Application of a Fasting-mimicking Diet in Obese Patients With Periodontitis Stage III-IV

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Periodontitis (Stage 3); Periodontitis Stage IV
• Intervention / Treatment: Dietary supplement: Fast mimicking diet group; Procedure: Normal diet group

Detailed Description

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

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: İpek Özgü; Phone Number: +90 545 525 83 08; Email: ipekozgu7@gmail.com

Study Locations

• Turkey (Türkiye)
  • Antalya, Turkey (Türkiye), 07070
    • Akdeniz University Faculty of Dentistry
    • Contact: İpek Özgü, MSc, Dr.; Phone Number: +90 545 525 83 08; Email: ipekozgu7@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Fasting mimicking diet group; Participants will receive standard non-surgical periodontal therapy and three 5-day cycles of a fasting-mimicking diet administered around the treatment period.	Dietary supplement: Fast mimicking diet group; Participants assigned to this intervention will undergo standard non-surgical periodontal therapy and will receive a fasting-mimicking diet (FMD) in three 5-day cycles administered around the treatment period. The FMD is a plant-based, calorie-restricted dietary program composed of foods generally recognized as safe, including vegetable-based soups, energy bars, energy drinks, cracker snacks, olives, herbal teas, and supplements. The regimen provides approximately 1,100 kcal on day 1 and approximately 750 kcal per day on days 2 to 5.
Active Comparator: Normal diet group; Participants will receive standard non-surgical periodontal therapy and will continue their usual diet during the study period.	Procedure: Normal diet group; Participants assigned to this intervention will undergo standard non-surgical periodontal therapy and will continue their usual diet without receiving the fasting-mimicking diet during the assigned study phase.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum CRP values	CRP level will be evaluated biochemically	at 90- and 360 days post-treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum CRP values		baseline, 1 day post-treatment, 7 days post-treatment, 45 days post-treatment, 180 days post-treatment, 225 days post-treatment, 270 days post-treatment
Analysis of inflammatory cytokines in GCF		baseline, 1 day post-treatment, 7 days post-treatment, 45 days post-treatment, 180 days post-treatment, 225 days post-treatment, 270 days post-treatment
Analysis of sub-gingival plaque samples	Relative abundance of selected periodontal pathogens in sub-gingival plaque samples	baseline, 90 days post-treatment, 180 days post-treatment and 360 days post-treatment
Patients reported quality of life measurements	Patients' outcomes will be assessed by Oral Health Impact Profile-14 (OHIP-14) questionnaire which is used to evaluate the impact oral health (including functional limitations, pain, physiological discomfort, physical disability, social disability, sense of taste, diet unsatisfactory and handicap) on person's life. The Oral Health Impact Profile-14 (OHIP-14) was designed to assess patients' perception of the impact of oral disorders on their quality of life (QoL).	baseline, 90 days post-treatment, 180 days post-treatment and 360 days post-treatment
Analysis of stool samples	Changes in gut microbiome composition in stool samples	Baseline and at 90 days post-treatment, 180 days post-treatment and 360 days post-treatment

Collaborators and Investigators

• Sponsor: Akdeniz University
• Investigators: Study Director: Luigi Nibali, Prof. Dr., King's College London, Guy's Hospital; Principal Investigator: Kemal Üstün, Prof. Dr., Akdeniz University; Principal Investigator: Mükerrem Hatipoğlu, Prof. Dr., Akdeniz University; Study Director: Giuseppe Mainas, Dr., King's College London, Guy's Hospital

Publications and helpful links

General Publications

• Mainas G, Ozgu I, Sari A, Vinciguerra M, Ide M, Ayakta BB, Ustun K, Nibali L. The application of a fasting-mimicking diet in periodontitis. A feasibility study. J Dent. 2025 May;156:105644. doi: 10.1016/j.jdent.2025.105644. Epub 2025 Feb 19.

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: April 10, 2026
• First Submitted That Met QC Criteria: April 17, 2026
• First Posted (Actual): April 24, 2026

Study Record Updates

• Last Update Posted (Actual): April 24, 2026
• Last Update Submitted That Met QC Criteria: April 17, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: periodontitis; fasting mimicking diet; non surgical treatment; systemic response
• Additional Relevant MeSH Terms: Periodontal Diseases; Mouth Diseases; Stomatognathic Diseases; Periodontitis
• Other Study ID Numbers: Akdeniz-U

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No