A new study published in Inflammopharmacology reports that L-carnitine, when administered alongside conventional disease-modifying antirheumatic drugs (DMARDs), may significantly improve clinical symptoms and reduce systemic inflammation in patients with active rheumatoid arthritis (RA). The findings suggest promising clinical benefits, although the supplement’s effects on key inflammatory signaling pathways remain unclear. In the randomized controlled trial, researchers enrolled 46 RA patients and divided them into two equal groups. Both groups received standard DMARD therapy consisting of methotrexate, leflunomide, and hydroxychloroquine, while the intervention group received an additional dose of L-carnitine at 500 mg twice daily over a 12-week period.
Throughout the study, investigators tracked a broad set of clinical and laboratory indicators, including tender and swollen joint counts, pain intensity measured through a visual analogue scale, morning stiffness duration, the Disease Activity Score in 28 joints, and functional capability based on the Modified Health Assessment Questionnaire. Laboratory analyses focused on C-reactive protein levels and the inflammatory markers STAT3 and TGF-β1.
By the end of the 12-week period, patients receiving L-carnitine experienced notable improvements in several clinical categories compared to their baseline measurements, including morning stiffness, pain levels, tender joint counts, CRP concentrations, overall disease activity, and daily functional performance. Meanwhile, the control group displayed a significant rise in STAT3 levels, a change not observed in the L-carnitine group. Despite these differences, the study found no significant alterations in STAT3 or TGF-β1 values among those taking L-carnitine, leaving the supplement’s influence on the JAK/STAT pathway inconclusive. Swollen joint counts also remained unchanged in both groups, suggesting that inflammation-related swelling may respond more slowly or require longer treatment durations.
The study findings are particularly notable because L-carnitine, a naturally occurring compound synthesized from lysine and methionine, is already well-established for its metabolic role in transporting long-chain fatty acids into mitochondria. Beyond this function, L-carnitine has demonstrated anti-inflammatory, antioxidant, and cytoprotective properties in previous experimental studies. RA is driven in part by inflammatory mediators like TGF-β1, a cytokine known to be elevated in the synovial tissues of RA patients. TGF-β1 contributes to disease progression by promoting fibroblast proliferation, thickening of synovial tissue, and the breakdown of cartilage through enzymes such as aggrecanase-1. Preclinical research has also suggested that L-carnitine may modulate elements of the JAK/STAT signaling cascade, including potential suppression of STAT3, though this trial did not confirm such effects in human RA patients.
These results point to the potential value of L-carnitine as an adjunct therapy capable of enhancing the clinical benefits of conventional DMARDs, primarily through reducing systemic inflammation and improving patient symptoms. However, the researchers emphasize that the molecular mechanisms underlying these improvements remain uncertain. They call for larger, longer-term clinical studies to better understand whether L-carnitine can meaningfully influence inflammatory signaling pathways and to determine its full therapeutic role in managing rheumatoid arthritis.
References
- Eldisouky AA, Hegazy SK, Abd Elghany SE. L-carnitine as a novel approach for pain and inflammation relief in rheumatoid arthritis. Inflammopharmacology. 2025 Nov;33(11):6805-6811.
- Khodir SA, Al-Gholam MA, Salem HR. L-Carnitine potentiates the anti-inflammatory and antinociceptive effects of diclofenac sodium in an experimentally-induced knee osteoarthritis rat model. Iran J Basic Med Sci. 2020 Aug;23(8):1035-1044.