Complementary therapies for patients with systemic sclerosis

Abstract

Patients with systemic sclerosis often seek information regarding complementary and nutrition-based therapy. Some study results have shown that vitamins D and E, probiotics, turmeric, l-arginine, essential fatty acids, broccoli, biofeedback, and acupuncture may be beneficial in systemic sclerosis care. However, large randomized clinical trials have not been conducted. This review summarizes current data regarding various complementary therapies in systemic sclerosis and concludes with recommendations.

Keywords: Systemic sclerosis; alternative therapy; autoimmune disease; complementary therapy; curcumin; dietary supplement; nutrition; vitamin D; vitamin E.

Figure 1.

Vitamin D regulation of calcium homeostasis, bone health, and immune system. Vitamin D is acquired from two sources: the skin and the gastrointestinal tract. In skin, ultraviolet light and heat converts 7-dehydrocholesterol to cholecalciferol. In the gastrointestinal tract, inactive vitamin D is absorbed from dietary sources such as milk, cheese, and legumes. Inactive vitamin D is converted to the active form, calcitriol, via hydroxylation in the liver and kidneys resulting in increased intestinal calcium and phosphorus absorption, increased bone resorption and bone matrix mineralization, and immune response regulation.

Figure 2.

Curcumin inhibition of IkBα phosphorylation. Lipopolysaccharide (LPS) binds Toll-like receptor 4 (TLR-4) and activates IκBα kinase (IKK). Activated IKK phosphorylates IκBα, activating nuclear factor (NF)-κB that then travels to the nucleus and inhibits apoptosis and increases cell proliferation and angiogenesis of tumor cells (Panel A). Curcumin suppresses IKK activation, thus preventing phosphorylated IκBα activation of NF-κB and blocking its pro-inflammatory effects (Panel B).

Figure 3.

Effect of curcumin on transforming growth factor beta. Transforming growth factor beta (TGF-β) acts on dermal fibroblasts to promote cell growth and proliferation. Addition of curcumin leads to increased transforming growth interacting factor (TGIF) expression which dampens TGF-β effects.

Figure 4.

Mechanism of action of sulforaphane. Lipopolysaccharides in gram-negative bacteria activate Toll-like receptor 4 and induce production of pro-inflammatory cytokines (e.g. tumor necrosis factor-α (TNF-α), interleukin-1-β (IL-1β)). The transcription factor, Nrf2, is bound by Keap-1 in the cytoplasm, but cruciferous vegetable-derived sulforaphane liberates and activates Nrf2 permitting its nuclear translocation. In the nucleus, Nrf2 disrupts recruitment of RNA polymerase II to LPS-induced pro-inflammatory genes, such as IL-6 and IL-1β. Nrf2 is hypothesized to also inhibit the activation of NF-κB, a pro-inflammatory transcription factor.