Background/Purpose: A comprehensive metabolomic screen of sera from patients with Systemic Lupus Erythematosus (SLE) has shown that the concentrations of many substrates for energy generation, as well as physiological antioxidants, are reduced when compared to sera from healthy controls. It is possible that these metabolic alterations underlie one of the most common patient reported features of SLE – fatigue. The metabolomic studies also noted reduced omega-3 fatty acids (omega-3 FAs). Given that omega-3 FAs are powerful anti-oxidants, the reduction in these FAs may be causally related to the tremendous degree of oxidative stress and lipid peroxidation seen in lupus. Supplementation with omega-3 FAs in SLE has been shown to increase anti-oxidants and reduce reactive oxygen species to more closely resemble healthy controls. The effect of omega-3 FA supplementation on the serum metabolome and clinical measures of fatigue are the subject of a randomized clinical trial. 

Methods: Fifty SLE patients were recruited, 25 supplemented with omega-3 FAs and 25 with olive oil placebo. At baseline and after 6 months of FA supplementation, Short Form-36 (SF-36), Fatigue Severity Scale (FSS), SLE Disease Activity Index (SLEDAI), and Physician Global Assessment (PGA) were completed; serum was also collected to perform metabolomic analysis. Demographic information and baseline clinical laboratory data were collected from the electronic medical record.

Results: Eighteen subjects receiving FA and 14 placebo patients completed the study. The FA patients were: 14 female, 4 male, 10 black and 8 Hispanic patients aged 43 ± 8 years. The placebo patients were: 11 female, 3 male, 1 white, 6 black, and 7 Hispanic patients aged 35 ± 11 years. Each group had an average of 6 ACR criteria for SLE. The SF-36 total scores pre- and post-treatment were compared using a paired t test and noted a significant improvement in the omega-3 patients (32.60 vs.42.19, p=0.0076), and no significant change in placebo patients (60.58 vs. 64.76, p=0.235). The SF-36 Vitality/Fatigue also yielded significant improvement in the omega-3 group (29.44 vs. 39.17, p=0.023) and no significant change in the placebo group (52.50 vs. 52.86, p=0.92). PGA improved significantly in the omega-3 group (1.21 vs. 0.56, p=0.0018), and did not significantly change in the placebo group (0.94 vs. 0.92, p=0.95). No significant changes were noted for FSS or SLEDAI in either group. Metabolomic data are currently being analyzed.

Conclusion: In this placebo-controlled 6-month trial of omega-3 FA supplementation in SLE, improvement was noted in both the total SF-36 quality of life measure as well as the Vitality/Fatigue sub-score. There were also two assessments of disease activity, but only the PGA noted significant improvement in the omega-3 group. Serum from the subjects in this cohort is now under analysis for markers of oxidative stress and antioxidant response and will be correlated with patient-reported outcomes as well as disease activity.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/impact-of-omega-3-fatty-acids-on-quality-of-life-in-systemic-lupus-erythematosus/