Key messages

• The Mediterranean diet may make little or no difference in pain and disease activity for patients with rheumatoid arthritis (low certainty evidence). 
• We are uncertain whether Mediterranean diet improves functionality, morning stiffness and quality of life in rheumatoid arthritis as the certainty of the evidence has been assessed as very low. 
• Mediterranean diet may slightly increase weight among rheumatoid arthritis patients (low certainty evidence).

What is the evidence.
See evidence matrix  in Epistemonikos later

We found seven systematic reviews [1], [2], [3], [4], [5], [6], [7] which included four primary studies, reported in six references [8], [9], [10], [11], [12], [13] of which only one was a randomized trial [8]. The information provided by the observational studies did not increase the level of certainty of the evidence, nor did add new relevant information. Therefore the table presented and the summary is based on the only randomized trial. 

What types of patients were included*

The trial was conducted in Sweden [8] and included 51 patients, mostly women (82.3%), with rheumatoid arthritis diagnosed by criteria ACR 1987, with at least two years from diagnosis and controlled disease according to the clinician criteria at randomization. The trial excluded patients who already had a vegetarian or Mediterranean diet, with high doses of corticosteroids, or recent adjustments in therapy.

What types of interventions were included*

The trial [8] evaluated a Mediterranean diet high in oils for 12 weeks in the intervention group, compared to Western diet in the control group.

The intervention was conducted in two stages with three weeks of education and diet in the hospital, followed by nine weeks of strict clinical follow-up where the food included in the diet was provided.

What types of outcomes
were measured

The trial [8] evaluated multiple outcomes, which were grouped by the systematic reviews as follows:

• Pain (visual analogue scale, VAS)
• Functionality (Health Assessment Questionnaire, HAQ)
• Morning stiffness (minutes)
• Activity Score (Disease Activity Score, DAS 28)
• Vitality (SF-36)
• Weight (kg) at week 12 of the intervention. 
• Inflammatory parameters (C reactive protein, CRP) 

To whom this evidence does and does not apply

• These results are applicable to patients with rheumatoid arthritis with controlled disease. The population with uncontrolled (active) disease was explicitly excluded from the trial and it is reasonable, from the clinical point of view, to expect a different effect in these cases.

• The outcomes selected are those considered critical for decision-making by the authors of this summary, among those reported in the analyzed trial. In the case of having had information about other relevant outcomes such as ACR 20 or ACR 70 these would have been incorporated as well.
• It is important to emphasize that although the effect observed in some outcomes is statistically significant in favor of the Mediterranean diet, the magnitude of the benefit does not exceed the thresholds usually defined to consider the effect clinically relevant. It is not possible to establish whether the Mediterranean diet really has a small but existing effect, or if it is only a spurious finding derived from the methodological limitations of the trial.

• This is an intervention where the benefits on symptoms and progression of rheumatoid arthritis are uncertain in some outcomes and not clinically relevant in others. 
• Although the adverse effects of the intervention are minimal, which translates into treatment withdrawal rates due to adverse effects that were not different from the control group [7], it is important to note that a higher final weight was reported.

• This intervention has costs associated to both food and the necessary processes to get people to incorporate it efficiently into their lives. For example, in the trial analyzed, a first stage of intensive education was carried out in an in-hospital setting, followed by an out-of-hospital follow-up managed by the health team, including the appropriate food for the study participants. The total cost of implementing an intervention with these characteristics depends to a large extent on whether there are nutritional programs that are responsible for training dietary changes or food provision for patients. 
• None of the identified studies reported a formal cost or cost-benefit analysis.

• When faced with the evidence presented in this summary, most patients and treating physicians should lean against its use. 
• However, people might be inclined in favor of its use, since there is a positive perception regarding the possible benefits that the Mediterranean diet has on other diseases that are not related to rheumatoid arthritis symptoms and progression (cardiovascular effects, cancer, dementia, among others).

Differences between this summary and other sources

• The results of this summary are in general in agreement with the reviews analyzed, in terms of the limitations of existing evidence and the associated uncertainty. 
• Although the conclusions presented by the authors of the trial are concordant with this summary, they are in general more optimistic on interpreting the results, based on the effect on some surrogate outcomes, such as plasma markers of inflammation [8]. 
• In the main clinical guidelines, such as the American College of Rheumatology 2015 [14] and the European League Against Rheumatism 2016 [15], the Mediterranean diet is not mentioned.

• The conclusions of this summary are likely to change when new evidence is available, due to the existing uncertainty. 
• Two relevant randomized trials were identified in the International Clinical Trials Registry Platform of the World Health Organization [16], [17], but their results have not yet been published. These could shed new light on this debate.