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

Official title

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

Overview

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.

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.

Interventions

• 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.
• 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.
• Other Control (Usual Diet)
  Participants will continue their habitual diet without specific dietary modifications. General healthy eating advice may be provided.

Primary outcome measures

• 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]
• 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]

Secondary outcome measures (12)

• 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]
• 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]
• 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]
• 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]
• Compare the effect of the Mediterranean diet and Plaeolithic diet on the rate of change in Hemoglobin (HB). [Time frame: 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]
• Compare the effect of the Mediterranean diet and Plaeolithic diet on the rate of change in Erythrocyte Sedimentation Rate (ESR). [Time frame: 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]
• Compare the effect of mediterranean diet and plaeolithic diet on the rate of change in Total cholesterol level (mg/dL) [Time frame: 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]
• 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]
• Compare the effect of the Mediterranean diet and the Paleolithic diet on the rate of change in Triglycerides (mg/dL) [Time frame: 12 weeks]

Eligibility criteria

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).

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Triple blind

Primary purpose

Treatment

Study locations

Egypt · 1 center

• Kasr Al Ainy Hospital, Faculty of Medicine, Cairo University — Cairo

Publications

• Hollywood JB, Hutchinson D, Feehery-Alpuerto N, Whitfield M, Davis K, Johnson LM. The Effects of the Paleo Diet on Autoimmune Thyroid Disease: A Mixed Methods Review. J Am Nutr Assoc. 2023 Nov-Dec;42(8):727-736. doi: 10.1080/27697061.2022.2159570. Epub 2023 Jan 4. PMID 36598468
• Daien C, Czernichow S, Letarouilly JG, Nguyen Y, Sanchez P, Sigaux J, Beauvais C, Desouches S, Le Puillandre R, Rigalleau V, Riviere P, Romon M, Semerano L, Seror R, Sfedj S, Tournadre A, Vacher D, Wendling D, Flipo RM, Sellam J. Dietary recommendations of the French Society for Rheumatology for patients with chronic inflammatory rheumatic diseases. Joint Bone Spine. 2022 Mar;89(2):105319. doi: 10 PMID 34902577
• England BR, Smith BJ, Baker NA, Barton JL, Oatis CA, Guyatt G, Anandarajah A, Carandang K, Chan KK, Constien D, Davidson E, Dodge CV, Bemis-Dougherty A, Everett S, Fisher N, Fraenkel L, Goodman SM, Lewis J, Menzies V, Moreland LW, Navarro-Millan I, Patterson S, Phillips LR, Shah N, Singh N, White D, AlHeresh R, Barbour KE, Bye T, Guglielmo D, Haberman R, Johnson T, Kleiner A, Lane CY, Li LC, Maste PMID 37227116
• Afifi L, Danesh MJ, Lee KM, Beroukhim K, Farahnik B, Ahn RS, Yan D, Singh RK, Nakamura M, Koo J, Liao W. Dietary Behaviors in Psoriasis: Patient-Reported Outcomes from a U.S. National Survey. Dermatol Ther (Heidelb). 2017 Jun;7(2):227-242. doi: 10.1007/s13555-017-0183-4. Epub 2017 May 19. PMID 28526915
• McNeill J, Zinn C, Mearns G, Grainger R. Elimination reintroduction diets and oral food challenge in adults with rheumatoid arthritis: a scoping review. Nutr Res Rev. 2025 Dec;38(2):699-716. doi: 10.1017/S0954422425000083. Epub 2025 Apr 4. PMID 40181632

Identifiers

NCT: NCT07438652 · CU-FM-RA-DIET-001

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗