Prospective Cohort Study of Caffeinated Beverage Intake as a Potential Trigger of Headaches among Migraineurs

  • Elizabeth Mostofsky
    Reprint Address: Elizabeth Mostofsky, ScD, Department of Epidemiology, Harvard T.H. Chan School of Public Health, Kresge Building, Room 505-B, 677 Huntington Ave., Boston, MA 02115.
    Cardiovascular Epidemiology Research Unit, Beth Israel Deaconess Medical Center, Boston, Mass

    Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Mass
    Search for articles by this author
  • Murray A. Mittleman
    Cardiovascular Epidemiology Research Unit, Beth Israel Deaconess Medical Center, Boston, Mass

    Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Mass

    Harvard Medical School, Boston, Mass
    Search for articles by this author
  • Catherine Buettner
    Harvard Medical School, Boston, Mass

    Department of Medicine, Mount Auburn Hospital, Cambridge, Mass
    Search for articles by this author
  • Wenyuan Li
    Cardiovascular Epidemiology Research Unit, Beth Israel Deaconess Medical Center, Boston, Mass

    Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Mass
    Search for articles by this author
  • Suzanne M. Bertisch
    Harvard Medical School, Boston, Mass

    Department of Sleep Medicine, Beth Israel Deaconess Medical Center, Boston, Mass

    Sleep Medicine Epidemiology Program, Division of Sleep and Circadian Disorders, Brigham and Women's Hospital, Boston, Mass
    Search for articles by this author



      We aimed to evaluate the role of caffeinated beverage intake as a potential trigger of migraine headaches on that day or on the following day.


      In this prospective cohort study, 101 adults with episodic migraine completed electronic diaries every morning and evening. Ninety-eight participants completed at least 6 weeks of diaries in March 2016-October 2017. Every day, participants reported caffeinated beverage intake, other lifestyle factors, and the timing and characteristics of each migraine headache. We compared a participant's incidence of migraines on days with caffeinated beverage intake to the incidence of migraines among the same individual on days with no intake, accounting for day of week. We used conditional logistic regression to estimate odds ratios (OR) and 95% confidence intervals.


      Among 98 participants (86 women, 12 men) with mean age 35.1 years, 83% white, and 10% Hispanic or Latino, the average age when headaches started was 16.3 years. In total, the participants reported 825 migraines during 4467 days of observation. There was a statistically significant nonlinear association between the number of caffeinated beverages and the odds of migraine headache occurrence on that day (P-quadratic trend = .024), though estimates for each level of intake were not statistically significant. The associations varied according to habitual intake and oral contraceptive use.


      There was a nonlinear association between caffeinated beverage intake and the odds of migraine headache occurrence on that day. This suggests that high levels of caffeinated beverage intake may be a trigger of migraine headaches on that day.


      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to The American Journal of Medicine
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • The International Classification of Headache Disorders
        3rd edition (beta version).
        Cephalalgia. 2013; 33: 629-808
        • GBD 2016 Headache Collaborators
        Global, regional, and national burden of migraine and tension-type headache, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016.
        Lancet Neurol. 2018; 17: 954-976
        • Burch R.C.
        • Loder S.
        • Loder E.
        • Smitherman T.A.
        The prevalence and burden of migraine and severe headache in the United States: updated statistics from government health surveillance studies.
        Headache. 2015; 55: 21-34
        • Stewart W.F.
        • Ricci J.A.
        • Chee E.
        • Morganstein D.
        • Lipton R.
        Lost productive time and cost due to common pain conditions in the US workforce.
        JAMA. 2003; 290: 2443-2454
        • Bonafede M.
        • Sapra S.
        • Shah N.
        • Tepper S.
        • Cappell K.
        • Desai P.
        Direct and indirect healthcare resource utilization and costs among migraine patients in the United States.
        Headache. 2018; 58: 700-714
        • Messali A.
        • Sanderson J.C.
        • Blumenfeld A.M.
        • et al.
        Direct and indirect costs of chronic and episodic migraine in the United States: a web-based survey.
        Headache. 2016; 56: 306-322
        • Peatfield R.C.
        Relationships between food, wine, and beer-precipitated migrainous headaches.
        Headache. 1995; 35: 355-357
        • Van den Bergh V.
        • Amery W.K.
        • Waelkens J.
        Trigger factors in migraine: a study conducted by the Belgian Migraine Society.
        Headache. 1987; 27: 191-196
        • Kelman L.
        The triggers or precipitants of the acute migraine attack.
        Cephalalgia. 2007; 27: 394-402
        • Frary C.D.
        • Johnson R.K.
        • Wang M.Q.
        Food sources and intakes of caffeine in the diets of persons in the United States.
        J Am Diet Assoc. 2005; 105: 110-113
        • Lipton R.B.
        • Diener H.C.
        • Robbins M.S.
        • Garas S.Y.
        • Patel K.
        Caffeine in the management of patients with headache.
        J Headache Pain. 2017; 18: 107
        • Fried N.T.
        • Elliott M.B.
        • Oshinsky M.L.
        The role of adenosine signaling in headache: a review.
        Brain Sci. 2017; 7
        • Lipton R.B.
        • Pavlovic J.M.
        • Haut S.R.
        • Grosberg B.M.
        • Buse D.C.
        Methodological issues in studying trigger factors and premonitory features of migraine.
        Headache. 2014; 54: 1661-1669
        • Park J.W.
        • Chu M.K.
        • Kim J.M.
        • Park S.G.
        • Cho S.J.
        Analysis of trigger factors in episodic migraineurs using a amartphone headache diary applications.
        PLoS One. 2016; 11e0149577
        • Wober C.
        • Brannath W.
        • Schmidt K.
        • et al.
        Prospective analysis of factors related to migraine attacks: the PAMINA study.
        Cephalalgia. 2007; 27: 304-314
        • Headache Classification Subcommittee of the International Headache Society
        The International Classification of Headache Disorders: 2nd edition.
        Cephalalgia. 2004; 24: 9-160
        • Harris P.A.
        • Taylor R.
        • Thielke R.
        • Payne J.
        • Gonzalez N.
        • Conde J.G.
        Research electronic data capture (REDCap)--a metadata-driven methodology and workflow process for providing translational research informatics support.
        J Biomed Inform. 2009; 42: 377-381
        • Patel S.R.
        • Weng J.
        • Rueschman M.
        • et al.
        Reproducibility of a standardized actigraphy scoring algorithm for sleep in a US Hispanic/Latino population.
        Sleep. 2015; 38: 1497-1503
        • Watson D.
        • Clark L.A.
        • Tellegen A.
        Development and validation of brief measures of positive and negative affect: the PANAS scales.
        J Pers Soc Psychol. 1988; 54: 1063-1070
        • Buysse D.J.
        • Thompson W.
        • Scott J.
        • et al.
        Daytime symptoms in primary insomnia: a prospective analysis using ecological momentary assessment.
        Sleep Med. 2007; 8: 198-208
        • Kosinski M.
        • Bayliss M.S.
        • Bjorner J.B.
        • et al.
        A six-item short-form survey for measuring headache impact: the HIT-6.
        Qual Life Res. 2003; 12: 963-974
        • Maclure M.
        • Mittleman M.A.
        Should we use a case-crossover design?.
        Annu Rev Public Health. 2000; 21: 193-221
        • Mostofsky E.
        • Coull B.A.
        • Mittleman M.A.
        Analysis of observational self-matched data to examine acute triggers of outcome events with abrupt onset.
        Epidemiology. 2018; 29: 804-816
        • Abernethy D.R.
        • Todd E.L.
        Impairment of caffeine clearance by chronic use of low-dose oestrogen-containing oral contraceptives.
        Eur J Clin Pharmacol. 1985; 28: 425-428
        • Patwardhan R.V.
        • Desmond P.V.
        • Johnson R.F.
        • Schenker S.
        Impaired elimination of caffeine by oral contraceptive steroids.
        J Lab Clin Med. 1980; 95: 603-608
        • Goadsby P.J.
        • Silberstein S.D.
        Migraine triggers: harnessing the messages of clinical practice.
        Neurology. 2013; 80: 424-425
        • Zaeem Z.
        • Zhou L.
        • Dilli E.
        Headaches: a review of the role of dietary factors.
        Curr Neurol Neurosci Rep. 2016; 16: 101
        • Peris F.
        • Donoghue S.
        • Torres F.
        • Mian A.
        • Wober C.
        Towards improved migraine management: determining potential trigger factors in individual patients.
        Cephalalgia. 2017; 37: 452-463
        • Baldacci F.
        • Vedovello M.
        • Ulivi M.
        • et al.
        How aware are migraineurs of their triggers?.
        Headache. 2013; 53: 834-837
        • Hougaard A.
        • Amin F.M.
        • Hauge A.W.
        • Ashina M.
        • Olesen J.
        Provocation of migraine with aura using natural trigger factors.
        Neurology. 2013; 80: 428-431
        • Varkey E.
        • Gruner Svealv B.
        • Edin F.
        • Ravn-Fischer A.
        • Cider A.
        Provocation of migraine after maximal exercise: a test-retest study.
        Eur Neurol. 2017; 78: 22-27
        • Green A.
        • Stuart C.A.
        • Pietrzyk R.A.
        • Partin M.
        Photochemical cross-linking of 125I-hydroxyphenylisopropyl adenosine to the A1 adenosine receptor of rat adipocytes.
        FEBS Lett. 1986; 206: 130-134
        • Echeverri D.
        • Montes F.R.
        • Cabrera M.
        • Galan A.
        • Prieto A.
        Caffeine's vascular mechanisms of action.
        Int J Vasc Med. 2010; 2010834060
        • Fredholm B.B.
        • Battig K.
        • Holmen J.
        • Nehlig A.
        • Zvartau E.E.
        Actions of caffeine in the brain with special reference to factors that contribute to its widespread use.
        Pharmacol Rev. 1999; 51: 83-133
        • Green R.M.
        • Stiles G.L.
        Chronic caffeine ingestion sensitizes the A1 adenosine receptor-adenylate cyclase system in rat cerebral cortex.
        J Clin Invest. 1986; 77: 222-227
        • Ribeiro J.A.
        • Sebastiao A.M.
        Caffeine and adenosine.
        J Alzheimers Dis. 2010; 20: S3-S15
        • Advokat C.D.
        • Comaty J.E.
        • Julien R.M.
        Caffeine and nicotine.
        in: A Primer of Drug Action: a Comprehensive Guide to the Actions, Uses, and Side Effects of Psychoactive Drugs. 13th ed. Worth Publishers, New York2014: 167-175 (Chapter 6)
        • Attipoe S.
        • Leggit J.
        • Deuster P.A.
        Caffeine content in popular energy drinks and energy shots.
        Mil Med. 2016; 181: 1016-1020
        • Stavric B.
        • Klassen R.
        • Watkinson B.
        • Karpinski K.
        • Stapley R.
        • Fried P.
        Variability in caffeine consumption from coffee and tea: possible significance for epidemiological studies.
        Food Chem Toxicol. 1988; 26: 111-118