TY - JOUR

T1 - Causal Associations Between Carnitine-Related Metabolites and Spinal Pain

T2 - A Bidirectional Mendelian Randomization Study

AU - Chiu, Abby Pei Ting

AU - Elgaeva, Elizaveta

AU - Arendt-Nielsen, Lars

AU - Curatolo, Michele

AU - Suri, Pradeep

N1 - Chiu, A. P.-T., E. Elgaeva, L. Arendt-Nielsen, M. Curatolo, and P. Suri. 2026. “ Causal Associations Between Carnitine-Related Metabolites and Spinal Pain: A Bidirectional Mendelian Randomization Study.” European Journal of Pain 30, no. 9: e70407. https://doi.org/10.1002/ejp.70407. P.S. is supported by the Clinical, Learning, Evidence, And Research(CLEAR) Center, at the University of Washington, which is fundedby NIAMS/NIH P30AR072572. The work of E.E. was supportedby the budget project of the Institute of Cytology and Genetics №FWNR-2026- 0023.

PY - 2026/9/28

Y1 - 2026/9/28

N2 - 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.

AB - 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.

KW - L-carnitine

KW - Mendelian randomization

KW - acetyl-L-carnitine

KW - causation

KW - epidemiology

KW - spinal pain

KW - ацетил-L-карнитин

KW - причинно-следственная связь

KW - эпидемиология

KW - L-карнитин

KW - менделевская рандомизация

KW - боль в позвоночнике

UR - https://www.mendeley.com/catalogue/38e18446-fabb-310e-9dac-752164278b09/

UR - https://www.scopus.com/pages/publications/105051950573

U2 - 10.1002/ejp.70407

DO - 10.1002/ejp.70407

M3 - Article

C2 - 42804423

VL - 30

JO - European Journal of Pain

JF - European Journal of Pain

SN - 1532-2149

IS - 9

ER -