Migraine: Serotonin, Magnesium, Vitamin B2, and Preventive Treatment

What is a migraine, and how does it differ from a headache?

Migraine is a chronic, recurrent neurological disorder that differs from tension headaches in its pathophysiology, symptoms, and severity. It affects approximately 15% of adults (with a 3:1 female-to-male prevalence) and is the third leading cause of disability worldwide, according to the WHO. Unlike tension headaches (bilateral pain, pressure, mild to moderate intensity), migraine is characterized by unilateral, throbbing pain of moderate to severe intensity, worsened by physical activity, and associated with nausea, photophobia, and phonophobia. Migraine with aura (visual, sensory, or motor) reflects an invading cortical depression (ICD)—a neuronal depolarization wave that spreads slowly across the cortex—and affects 25 to 30% of migraine sufferers.

What are the four phases of a migraine attack?

A typical migraine attack unfolds in four successive phases:

• Prodromal phase (12 to 24 hours beforehand): warning signs—repeated yawning, irritability, neck stiffness, specific food cravings, and increased sensitivity to light.
• Aura phase (20 to 60 minutes): transient, reversible neurological symptoms—scintillating scotomas, phosphenes, progressive paresthesias in a limb.
• Pain phase (4 to 72 hours): unilateral throbbing pain, nausea, vomiting, sensory hypersensitivity. Cutaneous allodynia develops gradually if the attack is not treated promptly.
• Recovery phase or postdrome (a few hours to 2 days): intense fatigue, difficulty concentrating, persistent sensitivity to stimuli.

What is the role of serotonin in migraine?

Serotonin (5-HT) is central to the pathophysiology of migraine. Before the attack, levels rise; during the painful phase, they drop sharply, triggering vasodilation of the meningeal arteries and the release of CGRP, a central pro-inflammatory mediator of migraine pain. Triptans—the standard-of-care treatments for acute attacks—are 5-HT1B/1D receptor agonists that induce meningeal vasoconstriction and inhibit the release of CGRP. Tryptophan, a precursor to serotonin, and 5-HTP (5-hydroxytryptophan) are being studied as nutritional supplements to help maintain stable serotonin levels between attacks.

Which dietary supplements prevent migraines?

Several supplements have sufficient evidence to support their use in migraine prevention:

• Magnesium (400 to 600 mg/day of citrate): reduces the frequency of attacks by 41% compared to placebo in several randomized trials. Recommended by the French Society for the Study of Migraines and Headaches.
• Vitamin B2 (riboflavin, 400 mg/day): improves mitochondrial metabolism in neurons and reduces the frequency of attacks by 50% in responders, according to the study by Schoenen et al.
• Coenzyme Q10 (300 mg/day): a cofactor in the mitochondrial respiratory chain, reduces the frequency of migraines by 47.6% compared to placebo in the study by Sandor et al. (2005).
• Omega-3 EPA/DHA: reduce the production of CGRP and pro-inflammatory mediators involved in the sensitization of meningeal nociceptors. Recent meta-analyses confirm a reduction in the frequency and duration of attacks.

Catamenial Migraines: What Is the Link to Female Hormones?

Catamenial migraines (related to the menstrual cycle) account for approximately 60% of migraines in women. They typically occur within 2 days before and 3 days after menstruation, in response to a drop in estrogen levels. This drop in estrogen triggers vasodilation of the meningeal arteries and the release of pro-inflammatory prostaglandins. Catamenial migraines are often longer-lasting, more severe, and less responsive to triptans than other types of migraines. Magnesium (starting 10 days before menstruation), omega-3s, and vitamin B6 (a cofactor in serotonin synthesis) can reduce their frequency. Hormonal contraception and conventional preventive treatments require specialized medical advice.

How can you reduce the duration and intensity of a migraine attack?

During an attack, several non-pharmacological measures can reduce its intensity:

• Rest in a dark, quiet room: photophobia and phonophobia make sensory stimuli particularly painful.
• A cold compress on the back of the neck: reduces vasodilation of the meningeal arteries and alleviates throbbing pain.
• Pressure on acupressure points (LI4, between the thumb and index finger): This can reduce pain by activating descending inhibitory pathways.
• Drink plenty of fluids: Vomiting and sweating during severe attacks cause dehydration, which worsens and prolongs the attack.

Acute-phase medications (triptans, antiemetics) should be taken as early as possible during the painful phase for maximum effectiveness. A delay in treatment of more than 2 hours is associated with reduced effectiveness and an increased risk of recurrence.