This protocol complies with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines ¹² to guarantee a thorough and transparent process. The methodology adheres to the standards set by the F1000 journal. Furthermore, this protocol has been registered in PROSPERO, the international prospective register of systematic reviews, since September 2024 with the registration number CRD42024584029.

The primary objective of the study is to assess the effectiveness of phytotherapy in comparison to standard antifungal treatments for oral candidiasis. The secondary objectives of this study are to describe potential side effects of phytotherapy substances used against oral candidiasis, to determine their minimum inhibitory concentrations if mentionned and to propose recommendations for future research to address gaps identified in the current study, particularly regarding the comparative effectiveness of phytotherapy versus traditional antifungal treatments.

Inclusion criteria

The PICO format is used to define inclusion criteria, specifying the essential elements of the research question. ¹³

The research question formulated for this systematic review is: “Is phytotherapy an effective alternative for treating oral candidiasis?”

Type of population: patients diagnosed with acute or chronic non invasive oral candidiasis, whether in good general condition or not. Eligible participants do not have other oral conditions such as active lichen planus, bullous diseases, neutropenic ulcers, or mucositis.

Intervention type: This systematic review will explore the use of phytotherapy in patients diagnosed with oral candidiasis. The intervention will involve various forms of phytotherapy, such as essential oils, gels, mouthwashes, and ointments, without concurrent antifungal treatment.

Comparaison group: The reference treatment for comparison is conventional antifungal medications locally applied on the oral mucosa.

Types of outcomes: This systematic review will evaluate the effectiveness of phytotherapy for treating oral candidiasis, focusing on key outcomes such as symptoms resolution and normalization of oral mucosa confirmed clinically, or by mycological exams. Additionally, it will assess potential side effects of phytotherapy on both oral mucosa and overall health.

Measures of effect: This systematic review will assess outcomes through both quantitative and qualitative measures. Quantitative assessments will involve statistical analysis of Candida colony counts on denture surfaces or oral samples before and after phytotherapy, as well as the p-value significance between study and control groups.

Qualitative measures will include evaluating the application technique of phytotherapy through observational data, determining the minimum inhibitory concentration for each component, and analyzing patient-reported outcomes. Meta-analytical methods may be applied to integrate and compare results from the published studies.

Study types: The articles included will primarily consist of randomized controlled trials (RCTs) that investigate phytotherapy use for oral candidiasis treatment. These studies will focus on symptom resolution and treatment effectiveness compared to conventional antifungals, and must be selected for their rigorous methodology to effectively achieve the research objectives.

Excluded articles will involve case reports, case series, animal studies, in vitro research, abstracts, and retrospective studies. Additionally, RCTs without follow-up, those comparing different types of phytotherapy in the control group, and those involving systemic antifungals will be excluded. Studies with inadequate data or methodological quality will also be excluded to maintain the review’s reliability and relevance.

A comprehensive search strategy involves a list of pertinent keywords and Medical Subject Headings (MeSH) terms associated with the research topic (e.g., “Candidiasis, Oral,” “Phytotherapy”). To ensure a broad search, synonyms, variations, and related terms are included. Boolean operators (AND, OR, NOT) are used to combine these keywords and terms, and search strategies are adapted to the unique syntax of each database.

In addition to MEDLINE, the search will cover databases like as EBSCO, Scopus, Cochrane Central, and EMBASE to minimize the risk of missing pertinent studies. Grey literature and ongoing clinical trials will also be sought through sources like clinical trial registries evaluated by an expert panel.

All articles found up to the date of the literature search will be reviewed to determine if they meet the inclusion criteria.

Study selection

All identified studies will be imported into EndNote software, with duplicates removed. Titles and abstracts will be reviewed by two independent reviewers based on the inclusion criteria. Eligible studies will then be retrieved in full and assessed for data extraction by the same reviewers. Reasons for excluding full-text studies not meeting the criteria will be documented and included in the final analysis. Discrepancies between reviewers will be resolved with a third reviewer. The search results will be presented in the final systematic review following PRISMA guidelines.

Evaluation of methodological quality and risk of bias

The methodological quality and risk of bias of the included studies will be evaluated with standardized tools. Risk of bias will be assessed based on Joanna Briggs Institute (JBI) criteria for RCTs, ¹⁴ which includes 13 items: 1) randomization, 2) allocation, 3) similarity of treatment groups at baseline, 4) blinding of participants, 5) blinding of personnel, 6) blinding of outcome assessors, 7) identical treatment of groups except for the intervention, 8) follow-up, 9) intention-to-treat analysis, 10) uniform outcome measurement, 11) reliable outcome measurement, 12) statistical analysis, and 13) trial design. Two independent reviewers will perform the assessments and score the studies to reduce bias and increase reliability. ¹⁵ Discrepancies will be addressed through discussion or by involving a third reviewer to achieve consensus. This approach will guarantee that the review’s conclusions are underpinned by high-quality evidence.

Data extracted from the selected studies will include participant demographics and study characteristics (publication year, author, study design). Additional details will cover the type of candidiasis, phytotherapy type and dose, application mode, intervention modalities, and outcome measures such as symptom resolution and side effects. Two reviewers will independently synthesize the data from all included clinical trials into comprehensive tables using a standardized extraction process. Discrepancies will be handled through discussion, and if required, a third reviewer will be involved. This structured approach guarantees accurate and dependable data extraction for future analysis.

Synthesis of data and statistical analysis

The extracted data will be used to evaluate the efficacy of phytotherapy in the treatment of oral candidiasis. The initial descriptive analysis will outline the study specifics, participant characteristics, intervention modalities, and outcome measures. Quantitative synthesis, including meta-analysis when appropriate, will compute effect sizes (mean differences, odds ratios, risk ratios) with 95% confidence intervals and evaluate heterogeneity using statistical tests like Cochran’s Q and I-squared. Heterogeneity among studies is assessed to determine whether differences in effect sizes are due to chance or other factors. ¹⁶

Findings will be interpreted regarding clinical relevance, addressing methodological strengths and limitations and suggesting future research directions in phytotherapy for oral candidiasis. A forest plot will be used to provide a visual representation of the effect sizes and confidence intervals from individual studies and the overall pooled effect. ¹⁷