What are the recommended doses of magnesium and riboflavin (Vitamin B2) for migraine prevention?

Dosing Magnesium and Riboflavin for Migraine Prevention

For migraine prevention, use riboflavin 400 mg daily and magnesium 600 mg daily (as magnesium dicitrate), though these agents have only fair evidence for modest efficacy and should not replace first-line therapies like propranolol, timolol, amitriptyline, or divalproex sodium in patients without contraindications. 1, 2, 3, 4

Evidence Quality and Positioning

The U.S. Headache Consortium and American College of Physicians classify both riboflavin and magnesium as having "fair evidence for modest efficacy" with methodological limitations in existing trials, requiring more robust studies. 1, 2 These agents occupy a secondary role in migraine prevention, not first-line status.

Riboflavin Dosing

• Use 400 mg daily as the evidence-based dose for migraine prophylaxis. 3
• A landmark randomized controlled trial demonstrated that riboflavin 400 mg reduced headache days with 59% of patients achieving ≥50% reduction in frequency (number-needed-to-treat = 2.3), compared to only 15% with placebo. 3
• The treatment requires 2-3 months to assess efficacy, as clinical benefits do not manifest immediately. 1, 2
• Adverse events are minimal—primarily diarrhea and polyuria—making it well-tolerated. 3

Magnesium Dosing

• Use 600 mg daily of magnesium dicitrate for migraine prevention, which represents the high-dose regimen with the strongest supporting evidence. 4
• A systematic review classified magnesium as "Grade C (possibly effective)" with one Class I trial showing significant reduction in migraine attacks and two Class III trials demonstrating efficacy. 4
• Meta-analysis data confirm that oral magnesium significantly reduces both migraine frequency and intensity. 5
• Magnesium requires 2-3 months for adequate trial duration before declaring treatment failure. 1

When to Consider These Agents

Use riboflavin and magnesium in the following clinical scenarios:

• Patients who refuse or have contraindications to first-line agents (propranolol 80-240 mg/day, timolol 20-30 mg/day, amitriptyline 30-150 mg/day, divalproex sodium 500-1500 mg/day). 1, 2
• As adjunctive therapy to first-line agents when partial response is achieved but further improvement is desired. 6
• Patients preferring non-prescription options with minimal side effect profiles and low cost. 3, 4
• Pediatric populations where evidence for riboflavin is relatively stronger than other complementary agents. 7

Combination Therapy

A proprietary combination of magnesium, riboflavin, and coenzyme Q10 showed statistically significant reduction in migraine pain intensity (p=0.03) and HIT-6 burden scores (p=0.01) compared to placebo, though migraine frequency reduction only trended toward significance (p=0.23). 6 This suggests potential synergistic effects, though individual agent efficacy remains modest.

Critical Pitfalls to Avoid

• Do not use these agents as first-line therapy when patients have no contraindications to propranolol, timolol, amitriptyline, or divalproex sodium, which have stronger evidence. 1, 2
• Do not discontinue prematurely—many clinicians stop before the required 2-3 month trial period needed to assess true efficacy. 1, 2
• Ensure patients limit acute medication use to less than twice weekly to prevent medication overuse headache, which interferes with preventive treatment effectiveness. 1, 8
• Avoid interfering medications like ergotamine during preventive treatment. 1

Indications for Any Preventive Therapy

Initiate preventive treatment (whether riboflavin/magnesium or first-line agents) when patients meet these criteria:

• ≥2 migraine attacks per month producing disability lasting ≥3 days per month. 1, 2
• Contraindication to or failure of acute treatments. 1, 2
• Use of abortive medications more than twice per week. 1, 2
• Presence of uncommon migraine conditions (hemiplegic migraine, prolonged aura, migrainous infarction). 1, 2

Practical Implementation

Start both agents simultaneously at full therapeutic doses (riboflavin 400 mg daily, magnesium 600 mg daily) rather than titrating, as these supplements lack the dose-dependent side effects seen with prescription medications. 3, 4 Monitor for gastrointestinal symptoms with magnesium (diarrhea being most common) and adjust formulation if needed. 4 Reassess efficacy at 3 months using headache diaries tracking attack frequency, severity, duration, and disability. 1