Effects and mechanisms of acupuncture and electroacupuncture for functional dyspepsia: A systematic review

Table 1 Rome IV criteria for functional dyspepsia

Functional dyspepsia diagnostic criteria12
One or more of the following:
Bothersome postprandial fullness
Bothersome early satiation
Bothersome epigastric pain
Bothersome epigastric burning
AND
No evidence of structural disease (including at upper endoscopy) that is likely to explain the symptoms
Postprandial distress syndrome diagnostic criteria2
Must include one or both of the following at least 3 d per wk:
Bothersome postprandial fullness (i.e. severe enough to impact on usual activities)
Bothersome early satiation (i.e. severe enough to prevent finishing a regular-size meal)
No evidence of organic, systemic, or metabolic disease that is likely to explain the symptoms on routine investigations (including at upper endoscopy)
Supportive remarks:
Postprandial epigastric pain or burning, epigastric bloating, excessive belching, and nausea can also be present
Vomiting warrants consideration of another disorder
Heartburn is not a dyspeptic symptom but may often coexist
Symptoms that are relieved by evacuation of feces or gas should generally not be considered as part of dyspepsia
Other individual digestive symptoms or groups of symptoms, e.g., from gastroesophageal reflux disease and the irritable bowel syndrome may coexist with PDS
Epigastric pain syndrome diagnostic criteria2
Must include at least 1 of the following symptoms at least 1 d a week:
Bothersome epigastric pain (i.e. severe enough to impact on usual activities)
AND/OR
Bothersome epigastric burning (i.e. severe enough to impact on usual activities)
No evidence of organic, systemic, or metabolic disease that is likely to explain the symptoms on routine investigations (including at upper endoscopy)
Supportive remarks:
Pain may be induced by ingestion of a meal, relieved by ingestion of a meal, or may occur while fasting
Postprandial epigastric bloating, belching, and nausea can also be present
Persistent vomiting likely suggests another disorder
Heartburn is not a dyspeptic symptom but may often coexist
The pain does not fulfill biliary pain criteria
Symptoms that are relieved by evacuation of feces or gas generally should not be considered as part of dyspepsia
Other digestive symptoms (such as from gastroesophageal reflux disease and the irritable bowel syndrome) may coexist with EPS

¹Must fulfill criteria for B1a. Postprandial distress syndrome and/or epigastric pain syndrome.

²Criteria fulfilled for the last 3 mo with symptom onset at least 6 mo before diagnosis. EPS: Epigastric pain syndrome; PDS: Postprandial distress syndrome.

Table 2 Characteristics of included studies of acupuncture vs sham, medication or no treatment in treating functional dyspepsia

Ref.	Study design	Partial inclusion (details)	Participants	Interventions (acupoints)	Main results (scales)	Mechanism research
Liu et al[26], 2008	Cross-over	Yes (chronic stage included)	n: 27 (F 18); Age (mean): 40.3 ± 4.5; groups (n): Verum A (27), Sham A (27); Diagnosis: Rome II	EXP: TEA (PC6, ST36); CONT: Sham TEA (2 non-acupoints); duration and frequency: 30 min, twice per day, for 2 wk	Decreased dyspepsia symptom scores by 55% in TEA group (dP < 0.01) (symptom scores without identified source)	Gastric motility (myoelectrical activity); neuroactivity (autonomic function); GI hormones
Zeng et al[27], 2012	Parallel	No	n: 64 (F 39); Age (mean, 95%CI): Verum A (23.97, 22.90-25.04), sham A (23.83, 22.67-25.00); groups (n): Verum A (34), sham A (30); diagnosis (subtype): Rome III (PDS)	EXP: EA (ST34, ST36, ST40, ST42); CONT: Sham EA (4 non-acupoints); duration and frequency: 30 min, once per day, 20 sessions in 4 wk	Decreased symptom score in EA greater than sham EA (gP < 0.05) (SID); clinically improved QOL in EA not in sham EA (NDI for QOL)	Brain function
Ji et al[28], 2014	Cross-over	No	n: 28; age (mean): 44.1 ± 9.4; Groups (n): Verum A (28), sham A (28); diagnosis (subtype): Rome III (PDS)	EXP: TEA (PC6, ST36); CONT: Sham TEA (2 non-acupoints); duration and frequency: 2 h, thrice per day, for 2 wk	Improved dyspeptic symptoms in TEA (cP < 0.05) not in sham TEA (GCSI); improved 4 domains of QOL in TEA (cP < 0.05) not in sham TEA (SF-36)	Gastric motility (myoelectrical activity and gastric emptying); gastric accommodation; mental status
Jin et al[29], 2015	Parallel	Yes (serum gastrin concentration and gastric slow wave excluded)	n: 56 (F 35); age (mean): Verum A (49.29 ± 10.32), sham A (48.25 ± 11.40); groups (n): Verum A (28), sham A (28); diagnosis: Rome III	EXP: MA (ST36, KI3 ± GB4, PC6, HT7); CONT: Sham MA (non-acupoints); duration and frequency: 20-60 min in EXP/20 min in CONT, once every other d, for 4 wk	Improved dyspeptic symptoms in MA and better than sham MA (iP < 0.05) (NDI); improved QOL in MA and greater than sham MA (iP < 0.05) (SF-36)	Mental status
Xu et al[30], 2015	Cross-over	Yes (TEA and sham TEA sessions included)	n: 8; age (mean): Not mentioned; groups (n): Verum A (8), sham A (8); diagnosis (subtype): Rome III (PDS)	EXP: TEA (PC6, ST36); CONT: Sham TEA (2 non-acupoints); Duration and frequency: 30 min, for 1 session	Improved dyspeptic symptoms in TEA and greater than sham TEA (cP < 0.05) (GCSI)	Gastric motility (myoelectrical activity); gastric accommodation; neuroactivity (autonomic function)
Zhang et al[31], 2015	Parallel	Yes (EA and control groups included)	n: 319 (F 157); age (mean): EA (42.6 ± 11.9); CONT (41.8 ± 12.2); groups (n): EA (159), CONT (160); diagnosis: Rome III	EXP: EA (ST36, CV12, PC6, LR3, SP4); CONT: Oral pantoprazole, amitriptylines and mosapride; duration and frequency: 15 min, twice per day, 5-d per wk in EXP; pantoprazole 20 mg with amitriptylines 5 mg, twice per day, and mosapride 5 mg, thrice per day in CONT; for 4 wk	Decreased symptom scores in EA and greater than CONT (aP < 0.05) (symptom scores without identified source); increased QOL scores in EA and better than CONT (aP < 0.05) (SF-36)	GI hormones; gastric motility (myoelectrical activity and gastric emptying)
Ko et al[32], 2016	Cross-over	Yes (from baseline to the first 4-wk included)	n: 76 (F 53); age (mean): MA (49.4 ± 12.1); CONT (49.1 ± 14.5); groups (n): MA (37), CONT (39); diagnosis: Rome III	EXP: MA (LI4, ST36, LR3, SP4, CV12 ± GB21, SI14, PC6, EX-HN5, ST34); CONT: No treatment; duration and frequency: 15 min, twice weekly, for 4 wk	Significantly higher PR in MA than CONT (eP < 0.001); lower symptom scores in MA than CONT (aP < 0.05) (NDI); improved QOL in MA (eP < 0.001) not in CONT (FD-QOL scale)	Mental status
Qiang et al[33], 2018	Parallel	No	n: 64 (F 38); age (mean): EA (42.6 ± 11.9); CONT (41.8 ± 12.2); groups (n): EA (32), CONT (32); diagnosis: Rome III	EXP: EA (ST36, SP6, SP4, PC6); CONT: Oral mosapride; duration and frequency: 30 min, once per day in EXP; 5 mg, thrice per day in CONT; for 30 d	Decreased symptom score in EA and greater than CONT (aP < 0.05) (LDQ); increased QOL scores in EA and better than CONT (aP < 0.05) (FD-QOL scale)	GI hormones

^aP < 0.05, ^bP < 0.01,

^eP < 0.001 vs control group;

^cP < 0.05,

^dP < 0.01, ^fP < 0.001 vs sham TEA;

^gP < 0.05 vs sham EA;

ⁱP < 0.05 vs sham MA. A: Acupuncture; CONT: Control group; EA: Electroacupuncture; EXP: Experimental group; F: Female; FD-QOL: Functional dyspepsia-related quality of life; GCSI: Gastroparesis cardinal symptom index; GI: Gastrointestinal; LDQ: Leeds dyspepsia questionnaire; MA: Manual acupuncture; NDI: Nepean dyspepsia index; PDS: Postprandial distress syndrome; PR: Proportion of responders; QOL: Quality of life; SF-36: Short form 36 health survey questionnaires; SID: Symptom index of dyspepsia; TEA: Transcutaneous electrical acustimulation; CI: Confidence interval.

Table 3 Characteristics of included studies in mechanism research

Ref.	Detecting items	Research techniques	Main results
Gastric motility
Liu et al[26], 2008	Gastric myoelectrical activity	EGG	Gastric slow wave not altered by TEA
Ji et al[28], 2014	Gastric myoelectrical activity; Gastric emptying	EGG; Radiogram	Increased percentage of normal slow wave in both fasting and postprandial stages in TEA (dP < 0.01) not in sham TEA; accelerated gastric emptying in TEA (fP < 0.001) not in sham TEA
Xu et al[30], 2015	Gastric myoelectrical activity	EGG	Increased dominant power and percentage of normal slow wave in postprandial stage in TEA compared with sham TEA (cP < 0.05)
Zhang et al[31], 2015	Gastric myoelectrical activity; gastric emptying	EGG; B-ultrasound	Improved basic frequency and slow wave frequency in EA compared with CONT (aP < 0.05); increased gastric half-emptying time and antrum movement index in EA compared with CONT (aP < 0.05)
Gastric accommodation
Ji et al[28], 2014	Gastric accommodation	Nutrient drinking test	Improved threshold of satiety volume (dP < 0.01) and maximum tolerance volume (fP < 0.001) in TEA not in sham TEA
Xu et al[30], 2015	Gastric accommodation	Satiety drinking test	Increased maximum tolerable volume in TEA compared with sham TEA (cP < 0.05)
GI hormones
Liu et al[26], 2008	Plasma NPY and motilin levels	Radioimmunoassay	Increased plasma NPY but not motilin level in TEA (cP < 0.05) not in sham TEA
Zhang et al[31], 2015	Plasma motilin level	Radioimmunoassay	Increased plasma motilin level in EA compared with CONT (aP < 0.05)
Qiang et al[33], 2018	Serum ghrelin, CGRP and GLP-1 levels	ELISA	Increased serum ghrelin and GLP-1 levels and decreased CGRP level in EA compared with CONT (aP < 0.05)
Mental status
Ji et al[28], 2014	Anxiety and depression	SAS/SDS	Decreased anxiety (dP < 0.01) and depression (cP < 0.05) scores in TEA not in sham TEA
Jin et al[29], 2015	Anxiety and depression	SAS/SDS	Improved anxiety (kP < 0.0001) and depression (kP < 0.001) status in MA compared with sham MA
Ko et al[32], 2016	Anxiety and depression	STAI/BDI	Decreased anxiety and depression scores in MA (bP < 0.01) not in CONT
Central and autonomic functions
Liu et al[26], 2008	Autonomic function	HRV derived from ECG	In fasting stage, higher HF activity (cP < 0.05) and lower LF/HF ratio (cP < 0.05) in TEA than that before the treatment but not in sham TEA
Zeng et al[27], 2012	Cerebral glycometabolism changes	PET-CT scans	Extensive deactivation in cerebral activities in EA compared with the sham EA(fP < 0.001)
Xu et al[30], 2015	Autonomic function	HRV derived from ECG	Enhanced vagal activity in TEA compared with sham TEA (fP < 0.001)

^aP < 0.05,

^bP < 0.01 vs control group;

^cP < 0.05,

^dP < 0.01,

^fP < 0.001 vs sham TEA;

^kP < 0.001 vs sham EA. BDI: Beck depression inventory; CGRP: Calcitonin gene-related peptide; CONT: Control group; EA: Electroacupuncture; ECG: Electrocardiogram; EGG: Electrogastrogram; GI: Gastrointestinal; GLP-1: Glucagon-like peptide-1; HRV: Heart rate variability; MA: Manual acupuncture; NPY: Neuropeptide Y; SAS: Zung’s self-rating anxiety scale; SDS: Zung’s self-rating depression scale; STAI: State-trait anxiety inventory; PET-CT: Fluorine-18 fluorodeoxy glucose positron emission tomography computed tomography; TEA: Transcutaneous electrical acustimulation; ELISA: Enzyme linked immunosorbent assay.