Letter: ginger as anti‐emetic for acute gastroenteritis in children—interpreting evidence gingerly

Abstract

Nocerino et al found that oral ginger extracts effectively and safely improved vomiting in children with acute gastroenteritis (AGE). The authors attempt to bridge the gap on the controversial use of ginger as antiemetic, although commendable, still fails by a large margin due to inherent weakness in the methodology we wish to address.1 Firstly, none of the cited previous studies favour ginger dosing/ intervention in the paediatric group. These included opinionated narratives and systematic reviews demonstrating unclear to no clinical benefit on vomiting and clinical trials showing no added benefit of ginger to a standard of care (Table S1). There is no strong evidence comparing ginger against placebo in an acute setting, and the wrong choice of placebo might have resulted in confirmational biases. In AGE, the authors choice of placebo seems biased towards positive outcomes with ginger compared with a treatment known to be inferior, revealing nonrecognition of “clinical equipoise,” thereby inviting “confirmation” and “framing and ambiguity effect” types of cognitive biases.24 The placebo also contained anise and stevia; both agents worsen nausea and vomiting.5,6 Sample calculation was inapprorpiately extrapolated from an ondansetron superiority design trial. Ideally, the authors should have designed a noninferiority trial against a better placebo or an equivalence trial against the validated 5HT3 antagonist ondansetron. The authors misquote ginger as an efficacious agent through a metanalysis, which demonstrated that current evidence does not support the benefits of ginger in nausea and vomiting.7 The authors did not provide data on the pharmacokinetics (bioavailability and bioefficacy), storage kinetics, dosing rationale of the used proprietary ginger product via invitro and small animal invivo studies. Gingerassociated active compounds are highly volatile, easily oxidized, affected by heat, sample type, and timesensitive.8 Moreover, the ideal type, dose and safety of ginger extract in a paediatric group are not well characterised because of the limited generalizability from published trials, and heterogeneous data sourcing (chemotherapy, pregnancy). Additional issues include weakness in the ascertainment of adverse events due to differences in treatment arms; limited sample size possibly excluded highrisk population and statistical analysis did not consider biological plausibility and latency of adverse events in children. A recent systematic review of clinical trials of ginger indicated divided lower daily dosage of 1500 mg ginger as beneficial for nausea relief but not vomiting in adults with extensive caveats. As with the current study, most gingerrelated randomized trials seldom meet the criterion of “high quality evidence because of small sample size and use of unstandardized formulation and evaluation systems.”9,10 Thus, the considerable existing literature on ginger with higher dosing does not convincingly support the authors clinical findings. Ideally, future studies would include identification, standardization and testing of gingerrelated bioactive compound(s) with antiemetic potential rather than the use of “whole” ginger extracts. Meanwhile, wellcontrolled, dosefinding, standardized extractbased studies on ginger are lacking, and the Nocerino et al study adds to this uncertainty.