What is the recommended dose of riboflavin (B2) for an adult patient with headaches?

Riboflavin Dosing for Headache Prophylaxis

For migraine prophylaxis in adults, use riboflavin 400 mg daily, which has demonstrated superior efficacy in reducing attack frequency and headache days compared to placebo. 1

Recommended Dosing Protocol

Standard Prophylactic Dose

• 400 mg daily as a single oral dose is the evidence-based dosing for migraine prevention 1
• This dose has shown that 59% of patients achieve at least 50% reduction in headache days (number-needed-to-treat = 2.3) 2
• Treatment duration should be 3-6 months to assess full therapeutic benefit 3, 2

Alternative Dosing Considerations

• Some protocols use 200 mg twice daily (total 400 mg/day) rather than a single dose 1
• In pediatric/adolescent populations, doses of 200-400 mg daily have been used successfully 3

Clinical Implementation

Treatment Timeline

• Initiate at 400 mg daily from the start—no titration required 1
• Assess response after 3 months minimum, as full benefit may take this long to manifest 3, 2
• Continue for 4-6 months if showing benefit, then reassess need for ongoing prophylaxis 3

Expected Outcomes

• Significant reduction in attack frequency (p = 0.005) and headache days (p = 0.012) compared to placebo 2
• 59% of patients achieve ≥50% reduction in headache frequency versus 15% with placebo 2
• 77% of patients report improved effectiveness of abortive medications during riboflavin treatment 3

Safety Profile and Monitoring

Adverse Effects

• Excellent tolerability with minimal side effects at 400 mg dosing 1, 2
• Most common: yellow-colored urine (benign and expected) 1
• Rare: diarrhea, polyuria, increased appetite—all mild and self-limiting 3, 2

Important Safety Caveat

• Doses >100 mg repeatedly consumed have theoretical potential to form toxic peroxides and hepato/cytotoxic tryptophan-riboflavin adducts when exposed to light 1
• However, the 400 mg dose for migraine has not shown serious adverse events in clinical trials 2
• No routine monitoring required for riboflavin supplementation 1

Critical Clinical Considerations

Nutritional Context

• Riboflavin deficiency frequently coexists with pyridoxine, folate, and niacin deficiencies—consider screening for multiple B-vitamin deficiencies if clinical suspicion exists 1, 4
• Riboflavin interferes with iron handling and can contribute to anemia when iron intakes are low 1, 4

Mechanism of Action

• The therapeutic effect in migraine is unrelated to nutritional deficiency correction—it works through supporting mitochondrial energy metabolism at pharmacologic doses 1
• This explains why the prophylactic dose (400 mg) is 333 times higher than the standard nutritional requirement (1.2 mg/day) 1

Cost-Effectiveness

• Riboflavin is an inexpensive, low-cost prophylactic option compared to other migraine preventive medications 5, 2, 6
• The number-needed-to-treat of 2.3 makes this one of the most efficient prophylactic interventions available 2

Patient Selection

• Best evidence exists for adult patients with migraine 5, 7, 2
• Pediatric/adolescent data show promise but are less robust 7, 3
• Consider as first-line prophylaxis given excellent safety profile, low cost, and proven efficacy 2, 6