Written by Tabish Mehraj, PhD. This study showed that the treatment group achieved greater reductions in ΔPPD and gains in ΔCAL across multiple tooth categories and surfaces. Metabolomic profiling revealed distinct Δ patterns, with 17 metabolites differing between groups. Several, including tentatively identified valine, cinnamic acid, 10‑hydroxy-2-decenoic acid, and cortisol, correlated with periodontal improvements.

Periodontitis is a preventable inflammatory condition that damages the supporting tissues of the teeth among the elderly population. There is increased systemic inflammation, altered microbial composition, and these factors worsen periodontal disease. There are treatment options such as root planning and scaling, but many patients continue to suffer from incomplete periodontal recovery. This randomized, double-blind, placebo-controlled clinical trial investigated whether supplementation with a standardized olive leaf extract (OLE) enriched to 40% oleuropein could enhance periodontal outcomes when used alongside conventional periodontal therapy. Standardized plant extracts may provide adjunctive therapeutic benefits. Oleuropein is a primary phenolic compound in olive leaf extract (OLE), that works by scavenging free radicals, inhibiting inflammatory mediators (TNF-α, IL-1β), and suppressing the growth of periodontal pathogens.

The OLIVAGING trial enrolled 60 participants aged 50 years or older with periodontitis. Participants were grouped to receive either 200 mg/day of OLE (80 mg oleuropein) or a placebo for 120 days. The two main indicators of periodontal health were assessed: any alteration in clinical attachment level (CAL) and probing pocket depth (PPD). Moreover, untargeted plasma metabolomic analysis was performed. Of the 60 participants who started the study, 43 completed it, including 23 in the OLE group and 20 in the placebo group.

Results/Key Findings

• Baseline demographic and periodontal characteristics were similar between the treatment and placebo groups, allowing a fair comparison of outcomes.

• Both groups showed improvement following periodontal therapy, but the oleuropein-enriched olive leaf extract (OLE) group showed significantly greater reductions in probing pocket depth (PPD).

• Whole-mouth buccal and lingual PPD reductions were substantially greater in the OLE group (14.9 mm and 14.5 mm, respectively) than in the placebo group (8.3 mm for both).

• Clinical attachment level gains were generally greater with OLE, although improvements were modest and not consistently significant across all tooth types.

• No serious adverse events were reported, suggesting that OLE is a safe and well-tolerated adjunct to conventional periodontal therapy.

• Certain metabolites were elevated in the treatment group, cinnamic acid, valine, and 10-hydroxy-2-decenoic acid (10-HDA) were negatively correlated with changes in PPD.

• The metabolomic findings suggest that OLE supplementation may promote periodontal healing through multiple interconnected pathways involving inflammation reduction, oxidative stress attenuation, immune regulation, and tissue repair.

The study possesses several strengths. Firstly, the randomized, double-blinded design minimizes bias and strengthens reliability. Secondly, the use of a standardized oleuropein extract ensured consistency, thereby improving reproducibility and potential clinical applicability. The integration of clinical periodontal assessments with advanced metabolomic profiling provided valuable mechanistic insights and identified potential biomarkers associated with treatment response. Finally, the intervention demonstrated a favorable safety profile, supporting the feasibility of using plant-derived bio-actives as adjunctive therapies. Also, a major strength of the study was the inclusion of metabolomics to assess the biological responses to supplementation.

Despite these strengths, the study has important limitations. The sample size was relatively small, 43, which limits the statistical power. To evaluate early periodontal healing, a 120-day intervention may not yield long-term clinical benefit or sustained metabolic effects. In addition, many metabolites were only tentatively identified by database matching rather than confirmed by authentic standards, introducing uncertainty about their exact identities. Furthermore, correlation analyses were examined, and cannot establish causality between metabolic changes and periodontal improvements.

In conclusion, supplementation with an oleuropein-enriched olive leaf extract improved periodontal outcomes in older adults receiving standard periodontal therapy. The treatment produced greater reductions in probing pocket depth, modest gains in clinical attachment, and significant alterations in systemic metabolic profiles associated with inflammation, oxidative stress, and tissue homeostasis. While larger, longer-term studies are needed to confirm these findings, the results support the potential of standardized olive leaf extract as a safe, multi-target adjunctive strategy for managing periodontitis in aging populations.

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Posted June 29, 2026.

Dr. Tabish Mehraj is a pharmaceutical scientist with expertise in pharmaceutics, drug delivery, and formulation development. She earned her PhD in Pharmaceutical Sciences from the University of Mississippi, where her research focused on the formulation, optimization, and characterization of lipid-based nanocarriers for targeted liver delivery of antimalarial therapeutics. Dr. Mehraj has also served as an ORISE Fellow at the U.S. Food and Drug Administration (FDA), where she evaluated the effects of formulation and process design on the quality and performance of intravaginal drug delivery systems and developed bio-relevant in vitro drug release testing methods. She has teaching experience in pharmaceutical and life sciences courses and has authored peer-reviewed publications, book chapters, and conference presentations. Dr. Mehraj is an active member of the American Association of Pharmaceutical Scientists and has been recognized by honor societies including Rho Chi and Gamma Beta Phi.

Reference:

1. Forbes-Hernández, T. Y., Vargas-Corral, F. G., Bullón, B., Rivas-García, L., Lipari, V., Giampieri, F., … & Quiles, J. L. (2026). Adjuvant treatment with an oleuropein-enriched olive leaf extract improves periodontal outcomes in older adults with periodontitis: Metabolomic insights from a randomized controlled trial. Phytomedicine, 158222.