title: Docosahexaenoic acid in the treatment of rheumatoid arthritis: A double-blind, placebo-controlled, randomized cross-over study with microalgae vs. sunflower oil.
abstract: The potential of fish or fish oil as supplier for eicosapentaenoic acid (EPA, C20:5n3) and docosahexaenoic acid (DHA, C22:6n3) for reducing cardiovascular risk factors and supporting therapy of chronic inflammatory diseases, has been investigated intensively, but our knowledge about the physiological effects of the individual compounds EPA and DHA are limited.
  
  
  
  In this double-blind pilot study, thirty-eight patients with defined RA were allocated to consume foods enriched with microalgae oil from Schizochytrium sp. (2.1 g 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 B2and 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.
authors.affiliation: Department of Nutritional Physiology, Institute of Nutrition, Friedrich Schiller University of Jena, Dornburger Str. 25, 07743 Jena, Germany; Department of Nutritional Biochemistry and Physiology, Institute of Nutrition, Friedrich Schiller University of Jena, Dornburger Str. 25, 07743 Jena, Germany; Competence Cluster for Nutrition and Cardiovascular Health (nutriCARD), Halle-Jena-Leipzig, Dornburger Str. 25, 07743 Jena, Germany. Electronic address: Christine.Dawczynski@uni-jena.de.
authors.forename: C
authors.initials: C
authors.lastname: Dawczynski
authors.affiliation: Department of Nutritional Physiology, Institute of Nutrition, Friedrich Schiller University of Jena, Dornburger Str. 25, 07743 Jena, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Dittrich
authors.affiliation: Department of Internal Medicine III, Jena University-Hospital, Erlanger Allee 101, 07747 Jena, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Neumann
authors.affiliation: Department of Internal Medicine III, Jena University-Hospital, Erlanger Allee 101, 07747 Jena, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Goetze
authors.affiliation: Department of Internal Medicine III, Jena University-Hospital, Erlanger Allee 101, 07747 Jena, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Welzel
authors.affiliation: Department of Internal Medicine III, Jena University-Hospital, Erlanger Allee 101, 07747 Jena, Germany.
authors.forename: P
authors.initials: P
authors.lastname: Oelzner
authors.affiliation: Department of Pharmaceutical/Medicinal Chemistry, Friedrich Schiller University of Jena, Philosophenweg 14, 07743 Jena, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Völker
authors.affiliation: Department of Pharmaceutical/Medicinal Chemistry, Friedrich Schiller University of Jena, Philosophenweg 14, 07743 Jena, Germany.
authors.forename: A M
authors.initials: AM
authors.lastname: Schaible
authors.affiliation: Department of Pharmaceutical/Medicinal Chemistry, Friedrich Schiller University of Jena, Philosophenweg 14, 07743 Jena, Germany.
authors.forename: F
authors.initials: F
authors.lastname: Troisi
authors.affiliation: Department of Pharmaceutical/Medicinal Chemistry, Friedrich Schiller University of Jena, Philosophenweg 14, 07743 Jena, Germany.
authors.forename: L
authors.initials: L
authors.lastname: Thomas
authors.affiliation: Department of Pharmaceutical/Medicinal Chemistry, Friedrich Schiller University of Jena, Philosophenweg 14, 07743 Jena, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Pace
authors.affiliation: Department of Pharmaceutical/Medicinal Chemistry, Friedrich Schiller University of Jena, Philosophenweg 14, 07743 Jena, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Koeberle
authors.affiliation: Department of Pharmaceutical/Medicinal Chemistry, Friedrich Schiller University of Jena, Philosophenweg 14, 07743 Jena, Germany.
authors.forename: O
authors.initials: O
authors.lastname: Werz
authors.affiliation: Department of Medical Statistics, Informatics and Documentation, Jena University-Hospital, Bachstr. 18, 07743 Jena, Germany.
authors.forename: P
authors.initials: P
authors.lastname: Schlattmann
authors.affiliation: Department of Nutritional Physiology, Institute of Nutrition, Friedrich Schiller University of Jena, Dornburger Str. 25, 07743 Jena, Germany; Department of Nutritional Biochemistry and Physiology, Institute of Nutrition, Friedrich Schiller University of Jena, Dornburger Str. 25, 07743 Jena, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Lorkowski
authors.affiliation: Department of Nutritional Physiology, Institute of Nutrition, Friedrich Schiller University of Jena, Dornburger Str. 25, 07743 Jena, Germany; Competence Cluster for Nutrition and Cardiovascular Health (nutriCARD), Halle-Jena-Leipzig, Dornburger Str. 25, 07743 Jena, Germany.
authors.forename: G
authors.initials: G
authors.lastname: Jahreis
mesh_terms: D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D018592:Cross-Over Studies; D004281:Docosahexaenoic Acids / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D005858:Germany; D006801:Humans; D008297:Male; D058086:Microalgae; D008875:Middle Aged; D010865:Pilot Projects; D010938:Plant Oils / Q000627:therapeutic use*; D000074242:Sunflower Oil / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D010938:Plant Oils; D000074242:Sunflower Oil; D004281:Docosahexaenoic Acids
keywords: Diseases activity; Docosahexaenoic acid; Docosanoids; Inflammation; Nutrition; Rheumatoid arthritis