Gastric emptying is slow in chronic fatigue syndrome
© Burnet and Chatterton; licensee BioMed Central Ltd. 2004
Received: 15 October 2004
Accepted: 26 December 2004
Published: 26 December 2004
Gastrointestinal symptoms are common in patients with Chronic Fatigue Syndrome (CFS). The objective of this study was to determine the frequency of these symptoms and explore their relationship with objective (radionuclide) studies of upper GI function.
Thirty-two (32) patients with CFS and 45 control subjects completed a questionnaire on upper GI symptoms, and the 32 patients underwent oesophageal clearance, and simultaneous liquid and solid gastric emptying studies using radionuclide techniques compared with historical controls.
The questionnaires showed a significant difference in gastric (p > 0.01) symptoms and swallowing difficulty. Nocturnal diarrhoea was a significant symptom not previously reported.
5/32 CFS subjects showed slightly delayed oesophageal clearance, but overall there was no significant difference from the control subjects, nor correlation of oesophageal clearance with symptoms. 23/32 patients showed a delay in liquid gastric emptying, and 12/32 a delay in solid gastric emptying with the delay significantly correlated with the mean symptom score (for each p ≪ 0.001).
GI symptoms in patients with chronic fatigue syndrome are associated with objective changes of upper GI motility.
Chronic Fatigue Syndrome (CFS) is a descriptive term used to define a classifiable pattern of symptoms that cannot be attributed to any alternative condition . It can be associated with immunological alterations, neuro-endocrine changes , sleep disturbance and disturbed neurocognitive performance with abnormal cerebral perfusion , but the pathophysiological significance of these is uncertain. Skeletal neuromuscular function is usually normal in CFS sufferers .
Many with CFS have gastro-intestinal (GI) symptoms, which are often unrecognised as being part of CFS. The commonest of the upper GI symptoms include fullness and bloating after a small meal, abdominal distension, nausea, and loss of appetite. Lower GI tract symptoms have considerable overlap with irritable bowel syndrome .
The hypothesis explored in this paper is that symptoms of possible upper gastrointestinal origin are more common in patients with CFS and are related to upper gastrointestinal motility as assessed by radionuclide methods.
Consecutive patients with CFS who met the Fukuda criteria  for CFS were all seen by a single physician (RB). Patients with any medical condition which could account for chronic fatigue, a BMI > 30, previous GI surgery or medication affecting the rate of gastric emptying were excluded. Overt psychiatric disease was excluded at the interview. The patients were asked to self assess their percentage reduction in activity from prior to the onset of CFS as a marker of severity. Gastro-Intestinal symptoms were evaluated in patients and controls by a standard questionnaire prior to the gastric emptying studies .
Symptoms were divided into "oesophageal" (dysphagia, heart burn, acid regurgitation), "gastric": (anorexia, nausea, early satiety, bloating, abdominal distension, intermittent abdominal pain), "other" frequency of bowel actions, consistency of stools, presence or absence of diarrhoea, urgency and timing.
Symptoms were scored. 0, none, 1, mild (symptom could be ignored), 2, moderate (symptom could not be ignored, but did not influence daily activities), 3, severe, (symptom influenced daily activities). A mean symptom score (maximum score 3) for the 6 gastric symptoms, and 3 oesophageal symptoms was obtained.
The volunteer control subjects who completed the questionnaire were in regular full time employment, with no history of excessive fatigue, on no GI medication, and had no previous GI surgery.
Radionuclide measurement of upper GI motility
Details and normal ranges of this double isotope test have been previously published . The solid meal consisted of 100 g of cooked ground beef containing 40MBq in-vivo labelled 99mTc-sulfur colloid-chicken liver, and the liquid meal consisted of 150 ml of 10% dextrose in water containing with 20 MBq of 67Ga-ethylenediaminetetraacetic acid (EDTA). All medication (except oral contraceptives) was discontinued for 24 hours prior to each study. The test was performed at 10 am (after an overnight fast) and monitored for at least two hours with the subject in the sitting position with the scintillation camera behind. The study commenced with a standardised oesophageal clearance study (solid bolus) followed by eating the solid meal and then immediately drinking the glucose solution. Each study was continued for at least 2 hours. Oesophageal clearance was expressed as time to 95% clearance (ref range < 93 sec) , Liquid gastric emptying as half-clearance time (ref 4–31 minutes) and solid emptying as amount remaining at 100 min (ref 4–61%).
The GI questionnaires were compared between CFS and control by Chi2, and Gastric emptying indices compared with historical normal range (t test comparison of means), and correlated with the mean symptom score (± SD).
The Study was approved by The Human Research Ethics Committee of the Royal Adelaide Hospital and informed consent given by the subjects.
Characteristics of CFS subjects vs controls. (SD)
F 22, M10
F 37, M 8
38.5 ± 13.9
34.4 ± 8.5
68.1 ± 12.1
71.8 ± 11.6
Duration CFS (yr)
9.5 ± 6.8
Severity, % reduction activity
Percentage frequency of any gastrointestinal symptoms.
CFS % (n = 32)
CONTROLS % (n = 45)
Fullness after small meal
Loss of appetite
Bowel movements/ day (mean)
Consistency Formed %
Nocturnal diarrhoea %
Faecal Urgency %
G-I symptoms are common in patients with CFS. Abdominal pain is distressing , often requiring analgesia for relief. A previously unrecorded symptom in CFS patients is nocturnal diarrhoea, which disrupts an already disturbed sleep pattern. The most common upper GI symptom is fullness and bloating after a small meal. The usual medical explanation for the gut symptoms is 'irritable bowel'. Unless specific G-I questions are put to the CFS patient they will not spontaneously discuss these symptoms.
An abnormality in solid or liquid emptying or combinations of these study parameters was more common in the more symptomatic patients, and liquid was more frequently affected. This is the opposite of the abnormality seen in diabetic subjects , where the major abnormality, delay in the solid phase of gastric emptying has been ascribed to autonomic dysfunction or hyperglycaemia. A group of elderly subjects with a number of neurological defects showed a delay in the liquid rather than the solid emptying .
Symptoms and delayed gastric emptying in diabetic gastroparesis studies have not correlated well. In this study there is a good correlation with symptoms. The commonest of these was early satiety, fullness and bloating after eating. There was though a poor correlation with oesophageal symptoms and a disorder of oesophageal emptying.
GI motility is complex, with central, local neuromuscular and humoral influences. Non-specific endocrine disturbances have been demonstrated in CFS, but the relevance of these is unknown with regard to GI disturbances. Skeletal muscle fatigue appears to be of central rather than peripheral origin, but again it is not known whether this may be extrapolated to visceral muscle.
Inconclusive central changes have been documented. The impact of disturbed sensory function is unknown, and this could also involve peripheral nerves or the central processing of sensory information.
Diagnostically, there is overlap between CFS, functional dyspepsia and fibromyalgia and all may be related to abnormal sensory processing [10, 12, 13]. Altered gastric emptying has been shown in association with irritable bowel syndrome .
These observations indicate that there is measurable disturbance in upper gut motility corresponding with symptoms in CFS. Although the cause for these findings is not apparent in this study, the more prominent delay in liquid rather than solid emptying may point to a central rather than a peripheral aetiology. The gastro-intestinal tract and function should be properly investigated and the symptoms not necessarily be ascribed to irritable bowel syndrome.
RB examined the patients and analysed the clinical data, BC performed the Nuclear Medicine studies, drafted the manuscript and performed the statistics. Both read and approved the final manuscript.
- Working Group of the Royal Australasian College of Physicians Chronic fatigue syndrome. Clinical practice guidelines–2002. Med J Aust. 2002, 176 (Suppl): S23-56.Google Scholar
- Cleare AJ: The neuroendocrinology of chronic fatigue syndrome. Endocr Rev. 2003, 24: 236-52.View ArticlePubMedGoogle Scholar
- Schmaling KB, Lewis DH, Fiedelak JI, Mahurin R, Buchwald DS: Single-photon emission computerized tomography and neurocognitive function in patients with chronic fatigue syndrome. Psychosom Med. 2003, 65: 129-36. 10.1097/01.PSY.0000038942.33335.9B.View ArticlePubMedGoogle Scholar
- Sargent C, Scroop GC, Nemeth PM, Burnet RB, Buckley JD: Maximal oxygen uptake and lactate metabolism are normal in chronic fatigue syndrome. Med Sci Sports Exerc. 2002, 34: 51-6. 10.1097/00005768-200201000-00009.View ArticlePubMedGoogle Scholar
- Gomborone JE, Gorard DA, Dewsnap PA, Libby GW, Farthing MJ: Prevalence of irritable bowel syndrome in chronic fatigue. J R Coll Physicians Lond. 1996, 30 (6): 512-3.PubMedGoogle Scholar
- Fukuda K, Straus SE, Hickie I, Sharpe MC, Dobbins JG, Komaroff A: The chronic fatigue syndrome: a comprehensive approach to its definition and study. Ann Intern Med. 1994, 121: 953-959.View ArticlePubMedGoogle Scholar
- Horowitz M, Harding PE, Chatterton BE, Collins PJ, Shearman DJ: Acute and chronic effects of domperidone on gastric emptying in diabetic autonomic neuropathy. Dig Dis Sci. 1985, 30: 1-9.View ArticlePubMedGoogle Scholar
- Horowitz M, Harding PE, Maddox AF, Wishart JM, Akkermans LM, Chatterton BE, Shearman DJ: Gastric and oesophageal emptying in patients with type 2 diabetes mellitus. Diabetologicia. 1989, 32: 151-159. 10.1007/BF00265086.View ArticleGoogle Scholar
- Maddern GJ, Horowitz M, Jamieson GG, Chatterton BE, Collins PJ, Roberts-Thomson P: Abnormalities of esophageal and gastric emptying in progressive systemic sclerosis. Gastroenterology. 1984, 87: 922-6.PubMedGoogle Scholar
- Wilhelmsen I: Somatization, sensitization, and functional dyspepsia. Scand J Psychol. 2002, 43: 177-80. 10.1111/1467-9450.00284.View ArticlePubMedGoogle Scholar
- Evens MA, Trigg EJ, Cheung M: Gastric emptying rate in the elderly: Implications for drug therapy. J Am Geriatric Soc. 1981, 29: 201-5.View ArticleGoogle Scholar
- Fisher M, Krilov LR, Ovadia M: Chronic fatigue syndrome and eating disorders: concurrence or coincidence?. Int J Adolesc Med Health. 2002, 14: 307-16.PubMedGoogle Scholar
- Whitehead WE, Palsson O, Jones KR: Systematic review of the comorbidity of irritable bowel syndrome with other disorders: what are the causes and implications?. Gastroenterology. 2002, 122: 1140-56.View ArticlePubMedGoogle Scholar
- Caballero-Plasencia AM, Valenzuela-Barranco M, Herrerias-Gutierrez JM, Esteban-Carretero JM: Altered gastric emptying in patients with irritable bowel syndrome. Eur J Nucl Med. 1999, 26: 404-9. 10.1007/s002590050404.View ArticlePubMedGoogle Scholar
- The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-230X/4/32/prepub
This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.