Improvement of migraine symptoms with a proprietary supplement containing riboflavin, magnesium and Q10: a randomized, placebo-controlled, double-blind, multicenter trial

Charly Gaul, Hans-Christoph Diener, Ulrich Danesch, Migravent® Study Group, Andreas Peikert, Holger Kaube, Susanne Urban, Walter Albrecht, Rüdiger Schellenberg, Manuela Thinesse-Mallwitz, Andreas Straube, Stefan Ries, Karl-Otto Sigel, Martin L J Wimmer, Charly Gaul, Hans-Christoph Diener, Ulrich Danesch, Migravent® Study Group, Andreas Peikert, Holger Kaube, Susanne Urban, Walter Albrecht, Rüdiger Schellenberg, Manuela Thinesse-Mallwitz, Andreas Straube, Stefan Ries, Karl-Otto Sigel, Martin L J Wimmer

Abstract

Background: Non-medical, non-pharmacological and pharmacological treatments are recommended for the prevention of migraine. The purpose of this randomized double-blind placebo controlled, multicenter trial was to evaluate the efficacy of a proprietary nutritional supplement containing a fixed combination of magnesium, riboflavin and Q10 as prophylactic treatment for migraine.

Methods: 130 adult migraineurs (age 18 - 65 years) with ≥ three migraine attacks per month were randomized into two treatment groups: dietary supplementation or placebo in a double-blind fashion. The treatment period was 3 months following a 4 week baseline period without prophylactic treatment. Patients were assessed before randomization and at the end of the 3-month-treatment-phase for days with migraine, migraine pain, burden of disease (HIT-6) and subjective evaluation of efficacy.

Results: Migraine days per month declined from 6.2 days during the baseline period to 4.4 days at the end of the treatment with the supplement and from 6.2.days to 5.2 days in the placebo group (p = 0.23 compared to placebo). The intensity of migraine pain was significantly reduced in the supplement group compared to placebo (p = 0.03). The sum score of the HIT-6 questionnaire was reduced by 4.8 points from 61.9 to 57.1 compared to 2 points in the placebo-group (p = 0.01). The evaluation of efficacy by the patient was better in the supplementation group compared to placebo (p = 0.01).

Conclusions: Treatment with a proprietary supplement containing magnesium, riboflavin and Q10 (Migravent® in Germany, Dolovent® in USA) had an impact on migraine frequency which showed a trend towards statistical significance. Migraine symptoms and burden of disease, however, were statistically significantly reduced compared to placebo in patients with migraine attacks.

Figures

Figure 1
Figure 1
Consort diagram showing recruitment and flow of participants through trial.

References

    1. Goadsby PJ, Lipton RB, Ferrari MD. Migraine - current understanding and treatment. N Engl J Med. 2002;346:257–270. doi: 10.1056/NEJMra010917.
    1. Silberstein SD, Holland S, Freitag F, Dodick DW, Argoff C, Ashman E. Evidence-based guideline update: Pharmacologic treatment 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;78:1337–1345. doi: 10.1212/WNL.0b013e3182535d20.
    1. Diener HC, Evers S, Förderreuther S, Freilinger T, Fritsche G, Gaul C, Göbel H, Haag G, Heinze A, Holle D, Jürgens T, Katsarava Z, Kropp P, Limmroth V, Malzacher R, Marziniak M, May A, Meier U, Obermann M, Ruschewya R, Straube A, Sandor P, Gantenbein A, Lampl C, Brössner G. Therapie der Migräne. In: Diener HC, Weimar C, Berlit P, Deuschl G, Elger C, Gold R, Hacke W, Hufschmidt A, Mattle H, Meier U, Oertel WH, Reichmann H, Schmutzhard E, Wallesch C-W, Weller M, editors. Leitlinien für Diagnostik und Therapie in der Neurologie, 5th edn. Stuttgart: Thieme; 2012. pp. 688–717.
    1. Tfelt-Hansen PC. Evidence-based guideline update: pharmacologic treatment 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;26:869–870. doi: 10.1212/01.wnl.0000427909.23467.39.
    1. Diener HC, Danesch U. Wirksamkeit chemischer, pflanzlicher und diätetischer Migräneprophylaktika. MMW Fortschr Med. 2009;151:42–45.
    1. Gaul C, Eismann R, Schmidt T, May A, Leinisch E, Wieser T, Evers S, Henkel K, Franz G, Zierz S. Use of complementary and alternative medicine in patients suffering from primary headache disorders. Cephalalgia. 2009;29:1069–1078. doi: 10.1111/j.1468-2982.2009.01841.x.
    1. Hershey AD, Powers SW, Benntti AL, deGrauw TJ. Chronic daily headaches (CDH) in children: characteristics and treatment response. Headache. 1999;39:358.
    1. Hershey AD, Powers SW, Vockell AL, Lecates SL, Ellinor PL, Segers A, Burdine D, Manning P, Kabbouche MA. Coenzyme Q10 deficiency and response to supplementation in pediatric and adolescent migraine. Headache. 2007;47:73–80. doi: 10.1111/j.1526-4610.2007.00652.x.
    1. Mauskop A, Altura BM. Role of magnesium in the pathogenesis and treatment of migraines. Clin Neurosci. 1998;5:24–27.
    1. Sparaco M, Feleppa M, Lipton RB, Rapoport AM, Bigal ME. Mitochondrial dysfunction and migraine: evidence and hypotheses. Cephalalgia. 2006;26:361–372. doi: 10.1111/j.1468-2982.2005.01059.x.
    1. Lodi R, Iotti S, Cortelli P, Pierangeli G, Cevoli S, Clementi V, Soriani S, Montagna P, Barbiroli B. Deficient energy metabolism is associated with low free magnesium in the brains of patients with migraine and cluster headache. Brain Res Bull. 2001;54:437–441. doi: 10.1016/S0361-9230(01)00440-3.
    1. Bianchi A, Salomone S, Caraci F, Pizza V, Bernardini R, D'Amato CC. Role of magnesium, coenzyme Q10, riboflavin, and vitamin B12 in migraine prophylaxis. Vitam Horm. 2004;69:297–312. doi: 10.1016/S0083-6729(04)69011-X.
    1. Schellenberg R. Mit bilanzierter Diät erfolgreich gegen die Migräne? Schmerztherapie. 2011;3:17.
    1. Headache Classification Subcommittee The international classification of headache disorders. 2nd edition. Cephalalgia. 2004;24(Suppl 1):1–160.
    1. Kosinski M, Bayliss MS, Bjorner JB, Ware JE, Jr, Garber WH, Batenhorst A, Cady R, Dahlöf CG, Dowson A, Tepper S. A six-item short-form survey for measuring headache impact: the HIT-6. Qual Life Res. 2003;12:963–974. doi: 10.1023/A:1026119331193.
    1. Diener HC, Hartung E, Chrubasik J, Evers S, Schoenen J, Eikermann A, Latta G, Hauke W, Group S. A comparative study of oral acetylsalicyclic acid and metoprolol for the prophylactic treatment of migraine. A randomized, controlled, double-blind, parallel group phase III study. Cephalalgia. 2001;21:120–128. doi: 10.1046/j.1468-2982.2001.00168.x.
    1. Linde K, Rossnagel K (2004) Propranolol for migraine prophylaxis. Cochrane Database Syst Rev, Issue 2. Art. No.: CD003225. doi:10.1002/14651858.CD003225.pub2
    1. Diener HC, Matias-Guiu J, Hartung E, Pfaffenrath V, Ludin HP, Nappi G, De Beukelaar F. Efficacy and tolerability in migraine prophylaxis of flunarizine in reduced doses: a comparison with propranolol 160 mg daily. Cephalalgia. 2002;22:209–221. doi: 10.1046/j.1468-2982.2002.t01-1-00309.x.
    1. Diener HC, Tfelt-Hansen P, Dahlöf C, Láinez MJ, Sandrini G, Wang SJ, Neto W, Vijapurkar U, Doyle A, Jacobs D, MIGR-003 Study Group Topiramate in migraine prophylaxis–results from a placebo-controlled trial with propranolol as an active control. J Neurol. 2004;251:943–950. doi: 10.1007/s00415-004-0464-6.
    1. Linde M, Mulleners WM, Chronicle EP, McCrory DC (2013) Valproate (valproic acid or sodium valproate or a combination of the two) for the prophylaxis of episodic migraine in adults. Cochrane Database Syst Rev Issue 6. Art. No.: CD010611. doi:10.1002/14651858.CD010611
    1. Silberstein SD, Neto W, Schmitt J, Jacobs D, MIGR-001 Study Group Topiramate in migraine prevention: results of a large controlled trial. Arch Neurol. 2004;61:490–495. doi: 10.1001/archneur.61.4.490.
    1. Linde M, Mulleners WM, Chronicle EP, McCrory DC (2013) Topiramate for the prophylaxis of episodic migraine in adults. Cochrane Database Syst Rev Issue 6. Art. No.: CD010610. doi:10.1002/14651858.CD010610
    1. Peikert A, Wilimzig C, Kohne-Volland R. Prophylaxis of migraine with oral magnesium: results from a prospective, multi-center, placebo-controlled and double-blind randomized study. Cephalalgia. 1996;16:257–263. doi: 10.1046/j.1468-2982.1996.1604257.x.
    1. Taubert K. Magnesium in migraine. Results of a multicenter pilot study. Fortschr Med. 1994;112:328–330.
    1. Köseoglu E, Talaslioglu A, Gönül AS, Kula M. The effects of magnesium prophylaxis in migraine without aura. Magnes Res. 2008;21:101–108.
    1. 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;15:481–488.
    1. Facchinetti F, Sances G, Borella P, Genazzani AR, Nappi G. Magnesium prophylaxis of menstrual migraine: effects on intracellular magnesium. Headache. 1991;31:298–301. doi: 10.1111/j.1526-4610.1991.hed3105298.x.
    1. Pfaffenrath V, Wessely P, Meyer C, Isler HR, Evers S, Grotemeyer KH, Taneri Z, Soyka D, Gobel H, Fischer M. Magnesium in the prophylaxis of migraine–a double-blind placebo-controlled study. Cephalalgia. 1996;16:436–440. doi: 10.1046/j.1468-2982.1996.1606436.x.
    1. 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;43:601–610. doi: 10.1046/j.1526-4610.2003.03102.x.
    1. Schoenen J, Jacquy J, Lenaerts M. Effectiveness of high-dose riboflavin in migraine prophylaxis. A randomized controlled trial Neurology. 1998;50:466–470.
    1. Maizels M, Blumenfeld A, Burchette R. A combination of riboflavin, magnesium, and feverfew for migraine prophylaxis: a randomized trial. Headache. 2004;44:885–890. doi: 10.1111/j.1526-4610.2004.04170.x.
    1. Boehnke C, Reuter U, Flach U, Schuh-Hofer S, Einhäupl KM, Arnold G. High-dose riboflavin treatment is efficacious in migraine prophylaxis: an open study in a tertiary care centre. Eur J Neurol. 2004;11:475–477. doi: 10.1111/j.1468-1331.2004.00813.x.
    1. Schoenen J, Lenaerts M, Bastings E. High-dose riboflavin as a prophylactic treatment of migraine: results of an open pilot study. Cephalalgia. 1994;14:328–329. doi: 10.1046/j.1468-2982.1994.1405328.x.
    1. Bruijn J, Duivenvoorden H, Passchier J, Locher H, Dijkstra N, Arts WF. Medium-dose riboflavin as a prophylactic agent in children with migraine: a preliminary placebo-controlled, randomised, double-blind, cross-over trial. Cephalalgia. 2010;3012:1426–1434. doi: 10.1177/0333102410365106.
    1. MacLennan SC, Wade FM, Forrest KM, 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;23:1300–1304. doi: 10.1177/0883073808318053.
    1. Rozen TD, Oshinsky ML, Gebeline CA, Bradley KC, Young WB, Shechter AL, Silberstein SD. Open label trial of coenzyme Q10 as a migraine preventive. Cephalalgia. 2002;22:137–141. doi: 10.1046/j.1468-2982.2002.00335.x.
    1. Sándor PS, Di Clemente L, Coppola G, Saenger U, Fumal A, Magis D, Seidel L, Agosti RM, Schoenen J. Efficacy of coenzyme Q10 in migraine prophylaxis: a randomized controlled trial. Neurology. 2005;64:713–715. doi: 10.1212/01.WNL.0000151975.03598.ED.
    1. Slater SK, Nelson TD, Kabbouche MA, LeCates SL, Horn P, Segers A, Manning P, Powers SW, Hershey AD. A randomized, double-blinded, placebo-controlled, crossover, add-on study of CoEnzyme Q10 in the prevention of pediatric and adolescent migraine. Cephalalgia. 2011;31:897–905. doi: 10.1177/0333102411406755.
    1. Di Lorenzo C, Pierelli F, Coppola G, Grieco GS, Rengo C, Ciccolella M, Magis D, Bolla M, Casali C, Santorelli FM, Schoenen J. Mitochondrial DNA haplogroups influence the therapeutic response to riboflavin in migraineurs. Neurology. 2009;72:1588–1594. doi: 10.1212/WNL.0b013e3181a41269.
    1. Smelt AF, Assendelft WJ, Terwee CB, Ferrari MD, Blom JW. What is a clinically relevant change on the HIT-6 questionnaire? An estimation in a primary-care population of migraine patients. Cephalalgia. 2014;34:29–36. doi: 10.1177/0333102413497599.

Source: PubMed

Sponsorer og samarbejdspartnere

Medicinske tilstande

Narkotikainterventioner

3
Abonner