Generic placeholder image

Current Neurovascular Research

Editor-in-Chief

ISSN (Print): 1567-2026
ISSN (Online): 1875-5739

Research Article

The Association between Serum Total Bilirubin and Severe Headaches or Migraine in American Adults

Author(s): Yuting He, Hao Huang, Lingao Dai and Xiaoping Wang*

Volume 20, Issue 5, 2023

Published on: 01 December, 2023

Page: [519 - 527] Pages: 9

DOI: 10.2174/0115672026284009231120065521

Price: $65

Abstract

Background: Studies about the association between bilirubin and migraine were few. Therefore, the purpose of this study was to investigate the association between serum total bilirubin and the prevalence of severe headaches or migraine.

Methods: A multivariable logistic regression was used to assess the association between serum total bilirubin concentration and severe headaches or migraine. We also performed stratified analyses, interaction analyses and multiple interpolations in the sensitivity analysis.

Results: This cross-sectional study included 12,552 adults from the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2004. The overall incidence of migraine was 19.99% (2,509/12,552). With every 1 mg/dl increase in bilirubin, the prevalence of migraine decreased by 23% (95% CI: 0.64, 0.93) after adjustment of all related covariates. Similarly, the risk of migraine was reduced by 17% (95% CI: 0.72, 0.97) in the Q4 group (the fourth quartile, highest serum total bilirubin level) compared with the Q1 group (the lowest level). Furthermore, interaction effects by age groups were significant in this relationship (P for interaction = 0.0004). In the Q4 group compared with Q1, inverse associations were observed in those aged ≥40 years (OR: 0.71,95% CI: 0.59, 0.85) in the stratified analysis.

Conclusion: These findings support an association between serum total bilirubin and severe headaches or migraine, revealing an inverse association between serum total bilirubin quartiles and severe headaches or migraine in American adults. Age could play an important role in this association.

[1]
Eigenbrodt AK, Ashina H, Khan S, et al. Diagnosis and management of migraine in ten steps. Nat Rev Neurol 2021; 17(8): 501-14.
[http://dx.doi.org/10.1038/s41582-021-00509-5] [PMID: 34145431]
[2]
Harris L, L’Italien G, Kumar A, et al. Real-world assessment of the relationship between migraine-related disability and healthcare costs in the United States. Headache 2022; 62(4): 473-81.
[http://dx.doi.org/10.1111/head.14289] [PMID: 35343590]
[3]
Burch R, Rizzoli P, Loder E. The prevalence and impact of migraine and severe headache in the united states: Figures and trends from government health studies. Headache 2018; 58(4): 496-505.
[http://dx.doi.org/10.1111/head.13281] [PMID: 29527677]
[4]
Eising E. A Datson N, van den Maagdenberg AMJM, Ferrari MD. Epigenetic mechanisms in migraine: A promising avenue? BMC Med 2013; 11(1): 26.
[http://dx.doi.org/10.1186/1741-7015-11-26] [PMID: 23379668]
[5]
Yazar HO, Yazar T, Aygün A. Kaygisiz Ş, Kirbaş, D. Evaluation of simple inflammatory blood parameters in patients with migraine. Ir J Med Sci 2020; 189(2): 677-83.
[http://dx.doi.org/10.1007/s11845-019-02136-y] [PMID: 31758522]
[6]
Kawamura K, Ishikawa K, Wada Y, et al. Bilirubin from heme oxygenase-1 attenuates vascular endothelial activation and dysfunction. Arterioscler Thromb Vasc Biol 2005; 25(1): 155-60.
[http://dx.doi.org/10.1161/01.ATV.0000148405.18071.6a] [PMID: 15499042]
[7]
Barañano DE, Rao M, Ferris CD, Snyder SH. Biliverdin reductase: A major physiologic cytoprotectant. Proc Natl Acad Sci 2002; 99(25): 16093-8.
[http://dx.doi.org/10.1073/pnas.252626999] [PMID: 12456881]
[8]
Stocker R, Yamamoto Y, McDonagh AF, Glazer AN, Ames BN. Bilirubin is an antioxidant of possible physiological importance. Science 1987; 235(4792): 1043-6.
[http://dx.doi.org/10.1126/science.3029864] [PMID: 3029864]
[9]
Kunutsor SK, Bakker SJ, Gansevoort RT, Chowdhury R, Dullaart RPJA. Circulating total bilirubin and risk of incident cardiovascular disease in the general population. Arterioscler Thromb Vasc Biol 2015; 35(3): 716-24.
[http://dx.doi.org/10.1161/ATVBAHA.114.304929]
[10]
Choi Y, Lee SJ, Spiller W, Jung KJ, Lee J-Y, Kimm H, et al. Causal associations between serum bilirubin levels and decreased stroke risk: a two-sample Mendelian randomization study. Arterioscler Thromb Vasc Biol 2020; 40(2): 437-45.
[http://dx.doi.org/10.1161/ATVBAHA.119.313055]
[11]
Dohi K, Mochizuki Y, Satoh K, Jimbo H, Hayashi M, Toyoda I, et al. Transient elevation of serum bilirubin (a heme oxygenase-1 metabolite) level in hemorrhagic stroke: Bilirubin is a marker of oxidant stress. Acta Neurochir Suppl 2003; 86: 247-9.
[http://dx.doi.org/10.1007/978-3-7091-0651-8_53]
[12]
Soleimanpour H. Bilirubin: From a disease predictor to a potential therapeutic in stroke. Int J Aging 2023; 1: e1.
[http://dx.doi.org/10.34172/ija.2023.e1]
[13]
Targher G. Risk of ischemic stroke and decreased serum bilirubin levels: Is there a causal link? Arterioscler Thromb Vasc Biol 2014; 34(4): 702-4.
[http://dx.doi.org/10.1161/ATVBAHA.114.303279] [PMID: 24665123]
[14]
Calabrese V, Guagliano E, Sapienza M, Panebianco M, Calafato S, Puleo E, et al. Redox regulation of cellular stress response in aging and neurodegenerative disorders: Role of vitagenes. Neurochem Res 2007; 32(4-5): 757-3.
[http://dx.doi.org/10.1007/s11064-006-9203-y]
[15]
Jayanti S, Moretti R, Tiribelli C, Gazzin S. Bilirubin: A promising therapy for Parkinson’s disease. Int J Mol Sci 2021; 22(12): 6223.
[http://dx.doi.org/10.3390/ijms22126223] [PMID: 34207581]
[16]
Yao JK, Reddy R. Abnormal age-related changes of plasma antioxidant proteins in Schizophrenia. Psychiatry Res 2000; 97(2-3): 137-51.
[http://dx.doi.org/10.1016/S0165-1781(00)00230-4]
[17]
Iłżecka J. Serum bilirubin concentration in patients with amyotrophic lateral sclerosis. Clin Neurol Neurosurg 2003; 105(4): 237-40.
[http://dx.doi.org/10.1016/S0303-8467(03)00031-3]
[18]
Gilhus NE, Deuschl GJNRN. Neuroinflammation-A common thread in neurological disorders. Nat Rev Neurol 2019; 15(8): 429-30.
[http://dx.doi.org/10.1038/s41582-019-0227-8]
[19]
Peng YF, Xie LQ, Xiang Y, Xu GD. Serum bilirubin and their association with C-reactive protein in patients with migraine. J Clin Lab Anal 2016; 30(6): 982-5.
[http://dx.doi.org/10.1002/jcla.21967] [PMID: 26996761]
[20]
Yang Z, Xu P. Evaluation of simple antioxidant blood parameters in patients with migraine. Front Neurol 2022; 13: 939363.
[http://dx.doi.org/10.3389/fneur.2022.939363]
[21]
Elshony HS, El Sheikh WM, Melake MS. Association between serum bilirubin and migraine in children and adolescents. Egypt J Neurol Psychiat Neurosurg 2020; 56(1): 85.
[http://dx.doi.org/10.1186/s41983-020-00217-9]
[22]
Melake M, El-Sheikh W, El-shony H. Serum bilirubin as a neuroinflammatory biomarker in chilhood and adolescent migraine. J Neurol Sci 2019; 405: 49.
[http://dx.doi.org/10.1016/j.jns.2019.10.306]
[23]
Huang H, He K. The association between dietary fiber intake and severe headaches or migraine in US adults. Front Nutr 2023; 9: 1044066.
[http://dx.doi.org/10.3389/fnut.2022.1044066] [PMID: 36687687]
[24]
Meng SH, Zhou HB, Li X, et al. Association between dietary iron intake and serum ferritin and severe headache or migraine. Front Nutr 2021; 8: 685564.
[http://dx.doi.org/10.3389/fnut.2021.685564] [PMID: 34295917]
[25]
Meng S-H, Wang M-X, Kang L-X, Fu J-M, Zhou H-B, Li X, et al. Dietary intake of calcium and magnesium in relation to severe headache or migraine. Front Nutr 2021; 8: 653765.
[http://dx.doi.org/10.3389/fnut.2021.653765]
[26]
Buse DC, Loder EW, Gorman JA, et al. Sex differences in the prevalence, symptoms, and associated features of migraine, probable migraine and other severe headache: results of the American Migraine Prevalence and Prevention (AMPP) Study. Headache 2013; 53(8): 1278-99.
[http://dx.doi.org/10.1111/head.12150] [PMID: 23808666]
[27]
Žiberna L, Jenko-Pražnikar Z, Petelin A. Serum bilirubin levels in overweight and obese individuals: The importance of anti-inflammatory and antioxidant responses. Antioxidants 2021; 10(9): 1352.
[http://dx.doi.org/10.3390/antiox10091352] [PMID: 34572984]
[28]
Djoussé L, Levy D, Cupples LA, Evans JC, D’Agostino RB. Total serum bilirubin and risk of cardiovascular disease in the Framingham offspring study. Am J Cardiol 2001; 87(10): 1196-200.
[http://dx.doi.org/10.1016/S0002-9149(01)01494-1]
[29]
Yang M, Ni C, Chang B, et al. Association between serum total bilirubin levels and the risk of type 2 diabetes mellitus. Diabetes Res Clin Pract 2019; 152: 23-8.
[http://dx.doi.org/10.1016/j.diabres.2019.04.033] [PMID: 31078667]
[30]
Tan J, Pei G, Xu Y, et al. Serum bilirubin is correlated with the progression of iga vasculitis with nephritis. Front Med 2021; 8: 596151.
[http://dx.doi.org/10.3389/fmed.2021.596151] [PMID: 34169080]
[31]
Sacco S, Pistoia F, Degan D, Carolei AJC. Conventional vascular risk factors: Their role in the association between migraine and cardiovascular diseases. Cephalalgia 2015; 35(2): 146-64.
[http://dx.doi.org/10.1177/0333102414559551]
[32]
Wabnitz A, Bushnell CJC. Migraine, cardiovascular disease, and stroke during pregnancy: systematic review of the literature. Cephalalgia 2015; 35(2): 132-9.
[http://dx.doi.org/10.1177/0333102414554113]
[33]
Olesen J, Burstein R, Ashina M, Tfelt-Hansen PJTLN. Origin of pain in migraine: Evidence for peripheral sensitisation. Lancet Neurol 2009; 8(7): 679-90.
[http://dx.doi.org/10.1016/S1474-4422(09)70090-0]
[34]
Aczél T, Körtési T, Kun J, et al. Identification of disease- and headache-specific mediators and pathways in migraine using blood transcriptomic and metabolomic analysis. J Headache Pain 2021; 22(1): 117.
[http://dx.doi.org/10.1186/s10194-021-01285-9] [PMID: 34615455]
[35]
Vítek L, Jirásková A, Malíková I, et al. Serum bilirubin and markers of oxidative stress and inflammation in a healthy population and in patients with various forms of atherosclerosis. Antioxidants 2022; 11(11): 2118.
[http://dx.doi.org/10.3390/antiox11112118] [PMID: 36358491]
[36]
Woronyczová J, Nováková M. Leníček M, Bátovský M, Bolek E, Cífková R, et al. Serum bilirubin concentrations and the prevalence of Gilbert syndrome in elite athletes. Sports Med Open 2022; 8(1): 84.
[http://dx.doi.org/10.1186/s40798-022-00463-6]
[37]
Vítek L, Novotný L, Žák A. Staňková B, Zima T, Polito A, et al. Relationship between serum bilirubin and uric acid to oxidative stress markers in Italian and Czech populations. J Appl Biomed 2013; 11(4): 209-11.
[http://dx.doi.org/10.2478/v10136-012-0030-y]
[38]
Xie KH, Liu LL, Su CY, et al. Low antioxidant status of serum uric acid, bilirubin, albumin, and creatinine in patients with benign paroxysmal positional vertigo. Front Neurol 2020; 11: 601695.
[http://dx.doi.org/10.3389/fneur.2020.601695] [PMID: 33329359]
[39]
Kim DE, Lee Y, Kim M, Lee S, Jon S, Lee SH. Bilirubin nanoparticles ameliorate allergic lung inflammation in a mouse model of asthma. Biomaterials 2017; 140: 37-44.
[http://dx.doi.org/10.1016/j.biomaterials.2017.06.014] [PMID: 28624706]
[40]
Zhao X, Li L, Zhang H. The relationship between serum bilirubin and inflammatory bowel disease. Gastroenterology 2019; 156: S390.
[http://dx.doi.org/10.1155/2019/5256460]
[41]
Ghavami A, Khorvash F, Khalesi S, Heidari Z, Askari G. The effects of synbiotic supplementation on oxidative stress and clinical symptoms in women with migraine: A double-blind, placebo-controlled, randomized trial. J Funct Foods 2021; 86: 104738.
[http://dx.doi.org/10.1016/j.jff.2021.104738]
[42]
Li Y, Huang B, Ye T, Wang Y, Xia D, Qian JJII. Physiological concentrations of bilirubin control inflammatory response by inhibiting NF-κB and inflammasome activation. Int Immunopharmacol 2020; 84: 106520.
[http://dx.doi.org/10.1016/j.intimp.2020.106520]
[43]
Silberstein S, Loder E, Diamond S, Reed M, Bigal ME, Lipton RB, et al. Probable migraine in the United States: Results of the American Migraine Prevalence and Prevention (AMPP) study. Cephalalgia 2007; 27(3): 220-9.
[http://dx.doi.org/10.1111/j.1468-2982.2006.01275.x]
[44]
Goadsby PJ, Holland PR, Martins-Oliveira M, Hoffmann J, Schankin C, Akerman S. Pathophysiology of migraine: A disorder of sensory processing. Physiol Rev 2017; 97(2): 553-622.
[http://dx.doi.org/10.1152/physrev.00034.2015] [PMID: 28179394]
[45]
Yasin S, Altunisik E. Decreased serum uric acid level as an indicator of altered oxidative balance in patients with migraine. Cureus 2022; 14(12): e32136.
[http://dx.doi.org/10.7759/cureus.32136] [PMID: 36601146]
[46]
Cao L, Xue L, Luo DM. Lower serum bilirubin concentration in patients with migraine. Int J Clin Exp Med 2015; 8(8): 13398-402.
[PMID: 26550273]
[47]
Madhavan M, Wattigney WA, Srinivasan SR, Berenson GSJA. Serum bilirubin distribution and its relation to cardiovascular risk in children and young adults. Atherosclerosis 1997; 131(1): 107-3.
[http://dx.doi.org/10.1016/S0021-9150(97)06088-7]
[48]
Kao T-L, Chen Y-L, Kuan Y-P, Chang W-C, Ho Y-C, Yeh S, et al. Estrogen-estrogen receptor α signaling facilitates bilirubin metabolism in regenerating liver through regulating cytochrome P450 2A6 expression. Cell Transplant 2017; 26(11): 1822-9.
[http://dx.doi.org/10.1177/0963689717738258]
[49]
Chen X, Yang S, Yang Y, et al. Exploring the relationship of peripheral total bilirubin, red blood cell, and hemoglobin with blood pressure during childhood and adolescence. J Pediatr (Rio J) 2018; 94(5): 532-8.
[http://dx.doi.org/10.1016/j.jped.2017.07.018] [PMID: 29107800]
[50]
Wu N, Zhai X, Feng M, Li J, Yu N, Zhang F, et al. The gender-specific bidirectional relations between chronic diseases and total bilirubin/urea in the elderly population: A 3-year longitudinal study. Front Public Health 2022; 10: 1003505.
[http://dx.doi.org/10.3389/fpubh.2022.1003505]
[51]
Sun Z, Chai J, Zhou Q, Xu JJBM. Establishment of gender-and age-specific reference intervals for serum liver function tests among the elderly population in northeast China: A retrospective study. Biochem Med 2022; 32(2): 020707.
[http://dx.doi.org/10.11613/BM.2022.020707]
[52]
Martin BC, Dorfman JH, McMillan JA. Prevalence of migraine headache and association with sex, age, race, and rural/urban residence: A population-based study of Georgia Medicaid recipients. Clin Ther 1994; 16(5): 855-72.
[53]
Bigal ME, Liberman JN, Lipton RB. Age-dependent prevalence and clinical features of migraine. Neurology 2006; 67(2): 246-51.
[http://dx.doi.org/10.1212/01.wnl.0000225186.76323.69] [PMID: 16864816]
[54]
Manandhar K, Risal A, Steiner TJ, Holen A, Linde M. The prevalence of primary headache disorders in Nepal: A nationwide population-based study. J Headache Pain 2015; 16(1): 95.
[http://dx.doi.org/10.1186/s10194-015-0580-y] [PMID: 26554602]
[55]
Stewart WF, Lipton RB, Liberman JJN. Variation in migraine prevalence by race. Neurology 1996; 47(1): 52-9.
[http://dx.doi.org/10.1212/WNL.47.1.52]
[56]
Lebedeva ER. Sex and age differences in migraine treatment and management strategies. Int Rev Neurobiol 2022; 164: 309-47.
[http://dx.doi.org/10.1016/bs.irn.2022.07.003] [PMID: 36038208]
[57]
Merle D. The impact of migraine on the health and well-being of women. J Womens Health 2007; 16(9): 1269-80.
[http://dx.doi.org/10.1089/jwh.2007.0388]
[58]
Raut S, Singh U, Sarmah D, Datta A, Baidya F, Shah B, et al. Migraine and ischemic stroke: Deciphering the bidirectional pathway. ACS Chem Neurosci 2007; 11(11): 1525-38.
[http://dx.doi.org/10.1021/acschemneuro.0c00137]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy