What are the clinical effects of Ginger?

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The clinical effects of ginger have been introduced as six subsections: nausea and vomiting, gastrointestinal function, pain, inflammation, metabolic syndromes, and other symptoms....

The clinical effects of ginger have been introduced as six subsections: nausea and vomiting, gastrointestinal function, pain, inflammation, metabolic syndromes, and other symptoms.


Clinical applications of ginger with an expectation of clinical benefits are receiving significant attention. This systematic review aims to provide a comprehensive discussion in terms of the clinical effects of ginger in all reported areas. Following the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guideline, randomized controlled trials on the effects of ginger were investigated. Accordingly, 109 eligible papers were fully extracted in terms of study design, population characteristics, evaluation systems, adverse effects, and main outcomes. The reporting quality of the included studies was assessed based on the Cochrane Collaboration’s tool for assessing the risk of bias in randomized trials and integrated together with studies that investigated the same subjects. The included studies that examined the improvement of nausea and vomiting in pregnancy, inflammation, metabolic syndromes, digestive function, and colorectal cancer’s markers were consistently supported, whereas other expected functions were relatively controversial. Nevertheless, only 43 clinical trials (39.4%) met the criterion of having a ‘high quality of evidence.’ In addition to the quality assessment result, small populations and unstandardized evaluation systems were the observed shortcomings in ginger clinical trials. Further studies with adequate designs are warranted to validate the reported clinical functions of ginger.

1. Introduction
Ginger (Zingiber officinale Roscoe), a well-known herbaceous plant, has been widely used as a flavoring agent and herbal medicine for centuries. Furthermore, the consumption of the ginger rhizome is a typical traditional remedy to relieve common health problems, including pain, nausea, and vomiting [1]. Notably, a prominent number of randomized clinical trials (RCTs) have been conducted to examine ginger’s antiemetic effect in various conditions such as motion sickness, pregnancy, and post-anesthesia [2,3,4]. More than approximately 100 compounds have reportedly been isolated from ginger [5]. Specifically, the major classes of ginger compounds are gingerol, shogaols, zingiberene, and zingerone, as well as other less common compounds, including terpenes, vitamins, and minerals [6]. Among them, gingerols are considered as the primary components, reported to possess several bioactivities [7]. As a result, many related biological activities have been explored such as those of antioxidant, antimicrobial, and anti-neuroinflammation, just to name a few [8]. Moreover, in recent years, the role of ginger has been extended to anticancer, chemotherapy-induced nausea and vomiting (CINV), and fatigue, as well as improvements in the quality of life in daily human work [9,10].


These potential pharmacological and physiological activities have led to a significant increase in the number of investigations on the health benefits of ginger. Regarding clinical aspects, there has been a trend of accumulative evidence in terms of ginger efficacy on human health. Indeed, a remarkable number of RCTs that have aimed to discover the benefits of ginger by reducing symptoms have been conducted. For example, multiple RCTs evaluated the effectiveness of ginger supplementation in reducing CINV in cancer patients, as well as in dysmenorrhea [11]. Moreover, several systematic reviews and meta-analysis (SR–MA), which aimed to assess the clinical ginger effectiveness, have been completed. In particular, Chen et al. conducted an SR–MA of oral ginger intake and found that ginger could effectively control menstrual pain in dysmenorrhea [11]. Another SR–MA study revealed that ginger improved lipid profiles and benefited the glucose control, insulin sensitivity, and glycosylated hemoglobin of type 2 diabetes mellitus [12]. In addition, ginger’s potency has been regularly proposed in arthritis, gastric dysfunction, and cancers [6,13,14].


Though several systematic reviews have been conducted, limitations regarding the reporting quality still persist. Important subjects that need further investigation include, but are not limited to, heterogeneous population, less stringent criteria, inadequate quality assessment, and inconsistent results. More importantly, there is still a lack of a comprehensive review in terms of critically assessing and comparing the quality of the evidence derived from RCTs in different domains of their efficacy. This study aimed to provide a systematic summarization of the effectiveness of oral ginger in human health and diseases in current RCTs. In addition, we evaluated ginger efficacy in every reported clinical-related aspect to provide future directions for the clinical research of ginger. Furthermore, we evaluated the ongoing development and achievement of ginger-related randomized clinical trials in specific representative topics. Finally, the shortcomings of available RCTs in terms of the ginger effect investigation were discussed.

2. Materials and Methods
2.1. Literature Search Strategy
The study follows the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines (Table S1) [15]. A systematic search was conducted on six libraries, including four English databases and two Korean databases. Firstly, for English literature, we searched Pubmed, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), and Clinical Trials (ClinicalTrial.gov) with the query: “Zingiber officinale” OR “Z. officinale” OR “Ginger.” Next, two Korean databases, Korean studies Information Service System (KISS) and National Digital Science Library (NDSL), were searched using the query: “Zingiber officinale” OR “Z. officinale” OR “Ginger” and Korean language terms related to ginger. Data were collected up to July 2019 and regularly updated by manual search. There was no limitation in the search period.


2.2. Inclusion and Exclusion Criteria
We first imported the search results to Endnote X9 and performed the duplication removal step. The remaining papers were screened for title and abstract. This study focused on randomized clinical trials investigating the efficacy of ginger to improve human health as well as to support human disease. For that reason, any paper that reported the effectiveness of ginger in clinical aspects was included in this study. Inappropriate articles were excluded for the following reasons: (1) not clinical trials; (2) not related topic; (3) irrelevant data for analysis; (4) secondary analysis; (5) unavailable abstract or full-text; (6) duplication; and (7) case reports, letters, commentaries, meeting records, or review articles. At least two authors performed this step to evaluate the eligibility of each item. Next, the qualification of each paper was assessed by reading the full-text, and the qualified articles were collected for the next extraction data step. In addition, a manual search was also conducted by screening the reference lists of the selected articles. Finally, the qualified papers were included for the data extraction process.


2.3. Data Extraction
The details of demographic populations and study design information, including year, sample allocation, sample size, age, study design, symptom and disease, treatment and control group intervention information, duration of therapy, and blinding, were extracted. Importantly, we extracted the evaluation outcome system, key findings, and adverse effects of each study, as well as their found side effects, if any.


2.4. Quality Assessment
The Cochrane Collaboration’s tool was employed to evaluate the risk of bias in individual research for quality assessment [16]. The tool included seven items that aimed to evaluate the quality of study design (e.g., randomization), the result (e.g., outcome reporting), and other biases. All items were independently assessed and scored by at least two reviewers to avoid personal bias. Seven items were evaluated for all 109 studies, which were scored into three scales: H indicates a high risk of bias, U indicates an unclear risk of bias, and L indicates a low risk of bias. Additionally, each essential function was scored based on seven quality reporting items: 0 points for a high risk, 1 point for an unclear risk, and 2 points for a low risk of bias, and the quality assessment score (QA score) as the sum of each point. We set the criteria at the QA score of 10 or above as a ‘high quality of evidence.’

3. Results
3.1. Study Selection
After a systematical search that selectively focused on the study design of the clinical trials, we retrieved 221, 222, 59, and five papers from PubMed, Embase, Clinical Trials, and CENTRAL, respectively. Subsequently, 101 duplication records were eliminated. Next, the titles and abstracts of the remaining records were screened for eligibility for the extraction process. Finally, 137 records were included for the full-text monitoring, and 109 qualified articles, including manual search papers remained for the final data extraction step. Similarly, we extended our search method to two Korean literatures databases (KISS and NDSL) and retrieved a remarkable number of studies (n = 790 after duplication removal). Unfortunately, no Korean papers qualified after the standard flow of evaluation. The workflow of this study is shown in Figure 1.