Gastroparesis and Delayed Gastric Emptying
1 Burnet et al. 2004 — Gastric Emptying Is Slow in Chronic Fatigue Syndrome
Full Citation:: Burnet RB, Chatterton BE. Gastric emptying is slow in chronic fatigue syndrome. BMC Gastroenterology. 2004;4:32. DOI:: 10.1186/1471-230X-4-32 PMID:: 15619332 Study Design:: Cohort with radionuclide (scintigraphic) oesophageal clearance and simultaneous liquid/solid gastric emptying; historical controls; GI symptom questionnaire. Sample Size:: 32 CFS patients + 45 questionnaire controls; 32 underwent emptying studies. Key Findings::
- 23/32 patients showed delayed liquid gastric emptying and 12/32 delayed solid emptying
- Delay significantly correlated with mean upper GI symptom score (p $<$ 0.001)
- Nocturnal diarrhoea was a significant, previously unreported symptom
- Oesophageal clearance was not significantly different from controls and did not correlate with symptomsConclusion:: Upper GI symptoms in chronic fatigue syndrome are associated with objective changes in gastric emptying, providing direct radionuclide evidence of delayed gastric emptying in ME/CFS. Limitations:: n=32 moderate; single-centre; historical rather than matched contemporaneous controls; diagnostic criteria (Fukuda-era) not precisely stated in abstract; not independently replicated as a cohort.
2 Corrado et al. 1998 — Normal Gastric Emptying and Myoelectrical Activity in an Adolescent With CFS (Null)
Full Citation:: Corrado G, Riezzo G, Rea P, Pacchiarotti C, Cavaliere M, Cardi E. Normal gastric emptying time and myoelectrical activity in an adolescent with chronic fatigue syndrome. Italian Journal of Gastroenterology and Hepatology. 1998;30(4):444–445. PMID:: 9789150 Study Design:: Case report (single adolescent with CFS); gastric emptying time + electrogastrography (myoelectrical activity). Sample Size:: n=1. Key Findings::
- Normal gastric emptying time in the adolescent with CFS
- Normal myoelectrical activity on electrogastrographyConclusion:: This isolated single-case observation did not reproduce delayed gastric emptying; it is the null/negative data point for the ME/CFS gastric-emptying question. Limitations:: n=1 case report; pediatric/adolescent; low evidentiary weight; does not contradict the larger n=32 Burnet 2004 cohort.
3 Debourdeau et al. 2024 — Gastric Volumetry: Fundic Compliance and Visceral Hypersensitivity in Gastroparesis
Full Citation:: Debourdeau A, Gonzalez JM, Mathias F, Prost C, Barthet M, Vitton V. Gastric volumetry for the assessment of fundic compliance and visceral hypersensitivity in patients with gastroparesis: a retrospective comparative study. Scandinavian Journal of Gastroenterology. 2024;59(3):254–259. DOI:: 10.1080/00365521.2023.2279928 PMID:: 37975245 Study Design:: Retrospective comparative study; gastric volumetry to measure fundic compliance and visceral hypersensitivity in gastroparesis. Key Findings::
- Gastroparesis overlaps with impaired gastric accommodation and visceral hypersensitivity, the hallmark functional-dyspepsia mechanisms
- Volumetric assessment refines gastroparesis beyond simple emptying delayConclusion:: Gastroparesis and functional dyspepsia share accommodation and visceral-hypersensitivity physiology; this competing-mechanism overlap informs interpretation of GI symptoms in ME/CFS. Limitations:: Retrospective; single-centre; small/unstated sample; general gastroparesis population (not ME/CFS).
4 Wise et al. 2021 — Gastric Emptying Scans: Poor Adherence to National Guidelines
Full Citation:: Wise JL, Vazquez-Roque MI, McKinney CJ, Zickella MA, Crowell MD, Lacy BE. Gastric emptying scans: poor adherence to national guidelines. Digestive Diseases and Sciences. 2021;66(9):2897–2906. DOI:: 10.1007/s10620-020-06314-2 PMID:: 32418002 Study Design:: Multi-centre chart audit of gastric emptying scintigraphy (GES) protocol adherence. Key Findings::
- Widespread non-adherence to standardized GES protocols (meal standardization, 4-hour imaging, normative interpretation)
- Protocol variability undermines the comparability and validity of gastric-emptying resultsConclusion:: Diagnostic gastric-emptying studies in ME/CFS (and elsewhere) must be interpreted with attention to protocol adherence, otherwise false-positive and false-negative results are common. Limitations:: Audit of general-practice GES (not ME/CFS-specific); focuses on methodology rather than clinical outcomes.
5 Ingrosso et al. 2023 — Efficacy and Safety of Drugs for Gastroparesis: Network Meta-analysis
Full Citation:: Ingrosso MR, Camilleri M, Tack J, Ianiro G, Black CJ, et al. Efficacy and safety of drugs for gastroparesis: systematic review and network meta-analysis. Gastroenterology. 2023;164(4):642–654. DOI:: 10.1053/j.gastro.2022.12.014 PMID:: 36581089 Study Design:: Systematic review + network meta-analysis of prokinetic and anti-nausea drugs for gastroparesis. Key Findings::
- Best available comparative evidence for metoclopramide, domperidone, erythromycin, prucalopride, and related agents
- Includes adverse-effect and safety comparisons across prokineticsConclusion:: Provides the treatment-evidence backbone for prokinetic selection in gastroparesis, with explicit efficacy and safety trade-offs; no ME/CFS-specific data exist. Limitations:: General gastroparesis population (not ME/CFS); drug-specific subgroups vary in size; placebo-response and protocol heterogeneity across trials.
6 Patel et al. 2024 — Safety and Efficacy of 5-HT4 Agonists for Gastroparesis: Meta-analysis of RCTs
Full Citation:: Patel P, Zaher EA, Khataniar H, Ebrahim MA, Loganathan P, et al. Safety and efficacy of highly selective 5-hydroxytryptamine receptor 4 agonists for diabetic and idiopathic gastroparesis: a systematic review and meta-analysis of randomized controlled trials. Cureus. 2024;16(1):e51851. DOI:: 10.7759/cureus.51851 PMID:: 38327939 Study Design:: Systematic review and meta-analysis of RCTs of highly selective 5-HT4 agonists (prucalopride, velusetrag) for diabetic and idiopathic gastroparesis. Key Findings::
- 5-HT4 agonists improve gastric emptying and symptom measures in gastroparesis
- No excess pooled cardiovascular or QT signal was found in these RCTsConclusion:: Prucalopride-class prokinetics are a comparatively safer prokinetic option; relevant where cholinergic vagal drive is impaired and 5-HT4 agonism is an alternative pathway. Limitations:: Published in Cureus (lower-tier journal); general gastroparesis population; QT assessment across heterogeneous RCT protocols.
7 Camilleri & Jencks 2025 — Pharmacologic Treatments for Gastroparesis
Full Citation:: Camilleri M, Jencks KJ. Pharmacologic treatments for gastroparesis. Pharmacological Reviews. 2025;77(2):100019. DOI:: 10.1016/j.pharmr.2024.100019 PMID:: 40148033 Study Design:: Comprehensive pharmacology review of gastroparesis treatment (prokinetics, antiemetics, pylorus-targeting agents, neuromodulators). Key Findings::
- Glucagon-like peptide-1 agonists and opioid agents are recognised causes of medication-induced gastroparesis
- Metoclopramide remains the only FDA-approved drug for gastroparesisConclusion:: Provides the general gastroenterology guidance basis for the contraindication caution on GLP-1 receptor agonists in gastroparesis. Limitations:: Review (not primary data); general gastroparesis population (not ME/CFS).
8 Nauck et al. 2011 — GLP-1-Induced Deceleration of Gastric Emptying in Humans
Full Citation:: Nauck MA, Kemmeries G, Holst JJ, Meier JJ. Rapid tachyphylaxis of the glucagon-like peptide 1-induced deceleration of gastric emptying in humans. Diabetes. 2011;60(5):1561–1565. DOI:: 10.2337/db10-0474 PMID:: 21430088 Study Design:: Human mechanistic study; nine healthy volunteers, intravenous GLP-1 versus placebo, two liquid mixed meals, gastric-emptying measurement. Key Findings::
- GLP-1 lowers postprandial glycaemia primarily through inhibition of gastric emptying
- GLP-1 significantly decelerated gastric emptying; the effect attenuated by the second meal (rapid tachyphylaxis, vagally mediated)Conclusion:: Establishes the emptying-slowing pharmacology of GLP-1 that underlies the contraindication caution for GLP-1 receptor agonists in gastroparesis. Limitations:: Small (n=9) healthy-volunteer mechanistic study; native GLP-1 infusion rather than a long-acting receptor agonist; not ME/CFS.
9 Gupta & Lee 2016 — Diet and Complementary Medicine for Chronic Nausea/Vomiting and Gastroparesis
Full Citation:: Gupta E, Lee LA. Diet and complementary medicine for chronic unexplained nausea and vomiting and gastroparesis. Current Treatment Options in Gastroenterology. 2016;14(4):401–409. DOI:: 10.1007/s11938-016-0104-0 PMID:: 27696279 Study Design:: Clinical review of dietary and complementary-medicine management for gastroparesis and chronic unexplained nausea/vomiting. Key Findings::
- Small, frequent, low-fat, low-fibre meals and liquid-nutrient optimisation are first-line dietary strategies
- Feeding strategies are central to nutritional management where oral intake failsConclusion:: Provides the nutritional-management framework (small meals, nutrient-dense liquids, feeding escalation) directly applicable to a severe ME/CFS case with gastroparesis. Limitations:: Review (not trial); general population; limited complementary-medicine evidence base.
10 Grover et al. 2011 — Cellular Changes in Diabetic and Idiopathic Gastroparesis
Full Citation:: Grover M, Farrugia G, Lurken MS, Bernard CE, Faussone-Pellegrini MS, et al. Cellular changes in diabetic and idiopathic gastroparesis. Gastroenterology. 2011;140(5):1575–1585.e8. DOI:: 10.1053/j.gastro.2011.01.046 PMID:: 21300066 Study Design:: Multicentre human gastric antral tissue study comparing gastroparesis and controls. Key Findings::
- Loss of interstitial cells of Cajal (ICC) in diabetic and idiopathic gastroparesis
- Decreased enteric nerve fibres and altered macrophage populations in gastric antrumConclusion:: Gastroparesis involves enteric neuronal and ICC loss, not merely functional vagal failure; this is the structural mechanistic substrate relevant to the autonomic gastroparesis hypothesis. Limitations:: Cross-disease (diabetic/idiopathic gastroparesis, not ME/CFS); tissue sampling from surgical/specialist cohorts; no direct ME/CFS gastric histology.
11 Wang et al. 2009 — ICC and Enteric Nerve Loss and Decreased Gastric Emptying in Diabetic Mice
Full Citation:: Wang XY, Huizinga JD, Diamond J, Liu LWC. Loss of intramuscular and submuscular interstitial cells of Cajal and associated enteric nerves is related to decreased gastric emptying in streptozotocin-induced diabetes. Neurogastroenterology and Motility. 2009;21(10):1095–e92. DOI:: 10.1111/j.1365-2982.2009.01336.x PMID:: 19566589 Study Design:: Animal model (streptozotocin-induced diabetes in rodents); ICC + enteric nerve quantitation vs gastric emptying. Key Findings::
- Streptozotocin diabetes caused loss of intramuscular and submuscular ICC and associated enteric nerves
- This loss was related to decreased gastric emptyingConclusion:: Animal-model support that ICC and enteric-neuron loss causally drive delayed gastric emptying. Limitations:: Animal model (cross-species inference); rodent streptozotocin model is not ME/CFS.
12 Tseng et al. 2019 — Nonoral Nutrition and Hydration Support in Adults With POTS
Full Citation:: Tseng AS, Traub NA, Harris LA, Crowell MD, Hoffman-Snyder CR, et al. Factors associated with use of nonoral nutrition and hydration support in adult patients with postural tachycardia syndrome. JPEN. Journal of Parenteral and Enteral Nutrition. 2019;43(6):734–741. DOI:: 10.1002/jpen.1493 PMID:: 30561086 Study Design:: Retrospective cohort of adult POTS patients at a tertiary referral centre. Key Findings::
- GI dysmotility and feeding intolerance were factors associated with need for nonoral (enteral/parenteral) nutrition
- Autonomic cohorts require enteral/parenteral support, documenting the nutritional-failure risk in dysautonomiaConclusion:: Provides the clinical precedent that autonomic (POTS) cohorts progress to nonoral nutritional support, directly relevant to severe ME/CFS with gastroparesis and nutritional failure. Limitations:: POTS population (weight 0.80); retrospective; single-centre.
13 Aziz et al. 2025 — AGA Clinical Practice Update: GI and Autonomic/Immune Dysfunction in Hypermobile EDS
Full Citation:: Aziz Q, Harris LA, Goodman BP, Simrén M, Shin A. AGA clinical practice update on gastrointestinal manifestations and autonomic or immune dysfunction in hypermobile Ehlers-Danlos syndrome: expert review. Clinical Gastroenterology and Hepatology. 2025;23(8):1291–1302. DOI:: 10.1016/j.cgh.2025.02.015 PMID:: 40387691 Study Design:: Expert-consensus AGA Clinical Practice Update (expert review). Key Findings::
- GI dysmotility and gastroparesis co-occur with autonomic dysfunction and POTS in hypermobile Ehlers-Danlos syndrome
- Provides a diagnostic and management framework for GI + autonomic overlapConclusion:: A transferable framework for the ME/CFS-hEDS-POTS severe case presenting with gastroparesis and dysautonomia. Limitations:: hEDS/POTS population (weight 0.80); expert consensus, not trial data.
14 Shakhatreh et al. 2019 — Metoclopramide for Diabetic Gastroparesis (Harm/Safety)
Full Citation:: Shakhatreh M, Jehangir A, Malik Z, Parkman HP. Metoclopramide for the treatment of diabetic gastroparesis. Expert Review of Gastroenterology and Hepatology. 2019;13(8):711–721. DOI:: 10.1080/17474124.2019.1645594 PMID:: 31314613 Study Design:: Clinical review of metoclopramide pharmacology, efficacy, and tolerability in diabetic gastroparesis. Key Findings::
- Metoclopramide is the only FDA-approved drug for gastroparesis; acts via dopamine antagonism (peripheral prokinetic + central anti-emetic)
- Carries a black-box warning for use beyond 12 weeks due to tardive dyskinesia (TD), which may be irreversible
- Other CNS side effects: drowsiness, restlessness, hyperprolactinaemiaConclusion:: The chronic-use safety conflict is central: metoclopramide is effective but TD risk limits long-term use, so duration and monitoring matter in a chronic ME/CFS gastroparesis patient. Limitations:: Review; general gastroparesis population (diabetic focus); does not address ME/CFS-specific risk or drug interactions.