This study will evaluate whether a fasting-mimicking diet (FMD) can improve the systemic and periodontal response to non-surgical periodontal treatment in obese adults with severe periodontitis. Periodontitis is a serious inflammatory disease that damages the tissues supporting the teeth and may also contribute to inflammation elsewhere in the body. Obesity is also associated with increased systemic inflammation, which may worsen periodontal disease and affect treatment outcomes.

In this pilot randomized cross-over clinical trial, eligible participants will receive full-mouth non-surgical periodontal therapy and will be assigned either to an FMD group or to a control group continuing their usual diet. The FMD will be administered in three 5-day cycles around the periodontal treatment period. After a wash-out period, the groups will switch interventions.

The study will assess whether FMD can reduce systemic inflammation, measured primarily by serum C-reactive protein (CRP), and improve periodontal healing after treatment. Additional outcomes include clinical periodontal measurements, inflammatory markers in gingival crevicular fluid, and changes in oral and gut microbiota. Findings from this study will help determine the feasibility of this dietary approach and provide preliminary data for a larger clinical trial.

Periodontitis is a chronic, biofilm-associated inflammatory disease that leads to destruction of the tooth-supporting tissues and may contribute to systemic inflammation. Obesity is also characterized by a heightened inflammatory burden and may adversely influence periodontal disease severity and treatment response. Although non-surgical periodontal therapy is effective in reducing periodontal inflammation, the short- and medium-term systemic inflammatory response after treatment may vary between individuals. Nutritional strategies that can modulate inflammation may therefore represent a promising adjunctive approach in periodontal care. Previous evidence suggests that dietary restriction regimens may improve periodontal parameters and reduce local and systemic inflammatory burden; however, robust human trials remain limited, particularly in obese individuals with severe periodontitis. In addition, fasting-mimicking diet (FMD) protocols have shown beneficial effects on inflammatory and metabolic pathways and may influence both host response and microbial ecology. No clinical trial has specifically investigated the effects of FMD in obese patients with severe periodontitis.

This study is designed as a pilot, randomized, cross-over clinical trial to investigate whether a fasting-mimicking diet can modify the systemic and periodontal response to non-surgical periodontal therapy in obese adults with stage III-IV periodontitis. The clinical phase will be carried out at Akdeniz University, while laboratory analyses will be performed at King's College London. After baseline assessment, participants will receive standardized step 1 and step 2 periodontal treatment, including oral hygiene instruction, risk-factor control, and full-mouth supra- and subgingival professional mechanical plaque removal. Residual pockets will be re-instrumented during follow-up according to the study schedule.

Participants will be allocated to one of two study sequences. In the intervention phase, participants assigned to the test condition will follow three cycles of a 5-day fasting-mimicking diet administered around the periodontal treatment period, while participants in the control condition will continue their usual diet. After a wash-out period, the two groups will cross over, allowing each participant to contribute data under both dietary conditions. Because masking of diet allocation is not feasible, the study is designed with blinding of the outcome assessor and statistician. Randomization and allocation concealment will be centrally organized. Compliance with the dietary intervention will be monitored using daily diet questionnaires, and adverse events will be recorded throughout the study period.

The study will evaluate the biological and clinical effects of FMD using an integrated approach. Systemic inflammation will be assessed primarily through serum C-reactive protein measurements. Local inflammatory response will be examined using gingival crevicular fluid biomarkers, including inflammatory cytokines and matrix metalloproteinase-8. In addition, subgingival plaque and stool samples will be analyzed to explore whether the intervention is associated with measurable changes in oral and gut microbiota composition and function. Clinical periodontal outcomes and patient-reported measures will also be collected longitudinally. This pilot trial is intended to generate preliminary evidence on feasibility, adherence, biological effect size, and outcome variability, thereby informing the design and sample size calculation of a future larger-scale trial

Inclusion Criteria:

• 18-70-year-old patients,
• Severe Periodontitis (Stages III-IV),
• Systemically healthy,
• Overweight (body mass index - BMI > 30 kg/m2),
• Absence of hopeless teeth, acute dental conditions, endo-perio lesions and necrotising periodontal diseases,
• Minimum of 20 teeth present.

Exclusion Criteria:

• Current smokers,
• Pregnant women,
• Patients drinking more than 20 units of alcohol weekly,
• Taking medications including systemic anti-inflammatory medication within 3 months of the study,
• Periodontal treatment and/or systemic antibiotics intake within preceding 3 months
• Denture wearer/presence of dental implants,
• Significant food allergies and/or special dietary requirements which would make the subject unable to consume the food provided.

Due to the nature of the dietary intervention, participants and treating clinicians cannot be blinded. However, clinical outcome assessors and the statistician will remain blinded to treatment allocation until completion of the analysis.