Study Description: Systemic lupus erythematosus (SLE) occurs predominantly in women and is driven by type I interferon dysregulation and neutrophil hyperresponsiveness. Neutrophils in females have reduced mitochondrial bioenergetic capacity which affects immunometabolism. Nicotinamide adenine dinucleotide (NAD)+ boosting with nicotinamide riboside blunts type 1 IFN activation in-vivo in monocytes of healthy subjects and ex-vivo in SLE subjects. These findings support the proposal of the hypothesis that NAD+ boosting by NR supplementation will modulate metabolic pathways in lupus and blunt type 1 interferon signaling. Moreover, as type 1 interferon drives endothelial dysfunction, linked to increased cardiovascular risk, the effect of NR on endothelial function will be examined. Objectives: Primary Objective: Evaluate the effect of NR vs. placebo on immunometabolic and inflammatory remodeling in female SLE subjects: Exploratory Objective: Compare and characterize myeloid cell bioenergetic and immunometabolic profiles in healthy control and SLE female subjects Endpoints: Primary Endpoint: The primary end point will be to assess the effect of NR on blunting type I IFN signaling by measuring monocytic secretion of IFN-beta secretion compared to baseline in response to placebo vs. NR supplemented in SLE study subjects. Exploratory Endpoints: Healthy control vs. SLE subjects: * Compare type I IFN transcript profiles in monocytes and neutrophils at baseline and in response to activation. * Assess cell bioenergetics including: 1) monocyte and neutrophil metabolic flux mass spectroscopy of 13C-glucose and 13Cglutamine analysis to investigate their metabolic fates; (iii) Mitochondrial oxygen consumption (using glucose, amino acid, and fatty acid substrates) and glycolysis rates. SLE baseline vs. NR/placebo supplementation: Baseline vs. 6 weeks of NR/placebo: -Assess effect of NR on bioenergetics by measuring steady-state metabolite levels comparing changes in placebo vs. NR groups in monocytes and neutrophils. Baseline vs. 12 weeks of NR/placebo: * Whole blood NAD+ levels (batched and measured at the end of study enrollment period) * Explore effects of NR on gene regulation using monocyte and neutrophils by RNA-seq and chromatin remodeling analysis. * Determine the effect of NR vs placebo on endothelial dysfunction in SLE subjects
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* INCLUSION CRITERIA: In order to be eligible to participate in this study, an individual must meet all of the following criteria: SLE subjects: * Female subjects 18 years or older who meets \> 3 of 11 modified Am. Coll. of Rheumatology (ACR) (1997) Revised Criteria for SLE and mild/moderate disease activity defined as an SLE Disease Activity Index 2000(SLEDAI 2K) between zero and less than or equal to 14 at screening; * If on glucocorticoids, the dose must be less than or equal to 20 mg daily and stable for at least 4 weeks prior to screening; * If on hydroxychloroquine or other antimalarials such as chloroquine or quinacrine, dose must have been stable for the 12 weeks prior to screening. The max. allowed doses - hydroxychloroquine 400 mg/day, chloroquine phosphate 500 mg/day and quinacrine 100 mg/day; * If on immunosuppressive drugs (methotrexate, azathioprine, mycophenolate mofetil, cyclosporine, tacrolimus); dose must have been stable for the 12 weeks prior to screening * Subjects of childbearing potential must agree to practice effective birth control for the duration of the study; * Stated willingness to comply with all study procedures and availability for the duration of the study; * Agreement to adhere to Lifestyle Considerations throughout study duration; * Ability of subject to understand and the willingness to sign a written informed consent document. * If on vitamin B3 or tryptophan supplementation at screening, willing to stop it at least 6 weeks before the baseline visit. Control subjects: * Female subjects 18 years or older * No history of autoimmune or inflammatory disease * If on vitamin B3 or tryptophan supplementation at screening, willing to stop it at least 6 weeks before the blood draw visit. EXCLUSION CRITERIA: SLE Subjects: * Active renal or central nervous system disease or major renal or hepatic dysfunction; * Treatment with rituximab, belimumab or any other biologic agent within the 6 months prior to screening * Treatment with cyclophosphamide or IVIG within the 6 months prior to screening and or increase in glucocorticoid dose within 4 weeks of screening; * Pregnancy or lactation (nursing) * Treatment with another investigational drug or other intervention within 6 months of screening Control Subjects: * Inability to sign consent * Pregnancy or nursing Pregnant women are excluded from participation on this study. Self-reported pregnancy status may be accepted from female control participants of child-bearing potential for a blood draw which is considered a minimal risk procedure.