Background: Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease often affecting the central nervous system, resulting in neuropsychiatric SLE (NPSLE). Cognitive dysfunction, a common manifestation, significantly impacts quality of life. Vitamin D3, recognized for its neuroprotective and cognitive-enhancing properties, is a potential therapeutic option for NPSLE. Objectives: This randomized controlled trial (RCT) evaluates the effects of vitamin D3 supplementation on cognitive function in NPSLE patients. Methods: NPSLE patients (N = 72) of standard SLE care were allocated into an intervention group (n = 34) receiving vitamin D3 (40,000 IU) supplementation/week for 6 weeks, then 2000 IU/day for 3 months, and a control group (n = 38) without vitamin D3. Serum vitamin D3 concentration, mini-mental state examination (MMSE) scores, and brain hypo-perfusion images by single-photon emission computed tomography (SPECT) were obtained at baseline and after 6 months of follow-up. Results: Baseline characteristics (age, gender, BMI, waist-to-hip-ratio) were independent between groups. After the intervention, concentration of vitamin D3 (ng/mL) rose from 16.2 ± 4.9 to 28.3 ± 5.3 within the “intervention group” (P ≤ 0.001). Similarly, the mean differences of MMSE scores were significantly higher in Cases than Controls (2.2 vs. 0.3). Analysis of covariance (ANCOVA) revealed large effect sizes for vitamin D concentration (η2p = 0.714) and medium effect sizes (η2p = 0.460) for MMSE scores. Furthermore, an insignificant (P > 0.05) shift (moderate to mild) of brain hypo-perfusion level was observed over time. Conclusion: Vitamin D3 supplementation effectively increased serum vitamin D concentration by supporting its role as an adjunctive therapy in NPSLE patients, leading to improvements in cognitive function and brain perfusion levels.
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