Association Between Serum Methylmalonic Acid (A Marker of Mitochondrial Dysfunction) and Serum Neurofilament Light Chains in a U.S. Population: a Cross‐Sectional Analysis From NHANES 2013–2014

Abstract Introduction Serum neurofilament light chain (sNfL) is an emerging biomarker of neuronal damage in various neurological disorders. Methylmalonic acid (MMA) serves as a biomarker for mitochondrial dysfunction. This study aimed to investigate the relationship between MMA and sNfL. Methods Dat...

Full description

Saved in:
Bibliographic Details
Main Authors: Jun Wei, Yang Liu, Ya Li
Format: Article
Language:English
Published: Wiley 2025-08-01
Series:Brain and Behavior
Subjects:
Online Access:https://doi.org/10.1002/brb3.70775
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1849390742892445696
author Jun Wei
Yang Liu
Ya Li
author_facet Jun Wei
Yang Liu
Ya Li
author_sort Jun Wei
collection DOAJ
description Abstract Introduction Serum neurofilament light chain (sNfL) is an emerging biomarker of neuronal damage in various neurological disorders. Methylmalonic acid (MMA) serves as a biomarker for mitochondrial dysfunction. This study aimed to investigate the relationship between MMA and sNfL. Methods Data were obtained from the 2013–2014 National Health and Nutrition Examination Survey (NHANES). Multiple linear regression modeling was employed to confirm the association between MMA and sNfL, while smooth curve fitting was utilized to explore the potential nonlinear relationship. Subgroup analyses and interaction tests were conducted to assess the stability of the association across different subgroups. Results This study included 2,070 participants with a mean age of 46.89 ± 15.36 years. In the fully adjusted model, each 1 nmol/L increase in serum MMA was associated with a 3.11 pg/mL increase in sNfL (95% CI: 0.91 to 5.31; p = 0.0056). Participants in the highest quartile of MMA had significantly higher sNfL levels compared to those in the lowest quartile (β = 5.09; 95% CI: 2.30 to 7.87; p = 0.0004). A nonlinear relationship was observed, with an inflection point at 5.51 nmol/L of MMA, while above the threshold, MMA was strongly associated with higher sNfL levels (β = 12.57, 95% CI: 7.14 to 17.99; p < 0.0001). Subgroup analyses further suggested stronger associations among individuals with diabetes or low vitamin B12 status (P for interaction < 0.05). Conclusions Our study found a significant positive association between serum MMA and sNfL. Further prospective studies are warranted.
format Article
id doaj-art-9fdb50be47d0429ca424d2c4d7eacf37
institution Kabale University
issn 2162-3279
language English
publishDate 2025-08-01
publisher Wiley
record_format Article
series Brain and Behavior
spelling doaj-art-9fdb50be47d0429ca424d2c4d7eacf372025-08-20T03:41:21ZengWileyBrain and Behavior2162-32792025-08-01158n/an/a10.1002/brb3.70775Association Between Serum Methylmalonic Acid (A Marker of Mitochondrial Dysfunction) and Serum Neurofilament Light Chains in a U.S. Population: a Cross‐Sectional Analysis From NHANES 2013–2014Jun Wei0Yang Liu1Ya Li2School of Basic Medical Sciences Jilin Medical University Jilin ChinaSchool of Basic Medical Sciences Jilin Medical University Jilin ChinaSchool of Basic Medical Sciences Jilin Medical University Jilin ChinaAbstract Introduction Serum neurofilament light chain (sNfL) is an emerging biomarker of neuronal damage in various neurological disorders. Methylmalonic acid (MMA) serves as a biomarker for mitochondrial dysfunction. This study aimed to investigate the relationship between MMA and sNfL. Methods Data were obtained from the 2013–2014 National Health and Nutrition Examination Survey (NHANES). Multiple linear regression modeling was employed to confirm the association between MMA and sNfL, while smooth curve fitting was utilized to explore the potential nonlinear relationship. Subgroup analyses and interaction tests were conducted to assess the stability of the association across different subgroups. Results This study included 2,070 participants with a mean age of 46.89 ± 15.36 years. In the fully adjusted model, each 1 nmol/L increase in serum MMA was associated with a 3.11 pg/mL increase in sNfL (95% CI: 0.91 to 5.31; p = 0.0056). Participants in the highest quartile of MMA had significantly higher sNfL levels compared to those in the lowest quartile (β = 5.09; 95% CI: 2.30 to 7.87; p = 0.0004). A nonlinear relationship was observed, with an inflection point at 5.51 nmol/L of MMA, while above the threshold, MMA was strongly associated with higher sNfL levels (β = 12.57, 95% CI: 7.14 to 17.99; p < 0.0001). Subgroup analyses further suggested stronger associations among individuals with diabetes or low vitamin B12 status (P for interaction < 0.05). Conclusions Our study found a significant positive association between serum MMA and sNfL. Further prospective studies are warranted.https://doi.org/10.1002/brb3.70775associationNHANESserum methylmalonic acidserum neurofilament light chain
spellingShingle Jun Wei
Yang Liu
Ya Li
Association Between Serum Methylmalonic Acid (A Marker of Mitochondrial Dysfunction) and Serum Neurofilament Light Chains in a U.S. Population: a Cross‐Sectional Analysis From NHANES 2013–2014
Brain and Behavior
association
NHANES
serum methylmalonic acid
serum neurofilament light chain
title Association Between Serum Methylmalonic Acid (A Marker of Mitochondrial Dysfunction) and Serum Neurofilament Light Chains in a U.S. Population: a Cross‐Sectional Analysis From NHANES 2013–2014
title_full Association Between Serum Methylmalonic Acid (A Marker of Mitochondrial Dysfunction) and Serum Neurofilament Light Chains in a U.S. Population: a Cross‐Sectional Analysis From NHANES 2013–2014
title_fullStr Association Between Serum Methylmalonic Acid (A Marker of Mitochondrial Dysfunction) and Serum Neurofilament Light Chains in a U.S. Population: a Cross‐Sectional Analysis From NHANES 2013–2014
title_full_unstemmed Association Between Serum Methylmalonic Acid (A Marker of Mitochondrial Dysfunction) and Serum Neurofilament Light Chains in a U.S. Population: a Cross‐Sectional Analysis From NHANES 2013–2014
title_short Association Between Serum Methylmalonic Acid (A Marker of Mitochondrial Dysfunction) and Serum Neurofilament Light Chains in a U.S. Population: a Cross‐Sectional Analysis From NHANES 2013–2014
title_sort association between serum methylmalonic acid a marker of mitochondrial dysfunction and serum neurofilament light chains in a u s population a cross sectional analysis from nhanes 2013 2014
topic association
NHANES
serum methylmalonic acid
serum neurofilament light chain
url https://doi.org/10.1002/brb3.70775
work_keys_str_mv AT junwei associationbetweenserummethylmalonicacidamarkerofmitochondrialdysfunctionandserumneurofilamentlightchainsinauspopulationacrosssectionalanalysisfromnhanes20132014
AT yangliu associationbetweenserummethylmalonicacidamarkerofmitochondrialdysfunctionandserumneurofilamentlightchainsinauspopulationacrosssectionalanalysisfromnhanes20132014
AT yali associationbetweenserummethylmalonicacidamarkerofmitochondrialdysfunctionandserumneurofilamentlightchainsinauspopulationacrosssectionalanalysisfromnhanes20132014