Omega-3 in SLE: a double-blind, placebo-controlled randomized clinical trial of endothelial dysfunction and disease activity in systemic lupus erythematosus

Abstract

Accelerated atherosclerosis remains a major cause of death in late systemic lupus erythematosus (SLE). Omega-3 has been reported to have benefit for endothelial dysfunction, one of the earliest stages of atherosclerosis, and to reduce disease activity in SLE. We performed a randomized, double-blind placebo-controlled trial to examine the effect of Omega-3 on endothelial function, disease activity, inflammatory markers and lipids in SLE. SLE patients (n = 85, mean age 47, 55 % Caucasian, 38 % African-American, 94 % female) were randomly assigned to 3 g of Omega-3 (Lovaza, GSK) versus placebo for 12 weeks. Endothelial function was measured at baseline and at 12 weeks using flow-mediated dilation, calculated using high-resolution B-mode ultrasound of the brachial artery diameter in response to vasoactive stimuli (hyperemia). Disease activity was measured using the physician global assessment and SELENA-SLEDAI score. Inflammatory markers (sICAM-1, sVCAM-1, IL-6) and fasting lipid profile were done at baseline and 12-week follow-up. There was no difference between the treatment groups with respect to changes in flow-mediated dilation parameters or disease activity. An average increase in LDL cholesterol of 3.11 mg/dL (±21.99) was found with Omega-3 versus a decrease of 1.87 mg/dL (±18.29) with placebo (p = 0.0266). In this trial, Omega-3 did not improve endothelial function, disease activity, nor reduce inflammatory markers in SLE. Longer trials might be required if there are delayed clinical effects. There was evidence that Omega-3 may increase LDL cholesterol, but not the LDL/HDL ratio.

Targeting the inflammasome in rheumatic diseases

“…Consumption of ω-3 FA have shown substantial benefit in murine models of lupus; they reduce inflammatory cytokine production, including lowering levels of IL-1β and IL-18(52, 53). One short-term, placebo controlled trial of ω-3FA did not show significant benefit to disease activity over 12 weeks(54), but the baseline SELENA-SLEDAI disease activity was low in these patients (mean of 1.5). Another placebo-controlled trial of ω-3FA in lupus patients with higher baseline activity (mean SLAM-R 10.2) showed improvement in both BILAG and SLAM-R scores(55).…”

Ácidos graxos poli‐insaturados ômega‐3 e lúpus eritematoso sistêmico: o que sabemos?

“…No entanto, alguns ensaios clínicos sugerem que a suplementação com essa classe de lipídeos pode representar terapia adicional ao tratamento farmacológico tradicional dessa doença devido às propriedades anti-inflamatórias. [17][18][19][20][21][22][23][24][25] Parece haver diferença nos níveis de ácidos graxos nas hemácias e no plasma de indivíduos com LES e naqueles sem a doença. No entanto, não se sabe se essa diferença ocorre devido à dieta inadequada ou à própria doença.…”

“…Já quanto ao perfil lipídico, os pacientes que receberam -3 apresentaram aumento significativo dos níveis de LDL-c, enquanto aqueles do grupo placebo apresentaram redução significativa dessa lipoproteína. 25 Os estudos avaliando o efeito dos ácidos graxos ômega-3 no LES estão listados na tabela 1.…”

“…[17][18][19][20][21][22][23][24][25] Essa classe de lipídeos está relacionada com a produção de eicosanoides com menor ação inflamatória do que os produzidos pelos ácidos graxos pertecentes à família -6, além da redução dos níveis séricos de citocinas inflamatórias e da ativação de linfócitos T.…”

“…No entanto, parece haver relação entre o consumo deste tipo de gordura e a diminuição das manifestaç ões e da atividade inflamatória da doença. [17][18][19][20][21][22][23][24][25] Os autores apresentam revisão da literatura científica sobre os efeitos dos ácidos graxos ômega-3 em pacientes com LES.…”