What is the recommended dose of riboflavin (Vitamin B2) for migraine prevention?

Riboflavin Dose for Migraine Prevention

For migraine prophylaxis, the recommended dose of riboflavin is 400 mg daily as a single oral dose. This high-dose regimen has demonstrated efficacy in reducing migraine frequency and intensity with excellent tolerability and minimal side effects.

Dosing Recommendations

Standard Prophylactic Dose

• 400 mg daily is the established dose for migraine prevention in adults 1
• This dose should be taken as a single oral dose 2, 3
• Treatment duration should be at least 3 months before assessing efficacy 1

Pediatric and Adolescent Dosing

• 200-400 mg daily has been used in pediatric and adolescent patients 4
• The lower dose of 200 mg may be considered initially in younger patients, with escalation to 400 mg if needed 4

Expected Clinical Benefits

Efficacy Timeline

• Significant benefits typically become apparent at 3-4 months after initiation 1
• In the pivotal randomized controlled trial, 59% of patients achieved a ≥50% reduction in headache days (compared to 15% with placebo), yielding a number-needed-to-treat of 2.3 2
• Attack frequency and headache days are significantly reduced compared to placebo 2

Clinical Outcomes

• Reduction in migraine attack frequency 2, 4
• Decreased intensity of migraine pain 4, 5
• Improved burden of disease scores 5
• Enhanced effectiveness of abortive medications (77% of patients in one study) 4

Safety Profile

Tolerability

• Riboflavin at 400 mg daily is extremely well-tolerated with minimal adverse effects 1
• Common benign effect: yellow-colored urine (not clinically significant) 1
• Rare minor side effects include diarrhea and polyuria 2

Important Safety Caveat

• While generally safe, repeatedly consumed pharmacologic doses >100 mg have theoretical potential to react with light, forming potentially toxic peroxides 1
• However, clinical trials have not demonstrated serious adverse events at the 400 mg dose 2, 3
• This remains a theoretical concern rather than a documented clinical problem in migraine prophylaxis

Clinical Context and Positioning

Advantages of Riboflavin

• Low cost compared to other prophylactic agents 2, 3
• Excellent safety profile with minimal drug interactions 2
• Can be used when other prophylactic medications are contraindicated or poorly tolerated 1

Comparison to First-Line Agents

• Traditional first-line agents include propranolol (80-240 mg/day), timolol (20-30 mg/day), amitriptyline (30-150 mg/day), and divalproex sodium (500-1500 mg/day) 1
• Riboflavin represents an alternative option, particularly valuable for patients who cannot tolerate or have contraindications to these medications 1

Combination Therapy

• Some evidence suggests riboflavin can be combined with other supplements (magnesium, CoQ10), though data for combination therapy are mixed 6, 5
• Riboflavin as a single agent has the strongest evidence base 2, 6

Practical Implementation

Initiation Strategy

• Start with 400 mg daily as a single dose 2, 3
• Set patient expectations for a 3-4 month trial before assessing efficacy 1
• Monitor for reduction in attack frequency and headache days as primary outcomes 2

When to Consider Riboflavin

• Patients seeking low-cost prophylactic options 2, 3
• Patients with contraindications to beta-blockers, tricyclic antidepressants, or anticonvulsants 1
• Patients who have experienced intolerable side effects with traditional prophylactic agents 2
• Pediatric and adolescent patients (consider starting at 200 mg) 4