Causal Associations Between Carnitine‐Related Metabolites and Spinal Pain: A Bidirectional Mendelian Randomization Study

ABSTRACT Background Spinal pain is the leading cause of disability worldwide. Previous studies have suggested the therapeutic effects of acetyl‐L‐carnitine (ALC) and L‐carnitine (LC) supplementation in specific chronic pain conditions, but not others. Mendelian randomization (MR) is an analytical approach using genetic variants for estimating causal associations. This bidirectional MR study aimed to examine the potential causal associations of ALC and LC on spinal pain (forward), and vice versa (reverse). Methods To obtain genetic instrumental variables, we used summary statistics from large publicly available genome‐wide association analyses datasets, with sample sizes between 6128 and 1,028,947 participants, for ALC, LC and spinal pain. We conducted MR analyses of potential causal associations using inverse‐variance weighted analysis and Causal Analysis Using Summary Effect. Results There were no statistically significant causal associations between ALC and spinal pain or LC and spinal pain in either forward or reverse directions. Results from secondary analyses were consistent with the primary analyses. Conclusions Although some prior evidence supports the effectiveness of ALC and LC supplementation in improving pain intensity in some pain conditions, results from this bidirectional MR study do not suggest causal effects of physiologic levels of ALC or LC on spinal pain, nor causal effects of spinal pain on ALC or LC. Significance Although some prior evidence supports the effectiveness of acetyl‐L‐carnitine (ALC) and L‐carnitine (LC) supplementation in improving pain intensity in some pain conditions, results from this bidirectional MR study do not suggest causal effects of circulating levels of ALC or LC on spinal pain, nor vice versa.