamines for MCAS management may cause increased appetite in some patients 3
  • Certain pain medications may affect metabolism or appetite 2

Dietary Interventions

• Patients with hEDS and MCAS often follow specialized diets that may affect nutritional intake and weight:
  • Low-histamine diets for MCAS 3
  • Gastroparesis diets (small particle diet) 1
  • Various elimination diets (low FODMAP, gluten-free, dairy-free) 1, 3
• These dietary interventions should be delivered with appropriate nutritional counseling to avoid restrictive eating patterns 1

Clinical Implications

• When managing patients with hEDS and/or MCAS who are concerned about weight:
  • Focus on treating the most prominent symptoms and abnormal GI function test results 1
  • Consider the impact of medications on weight and metabolism 3, 2
  • Provide nutritional counseling when implementing dietary interventions 1
  • Address potential activity limitations related to joint hypermobility and pain 2

Research Limitations

• The relationship between hEDS, POTS, and MCAS is still being investigated, with limited experimental evidence of biological mechanisms 1
• The diagnosis of MCAS is often suspected but confirmed in only a small percentage of patients (2% in one prospective study) 4
• The co-occurrence of these conditions is notable - one study found 31% of patients with POTS and EDS also had MCAS, compared to only 2% in patients without POTS and EDS 5

While hEDS and MCAS affect multiple body systems and can impact nutritional status, activity levels, and medication needs, current clinical guidelines do not establish a direct causal relationship between these conditions and obesity through adipose tissue effects.