Vitamin D and Curcumin Piperine Attenuates Disease Activity and Cytokine Levels in Systemic Lupus Erythematosus Patients
Condition: Systemic Lupus Erythematosus
MeSH terms: Lupus Erythematosus, Systemic
Study type: Interventional
Phase: Phase 2

Summary: 
      Systemic lupus erythematosus (SLE) is a chronic systemic autoimmune disease with a relatively
      high mortality and morbidity rate, especially in developing countries such as Indonesia. In
      Indonesia, a previous study demonstrated that almost 71% of SLE patients experience
      hypovitaminosis D, with serum vitamin D 25 levels less than 30 ng/ml. Several factors
      contribute to the low vitamin D levels among SLE patients. Less exposure to sunlight or
      insufficient vitamin D intake contributes to SLE patients low vitamin D levels. Some other
      studies also revealed that vitamin D metabolism gene polymorphisms are also associated with
      patients with SLE.

      Vitamin D is essential for bone health and has an essential role in immune system modulation
      and controlling autoimmune diseases, including SLE. Another study demonstrates that curcumin
      supplementation in premenopausal women and dysmenorrhea improves vitamin D levels. Despite
      the promising properties of curcumin in improving vitamin D biological actions, our previous
      study reveals that the addition of curcumin in vitamin D administration do not significantly
      improve the disease activity or cytokine imbalance in SLE patients. The synergistic property
      of curcumin with vitamin D in regulating immune cells is an open opportunity for researchers
      to increase the response to vitamin D3 therapy.

      Several studies have reported the efficacy of vitamin D or curcumin for SLE treatment.
      However, none mentioned the combination of curcumin added with piperine and vitamin D3. We
      hypothesized that adding curcumin piperine with vitamin D3 as a complementary treatment in
      SLE patients would improve the clinical symptoms or cytokine balance among SLE patients.
      Therefore, this study aims to observe the effects of adding curcumin-piperine with vitamin D3
      in clinical outcomes and cytokines levels in SLE patients with hypovitaminosis D.
    

Detailed description: 
      Systemic lupus erythematosus (SLE) is a chronic systemic autoimmune disease with a relatively
      high mortality and morbidity rate, especially in developing countries such as Indonesia. In
      Indonesia, a previous study demonstrated that almost 71% of SLE patients experience
      hypovitaminosis D, with serum vitamin D (25(OH)D3) levels less than 30 ng/ml. Several factors
      contribute to the low vitamin D levels among SLE patients. Less exposure to sunlight or
      insufficient vitamin D intake contributes to SLE patients' low vitamin D levels. Some other
      studies also revealed that vitamin D metabolism gene polymorphisms are also associated with
      patients with SLE.

      Vitamin D is essential for bone health and has an essential role in immune system modulation
      and controlling autoimmune diseases, including SLE. An increase in the pro-inflammatory
      cytokine, such as interleukin-6 (IL-6), is found in SLE patients with hypovitaminosis D. SLE
      patients with hypovitaminosis D have a more severe clinical condition and disease activity.
      However, previous meta-analysis shows that vitamin D supplementation is effective in
      increasing the serum 25(OH)D levels, may improve fatigue, and is well-tolerated in patients
      with SLE. However, it does not seem to have significant effects in decreasing the positivity
      of anti-dsDNA and disease activity. Thus, another approach to enhance the effect of vitamin D
      to suppress the pro-inflammatory condition in SLE should be considered.

      Curcumin is a phenolic compound widely found in ginger, turmeric, and curcuma plants and has
      the potential as an immunomodulator for the complementary treatment of SLE. Curcumin acts as
      an activator or inhibitor of several transcription factors that play a role in activating and
      differentiating Th1, Th2, Th17, and Tregs. In a previous report, curcumin synergistically
      interacts with vitamin D because it is also a natural ligand for the vitamin D receptor
      (VDR). Previous studies reveal that administering a combination of curcumin and vitamin D3
      resulted in a better recovery of neuronal cells from Alzheimer's disease. Another study
      demonstrates that curcumin supplementation in premenopausal women and dysmenorrhea improves
      vitamin D levels.

      Despite the promising properties of curcumin in improving vitamin D biological actions, our
      previous study reveals that the addition of curcumin in vitamin D administration do not
      significantly improve the disease activity or cytokine imbalance in SLE patients. Because of
      the pharmacokinetics of curcumin, this substance is poorly absorbed in the gut and has low
      bioavailability when administered by the oral route. Therefore, special treatment is needed
      to improve the bioavailability of curcumin. One of the potential strategies is adding the
      piperine when administering curcumin orally. Piperine can be found in plants of the
      Piperaceae family, including 2-7.4% of black pepper and white pepper (Piper nigrum L.).
      Piperine also has antioxidant, immunomodulatory, and anti-inflammatory activities. Piperine
      can increase the in vivo bioavailability of curcumin by inhibiting its metabolism and
      reducing the required dose of curcumin in the clinical setting. Piperine can also increase
      cell membrane permeability, thereby increasing drug absorption. Piperine binds to several
      areas of the enzyme to form a hydrogen bond complex with curcumin that can increase its
      bioavailability up to twenty times.

      The synergistic property of curcumin with vitamin D in regulating immune cells is an open
      opportunity for researchers to increase the response to vitamin D3 therapy. Several studies
      have reported the efficacy of vitamin D or curcumin for SLE treatment. However, none
      mentioned the combination of curcumin added with piperine and vitamin D3. We hypothesized
      that adding curcumin piperine with vitamin D3 as a complementary treatment in SLE patients
      would improve the clinical symptoms or cytokine balance among SLE patients. Therefore, this
      study aims to observe the effects of adding curcumin-piperine with vitamin D3 in clinical
      outcomes and cytokines levels in SLE patients with hypovitaminosis D.
    

Intervention name(s): Observe the clinical outcome and inflammatory cytokines levels in patients with systemic lupus erythematosus (SLE) after being supplemented with Cholecalciferol (Vitamin D3) and Curcumin-Piperine.
Intervention type(s): Drug
Intervention description(s): All patients and physicians were blinded to group assignment and treatment allocation. All subjects received the tablets for three months. All subjects were still required to consume their routine medications during the supplementation according to the disease activity. Patients were evaluated at baseline and after the end of supplementation for clinical and laboratory parameters. Adherence to therapy was assessed by monthly pill counts of returned tablets and biweekly phone calls to the patients.
Intervention MeSH terms: Vitamin D; Cholecalciferol; Curcumin; Piperine
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Patients who fulfilled the inclusion and exclusion criteria were randomized into three parallel groups: Vitamin D + placebo (group I), Curcumin-Piperine + placebo (group II), and vitamin D + Curcumin-Piperine (group III). All patients and physicians were blinded to group assignment and treatment allocation
Masking: Double (Participant, Investigator)
Primary purpose: Treatment
Keywords: systemic lupus erythematosus; vitamin D; curcumin; piperine; disease activity