Medicines Q&As
Q&A 424.1
Can riboflavin reduce the incidence of migraines in adults?
Prepared by UK Medicines Information (UKMi) pharmacists for NHS healthcare professionals
Before using this Q&A, read the disclaimer at www.ukmi.nhs.uk/activities/medicinesQAs/default.asp
Date prepared: 6th November 2013
Background
Riboflavin (vitamin B2) is an essential vitamin required for tissue respiration which may be found in
foods such as milk, meat, eggs, nuts, and vegetables.1
UK guidelines for the management of headaches advise that riboflavin at a dose of 400mg daily may
be effective in reducing migraine frequency and intensity for some patients. This recommendation
refers to self-purchase only as there is no licensed riboflavin product available in the UK, nor any cost
effectiveness data to justify its use on NHS prescription.2,3
Answer
Mechanism of action
Riboflavin is converted into a co-enzyme called riboflavin-5-phosphate, which is then in turn converted
into flavin adenine dinucleotide. These co-enzymes act as hydrogen carriers for a number of enzymes
involved in oxidation-reduction reactions in the mitochondrial chain.1
Although the molecular causes of migraine are not well understood, it would appear that a reduction
in mitochondrial oxidative metabolism may be involved. It would therefore follow that riboflavin
supplementation may reduce migraine frequency or severity4.
One study has suggested that patients with a mitochondrial DNA haplogroup H are significantly less
likely to respond to riboflavin treatment than other haplotypes.5
Evidence
There are no good quality meta-analyses or systematic reviews looking at the effect of riboflavin on
migraine.
A small (n=55) randomized placebo controlled trial by Shoenen et al6 found that riboflavin was
significantly better than placebo at reducing frequency of migraine attacks. Riboflavin appeared to
reduce the attack frequency by on average by two episodes (with a range of one extra episode to four
fewer episodes p=0.0001) Attack length also seemed to be significantly reduced by 3 days on
average (with a range of one day longer to nine days shorter, p=0.0001) Patients included were
between 18-65 years, with a history of migraine of at least one year’s duration and consisting of
between two and eight attacks per month, with no more than 5 days of interval headaches. The effect
of riboflavin appeared one month after beginning treatment, and appeared to be maximal at 3 months,
when the study ended. Numbers needed to treat compared to placebo were 2.3 for headache days,
2.8 for attack frequency and 3.1 or migraine index.6
An open-label trial including 23 patients found a significant reduction in headache frequency (4
attacks per month vs. 2 attacks per month, p<0.001, but the ranges overlap: from 3-5 attacks at
baseline and 2-3 after 3 months) and the use of migraine abortive drugs (7 units vs. 4.5 units,
p=0.016) after 3 months of treatment with riboflavin 400mg daily. No significant difference was found
in migraine attack duration or intensity during the study period. The majority of improvement appeared
to occur within the first three months of treatment. The usefulness of this study is limited by its openlabel design and very small participant numbers. 7
Available through NICE Evidence Search at www.evidence.nhs.uk
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Medicines Q&As
Other trials conducted are limited by their extremely small size or other methodological flaws.
Safety
Riboflavin appears to be well-tolerated. It may cause a discolouration of the urine. Diarrhoea and
polyuria have been reported in patients using doses 400mg per day.1 Facial erythema was reported in
one trial.7 There is not enough information on the use of high doses of riboflavin in pregnancy or
lactation, so it should be avoided where possible in levels above the recommended daily allowance of
1.4-1.6mg.1
Summary
Based on a limited amount of evidence, riboflavin significantly reduces the frequency of migraine
attacks. However, evidence is currently limited to small trials, some of which have major design flaws.
Further information on the effects of riboflavin on reducing migraine intensity or duration is required.
Larger, robust trials are required to conclusively establish its role in the prevention of migraine.
Riboflavin appears to be well tolerated.
UK Guidelines advise that riboflavin may be useful in preventing migraines. This recommendation
refers to self-purchase only as there is no licensed riboflavin product available in the UK, nor any cost
effectiveness data to justify its use on NHS prescription
Limitations
This Q&A looks only at the use of riboflavin in adults of 18 years and over. It does not include data for
riboflavin used in combination with other agents.
Quality Assurance
Prepared by
Hayley Johnson, Regional Drug & Therapeutics Centre, Newcastle
Date Prepared
6th November 2013
Checked by
Nancy Kane, Regional Drug & Therapeutics Centre, Newcastle
Date of check
23rd December 2013
Search strategy
Embase:
*Riboflavin AND *Migraine [limit to: (Human Age Groups Adult 18 to 64 years or 65+ years
Medline
*Riboflavin AND *Migraine disorders [limit to: Humans and (Age Group All Adult 19 plus years)]
In-house resources
Micromedex
Medicines Complete
References
1
Therapeutic Research Facility: Riboflavin monograph. Natural Medicines Comprehensive Database.
Accessed via http://naturaldatabase.therapeuticresearch.com on 6th November 2013
Available through NICE Evidence Search at www.evidence.nhs.uk
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2
National Institute of Health and Care Excellence and the National Clinical Guideline Centre. Clinical
Guidance CG150: Headaches. September 2012. Accessed via
http://guidance.nice.org.uk/CG150/Guidance/pdf/English on 6th November 2013
3 Migraine. Clinical Knowledge Summaries, Last revised August 2013. Accessed via
http://cks.nice.org.uk/ on 7th November 2013
4 Sparaco M, Feleppa M, Lipton R et al. Mitochondrial dysfunction and migraine : evidence and
hypotheses. Cephalagia 2005; 26: 361-372
5 Di Lorenzo C, Pierelli F, Coppola G et al. Mitochondrial DNA haplogroups influence the therapeutic
response to riboflavin in migraineurs. Neurology 2009; 72(18):1588-1594
6 Shoenen J, Jacquy J, and Lenarts M. Effectiveness of high dose riboflavin in migraine prophylaxis: a
randomized controlled trial. Neurology 1998; 50(2): 466-470
7 Boehnke C, Reuter U, Flach U et al. High-dose riboflavin treatment is efficacious in migraine
prophylaxis: an open study in a tertiary care centre. European Journal of neurology 2004. 11(7): 475477
Available through NICE Evidence Search at www.evidence.nhs.uk
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