Valorisation, Green Extraction Development, and Metabolomic Analysis of Wild Artichoke By-Product Using Pressurised Liquid Extraction UPLC-HRMS and Multivariate Data Analysis.

Valorisation of food by-products has recently attracted considerable attention due to the opportunities to improve the economic and environmental sustainability of the food production chain. Large quantities of non-edible parts of the artichoke plant (Cynara cardunculus L.) comprising leaves, stems, roots, bracts, and seeds are discarded annually during industrial processing. These by-products contain many phytochemicals such as dietary fibres, phenolic acids, and flavonoids, whereby the most challenging issue concerns about the recovery of high-added value components from these by-products. The aim of this work is to develop a novel valorisation strategy for the sustainable utilisation of artichoke leaves' waste, combining green pressurised-liquid extraction (PLE), spectrophotometric assays and UPLC-HRMS phytochemical characterization, to obtain bioactive-rich extract with high antioxidant capacity. Multivariate analysis of the major selected metabolites was used to compare different solvent extraction used in PLE.

Development of an antioxidant formula based on peanut by-products and effects on sensory properties and aroma stability of fortified peanut snacks during storage.

BACKGROUND: An antioxidant formula based on peanut skins and hulls was developed and characterized for total and single polyphenols, as well as antioxidant power, considering the contribution provided by each peanut by-product. Subsequently, it was evaluated for its effect on the sensory properties and aroma stability of peanut bars over a 100-day period. To this purpose, snacks fortified, or not, with the natural additive were experimentally produced. RESULTS: Peanut hulls contributed to a greater extent than skins with respect to boosting the content of bioactives and the antioxidnt activity of the antioxidant formula, which was marked by a phenol content of (approximately 807 mg gallic acid equivalents g-1 ) and a 2,2-diphenyl-1-picrylhydrazyl activity similar to that of butylated hydroxytoluene (85.96% and 89.30%, respectively). From a sensory perspective, the incorporation of the formulation in snacks caused only a slightly stronger perception of astringent and bitter notes. Pyrazines, phenol, furan and pyrrole derivatives defined the aroma of snacks, being more abundant in fortified than in conventional samples. Such volatiles faded over storage, with different trends in the examined products. For example, the sum of 2,5-dimethylpyrazine, 2-ethylpyrazine and 2,3-dimethylpyrazine was 9.49 and 8.87 ppm at day 15; 5.57 and 7.16 ppm at day 45; and 5.03 and 4.65 ppm at day 100, respectively, in fortified and conventional snacks. Hydroxymethylfurfural decreased constantly over storage in conventional samples and only after day 45 in fortified bars. CONCLUSION: Overall, the antioxidant formulation did not compromise the sensory desirability of peanut snacks and induced a preservative effect on their aroma, especially during the first 15 days of storage. © 2020 Society of Chemical Industry.

Determination of Chloramphenicol in Honey Using Salting-Out Assisted Liquid-Liquid Extraction Coupled with Liquid Chromatography-Tandem Mass Spectrometry and Validation According to 2002/657 European Commission Decision.

Honey is a natural food widely consumed due to its high content in nutrients and bioactive substances. In order to prevent hive infections, xenobiotics such as pesticides and antibiotics are commonly used. Chloramphenicol (CAP) is a broad-spectrum antibiotic used to treat honeybee larvae diseases. However, CAP has toxic and nondose-dependent effects in sensitive subjects; for this reason, its use has been prohibited in food-producing animals, such as the honeybee. In this study, we proposed a rapid, simple, and cheap analytical method, based on salting-out assisted liquid-liquid extraction coupled with UHPLC MS/MS detection for the accurate determination of CAP in honey to be used in routine analyses. The parameters that influence the extraction efficiency have been optimized using an experimental design in order to maximize the recovery of the analyte by reducing the matrix effects. Therefore, the developed method was internally validated according to the 2002/657/EC Decision guidelines and applied to the analysis of 96 honey samples.

Pressurized hot water extraction of bioactive compounds from artichoke by-products.

Artichoke by-products are a suitable source of health-promoting ingredients for the production of dietary supplements and food additives. A pressurized hot water extraction (PHWE) was developed to recover caffeoylquinic acids (CQAs) and flavone glycosides (FLs) from agro-industrial artichoke by-products. The main factors influencing PHWE efficiency and CQA isomerization (temperature, numbers of cycles, modifier, and extraction time) were carefully studied and optimized by response surface design. The proposed PHWE procedure provides an exhaustive extraction of CQAs and FLs (recoveries: 93-105% and 90-105%) from artichoke external bracts and leaves of different cultivars (p > 0.05), without significant formation of artefacts generated by high temperatures. PHWE extracts showed CQA and FL levels (14-37 mg/g and 3-19 mg/g, respectively) comparable to commercial products and marked antioxidative effects (EC50 11-83 µg/mL) by cellular antioxidant activity assay in human hepatocarcinoma HepG2 cells. These results proved that PHWE is an excellent green technique to recover bioactive compounds from artichoke agro-industrial residues.

Development of an improved online comprehensive hydrophilic interaction chromatography × reversed-phase ultra-high-pressure liquid chromatography platform for complex multiclass polyphenolic sample analysis.

In this study, an improved online comprehensive two-dimensional liquid chromatography platform coupled to tandem mass spectrometry was developed for the analysis of complex polyphenolic samples. A narrowbore hydrophilic interaction chromatography column (150 × 2.0 mm, 3.0 µm, cross-linked diol) was employed in the first dimension, while a reversed-phase column based on monodisperse sub-2 µm fully porous particles (50 × 3.0 mm, 1.9 µm d.p.) with high surface area (410 m2 /g) was employed in the second dimension. The combination of a trapping column modulation interface with the high retentive fully porous monodisperse reversed-phase column in the second dimension resulted in higher peak capacity values (1146 versus 867), increased sensitivity, sharper and more symmetrical peaks in comparison with a conventional loop-based method, with the same analysis time (70 min). The system was challenged against a complex polyphenolic extract of a typical Italian apple cultivar, enabling the simultaneous separation of multiple polyphenolic classes, including oligomeric procyanidins, up to degree of polymerization of 10. Hyphenation with an ion trap time-of-flight mass spectrometer led to the tentative identification of 121 analytes, showing how this platform could be a powerful analytical tool for the accurate profiling of complex polyphenolic samples.

Flavonoid Composition of Tarocco (Citrus sinensis L. Osbeck) Clone "Lempso" and Fast Antioxidant Activity Screening by DPPH-UHPLC-PDA-IT-TOF.

INTRODUCTION: Clonal selection and hybridisation are valid strategies to obtain fruits with enhanced sensorial and nutraceutical properties. Within Citrus sinensis varieties, Tarocco clone "Lempso" is a typical product of the Calabria region (Italy) characterised by its red pulp. This is the first report concerning its accurate profiling. OBJECTIVE: To characterise in detail the flavonoid composition of Lempso clone and to compare its antioxidant potential with other Citrus varieties by a fast screening method. METHODOLOGY: Extracts were subjected to solid phase extraction and the qualitative/quantitative profile was elucidated through ultra-high performance liquid chromatography (UHPLC) coupled to photodiode array (PDA) and ion trap time-of-flight (IT-TOF) mass spectrometry detection, and compared to both Cleopatra mandarin (Citrus reticulata) and blood orange (Citrus sinensis (L.) Osbeck) Sanguinello varieties. The antioxidant activity was assessed by pre-column 2,2'-diphenyl-1-picrylhydrazyl (DPPH) reaction coupled to UHPLC-PDA. RESULTS: Lempso is characterised by flavonoids (17) and anthocyanins (8). Flavanones content (Hesperidin: 57.19 ± 0.49, Vicenin-2: 4.59 ± 0.03, Narirutin: 5.78 ± 0.13 mg/100 mL) was considerably higher than Cleopatra and Sanguinello varieties. The developed DPPH-UHPLC-PDA method provides information regarding the single contributions to antioxidant activity, highlighting how Ferulic acid, Quercetin and Cyanidin derivatives possess considerable radical scavenging activity (> 50%). The total antioxidant activity was also evaluated and compared with positive controls, showing higher scavenging activity than Cleopatra and Sanguinello (IC50 : 333.76 ± 10.81 µg/mL vs. 452.62 ± 10.81 and 568.39 ± 26.98 µg/mL, respectively). CONCLUSION: These data evidence the nutraceutical potential of Lempso variety, which could be an ingredient for functional beverages. Copyright © 2017 John Wiley & Sons, Ltd.

Bioavailable Citrus sinensis Extract: Polyphenolic Composition and Biological Activity.

Citrus plants contain large amounts of flavonoids with beneficial effects on human health. In the present study, the antioxidant and anti-inflammatory potential of bioavailable polyphenols from Citrus sinensis was evaluated in vitro and ex vivo, using the murine macrophages cell line J774A.1 and primary peritoneal macrophages. Following simulated gastro-intestinal digestion, the in vitro bioavailability of Citrus sinensis polyphenolic extract was assessed using the human cell line Caco-2 grown as monolayers on a transwell membrane. Data demonstrated a relative permeation of its compounds (8.3%). Thus, the antioxidant and anti-inflammatory effect of polyphenolic Citrus sinensis fraction (Cs) was compared to the bioavailable one (CsB). Results revealed that Citrus extract were able to reduce macrophages pro-inflammatory mediators, including nitric oxide, iNOS, COX-2 and different cytokines. Moreover, the effect of Citrus sinensis polyphenols was associated with antioxidant effects, such as a reduction of reactive oxygen species (ROS) and heme-oxygenase-1 (HO-1) increased expression. Our results provide evidence that the bioavailable polyphenolic constituents of the Citrussinensis extract accumulate prevalently at intestinal level and could reach systemic circulation exerting their effect. The bioavailable fraction showed a higher anti-inflammatory and antioxidant potential compared to the initial extract, thus highlighting its potential nutraceutical value.

Anti-inflammatory and antioxidant activity of polyphenolic extracts from Lactuca sativa (var. Maravilla de Verano) under different farming methods.

BACKGROUND: Besides their nutritional value, vegetables are a source of health-promoting compounds, such as polyphenols, and their content can be influenced by the particular farming method. In this study polyphenolic extracts from Lactuca sativa (var. Maravilla de verano) plants cultivated with different farming methods were chemically characterised and tested in vitro and ex vivo inflammation models. RESULTS: The tested extacts (250-2.5 µg mL(-1) ) were able to reduce both the inflammatory and oxidative stress in LPS-stimulated J774A.1 murine monocyte macrophage cells, by lowering the release of nitric oxide (NO) and reactive oxygen species (ROS) and promoting nuclear translocation of nuclear factor (erythroid-derived 2)-like 2; (Nrf2) and nuclear factor-κB (NF-κB). In this regard, quantitative profiles revealed different amounts of polyphenols, in particular quercetin levels were higher in plants under mineral fertilised treatment. Those extract showed an enhanced anti-inflammatory and antioxidant activity. CONCLUSION: Our data showed the anti-inflammatory and antioxidant potential of Maravilla de Verano polyphenolic extracts. The effect of farming methods on polyphenolic levels was highlighted. The higher reduction of inflammatory mediators release in extracts from plants cultivated under mineral fertilisation treatment was correlated to the higher amount of quercetin. These results can be useful for both nutraceutical or agronomic purposes. © 2016 Society of Chemical Industry.

A fully automated method for simultaneous determination of aflatoxins and ochratoxin A in dried fruits by pressurized liquid extraction and online solid-phase extraction cleanup coupled to ultra-high-pressure liquid chromatography-tandem mass spectrometry.

According to current demands and future perspectives in food safety, this study reports a fast and fully automated analytical method for the simultaneous analysis of the mycotoxins with high toxicity and wide spread, aflatoxins (AFs) and ochratoxin A (OTA) in dried fruits, a high-risk foodstuff. The method is based on pressurized liquid extraction (PLE), with aqueous methanol (30%) at 110 °C, of the slurried dried fruit and online solid-phase extraction (online SPE) cleanup of the PLE extracts with a C18 cartridge. The purified sample was directly analysed by ultra-high-pressure liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) for sensitive and selective determination of AFs and OTA. The proposed analytical procedure was validated for different dried fruits (vine fruit, fig and apricot), providing method detection and quantification limits much lower than the AFs and OTA maximum levels imposed by EU regulation in dried fruit for direct human consumption. Also, recoveries (83-103%) and repeatability (RSD < 8, n = 3) meet the performance criteria required by EU regulation for the determination of the levels of mycotoxins in foodstuffs. The main advantage of the proposed method is full automation of the whole analytical procedure that reduces the time and cost of the analysis, sample manipulation and solvent consumption, enabling high-throughput analysis and highly accurate and precise results.

The LimoFish Circular Economy Process for the Marine Bioeconomy.

The outcomes of applying the zero-waste extraction "LimoFish" process based on defatting fish processing waste with limonene to leftovers of European sardine (Sardina pilchardus) and European anchovy (Engraulis encrasicolus), compared to conventional extraction with oil-derived solvents such as n-hexane and with petroleum ether, show that the process has general applicability. Meeting the principles of green extraction and those of the marine biorefinery requiring high process efficiency, the process establishes an "innovation through integration" circular economy production route enabling the marine bioeconomy.

UHPLC-PAD Protocol for the Simultaneous Identification of Polyphenols and Bitter Acids: Organoleptic and Nutraceutical Fingerprinting of Bergamot-Flavored Craft Beer.

In this study, a UHPLC-PDA method for the simultaneous identification of polyphenols and bitter acids (alpha, beta, and isoalpha) in beer was developed. The resulting chemical profiles were leveraged to distinguish the characteristics of four (IPA, Lager, Blanche, ALE) bergamot-flavored beers, produced on a pilot-scale plant. In a streamlined 29 min analysis, thirty polyphenols and fourteen bitter acids were successfully identified under optimized separation conditions. Validation, encompassing parameters such as LOD (from 0.028 ppm for isorhamnetin to 0.106 for narirutin), LOQ (from 0.077 ppm for naringenin to 0.355 for narirutin), R2 (always more than 0.9992), repeatability (from 0.67% for tangeretin to 6.38% for myricetin), and reproducibility (from 0.99% for sinensetin to 6% for naringin), was conducted for polyphenol quantification using constructed calibration curves with seven levels. Exploring polyphenolic components as potential discriminators among different beer styles, a total of thirty-two polyphenolic compounds were identified and quantified, including characteristic bergamot peel polyphenols like neoeriocitrin (from 7.85 ppm for CBS2 to 11.95 ppm in CBS1); naringin (from 4.56 ppm for CBS4 to 10.96 in CBS1), and neohesperidin (from 5.93 in CBS3 to 15.95 for CBS2). The multivariate analysis provided additional insights into variations among specific beer styles, revealing discrepancies in the presence or relative concentrations of specific compounds linked to brewing ingredients and processes. This research enhances the fingerprinting of the chemistry governing beer quality through a straightforward and cost-effective analytical approach.

Exploring Influence of Production Area and Harvest Time on Specialized Metabolite Content of Glycyrrhiza glabra Leaves and Evaluation of Antioxidant and Anti-Aging Properties.

Calabrian Glycyrrhiza glabra is one of the most appreciated licorice varieties worldwide, and its leaves are emerging as a valuable source of bioactive compounds. Nevertheless, this biomass is usually discarded, and its valorization could contribute to boost the economic value of the licorice production chain. In this study, the effects of production area and harvest time on the specialized metabolite content of G. glabra leaves (GGL) and also the antioxidant and anti-aging properties are evaluated to explore the potential of this untapped resource and to select the most optimal harvesting practices. GGL exhibited high levels of specialized metabolites (4-30 g/100 g of dry leaf) and the most abundant ones are pinocembrin, prenylated flavanones (licoflavanone and glabranin), and prenylated dihydrostilbenes. Their levels and antioxidant capacity in extracts are influenced by both production area and harvest time, showing a decisive role on specialized metabolites accumulation. Interestingly, GGL extracts strongly attenuate the toxicity of α-synuclein, the intracellular reactive oxygen species (ROS) content, and cellular senescence on Saccharomyces cerevisiae expressing human α-synuclein model, showing great potential to prevent aging and age-related disorders. These results provide insights into the phytochemical dynamics of GGL, identifying the best harvesting site and period to obtain bioactive-rich sources with potential uses in the food, nutraceutical, and pharmaceutical sectors.

Rapid analysis of aflatoxin M1 in milk using dispersive liquid-liquid microextraction coupled with ultrahigh pressure liquid chromatography tandem mass spectrometry.

A simple, rapid, and sensitive method based on simultaneous protein precipitation and extraction of aflatoxin M1 (AFM1) followed by dispersive liquid-liquid microextraction (DLLME) and ultrahigh pressure liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) analysis was developed for the determination of AFM1 in milk samples. In order to precipitate the proteins and extract AFM1 from milk, a sample pretreatment using acetonitrile and NaCl as the extraction/denaturant solvent and salting-out agent, respectively, was optimised. Subsequently, the acetonitrile (upper) phase, containing AFM1, was used as the disperser solvent in DLLME, and extractant (chloroform) and water were added in turn to the extract to perform the DLLME process. The main parameters affecting the extraction efficiency of the whole analytical procedure, such as acetonitrile volume, amount of salt, type and volume of extractant and water volume, were carefully optimised by experimental design. Under optimum conditions, the developed method provides an enrichment factor of 33 and detection and quantification limits (0.6 and 2.0 ng kg(-1), respectively) below the maximum levels imposed by current regulations for AFM1 in milk and infant milk formulae. Recoveries (61.3-75.3%) and repeatability (RSD < 10, n = 3), tested in different types of milk at four AFM1 levels, met the performance criteria required by EC Regulation No. 401/2006. Moreover, the matrix effect on the signal intensity of the analyte was negligible. The proposed method provides a rapid extraction and an accurate determination of AFM1 in milk and formula milk using a simple and inexpensive sample preparation procedure.

A Predictive Model to Correlate Amino Acids and Aromatic Compounds in Calabrian Honeys.

To better understand the biochemistry of the organoleptic properties of honey influencing its commercial value, a predictive model for correlating amino acid profiles to aromatic compounds was built. Because the amino acid composition of different varieties of honey plays a key role as a precursor of specific aroma bouquets, it is necessary to relate the amino acid typesetting to aromatic molecules. A selection of unifloral honeys produced in Calabria, South Italy, were used, and a new methodology based on the use of HILIC-UHPLC-ESI-MS/MS and HS-SPME-GC-MS combined with multivariate processing has been developed. This study, carried out for the first time on honey, shows its excellent potential as a modern analytical tool for a rapid multicomponent analysis of food-quality indicators. Data obtained showed strong positive linear correlations between aldehydes and isoleucine, valine, leucine, and phenylalanine. Furans are correlated with isoleucine, leucine, and phenylalanine; hydrocarbons with serine, glutamic acid, and aspartic acid; and ketones with serine, alanine, glutamine, histidine, asparagine, and lysine. Alcohols were more associated with tyrosine than esters with arginine. Proline, tryptophan, and threonine showed poor correlations with all the classes of aroma compounds.

Target screening method for the quantitative determination of 118 pyrrolizidine alkaloids in food supplements, herbal infusions, honey and teas by liquid chromatography coupled to quadrupole orbitrap mass spectrometry.

An analytical procedure for the screening of 118 pyrrolizidine alkaloids (PAs) was successfully validated and applied to their quantitative determination in food supplements, herbal infusions, honey, and teas. It provides the reliable analyte identification by high-resolution tandem mass spectrometry (HRMS/MS), the accurate determination of 21 regulated PAs, and broad contamination profiles. 10% of 281 analyzed samples resulted contaminated at levels above the maximum levels (MLs) of European legislation. The contamination of herbal infusions of mixed plants can represent a possible health concern (23%; mean of PA sum above ML). A high number of PAs not included in the regulation was detected in honey and herbal food supplements, but their contribution was only relevant to the overall level in honey. The results indicate the need to continue collecting contamination data in food supplements and infusions of mixed herbs and to expand the PA-pool to be monitored in honey and related products.

An analytical platform for the screening and identification of pyrrolizidine alkaloids in food matrices with high risk of contamination.

An analytical platform for the detection of pyrrolizidine alkaloids (PAs) in honey, pollen, teas, herbal infusions, and dietary supplements is proposed; it includes a wide-scope suspect screening method, based on a diagnostic product ion filtering strategy for the characterization of PAs, and a target screening and identification method for the high-throughput detection of 118 PAs of a high-resolution mass spectral library. Salting-out assisted liquid-liquid extraction of aqueous extracts combined to ultra-high performance liquid chromatography-high-resolution tandem mass spectrometry was employed. The limit of identification (0.6-30 µg kg-1) of 28 standards were fit-for-purpose in PA-monitoring applications, with a false negative rate <1.3 % at 4 µg L-1. The wide-scope suspect screening method allowed the tentative identification of 88 compounds. The screening of 282 commercial samples revealed a broad contamination of the studied matrices, demonstrating the effectiveness of the platform in detecting and identifying both target and untarget PAs.

Effect of microbial fermentation on functional traits and volatiloma profile of pâté olive cake.

In this study, the pâté olive cake (POC), a by-product of the olive oil industry, was subjected to fermentation in a bioreactor using three microbial strains, Lactiplantibacillus plantarum, Wickerhamomyces anomalus and Candida boidinii, previously isolated from fermented table olive brines. Chemical, microbiological and molecular analyses were carried out at the beginning and at the end of fermentation. The lowest pH value (4.09) was reached after 10 days in sample inoculated with C. boidinii. Microbiological analyses exhibited the dominance of yeasts throughout the whole process (from 5.5 to 7.80 Log10 CFU/g), as confirmed by PCR-DGGE analysis. The microbial cultures affected both phenolic and volatile organic compound profiles. Moreover, the POC samples treated with different microbial strains were investigated for biological assays. The sample fermented with W. anomalus showed the greatest diffusion speed of transepithelial transport through Caco-2 cell, the highest inhibitory activity towards the tested cyclooxygenases and the highest antioxidant activity.

LC-MS and GC-MS Data Fusion Metabolomics Profiling Coupled with Multivariate Analysis for the Discrimination of Different Parts of Faustrime Fruit and Evaluation of Their Antioxidant Activity.

The comparative chemical composition of different part of Faustrime fruits (peels, pulp, albedo, and seeds) extracted with different solvents was determined by GC-MS and UHPLC-HRMS QTof. The obtained data were also combined for their in vitro antioxidant activity by multivariate analysis to define a complex fingerprint of the fruit. The principal component analysis model showed the significative occurrence of volatile organic compounds as α-bisabolol and α-trans-bergamotol in the pulp and albedo, hexanoic acid in the seeds, and several coumarins and phenolics in the peels. The higher radical scavenging activity of the pulp was related to the incidence of citric acid in partial least square regression.

AnchoisFert: A New Organic Fertilizer from Fish Processing Waste for Sustainable Agriculture.

The "AnchoisFert", the solid residue comprised of milled anchovy leftovers after fish oil extraction with biobased limonene, is a powerful organic fertilizer. Employed to promote the growth of Tropea's red onion (Allium cepa), the fertilizer turns out to largely be superior to commonly used organic (manure) and chemical (nitrogen phosphorous potassium) fertilizers. Rich in proteins, organic carbon, flavonoids, magnesium, potassium, phosphate and sulfate, and devoid of antibiotics and antibiotic resistance genes, the new organic fertilizer can replace both conventional organic and inorganic fertilizers. This discovery closes the fishing material cycle for the most fished species across the seas opening the route to a new class of organic fertilizers of exceptional performance derived from abundant biowaste via a low-cost and environmentally-friendly circular economy process.

Efficacy of ginger as antiemetic in children with acute gastroenteritis: a randomised controlled trial.

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.