Efficacy of Resistance Exercise and an Anti-Inflammatory Diet on Pain, Disease Activity, Functional Status, and Quality of Life in Patients With Rheumatoid Arthritis
Phase: NA
Conditions: Rheumatoid Arthritis
Sponsor: Berra Yamuç Tanrıöğen

Study Protocol / Research Summary 
 
Official Title of the Study: 
 Efficacy of Anti-inflammatory Diet and Resistance Exercise on Disease Activity, Pain, Physical 
Function, and Quality of Life in Patients with Rheumatoid Arthritis: A Randomized Controlled 
Trial 
 
Document Date: 
22 November 2025   
Prepared By: 
Berra YAMUÇ TANRIÖĞEN 
Purpose of Document: 
This document contains summary, hypothesis, objectives, scientific rationale, materials and 
methods, planned statistical analysis, and references supporting the study design and 
interventions. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
1. Study Participants 
1.a. Number of Participants 
 Healthy Volunteers: 0 
 Patient Volunteers: 80 
 Duration of Participation: Baseline, 6 weeks, 3 months 
1.b. Inclusion Criteria 
1. Participant voluntarily agrees to participate and signs informed consent. 
2. Age ≥ 18 years. 
3. Low to moderate rheumatoid arthritis disease activity (DAS28). 
1.c. Exclusion Criteria 
1. Age < 18 years 
2. Uncontrolled diabetes or other metabolic/endocrine disorders 
3. Uncontrolled hypertension 
4. Medication changes within the last month 
5. BMI > 40 (morbid obesity) 
6. Pregnancy 
7. Chronic kidney disease 
8. Psychiatric disorders 
9. Alcoholism 
10. Conditions contraindicating exercise (congestive heart failure, lung disease, 
cancer, active infection, recent fracture, recent ligament/tendon injury) 
1.d. Gender and Age 
 Both sexes, age ≥ 18 years 
 
2. Study Summary 
2.a. Hypothesis, Objectives, and Scientific Rationale 
Rheumatoid arthritis (RA) is a systemic, progressive inflammatory disease causing 
structural damage in small and large joints, often presenting as symmetrical polyarthritis. 
Its prevalence is approximately 1%. RA is multifactorial, arising from genetic and 
environmental factors. Environmental factors such as diet, smoking, infections, 
sedentary lifestyle, and socioeconomic status are associated with disease onset and 
activity. The primary goal of RA treatment is to achieve remission, and in addition to 
disease-modifying antirheumatic drugs (DMARDs), lifestyle interventions such as diet 
and exercise are recommended. 

Recent studies highlight the role of dietary modification in RA. Anti-inflammatory diets, 
emphasizing fish, fresh fruits and vegetables, vitamin D, and omega-3 intake while 
limiting salt, sugar, red meat, and gluten-rich foods, have been shown to reduce 
proinflammatory cytokines and disease activity. Physical activity increases fat 
metabolism and exerts anti-inflammatory effects via myokine release; moderate to high-
intensity aerobic and resistance exercises performed 2–3 times per week improve pain, 
swollen joint count, quality of life, and disease activity. 
Aim: To evaluate the effects of anti-inflammatory diet and resistance exercise, in 
addition to standard medical treatment, on RA disease activity, pain, functional status, 
and quality of life. The interventions aim to support disease remission. 
2.b. Materials and Methods 
This study will be conducted with RA patients aged ≥18 years presenting to the Physical 
Medicine and Rehabilitation clinic. Eighty patients will be randomized into four groups 
(20 per group): 1. Anti-inflammatory diet 2. Anti-inflammatory diet + resistance band 
exercise 3. Resistance band exercise only 4. Control (standard RA treatment) 
Data collected will include anthropometric measurements, personal information, and 
current medications. Evaluations will be performed at baseline, 6 weeks, and 3 months 
and include: dietary intake frequency, SF-36, DAS28, VAS, 6-minute walk test, 30-
second chair stand test, handgrip strength, and AIMS2. Exercise sessions will be 
supervised in the FTR unit 3 times per week for 6 weeks. Diet intervention will last 3 
months under dietitian supervision. Written informed consent will be obtained. 
2.c. References Used in Sections 2.a and 2.b 
1. Cush JJ. Rheumatoid Arthritis: Early Diagnosis and Treatment. Med Clin North 
Am. 2021 Mar;105(2):355-365. doi: 10.1016/j.mcna.2020.10.006. PMID: 
33589108. 
2. Alamanos Y, Drosos AA. Epidemiology of adult rheumatoid arthritis. Autoimmun 
Rev. 2005 Mar;4(3):130-6. doi: 10.1016/j.autrev.2004.09.002. PMID: 15823498. 
3. Shekhar KV, Pathak MM, Pisulkar G. Diet and Lifestyle Impact on Rheumatoid 
Arthritis: A Comprehensive Review. Cureus. 2023 Nov 10;15(11):e48625. doi: 
10.7759/cureus.48625. PMID: 38084187; PMCID: PMC10710847. 
4. England BR, Smith BJ, et al. 2022 American College of Rheumatology Guideline 
for Exercise, Rehabilitation, Diet, and Additional Integrative Interventions for 
Rheumatoid Arthritis. Arthritis Care Res (Hoboken). 2023;75(8):1603-1615. doi: 
10.1002/acr.25117. PMID: 37227116. 
5. Rondanelli M, Perdoni F, et al. Ideal food pyramid for patients with rheumatoid 
arthritis: A narrative review. Clin Nutr. 2021 Mar;40(3):661-689. doi: 
10.1016/j.clnu.2020.08.020. PMID: 32928578. 
6. Winkvist A, Bärebring L, et al. A randomized controlled cross-over trial 
investigating the effect of anti-inflammatory diet on disease activity and quality of 
life in rheumatoid arthritis: the ADIRA study protocol. Nutr J. 2018;17(1):1-8. 
7. Hernández-Hernández MV, Díaz-González F. Role of physical activity in the 
management and assessment of rheumatoid arthritis patients. Reumatol Clin. 

2017 Jul-Aug;13(4):214-220. doi: 10.1016/j.reuma.2016.04.003. PMID: 
27263964. 
8. Baillet A, Vaillant M, et al. Efficacy of resistance exercises in rheumatoid arthritis: 
meta-analysis of randomized controlled trials. Rheumatology (Oxford). 
2012;51:519–527. 
 
 
Planned Statistical Analysis 
Data will be analyzed using Linear Mixed Models (LMM) to evaluate the effects of group 
(control, exercise, diet, diet+exercise), time (baseline, 6 weeks, 3 months), and their 
interaction on body composition (e.g., body weight, fat mass, visceral fat, body fat 
percentage, total body water, total body water percentage, skeletal muscle mass, 
muscle mass, muscle mass percentage, waist circumference, hip circumference, waist-
to-hip ratio, upper arm circumference), functional measurements (sit-to-stand test, 6-
minute walk test), and quality of life outcomes (AIMS2, VAS, SF-36). LMM will be 
preferred because it does not require the sphericity assumption for repeated measures. 
The significance of group, time, and group×time effects will be assessed using likelihood 
ratio (LR) tests. In cases where LMM does not converge (e.g., due to singular matrix 
errors), ordinary least squares (OLS) regression will be used as an alternative. Normality 
will be checked using the Shapiro-Wilk test and Omnibus test (for skewness and 
kurtosis), and results will be interpreted cautiously if normality is violated (Omnibus p < 
0.05). 
Post-hoc comparisons will initially be performed using Estimated Marginal Means 
(EMMeans) for pairwise comparisons; however, if computational issues arise (e.g., 
shape mismatch errors), Bonferroni-corrected pairwise tests will be used instead. Effect 
sizes will be calculated as partial eta-squared (ηp²) for LMM and Cohen’s d for pairwise 
comparisons; ηp² values will be interpreted as small (0.01–0.059), medium (0.06–0.139), 
or large (≥0.14), and Cohen’s d values as small (0.2–0.49), medium (0.5–0.79), or large 
(≥0.8). Autocorrelation in OLS models will be assessed using the Durbin-Watson 
statistic, with values <1 indicating potential autocorrelation risk. 
Demographic characteristics will be compared using the Kruskal-Wallis test for 
continuous variables (e.g., age) and the chi-square test for categorical variables (e.g., 
sex). Subgroup analyses according to serostatus and RF/Anti-CCP categories will be 
conducted using LMM whenever possible. All analyses will be performed in Python 
(version 3.8) using the statsmodels and pingouin libraries. Statistical significance will be 
set at p < 0.05, and results will be interpreted considering the limited statistical power 
due to sample size (100, approximately 25 per group).