Gastrointestinal Symptoms and Systemic Comorbidities in Patients With <scp>POTS</scp> : A Systematic Review and Meta‐Analysis

BACKGROUND: Patients with postural orthostatic tachycardia syndrome (POTS) frequently report higher rates of chronic gastrointestinal symptoms, disorders of gut-brain interaction (DGBI), and extra-intestinal co-morbidities. We conducted a systematic review and meta-analysis to assess the prevalence of gastrointestinal symptoms and comorbid conditions in POTS patients. METHODS: Electronic databases were searched from inception until May 2025 for studies reporting gastrointestinal symptoms in POTS patients. A random-effects model was used to pool the proportion of POTS patients reporting gastrointestinal symptoms, and sub-group analyses were conducted. RESULTS: The final dataset includes 19 studies, with 8268 POTS patients, revealing that 57.9% (95% CI 38.4-75.2) had at least one gastrointestinal symptom. The most common gastrointestinal symptom was nausea (70.1%, 95% CI 51.5-83.7) followed by bloating (64.9%, 95% CI 48.5-78.4), abdominal pain (60.4%, 95% CI 39.2-78.3) and postprandial fullness (60.4%, 95% CI 45.6-73.6). Irritable bowel syndrome was the most prevalent DGBI, affecting 26.8% (95% CI 15.3-42.4) of POTS patients. The most common extraintestinal comorbidity was anxiety, reported in 42.9% (95% CI 22.7-65.8), followed by chronic fatigue (40.9%, 95% CI 21.1-64.2), migraine (35.6%, 95% CI 27.0-45.2), depression (34.4%, 95% CI 19.0-54.0), and fibromyalgia (21.6%, 95% CI 12.8-34.2). Approximately one third reported mast cell activation syndrome (36.3%, 95% CI 17.8-60.0) and joint hypermobility syndrome (31%, 95% CI 24.4-38.5). There was substantial heterogeneity seen in the primary and most subgroup analyses. CONCLUSIONS: Overall, 60% of POTS patients report concurrent gastrointestinal symptoms, with nausea being the most common. IBS affects 25% of patients with POTS. Notably, extra-intestinal comorbidities-primarily anxiety, chronic fatigue, migraines, depression, and fibromyalgia-are more prevalent than gastrointestinal conditions in this population.