Docosahexaenoic acid in the treatment of rheumatoid arthritis: A double-blind, placebo-controlled, randomized cross-over study with microalgae vs. sunflower oil

Abstract

In this double-blind pilot study, thirty-eight patients with defined RA were allocated to consume foods enriched with microalgae oil from Schizochytrium sp. (2.1g DHA/d) or sunflower oil (placebo) for 10 weeks (cross-over), maintaining the regular RA medication during the study. In contrast to placebo, the daily consumption of DHA led to a decline in the sum of tender and swollen joints (68/66) from 13.9±7.4 to 9.9±7.0 (p=0.010), total DAS28 from 4.3±1.0 to 3.9±1.2 (p=0.072), and ultrasound score (US-7) from 15.1±9.5 to 12.4±7.0 (p=0.160). The consumption of placebo products caused an increase of the n-6 PUFA linoleic acid and arachidonic acid (AA) in erythrocyte lipids (EL, p<0.05). The amount of DHA was doubled in EL of DHA-supplemented patients and the ratios of AA/EPA and AA/DHA dropped significantly. We speculate that the production of pro-inflammatory/non-resolving AA-derived eicosanoids might decrease in relation to anti-inflammatory/pro-resolving DHA- and EPA-derived lipid mediators. In fact, plasma concentrations of AA-derived thromboxane B2 and the capacity of blood to convert AA to the pro-inflammatory 5-lipoxygenase product 5-hydroxyeicosatetraenoic acid were significantly reduced, while levels of the DHA-derived maresin/resolvin precursors 14-/17-hydroxydocosahexaenoic acid significantly increased due to DHA supplementation. The study shows for the first time that supplemented microalgae DHA ameliorates disease activity in patients with RA along with a shift in the balance of AA- and DHA-derived lipid mediators towards an anti-inflammatory/pro-resolving state.