Table 3.

Adverse effects and reasons for withdrawal and/or dropout

ID	Author	Year	Adverse events (n)	Reasons for withdrawal
				Intervention group (n)	Control group (n）
1	Roman et al 26	2018	Intestinal discomfort (2)	Reasons unrelated to the intervention (2)	Non-therapeutic adherence (2)
2	Farhangi et al 21	2018	No serious adverse events	Did not consume the supplement (1)	Received anti-inflammatory medication (2), diet change (1), did not consume the supplement (3)
3	Schumann et al*22	2018	FODMAP group: a major depressive episode (1), a mild self-reported depressive episode (1), unwanted loss of weight (1)	Due to the adverse events (1), scheduling problems (1), compliance (2)	Loss of interest (1), scheduling problems (2)
			Yoga group: a newly diagnosed deep leg vein thrombosis (1), back pain (1)
4	Sawada et al 17	2017	Abdominal pain, sleep disturbance, particularly in the placebo group	No data provided
5	Sanchez et al 23	2017	No data provided	Poor compliance to the treatment (1)
6	Romijn et al 27	2017	Dry mouth, sleep disruption	Antibiotic use (1), antidepressant use (2), participant choice (4)	Antibiotic use (2), stressful life events (1)
7	Pinto-Sanchez et al 18	2017	No serious adverse events related to study product	Antibiotic use (3), antidepressant use (1)	Antibiotic use (1), antidepressant use (1)
8	Kelly et al 20	2017	Side effects were negligible	No data provided
9	Eswaran et al 28	2017	No data provided	Lost to follow-up: not returning calls (1), started antibiotics (1), too expensive (1); discontinued intervention: too limiting (1), moved out of state (1)	Discontinued intervention: failed to make symptom reports (2)
10	Colica et al 29	2017	No data provided	2 subjects voluntarily stopped the treatment	1 subject voluntarily stopped the treatment
11	Azpiroz et al 30	2017	Intake of scFOS was well tolerated and the number of adverse events was similar in the scFOS (18) and placebo (21) groups†	Colonic lavage prior to the rectal sensitivity test (1), antibiotic treatment (1)
12	Lyra et al 31	2016	Treatment-emergent AEs: GI disorders, gastroenteritis and influenza IP-related AEs: mild GI symptoms (7 placebo, 7 low dose and 9 high dose) Two SAE cases: pneumonia and syncope; neither was associated with the IP or any trial procedure	Low dose—adverse event (4), lost to follow-up (3), other (4), protocol violation (1), withdrawal of consent (5) High dose—adverse event (10), other (3), protocol violation (1), withdrawal of consent (4)	Adverse event (3), lost to follow-up (2), other (2), protocol violation (3), withdrawal of consent (6)
13	Steenbergen et al 32	2015	No data provided	No data provided
14	Lorenzo-Zúñiga et al 33	2014	No adverse drug reactions	High dose: loss to follow-up (3), discontinued intervention (3) Low dose: loss to follow-up (3), discontinued intervention (3)	Loss to follow-up (5), discontinued intervention (5)
15	Peters et al 34	2014	No data provided‡	No data provided
16	Alipour et al 35	2014	No adverse effects	Did not follow the study protocol (8/6)
17	Yuman and Yingwei36	2013	No data provided	No data provided
18	Messaoudi et al 19	2011	No data provided	No data provided
19	Simrén et al 37	2010	No adverse events	Lack of effect of the treatment (5), factors unrelated to the study (2)
20	Silk et al 38	2009	Moderate diarrhoea (1–3.5 g placebo), mild nausea (1–7.0 g placebo, 1–3.5 g prebiotic)	Felt the study was too demanding (3), felt the placebo caused diarrhoea (1), took part in another probiotic study (1), took a commercially available probiotic preparation during baseline (2)
21	Rao et al 39	2009	No significant adverse events	Reasons unrelated to the intervention (4)

GI disorders refer to gastrointestinal tract disorders, including abdominal discomfort, abdominal distension, abdominal pain, constipation, diarrhoea and flatulence.

*None of these events were adjudged to relate to the study interventions.

†Did not provide details.

‡One patient ceased the whey challenge (treatment first received) prematurely because of intolerable symptoms after lunch on day 2.

AE, adverse effect; FODMAP, fermentable oligosaccharides, disaccharides, and monosaccharides and polyols; GI, gastrointestinal; IP, investigational product; SAE, serious adverse event; scFOS, short-chain fructooligosaccharides.