Inflammation Factors Mediate Association of Muscle Mass and Migraine: NHANES 1999–2004 and Mendelian Randomization

Chunyan Jia, Hong Li, Shaonan Yang, Yue Liu, Lijun Liu, Aijun Ma, Liang Zhang Department of Neurology, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao, People’s Republic of ChinaCorrespondence: Liang Zhang, Department of Neurology, The Affiliated Hospital of Qingdao Univer...

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Main Authors: Jia C, Li H, Yang S, Liu Y, Liu L, Ma A, Zhang L
Format: Article
Language:English
Published: Dove Medical Press 2025-05-01
Series:Journal of Pain Research
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Online Access:https://www.dovepress.com/inflammation-factors-mediate-association-of-muscle-mass-and-migraine-n-peer-reviewed-fulltext-article-JPR
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author Jia C
Li H
Yang S
Liu Y
Liu L
Ma A
Zhang L
author_facet Jia C
Li H
Yang S
Liu Y
Liu L
Ma A
Zhang L
author_sort Jia C
collection DOAJ
description Chunyan Jia, Hong Li, Shaonan Yang, Yue Liu, Lijun Liu, Aijun Ma, Liang Zhang Department of Neurology, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao, People’s Republic of ChinaCorrespondence: Liang Zhang, Department of Neurology, The Affiliated Hospital of Qingdao University, 16 Jiangsu Road, Shinan District, Qingdao, Shandong, 266071, People’s Republic of China, Tel +86-178-5329-7291, Email drzhangliang@126.com Lijun Liu, Department of Neurology, The Affiliated Hospital of Qingdao University, 16 Jiangsu Road, Shinan District, Qingdao, Shandong, 266071, People’s Republic of China, Tel +86-178-5329-0950, Email superdrjenny@126.comPurpose: The relationship between adipose-muscle distribution and its effect on migraine remains unclear. This study examines the association between muscle mass and migraine prevalence and evaluates potential mediation by systemic inflammatory biomarkers.Methods: Using a cross-sectional design, we analyzed data from 10,400 participants in the National Health and Nutrition Examination Survey (NHANES) (1999– 2004). The association between appendicular lean mass normalized to body mass index (ALM/BMI) and migraine prevalence was evaluated through weighted logistic regression and subgroup analyses. Mediation analyses were conducted to examine the potential mediating roles of inflammatory markers, including C-reactive protein (CRP), white blood cell count (WBC), and neutrophils, in the relationship between ALM/BMI and migraine prevalence. Genetic causality was investigated via two-sample Mendelian randomization (MR) using genome-wide association study (GWAS) data.Results: 20% of total participants reported migraines. A higher ALM/BMI ratio was inversely associated with migraine after full adjustment (OR = 0.243; 95% CI: 0.122– 0.487, p < 0.001). Vigorous activity reduced migraine susceptibility by 24% (OR = 0.760; 95% CI: 0.663– 0.872, p < 0.001). CRP, WBC and neutrophils mediated 2.0% (p = 0.024), 3.1% (p = 0.011), and 2.8% (p = 0.019) of the ALM/BMI-migraine association, respectively. The inverse-variance weighted approach (IVW) in MR analysis indicated that higher basal metabolic rate (BMR) reduced migraine risk (OR = 0.996, 95% CI: 0.992– 0.998, p = 0.004) and headache risk (OR = 0.998, 95% CI: 0.997– 1.000, p = 0.018). Fat-free mass also exhibited protective effects on migraines (OR = 0.997, 95% CI: 0.994– 1.000, p = 0.045).Conclusion: Increased muscle mass is associated with reduced migraine risk, partially mediated by attenuating systemic inflammation. These findings provide us with an approach of health management to prevent migraines.Keywords: appendicular muscle mass, basal metabolic rate, migraine, inflammation, national health and nutrition examination survey, Mendelian randomization
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spelling doaj-art-e5c6490aa6eb49569347324b14d6df332025-08-20T03:09:32ZengDove Medical PressJournal of Pain Research1178-70902025-05-01Volume 18Issue 122692283102618Inflammation Factors Mediate Association of Muscle Mass and Migraine: NHANES 1999–2004 and Mendelian RandomizationJia C0Li H1Yang SLiu Y2Liu LMa A3Zhang L4Department of NeurologyDepartment of NeurologyneurologyDepartment of NeurologyDepartment of NeurologyChunyan Jia, Hong Li, Shaonan Yang, Yue Liu, Lijun Liu, Aijun Ma, Liang Zhang Department of Neurology, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao, People’s Republic of ChinaCorrespondence: Liang Zhang, Department of Neurology, The Affiliated Hospital of Qingdao University, 16 Jiangsu Road, Shinan District, Qingdao, Shandong, 266071, People’s Republic of China, Tel +86-178-5329-7291, Email drzhangliang@126.com Lijun Liu, Department of Neurology, The Affiliated Hospital of Qingdao University, 16 Jiangsu Road, Shinan District, Qingdao, Shandong, 266071, People’s Republic of China, Tel +86-178-5329-0950, Email superdrjenny@126.comPurpose: The relationship between adipose-muscle distribution and its effect on migraine remains unclear. This study examines the association between muscle mass and migraine prevalence and evaluates potential mediation by systemic inflammatory biomarkers.Methods: Using a cross-sectional design, we analyzed data from 10,400 participants in the National Health and Nutrition Examination Survey (NHANES) (1999– 2004). The association between appendicular lean mass normalized to body mass index (ALM/BMI) and migraine prevalence was evaluated through weighted logistic regression and subgroup analyses. Mediation analyses were conducted to examine the potential mediating roles of inflammatory markers, including C-reactive protein (CRP), white blood cell count (WBC), and neutrophils, in the relationship between ALM/BMI and migraine prevalence. Genetic causality was investigated via two-sample Mendelian randomization (MR) using genome-wide association study (GWAS) data.Results: 20% of total participants reported migraines. A higher ALM/BMI ratio was inversely associated with migraine after full adjustment (OR = 0.243; 95% CI: 0.122– 0.487, p < 0.001). Vigorous activity reduced migraine susceptibility by 24% (OR = 0.760; 95% CI: 0.663– 0.872, p < 0.001). CRP, WBC and neutrophils mediated 2.0% (p = 0.024), 3.1% (p = 0.011), and 2.8% (p = 0.019) of the ALM/BMI-migraine association, respectively. The inverse-variance weighted approach (IVW) in MR analysis indicated that higher basal metabolic rate (BMR) reduced migraine risk (OR = 0.996, 95% CI: 0.992– 0.998, p = 0.004) and headache risk (OR = 0.998, 95% CI: 0.997– 1.000, p = 0.018). Fat-free mass also exhibited protective effects on migraines (OR = 0.997, 95% CI: 0.994– 1.000, p = 0.045).Conclusion: Increased muscle mass is associated with reduced migraine risk, partially mediated by attenuating systemic inflammation. These findings provide us with an approach of health management to prevent migraines.Keywords: appendicular muscle mass, basal metabolic rate, migraine, inflammation, national health and nutrition examination survey, Mendelian randomizationhttps://www.dovepress.com/inflammation-factors-mediate-association-of-muscle-mass-and-migraine-n-peer-reviewed-fulltext-article-JPRAppendicular muscle massbasal metabolic ratemigraineinflammationnational health and nutrition examination surveyMendelian randomization
spellingShingle Jia C
Li H
Yang S
Liu Y
Liu L
Ma A
Zhang L
Inflammation Factors Mediate Association of Muscle Mass and Migraine: NHANES 1999–2004 and Mendelian Randomization
Journal of Pain Research
Appendicular muscle mass
basal metabolic rate
migraine
inflammation
national health and nutrition examination survey
Mendelian randomization
title Inflammation Factors Mediate Association of Muscle Mass and Migraine: NHANES 1999–2004 and Mendelian Randomization
title_full Inflammation Factors Mediate Association of Muscle Mass and Migraine: NHANES 1999–2004 and Mendelian Randomization
title_fullStr Inflammation Factors Mediate Association of Muscle Mass and Migraine: NHANES 1999–2004 and Mendelian Randomization
title_full_unstemmed Inflammation Factors Mediate Association of Muscle Mass and Migraine: NHANES 1999–2004 and Mendelian Randomization
title_short Inflammation Factors Mediate Association of Muscle Mass and Migraine: NHANES 1999–2004 and Mendelian Randomization
title_sort inflammation factors mediate association of muscle mass and migraine nhanes 1999 amp ndash 2004 and mendelian randomization
topic Appendicular muscle mass
basal metabolic rate
migraine
inflammation
national health and nutrition examination survey
Mendelian randomization
url https://www.dovepress.com/inflammation-factors-mediate-association-of-muscle-mass-and-migraine-n-peer-reviewed-fulltext-article-JPR
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