NCCIH Clinical Digest

for health professionals

Dietary Supplements for Headaches: What the Science Says

June 2021

Clinical Guidelines, Scientific Literature, Info for Patients: 
Dietary Supplements for Headaches

Man looking at pill bottle

Several dietary supplements, including riboflavin, coenzyme Q10, and the herbs butterbur and feverfew, have been studied for headaches and migraine, with some promising results in preliminary studies. However, more rigorous studies are needed before definitive conclusions can be drawn.

Butterbur

Butterbur appears to help reduce the frequency of migraines in adults and children; however, there are serious safety concerns.
 

What Does the Research Show?

  • In 2012, the American Academy of Neurology recommended its use for preventing migraines. However, the Academy stopped recommending it in 2015 because of serious concerns about possible liver toxicity.

Safety

  • Some butterbur products contain pyrrolizidine alkaloids (PAs), which can damage the liver, lungs, and blood circulation, and possibly cause cancer. Only butterbur products that have been processed to remove PAs and are labeled or certified as PA-free should be considered for use.
  • Several studies, including a few studies of children and adolescents, have reported that PA-free butterbur products seem to be safe when taken by mouth in recommended doses for up to 16 weeks. However, some products claiming to be PA-free may not in fact be. A 2019 review found that recent cases of clinically apparent liver injury have been reported with use of several commercial preparations of butterbur, suspected to be due to residual PA contamination.
  • Butterbur products with PAs should not be used during pregnancy or while breastfeeding because they may cause birth defects or liver damage. Little is known about whether it’s safe to use PA-free butterbur during pregnancy or while breastfeeding.
  • PA-free butterbur is generally well tolerated but can cause side effects such as belching, headache, itchy eyes, diarrhea, breathing difficulties, fatigue, upset stomach, and drowsiness.
  • Butterbur may cause allergic reactions in people who are sensitive to plants such as ragweed, chrysanthemums, marigolds, and daisies.

Coenzyme Q10

There is some limited evidence that coenzyme Q10 may help reduce the duration and frequency of migraines.
 

What Does the Research Show?

  • A 2019 meta-analysis of five studies involving 346 patients (120 pediatric and 226 adult participants) found that coenzyme Q10 was comparable with placebo with respect to migraine attacks per month and migraine severity per day. However, coenzyme Q10 was shown to be more effective than placebo in reducing the number of migraine days per month and migraine duration.
  • Another 2019 meta-analysis of 6 studies involving a total of 371 participants found that coenzyme Q10 supplementation appeared to have beneficial effects in reducing duration and frequency of migraine attack.

Safety

  • No serious side effects of CoQ10 have been reported. Mild side effects such as insomnia or digestive upsets may occur.
  • Coenzyme Q10 may interact with anticoagulants as well as insulin, and it may not be compatible with some types of chemotherapeutic agents.

Feverfew

Some research suggests that feverfew may help prevent migraine headaches, but results have been mixed. Some studies have suggested that feverfew may reduce migraine headache frequency, as well as some symptoms, such as pain, nausea/vomiting, and light sensitivity.
 

What Does the Research Show?

  • A 2020 Cochrane review (an update to a previous Cochrane review, which added one larger rigorous study) of 6 studies involving 561 participants found a difference in effect between feverfew and placebo of 0.6 migraine attacks per month. However, the reviewers noted that this constitutes low quality evidence, which needs to be confirmed in larger rigorous trials with stable feverfew extracts and clearly defined migraine populations before firm conclusions can be drawn.
  • A 2019 review on migraine headache prophylaxis found that feverfew is probably effective.

Safety

  • No serious side effects have been reported from feverfew use. Side effects can include nausea, digestive problems, and bloating; if the fresh leaves are chewed, sores and irritation of the mouth may occur.
  • People who are sensitive to ragweed and related plants may experience allergic reactions to feverfew.

Magnesium

Research on the use of magnesium supplements to prevent or reduce symptoms of migraine headaches is limited. There is some evidence that magnesium supplementation may provide modest reductions in the frequency of migraines.

 

What Does the Research Show?

  • A 2018 systematic review of five studies found Grade C (possibly effective) evidence for prevention of migraine with magnesium. However, a 2021 review concluded that even if the preliminary results are very promising, more rigorous studies have to be designed to confirm the efficacy of magnesium for headache.
  • A 2009 review found that three of four small, short-term, placebo-controlled trials showed modest reductions in the frequency of migraines in patients given up to 600 mg/day magnesium. Because the typical dose of magnesium used for migraine prevention exceeds the Tolerable Upper Intake Level (UL), this treatment should be used only under the direction and supervision of a healthcare provider.

Safety

  • High doses of magnesium from dietary supplements or medications often result in diarrhea that can be accompanied by nausea and abdominal cramping. Forms of magnesium most commonly reported to cause diarrhea include magnesium carbonate, chloride, gluconate, and oxide.
  • Very large doses of magnesium-containing laxatives and antacids (typically providing more than 5,000 mg/day of magnesium) have been associated with magnesium toxicity, including fatal hypermagnesemia. Symptoms of magnesium toxicity, which usually develop after serum concentrations exceed 1.74–2.61 mmol/L, can include hypotension, nausea, vomiting, facial flushing, retention of urine, ileus, depression, and lethargy before progressing to muscle weakness, difficulty breathing, extreme hypotension, irregular heartbeat, and cardiac arrest. The risk of magnesium toxicity increases with impaired renal function or kidney failure because the ability to remove excess magnesium is reduced or lost.

Riboflavin

Some, but not all, of the few small studies conducted to date have found evidence of a beneficial effect of riboflavin supplements on migraine headaches in adults and children.

 

What Does the Research Show?

  • A 1998 randomized controlled trial of 55 participants with migraines compared treatment with 400 mg riboflavin daily with placebo for 12 weeks. The results, 4 months after the trial, showed that the reduction in migraine attacks per month was greater for patients treated with riboflavin (56 percent) compared to the placebo group (19 percent).
  • A 2020 review concluded that overall, studies to date report that riboflavin has similar efficacy to valproate for migraine prophylaxis, but has a more tolerable side effect profile.

Safety

  • Adverse effects from high riboflavin intakes from foods or supplements (400 mg/day for at least 3 months) have not been reported. A 2021 review found that in all of the studies included in the review, riboflavin was well tolerated without major side effects or safety concerns.

References

  • Barmherzig R, Rajapakse T. Nutraceuticals and behavioral therapy for headache. Current Neurology and Neuroscience Reports. 2021;21(7):33.
  • Butterbur. LiverTox: clinical and research information on drug-induced liver injury. Bethesda, MD: National Institute of Diabetes and Digestive and Kidney Diseases; 2012–. Accessed at https://pubmed.ncbi.nlm.nih.gov/31643176/ on June 28, 2021.
  • Grazzie L, Toppo C, D’Amico D, et al. Non-pharmacological approaches to headaches: non-invasive neuromodulation, nutraceuticals, and behavioral approaches. International Journal of Environmental Research and Public Health. 2021;18(4):1503.
  • Ha H, Gonzalez A. Migraine headache prophylaxis. American Family Physician. 2019;99(1):17-24.
  • Sazali S, Badrin S, Norhayati MN, et al. Coenzyme Q10 supplementation for prophylaxis in adult patients with migraine—a meta-analysis. BMJ Open. 2021;11(1):e039358.
  • Schoenen J, Jacquy J, Lenaerts M. Effectiveness of high-dose riboflavin in migraine prophylaxis. A randomized controlled trial. Neurology. 1998;50(2):466-470.
  • Stubberud A, Varkey E, McCrory DC, et al. Biofeedback as prophylaxis for pediatric migraine: a meta-analysis. Pediatrics. 2016;138(2):e20160675.
  • Sun-Edelstein C, Mauskop A. Role of magnesium in the pathogenesis and treatment of migraine. Expert Review of Neurotherapeutics. 2009;9(3):369-379.
  • Thompson AP, Thompson DS, Jou H, et al. Relaxation training for management of paediatric headache: a rapid review. Paediatrics & Child Health. 2019;24(2):103-114.
  • Urits I, Gress K, Charipova K, et al. Pharmacological options for the treatment of chronic migraine pain. Best Practice & Research. Clinical Anaesthesiology. 2020;34(3):383-407.
  • von Luckner A, Riederer F. Magnesium in migraine prophylaxis—is there an evidence-based rationale? A systematic review. Headache. 2018;58(2):199-209.
  • Wider B, Pittler MH, Ernst E. Feverfew for preventing migraine. Cochrane Database of Systematic Reviews. 2015;4(4):CD002286. 
  • Youssef PE, Mack KJ. Episodic and chronic migraine in children. Developmental Medicine and Child Neurology. 2020;62(1):34-41.
  • Zeng Z, Li Y, Lu S, et al. Efficacy of CoQ10 as supplementation for migraine: a meta-analysis. Acta Neurologica Scandinavica. 2019;139(3):284-293.

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