Table 2.

Characteristics of the studies assessing the efficacy of a fructose- or lactose-restricted diet in the treatment of functional gastrointestinal disorders in children.

Author- Journal- Year of Publication	Type of Study	Diagnosis	Study Groups and Sample	Intervention	Duration	Age	Outcomes	Tools Used	Evaluation	Study Results	Adherence to the Intervention
Fructose Intolerance/Malabsorption
Wirth, S. et al. Klin Padiatr 2014 [28]	2 site-prospective, blinded RCT	Children with RAP for >3 months with positive F-HBT	n = 116 total sample/n = 103 completed the study. FRD (n = 51) or regular diet (RD) (n = 52)	FRD: detailed dietary counselling for fructose restriction plus 10 recipes for warm meals. Regular diet: instructions no to alter their diet	2 weeks (plus 2 additional weeks for children with positive F-HBT within FRD group).	3–18 years (3.4 to 16.4 years, n = 103)	abdominal pain intensity, changes of pain frequency, secondary symptom score (SSS) (range 0–24) 8 parameters evaluated: nausea, vomiting, fatigue, sleep disturbance, headache, dizziness, anorexia and use of pain relievers (Scores 0 to 3).	10-point Likert scale (0 = no pain, 10 = very strong pain) for pain intesity, 3-poin scale (0 = never, 3 = frequent) for SSS, pain frequency was recorded through questainnaire. Adherence to the diets was assessed through questionnaire at the 2-week follow up.	F-HBT with 1 g fructose/kg body weight and a maximum of 25 g in a 10% solution after 8h fasting.	Abdominal pain intensity: reduced in FRD (p < 0.001) but not in RD (p > 0.5). Within FRD, children with both positive and negative F-HBTs reduced abdominal pain. Abdominal pain frequency: both groups reduced pain frequency (74% vs. 57%). SSS results: FRD: SSS reduced from 6 to 3.5, p < 0.002, RD: no statistical change. Within FRD, children with negative F-HBTs reduced SSS (p < 0.004).	No data reported although adherence was assessed by the authors.
Wintermeyer, P. et al. Klin Padiatr 2012 [43]	single arm clinical trial	Children with RAP for the previous 3 months with positive F-HBT	n = 75 in FRD / no control group	FRD:detailed dietary advice with a list of allowed and not allowed foods were given / option to call dietitian in case of questions.	4 weeks	3–14 years	Frequency and intensity of abdominal pain, stool frequency per day, nausea, problems to fall asleep, missed school days per week, and use of pain relievers	A questionnaire asking participants for clinical symptoms, e.g. frequency of pain, pain intensity, GI symptoms and adherence to the diet was used. Pain intensity was assessed through a 10-point Likert scale questionnaire (0 = no pain, 10 = very strong pain)	F-HBT with 1 g fructose/ kg body weight with a maximum of 25 g in a 10% solution after an 8–12 h fasting period	At the end of the study, pain frequency/w (1 vs.4, p < 0.001) and the intensity of pain (3 vs.6, p < 0.001) reduced compared to baseline. Daily stool frequency, nausea, problems to fall asleep, missed school days also improved significantly (all p < 0.05).	80% of patients declared adherence to fructose restricted diet for more than 3 weeks and 88% for more than 2 weeks.
Escobar, J. et al. Gastroenterology 2014 [44]	single arm clinical trial	Children with chronic abdominal pain	121 of 222 patients (54.5%) with positive F-HBT were placed on FRD	1-hour individual consultation with a dietitian, a list of allowed and not allowed foods and a sample menu	2 months	2−19 years	Resolution of GI symptoms	A standard pain scale. Adherence to the diet was assessed through patient report.	F-HBT with 1 g/kg fructose to a maximum of 25 g after 12 h of fasting	At the end of the study, 93/121 patients (76.9%) reported resolution of GI with FRD (p < 0.0001). Moreover, 55/101 patients (54.4%) with negative F-BHT reported resolution of symptoms without a FRD (p = 0.37).	All patients with positive F-HBT reported near universal adherence to the dietary restrictions.
Fructose or Lactose Intolerance/Malabsorption
Gijsbers, R. et al. Acta Paediatrica 2012 [45]	randomized double-blind placebo-controlled trial	Children with RAP and positive F-HBT or L-HBT	LM/LI patients => initial screen phase: n = 210 with 57 positive L-HBT, elimination phase: n = 38/57 with 24 positive L-HBT. Open provocation phase: n = 23/24 with n = 7 positive L-HBT. DBPC phase: n = 6/7 with n = 6 negative L-HBT. FM/FI patients => initial screen phase: n = 121 with 79 positive F-HBTs, elimination phase: n = 49/79 with n = 32 positive F-HBTs, provocation phase: n = 31/32 with n = 13 positive F-HBTs, DBPC phase: n = 8/13 with n = 8 negative F-HBTs.	DBPC: containers with 25 g lactose or fructose and 2 with glucose in amounts that resulted in the same sweetness, numbered 1 through 4 in a randomized way.	6 months	4.1–16.0 years [mean age 8.8]	Resolution of GI symptoms	Not defined	F-HBTs and L-HBTs of 2 g/kg, with a maximum of 50 g in a 16.7% (50 g/300 mL) solution	After the DBPC phase, all patients with positive F-HBTs or positive-HBTs tested negative. No causal relationship between DBPC and FAP was proven by researchers.	NR
Lactose Intolerance/malabsoprtion
Gremse, D.A. et al. Clin Pediatrics, 2003 [46]	double-blind, crossover RCT	Children with IBS and positive L-HBT	Interventiong group: 240 mL of lactose-hydrolyzed milk or lactose-containing milk along with LRD (n = 33 in a crossover design)	Intervention group: Lactose-free milk prepared with 2.0 g of lactase per 1.9 L milk. Control group: lactose-containing milk +aspartame 1.5 g per 1.9 L of milk.	2 weeks	3–17 years	pain severity, total GI symptoms score	Food diaries were used to assess adherence to the LFD, pain diaries collected weekly, pain severity assesed by with a 4- likert scale (0, no symptoms; to 4, severe symptoms), total symptom score for each patient.	L-HBTs of 1 g/kg (up to 50 g) was given in a 10% solution after overning fasting	At the end of the study, abdominal pain severity decreased in the intervention compared to the control group (4.1 ± 1.4 vs. 7.5 ± 2.7, p = 0.021). Within the control group, 23/30 reported more symptoms. However, 7/30 reported less or no symptoms, although compliant with the diet.	Fully adherence to the LFD.