Mediterranean Diet in Axial Spondyloarthritis

An Observational Study in an Italian Monocentric Cohort

Francesca Ometto; Augusta Ortolan; Davide Farber; Mariagrazia Lorenzin; Giulia Dellamaria; Giacomo Cozzi; Marta Favero; Romina Valentini; Andrea Doria; Roberta Ramonda


Arthritis Res Ther. 2021;23(219) 

In This Article

Patients and Methods

AxSpA patients followed at the Padova University Hospital (Veneto Region, Italy) were offered advice by a nutritionist for a 6-month period, starting in May 2019. We collected the information of the patients in the nutritional group (N) and of a comparable group of consecutive axSpA patients who did not receive nutritional advice, controls (C). All patients were assessed every 6 months (T0 and T6) by a rheumatologist trained in the clinical assessment of axSpA and blinded to the study group. Patients in N underwent the nutritional evaluation in the day of the visits (T0 and T6) and in between every 2 months. Clinical assessment, laboratory tests, and assessment of the adherence to the MD and of cardiovascular risk were collected for all patients at T0 and T6.


We included patients who underwent two consecutive rheumatological assessments since May 2019. Only patients fulfilling the following criteria were included in the analysis: age ≥ 18 years, diagnosis of axial involvement (axSpA) according to ASAS 2009 criteria,[18] and stable (≥ 6 months) biological/targeted synthetic disease-modifying antirheumatic drug (b/tsDMARD) treatment. Exclusion criteria were rheumatological conditions other than axSpA, ongoing specific diet or optimal MD, and concomitant diabetes mellitus/metabolic syndrome. Patients were allowed to change treatment in case of suboptimal disease control. However, in order to ensure a homogenous cohort of patients with stable treatment, patients with very high disease activity (i.e., ASDAS-CRP ≥ 3.5) were excluded. Eighty-one patients in N and 80 controls were consecutively enrolled.

The local medical ethical committee approved the study (Protocol No. 52723), and informed consent was obtained from all patients at study inclusion. The study was conducted in compliance with the Declaration of Helsinki of 1975/1983.

Nutritional Advice

Patients in N underwent an interview with a nutritionist at T0. Dietary habits were assessed through the PREDIMED questionnaire[17] and through a 24-h recall of meals consumed the previous day. Based on these evaluations, the nutritionist suggested dietary modifications in order to improve their adherence to the MD. Key recommendations of the nutritionist were as follows: fractionate daily caloric intake into 3 main meals and two snacks; ensure a daily caloric intake mainly consisting of carbohydrates (55%) preferably with low glycemic index, followed by fats (20–30%) and proteins (10–15%); include adequate amounts of fibers (25–30 g daily) and water (1.5–2 l daily); consumption of vegetables, fruits, sugar-free cereals, and olive oil in every meal; use of olive oil as the main culinary fat; daily consumption of low-fat dairy products and nuts and a moderate wine consumption; weekly consumption of fish, white meat, and legumes; reduced weekly consumption of red meat, eggs, and potatoes; limit the use of salt; and only occasional consume of pastries, sweets, and soft drinks. Importantly, adoption of a non-sedentary lifestyle and regular physical activity were also recommended (Additional file 1).[18] Every 2 months, the nutritionist asked the patients about their dietary habits and recalled the dietary modifications suggested at T0.

Clinical Assessment

At T0, sociodemographic information and information about disease history and treatments were collected. Clinical assessments were collected at T0 and T6 and included weight, height, body mass index (BMI), blood pressure, tender joint count (TJC), swollen joint count (SJC), dactylitis, Bath Ankylosing Score Metrology Index (BASMI), Maastricht Ankylosing Spondylitis Enthesitis Score (MASES), Leeds Enthesitis Index (LEI), Psoriasis Area Severity Index (PASI), physician assessment of disease on visual analogic scale (VAS), and patient-reported outcomes (PREDIMED questionnaire, the Italian version of 5-item compliance questionnaire for rheumatology (I-CQR5),[19] Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), Health Assessment Questionnaire (HAQ), patient VAS global, and patient VAS pain). Ankylosing Spondylitis Disease Activity Score (ASDAS) with C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) scores were also computed. The following laboratory measures were collected at T0 and T6 for disease activity assessment, diet, and cardiovascular risk monitoring in clinical practice:[16] hemoglobin (HB), white blood count (WBC), platelets, (PLT) ESR, CRP, urate, glycated hemoglobin (HbA1c), fasting blood glucose (FBG), low-density lipoprotein cholesterol (LDL-c), high-density lipoprotein cholesterol (HLD-c), triglycerides, total cholesterol (TC), glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT), gamma-glutamyltransferase (GGT), creatinine, and thyroid-stimulating hormone (TSH).

Dietary and Lifestyle Assessments

In both groups, patients were administered the Italian version of the PREDIMED questionnaire (Additional file 2) at T0 and T6. The score is computed as the sum of scores of each question, with higher values indicating a higher adherence to the MD (≤ 5 low adherence, 6–9 moderate adherence, ≥ 10 high adherence). Questions about continuous physical activity (yes/no) and the frequency of physical activity (< 1/weekly; 1/weekly; ≥ 2 weekly) were also administered.

Cardiovascular Risk Assessment

Cardiovascular risk assessment in this study was evaluated with the systematic coronary risk evaluation (SCORE) and CUORE indices at T0 and T6. In chronic inflammatory arthritis, SCORE for the appropriate country (i.e., low-risk countries for Italy) is recommended;[20] alternatively, the cardiovascular risk index recommended by national guidelines may be used, such as the Italian CUORE.[21] The computation of each index is detailed in Additional file 3.


b/tsDMARDs considered were adalimumab, certolizumab pegol, etanercept, golimumab, infliximab, secukinumab, ustekinumab, and apremilast; csDMARD were sulfasalazine and methotrexate. NSAIDs and low-dose corticosteroid treatment were also admitted.

Study Outcomes

To evaluate an improvement in the adherence to the MD, the T0–T6 change in the PREDIMED score was considered. An improvement ≥ 20% of the T0 value was considered as a positive outcome. As a measure of clinical improvement, the ASDAS-CRP index was considered, which comprehends both clinical and laboratory measures.[22] The CRP-based index was also chosen, since it is required for the medical prescription of rheumatological treatments in the Veneto Region. The T0–T6 change was computed and an improvement ≥ 20% of the T0 value was considered as a positive outcome. Despite measures for clinically relevant improvement with ASDAS-CRP are available,[23] a 20% cutoff was deemed appropriate in order to include also small improvements in clinical activity after a 6-month dietary modification.

Statistical Analysis

Characteristics of the patients are presented in all the study population and according to the study group. To identify potential biases in the study, univariate analysis tests were run to identify potential differences in T0 characteristics between C and N. Multivariate analysis was run to identify determinants of a ≥ 20% improvement from T0 in the PREDIMED score and in ASDAS-CRP. Variables included in the multivariate analysis were all those achieving a p < 0.10 in univariate analysis. Collinearity was assessed by the variance inflation factor (VIF), adopting a cutoff of VIF = 2 as an exclusion criterion. A logistic regression model was used, with a backward elimination approach. The results of multivariate logistic regression analysis are presented as the odds ratio (OR) with the corresponding 95% confidence interval (CI). Analyses were performed using SPSS version 24.0.