Migraine is an episodic or chronic primary neurovascular disorder (a type of dysfunction of the central and peripheral pain pathways and intracranial vascular system) characterized by moderate to severe, recurrent, unilateral or bilateral pulsatile headaches, usually lasting hours to days.
Migraine attacks may be insidious or accompanied by aura, which may include fatigue, yawning, difficulty concentrating, nausea, vomiting, sensitivity to light, sound, touch, or smell, and approximately 25% of migraine patients have transient visual disturbances, motor symptoms, or speech disturbances prior to the onset
Although the exact cause of migraine is unknown, it is thought to be influenced by a number of different factors.
Genetic components are observed in 65% to 90% of cases. In addition, the incidence is 3 times higher in women than in men, which is mostly attributed to hormonal fluctuations, especially estrogen.
On average, people with migraines have one or two attacks a month. More than two-thirds of migraine sufferers in women and nearly half of migraine sufferers in men have episodes that last longer than a day.
In addition to the pain and discomfort at the onset, the cumulative effects of migraine can also affect daily life, family, partner, friends, and work relationships.
What are the triggers of migraines?
Although the pathophysiology of migraine is not fully understood, there is evidence that dietary factors may play a role in several mechanisms, influencing the regulation of neuropeptides, nerve receptors and ion channels, the sympathetic nervous system, and brain glucose metabolism, or by causing inflammation, nitric oxide release, and vasodilation.
Most of the information about foods that may cause headaches comes from patient self-reports, not from randomized scientific studies.
Despite the lack of scientific evidence, the most common foods reported to trigger headaches include the following: Note 1
Cheese, certain fresh fruits including ripe bananas, citrus fruits, papaya, red plums, raspberries, kiwifruit, pineapple, avocado.
Pickled foods (pickles, olives, sauerkraut), yeast products (doughnuts, cakes), alcohol (wine, beer, whiskey and champagne are most common), legumes, fermented dairy products, sour cream, yogurt, chocolate.
Caffeinated beverages (including coffee, tea, and cola), aspartame and other artificial sweeteners, onions, garlic.
Dried fruits (figs, raisins, dates), peanuts, peanut butter, almonds and other nuts and seeds, tomato products, potato chips, chicken liver and other offal meats, smoked fish, meat products containing nitrates, nitrites (including hot dogs, sausages, bacon, luncheon meats), products containing MSG.
In addition, common triggers of migraines include:
Stress, hormonal changes (up to 75% of women experience migraine attacks around menstruation)
Weather changes (such as temperature, pressure, or even seasonal changes)
Altered or irregular sleep schedule, perfume or smell, muscle tension in the neck and shoulders
Light (bright or flashing lights), smoking, heat
Sudden strenuous exercise, sexual activity, dehydration, prolonged or sudden loud noise
Missed a meal / hunger / fasting (Note 2)
What are the adjunctive therapies that are beneficial for migraine?
1. Vitamin D
Vitamin D deficiency is an emerging global health problem that affects about 30% to 80% of children and adults worldwide, and deficiency can be caused by a variety of factors, mainly insufficient sun exposure.
Other risk factors include aging, dark skin, latitude, winter, clothing, sunscreen, air pollution, smoking, staying at home, obesity, malabsorption, drug use (including antiepileptic drugs, glucocorticoids, human immunodeficiency virus drugs, and anti-rejection drugs).
A meta-analysis (6 randomized controlled trials, 301 migraine patients) noted that vitamin D supplementation significantly reduced the number of headache attacks, headache days, and Migraine Disability Assessment Questionnaire (MIDAS) scores per month compared with controls, but had no clear effect on episode duration and severity. Note 1
*Conclusion: Vitamin D supplementation may have a positive effect on migraine, but due to small sample sizes and sample heterogeneity, more studies are needed to further validate
2. Magnesium
Magnesium is an essential mineral that acts as a cofactor to maintain homeostasis through more than 300 biochemical reactions
The biological functions of magnesium are broad and diverse, including nucleic acid production, participation in all adenosine triphosphate (ATP) catalytic reactions, modulation of intracellular calcium concentration flux-mediated activities (e.g., insulin release, muscle contraction), cell and tissue integrity, and DNA/RNA and protein synthesis and integrity.
A meta-analysis (21 randomized controlled trials with 1737 migraine patients) noted that intravenous magnesium significantly relieved acute migraine within 15–45 minutes, 120 minutes, and 24 hours, while oral magnesium significantly reduced migraine frequency and intensity. Note 1
*Conclusion: Intravenous magnesium and oral magnesium should be used as adjunctive therapies for the treatment of acute migraine and migraine prevention, respectively, but more precisely designed studies are needed to support this
3. Riboflavin, also known as vitamin B2
Riboflavin is a water-soluble vitamin that is part of the B vitamin, also known as vitamin B2
In humans, riboflavin is an important component of two coenzymes (flavin mononucleosides (FMN) and flavotinadenine dinucleotide (FAD)), which are coenzymes for many enzymatic reactions and perform critical metabolic functions in biological oxidation-reduction reactions by regulating the transfer of electrons, related to energy production, antioxidant protection, and homocysteine metabolism.
Poor riboflavin status can lead to a variety of clinical abnormalities, including growth retardation, sore throat, bad breath, anemia, kidney damage, neurodegenerative disease, and possibly even cancer
In general, riboflavin deficiency is extremely rare in advanced countries because riboflavin sources are usually common foods (cereals, milk, and meat)
A meta-analysis (8 RCTs and 1 controlled trial with 673 migraine patients) noted that vitamin B2 supplementation (400 mg daily for 3 months) significantly reduced migraine days, duration, frequency, and pain scores. Note 1
*Conclusion: Vitamin B2 may be a positive help for migraine prevention, but there is still more evidence to determine its long-term efficacy and duration, multivitamin and migraine prevention effect at different doses.
4. Melatonin
Melatonin is a “clock factor” produced by the pineal gland that dominates the regular circadian rhythm in humans, and its receptors MT1 and MT2 are found to be widely present in cells and tissues.
So far, melatonin has been shown to be effective with epilepsy, insomnia, depression, Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, cancer, hair loss, obesity, diabetes, eye lesions, systemic lupus erythematosus, rheumatoid arthritis, scimiosis, ischemic heart disease, hypertension and Stein-Livingser syndrome… and other diseases related.
A meta-analysis of 25 randomized controlled trials with 4499 migraine patients noted that oral melatonin helped improve migraine frequency. Note 1
In addition, taking into account improvements in migraine attack frequency, response rate, withdrawal rate, and adverse event rate, of all the investigated interventions, oral melatonin 3 mg at bedtime (immediate-release/immediate/immediate) was the most ideal pharmacological intervention with the best improvement.
The mechanism behind melatonin may be related to melatonin inhibiting nitric oxide synthesis, inhibiting dopamine release, antagonizing glutamate-induced excitotoxicity, inhibiting the release of calcitonin gene-associated peptides (CGRP), increasing β-endorphin release and other mechanisms.
*Conclusion: For migraine, oral melatonin may reduce the frequency of attacks, but due to insufficient statistical data (e.g., heterogeneity of participant characteristics and small number of trials in some treatment groups), more research is needed to further confirm the optimal dose and duration of treatment
5. Exercise
Exercise is defined as planned, structured, repetitive and purposeful physical activity in the sense that improving or maintaining physical health is the goal.
In most cases, exercise is one of the best ways to manage chronic pain and can also have an impact on mental health, such as elevating mood, reducing stress and depression, which are often associated with chronic pain, so understanding the mechanisms of exercise-induced analgesia is important to better develop physical activity-related treatment options for pain patients.
A meta-analysis (21 clinical trials with 1195 migraine patients) found that all exercise interventions helped reduce migraine frequency compared with placebo, but strength/resistance training had the highest effect, followed by high- and moderate-intensity aerobic exercise. Note 1
The possible reasons why strength/resistance training works best are related to muscle strengthening and repair, especially the major muscles involving the shoulders, neck and upper extremities, since neck pain coexists highly with migraine in the clinical population. Note 2
*Conclusion: Exercise can help reduce the burden of migraine, especially with strength training exercise regimens
6. Coenzyme Q10
Coenzyme Q10, also known as ubiquinone or CoQ10, is a fat-soluble benzoquinone compound with 10 isoprene groups on the side chain, a fat-soluble biomolecule ubiquitous in almost all animal and bacterial mitochondria and a component of the electron transport chain responsible for the production of adenosine triphosphate (ATP) molecules from aerobic cell respiration.
Therefore, in functional organs with high ATP requirements, such as the kidneys, heart, liver, CoQ10 concentration is very high.
In addition, CoQ10 is an intracellular antioxidant that protects membrane phospholipids, mitochondrial membrane proteins, and LDL-C from free radical-induced oxidative damage.
Up to now, coenzyme Q10 has been widely used in the intervention and treatment of various diseases or disorders such as cardiovascular disease, diabetes, kidney disease, Parkinson’s disease, Huntington’s disease, cancer and infertility.
A meta-analysis (5 studies, 346 migraine patients) showed that oral coenzyme Q10 (used for 3 months, daily dose of 100 to 400 mg) reduced the number of days/month and duration of monthly attacks compared with placebo, but did not significantly change severity/day and attacks/month. Note 1
*Conclusion: Coenzyme Q10 may be of positive help to improve migraine, but limited by the small sample size, more large trials are still needed for further verification