Efficacy of Ginger as Antiemetic in Children With Acute Gastroenteritis

A Randomised Controlled Trial

Rita Nocerino; Gaetano Cecere; Maria Micillo; Giulio De Marco; Pasqualina Ferri; Mariateresa Russo; Giorgio Bedogni; Roberto Berni Canani

Disclosures

Aliment Pharmacol Ther. 2021;54(1):24-31.

Abstract and Introduction

Abstract

Background: Ginger is a spice with a long history of use as a traditional remedy for nausea and vomiting. No data on the efficacy of ginger are presently available for children with vomiting associated with acute gastroenteritis (AGE).

Aim: To test whether ginger can reduce vomiting in children with AGE.

Methods: Double-blind, randomised placebo-controlled trial in outpatients aged 1 to 10 years with AGE-associated vomiting randomised to ginger or placebo. The primary outcome was the occurrence of ≥1 episode of vomiting after the first dose of treatment. Severity of vomiting and safety were also assessed.

Results: Seventy-five children were randomised to the ginger arm and 75 to the placebo arm. Five children in the ginger arm and 4 in the placebo arm refused to participate in the study shortly after randomisation, leaving 70 children in the ginger arm and 71 in the placebo arm (N = 141). At intention-to-treat analysis (N = 150), assuming that all children lost to follow-up had reached the primary outcome, the incidence of the main outcome was 67% (95% CI 56 to 77) in the ginger group and 87% (95% CI 79 to 94) in the placebo group, corresponding to the absolute risk reduction for the ginger versus the placebo group of −20% (95% CI −33% to −7%, P = 0.003), with a number needed to treat of 5 (95% CI 3 to 15).

Conclusion: Oral administration of ginger is effective and safe at improving vomiting in children with AGE.

Trial registration: The trial was registered on https://clinicaltrials.gov/ with the identifier NCT02701491.

Introduction

Vomiting is a common symptom in childhood and has many causes, ranging from self-limited to life-threatening conditions.^[1] Vomiting is the presenting symptom in up to 75% of children with acute gastroenteritis (AGE), where it contributes to fluid loss, failure of oral rehydration therapy, and emergency admission to the hospital.^[2,3] Nearly 80% of Italian pediatricians prescribe antiemetic drugs to children with AGE, mostly off-label.^[4–6] The antiemetic drugs most frequently prescribed in Europe and Italy are domperidone, a dopamine receptor antagonist, and ondansetron, a 5-HT₃ antagonist.^[6] Current evidence shows that ondansetron but not domperidone is effective for the treatment of AGE-associated vomiting in the emergency setting.^[2,7]

Ginger (Zingiber officinale) is a spice with a long history of use as traditional remedy for nausea and vomiting.^[8] The active phenolic compounds of ginger, that is, gingerols, zingiberene and shogaols, have also anti-inflammatory and anti-oxidant properties. The antiemetic action of ginger has been investigated in various conditions including motion sickness, pregnancy, post-anesthesia, post-surgery, and chemotherapy-induced nausea and vomiting.^[9–25] Given at doses up to 2 g/day, ginger is effective at controlling vomiting without side effects. Besides its general anti-inflammatory action,^[26,27] potential mechanisms of action of ginger include the inhibition of 5-HT₃ and muscarinic acetylcholine (M3) receptors, and the modulation of esophageal and gastrointestinal motility.^[17,26,28]

The pharmacological properties of ginger have been investigated mostly in adults, and no data are available on its effects in children. However, many ginger-based food supplements are increasingly available on the market and are used for the prevention and treatment of vomiting in children without any proof of efficacy. Therefore, the present randomised trial was designed to test whether ginger can reduce AGE-associated vomiting in children.

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Abstract and Introduction
Methods
Results
Discussion
References

Table 1. Composition of ginger and placebo
	Placebo (% of weight)	Ginger (% of weight)
Water	48.37	47.37
Fructose	40	40
Sodium citrate	5	5
Anise	0.02	0.02
Vitamin B1	0.03667	0.03667
Vitamin B6	0.04665	0.04665
Vitamin B2	0.04668	0.04668
L-alanine	0.25	0.25
Potassium citrate	4.25	4.25
Citric acid	1.75	1.75
Aroma	0.18	0.18
Potassium sorbate	0.03	0.03
Stevia Rebaudiana	0.02	0.02
Zingiber officinale hydroglycerin extract	—	1
Total	100	100

Note: 20 drops dose contained 10 mg of ginger.

Table 2. Baseline features of the placebo and ginger arms
	Placebo (n = 75)	Ginger (n = 75)
Male gender, n (%)	36 (48)	39 (52)
Age (years)	6 (4; 9)	5 (3; 7)
Cesarean delivery, n (%)	44 (59)	49 (65)
Gestational age (weeks)	39 (38; 40)	39 (38; 40)
Breastfeeding, n (%)	47 (63)	40 (53)
Breastfeeding duration (months)	6 (3; 9)	4 (3; 7)
Age at weaning (months)	4 (4; 5)	4 (4; 5)
Vomiting (episodes in the previous 4 h)	4 (3; 5)	4 (3; 5)
Diarrhea (bowel movements in the previous 4 h)	1 (1; 1)	1 (1; 2)
Body weight (kg)	23 (15; 31)	19 (15; 27)
Body weight (SDS WHO)	0.55 (0.01; 0.94)	0.66 (−0.08; 1.15)
Height (m)	1.16 (1.03; 1.31)	1.06 (0.98; 1.25)
Height (SDS WHO)	−0.08 (−0.41; 0.19)	0.16 (−0.28; 0.46)
BMI (kg/m²)	17 (16; 19)	17 (16; 19)
BMI (SDS WHO)	0.81 (0.26; 1.33)	0.83 (0.02; 1.54)

Note: Continuous variables are reported as median (50th percentile) and interquartile range (IQR, 25th and 75th percentiles). Discrete variables are reported as the number and proportion of subjects with the characteristic of interest.
Abbreviations: BMI, body mass index; SDS, standard deviation scores; WHO, World Health Organization.

Table 3. Incidence of the primary outcome in the ginger and placebo arms
	ITT equal case scenario	ITT worst-case scenario	PPA
Placebo event rate placebo	65/75 0.87 [0.79 to 0.94]	61/75 0.81 [0.73 to 0.90]	61/71 0.86 [0.78 to 0.94]
Ginger event rate ginger	50/75 0.67 [0.56 to 0.77]	50/75 0.67 [0.56 to 0.77]	45/70 0.64 [0.53 to 0.76]
Absolute risk reduction (ginger-placebo)	−0.20^a [−0.33 to −0.07] P = 0.003 (Wald)	−15^a [−0.29 to −0.006] P = 0.038 (Wald)	−0.22^a [−0.35 to −0.08] P = 0.002 (Wald)
Number needed to treat	5^b [3 to 15]	7^b [4 to 167]	5^b [3 to 14]
Number of children	150	150	141

Note: Values are proportions and 95% confidence interval (in square brackets) from binomial regression. The ITT "equal case scenario" analysis assumes the occurrence of the best outcome (no vomiting) in the 5 children lost to follow-up in the ginger arm and of the same outcome (no vomiting) in the 4 children lost to follow-up in the placebo arm. The ITT "worst case scenario" analysis assumes the occurrence of the worst outcome (vomiting) in the 5 children lost to follow-up in the ginger arm and of the best outcome (no vomiting) in the 4 children lost to follow-up in the placebo arm.
Abbreviations: ITT, intention-to treat analysis; PPA, per-protocol analysis.
^a95 confidence interval calculated from binomial regression.
^b95 confidence interval calculated from Bender's formula.

Table 4. Incidence of vomiting 24 and 48 h after the first dose of treatment (secondary outcome, per-protocol analysis)
	24 h after the first dose of treatment	48 h after the first dose of treatment
Placebo event rate	61/71 0.86 [0.78 to 0.94]	41/71 0.58 [0.46 to 0.69]
Ginger event rate	45/70 0.64 [0.53 to 0.76]	27/70 0.39 [0.27 to 0.50]
Absolute risk reduction (ginger-placebo)	−0.22 [−0.38 to −0.06]^a P = 0.005 (Wald)^b	−0.19 [−0.38 to −0.01]^a P^b = 0.04 (Wald)^b

Note: Values are proportions and 95% confidence intervals (in square brackets) from binomial regression.
^aBonferroni's corrected 95% confidence interval (correction for two comparisons).
^bBonferroni's corrected p value (correction for two comparisons).

Table 5. Number of episodes of vomiting 24 and 48 h after the first dose of treatment (secondary outcome, per-protocol analysis)
	24 h after the first dose of treatment	48 h after the first dose of treatment
Number of episodes of vomiting—placebo	2.03 [1.67 to 2.39]	1.18 [0.85 to 1.52]
Number of episodes of vomiting—ginger	1.49 [1.12 to 1.86]	0.54 [0.33 to 0.75]
Difference in the number of episodes of vomiting (ginger-placebo)	−0.54 [−1.13 to 0.05]^a P = 0.08 (Wald)^b	−0.64 [−1.09 to −0.19]^a P = 0.003 (Wald)^a

Note: Values are means and 95% confidence intervals (in square brackets) calculated from negative binomial regression.
^aBonferroni's corrected 95% confidence interval (correction for two comparisons).
^bBonferroni's corrected P value (correction for two comparisons).