Indigestion, also known as dyspepsia or upset stomach, is a condition of impaired digestion.[2] Symptoms may include upper abdominal fullness, heartburn, nausea, belching, or upper abdominal pain.[3] People may also experience feeling full earlier than expected when eating.[4] Indigestion is relatively common, affecting 20% of people at some point during their life, and is frequently caused by gastroesophageal reflux disease (GERD) or gastritis.[1][5]

Other namesDyspepsia
SymptomsUpper abdominal pain[1]

Indigestion is subcategorized as "organic" or "functional", but making the diagnosis can prove challenging for physicians.[6] Organic indigestion is the result of an underlying disease, such as gastritis, peptic ulcer disease (an ulcer of the stomach or duodenum), or cancer.[6] Functional indigestion (previously called nonulcer dyspepsia)[7] is indigestion without evidence of underlying disease.[8] Functional indigestion is estimated to affect about 15% of the general population in western countries and accounts for a majority of dyspepsia cases.[7][9]

In elderly patients (60 years of age or older) or with worrisome symptoms such as trouble swallowing, weight loss, or blood loss, an endoscopy (a procedure whereby a camera attached to a flexible tube is inserted down the throat and into the stomach) is recommended to further assess and find a potential cause.[1] In patients younger than 60 years of age, testing for the bacteria H. pylori and if positive, treatment of the infection is recommended.[1] More details about how indigestion is diagnosed and treated can be found below.

Signs and symptomsEdit


Patients experiencing indigestion likely report one, a combination of, or all of the following symptoms:[6][10]

  • upper abdominal pain or discomfort
  • bloating
  • early satiety
  • postprandial fullness
  • nausea with or without vomiting
  • anorexia
  • regurgitation
  • belching


There may be abdominal tenderness, but this finding is nonspecific and is not required to make a diagnosis.[10] However, there are physical exam signs that may point to a different diagnosis and underlying cause for a patient's reported discomfort. A positive Carnett sign (focal tenderness that increases with abdominal wall contraction and palpation) suggests an etiology involving the abdominal wall musculature. Cutaneous dermatomal distribution of pain may suggest a thoracic polyradiculopathy. Tenderness to palpation over the right upper quadrant, or Murphy's sign, may suggest cholecystitis or gallbladder inflammation.[11]

Alarm symptomsEdit

Also known as Alarm features, alert features, red flags, or warning signs in gastrointestinal (GI) literature.

Alarm features are thought to be associated with serious gastroenterologic disease and include:[12]


Indigestion is a diagnosis related to a combination of symptoms that can be attributed to "organic" or "functional" causes.[13] Organic dyspepsia should have pathological findings upon endoscopy, like an ulcer in the stomach lining in peptic ulcer disease.[13] Functional dyspepsia is unlikely to be detected on endoscopy but can be broken down into two subtypes, epigastric pain syndrome (EPS) and post-prandial distress syndrome (PDS).[14] In addition, indigestion could be caused by medications, food, or other disease processes.

Organic DyspepsiaEdit


Esophagitis is an inflammation of the esophagus, most commonly caused by gastroesophageal reflux disease (GERD).[6] It is defined by the sensation of "heartburn" or a burning sensation in the chest as a result of inappropriate relaxation of the lower esophageal sphincter at the site where the esophagus connects to the stomach. It is often treated with proton pump inhibitors. If left untreated, the chronic damage to the esophageal tissues poses a risk of developing cancer.[6] A meta-analysis showed risk factors for developing GERD included age equal to or greater than 50, smoking, the use of non-steroid anti-inflammatory medications, and obesity.[15]


Common causes of gastritis include peptic ulcer disease, infection, or medications.

Peptic Ulcer DiseaseEdit
Helicobacter pylori infectionEdit

The role of Helicobacter pylori in functional dyspepsia is controversial, and no clear causal relationship has been established. This is true for both the symptom profile and pathophysiology of functional dyspepsia. Although some epidemiologic studies have suggested an association between H. pylori infection and functional dyspepsia, others have not. The discrepancy may stem in part from differences in methodology and lack of adequate consideration of confounding factors such as past history of peptic ulcer disease and socioeconomic status.[16] Controlled trials disagree about whether or not H. pylori eradication is beneficial in functional dyspepsia, with roughly half of the trials showing improvement and the other half no improvement. In a multicenter U.S. trial that randomized 240 people to treatment or placebo, and followed them for 12 months, 28% of treated people versus 23% of those receiving placebo reported relief of symptoms at the 12-month follow-up. Similarly, recent European trials have not shown significant differences in symptoms after H. pylori eradication as compared with controls. Systematic reviews of eradication have been conducted, with varying results. A systematic review in the Annals of Internal Medicine suggested no statistically significant effect, with an odds ratio (OR) for treatment success versus control of 1.29 (95% CI, 0.89–1.89; P = 0.18). Still, no effect was seen after adjusting for heterogeneity and for cure of H. pylori. In contrast, a Cochrane review found a small but statistically significant effect in curing symptoms (H. pylori cure vs placebo, 36% vs 30%, respectively).[17][18]

Pancreatobiliary DiseaseEdit

These include cholelithiasis, chronic pancreatitis, and pancreatic cancer.

Duodenal micro-inflammationEdit

Duodenal micro-inflammation caused by an altered duodenal gut microbiota, reactions to foods (mainly gluten proteins) or infections may induce dyspepsia symptoms in a subset of people.[19]

Functional DyspepsiaEdit

Functional dyspepsia is the most common cause of chronic heartburn. More than 70% of people have no obvious organic cause for their symptoms after evaluation.[13] Symptoms may arise from a complex interaction of increased visceral afferent sensitivity, gastric delayed emptying (gastroparesis) or impaired accommodation to food. Anxiety is also associated with functional dyspepsia. In some people, it appears before the onset of gut symptoms; in other cases, anxiety develops after onset of the disorder, which suggests that a gut-driven brain disorder may be a possible cause. Although benign, these symptoms may be chronic and difficult to treat.[20]

Wheat and dietary fats can lead to dyspepsia and their reduction or withdrawal may improve symptoms.[21]

Food or drug intoleranceEdit

Acute, self-limited dyspepsia may be caused by overeating, eating too quickly, eating high-fat foods, eating during stressful situations, or drinking too much alcohol or coffee. Many medications cause dyspepsia, including aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs), antibiotics (metronidazole, macrolides), diabetes drugs (metformin, Alpha-glucosidase inhibitor, amylin analogs, GLP-1 receptor antagonists), antihypertensive medications (angiotensin converting enzyme [ACE] inhibitors, Angiotensin II receptor antagonist), cholesterol-lowering agents (niacin, fibrates), neuropsychiatric medications (cholinesterase inhibitors [donepezil, rivastigmine]), SSRIs (fluoxetine, sertraline), serotonin-norepinephrine-reuptake inhibitors (venlafaxine, duloxetine), Parkinson drugs (Dopamine agonist, monoamine oxidase [MAO]-B inhibitors), corticosteroids, estrogens, digoxin, iron, and opioids.[22]

Systemic DiseasesEdit

There are a number of systemic diseases that may involve dyspepsia, including coronary disease, congestive heart failure, diabetes mellitus, hyperparathyroidism, thyroid disease, and chronic kidney disease.

Post-infectious Causes of DyspepsiaEdit

Gastroenteritis increases the risk of developing chronic dyspepsia. Post-infectious dyspepsia is the term given when dyspepsia occurs after an acute gastroenteritis infection. It is believed that the underlying causes of post-infectious IBS and post-infectious dyspepsia may be similar and represent different aspects of the same pathophysiology.[23]


Psychosomatic and cognitive factors are important in the evaluation of people with chronic dyspepsia. The psychiatric hypothesis holds that the symptoms of dyspepsia may be due to depression, increased anxiety, or a somatization disorder. Epidemiological studies suggest there is an association between functional dyspepsia and psychological disorders. Symptoms of neurosis, anxiety, hypochondriasis, and depression are more common in people being evaluated for unexplained gastrointestinal complaints than in healthy controls. Comparisons of functional and organic dyspepsia have demonstrated that people with functional dyspepsia are less likely to have decreased stress or anxiety at 1-year follow-up after being reassured of having no serious disease. This suggests that functional dyspepsia symptoms are long-lasting, compared with those of organic dyspepsia, and that the emotional ties are strong.[24]


In people without red flags, it is recommended to test for H. pylori noninvasively and to perform upper GI endoscopy in those who test positive.[25] In most cases, the clinical history is of limited use in distinguishing between organic causes and functional dyspepsia. A large systematic review of the literature was recently performed to evaluate the effectiveness of diagnosing organic dyspepsia by clinical opinion versus computer models in people referred for upper endoscopy. The computer models were based on patient demographics, risk factors, historical items, and symptoms. The study showed that neither clinical impression nor computer models were able to adequately distinguish organic from functional disease.[26]

Medication-related dyspepsia is usually related to NSAIDs and can be complicated by bleeding or ulceration with perforation of the stomach wall.


Functional and undifferentiated dyspepsia have similar treatments. Drug therapy decisions are difficult because trials included heartburn in the definition of indigestion. This led to the results favoring proton pump inhibitors (PPIs), which are effective for the treatment of heartburn.

Traditional therapies used for this diagnosis include lifestyle modification, antacids, H2-receptor antagonists (H2-RAs), prokinetic agents, and antiflatulents. It has been noted that one of the most frustrating aspects of treating functional dyspepsia is that these traditional agents have been shown to have little or no efficacy.[27]

Acid suppressionEdit

Antacids and sucralfate were found to be no better than placebo in a literature review.[28] H2-RAs have been shown to have marked benefit in poor quality trials (30% relative risk reduction[28]), but only a marginal benefit in good quality trials.[27] Prokinetic agents would empirically seem to work well since delayed gastric emptying is considered a major pathophysiological mechanism in functional dyspepsia.[27] They have been shown in a meta-analysis to produce a relative risk reduction of up to 50%, but the studies evaluated to come to this conclusion used the drug cisapride which has since been removed from the market (now only available as an investigational agent)[29] due to serious adverse events such as torsades, and publication bias has been cited as a potential partial explanation for such a high benefit.[28] Modern prokinetic agents such as metoclopramide, erythromycin and tegaserod have little or no established efficacy and often result in substantial side effects.[28] Simethicone is of some value, as one trial suggests potential benefit over placebo and another shows equivalence with cisapride.[28] So, with the somewhat recent advent of the proton pump inhibitor (PPI) class of medications, the question of whether these new agents are superior to traditional therapy has arisen.[citation needed]

Currently, PPIs are, depending on the specific drug, FDA indicated for erosive esophagitis, gastroesophageal reflux disease (GERD), Zollinger-Ellison syndrome, eradication of H. pylori, duodenal and gastric ulcers, and NSAID-induced ulcer healing and prevention, but not functional dyspepsia. However, evidence-based guidelines and literature evaluate the use of PPIs for this indication. A helpful chart summarizing the major trials is available from the functional dyspepsia guidelines published in the World Journal of Gastroenterology in 2006.[27]


Due to the association of indigestion with non-celiac gluten sensitivity, a gluten-free diet can relieve the symptoms.[19]

Alternative medicineEdit

A 2002 systemic review of herbal products found that several herbs, including peppermint and caraway, have anti-dyspeptic effects for non-ulcer dyspepsia with "encouraging safety profiles".[30] A 2004 meta-analysis of the multiple herbal extract Iberogast found it to be more effective than placebo in people with functional dyspepsia.[31]


The word dyspepsia is from the Greek δυσ- dys-, "bad" or "difficult", and πέψις pepsis "digestion".[citation needed]

See alsoEdit


  1. ^ a b c d e Eusebi, Leonardo H; Black, Christopher J; Howden, Colin W; Ford, Alexander C (11 December 2019). "Effectiveness of management strategies for uninvestigated dyspepsia: systematic review and network meta-analysis". BMJ. 367: l6483. doi:10.1136/bmj.l6483. PMC 7190054. PMID 31826881.
  2. ^ "dyspepsia" at Dorland's Medical Dictionary
  3. ^ Duvnjak, Marko (2011). Dyspepsia in clinical practice (1. Aufl. ed.). New York: Springer. p. 2. ISBN 9781441917300.
  4. ^ Talley NJ, Vakil N (October 2005). "Guidelines for the management of dyspepsia". Am. J. Gastroenterol. 100 (10): 2324–37. PMID 16181387.
  5. ^ Zajac, P; Holbrook, A; Super, ME; Vogt, M (March–April 2013). "An overview: Current clinical guidelines for the evaluation, diagnosis, treatment, and management of dyspepsia". Osteopathic Family Physician. 5 (2): 79–85. doi:10.1016/j.osfp.2012.10.005.
  6. ^ a b c d e Greenberger, Norton; Blumberg, R.S.; Burakoff, Robert (2016). Current diagnosis & treatment. Gastroenterology, hepatology, and endoscopy (3 ed.). New York. ISBN 978-1-259-25097-2. OCLC 925478002.
  7. ^ a b Saad RJ, Chey WD (August 2006). "Review article: current and emerging therapies for functional dyspepsia" (PDF). Aliment. Pharmacol. Ther. 24 (3): 475–92. doi:10.1111/j.1365-2036.2006.03005.x. hdl:2027.42/74835. PMID 16886913.
  8. ^ van Kerkhoven LA, van Rossum LG, van Oijen MG, Tan AC, Laheij RJ, Jansen JB (September 2006). "Upper gastrointestinal endoscopy does not reassure people with functional dyspepsia" (PDF). Endoscopy. 38 (9): 879–85. doi:10.1055/s-2006-944661. PMID 16981103. Archived from the original (PDF) on 2011-07-27.
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  10. ^ a b "Rome IV Criteria". Rome Foundation. Retrieved 2022-01-19.
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  14. ^ Sayuk, Gregory S.; Gyawali, C. Prakash (2020-09-01). "Functional Dyspepsia: Diagnostic and Therapeutic Approaches". Drugs. 80 (13): 1319–1336. doi:10.1007/s40265-020-01362-4. ISSN 1179-1950.
  15. ^ Eusebi, Leonardo H.; Ratnakumaran, Raguprakash; Yuan, Yuhong; Solaymani-Dodaran, Masoud; Bazzoli, Franco; Ford, Alexander C. (March 2018). "Global prevalence of, and risk factors for, gastro-oesophageal reflux symptoms: a meta-analysis". Gut. 67 (3): 430–440. doi:10.1136/gutjnl-2016-313589. ISSN 1468-3288. PMID 28232473.
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  29. ^ Information regarding withdrawal of Propulsid (cisapride) by Janssen Pharmaceutica. From FDA
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  31. ^ Melzer J, Rösch W, Reichling J, Brignoli R, Saller R (2004). "Meta-analysis: phytotherapy of functional dyspepsia with the herbal drug preparation STW 5 (Iberogast)". Aliment. Pharmacol. Ther. 20 (11–12): 1279–87. doi:10.1111/j.1365-2036.2004.02275.x. PMID 15606389.

External linksEdit