Nutraceuticals for Concussion – Part 2: Riboflavin

Concussions are highly challenging to treat and there are very few evidence-based interventions that have been shown to consistently shorten recovery times. It is important for the sports medicine practitioner to have as many tools in their toolbox as possible and to have a solid understanding when these tools may be effective. I have seen many nutritional supplements proposed for concussions, and I believe that they have a potential role in concussion management. I decided to conduct a review of the current literature exploring the evidence and logic behind the more common supplements used. This article will be the fourth in this series, “Nutraceuticals for Concussion…”

This was written in 2016. I will try to update this post if new information comes out since this was written, but please be aware that this a information may become outdated before I am able to do so.

Again…the purposes of my blog posts are to facilitate thought and discussion or perhaps even motivate research to answer the remaining questions on this topic. That is all. If you think that you have a concussion, please go see a concussion specialist.

Lets get to know Riboflavin…

Riboflavin (Vitamin B2) is a component of two co-enzymes, flavin adenine dinucleotide (FAD) and flavin mononucleotide (FMN). FAD and FMN are cofactors in the electron transport chain of the Krebs cycle, making riboflavin crucial for optimal mitochondrial function, and therefore cellular energy production and glucose metabolism [1, 2]. It also plays an important role in cellular membrane stabilization which is required for overall cellular health [3].

vitamin-B2-RiboflavinETC
Image Link: http://news4medico.com/electron-transport-chain/

Dysfunctional ATP production and glucose metabolism are are all central to the pathophysiology involved in concussions as well as migraine headaches, making riboflavin a potential tool for concussion management.

I was unable to identify a single study directly examining riboflavin supplementation and concussion recovery. There are, however, multiple studies supporting riboflavin supplementation for headaches, in particular migraines. Headaches are one of the most common symptoms experienced following a concussion, and energy deficits appear to be involved in the pathophysiology for both concussions and migraines making the migraine headache literature relevant to our investigation.

Numerous studies have implicated mitochondrial insufficiency in the pathophysiology of migraine headaches [4] making riboflavin an attractive nutraceutical for migraine prevention. There have been several studies evaluating its usefulness for migraines. Rather than deep-diving into each prospective study, I will say that the results have been mixed though the general consensus is more positive than negative for adults.

There are three studies demonstrating a positive effect for migraine prophylaxis in adults [5, 6, 7]. One study showed that there was a much greater benefit in individuals with specific genotypes for Complex 1 in the electron transport chain (see image above) making their mitochondria less efficient at baseline [6]. This demonstrates how genetic differences can account for certain treatments working in some people and not in others.

There are two studies examining the effectiveness of B2 for migraine prophylaxis in the pediatric population, and neither one was able to demonstrate a significant improvement [8, 9].

The American Academy of Neurology (AAN) Guidelines rate oral Riboflavin supplementation for migraine prevention/reduction as having a level B evidence for its effectiveness  [10]. In other words it is “probably effective” for adults.

The dose recommended for adults is 400mg daily, though the half life is only 1 hour, so breaking up the dose to twice daily or even three times daily maybe optimal [1]. The side effect profile based on these studies appears to be rather benign with polyuria, diarrhea, and bright yellow urine being noted. It is logical to start low and slowly titrate up while monitoring for gastrointestinal side-effects.

One recent systematic review on the topic concluded that they were unable to recommend its use for migraine prophylaxis or treatment in pediatric patients due to lack of evidence [11].

In my experience, many concussion patients suffer from headaches with migrainous characteristics. This is especially true in those who were experiencing migraines before the concussion. Because of the favorable side-effect profile, and the evidence indicating potential usefulness for migraines, Riboflavin is certainly another tool in the toolbox as an intervention for post-concussion in adults. Less so in the pediatric population.

I believe that the safest way to increase riboflavin levels is through dietary interventions. Foods high in riboflavin include…Beef liver, lamb, almonds, eggs, mushrooms, and seaweed. Oily fish such as mackerel, wild caught salmon, trout and sardines are high in riboflavin as well as omega-3 fatty acids, making them an especially attractive food choice when recovering from a concussion.

 

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References:

 

  1. Tepper, S.J., Nutraceutical and Other Modalities for the Treatment of Headache. CONTINUUM: Lifelong Learning in Neurology, 2015. 21(4, Headache): p. 1018-1031.
  2. Sun‐Edelstein, C. and A. Mauskop, Alternative headache treatments: nutraceuticals, behavioral and physical treatments. Headache: The Journal of Head and Face Pain, 2011. 51(3): p. 469-483.
  3. Taylor, F.R., Nutraceuticals and headache: the biological basis. Headache: The Journal of Head and Face Pain, 2011. 51(3): p. 484-501.
  4. Mauskop, A., et al., Intravenous magnesium sulfate rapidly alleviates headaches of various types. Headache: The Journal of Head and Face Pain, 1996. 36(3): p. 154-160.
  5. Schoenen, J., J. Jacquy, and M. Lenaerts, Effectiveness of high‐dose riboflavin in migraine prophylaxis A randomized controlled trial. Neurology, 1998. 50(2): p. 466-470.
  6. Di Lorenzo, C., et al., Mitochondrial DNA haplogroups influence the therapeutic response to riboflavin in migraineurs. Neurology, 2009. 72(18): p. 1588-1594.
  7. Maizels, M., A. Blumenfeld, and R. Burchette, A combination of riboflavin, magnesium, and feverfew for migraine prophylaxis: a randomized trial. Headache: The Journal of Head and Face Pain, 2004. 44(9): p. 885-890.
  8. Bruijn, J., et al., Medium-dose riboflavin as a prophylactic agent in children with migraine: a preliminary placebo-controlled, randomised, double-blind, cross-over trial. Cephalalgia, 2010. 30(12): p. 1426-1434.
  9. MacLennan, S.C., et al., High-Dose ribof lavin for migraine prophylaxis in children: a double-blind, randomized, placebo-controlled trial. Journal of child neurology, 2008. 23(11): p. 1300-1304.
  10. Holland, S., 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. Neurology, 2012. 78(17): p. 1346-1353.
  11. Pringsheim, T., et al., Canadian Headache Society guideline for migraine prophylaxis. Can J Neurol Sci, 2012. 39(2 Suppl 2): p. S1-59.

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