Table 1.

The positive influence of specific dietary nutrients on SLE.

Dietary Factors	Data on murine studies of SLE	Human studies that warrant further investigation	Proposed research directions
VE	VE supplementation to NZBWF1 diminished anti-dsDNA autoantibodies and counteracted oxidative stress (121).	Supplementation of VE with prednisolone reduced anti-dsDNA antibodies independently of its antioxidant activity (335). Supplementation of VE with Nigella sativa improved oxidative and nitrosative biomarkers and SLE disease activity favoring antioxidant therapy in SLE (124).	• Delineating the effects of VE independently of other components of treatment regimes. • Exploring the possible disease-stage-dependent or tissue-specific outcomes of VE supplementation.
VD	Low levels of VD promoted memory B cells in Act1-/- mouse (162). VD deficiency increased type 1 IFN gene expression in MRL/lpr mice (336). Treatment of MRL/lpr mice with VDR agonist paricalcitol mitigated lupus nephritis via modulating the NF-κB/NLRP3/caspase-1/IL-1β/IL-18 axis and suppressing NF-κB nuclear translocation (337).	A significant negative association between serum VD and memory B cells was confirmed in a cohort of SLE patients (162). SLE patients with high anti-dsDNA autoantibodies (338) or renal involvement (339) are at higher risk for developing hypovitaminosis D; and low levels of VD are correlated with high disease activity (161). Polymorphism in VDR genes has been reported in SLE patients (170).	• Investigating whether VD deficiency is a cause or a sequelae to autoimmune progression. • Reforming genetic association data linking certain genetic susceptibilities and possibilities of VD deficiency for better personalized therapeutic approaches. • Establishing the desired doses for prophylactic and/or therapeutic supplementation of VD for SLE patients. • Testing the potential efficacy and safety of VD supplementation on SLE-associated inflammatory and hemostatic markers in long-term studies.
VA	Supplementation of all-trans-retinoic acid (tRA) to murine lupus models drove disease-stage dependent effects on the development of lupus nephritis. During the active disease stages in MRL/lpr and pristane-induced lupus mouse models, tRA oral dosing showed beneficial effects on renal inflammation (172–174).	Hypovitaminosis A has been detected preceding the clinical diagnosis of SLE (169).	• Investigating whether VA deficiency is a driving factor for SLE progression. • Genome-wide association studies to establish whether polymorphisms in VA receptors are causally associated with SLE development. • Determining the desired doses of prophylactic and/or therapeutic supplementation of VA. • Testing the safety and efficacy of VA supplementation in SLE patients with different disease manifestations.
Se	Se supplementation improved the survival in NZB/NZW F1 mice (194). SE treatment attenuated SLE-associated splenomegaly in B6.Sle1b mice (195). SE supplementation in B6.Sle1b mice significantly reduced total and germinal center B cell numbers, and anti-dsDNA and anti-SmRNP autoantibodies (195).	Meta-analysis of genome-wide association studies predicted high Se levels to associate with a decreased risk for SLE (193). Circulatory Se levels are lower in patients with SLE compared to age- and sex-matched healthy controls (216).	• Exploring the potential therapeutic effect of Se supplementation for SLE patients in large-scale studies. • Elucidating the underlying mechanisms of the potential protective role of Se on the risk for SLE.
ω−3 PUFA	ω−3 enriched diets dramatically reduced lupus progression, mitigating glomerulonephritis and improving survival in different mouse models of SLE (258–261). ω−3 diminished anti-dsDNA antibodies (258, 261), and circulating immune complexes and their renal deposition (258). ω−3 potentiated the effects of antioxidant enzymes, enhancing the ability of renal cells to eliminate harmful free radicals (259, 261). ω−3 reduced the expression of renal pro-inflammatory cytokines including IFNγ, IL-12, TNFα (259, 261), and renal profibrotic molecules such as TGFβ and fibronectin-1 (261).	Fish oil (the marine source of ω−3) together with a low-fat diet significantly modified SLE activity (247). A population-based study suggested that a higher dietary intake of ω−3 fatty acids and lower ω−6: ω−3 ratios were positively associated with patient-reported favorable outcomes of SLE activity index (340).	• Conducting longer-term trials with larger patient sample sizes to establish the long-term outcomes of ω−3 PUFA supplementation on the SLE activity index. • Determining the therapeutic efficacy and safety of ω−3 PUFA as part of the therapeutic regimes that include other immunosuppressive agents.