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

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.

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.

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).

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.