Carnitine and Other Metabolites in Fibromyalgia a Clinical Perspective on a Mendelian Randomization Study

Fibromyalgia (FM) is a chronic pain disorder lacking reliable biomarkers. While metabolomic studies have suggested associations with various metabolites, including carnitine, establishing causality remains a challenge. This study integrates clinical metabolomic profiling with a Mendelian Randomization (MR) framework to investigate the potential causal influence of blood metabolites on FM.

In this study, 96 patients with Fibromyalgia and normal controls were recruited, and the carnitine level in peripheral blood was detected by ELISA method. And then, a two-sample Mendelian randomization (MR) method was used to test the potential causal relationship between 1400 metabolite biomarkers, including the level of carnitine, and Fibromyalgia. Additionally, for those metabolites demonstrating a causal link to Fibromyalgia in the initial MR analysis, a reverse Mendelian Randomization analysis was conducted to further validate these findings.

Carnitine levels were markedly decreased in patients with fibromyalgia compared with healthy controls. The MR analysis identified 10 metabolites potentially causally linked to fibromyalgia. Among them, carnitine has a causal relationship with Fibromyalgia and is a protective factor (OR 0.73, 95% CI: 0.59-0.91, p = 0.004). There are others, 4 metabolites showed protective effects, whereas 5 were linked to an elevated risk of the condition. The results were consistent among various MR methods, suggesting a strong correlation.

Our findings provide novel evidence supporting a potential causal, protective role of carnitine in FM pathogenesis, alongside other implicated metabolites. These results highlight the promise of metabolic pathways as targets for intervention, but future studies in larger, diverse populations are warranted to confirm these relationships.