3. Discussion
RA
DISEASE
In the present study we show, for the first time, erythrocyte oxylipin patterns in patients with RA undergoing a dietary intervention. This study has several strengths including the cross-over design, which is optimal for dietary interventions in patients who have not only different dietary habits to one another, but also variations in disease activity, co-morbidities, and pharmacological treatment. Data on erythrocyte fatty acids both pre and post intervention and control period also improve the possibility of correctly understanding the effects of diet intervention on oxylipins. Study limitations are the small sample size and a limited change in dietary PUFAs that only led to changes in a small number of erythrocyte oxylipins. Due to the lack of published results on effects of fatty-acid intake on erythrocyte oxylipin levels, we here discuss our results compared with previous findings in plasma by others. It must be emphasized that oxylipins in erythrocytes and in plasma are not necessarily reflective of each other; the bioactivity of compounds in plasma is often disputed and this was also a reason for our choice of quantifying oxylipins in erythrocytes. In addition, the patients in our study were women with RA and on anti-rheumatic pharmacological treatment and it is not known if the disease itself or anti-rheumatic treatment could influence oxylipin concentrations.Although no dietary interventions have reported effects on oxylipins, some studies have presented data on changes in plasma or serum oxylipins during EPA and DHA supplementation [It is possible that a more pronounced change after increased intake is found for CYP-derived epoxides, but these were not detected in erythrocytes in our study, where only hydroxy fatty acids derived from EPA were successfully quantified. In line with our results, CYP-derived epoxides in erythrocytes were not reported in the study by Fu et al. [Unexpectedly, mainly AA and DHA oxylipins in erythrocytes contributed to separate the blue mussel and control diets in the multivariate models. This could probably be explained by the broad changes in the fatty-acid pattern in erythrocytes caused by the dietary interventions. Further, the participants in the MIRA trial had a high intake of fish and shellfish in their habitual diet and hence only a moderately increased intake of EPA and DHA during intervention. The lack of effect on the oxylipin pattern could thus be due to an insufficient change in total intake of precursor fatty acids. In fact, Ostermann et al. found that low-dose supplementation of EPA and DHA did not result in changes in oxylipins [