Can the Mediterranean Diet Ward off Rheumatoid Arthritis?

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High adherence to a Mediterranean diet reduced the odds of developing rheumatoid arthritis (RA) among men and among persons with seropositive RA, observed Swedish investigators in a recent large, population-based, case-control study.¹

Background
The Mediterranean diet is a primarily plant-based diet that includes high amounts of fruit, vegetables, whole grains, and legumes; moderate amounts of fish, white meat, and alcohol; and low amounts of red meat and sugar. It has previously been shown to reduce overall mortality, cardiovascular disease, and cancer.

Little is known about the potential link between the Mediterranean dietary pattern and the risk of RA. Only one previous study, a cohort study from the Nurses’ Health Study (NHS) in the US, specifically investigated the association between the Mediterranean diet and the risk of RA. Another nested case-control study from Sweden analyzed the effect of the Mediterranean diet, but not the main outcome. While the NHS study included only women and the Swedish study did not investigate the effect in men and women separately, neither study found any association between the Mediterranean diet and the risk of RA.

Led by Kari Johansson of the Karolinska Institutet in Stockholm, Sweden, the researchers sought to investigate the association between the Mediterranean diet and the risk of RA, with RA subtype, gender, and other risk factors taken into account. The results were published in Arthritis Research & Therapy.

The study
The study included subjects from the Swedish Epidemiological Investigation of RA (EIRA), a population-based case-control study, from defined geographical areas of central Sweden. Data on 1721 patients with incident RA and 3667 controls, matched on age, gender, and residential area, were analyzed using conditional logistic regression. The current study included participants from 2005 to 2014.

A self-reported food frequency questionnaire (FFQ) was used to evaluate participants’ food intake during the last year before inclusion. The FFQ asked participants to indicate how often on average they had consumed various foods. Fat and energy intake were calculated by multiplying the average frequency of consumption of each food by the fat and energy content of age-specific portion sizes, according to the Swedish National Food Administration Database. Adherence to the Mediterranean diet was defined according to a score ranging between 0 and 9. A higher score corresponded to higher adherence.

A baseline questionnaire was also distributed to patients and controls to collect data on smoking, body mass index (BMI), education, level of physical activity, and the use of nutritional supplements. Additional covariates were considered when analyzing women only, including parity, age at menarche, and use of oral contraceptives and hormone replacement therapy.

The findings
The Mediterranean diet was associated with a decrease in the odds of developing RA, with one unit increase in the Mediterranean diet score corresponding to an 8% decrease in the odds of having RA. After additional adjustments for smoking, physical activity, education level, BMI, energy intake, and the use of supplements, the odds ratio (OR) was 0.95. High adherence to the Mediterranean diet (score 6-9) reduced the odds of developing RA by 34%, compared with low adherence (score 0-2), based on the crude model conditioned on matching factors. The association remained statistically significant after adjustment for covariates.

When stratified by gender, the inverse association between high adherence to the Mediterranean diet and RA was statically significant among men (OR = 0.49) but not among women (OR = 0.94). Adding the female-specific covariates did not change the results. When stratified by RA subtype, the inverse association between Mediterranean diet score and RA was observed only among seropositive patients. A high score corresponded to lower odds in rheumatoid factor (RF)-positive and anti-citrullinated protein antibody (ACPA)-positive patients, but not in RF-negative and ACPA-negative patients.

Study limitations
The EIRA study is one of the largest population-based, case-control studies that includes incident cases of RA. Though it has extensive information, making it possible to account for many potential confounders, there are limitations. First, the FFQ assessing dietary intake was self-reported, and any case-control study based on self-report may be prone to recall bias. Patients with early RA symptoms may also have changed their diet during the year before diagnosis, so reverse causation may exist. Finally, the Mediterranean diet score does not reflect the absolute Mediterranean diet, but the distribution of the score 0-9 in the studied population. As a result, two persons with identical nutritional intake, but from two different study populations, might end up with different scores.

Implications for physicians
The current study found an inverse association between the Mediterranean diet and the risk of RA, but only among men and only in seropositive RA. This suggests that men could be more likely to benefit from the Mediterranean diet. While these results demonstrate the importance of diet in the primary prevention of RA, they also show that the mechanisms likely differ between RA subgroups.

References:

1. Johansson K, Askling J, Alfredsson L, Di Giuseppe D; EIRA study group. Mediterranean diet and risk of rheumatoid arthritis: a population-based case-control study. Arthritis Res Ther. 2018;20:175. DOI: 10.1186/s13075-018-1680-2.