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Cited by 55Gastrointestinal motility and disordersCardiovascular Syncope and Autonomic DisordersHeart Rate Variability and Autonomic Control

Gastrointestinal symptoms in postural tachycardia syndrome: a systematic review

Open access
Mehr, Shahram E., Barbul, Adrian, Shibao, Cyndya A.·2018·Clinical Autonomic Research
DOI 10.1007/s10286-018-0519-xPMC PMC6314490
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Abstract

Gastrointestinal symptoms are among the most common complaints in patients with postural tachycardia syndrome (POTS). In some cases, they dominate the clinical presentation and cause substantial disabilities, including significant weight loss and malnutrition, that require the use of invasive treatment to support caloric intake. Multiple cross-sectional studies have reported a high prevalence of gastrointestinal symptoms in POTS patients with connective tissue diseases, such as Ehlers-Danlos, hypermobile type, and in patients with evidence of autonomic neuropathy. Previous studies that evaluated gastric motility in these patients reported a wide range of abnormalities, particularly delayed gastric emptying. The pathophysiology of gastrointestinal symptoms in POTS is likely multifactorial and probably depends on the co-morbid conditions. In patients with POTS and Ehlers-Danlos syndromes, structural and functional abnormalities in the gastrointestinal connective tissue may play a significant role, whereas in neuropathic POTS, the gastrointestinal tract motility and gut hormonal secretion may be directly impaired due to localized autonomic denervation. In patients with normal gastrointestinal motility but persistent gastrointestinal symptoms, gastrointestinal functional disorders should be considered. We performed a systematic review of the literature related to POTS and gastrointestinal symptoms have proposed possible mechanisms and discussed diagnosis and treatment approaches for delayed gastric emptying, the most common gastrointestinal abnormality reported in patients with POTS.

Integrity signals

Registry

Crossref · 10.1007/s10286-018-0519-x

Cites

68 of 68 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 31 cited sources checked · 0 supported · 0 flagged

  • Findingnone given

    There are no clinical trials testing specific interventions in patients with POTS and GI symptoms.

    “In the literature, there are no clinical trials that test the effect of specific interventions in patients with POTS and gastrointestinal symptoms.”
    Quote in the paperSubstantial claim
  • Findingcitation

    In the same h-EDS cohort, 60% had functional dysphagia with normal esophageal motility.

    “Furthermore, 60% had functional dysphagia with normal esophageal motility.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [19] Fikree A, Aziz Q, Sifrim D (2017) Mechanisms underlying reflux symptoms and dysphagia in patients with joint hypermobility syndrome, with and without postural tachycardia syndrome. Neurogastroenterol Motil 29(6). doi: https://doi.org/10.1111/nmo.13029 source

      Not checked in the free run.

  • Findingnone given

    There are no studies evaluating differences in the pathophysiology of the most common GI conditions in POTS versus non-POTS patients with similar symptoms.

    “Furthermore, there are no studies that evaluated differences in the pathophysiology of the most common gastrointestinal conditions described in POTS versus patients without POTS with similar symptoms.”
    Quote in the paperSubstantial claim
  • Findingnone given

    There is a poor correlation between improvement in gastric emptying from prokinetic agents and improvement in symptoms.

    “There is a poor correlation between the improvement in gastric emptying secondary to use of pro-kinetic agents and the improvement in symptoms.”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: Evidence from studies in non-POTS patients with gastroparesis or other GI conditions can guide treatment of GI symptoms in POTS patients.
  • Findingnone given

    Delayed gastric emptying or gastroparesis is one of the most common conditions reported in POTS.

    “One of the most common conditions reported in POTS is delayed gastric emptying or gastroparesis.”
    Quote in the paperNot a substantial claim
  • May combine two claims. 20
  • Classified as probably not a substantial claim. 4

  • May combine two claims.

    Findingcitation

    After a meal, POTS patients have a larger increase in mesenteric blood flow than controls, suggesting excessive splanchnic capacitance during resting conditions and possibly after a meal.

    “After a meal, POTS patients had a larger increase in mesenteric blood flow than in controls, and this suggests that they have excessive splanchnic capacitance during resting conditions and possibly after a meal.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [64] Tani H, Singer W, McPhee BR, Opfer-Gehrking TL, Haruma K, Kajiyama G, Low PA (2000) Splanchnic-mesenteric capacitance bed in the postural tachycardia syndrome (POTS). Auton Neurosci Basic Clin 86:107–113 source

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    Four studies of GI symptoms in POTS reported abnormal gastric motility, with rapid gastric emptying in 43% and delayed gastric emptying/gastroparesis in 20%.

    “Four of these studies that describe the GI symptoms in POTS also reported evidence of abnormal gastric motility- either rapid gastric emptying (43%) or delayed gastric emptying (gastroparesis, 20%) [5, 36, 48, 67].”
    Quote in the paperNot a substantial claim0 of 4 sources checked
    • cites [5] Antiel RM, Risma JM, Grothe RM, Brands CK, Fischer PR (2008) Orthostatic intolerance and gastrointestinal motility in adolescents with nausea and abdominal pain. J Pediatr Gastroenterol Nutr 46:285–288 source

      Not checked in the free run.

    • cites [36] Lawal A, Barboi A, Krasnow A, Hellman R, Jaradeh S, Massey BT (2007) Rapid gastric emptying is more common than gastroparesis in patients with autonomic dysfunction. Am J Gastroenterol 102:618–623 source

      Not checked in the free run.

    • cites [48] Park K-J, Singer W, Sletten DM, Low PA, Bharucha AE (2013) Gastric emptying in postural tachycardia syndrome: a preliminary report. Clin Auton Res 23:163–167 source

      Not checked in the free run.

    • cites [67] Wang LB, Culbertson CJ, Deb A, Morgenshtern K, Huang H, Hohler AD (2015) Gastrointestinal dysfunction in postural tachycardia syndrome. J Neurol Sci 359:193–196 source

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    POTS patients have increased resting mesenteric blood flow and reduced splanchnic vascular resistance despite normal systemic vascular resistance.

    “Tani et al. [64] reported an increase in resting mesenteric blood flow and reduced splanchnic vascular resistance in spite of normal systemic vascular resistance.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [64] Tani H, Singer W, McPhee BR, Opfer-Gehrking TL, Haruma K, Kajiyama G, Low PA (2000) Splanchnic-mesenteric capacitance bed in the postural tachycardia syndrome (POTS). Auton Neurosci Basic Clin 86:107–113 source

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    In a retrospective observational study, about 60% of patients with colonic transit abnormalities had h-EDS, and 22% had abnormal gastric emptying.

    “In a retrospective observational study, around 60% of patients with colonic transit abnormalities had h-EDS, and 22% had abnormal gastric emptying [47].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [47] Nelson AD, Mouchli MA, Valentin N, Deyle D, Pichurin P, Acosta A, Camilleri M (2015) Ehlers Danlos syndrome and gastrointestinal manifestations: a 20-year experience at Mayo Clinic. Neurogastroenterol Motil 27:1657–1666 source

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    In the h-EDS cohort, the POTS group was more likely to have esophageal hypomobility and pathological gastro-esophageal reflux.

    “The POTS group was more likely to have esophageal hypomobility and pathological gastro-esophageal reflux [19].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [19] Fikree A, Aziz Q, Sifrim D (2017) Mechanisms underlying reflux symptoms and dysphagia in patients with joint hypermobility syndrome, with and without postural tachycardia syndrome. Neurogastroenterol Motil 29(6). doi: https://doi.org/10.1111/nmo.13029 source

      Not checked in the free run.

  • May combine two claims.

    Findingreasoning

    The majority of studies evaluating gastric motility in POTS used gamma camera scintigraphy, but they differ in diet and measurement duration.

    “The majority of the studies that have evaluated gastric motility in POTS used gamma camera scintigraphy because this is a non-invasive test that is available in most radiological centers. However, these studies differ in the diet used and duration of the measurement.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingcitation

    In a large POTS cohort, celiac disease prevalence was 4%, higher than the 1% in age- and gender-matched controls (OR 4.1, 95% CI 1.3-13.0; p=0.03).

    “Penny et al., [51] reported that the prevalence of CD was 4% in a large POTS cohort; this prevalence was higher than the one reported in a control group (1%) matched for age and gender (OR: 4.1, 95% CI:1.3-13.0; p=0.03).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [51] Penny HA, Aziz I, Ferrar M, Atkinson J, Hoggard N, Hadjivassiliou M, West JN, Sanders DS (2016) Is there a relationship between gluten sensitivity and postural tachycardia syndrome? Eur J Gastroenterol Hepatol 28:1383–1387 source

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    In a cohort of 30 h-EDS patients (12 without POTS, 18 with POTS), 53% had pathological acid reflux, 21% hypersensitive reflux, and 25% functional reflux.

    “In this cohort, 53% of patients had pathological acid reflux, 21% had hypersensitive reflux, and 25% had functional reflux.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [19] Fikree A, Aziz Q, Sifrim D (2017) Mechanisms underlying reflux symptoms and dysphagia in patients with joint hypermobility syndrome, with and without postural tachycardia syndrome. Neurogastroenterol Motil 29(6). doi: https://doi.org/10.1111/nmo.13029 source

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    In patients with autonomic failure, active vasoconstriction of the superior mesenteric artery after a sympathetic stimulus does not occur, which may contribute to post-prandial hypotension.

    “Chaudhuri et al., [15] showed that in patients with autonomic failure, active vasoconstriction of the superior mesenteric artery (SMA) after a sympathetic stimulus does not occur which could contribute to the post-prandial hypotension.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [15] Chaudhuri KR, Thomaides T, Mathias CJ (1992) Abnormality of superior mesenteric artery blood flow responses in human sympathetic failure. J Physiol 457:477–489 source

      Not checked in the free run.

  • May combine two claims.

    Findingown data

    In patients with POTS, nausea and abdominal pain are the most common non-cardiovascular symptoms, with a pooled prevalence of about 69% across six studies (N=352).

    “In POTS patients, nausea and abdominal pain are the most frequent noncardiovascular symptoms; pooled data from six studies (N=352 patients) show a prevalence of ≈69%, Table 2.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The six studies pooled for GI symptom prevalence used comparable definitions and assessments of GI symptoms.

  • May combine two claims.

    Findingcitation

    Self-reported gluten sensitivity and IBS were more prevalent in the POTS cohort than in controls.

    “The prevalence of self-reported gluten sensitivity and IBS were also higher in the POTS cohort than in controls.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [51] Penny HA, Aziz I, Ferrar M, Atkinson J, Hoggard N, Hadjivassiliou M, West JN, Sanders DS (2016) Is there a relationship between gluten sensitivity and postural tachycardia syndrome? Eur J Gastroenterol Hepatol 28:1383–1387 source

      Not checked in the free run.

  • May combine two claims.

    Findingnone given

    POTS patients have impaired gastrointestinal motility, including delayed gastric emptying.

    “impaired GI motility such as delayed gastric emptying”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingcitation

    Gastrointestinal symptoms and abnormal gastrointestinal motility are more frequent in patients with h-EDS and neuropathic POTS than in other groups.

    “Cross-sectional studies suggest that GI symptoms and GI abnormal motility are more frequent in patients with h-EDS and neuropathic POTS than in other groups.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationcitation

    Loss of sympathetic inhibitory innervation, as in POTS patients with partial autonomic neuropathy, may cause excessive and uncoordinated GI tract activity.

    “The absence of sympathetic inhibitory innervation, as seen in POTS patients with partial autonomic neuropathy, may cause excessive and uncoordinated activity in the GI tract [11].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [11] Browning KN, Travagli RA (2014) Central nervous system control of gastrointestinal motility and secretion and modulation of gastrointestinal functions. Compr Physiol 4:1339–1368 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    The FDA has a black box warning against chronic metoclopramide use.

    “The Food and Drug Administration has a black box warning against the chronic use of metoclopramide [56].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [56] Rao AS, Camilleri M (2010) Review article: metoclopramide and tardive dyskinesia. Aliment Pharmacol Ther 31:11–19 source

      Not checked in the free run.

    • Rests on an assumption: Evidence from studies in non-POTS patients with gastroparesis or other GI conditions can guide treatment of GI symptoms in POTS patients.

  • May combine two claims.

    Interpretationnone given

    There is no consensus on the definition and diagnosis of autonomic neuropathy in POTS, which makes comparison across studies difficult.

    “One of the major challenges when comparing studies is the lack of consensus on the definition and diagnosis of autonomic neuropathy in POTS.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Interpretationnone given

    Gastroparesis is difficult and ill-defined to manage, with few effective treatments and a paucity of well-controlled trials.

    “This is a difficult and still ill-defined syndrome to manage, with few effective treatments and a paucity of well-controlled trials.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Metoclopramide is mainly a D2 antagonist that aids acetylcholine release, increasing antral contractility, antroduodenal tone, and gastric emptying.

    “It is mainly a dopamine type 2 receptor (D2) antagonist, aiding in the release of acetylcholine which increases antral contractility, antroduodenal tone, and gastric emptying [52].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [52] Perkel MS, Moore C, Hersh T, Davidson ED (1979) Metoclopramide therapy in patients with delayed gastric emptying: a randomized, double-blind study. Dig Dis Sci 24:662–666 source

      Not checked in the free run.

    • Rests on an assumption: Evidence from studies in non-POTS patients with gastroparesis or other GI conditions can guide treatment of GI symptoms in POTS patients.

  • May combine two claims.

    Premisecitation

    Metoclopramide's most serious side effect is extrapyramidal movement disorders, tardive dyskinesia, and akathisia in 30-40% of patients; drowsiness, fatigue, and depression also occur frequently.

    “Its most serious side effect is the occurrence of extrapyramidal movement disorders, tardive dyskinesia, and akathisia in a significant number of patients (30-40%). Drowsiness, fatigue, and depression also occur frequently.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [56] Rao AS, Camilleri M (2010) Review article: metoclopramide and tardive dyskinesia. Aliment Pharmacol Ther 31:11–19 source

      Not checked in the free run.

    • Rests on an assumption: Evidence from studies in non-POTS patients with gastroparesis or other GI conditions can guide treatment of GI symptoms in POTS patients.

  • May combine two claims.

    Premisecitation

    Denervation of the stomach causes abnormal gastric electrical activity and GI symptoms such as nausea, vomiting, abdominal discomfort/pain, and diarrhea, although gastric activity partly recovers over time.

    “Denervation of the stomach causes abnormal gastric electrical activity and produces GI symptoms such as nausea and vomiting, abdominal discomfort pain, and diarrhea. However, the gastric activity partly recovers after a period of time [11].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [11] Browning KN, Travagli RA (2014) Central nervous system control of gastrointestinal motility and secretion and modulation of gastrointestinal functions. Compr Physiol 4:1339–1368 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Prokinetic agents increase antral contractility, reduce gastric dysrhythmias, and improve coordination between the antrum and duodenum, with modest effect.

    “This group of drugs increases antral contractility, reduces gastric dysrhythmias, and improves coordination between the antrum and duodenum. The effect is modest, and responses are assessed clinically [63].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [63] Talley NJ (2003) Diabetic gastropathy and prokinetics. Am J Gastroenterol 98:264–271 source

      Not checked in the free run.

    • Rests on an assumption: Evidence from studies in non-POTS patients with gastroparesis or other GI conditions can guide treatment of GI symptoms in POTS patients.

  • May combine two claims.

    Premisecitation

    Domperidone has much less blood-brain barrier penetration than metoclopramide; it is used worldwide but not FDA-approved because of unconvincing efficacy data, though it has a good safety profile.

    “Domperidone, another D2-antagonist, has much less penetration through the blood-brain barrier when compared to metoclopramide. In use throughout the world, it has not been approved by the FDA, because of unconvincing efficacy data, although it possesses a good safety profile [61].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [61] Sugumar A, Singh A, Pasricha PJ (2008) A systematic review of the efficacy of domperidone for the treatment of diabetic gastroparesis. Clin Gastroenterol Hepatol 6:726–733 source

      Not checked in the free run.

    • Rests on an assumption: Evidence from studies in non-POTS patients with gastroparesis or other GI conditions can guide treatment of GI symptoms in POTS patients.
22 of 22

  • The paper relies on this without support.

    Evidence from studies in non-POTS patients with gastroparesis or other GI conditions can guide treatment of GI symptoms in POTS patients.

    “In the following section, we briefly summarized the current medical, and surgical treatment approaches for the most common gastrointestinal symptoms reported in POTS based on evidence from the literature derived from studies that enrolled non-POTS patients with these conditions.”

  • The paper relies on this without support.

    POTS patients with more GI complications also have increased post-prandial orthostatic symptoms.

    “It is noteworthy that patients with a higher occurrence of GI complications also complaint of increased post-prandial orthostatic symptoms.”

  • The paper relies on this without support.

    POTS patients have a high prevalence of functional GI disorders.

    “On the other hand, POTS patients also have a high prevalence of functional GI disorders.”

  • The paper relies on this without support.

    The six studies pooled for GI symptom prevalence used comparable definitions and assessments of GI symptoms.

    “pooled data from six studies (N=352 patients) show a prevalence of ≈69%, Table 2.”
4 of 4

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Multisystemic involvement is common in PoTS, with gastrointestinal symptoms (including nausea, irregular bowel movements, abdominal pain, bloating and constipation) the most frequent non-cardiovascular symptoms reported.

    “Multisystemic involvement is common, with gastrointestinal symptoms (including nausea, irregular bowel movements, abdominal pain, bloating and constipation) the most frequent non‐cardiovascular symptoms reported. 68 , 69”

    From Hypermobile Ehlers–Danlos syndrome and disorders of the gastrointestinal tract: What the gastroenterologist needs to know (2022) · cites this paper as [68]

  • The cause for these symptoms is likely to be multifactorial, but may be related to changes in splanchnic circulation, presence of small fiber neuropathy or altered vascular compliance related to the generalized tissue laxity in hEDS.

    “The cause for these symptoms is likely to be multifactorial, but may be related to changes in splanchnic circulation, presence of small fiber neuropathy or altered vascular compliance related to the generalized tissue laxity in hEDS. 68 , 69”

    From Hypermobile Ehlers–Danlos syndrome and disorders of the gastrointestinal tract: What the gastroenterologist needs to know (2022) · cites this paper as [68]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • The stated majority is not supported by the reported neuropathy-test proportion

    Minor

    The review says a majority of symptomatic POTS patients had evidence of autonomic neuropathy, but its description of two of the cited studies reports an abnormal QSART in only nearly 30%. The third study compares GI-symptom prevalence between neuropathy groups rather than establishing that a majority of symptomatic patients had neuropathy.

1 of 1

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Authors
Mehr, S. E., Barbul, A., & Shibao, C. A.
Affiliations
Vanderbilt University Medical Center (US)
Corresponding author
Shibao, Cyndya A.
ORCID
Venue
Clinical Autonomic Research
Publisher
Springer Science and Business Media LLC
Published
2018-03-16
Volume
28
Issue
4
Pages
411-421
ISSN
  • 0959-9851 (ISSN-L)
  • 1619-1560
DOI
10.1007/s10286-018-0519-x
PMC
PMC6314490
OpenAlex
W2791165999
Cited by
55
References
68
Citations by year
2026: 9 · 2025: 9 · 2024: 8 · 2023: 3 · 2022: 10 · 2021: 4 · 2020: 7 · 2019: 3 · 2018: 1
FWCI
0.67
Type
journal article
Language
en
Open access
Licence
Locations
  • Clinical Autonomic Research (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health (5T32007569, rr000445, U54NS065736)
  • Doris Duke Charitable Foundation
  • VANDERBILT CTSA
Topics
  • Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
  • Health Sciences › Medicine › Surgery › Cardiovascular Syncope and Autonomic Disorders
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Rate Variability and Autonomic Control
Keywords
postural orthostatic tachycardia syndrome, gastrointestinal symptoms, delayed gastric emptying, Ehlers-Danlos syndrome, hypermobility type, autonomic neuropathy, gastric motility, gastrointestinal hormones, malnutrition, weight loss, connective tissue diseases
MeSH terms
Gastrointestinal Diseases, Humans, Postural Orthostatic Tachycardia Syndrome

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