Placebo-controlled randomized clinical trial of fish oil's impact on fatigue, quality of life, and disease activity in Systemic Lupus Erythematosus

Abstract

Introduction: A recent metabolomic screen of sera from patients with Systemic Lupus Erythematosus (SLE) found reduction of antioxidants and substrates for energy generation. These metabolic alterations may underlie one of the most common features of SLE--fatigue. The metabolomic studies also noted reduced omega-3 fatty acids, which are powerful anti- oxidants. This deficiency may be causally related to oxidative stress, inflammation, disease activity, and fatigue in SLE. Supplementation of omega-3 fatty acids using fish oil in SLE has been shown to reduce oxidative stress in other studies. The objective of this study is to evaluate the effect of fish oil supplementation on clinical measures of fatigue, quality of life, and disease activity as part of a randomized clinical trial.

Methods: Fifty SLE patients recruited in outpatient clinics were randomized 1:1 to fish oil supplementation or olive oil placebo, and blinded to their treatment group. At baseline and after 6 months of treatment, RAND Short Form-36 (RAND SF-36), Fatigue Severity Scale (FSS), SLE Disease Activity Index (SLEDAI), and Physician Global Assessment (PGA) were completed; serum was also collected for soluble mediator analysis.

Results: Thirty-two patients completed the study. PGA improved significantly in the fish oil group compared with the placebo group (p = 0.015). The RAND SF-36 Energy/fatigue and Emotional well-being scores demonstrated improvement trends (p = 0.092 and 0.070). No clear difference was seen in FSS and SLEDAI (p = 0.350 and p = 0.417). Erythrocyte sedimentation rate and serum IL-12 were reduced (p = 0.008 and p = 0.058); while serum IL-13 was increased by fish oil supplementation (p = 0.033).

Conclusions: In this randomized, placebo-controlled 6-month trial, SLE patients randomized to fish oil supplementation demonstrated improvement in their PGA, RAND SF-36, and some circulating inflammatory markers.

Trial registration: ClinicalTrials.gov Identifier: NCT02021513 (registered 13 December 2013).

Figures

Fig. 1

Trial Profile. Flow diagram of progress through phases of the randomized clinical trial

Fig. 2

Quality of Life Assessments. RAND Short Form-36 (SF-36) Dot plot of score changes from baseline to six months for a Energy/fatigue (p = 0.092) and b Emotional Well- Being (p = 0.070), a higher score is indicative of better quality of life or fatigue; therefore a positive delta denotes improvement. Fatigue Severity Scale c Dot plot of score changes from baseline to six months (p = 0.350), a lower score indicates less fatigue; therefore a negative delta denotes improvement. For all graphs, center bar represents median and upper and lower bars are the 25th and 75th percentiles. Data were analyzed with Mann–Whitney U tests

Fig. 3

Quality of Life Assessments. RAND Short Form-36 (SF-36) Radial representation of the means of the 8 subscales as assessed at baseline (solid line) and six months (dotted line). a Placebo completers (N = 14) & b Fish Oil completers (N = 18)

Fig. 4

Disease Activity Assessments. Physician’s Global Assessment a Dot plot of score changes (p = 0.015), a higher score is indicative of worse overall disease activity; therefore a negative delta denotes improvement. SELENA-SLEDAI b Dot plot of change scores (p = 0.42) and c Renal component delta for LN patients only, Placebo N = 10 and Fish Oil N = 14, (p = 0.35), a higher score is indicative of higher disease activity; therefore a negative delta denotes improvement. For all graphs, center bar represents median and upper and lower bars are the 25th and 75th percentiles. Data were analyzed with Mann–Whitney U tests

Fig. 5

Biomarkers. a Erythrocyte Sedimentation Rate (ESR) (p = 0.008), reduced in fish oil group b IL-13 (p = 0.033) elevated in fish oil group c IL-12 (p = 0.058), reduced in fish oil group. For all graphs, center bar represents median and upper and lower bars are the 25th and 75th percentiles. Data were analyzed with Mann–Whitney U tests