Creatine supplementation as a dual therapeutic strategy for sarcopenia and immune dysregulation in systemic lupus erythematosus: A hypothesis-driven approach

Abstract

Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder characterized by profound immune dysregulation, primarily driven by abnormal toll-like receptor (TLR) signalling and the subsequent overproduction of type I and III interferons. Activated TLRs contribute to B cell hyperactivity, dendritic cell maturation, and the expansion of proinflammatory T cell subsets, thereby perpetuating systemic inflammation and tissue damage. Concurrently, patients with SLE often develop sarcopenia, a progressive loss of skeletal muscle mass and function, leading to frailty, reduced physical performance, and increased morbidity and mortality.

Creatine, a naturally occurring compound essential for ATP regeneration, is widely recognized for its ergogenic effects and is increasingly appreciated for its anti-inflammatory and immunomodulatory properties. Recent preclinical evidence suggests that creatine may attenuate TLR-mediated signalling and reduce the expression of proinflammatory cytokines.

Here, we propose a dual-action hypothesis whereby creatine supplementation in SLE may: (1) modulate innate immune activation by inhibiting TLR signalling and, consequently, dampen type I and III interferon responses; and (2) counteract sarcopenia by enhancing muscle bioenergetics and mitigating inflammation-induced catabolic processes.

The convergence of these mechanisms—orchestrated by creatine, an accessible and well-tolerated compound even at relatively high doses—may restore immunological homeostasis, preserve muscle function, and improve long-term clinical outcomes in patients with SLE.