Vitamin D Supplementation Improves Disease Activity, Fatigue in Patients With SLE

Vitamin D has been shown to improve both disease activity and fatigue in patients with systemic lupus erythematosus.

Supplementation of vitamin D has been shown to improve both disease activity and fatigue in patients with systemic lupus erythematosus (SLE), possibly due in part to the suppression of the interferon (IFN) signature gene expression, according to a study published in BMC Rheumatology.1

“In addition to the well-known role of vitamin D in calcium homeostasis and bone metabolism, vitamin D is important in the modulation of the immune system and inflammatory processes,” investigators stated. “Vitamin D deficiency is common in patients with SLE, possibly as a result of sun avoidance.”

Demographics, medication history, comorbidities, body mass index (BMI), disease information, SLE disease activity index (SLEDAI-2K) score and Systemic Lupus International Collaborating Clinics/American College of Rheumatology damage index (SDI) were collected for all patients with SLE attending the Rheumatology clinic at Mater Dei Hospital in Malta. Vitamin D deficiency was defined as serum 25-hydroxyvitamin D < 20 ng/mL and insufficiency was defined as serum 25-hydroxyvitamin D 21-29 ng/mL.

Eligible patients were aged 18 years or older, had a clinical diagnosis of SLE, and had deficient or insufficient levels of vitamin D. Participants filled out the Fatigue Severity Scale (FSS), Pittsburgh Sleep Quality Index (PSQI), visual analogue scale (VAS) for pain, Hospital Anxiety and Depression Scale (HADS), and the modified Health Assessment Questionnaire (mHAQ). Laboratory blood tests included serum calcium, serum 25-hydroxyvitamin D, complement 3 (C3), complement 4 (C4), full blood count, and renal function. A urinalysis, microscopy, and protein creatinine test were performed.

Those with vitamin D insufficiency received vitamin D3 8000 IU daily for 4 weeks, then 2000 IU for daily maintenance. Patients deemed deficient took D3 8000 IU daily for 8 weeks, followed by 2000 IU daily maintenance. At the 3-month mark, serum 25-hydroxyvitamin D and calcium levels were checked to ensure vitamin D levels. Patients who did not achieve adequate vitamin D levels (≥ 30 ng/mL) by 3 months were checked for vitamin D adherence and dosage was increased when necessary. Patients were then assessed at 6 and 12 months. Ethylenediaminetetraacetic acid (EDTA) was sampled at baseline and at 6 months to ensure RNA expression of interferon signature genes.

A total of 31 patients with SLE recruited from November 2016 and June 2017 participated in the study, with 13 patient exhibiting vitamin D deficiency and 18 with insufficiency. Of the patients analyzed, 11 were receiving both calcium and vitamin D at baseline. The average age of participants was 47.9 years and 90.3% were female. Vitamin D levels were 21.7 ng/mL at baseline.

At the 6-month mark, 83.9% of participants had sufficient levels of vitamin D, 9.7% were insufficient, and only 6.5% were deficient. At 12 months, 35.5% were sufficient, 54.8% were insufficient, and 9.7% were deficient. However, 64.5% of patients did not adhere to the vitamin D supplementation regime.

Disease activity, as noted by the SLEDAI-2K assessment (p = 0.028), was significantly improved at the 12-month mark. Prednisone and fatigue (FSS; p = 0.071) decreased after 1 year of vitamin D supplementation. Of deficient participants, SLEDAI-2K was significantly reduced at both 6 and 12 months (p = 0.030 and 0.046, respectively).

At the 6-month mark, IFN signature gene expression decreased from 2.666 (SD 1.703) to 2.225 (1.323). Those with a decrease in their IFN signature gene expression score had a simultaneous decrease in their SLEDAI-2K score when compared with those who had an increase in their IFN signature gene impression score (mean SLEDAI-2K 4.67; p = 0.015).

Sun exposure and increased levels of fatigue due to higher temperatures were minimized by avoiding recruiting participants during summer months. Additionally, investigators utilized a 12-month vitamin D supplementation schedule to reduce the effect of seasonality on patient fatigue. Another limitation was the lack of a placebo-controlled cohort, which may have created assessment bias regarding the self-assessment questionnaires. However, laboratory results included gene expression, which mitigated potential bias. Investigators recommend larger, placebo-controlled trials in the future.

“The correction of vitamin D deficiency in SLE patients has potential benefits with regards to the suppression in the expression of genes in the interferon pathway, consequentially resulting in an improvement in SLE disease activity,” investigators concluded. “Other potential benefits include the improvement of sleep quality and fatigue; although the factors related to fatigue in SLE are complex, and further studies in this respect are required.”


Magro R, Saliba C, Camilleri L, Scerri C, Borg AA. Vitamin D supplementation in systemic lupus erythematosus: relationship to disease activity, fatigue and the interferon signature gene expression. BMC Rheumatol. 2021;5(1):53. Published 2021 Dec 3. doi:10.1186/s41927-021-00223-1