MIGRAINE prevention with supplements

Migraines commonly occur in our post-concussion patients. While there is not any evidence for the use of supplements for post-traumatic headaches, post-traumatic headaches that look like migraines are often treated that same way migraines would be treated in the non-TBI population.

Many patients often ask about natural supplements for the prevention of migraines.

This page lays out some general knowledge about supplements that are often taken for migraine prevention.

Summary

A relationship between Magnesium deficiency and migraines was identified.

• 3 reputable studies on Magnesium’s use for migraine prevention were done (Peikert et al., 1996; Pfaffenrath et al., 1996; Koseoglu et al., 2008).
• There is level B evidence for its use in migraine prevention, which means it’s probably effective and should be considered.

1. More about magnesium

• It is an abundant mineral in the body
• It is present in a variety of foods
• The Recommended Daily Allowance (RDA) is 400-420mg (men); 310-360mg (women). Most adults take less than this in their diets.
• It is stored in cells and bone so measuring your serum (blood) levels of magnesium won’t reflect your body’s store of it. Your serum only contains less than 1% of your body’s store of magnesium.
• It has an important role in multiple physiological processes: it is a co-factor in more than 300 enzyme systems; it is used in protein synthesis, energy production, muscle/nerve function, blood sugar control and blood pressure control
• The amount of magnesium in your blood is largely regulated by your diet and kidneys

2. Which form of magnesium should I take?

• Magnesium citrate, aspartate, lactate seem to be better absorbed than magnesium chloride, oxide & sulfate

3. What are some precautions I should be aware of?

• Some people complain of diarrhea or loose stools with magnesium. The magnesium glycinate formulation may be helpful to mitigate this.
• Taking zinc in high doses (>140 mg/day) can interfere with absorption of magnesium.
• Those with kidney failure can experience toxicity from magnesium.
• There is a debate over whether it is safe in pregnancy

Summary

• 1 reputable study on Riboflavin’s use for migraine prevention was done (Schoenen et al. 1998)
• There is level B evidence for its use in migraine prevention, which means it’s probably effective and should be considered.

1. More about Riboflavin

• Also known as Vitamin B2, it is present in many foods
• RDA 1.3 mg (male); 1.1 mg (female)
• Deficiency rare unless vegan, dairy free (especially in pregnancy and athletes)
• There is limited absorption from the gastrointestinal tract
• It has an important role in multiple physiological processes: energy production; cellular function; growth and development; metabolism of fats, drugs and steroids

2. What are some precautions I should be aware of?

• There have been no observed toxicity or reports of adverse effects from high doses. There are no known clinically relevant interactions with medications.
• It is considered safe in pregnancy

Summary

• Six trials with 561 patients showing Mixed results: 4 positive trials, 2 negative trials
• There is level B evidence for its use in migraine prevention, which means it’s probably effective and should be considered.

1. More about Feverfew

• It’s a herb that grows naturally Europe, North America and South America
• Its dried leaves are made into supplement
• It has anti-inflammatory properties (inhibits prostaglandin synthesis)

2. What are some precautions I should be aware of?

• There have been no serious side effects reported
• Side effects if experienced tend to be mild: nausea, digestive problems, bloating
• If the fresh leaves are chewed it can cause sores and irritation of the mouth
• Withdrawal effects in those who use it regularly and discontinue it can include difficulty sleeping, headache, anxiety, stiff/painful muscles
• This is not recommended during pregnancy as it may cause uterine contractions

Summary

• 2 Randomized Controlled Trials (RCTs) of coenzyme Q10 as a migraine preventive (Sandor 2005, Dahiri 2017) showed a positive effect for CoEnzyme Q10
• There is level C evidence for its use in migraine prevention, which means it’s possibly effective and may be considered.

1. More about CoEnzyme Q10

• It is naturally present in the body
• It is used in mitochondrial function (produces cellular energy) and as an antioxidant

2. What are some precautions I should be aware of?

• There have been no serious side effects reported
• Most common side effects are mild and can include: insomnia, fatigue, nausea, diarrhea
• Rarely there can be increase in blood levels of AST and ALT (markers of liver inflammation)
• Uncertain safety in pregnancy and breastfeeding
• It may make warfarin less effective

Summary

• 2 RCTs of Butterbur using Petadolex formulation showed a positive effect
• There is level A evidence for its use in migraine prevention, which means it has been established as effective and should be offered for migraine prevention.
• There was a lot of controversy surrounding Butterbur and toxicity. Women’s College’s Centre for Headache on November 24, 2014  posted this on their website and have not removed it to date: “Attention all patients and physicians. Due to recent medical findings suggesting a safety concern, we are no longer recommending butterbur and we ask anyone currently on it, to stop taking it. Common brand names in Canada include Petadolex and Migranon.”

1. More about Butterbur

• It is a shrub that grows in Europe, Asia, North America and is used for medicinal purposes
• It got its name because of its large leaves which were used to wrap up butter in warm weather
• Main active components are petasin and isopetasin
• It has anti-inflammatory properties (Inhibits COX-2 & leukotriene biosynthesis) and is involved in calcium channel regulation

2. What are some precautions I should be aware of?

• It contains Pyrrolizidine Alkaloids (PAs) which are toxic to the liver (hepatoxic) and there have been case reports of serious liver injury to formulations of Butterbur.
• PA toxins are supposed to be removed in Petadolex formulation by the manufacturer, they may be present in other butterbur extracts
• Safety concerns have arisen in recent years where PA toxins were found in commercially available formulations and so Petadolex taken off the market in several countries and guidelines put by the American Academy of Neurology and the American Headche Society were discontinued because of this concern; new guidelines are pending.
• Safety of longer-term use has not been established
• Common side effects: belching, headache, itchy eyes, diarrhea, breathing difficulties, fatigue, drowsiness
• Allergic reactions possible, especially in those sensitive to plants such as ragweed, chrysanthemums, marigold, and daisies

3. What should I consider before considering Butterbur?

• The European Food Safety Authority considers an intake of 0.007 mcg of PA/kg of a person’s bodyweight per day as acceptable
• The National Center for Natural Products Research analyzed 21 commercial butterbur products in the US for petasins (active ingredient) and PAs (toxin)
• The results were as follows:
  • Safe & effective: 7/21 products (Petasin amount within the limits of the label claim and no detectable PAs, 3/7 were Petadolex formulation)
  • Not effective: 6/21 had no detectable amounts of petasin
  • Toxic: 7/21 had PA levels between 0.1 and 4.48 mcg/tablet
• The National Institute of Health recommends that if you are going to use butterbur, to only use it if it is labeled and certified as PA-free

4. Are supplements regulated?

• The FDA may inspect manufacturer’s production sites to ensure that they are complying with manufacturing guidelines.
• They also run an adverse event reporting program where patients volunteer information regarding side effects they experience
• The FDA has the power to remove a product from the market
• According to the FDA, companies:
  • can make claims of health benefit, nutrient content, structure/function
  • but they can’t make claims of specific disease treatment or prevention
• Unlike drugs, supplements don’t need FDA pre-market review for approval
• The FDA does not assess supplements for efficacy, safety or quality

5. What are some measures one can take to make sure that what they are getting has been analyzed by a 3^rd party?

Look for the seal by one of these 3^rd party companies that assess the integrity of supplements: National Science Foundation, Consumer Lab Testing, US Pharmocopoeia (USP).

There are studies that show a positive effect with the following:

1. Vitamin D

2. Lavender essential oil

3. Boswelia

The National Institutes of Health: Office of Dietary Supplements is a good resource to learn more about supplements you are researching.

Dahri, Monireh & Tarighat Esfanjani, Ali & Asghari-Jafarabadi, Mohammad & Hashemilar, Mazyar. (2018). Oral coenzyme Q10 supplementation in patients with migraine: Effects on clinical features and inflammatory markers. Nutritional Neuroscience. 1-9. 10.1080/1028415X.2017.1421039.

Diener HC, Rahlfs VW, Danesch U. The first placebo-controlled trial of a special butterbur root extract for the prevention of migraine: reanalysis of efficacy criteria. Eur Neurol 2004;51(2):89-97.

Grossman W, Schmidramsl H. An extract of Petasites hybridus is effective in the prophylaxis of migraine. Altern Med Rev 2001;6(3):303-310.

Koseoglu E, Talaslioglu A, Gonul AS, Kula M. The effects of magnesium prophylaxis in migraine without aura. Magnesium Res 21: 101–108, 2008.

Lipton, Richard & Göbel, Hartmut & M Einhäupl, K & Wilks, Kerri & Mauskop, Alexander. (2004). Petasites hybridus root (butterbur) is an effective preventive treatment for migraine. Neurology. 63. 2240-4. 10.1212/01.WNL.0000147290.68260.11.

Peikert, A., Wilimzig, C., & Köhne-Volland, R. (1996). Prophylaxis of Migraine with Oral Magnesium: Results From A Prospective, Multi-Center, Placebo-Controlled and Double-Blind Randomized Study. Cephalalgia, 16(4), 257–263.

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 doubleblind placebo-controlled study. Cephalalgia 16: 436 – 440, 1996.

Sandor, Peter & Di Clemente, Laura & Coppola, Gianluca & Saenger, U & Fumal, Arnaud & Magis, D & Seidel, Laurence & Agosti, Reto & Schoenen, Jean. (2005). Efficacy of coenzyme Q10 in migraine prophylaxis: A randomized controlled trial. Neurology. 64. 713-5.

Schoenen, Jean & Jacquy, J & Lenaerts, M. (1998). Effectiveness of high-dose riboflavin in migraine prophylaxis. A randomized controlled trial. Neurology. 50. 466-70. 10.1212/WNL.50.2.466.