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


This is the first study that evaluated the impact of a 6-month nutritional advice based on the MD in patients affected with axSpA. Nutritional advice was effective in improving the adherence to the MD in almost half of the patients. Older patients and those with a lower BMI were more prone to modify their diet after nutritional advice. Furthermore, patients who achieved an increase in the PREDIMED score seemed to benefit from an improvement in the disease activity of axSpA, although this may be more difficult in patients affected by psoriasis. Despite the brief study period, during which no major changes in laboratory or anthropometric measures were observed, a numerical improvement in the indices of cardiovascular risk was noted, particularly in patients receiving nutritional advice.

About one-third of the patients initially enrolled in the study dropped out and could not complete the evaluation at month 6. The main reason for lost-to-follow-up was the isolation protocol during the COVID-19 emergency in Italy in February–April 2020.

An overall moderate adherence to the MD emerged at baseline in the entire cohort with most of the patients reporting a moderate adherence to MD. This finding is consistent with a study conducted in another Italian cohort of psoriatic arthritis patients showing very similar baseline PREDIMED score and only a few patients with optimal adherence to MD.[24] After 6 months, half of the patients in the nutritional group improved their adherence to MD, and the percentage of patients showing a PREDIMED improvement ≥ 20% as compared to baseline was higher in the nutritional group than in controls. Such small changes in the PREDIMED total score were expected given that a small number of subjects are indeed reported to effectively modify their diet following a nutritional intervention over a 6–12-month period.[17,25] Regarding specific nutrients, following nutritional advice, patients increased their olive oil, fruit, vegetables, and mixed nuts intake. Health improvements relating the specific food intake are not comparable with studies conducted in different countries, given the array of dietary habits compared to Italy.[26,27]

The multivariable analysis revealed that receiving nutritional advice increased by almost 5-fold the odds of achieving a ≥ 20% improvement in adherence to MD. The patients in the nutritional group have therefore undoubtedly benefitted from the suggestions provided by the nutritionist. Also, tight follow-up with frequent assessments may have improved the adherence to the given dietary recommendations. Patients with a lower BMI were more prone to achieve a PREDIMED improvement, which may reflect the fact that patients with an already good dietary control are more acquainted with food management and with the specific nutritional properties of the food. In addition, we observed that older patients (i.e., in their fifties) were more prone to improve their diet. This may be due to various factors: older patients may have more time to prepare meals according to the suggestion of the nutritionist, or could also be more compliant to the physician's prescription.

No significant reduction in BMI was observed in any of the study groups, which was expected given the short duration of the study and mostly because the diet was not aimed at reducing the caloric intake. Notably, some studies in rheumatoid arthritis suggested that a slight increase in weight may also occur following MD introduction.[28] That being so, a stable BMI has not prejudiced the observed variations of disease activity in this study, which can be attributed to the diet modification.[29]

A slight worsening of HbA1c was observed in the patients receiving nutritional advice. This finding may be explained by the fact that the MD may induce a higher glucidic intake compared to other diets which recommend a lower carbohydrate intake. We hypothesized that nutritional advice promoting low sugar intake (including non-sugary cereals) and complex carbohydrates with low glycemic index may be beneficial. Another possible explanation is that patients may have consumed predominantly fruits with a high glycemic index.

Adherence to MD emerged as the most significant predictor of improved disease activity in our study (≥ 20% vs. baseline, PREDIMED), resulting in a 7-fold increased likelihood of improving ASDAS-CRP as well.

Previous studies on MD nutritional interventions in rheumatic diseases have shown a beneficial effect on disease control and possibly a reduced incidence of inflammatory arthritis,[2,4,5,8,9,11,13,18,22,23,25] though no comparable studies are currently available in axSpA patients. A recent Italian cross-sectional study, limited to psoriatic arthritis patients, confirmed the association between a better adherence to MD and improved clinical activity indices.[24] Two studies conducted in England and in Sweden showed that the implementation of MD in patients with rheumatoid arthritis was mainly associated with an improved perception of pain and disease activity but also clinical indices (e.g., CRP).[26,27] Likewise, in our study, both the patient's evaluation (on a VAS scale) and the laboratory measures of inflammation (i.e., CRP) improved in the patients who initiated MD.

This improvement may be attributed to specific MD nutrients. During the study, patients receiving nutritional advice increased the consumption of olive oil and nuts which are rich in oleic acid and other n-3 polyunsaturated fats. There is evidence that n-3 polyunsaturated fatty acid supplementation—EPA and DHA, found in fish oil—associates with better disease activity scores in patients with rheumatoid arthritis.[3,11,13] These findings are further corroborated by studies showing that olive oil reduces inflammatory cytokine production and autoantibody development, increases T regulatory cell activation, and decreases Th17 response.[7,8,30] Furthermore, saturated fats and dietary fibers may also have an immunomodulatory effect on the gut microbiome in patients with autoimmune diseases.[31]

Notably, although physical activity was not an outcome of the study, patients receiving nutritional advice more frequently reported increased physical activity as compared to controls. Physical activity reduces fatigue and improves sleep and innate immunity in SpA and rheumatoid arthritis patients.[32,33]

Psoriasis was negatively associated to ASDAS-CRP improvement, although this finding was not significant. Patients with psoriasis are known to have a heterogeneous disease, often representing a challenge for the rheumatologist.[34] Furthermore, these patients are often overweight, with an overlapping metabolic syndrome and a higher cardiovascular risk.[14–16,35–40] Probably, axSpA patients with psoriasis will need studies with specific nutritional interventions.

Overall, a low cardiovascular risk was observed in all SpA patients in our cohort, irrespective of their diet, in line with previous findings of lower cardiovascular risk linked to Southern European diets.[41,42] The lipid profile did not improve in our study nor did the blood pressure or SCORE and CUORE indices, which may be attributed to the short time of the study. Except from an improvement in blood pressure following a 6-week MD intervention in rheumatoid arthritis,[26] no other study reports improvements of cardiovascular risk factors over a short time in rheumatic diseases and specifically in SpA.[15]

The first limitation of this study is that the adherence to the MD was evaluated based on a questionnaire given to the patient and not with a regular meal control and hospital admission as in other studies in rheumatoid arthritis.[27] Questionnaires are prone to biased results from socially desirable answering.[43] Nonetheless, the adoption of a questionnaire allows to conduct a study in a large cohort of patients and is necessary to recall the dietary habits of the patients. Secondly, a 6-month study period may be regarded as a short time to evaluate diet and disease improvement following a dietary modification. An intrinsic problem of all studies considering nutritional intervention is to ensure an adequate and persistent adherence to the dietary modifications designed by the nutritionist: it has to be considered that a 6-month study challenges the patients' compliance, making it difficult to maintain strict control over their eating habits for the course of study. This difficulty was one of the main reasons of drop-outs from the study, which was also affected by the isolation measures during the COVID emergency.