Supplements for Migraine Prevention

By: Brooklyn A. Bradley, BS; Medically edited by Dr. Deena Kuruvilla, MD

Introduction:

This week’s blog post will highlight the use of supplements for migraine prevention. Supplements, AKA nutraceuticals, are a type of complementary and integrative medicine (CIM). CIM is often used in combination with mainstream medical therapy. CIM encompasses a variety of therapeutic approaches such as acupuncture, mindfulness/meditation and supplements. Some of the common nutraceuticals used for migraine prevention include riboflavin, coenzyme Q10, magnesium, vitamin D, and melatonin. It is important to discuss these complementary approaches with your provider to discover which therapy may be most efficacious with the best safety profile.

Riboflavin:

Riboflavin (B2) is a water-soluble B-vitamin with antioxidant, anti-aging, anti-inflammatory, anti-nociceptive, and anti-cancer properties (1). Riboflavin can be found in many foods and natural sources such as eggs, fish, nuts, fruits, rice, and dark green leafy vegetables. It has a role in cellular functions, most importantly, it helps with energy production (2). Brain energy metabolism has been found to be dysfunctional in people with migraine, thus riboflavin has been researched as a potential mediator in this mechanism (1).

In a randomized controlled trial (RCT) evaluating the effectiveness of high-dose riboflavin in migraine prevention, the researchers compared riboflavin (400 mg) and placebo in 55 patients with migraine for 3 months (3). Riboflavin was found to be superior to placebo in reducing frequency of migraine attacks (3). In a study investigating the efficacy of riboflavin for prevention of migraine, patients received 400 mg riboflavin (4). Headache frequency was significantly reduced from 4 days/month pre-treatment to 2 days/month at both the 3 and 6 month mark. However, headache intensity did not change significantly (4). 

For migraine, the most common dose of riboflavin is 400 mg daily. Riboflavin has a favorable side effect profile. When taken orally, riboflavin may cause the urine to have a more yellow color than normal depending on the dosage.

Coenzyme Q10:

Coenzyme Q10 (CoQ10), also known as ubiquinone, is a dietary supplement often recommended by primary care providers and specialists for numerous diseases. It is most often recommended for neurodegenerative diseases, fibromyalgia, mitochondrial diseases, and migraine. CoQ10 is a fat-soluble vitamin found naturally in the human body. It is vital for energy production in the body, and has the capacity to enhance blood flow and protect blood vessels (5).

In a RCT measuring the efficacy of CoQ10 for migraine prevention, 300 mg/day CoQ10 was administered to the treatment group, and their outcomes were compared to the placebo group (6). CoQ10 was found to be superior to placebo for attack-frequency and days-with-nausea (6). In a RCT studying oral CoQ10 supplementation in patients with migraine, these researchers took an interest in the effects on clinical features and inflammatory markers as well (7). Subjects received 400 mg/day CoQ10 or placebo for three months. CoQ10 reduced calcitonin gene-related peptide (CGRP) and TNF(tumor necrosis factor)-alpha levels significantly, which are two inflammatory markers. In addition, the patients in the CoQ10 group experienced improvement in frequency, severity, and duration of their migraine attacks (7).

CoQ10 has a relatively safe side effect profile and is generally well-tolerated. There is no established ideal dose of CoQ10; however, for adults 19 years and older it is recommended to take 30-200 mg daily. Side effects may include upper abdominal pain, nausea, and heartburn.

Magnesium:

Magnesium is commonly used in over-the-counter products for a variety of diseases. Magnesium is the fourth most common cation in the body and has a vital role in metabolism. It is often involved in muscle contraction, neural activity, and cardiac excitability. In addition, ATP, the source of energy use and storage in our cells, needs magnesium in order to function properly (8).

In a RCT studying the effects of oral magnesium in the prevention of migraine, oral 600 mg of magnesium was administered to the treatment group (9). It was reported that between weeks 9-12, the migraine attack frequency was reduced by 41.6% in the magnesium group (9). In a RCT comparing magnesium, sodium valproate, and concurrent magnesium-sodium valproate therapy for migraine prevention, all groups experienced a significant reduction in migraine characteristics (10). Magnesium may enhance the anti-migraine properties of sodium valproate (10).

Magnesium is considered an inexpensive and simple preventive treatment for patients with migraine. The suggested dosage for migraine is 600 mg; however, it is important to discuss this with your provider. Some common side effects of magnesium supplements include abdominal pain, nausea, cramping, and diarrhea. 

Vitamin D:

Vitamin D is commonly known as the “sunshine vitamin,” and it earns this name from its ability to produce the vitamin in the skin following a period of sun exposure (11). Vitamin D is required to maintain serum calcium concentration, which is necessary for musculoskeletal health. It is a hormone that can be obtained through dietary exposure and exposure to the sun. Vitamin D has many functions including myocardial contractility, insulin production, and the prevention of inflammatory bowel diseases (11).

In a RCT evaluating the use of simvastatin and vitamin D for migraine prevention, participants were randomly assigned to either simvastatin 20 mg 2x/day + vitamin D3 1000 International Units (IU) 2x/daily, or placebo tablets (12). The simvastatin + vitamin D3 caused a greater decrease in the number of migraine days in comparison to placebo. In the treatment group, 25% of patients experienced a 50% reduction in the number of migraine days at 12 weeks (12). In a RCT measuring the effect of vitamin D supplementation on symptoms and C-reactive protein (inflammatory marker) in migraine patients, vitamin D was administered for 10 weeks with 50,000 IU / week (13). Following treatment, there was a significant difference in headache frequency between the two groups (13).

The recommended dosage of vitamin D for adults is 1500 to 2000 IU daily. Some side effects of a very high dose of vitamin D include weakness, dry mouth, and nausea. It is important to discuss the dosage of vitamin D with your provider, as taking a high dosage for a long period of time is possibly unsafe and may affect your serum calcium levels. 

Melatonin:

Melatonin is naturally produced in the brain in response to darkness. It plays a role in the regulation of the body’s circadian rhythms, which is our internal clock. Being exposed to bright light often decreases the secretion of melatonin. Melatonin has other properties beyond its usefulness for sleep (14). According to research, melatonin has a role in cancer suppression, bone deposition, metabolic disorders, cardiovascular diseases, GI conditions, migraine, and neurodegenerative disorders (14). Overall, this hormone has anti-nociceptive and anti-inflammatory properties.

In a RCT comparing melatonin 3 mg to amitriptyline (tricyclic antidepressant with multiple purposes) 25 mg for migraine prevention, the mean headache frequency was reduced by 2.7 migraine headache days in the melatonin group, a decrease from 7.3 days to 4.6 days. In the amitriptyline group, the mean headache frequency was reduced by 2.2 migraine headache days, a decrease from 7.2 days to 5.0 days. Melatonin caused a reduction in headache frequency when compared to placebo (15). In a RCT studying the effects of melatonin on migraine prevention, participants in the migraine treatment group received a dose of 2 mg, 1 hour prior to bedtime for 8 weeks (16). The researchers found that the melatonin did not provide any significant effect over placebo (16). 

While there is no official recommended melatonin dosage for adults, a range of 0.5 to 5 mg is safe and effective. The most common side effects of melatonin supplementation include headache, dizziness, nausea, and drowsiness. There is a lack of high-quality RCTs evaluating the effects of long-term use of melatonin on the body. Thus, it is vital to discuss the use of melatonin with your provider so they can recommend the correct dosage based on your medical history.

Conclusion:

In conclusion, the goal of preventive migraine treatment is to reduce migraine frequency, severity, and duration. CIM approaches are often used in combination with mainstream medical therapy to achieve this goal. Supplements may be an efficacious option for patients who do not respond as successfully to mainstream medical therapy or have had side effects to mainstream medicine.

 

References:

  1. Suwannasom N, Kao I, Pruß A, et al (2020) Riboflavin: The Health Benefits of a Forgotten Natural Vitamin. Int J Mol Sci 21:950. https://doi.org/10.3390/ijms21030950
  2. Mosegaard S, Dipace G, Bross P, et al (2020) Riboflavin Deficiency—Implications for General Human Health and Inborn Errors of Metabolism. Int J Mol Sci 21:3847. https://doi.org/10.3390/ijms21113847
  3. Schoenen J, Jacquy J, Lenaerts M (1998) Effectiveness of high‐dose riboflavin in migraine prophylaxis A randomized controlled trial. Neurology 50:466–470. https://doi.org/10.1212/WNL.50.2.466
  4. Boehnke C, Reuter U, Flach U, et al (2004) High-dose riboflavin treatment is efficacious in migraine prophylaxis: an open study in a tertiary care centre. Eur J Neurol 11:475–477. https://doi.org/10.1111/j.1468-1331.2004.00813.x
  5. Sood B, Keenaghan M (2022) Coenzyme Q10. In: StatPearls. StatPearls Publishing, Treasure Island (FL)
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  7. Dahri M, Tarighat-Esfanjani A, Asghari-Jafarabadi M, Hashemilar M (2019) Oral coenzyme Q10 supplementation in patients with migraine: Effects on clinical features and inflammatory markers. Nutritional Neuroscience 22:607–615. https://doi.org/10.1080/1028415X.2017.1421039
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  10. Khani S, Hejazi SA, Yaghoubi M, Sharifipour E (2021) Comparative study of magnesium, sodium valproate, and concurrent magnesium-sodium valproate therapy in the prevention of migraine headaches: a randomized controlled double-blind trial. The Journal of Headache and Pain 22:21. https://doi.org/10.1186/s10194-021-01234-6
  11. Chauhan K, Shahrokhi M, Huecker MR (2022) Vitamin D. In: StatPearls. StatPearls Publishing, Treasure Island (FL)
  12. Buettner C, Nir R-R, Bertisch SM, et al (2015) Simvastatin and Vitamin D for Migraine Prevention: A Randomized Controlled Trial. Ann Neurol 78:970–981. https://doi.org/10.1002/ana.24534
  13. Mottaghi T, Askari G, Khorvash F, Maracy MR (2015) Effect of Vitamin D supplementation on symptoms and C-reactive protein in migraine patients. J Res Med Sci 20:477–482
  14. Savage RA, Zafar N, Yohannan S, Miller J-MM (2022) Melatonin. In: StatPearls. StatPearls Publishing, Treasure Island (FL)
  15. Gonçalves AL, Ferreira AM, Ribeiro RT, et al (2016) Randomised clinical trial comparing melatonin 3 mg, amitriptyline 25 mg and placebo for migraine prevention. J Neurol Neurosurg Psychiatry 87:1127–1132. https://doi.org/10.1136/jnnp-2016-313458
  16. Alstadhaug KB, Odeh F, Salvesen R, Bekkelund SI (2010) Prophylaxis of migraine with melatonin: A randomized controlled trial. Neurology 75:1527–1532. https://doi.org/10.1212/WNL.0b013e3181f9618c
Published On: August 11th, 2022