Nutraceuticals for Concussion – Part I: Magnesium

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this post if new information comes out since this was written, but please be aware that this a information may become outdated before I am able to do so.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 Magnesium…

Magnesium (Mg2+) is a vital and underappreciated element in human physiology and is the second most abundant cation in our intracellular fluid. In particular, Mg2+ is needed for adenine triphosphate (ATP) production and glucose metabolism [1], our primary source of life sustaining energy. It also inhibits NMDA glutamate receptors in our nervous systems, which are involved in neurological excitotoxicity (and resultant intracellular calcium release) when over activated.  Excitotoxicity occurs following traumatic brain injuries and severe concussions [2]. Mg2+ is also involved in vascular tone variation via its interaction with NMDA receptors [3,4,5,6,7]. Low magnesium levels (hypomagnesemia) appears to be associated with increased substance P release (an important mediator causing headache pain) [8, 9].

Excitotoxicity, aberrant glucose metabolism, decreased ATP production, and decreased cerebral blood flow [31, 32, 33] are all central to the pathophysiology involved in concussions making magnesium a potential tool for concussion management.

I was unable to identify a single study directly examining magnesium supplementation and concussion recovery. There are multiple studies looking at using magnesium for headaches, in particular migraines. Headaches are one of the most common symptoms experienced following a concussion, making the headache literature relevant to investigation for concussions. An association between low magnesium levels and anxiety/depressive symptoms has also been examined in the literature, and these are common concussion-related symptoms as well.

About 15% of the population has low magnesium levels [10] and this percentage is significantly increased in people who suffer from migraine headaches [11-13]. Rather than delving into each prospective study, I will say that the results have been mixed though the general consensus is more positive than negative.

Some studies seem to support the effectiveness of magnesium supplementation…

Peikert et al.  (migraine prevention) [14]
– Mauskop et al. (acute Migraine treatment) [15]
Facchinetti F. et al. (migraine prevention) [16]
Koseoglu et al (migraine prevention) [17]
Demirkaya S et al (acute Migraine treatment) [18]
Bigal et al (acute Migraine treatment) [19]

Other studies have not been able to show a significant difference.
Choi H et al (acute Migraine treatment) [20]
Pfaffenrath et al (migraine prevention) [21]
Wang et al (migraine prevention) [22]
Cete Y et al (acute Migraine treatment) [23]
Corbo J et al (acute Migraine treatment) [24]

The American Academy of Neurology (AAN) Guidelines rate oral Mg+ supplementation for migraine prevention/reduction as having a level B evidence for its effectiveness. In other words, it is “probably effective” per the AAN.

Some important points to pull-out of the above listed studies…

  1. It appears that magnesium is more effective in headache reduction/treatment in people with low systemic magnesium levels.  This can be most accurately measured by determining ionized magnesium levels in the blood (rather than total Mg2+ levels).
  2. Magnesium also appears to be most effective in people who experience migraines with aura.  This makes sense because Aura appears to be associated with low serum levels of magnesium.
  3. There is some evidence that up to 1 month of supplementation is required to see an effect for prevention/reduction of headaches.

Low magnesium levels have also been implemented in anxiety and depressive symptoms and supplementation has been studied with generally positive, but mixed results. It has also been demonstrated the any significant stressor (physical or psychological) is associated with decreased magnesium levels [25, 26, 27, 28, 29, 30].  It has even been suggested that magnesium levels play a role in the efficacy of antidepressant medications, though we have a long way to go to flesh that out. It is important to note, however, that anxiety, irritability and depressive symptoms are very common symptoms following a concussion.

natural calm

The configurations that have been used in the literature and seem relatively tolerable include magnesium glycinate, magnesium citrate, and/or magnesium chloride. Dose recommendations generally have ranged from 400 to 600mg daily.  We have a long way to go before dosing and specific configurations can be confidently recommended in terms of effectiveness. It is logical to start low and slowly titrate up while monitoring for gastrointestinal side-effects. Side-effects include diarrhea, nausea and other gastrointestinal problems. Flushing is also reported in the literature.

*Very Important*…  Because the kidneys are the primary regulators of our levels, Kidney Disease is a major contraindication to supplementing Mg2+ without very close physician supervision as it can cause arrhythmias, cardiac arrest, hypotension, altered mental status, and death!

It is also important to remember that the safest way to increase magnesium levels is through dietary interventions. Foods high in magnesium include your typical green leafy vegetables such as chard, spinach, broccoli, and collards. A lot of legumes have high magnesium levels including black eyed peas and lima beans. Seeds and nuts such as almonds and pumpkin seeds are loaded in magnesium. Some seafoods have decent levels as well, including salmon and sardines (two foods one should be encouraged to eat when suffering from a concussion for other reasons).

Some take home points…

  1. There is a logical mechanism for increasing Mg2+ in concussion patients
  2. This intervention does not appear to have been examined for concussion.
  3. It has been examined for migraine headaches and appears to have higher efficacy in those who have low magnesium levels and those who experience aura.
  4. There is a small body of evidence that low magnesium levels are associated with increased psychiatric issues including depression and anxiety, both of which are common concussion-related symptoms.
  5. Many more studies are needed

Thanks for reading!

References:

  1. Daniel, O. and A. Mauskop, Nutraceuticals in Acute and Prophylactic Treatment of Migraine. Current Treatment Options in Neurology, 2016. 18(4): p. 1-8.
  2. Tepper, S.J., Nutraceutical and Other Modalities for the Treatment of Headache. CONTINUUM: Lifelong Learning in Neurology, 2015. 21(4, Headache): p. 1018-1031.
  3. 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.
  4. Altura, B. and B. Altura, The role of magnesium in etiology of strokes and cerebrovasospasm. Magnesium, 1982. 1(277-291): p. 15.
  5. Altura, B.T. and B.M. Altura, Withdrawal of magnesium causes vasospasm while elevated magnesium produces relaxation of tone in cerebral arteries. Neuroscience letters, 1980. 20(3): p. 323-327.
  6. Turlapaty, P. and B.M. Altura, Magnesium deficiency produces spasms of coronary arteries: relationship to etiology of sudden death ischemic heart disease. Science, 1980. 208(4440): p. 198-200.
  7. Altura, B., et al., Mg2+-Ca2+ interaction in contractility of vascular smooth muscle: Mg2+ versus organic calcium channel blockers on myogenic tone and agonist-induced responsiveness of blood vessels. Canadian journal of physiology and pharmacology, 1987. 65(4): p. 729-745.
  8. Weglicki, W.B. and T.M. Phillips, Pathobiology of magnesium deficiency: a cytokine/neurogenic inflammation hypothesis. American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, 1992. 263(3): p. R734-R737.
  9. Moskowitz, M.A., The neurobiology of vascular head pain. Annals of neurology, 1984. 16(2): p. 157-168.
  10. Storer, R. and P. Goadsby. N-Methyl-D-Aspartate receptor channel complex blockers including memantine and magnesium inhibit nociceptive traffic in the trigeminocervical complex of the rat. in Cephalalgia. 2009. SAGE PUBLICATIONS LTD 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND.
  11. Welch, K. and N.M. Ramadan, Mitochondria, magnesium and migraine. Journal of the neurological sciences, 1995. 134(1): p. 9-14.
  12. Gallai, V., et al., Serum and salivary magnesium levels in migraine. Results in a group of juvenile patients. Headache: The Journal of Head and Face Pain, 1992. 32(3): p. 132-135.
  13. Mauskop, A., et al., Deficiency in serum ionized magnesium but not total magnesium in patients with migraines. Possible role of ICa2+/IMg2+ ratio. Headache: The Journal of Head and Face Pain, 1993. 33(3): p. 135-138.
  14. Peikert, A., C. Wilimzig, and R. Köhne-Volland, Prophylaxis of migraine with oral magnesium: results from a prospective, multi-center, placebo-controlled and double-blind randomized study. Cephalalgia, 1996. 16(4): p. 257-263.
  15. 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.
  16. Facchinetti, F., et al., Magnesium prophylaxis of menstrual migraine: effects on intracellular magnesium. Headache: The Journal of Head and Face Pain, 1991. 31(5): p. 298-301.
  17. Köseoglu, E., et al., The effects of magnesium prophylaxis in migraine without aura. Magnesium Research, 2008. 21(2): p. 101-108.
  18. Demirkaya, Ş., et al., Efficacy of intravenous magnesium sulfate in the treatment of acute migraine attacks. Headache: The Journal of Head and Face Pain, 2001. 41(2): p. 171-177.
  19. Bigal, M., et al., Intravenous magnesium sulphate in the acute treatment of migraine without aura and migraine with aura. A randomized, double-blind, placebo-controlled study. Cephalalgia, 2002. 22(5): p. 345-353.
  20. Choi, H. and N. Parmar, The use of intravenous magnesium sulphate for acute migraine: meta-analysis of randomized controlled trials. European Journal of Emergency Medicine, 2014. 21(1): p. 2-9.
  21. Pfaffenrath, V., et al., Magnesium in the prophylaxis of migraine—a double-blind, placebo-controlled study. Cephalalgia, 1996. 16(6): p. 436-440.
  22. Wang, F., et al., Oral magnesium oxide prophylaxis of frequent migrainous headache in children: a randomized, double‐blind, placebo‐controlled trial. Headache: The Journal of Head and Face Pain, 2003. 43(6): p. 601-610.
  23. Cete, Y., et al., A randomized prospective placebo-controlled study of intravenous magnesium sulphate vs. metoclopramide in the management of acute migraine attacks in the Emergency Department. Cephalalgia, 2005. 25(3): p. 199-204.
  24. Corbo, J., et al., Randomized clinical trial of intravenous magnesium sulfate as an adjunctive medication for emergency department treatment of migraine headache. Annals of emergency medicine, 2001. 38(6): p. 621-627.
  25. Sartori, S., et al., Magnesium deficiency induces anxiety and HPA axis dysregulation: modulation by therapeutic drug treatment. Neuropharmacology, 2012. 62(1): p. 304-312.
  26. De Souza, M.C., et al., A synergistic effect of a daily supplement for 1 month of 200 mg magnesium plus 50 mg vitamin B6 for the relief of anxiety-related premenstrual symptoms: a randomized, double-blind, crossover study. Journal of women’s health & gender-based medicine, 2000. 9(2): p. 131-139.
  27. Singewald, N., et al., Magnesium-deficient diet alters depression-and anxiety-related behavior in mice—influence of desipramine and Hypericum perforatum extract. Neuropharmacology, 2004. 47(8): p. 1189-1197.
  28. Jacka, F.N., et al., Association between magnesium intake and depression and anxiety in community-dwelling adults: the Hordaland Health Study. Australian and New Zealand Journal of Psychiatry, 2009. 43(1): p. 45-52.
  29. Fromm, L., et al., Magnesium attenuates post-traumatic depression/anxiety following diffuse traumatic brain injury in rats. Journal of the American College of Nutrition, 2004. 23(5): p. 529S-533S.
  30. Eby, G.A. and K.L. Eby, Rapid recovery from major depression using magnesium treatment. Medical hypotheses, 2006. 67(2): p. 362-370.
  31. Maugans, Todd A., et al. “Pediatric sports-related concussion produces cerebral blood flow alterations.” Pediatrics 129.1 (2012): 28-37.
  32. Meier, Timothy B., et al. “Recovery of cerebral blood flow following sports-related concussion.” JAMA neurology 72.5 (2015): 530-538.
  33. Wang, Yang, et al. “Cerebral blood flow alterations in acute sport-related concussion.” Journal of neurotrauma (2015).

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