• Expert opinion
  • 2015

Riboflavin (Vitamin B2) and Migraine: the Bridge over Troubled Mitochondria

Published on

01 July 2015

Bruno Colombo, PhD, University of Vita-Salute, Milan, Italy

Riboflavin, or vitamin B2, is an important micronutrients found in milk, eggs, organ meats, malted barley, leafy vegetables and particularly, yeast. 

Migraine is a common, painful and ultimately disabling condition. It is characterized by recurrent, moderate to severe headaches. Migraine symptoms vary widely between individuals. Attacks may last from four to 72 hours with highly variable frequency. Other clinical symptoms such as blurred vision, vertigo, or hallucination may accompany the headache attacks. 54% of migraine patients report that migraines have a major adverse effect on both their home and work lives.

The role of dysfunctional mitochondria as a causative agent of migraine is now well established. Mitochondrial dysfunction (abnormality of oxidative metabolism leads to decreased production of adenosine tri-phosphate (ATP) and energy metabolism. This in turn leads to an imbalance of calcium ions leading to an increase of neuronal excitability.  This causes a disturbance of neuronal information processing and thus a decreased migraine threshold and the triggering of cortical spreading depression. Healthy mitochondria also help provide homeostasis of calcium ions in normal cells. An imbalance of calcium ions leads to vaso-constriction and pain sensitisation.

Riboflavin is a precursor to the coenzymes, Flavin mono nucleotide (FMN) and flavin adenosine-dinucleotide (FAD), both of which are critical for electron transport within the mitochondria. Riboflavin is a vital component of mitochondrial energy production. It is necessary for the normal production of ATP which leads to membrane stability and ensures the smooth running of energy-related cellular functions. Riboflavin appears to be able to replete mitochondrial energy stores in migraine sufferers, enhancing both mitochondrial function and efficiency.

In 2004, a clinical study by Boehnke et al. showed the effectiveness of a high-dose riboflavin intervention in mitigating the effects of severe migraine. Patients in this trial received 400 mg/day of riboflavin for six months.  The average headache frequency reduced from four days a month to two days a month and there was a 35% reduction in the incidence of drugs taken by the patients for pain control. However, the maximum amount of riboflavin that can be absorbed from a single dose is just 27 mg. In addition, the half-life riboflavin is only around one hour.

Professor Colombo believes migraine is associated with structural brain damage. He believes lesions found in the white matter of the brain have been caused by vascular blood clots.

The American Academy of Neurology guidelines concludes that riboflavin is probably effective in the prophylaxis of migraine in adults based on level B evidence.

Professor Colombo concludes in his recent article: “Riboflavin could be considered for future combination in migraine treatments, so-called pharmacological synergy, considering the abundant scientific evidence supporting the theory of mitochondrial disturbance enhancing migraine disorder”.


  1. Colombo B., Saraceno L & Corni G, Riboflavin and migraine: the bridge over troubled mitochondria, Neurol Sci 2014; 35 Suppl 1:141–4.
  2. Shaik MM and Gan SH, Vitamin supplementation as possible prophylactic treatment against migraine with aura and menstrual migraine, Biomed Research International 2015, Article ID 46 9529.
  3. Stuart S and Griffiths LR, A possible role for mitochondria dysfunction in migraine, Molecular Genetics and Genomics 2012, 287 (11-12):837–844.
  4. Boehnke C. Reuter 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):475–477.
  5. Colombo B, Dalla Libera D and Comi G, Brain white matter lesions in migraine: what’s the meaning?, Neurol. Sci. 2011:32Suppl 1:S37–40.
  6. Holland S, Silberstein SD, Freitag F et al., Evidence-based guideline update: NSAIDS and other complementary treatments for episodic migraine prevention in adults: report of the Quality Standards Subcommittee of the American Academy of Neurology and the American Headache Society 2012.  Neurology 78:1346–1353.

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