Effect of Mediterranean vs Paleolithic Diet on RA Activity, Sarcopenia and QOL: 12-Week RCT

February 22, 2026 updated by: Gehad Maghraby, Kasr El Aini Hospital

Effect of Mediterranean and Paleolithic Dietary Interventions on Nutritional Status, Disease Activity, Sarcopenia, and Quality of Life in Adults With Rheumatoid Arthritis: A 12-Week Randomized Controlled Trial

This study aims to evaluate the effects of Mediterranean and Paleolithic dietary interventions on nutritional status, disease activity, fatigue, sleep, and quality of life in adults with rheumatoid arthritis (RA). Participants aged 40-60 years will be randomly assigned to follow either a Mediterranean diet, a Paleolithic diet, or continue their usual diet for 12 weeks. The study will assess anthropometric measurements, disease activity score (DAS28), laboratory biomarkers (CBC, CRP, ESR, lipid profile, fasting glucose, HbA1c), and patient-reported outcomes. The trial will determine whether these diets improve RA management and overall well-being.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease characterized by progressive erosive polyarthritis, impaired physical function, and reduced quality of life. Patients with RA are at increased risk of comorbidities such as cardiovascular disease, osteoporosis, infections, and mortality due to ongoing inflammation and long-term immunosuppressive therapy.

Diet and nutrition have gained attention as potential modulators of RA activity, partly due to their effects on systemic inflammation, gut microbiota, and antioxidant status. The Mediterranean diet (MD), rich in fruits, vegetables, olive oil, and limited meat, has shown beneficial effects on cardiovascular health, RA symptoms, and quality of life, although evidence is still of moderate certainty. The Paleolithic diet (PD), emphasizing lean meats, fish, fruits, vegetables, nuts, and seeds while excluding grains, dairy, and processed foods, has shown promising anti-inflammatory effects in autoimmune conditions, metabolic improvements, and reduction of RA-related symptoms in preliminary studies.

This randomized controlled trial will recruit adults aged 40-60 years with RA from the Kasr Al-Ainy Internal Medicine Inpatient and Outpatient Rheumatology Clinics. Participants will be randomly assigned to one of three groups: Mediterranean diet, Paleolithic diet, or control (usual diet) for 12 weeks. Baseline and post-intervention assessments will include:

Nutritional assessment via Food Frequency Questionnaire and Nutrition Awareness Questionnaire

Anthropometric measurements: weight, height, BMI, waist, and hip circumference

RA disease activity using DAS28

Laboratory investigations: CBC, CRP, ESR, lipid profile, fasting glucose, HbA1c

Patient-reported outcomes: fatigue, sleep quality, stress, and quality of life

The primary objective is to evaluate whether dietary interventions improve nutritional status and RA disease activity. Secondary objectives include comparing the effects of MD and PD on fatigue, sleep, stress, and overall quality of life. The study seeks to provide evidence for dietary strategies as adjunctive management for RA, improving both clinical and metabolic outcomes.

Study Type

Interventional

Enrollment (Estimated)

75

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Egypt
    • Al-Manial
      • Cairo, Al-Manial, Egypt, 11956
        • Recruiting
        • Kasr Al Ainy Hospital, Faculty of Medicine, Cairo University
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Patients classified as having rheumatoid arthritis according to the 2010 rheumatoid arthritis ACR/ EULAR classification criteria with a selected age group of 40 to 60 years old.

Exclusion Criteria:

  • Patients with comorbidities (e.g., diabetes mellitus, hypertension, gout, thyroid dysfunction).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Mediterranean Diet (MD)
Other: Mediterranean Diet (MD)
Participants will follow a Mediterranean diet for 12 weeks, emphasizing fruits, vegetables, whole grains, legumes, fish, and olive oil, with limited red meat and processed foods. Nutritional counseling and meal plans will be provided.
Active Comparator: Paleolithic Diet (PD)
Other: Paleolithic Diet (PD)
Participants will follow a Paleolithic diet for 12 weeks, focusing on lean meats, fish, fruits, vegetables, eggs, nuts, and seeds, while excluding grains, legumes, dairy, processed foods, refined sugars, and added salt. Nutritional counseling and meal plans will be provided.
Placebo Comparator: Control (usual diet)
Other: Control (Usual Diet)
Participants will continue their habitual diet without specific dietary modifications. General healthy eating advice may be provided.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Compare the effect of mediterranean diet and plaeolithic diet on the rate of change in the Rheumatoid Arthritis Disease Activity Score-28 (DAS-28 score)
Time Frame: 12 weeks
Disease activity will be evaluated using the Disease Activity Score based on 28 joints (DAS-28), a validated composite index that includes the number of tender and swollen joints (28-joint count), erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP), and patient global health assessment. The DAS-28 score ranges from 0 to 9.4, with higher scores indicating greater disease activity. The rate of change will be determined by calculating the difference in DAS-28 scores from baseline to the end of the intervention period (12 weeks) and comparing the mean change between the Mediterranean diet and Paleolithic diet groups.
12 weeks
Compare the effect of mediterranean diet and plaeolithic diet on rate of change of World Health Organization quality of life questionnaire (WHOQOL-BREF)
Time Frame: 12 weeks
Quality of life will be assessed using WHOQOL-BREF, a validated instrument that evaluates four domains: physical health, psychological health, social relationships, and environment. Domain scores are transformed to a scale ranging from 0 to 100, with higher scores indicating better quality of life. The rate of improvement will be determined by calculating the change in domain and total scores from baseline to the end of the intervention period (12 weeks) and comparing the mean change between the Mediterranean diet and Paleolithic diet groups.
12 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Compare the effect of mediterranean diet and plaeolithic diet on incidence of sarcopenia according to the European Working Group on Sarcopenia in Older People (EWGSOP2, 2019)
Time Frame: 12 weeks
Sarcopenia will be defined according to EWGSOP2 criteria as the presence of low muscle strength and low muscle mass. Low muscle strength will be assessed by handgrip dynamometry (<27 kg in men and <16 kg in women). Low muscle mass will be measured using bioelectrical impedance analysis (BIA) and expressed as appendicular skeletal muscle mass index (ASMI), with cut-off values of <7.0 kg/m² in men and <5.5 kg/m² in women. Physical performance will be evaluated using gait speed (≤0.8 m/s) to classify severe sarcopenia. Incidence will be defined as the proportion of participants who develop sarcopenia during the intervention period (from baseline to 12 weeks).
12 weeks
Compare the effect of the Mediterranean diet and Plaeolithic diet on the rate of change of the body mass index (BMI)
Time Frame: 12 weeks
Body mass index (BMI) will be calculated as weight in kilograms divided by height in meters squared (kg/m²). Body weight and height will be measured using standardized procedures. The rate of change in BMI will be determined by calculating the difference between baseline and the end of the intervention period ([insert duration, e.g., 12 weeks]) and comparing the mean change between the Mediterranean diet and Paleolithic diet groups.
12 weeks
Compare the effect of the Mediterranean diet and the Paleolithic diet on the rate of change in Waist-to-Hip Ratio (WHR)
Time Frame: 12 weeks
Waist circumference (cm) and hip circumference (cm) will be measured using a non-stretchable measuring tape according to standardized protocols. Waist-to-hip ratio (WHR) will be calculated as waist circumference divided by hip circumference. The rate of change in WHR will be determined by calculating the difference between baseline and the end of the intervention period (12 weeks) and comparing the mean change between the Mediterranean diet and Paleolithic diet groups.
12 weeks
Compare the effect of the Mediterranean diet and Plaeolithic diet on the rate of change in muscle mass assessed by Bioelectrical Impedance Analysis (BIA)
Time Frame: 12 weeks
Muscle mass will be assessed using bioelectrical impedance analysis (BIA) under standardized conditions. Appendicular skeletal muscle mass index (ASMI, kg/m²) will be calculated as appendicular skeletal muscle mass divided by height squared. The rate of change in ASMI will be determined by calculating the difference between baseline and the end of the intervention period (12 weeks) and comparing the mean change between the Mediterranean diet and Paleolithic diet groups.
12 weeks
Compare the effect of the Mediterranean diet and Plaeolithic diet on the rate of change in Hemoglobin (HB).
Time Frame: 12 weeks
Hemoglobin (HB) levels will be measured in g/dL using standard laboratory methods. The rate of change will be determined by calculating the difference between baseline and 12 weeks and comparing the mean change between the Mediterranean diet and Paleolithic diet groups.
12 weeks
Compare the effect of the Mediterranean diet and Plaeolithic diet on the rate of change in C-Reactive Protein (CRP).
Time Frame: 12 weeks
C-reactive protein (CRP) levels will be measured in mg/L using standardized laboratory assays. The rate of change will be determined by calculating the difference between baseline and 12 weeks and comparing the mean change between the Mediterranean diet and Paleolithic diet groups.
12 weeks
Compare the effect of the Mediterranean diet and Plaeolithic diet on the rate of change in Erythrocyte Sedimentation Rate (ESR).
Time Frame: 12 weeks
Erythrocyte sedimentation rate (ESR) will be measured in mm/hour using standard laboratory methods. The rate of change will be determined by calculating the difference between baseline and 12 weeks and comparing the mean change between the Mediterranean diet and Paleolithic diet groups.
12 weeks
Compare the effect of mediterranean diet and plaeolithic diet on the rate of change in Fasting Blood Glucose (FBG)
Time Frame: 12 weeks
Fasting blood glucose (FBG) will be measured in mg/dL after an overnight fast of at least 8 hours using standard laboratory techniques. The rate of change will be determined by calculating the difference between baseline and 12 weeks and comparing the mean change between the Mediterranean diet and Paleolithic diet groups.
12 weeks
Compare the effect of mediterranean diet and plaeolithic diet on the rate of change in Total cholesterol level (mg/dL)
Time Frame: 12 weeks
Total cholesterol will be measured after an overnight fast using standard laboratory assays (mg/dL). The rate of change will be determined by calculating the difference between baseline and 12 weeks and comparing the mean change between the Mediterranean diet and Paleolithic diet groups.
12 weeks
Compare the effect of mediterranean diet and plaeolithic diet on the rate of change in Low-density lipoprotein cholesterol (LDL-C, mg/dL)
Time Frame: 12 weeks
LDL-C will be measured after an overnight fast using standard laboratory assays. The rate of change will be determined by calculating the difference between baseline and 12 weeks and comparing the mean change between the Mediterranean diet and Paleolithic diet groups.
12 weeks
Compare the effect of the Mediterranean diet and the Paleolithic diet on the rate of change in High-density lipoprotein cholesterol (HDL-C, mg/dL)
Time Frame: 12 weeks
HDL-C will be measured after an overnight fast using standard laboratory assays. The rate of change will be determined by calculating the difference between baseline and 12 weeks and comparing the mean change between the Mediterranean diet and Paleolithic diet groups.
12 weeks
Compare the effect of the Mediterranean diet and the Paleolithic diet on the rate of change in Triglycerides (mg/dL)
Time Frame: 12 weeks
Triglycerides will be measured after an overnight fast using standard laboratory assays. The rate of change will be determined by calculating the difference between baseline and 12 weeks and comparing the mean change between the Mediterranean diet and Paleolithic diet groups.
12 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Kasr El Aini Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 17, 2026

Primary Completion (Estimated)

June 15, 2026

Study Completion (Estimated)

July 15, 2026

Study Registration Dates

First Submitted

February 15, 2026

First Submitted That Met QC Criteria

February 22, 2026

First Posted (Actual)

February 27, 2026

Study Record Updates

Last Update Posted (Actual)

February 27, 2026

Last Update Submitted That Met QC Criteria

February 22, 2026

Last Verified

February 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CU-FM-RA-DIET-001

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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