Health Condition

Migraine Headache

  • Butterbur

    Butterbur extract has been shown to significantly reduce the frequency of migraine attacks.

    Dose:

    Adults: 75 mg twice a day of an extract standardized to contain at least 15% petasins; children: reduce amount according to body weight
    Butterbur
    ×
     

    Double-blind trials have demonstrated that butterbur extract can reduce the frequency of migraine attacks significantly better than placebo.1,2 One study has also shown it helps reduce the frequency of migraine headaches in children and adolescents, though there was no control group so it is not as clear just how effective butterbur extract is in this population.3 In a double-blind trial, supplementing with an extract of butterbur (Petasites hybridus) for four months was significantly more effective than a placebo at reducing the frequency of migraine attacks.4 The amount of butterbur found to be effective was 75 mg twice a day of an extract standardized to contain at least 15% petasins. A smaller amount (50 mg twice a day) was ineffective. The most common side effect was burping.

  • Feverfew

    Feverfew is the most frequently used herb for the long-term migraine prevention. Continuous use of feverfew may reduce the severity, duration, and frequency of migraine headaches.

    Dose:

    Standardized herbal extract delivering 250 mcg of parthenolide per day
    Feverfew
    ×

    The most frequently used herb for the long-term prevention of migraines is feverfew.5 Four double-blind trials have reported that continuous use of feverfew leads to a reduction in the severity, duration, and frequency of migraine headaches,6,7,8,9 although one double-blind trial found feverfew to be ineffective.10

    Studies suggest that taking standardized feverfew leaf extracts that supply a minimum of 250 mcg of parthenolide per day is most effective. Results may not be evident for at least four to six weeks. Although there has been recent debate about the relevance of parthenolide as an active constituent,11 it is best to use standardized extracts of feverfew until research proves otherwise.

    A double-blind study found that a combination of feverfew and ginger may be effective for acute treatment of migraines. In that study, 63% of patients taking the herbal preparation experienced pain relief within 2 hours, whereas only 39% taking placebo experienced relief, a statistically significant difference. The product used in this study was a proprietary preparation called LipiGesic M (PuraMed BioScience, Inc., Schofield, WI). The liquid from 1-unit dose applicator was administered sublingually, held under the tongue for 60 seconds, and then swallowed. A second dose was given 5 minutes later. If pain persisted after 1 hour, a second treatment of 2-unit doses could be given.12 

  • Magnesium

    Compared with healthy people, migraine sufferers have been found to have lower magnesium levels. Supplementing with magnesium may reduce migraine frequency and relieve symptoms.

    Dose:

    360 to 600 mg daily
    Magnesium
    ×
     

    Compared with healthy people, people with migraines have been found to have lower blood and brain levels of magnesium.13,14,15,16 Preliminary research in a group of women (mostly premenopausal) showed that supplementing with magnesium (usually 200 mg per day) reduced the frequency of migraines in 80% of those treated.17 In a double-blind trial of 81 people with migraines, 600 mg of magnesium per day was significantly more effective than placebo at reducing the frequency of migraines.18 Another double-blind trial found that taking 360 mg of magnesium per day decreased the number of days on which premenstrual migraines occurred.19 One double-blind trial found no benefit from 486 mg of magnesium per day for three months. However, that study defined improvement according to extremely strict criteria, and even some known anti-migraine drugs have failed to show benefit when tested using those criteria.20 Intravenous magnesium has been reported to produce marked and sometimes complete symptom relief during acute migraines, usually within 15 minutes or less.21

  • Vitamin B2

    Studies have shown vitamin B2 to be effective at reducing the frequency and severity of migraine headaches.

    Dose:

    400 mg daily
    Vitamin B2
    ×
     

    One group of researchers treated 49 migraine patients with large amounts of vitamin B2 (400 mg per day). Both the frequency and severity of migraines decreased by more than two-thirds.22 In a follow-up three-month, double-blind trial, the same researchers reported that 59% of patients assigned to receive vitamin B2 had at least a 50% reduction in the number of headache days, whereas only 15% of those assigned to receive a placebo experienced that degree of improvement.23 The effects of vitamin B2 were most pronounced during the final month of the trial.24 In a preliminary study, a much smaller amount of vitamin B2 (25 mg per day for three months) reduced the frequency of migraines by about one-third in chronic migraine sufferers.25

    All of the studies that found riboflavin to be effective for preventing migraine were conducted in adults. In a double-blind trial, supplementation with 200 mg per day of riboflavin did not decrease the frequency or severity of migraines in children whose average age was 11 years.26

  • 5-HTP

    Several studies have found 5-HTP to be effective at reducing the frequency, severity, and duration of migraine headaches.

    Dose:

    200 to 600 mg daily for adults, 20 mg for every 10 pounds of body weight for children
    5-HTP
    ×
     

    The cause of migraine headache is believed to be related to abnormal serotonin function in blood vessels,27 and 5-HTP (5-hydroxytryptophan, which is converted by the body into serotonin) may affect this abnormality. In one study, 40 people with recurrent migraines received either 5-HTP (200 mg per day) or methysergide (a drug used to prevent migraines) for 40 days. Both compounds reduced the frequency of migraines by about 50%.28 Larger amounts of 5-HTP (600 mg per day) were also found to be as effective as medications for reducing migraine headache attacks in adults in two double-blind trials.29,30 Migraine attacks were reduced in frequency, severity, and duration in 90% of those taking 400 mg per day of 5-HTP in a double-blind placebo-controlled trial,31 though another trial found no benefit of 5-HTP.32 In another controlled study, 400 mg of dl-5-HTP (another form of 5-HTP) led to reduced consumption of pain-killing drugs and pain scores after one to two months.33 Children who suffered from migraines and had problems sleeping responded well to a daily amount of 5-HTP equal to 20 mg for every 10 pounds of body weight in a controlled trial,34 though an earlier study showed 5-HTP had no better effect than placebo for children with migraines.35

  • Alpha-Lipoic Acid

    In a small double-blind trial, supplementing with alpha-lipoic acid significantly reduced the frequency of migraine attacks.

    Dose:

    600 mg per day
    Alpha-Lipoic Acid
    ×
     

    In a small double-blind trial, supplementation with 600 mg of alpha-lipoic acid once a day for three months significantly reduced the frequency of migraine attacks. However, this improvement was not statistically significant when compared with the change in the placebo group.36 Additional research is needed to determine whether alpha-lipoic acid is effective for preventing migraines.

  • Coenzyme Q10

    In a preliminary trial, supplementation with coenzyme Q10 for three months reduced the average number of days with migraine headaches by 60%.

    Dose:

    100 to 150 mg daily
    Coenzyme Q10
    ×
     

    Blood levels of coenzyme Q10 have been found to be low in about one-third of migraine sufferers.37 In a preliminary trial, supplementation of migraine sufferers with 150 mg per day of coenzyme Q10 for three months reduced the average number of days with migraine headaches by 60%.38 The beneficial effect of coenzyme Q10 was confirmed in a four-month double-blind study. By the fourth month of treatment, a reduction in migraine frequency of 50% or greater occurred in 47.6% of people receiving 100 mg of coenzyme Q10 three times a day, but in only 14.4% of those receiving a placebo (a statistically significant difference).39 However, another double-blind trial found that coenzyme Q10 was not more effective than a placebo in children with recurrent migraines, although children receiving coenzyme Q10 appeared to improve faster than those given the placebo.40

  • Folic Acid

    Taking folic acid may improve migraines in people with high homocysteine levels and a certain genetic characteristic.

    Dose:

    5 mg per day
    Folic Acid
    ×
    In a preliminary trial, supplementation with 5 mg of folic acid per day for six months completely eliminated recurrent migraine attacks in 10 of 16 children and reduced the number of attacks by 50 to 75% in the other six children. The children selected to be in this study had elevated homocysteine levels (which can be reduced by folic acid supplementation), as well as a certain genetic characteristic known as a polymorphism of the methylenetetrahydrofolate reductase (MTHFR) gene.41 Further research is needed to determine whether folic acid supplementation would be beneficial for migraine patients who do not have these specific characteristics.
  • Ginger

    Anecdotal evidence suggests ginger may be used for migraines and the accompanying nausea.

    Dose:

    Refer to label instructions
    Ginger
    ×
    Anecdotal evidence suggests ginger may be used for migraines and the accompanying nausea. In a double-blind study, a sublingual preparation that contained both feverfew and ginger LipiGesic M (PuraMed BioScience, Inc., Schofield, WI) appeared to be beneficial for acute migraines.42 In another double-blind study, a single administration of 250 mg of ginger powder was as effective as the migraine drug, sumatriptan, in the treatment of acute migraines.43
  • Melatonin

    Pineal gland function and melatonin secretion may be disturbed in people with migraine headaches. Taking melatonin may correct this problem and reduce symptoms.

    Dose:

    Refer to label instructions
    Melatonin
    ×

    The function of the pineal gland and its cyclic secretion of melatonin may be disturbed in people with migraine headaches.44 Preliminary evidence suggests that 5 mg per day of melatonin, taken 30 minutes before bedtime, may reduce symptoms of migraine headache.45 A double-blind trial found that taking 3 mg of melatonin at bedtime each day for 12 weeks significantly decreased the frequency of migraines in people suffering from recurrent migraines.46 Another double-blind trial found that taking 2 mg of melatonin 1 hour before bedtime each day for 8 weeks was not more effective than a placebo for decreasing migraine frequency.47

    In the positive study described above, the reduction in migraine frequency was assessed only in the third month of treatment. It is possible that it takes a few months for melatonin to start working. The negative results in the other study cited above could have been due either to the shorter duration of treatment or to the lower amount of melatonin given.

  • Vitamin B12

    In a preliminary trial, vitamin B12 reduced the frequency of migraine attacks by at least 50% in 10 of 19 people with recurrent migraines.

    Dose:

    1 mg daily
    Vitamin B12
    ×
     

    In a preliminary trial, administration of 1 mg of vitamin B12 per day (by the intranasal route) for 3 months reduced the frequency of migraine attacks by at least 50% in 10 of 19 people with recurrent migraines.48 A placebo-controlled study is needed to determine how much of this improvement was due to a placebo effect.

  • Calcium

    Taking large amounts of the combination of calcium and vitamin D has been reported to produce a marked reduction in the incidence of migraines in several women.

    Dose:

    Refer to label instructions
    Calcium
    ×

    Caution: Calcium supplements should be avoided by prostate cancer patients.

    Taking large amounts of the combination of calcium (1,000 to 2,000 mg per day) and vitamin D has been reported to produce a marked reduction in the incidence of migraines in several women.49,50 However, the amount of vitamin D given to these women (usually 50,000 IU once a week), can cause adverse reactions, particularly when used in combination with calcium. This amount of vitamin D should be used only under medical supervision. Doctors often recommend that people take 800 to 1,200 mg of calcium and 400 IU of vitamin D per day. However, it is not known whether theses amounts would have an effect on migraines.

  • Chili Peppers

    Capsaicin, the active constituent of cayenne, may be applied inside the nose as a treatment for acute migraine under a doctor’s supervision.

    Dose:

    Refer to label instructions
    Chili Peppers
    ×
     

    There is preliminary evidence that capsaicin, the active constituent of cayenne, can be applied inside the nose as a treatment for acute migraine.51 However, as intranasal application of capsaicin produces a burning sensation, it should be used only under the supervision of a doctor familiar with its use.

  • Fish Oil

    Fish oil containing EPA and DHA has been reported to reduce migraine headache symptoms. Fish oil may help because of its effects in modifying hormone-like substances called prostaglandins.

    Dose:

    Refer to label instructions
    Fish Oil
    ×
     

    Fish oil containing EPA and DHA has been reported to reduce the symptoms of migraine headache in a double-blind trial using 1 gram of fish oil per 10 pounds of body weight.52,53 Fish oil may help because of its effects in modifying prostaglandins (hormone-like substances made by the body).

  • Ginkgo

    Ginkgo extract may also help because it inhibits the action of a substance known as platelet-activating factor, which may contribute to migraines.

    Dose:

    Refer to label instructions
    Ginkgo
    ×
     

    Ginkgo biloba extract may also help because it inhibits the action of a substance known as platelet-activating factor,54 which may contribute to migraines. No clinical trials have examined its effectiveness in treating migraines, however.

  • L-Tryptophan

    Preliminary research has found abnormally low levels of serotonin in the brains of people suffering a migraine attack, which was reversed with L-tryptophan supplements.

    Dose:

    Refer to label instructions
    L-Tryptophan
    ×

    Interest in the effects of serotonin on the mechanisms of migraine has led to therapeutic trials using serotonin precursors such as L-tryptophan and 5-hydroxytryptophan (5-HTP).55 Preliminary research has found abnormally low levels of serotonin in the brains of people suffering a migraine attack, which was reversed with L-tryptophan supplements.56 A small double-blind trial found that four of eight people had fewer and less intense migraines while receiving L-tryptophan (500 mg every six hours).57 Larger double-blind trials are needed to better evaluate L-tryptophan as a migraine prevention supplement.

    In one study, 40 people with recurrent migraines received either 5-HTP (200 mg per day) or methysergide (a drug used to prevent migraines) for 40 days. Both compounds reduced the frequency of migraines by about 50%.58 Larger amounts of 5-HTP (600 mg per day) were also found to be as effective as medications for reducing migraine headache attacks in adults in two double-blind trials.59,60 Migraine attacks were reduced in frequency, severity, and duration in 90% of those taking 400 mg per day of 5-HTP in a double-blind placebo-controlled trial,61 though another trial found no benefit of 5-HTP.62 In another controlled study, 400 mg per day of DL-5-HTP (another form of 5-HTP, equivalent to 200 mg per day of 5-HTP per day led to reduced consumption of pain-killing drugs and pain scores after one to two months.63 Children who suffered from migraines and had problems sleeping had an improvement in both migraines and sleep disorders after taking 5-HTP in the amount of 20 mg for every 10 pounds of body weight in a controlled trial,64 though an earlier study showed 5-HTP had no better effect than placebo for children with migraines.65

  • SAMe

    Preliminary research suggests that supplementing with SAMe may reduce symptoms for some migraine sufferers.

    Dose:

    Refer to label instructions
    SAMe
    ×
     

    Preliminary research also suggests that oral supplements of SAMe (S-adenosyl-L-methionine) may reduce symptoms for some migraine sufferers.66

  • Vitamin D

    Taking large amounts of the combination of calcium and vitamin D has been reported to produce a marked reduction in the incidence of migraines in several women.

    Dose:

    Refer to label instructions
    Vitamin D
    ×
     

    Taking large amounts of the combination of calcium (1,000 to 2,000 mg per day) and vitamin D has been reported to produce a marked reduction in the incidence of migraines in several women.67,68 However, the amount of vitamin D given to these women (usually 50,000 IU once a week), can cause adverse reactions, particularly when used in combination with calcium. This amount of vitamin D should be used only under medical supervision. Doctors often recommend that people take 800 to 1,200 mg of calcium and 400 IU of vitamin D per day. However, it is not known whether theses amounts would have an effect on migraines.

What Are Star Ratings
×
Reliable and relatively consistent scientific data showing a substantial health benefit.
Contradictory, insufficient, or preliminary studies suggesting a health benefit or minimal health benefit.
For an herb, supported by traditional use but minimal or no scientific evidence. For a supplement, little scientific support.

Holistic Options

Many reports have shown acupuncture to be useful in the treatment of migraines. In a preliminary trial, 18 of 26 people suffering from migraine headaches demonstrated an improvement in symptoms following therapy with acupuncture; they also had a 50% reduction in the use of pain medication.69 Previous preliminary trials have demonstrated similar results,70,71,72 which have also been confirmed in placebo-controlled trials.73,74 Improvement has been maintained at one73 and three69 years of follow-up. In preliminary research, patients suffering from chronic headaches of various types (including migraine, cluster, or tension headaches) have also experienced an improvement in symptoms following acupuncture treatment.77 In a trial comparing acupuncture to traditional drug therapy, a significantly greater cure rate was achieved in the acupuncture group relative to the drug treatment group (75% vs. 34%).78

Dry needling is a form of acupuncture that does not utilize traditional Chinese medicine diagnosis or traditional acupuncture points for treatment. Instead, acupuncture needles are inserted into painful muscle areas (trigger points). A study of 85 patients comparing dry needle acupuncture to conventional drug therapy found a similar reduction in frequency and duration of migraine attacks in both treatment groups.79

Percutaneous Electrical Nerve Stimulation (PENS) is an electrical nerve stimulation technique that has become increasingly popular in the complementary and alternative management of pain syndromes. PENS involves insertion of needle probes, similar to acupuncture, at specific therapeutic points and then applying low levels of electrical current. In one study, PENS was significantly more effective than needles alone at relieving pain in migraine headaches (tension headaches and post-traumatic headaches were also improved).80

Practitioners of manipulation report success in treating migraine with manipulation.81 Migraine sufferers are reported to often have neck pain, tenderness of the spinal joints of the neck,82 and limited ability to move the neck,83 all of which suggest the presence of neck problems that could respond to manipulation. Two preliminary trials reported significant benefit to 75–80% of migraine patients treated with manipulation,84,85 while a third preliminary trial reported reductions in headache frequency and duration, nausea, and sensitivity to light one year after the completion of a two-month course of manipulation.86 A controlled trial compared three types of manipulation and found all three provided significant improvement in headache frequency, severity, and duration.87,88 Another controlled trial compared two months of manipulation to sham (fake) manipulation and to placebo treatment with a non-functioning electrical unit. People in the manipulation group had significantly more improvement of headache frequency and duration, and of ability to function in daily life; they also used less medication.89 The largest controlled trial to date compared eight weeks of manipulation, drug therapy, or both treatments in combination. Manipulation was as effective as the medication in reducing an overall score of migraine suffering, but had fewer reported side effects.90

References

1. Diener HC, Rahlfs VW. Danesch U. The first placebo-controlled trial of a special butterbur extract for the prevention of migraine: reanalysis of efficacy criteria. Eur Neurol 2004;51:89–97.

2. Grossmann M, Schmidramsl H. An extract of Petasites hybridus is effective in the prophylaxis of migraine. Int J Clin Pharmacol Ther2000;38:430-5.

3. Pothmann R, Danesch U. Migraine prevention in children and adolescents: results of an open study with a special butterbur root extract. Headache2005;45:196-203.

4. Lipton RB, Gobel H, Einhaupl KM, et al. Petasites hybridus root (butterbur) is an effective preventive treatment for migraine. Neurology 2004;63:2240-4.

5. Volger BK, Pittler MH, Ernst E. Feverfew as a preventive treatment for migraine: a systematic review. Cephalagia 1998;18:704-8.

6. Murphy JJ, Hepinstall S, Mitchell JR. Randomized double-blind placebo controlled trial of feverfew in migraine prevention. Lancet 1988;2:189-92.

7. Johnson ES, Kadam NP, Hylands DM, Hylands PJ. Efficacy of feverfew as prophylactic treatment of migraine. Br Med J (Clin Res Ed) 1985;291:569-73.

8. Palevitch D, Earon G, Carasso R. Feverfew (Tanacetum parthenium) as a prophylactic treatment for migraine: A double-blind placebo-controlled study. Phytother Res 1997;11:508-11.

9. Diener HC, Pfaffenrath V, Schnitker J, et al. Efficacy and safety of 6.25 mg t.i.d. feverfew CO2-extract (MIG-99) in migraine prevention - a randomized, double-blind, multicentre, placebo-controlled study. Cephalalgia2005;25:1031-41.

10. De Weerdt CJ, Bootsma HPR, Hendriks H. Herbal medicines in migraine prevention. Phytomed 1996;3:225-30.

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12. Cady RK, Goldstein J, Nett R, et al. A double-blind placebo-controlled pilot study of sublingual feverfew and ginger (LipiGesic M) in the treatment of migraine. Headache 2011;51:1078-86

13. Gallai V, Sarchielli P, Coata G, et al. Serum and salivary magnesium levels in migraine. Results in a group of juvenile patients. Headache 1992;32:132-5.

14. Baker B. New research approach helps clarify magnesium/migraine link. Family Pract News 1993;Aug 15:16.

15. Barbiroli B, Lodi R, Cortelli P, et al. Low brain free magnesium in migraine and cluster headache: an interictal study by in vivo phosphorus magnetic resonance spectroscopy on 86 patients. Cephalalgia 1997;17:254.

16. Mazzotta G, Sarchielli P, Alberti A, Gallai V. Intracellular Mg++ concentration and electromyographical ischemic test in juvenile headache. Cephalalgia 1999;19:802-9.

17. Weaver K. Magnesium and migraine. Headache 1990;30:168 [letter].

18. 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;16:257-63.

19. Facchinetti F, Sances G, Borella P, et al. Magnesium prophylaxis of menstrual migraine: effects on intracellular magnesium. Headache 1991;31:298-301.

20. Pfaffenrath V, Wessely P, Meyer C, et al. Magnesium in the prophylaxis of migraine—a double-blind placebo-controlled study. Cephalalgia 1996;16:436-40.

21. Mauskop A, Altura BT, Cracco RQ, Altura BM. Intravenous magnesium sulphate relieves migraine attacks in patients with low serum ionized magnesium levels: a pilot study. Clin Sci 1995;89:633-6.

22. Schoenen J, Lenaerts M, Bastings E. High-dose riboflavin as a prophylactic treatment of migraine: results of an open pilot study. Cephalalgia 1994;14:328-9.

23. Schoenen J, Jacquy J, Lenaerts M. Effectiveness of high-dose riboflavin in migraine prophylaxis. A randomized controlled trial. Neurology 1998;50:466-70.

24. Schoenen J, Jacquy, Lenaerts M. High-dose riboflavin as a novel prophylactic antimigraine therapy: results from a double-blind, randomized, placebo-controlled trial. Cephalalgia 1997;17:244 [abstract].

25. Maizels M, Blumenfeld A, Burchette R. A combination of riboflavin, magnesium, and feverfew for migraine prophylaxis: a randomized trial. Headache2004;44:885-90.

26. MacLennan SC, Wade FM, Forrest KML, et al. High-dose riboflavin for migraine prophylaxis in children: a double-blind, randomized, placebo-controlled trial. J Child Neurol 2008;23:1300-4.

27. Kimball RW, Friedman AP, Vallejo E. Effect of serotonin in migraine patients. Neurology 1960;10:107-11.

28. Sicuteri F. The ingestion of serotonin precursors (L-5-hydroxytryptophan and L-tryptophan) improves migraine headache. Headache 1973;13:19-22.

29. Titus F, Davalos A, Alom J, Codina A. 5-hydroxytryptophan versus methysergide in the prophylaxis of migraine. Eur Neurol 1986;25:327-9.

30. Maissen CP, Ludin HP. Comparison of the effect of 5-hydroxytryptophan and propranolol in the interval treatment of migraine. Schweizerische Medizinische Wochenschrift /Journal Suisse de Medecine 1991;121:1585-90 [in German].

31. De Benedittis G, Massei R. 5-HT precursors in migraine prophylaxis: A double-blind cross-over study with L-5-hydroxytryptophan versus placebo. Clin J Pain 1986;3:123-9.

32. Mathew NT. 5-hydroxytryptophan in the prophylaxis of migraine. Headache 1978;18:111-3.

33. Bono G, Criscuoli M, Martignoni E, et al. Serotonin precursors in migraine prophylaxis. Advances in Neurology 1982;33:357-63.

34. De Giorgis G, Miletto R, Iannuccelli M, et al. Headache in association with sleep disorders in children: A psychodiagnostic evaluation and controlled clinical study ñ L-5-HTP versus placebo. Drugs Exp Clin Res 1987;13:425-33.

35. Santucci M, Cortelli P, Rossi PG, et al. L-5-Hydroxytryptophan versus placebo in childhood migraine prophylaxis: a double-blind crossover study. Cephalalgia 1986;6:155-7.

36. Magis D, Ambrosini A, Sandor P, et al. A randomized double-blind placebo-controlled trial of thioctic acid in migraine prophylaxis. Headache 2007;47:52-7.

37. Hershey AD, Powers SW, Vockell ALB, et al. Coenzyme Q10 deficiency and response to supplementation in pediatric and adolescent migraine. Headache 2007;47:73-80.

38. Rozen TD, Oshinsky ML, Gebeline CA,, et al. Open label trial of coenzyme Q10 as a migraine preventive. Cephalalgia2002;22:137-41.

39. Sandor PS, Di Clemente L, Coppola G, et al. Efficacy of coenzyme Q10 in migraine prophylaxis: a randomized controlled trial. Neurology2005;64:713-5.

40. Slater SK, Nelson TD, Kabbouche MA, 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.

41. Di Rosa G, Attina S, Spano M, et al. Efficacy of folic acid in children with migraine, hyperhomocysteinemia and MTHFR polymorphisms. Headache 2007;47:1342-4.

42. Cady RK, Goldstein J, Nett R, et al. A double-blind placebo-controlled pilot study of sublingual feverfew and ginger (LipiGesic M) in the treatment of migraine. Headache 2011;51:1078-86

43. Maghbooli M, Golipour F, Moghimi et al. Comparison between the efficacy of ginger and sumatriptan in the ablative treatment of the common migraine. Phytother Res. 2014;28:412–5.

44. Claustrat B, Brun J, Geoffriau M, et al. Nocturnal plasma melatonin profile and melatonin kinetics during infusion in status migrainosus. Cephalalgia 1997;17:511-7 (discussion 487).

45. Nagtegaal JE, Smits MG, Swart AC, et al. Melatonin-responsive headache in delayed sleep phase syndrome: preliminary observations. Headache 1998;38:303-7.

46. Goncalves AL, Martini Ferreira A, Ribeiro RT, et al. Randomised clinical trial comparing melatonin 3 mg, amitriptyline 25 mg and placebo for migraine prevention. J Neurol Neurosurg Psychiatry 2016;87:1127–32.

47. Alstadhaug KB, Odeh F, Salvesen R, Bekkelund SI. Prophylaxis of migraine with melatonin: a randomized controlled trial. Neurology 2010;75:1527-32.

48. van der Kuy PHM, Merkus FWHM, Lohman JJHM, ter Berg JWM, Hooymans PM. Hydroxocobalamin, a nitric oxide scavenger, in the prophylaxis of migraine: an open, pilot study. Cephalalgia 2002;22:513-9.

49. Thys-Jacobs S. Vitamin D and calcium in menstrual migraine. Headache 1994;34:544-6.

50. Thys-Jacobs S. Alleviation of migraines with therapeutic vitamin D and calcium. Headache 1994;34:590-2.

51. Levy RL. Intranasal capsaicin for acute abortive treatment of migraine without aura. Headache 1995;35:277 [letter].

52. McCarren T, Hitzemann R, Allen C, et al. Amelioration of severe migraine by fish oil (omega-3) fatty acids. Am J Clin Nutr 1985;41:874 [abstract].

53. Glueck CJ, McCarren T, Hitzemann R, et al. Amelioration of severe migraine with omega-3 fatty acids: a double-blind placebo controlled clinical trial. Am J Clin Nutr 1986;43:710 [abstract].

54. Chung KF, McCusker M, Page CP, et al. Effect of a ginkgolide mixture (BN 52063) in antagonising skin and platelet responses to platelet activating factor in man. Lancet 1987;i:248-51.

55. Kimball RW, Friedman AP, Vallejo E. Effect of serotonin in migraine patients. Neurology 1960;10:107-11.

56. Poloni M, Nappi G, Arrigo A, Savoldi F. Cerebrospinal fluid 5-hydroxyindoleacetic acid level in migrainous patients during spontaneous attacks, during headache-free periods and following treatment with L-tryptophan. Experientia 1974;30:640-1.

57. Kangasniemi P, Falck B, Langvik V-A, Hyyppa MT. Levotryptophan treatment in migraine. Headache 1978;18:161-6.

58. Sicuteri F. The ingestion of serotonin precursors (L-5-hydroxytryptophan and L-tryptophan) improves migraine headache. Headache 1973;13:19-22.

59. Titus F, Davalos A, Alom J, Codina A. 5-hydroxytryptophan versus methysergide in the prophylaxis of migraine. Eur Neurol 1986;25:327-9.

60. Maissen CP, Ludin HP. Comparison of the effect of 5-hydroxytryptophan and propranolol in the interval treatment of migraine. Schweizerische Medizinische Wochenschrift /Journal Suisse de Medecine 1991;121:1585-90 [in German].

61. De Benedittis G, Massei R. 5-HT precursors in migraine prophylaxis: A double-blind cross-over study with L-5-hydroxytryptophan versus placebo. Clin J Pain 1986;3:123-9.

62. Mathew NT. 5-hydroxytryptophan in the prophylaxis of migraine. Headache 1978;18:111-3.

63. Bono G, Criscuoli M, Martignoni E, et al. Serotonin precursors in migraine prophylaxis. Advances in Neurology 1982;33:357-63.

64. De Giorgis G, Miletto R, Iannuccelli M, et al. Headache in association with sleep disorders in children: A psychodiagnostic evaluation and controlled clinical study ñ L-5-HTP versus placebo. Drugs Exp Clin Res 1987;13:425-33.

65. Santucci M, Cortelli P, Rossi PG, et al. L-5-Hydroxytryptophan versus placebo in childhood migraine prophylaxis: a double-blind crossover study. Cephalalgia 1986;6:155-7.

66. Gatto G, Caleri D, Michelacci S, Sicuteri F. Analgesizing effect of a methyl donor (S-adenosylmethionine) in migraine: an open clinical trial. Int J Clin Pharmacol Res 1986;6:15-7.

67. Thys-Jacobs S. Vitamin D and calcium in menstrual migraine. Headache 1994;34:544-6.

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The information presented by TraceGains is for informational purposes only. It is based on scientific studies (human, animal, or in vitro), clinical experience, or traditional usage as cited in each article. The results reported may not necessarily occur in all individuals. Self-treatment is not recommended for life-threatening conditions that require medical treatment under a doctor's care. For many of the conditions discussed, treatment with prescription or over the counter medication is also available. Consult your doctor, practitioner, and/or pharmacist for any health problem and before using any supplements or before making any changes in prescribed medications. Information expires December 2025.