# Effect of Self‐Assembling Peptide on White Spot Lesions in Orthodontic Patients: A Systematic Review and Meta‐Analysis

## TL;DR

This study reviews evidence on whether a self-assembling peptide can reduce white spot lesions in orthodontic patients compared to fluoride or no treatment.

## Contribution

A systematic review and meta-analysis evaluating SAP's effectiveness for white spot lesions in orthodontic patients.

## Key findings

- SAP significantly reduced WSL severity compared to fluoride or control (SMD = −1.68).
- High heterogeneity (I² = 85.4%) and very low evidence certainty were observed.
- Findings suggest SAP may be more effective than topical fluoride for WSL reduction.

## Abstract

Objective: To evaluate the effect of self‐assembling peptide (SAP) on white spot lesions (WSLs) in orthodontic patients with fixed appliances.

Eligibility Criteria: Randomized and non‐randomized clinical studies, as well as in vitro studies, comparing SAP with fluoride or no treatment for WSLs in orthodontic patients were included. Outcomes assessed were WSL score, lesion size, or fluorescence loss. Case reports, case series, animal studies, and narrative reviews were excluded.

Information Sources: Comprehensive literature search of six databases was conducted up to May 16, 2025.

Risk of Bias: Risk of bias was assessed using tools appropriate to each study design: RoB‐2 for randomized controlled trials, ROBINS‐I for non‐randomized studies, and QUIN for in vitro studies.

Synthesis of Results: Random effects meta‐ analyses using standardized mean differences (SMDs) and their 95% confidence intervals (CIs) were performed, followed by subgroup, sensitivity analyses, and assessment of the quality of evidence was done using GRADE approach.

Included Studies: Eight studies (five randomized, two non‐randomized prospective, one in vitro) involving 395 participants were included.

Synthesis of Results: Meta‐analysis of eight studies showed a significant reduction in severity of WSLs with SAP compared to fluoride or control (SMD = −1.68; 95% CI: −2.71 to −0.67; p = 0.005), but with high heterogeneity (I
2 = 85.4%) and wide prediction interval (−4.20 to 0.82). Evidence certainty was very low due to risk of bias, inconsistency, imprecision, and indirectness.

Limitations of Evidence: The study is limited by the inclusion of less number of studies, one in‐vitro study, and some non‐randomized trials.

Interpretation/Conclusion: It can be concluded that very low‐level evidence is available that SAP can reduce the severity of WSLs associated with fixed orthodontic treatment more effectively than topical fluoride or no treatment.

Registration: PROPSERO Registration Number: (CRD420251112657).