The Evidence for the Role of Nutraceuticals in the Management of Pediatric Migraine: a Review

  • Serena L. Orr
Childhood and Adolescent Headache (S Evers, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Childhood and Adolescent Headache


Purpose of Review

Nutraceuticals are a form of complementary and alternative medicine that is commonly used by children and adolescents with migraine. In this review, observational studies, randomized controlled trials, systematic reviews, and meta-analyses on the efficacy and safety of single compound nutraceuticals for the management of migraine in children and adolescents were identified through a literature search of MEDLINE, Embase, and EBM Reviews—Cochrane Central Register of Controlled Trials.

Recent Findings

Twenty-one studies were reviewed, of which 11 were observational studies, 7 were randomized controlled trials, and 3 were systematic reviews. Six different nutraceuticals were included in the review: vitamin D, riboflavin, coenzyme Q10, magnesium, butterbur, and polyunsaturated fatty acids. All but three of the studies assessed the role of nutraceuticals in migraine prevention, while three studies evaluated the role of intravenous magnesium for acute migraine management. Overall, the quality and size of the studies were limited.


Due to low quality evidence and limited studies, no definite conclusions can be drawn on the efficacy of nutraceuticals for the treatment of pediatric migraine. Future studies are warranted in order to establish evidence upon which to define the role of nutraceuticals in this patient population.


Pediatric migraine Nutraceuticals Vitamins Prophylaxis Prevention Acute treatment 


Compliance with Ethical Standards

Conflict of Interest

Serena L. Orr declares no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.


Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    Abu-Arafeh I, Razak S, Sivaraman B, Graham C. Prevalence of headache and migraine in children and adolescents: a systematic review of population-based studies. Dev Med Child Neurol. 2010;52(12):1088–97.CrossRefPubMedGoogle Scholar
  2. 2.
    Feigin VL, Abajobir AA, Abate KH, Abd-Allah F, Abdulle AM, Abera SF, et al. Global, regional, and national burden of neurological disorders during 1990–2015: a systematic analysis for the global burden of disease study 2015. Lancet Neurol. 2017;16:877–97.CrossRefGoogle Scholar
  3. 3.
    El-Chammas K, Keyes J, Thompson N, Vijayakuman J, Becher D, Jackson J. A comparative effectiveness meta-analysis of drugs for the prophylaxis of pediatric migraine headache. JAMA Pediatr. 2013;167(3):250–8.CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Shamliyan T, Kane R, Ramakrishnan R, Taylor F. Migraine in children: preventive pharmacologic treatments. Rockv Agency Healthc Res Qual. 2013;28(108):1225–37.Google Scholar
  5. 5.
    Lai LL, Koh L, Ho JA-C, Ting A, Obi A. Off-label prescribing for children with migraines in US ambulatory care settings. J Manag Care Spec Pharm. 2017;23(3):382–7.CrossRefPubMedGoogle Scholar
  6. 6.
    •• Powers SW, Coffey CS, Chamberlin LA, Ecklund DJ, Klingner EA, Yankey JW, et al. Trial of amitriptyline, topiramate, and placebo for pediatric migraine. N Engl J Med. 2017;376(2):115–24. The CHAMP study is the highest quality pediatric migraine prevention trial to date. CrossRefPubMedGoogle Scholar
  7. 7.
    Hershey AD, Powers SW, Coffey CS, Eklund DD, Chamberlin LA, Korbee LL. Childhood and adolescent migraine prevention (CHAMP) study: a double-blinded, placebo-controlled, comparative effectiveness study of amitriptyline, topiramate, and placebo in the prevention of childhood and adolescent migraine. Headache. 2013;53(5):799–816.CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Evers S, Marziniak M, Frese A, Gralow I. Placebo efficacy in childhood and adolescence migraine: an analysis of double-blind and placebo-controlled studies. Cephalalgia. 2009;29(4):436–44.CrossRefPubMedGoogle Scholar
  9. 9.
    Kalra EK. Nutraceutical-definition and introduction. AAPS PharmSciTech. 2003;5(3):E25.Google Scholar
  10. 10.
    Dalla Libera D, Colombo B, Pavan G, Comi G. Complementary and alternative medicine (CAM) use in an Italian cohort of pediatric headache patients: the tip of the iceberg. Neurol Sci. 2014;35(S1):145–8.CrossRefPubMedGoogle Scholar
  11. 11.
    Bethell C, Kemper KJ, Gombojav N, Koch TK. Complementary and conventional medicine use among youth with recurrent headaches. Pediatrics. 2013;132(5):e1173–83.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    • Groenewald CB, Beals-Erickson SE, Ralston-Wilson J, Rabbitts JA, Palermo TM. Complementary and alternative medicine use by children with pain in the United States. Acad Ped. 2017;17(7):785–93. This study highlights the prevalence of complementary and alternative medicine use amongst children and adholescents with headache and other pain conditions. CrossRefGoogle Scholar
  13. 13.
    Kenney D, Jenkins S, Youssef P, Kotagal S. Patient use of complementary and alternative medicines in an outpatient pediatric neurology clinic. Pediatr Neurol. 2016;58:48–52.e7.CrossRefPubMedGoogle Scholar
  14. 14.
    Di Somma C, Scarano E, Barrea L, Zhukouskaya VV, Savastano S, Mele C, et al. Vitamin D and neurological diseases: an endocrine view. Int J Mol Sci. 2017;18(11):1–26.CrossRefGoogle Scholar
  15. 15.
    Potrykus A, Pilarska F. The role of vitamin D supply and its impact on headaches in children and teenagers. Eur J Paediatr Neurol. 2013;17:S81.CrossRefGoogle Scholar
  16. 16.
    Cayir A, Turan MI, Tan H. Effect of vitamin D therapy in addition to amitriptyline on migraine attacks in pediatric patients. Braz J Med Biol Res. 2014;47(4):349–54.CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Vogiatzi MG, Jacobson-Dickman E, DeBoer MD. Vitamin D supplementation and risk of toxicity in pediatrics: a review of current literature. J Clin Endocrinol Metab. 2014;99(4):1132–41.CrossRefPubMedGoogle Scholar
  18. 18.
    Reyngoudt H, Paemeleire K, Descamps B, De Deene Y, Achten E. 31P-MRS demonstrates a reduction in high-energy phosphates in the occipital lobe of migraine without aura patients. Cephalalgia. 2011;31(12):1243–53.CrossRefPubMedGoogle Scholar
  19. 19.
    Lodi R, Lotti S, Cortelli P, Pierangeli G, Cevoli S, Clementi V, et al. Deficient energy metabolism is associated with low free magnesium in the brains of patients with migraine and cluster headache. Brain Res Bull. 2001;54(4):437–41.CrossRefPubMedGoogle Scholar
  20. 20.
    Okada H, Araga S, Takeshima T, Nakashima K. Plasma lactic acid and pyruvic acid levels in migraine and tension-type headache. Headache. 1998;38:39–42.CrossRefPubMedGoogle Scholar
  21. 21.
    Lodi R, Kem GJ, Mon P, Pierangeli G, Cor P, Iot S. Quantitative analysis of skeletal muscle bioenergetics and proton efflux in migraine and cluster headache. J Neurol Sci. 1997;146(1):73–80.CrossRefPubMedGoogle Scholar
  22. 22.
    Lodi R, Motagna P, Soriani S, Iotti S, Arnaldi C, Cortelli P, et al. Deficit of brain and skeletal muscle bioenergetics and low brain magnesium in juvenile migraine: an in vivo 31 P magnetic resonance spectroscopy interictal study. Pediatr Res. 1997;42:866–71.CrossRefPubMedGoogle Scholar
  23. 23.
    Sangiorgi S, Mochi M, Riva R, Cortelli P, Monari L, Pierangeli G, et al. Abnormal platelet mitochondrial function in patients affected by migraine with and without aura. Cephalalgia. 1994;14(1):21–3.CrossRefPubMedGoogle Scholar
  24. 24.
    Barbiroli B, Montagna P, Cortelli P, Funicello R, Iotti S, Monari L, et al. Abnormal brain and muscle energy metabolism shown by 31P magnetic resonance spectroscopy in patients affected by migraine with aura. Neurology. 1992;42(6):1209–14.CrossRefPubMedGoogle Scholar
  25. 25.
    Montagna P, Sacquegna T, Martinelli P, Cortelli P, Bresolin N, Moggio M, et al. Mitochondrial abnormalities in migraine. Preliminary findings. Headache. 1988;28(7):477–80.CrossRefPubMedGoogle Scholar
  26. 26.
    Younis S, Hougaard A, Vestergaard MB, Larsson HBW, Ashina M. Migraine and magnetic resonance spectroscopy: a systematic review. Curr Opin Neurol. 2017;30(3):246–62.CrossRefPubMedGoogle Scholar
  27. 27.
    Taylor FR. Nutraceuticals and headache: the biological basis. Headache. 2011;51(3):484–501.CrossRefPubMedGoogle Scholar
  28. 28.
    Markley H. Prophylactic treatment of headaches in adolescents with riboflavin. Cephalalgia. 2009;29(S1):100.Google Scholar
  29. 29.
    Condó M, Posar A, Arbizzani A, Parmeggiani A. Riboflavin prophylaxis in pediatric and adolescent migraine. J Headache Pain. 2009;10(5):361–5.CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    MacLennan SC, Wade FM, Forrest KML, Ratanayake PD, Fagan E, Antony J. High-dose riboflavin for migraine prophylaxis in children: a double-blind, randomized, placebo-controlled trial. J Child Neurol. 2008;23(11):1300–4.CrossRefPubMedGoogle Scholar
  31. 31.
    Bruijn J, Duivenvoorden H, Passchier J, Locher H, Dijkstra N, Arts W-F. Medium-dose riboflavin as a prophylactic agent in children with migraine: a preliminary placebo-controlled, randomised, double-blind, cross-over trial. Cephalalgia. 2010;30(12):1426–34.CrossRefPubMedGoogle Scholar
  32. 32.
    • Namazi N, Heshmati J, Tarighat-Esfanjani A. Supplementation with riboflavin (vitamin B2) for migraine prophylaxis in adults and children: a review. Int J Vitam Nutr Res. 2015;85(1–2):79–87. This systematic review addresses the conclusions that can be drawn from the available data on riboflavin for migraine treatment. CrossRefPubMedGoogle Scholar
  33. 33.
    • Thompson DF, Saluja HS. Prophylaxis of migraine headaches with riboflavin: a systematic review. J Clin Pharm Ther. 2017;42(4):394–403. This systematic review addresses the conclusions that can be drawn from the available data on riboflavin for migraine treatment. CrossRefPubMedGoogle Scholar
  34. 34.
    Dahri M, Tarighat-Esfanjani A, Asghari-Jafarabadi M, Hashemilar M. Oral coenzyme Q10 supplementation in patients with migraine: effects on clinical features and inflammatory markers. Nutr Neurosci. 2018 1–9.Google Scholar
  35. 35.
    •• Goadsby PJ, Reuter U, Hallström Y, Broessner G, Bonner JH, Zhang F, et al. A controlled trial of erenumab for episodic migraine. N Engl J Med. 2017;377(22):2123–32. This is one of the two initial published randomized controlled trials assessing the efficacy and safety of CGRP receptor antagonists for migraine prevention in adults. CrossRefPubMedGoogle Scholar
  36. 36.
    •• Silberstein SD, Dodick DW, Bigal ME, Yeung PP, Goadsby PJ, Blankenbiller T, et al. Fremanezumab for the preventive treatment of chronic migraine. N Engl J Med. 2017;377(22):2113–22. This is one of the two initial published randomized controlled trials assessing the efficacy and safety of CGRP receptor antagonists for migraine prevention in adults. CrossRefPubMedGoogle Scholar
  37. 37.
    Wrobel Goldberg S, Silberstein SD. Targeting CGRP: a new era for migraine treatment. CNS Drugs. 2015;29(6):443–52.CrossRefPubMedGoogle Scholar
  38. 38.
    Hershey AD, Powers SW, A-LB V, Lecates SL, Ellinor PL, Segers A, et al. Coenzyme Q10 deficiency and response to supplementation in pediatric and adolescent migraine. Headache. 2007;47(1):73–80.CrossRefPubMedGoogle Scholar
  39. 39.
    Slater SK, Nelson TD, Kabbouche MA, LeCates SL, Horn P, Segers A, et al. A randomized, double-blinded, placebo-controlled, crossover, add-on study of CoEnzyme Q10 in the prevention of pediatric and adolescent migraine. Cephalalgia. 2011;31(8):897–905.CrossRefPubMedGoogle Scholar
  40. 40.
    Gallai V, Sarchielli P, Coata G, Firenza C, Morucci P, Abbritti G. Serum and salivary magnesium levels in migraine: results in a group of juvenile patients. Headache. 1992;32(2):132–5.CrossRefPubMedGoogle Scholar
  41. 41.
    Soriani S, Arnaldi C, DeCarlo L, Arcudi D, Mazzotta D, Battistella PA, et al. Serum and red blood cell magnesium levels in juvenile migraine patients. Headache. 1995;35(1):14–6.CrossRefPubMedGoogle Scholar
  42. 42.
    Aloisi P, Marrelli A, Porto C, Tozzi E, Cerone G. Visual evoked potentials and serum magnesium levels in juvenile migraine patients. Headache. 1997;37(6):383–5.CrossRefPubMedGoogle Scholar
  43. 43.
    Martinez Cardenas V, Rodriguez M, Burke M, Vasconcellos E. Efficacy and safety of intravenous magnesium sulfate treatment in pediatric patients with headaches. Headache. 2012;52(5):896.Google Scholar
  44. 44.
    Gertsch EA, Loharuka S, Wolter-Warmerdam KG, Tong S, Kedia S. Intravenous magnesium as abortive treatment for headaches in children. Ann Neurol. 2011;Conference(var.pagings):S167.Google Scholar
  45. 45.
    • Patniyot IR, Gelfand AA. Acute treatment therapies for pediatric migraine: a qualitative systematic review. Headache. 2016;56(1):49–70. This is a recent systematic review on the efficacy of acute interventions for pediatric migraine. CrossRefPubMedGoogle Scholar
  46. 46.
    Castelli S, Meossi C, Domenici R, Fontana F, Stefani G. Magnesium in the prophylaxis of primary headache and other periodic disorders in children. Pediatr Med Chir. 1993;15(5):481–8.PubMedGoogle Scholar
  47. 47.
    Gallelli L, Avenoso T, Falcone D, Palleria C, Peltrone F, Esposito M, et al. Effects of acetaminophen and ibuprofen in children with migraine receiving preventive treatment with magnesium. Headache. 2014;54(2):313–24.CrossRefPubMedGoogle Scholar
  48. 48.
    Wang F, Van Den Eeden SK, Ackerson LM, Salk SE, Reince RH, Elin RJ. Oral magnesium oxide prophylaxis of frequent migrainous headache in children: a randomized, double-blind, placebo-controlled trial. Headache. 2003;43(6):601–10.CrossRefPubMedGoogle Scholar
  49. 49.
    Sadler C, Vanderkagt L, Vohra S. Complementary, holistic and integrative medicine: butterbur. Pediatr Rev. 2007;28:235–8.CrossRefPubMedGoogle Scholar
  50. 50.
    Holland S, Silberstein SD, Freitag F, Dodick DW, Argoff C, Ashman E. Evidence-based guideline update: NSAIDs and other complementary treatments for episodic migraine prevention in adults: report of the Quality Standards Subcommittee of the American Academy of Neurology and the American Headache Society. Neurology. 2012;78(17):1346–53.CrossRefPubMedPubMedCentralGoogle Scholar
  51. 51.
    Pringsheim T, Davenport W, Mackie G, Worthington I, Aube M, Christie S, et al. Canadian headache society guideline for migraine prophylaxis. Can J Neurol Sci. 2012;39(S2):1–62.Google Scholar
  52. 52.
    Orr SL. Diet and nutraceutical interventions for headache management: a review of the evidence. Cephalalgia. 2016;36(12):1112–33.CrossRefPubMedGoogle Scholar
  53. 53.
    • Rajapakse T, Pringsheim T. Nutraceuticals in migraine: a summary of existing guidelines for use. Headache. 2016;56(4):808–16. This is a summary statement that describes the various guidelines for the use of nutraceuticals in migraine. CrossRefPubMedGoogle Scholar
  54. 54.
    Mauskop A. Evidence-based guideline update: NSAIDs and other complementary treatments for episodic migraine prevention in adults: report of the Quality Standards Subcommittee of the American Academy of Neurology and the American Headache Society. Neurology. 2013;80(9):868–9.CrossRefPubMedGoogle Scholar
  55. 55.
    Fiebich B, Grozdeva M, Hess S, Hüll M, Danesch U, Bodensieck A, et al. Petasites hybridus extracts in vitro inhibit COX-2 and PGE2 release by direct interaction with the enzyme and by preventing p42/44 MAP kinase activation in rat primary microglial cells. Planta Med. 2005;71(1):12–9.CrossRefPubMedGoogle Scholar
  56. 56.
    Wang G, Shum A, Lin Y, Liao J, Wu X, Ren J, et al. Calcium channel blockade in vascular smooth muscle cells: major hypotensive mechanism of S-petasin, a hypotensive sesquiterpene from Petasites formosanus. J Pharmacol Exp Ther. 2001;297(1):240–6.PubMedGoogle Scholar
  57. 57.
    Pothmann R, Danesch U. Migraine prevention in children and adolescents: results of an open study with a special butterbur root extract. Headache. 2005;45(3):196–203.Google Scholar
  58. 58.
    Oelkers-Ax R, Leins A, Parzer P, Hillecke T, Bolay HV, Fischer J, et al. Butterbur root extract and music therapy in the prevention of childhood migraine: an explorative study. Eur J Pain. 2008;12(3):301–13.CrossRefPubMedGoogle Scholar
  59. 59.
    Avula B, Wang Y-H, Wang M, Smillie TJ, Khan IA. Simultaneous determination of sesquiterpenes and pyrrolizidine alkaloids from the rhizomes of Petasites hybridus (L.) G.M. et Sch. and dietary supplements using UPLC-UV and HPLC-TOF-MS methods. J Pharm Biomed Anal. 2012;70:53–63.CrossRefPubMedGoogle Scholar
  60. 60.
    Danesch U, Rittinghausen R. Safety of a patented special butterbur root extract for migraine prevention. Headache. 2003;43(1):76–8.CrossRefPubMedGoogle Scholar
  61. 61.
    Prieto JM. Update on the efficacy and safety of Petadolex®, a butterbur extract for migraine prophylaxis. Bot Targets Ther. 2014;4:1–9.Google Scholar
  62. 62.
    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.CrossRefPubMedPubMedCentralGoogle Scholar
  63. 63.
    Simopoulos A. Omega-3 fatty acids in inflammation and autoimmune diseases. J Am Coll Nutr. 2002;21(6):495–505.CrossRefPubMedGoogle Scholar
  64. 64.
    Sadeghi O, Maghsoudi Z, Khorvash F, Ghiasvand R, Askari G. The relationship between different fatty acids intake and frequency of migraine attacks. Iran J Nurs Midwifery Res. 2015;20(3):334–9.PubMedPubMedCentralGoogle Scholar
  65. 65.
    Fayyazi A, Khajeh A, Ghazavi A, Sangestani M. Omega 3 in childhood migraines: a double blind randomized clinical trial. Iran J Child Neurol. 2016;10(1):14–21.Google Scholar
  66. 66.
    •• Le K, Yu D, Wang J, Ali AI, Guo Y. Is topiramate effective for migraine prevention in patients less than 18 years of age? A meta-analysis of randomized controlled trials. J Headache Pain. 2017;18(1):69. This is a systematic review and meta-analysis that pooled all of the evidence for topiramate in pediatric migraine prevention. CrossRefPubMedPubMedCentralGoogle Scholar
  67. 67.
    Job K, Kiang T, Constance J, Sherwin C, Enioutina E. Herbal medicines: challenges in the modern world. Part 4. Canada and United States. Expert Rev Clin Pharmacol. 2016;9(12):1597–609.CrossRefPubMedGoogle Scholar
  68. 68.
    Snyder FJ, Dundas ML, Kirkpatrick C, Neill KS. Use and safety perceptions regarding herbal supplements: a study of older persons in southeast Idaho. J Nutr Elder. 2009;28(1):81–95.CrossRefPubMedGoogle Scholar

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© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Division of NeurologyCincinnati Children’s Hospital Medical CenterCincinnatiUSA

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