Take the right magnesium supplement to relieve night cramps

A recent news article on Channel New Asia reported that “Magnesium may not ease nighttime leg cramps” [1] has prompted me to write on this topic to provide a more balanced view on the use of  magnesium supplements to relieve night cramps.

Leg cramps at night.

Inaccurate news coverage

This news article was based on the results of a recently published randomised, placebo-controlled trial conducted by a group of Israeli scientists. This was a 4-week clinical trial that found supplementation with magnesium oxide is no better than placebo (dummy pill) for the relieving of leg cramps at night (Nocturnal Leg Cramps, NLC) for older adults [2]. It is important to note that the research correctly concluded that:

Oral magnesium oxide was not superior to placebo for older adults experiencing NLC. The decrease in the mean number of NLC per week, from the screening to the treatment phase in both groups, is probably a placebo effect that may explain the wide use of magnesium for NLC.”

However, the conclusion was paraphrasing in the news article to be:

“Because magnesium wasn’t better than the placebo, this suggests that people who experience a reduction in nocturnal leg cramps after taking magnesium may just be experiencing a placebo effect, the researchers conclude”

While the original research only concluded that the effect of Oral magnesium oxide is no better than placebo in relieving night cramp, the news article has essentially generalised the results from this trial to all magnesium supplementation. This generalisation is made even with an independent researcher quoted saying, “There are differences in how well the body can use different forms of magnesium, such as citrate, aspartate, and oxide salts.” Essentially, warning against generalisation of the trial results.

This is an example of how mainstream media provides misinformation on complementary and alternative medicine (CAM). Not surprising, since a study on news media coverage of CAM found much of the information the public received about CAM was inaccurate or incomplete [3]. In here, I wish to provide a more balanced view on whether magnesium supplementation can help to relieve night cramps.

Muscle cramps and the role of magnesium

Magnesium – the fourth most abundant element in the body.

Many older people have experience of leg cramps at night. In fact, one large study showed that more that 50% of older people, both men and women, experienced such condition [4]. Leg cramps are also common during pregnancy with 33% to 50% of pregnant women experiencing leg cramps that also tend to get worse as the pregnancy progresses [4]. There are many potential causes of night cramp, among them include over exercising, standing or sitting too long, cold weather, dehydration, and  decreased amount of electrolytes which regulates muscle contractions and relaxation [5].

Magnesium is one of the important electrolytes in the body. Deficiency of magnesium has been associated with a wide spectrum of symptoms, with leg cramps being one of them. Successful treatment of muscle cramps in patients with low magnesium level through intravenous infusion and supplementation of magnesium had been reported in some early case reports [6]. As such, magnesium supplement has been widely marketed as a potential relief for night cramp.

Current evidence

Leg cramp is also common during pregnancy.

Besides the one clinical trial mentioned earlier, there had been several other clinical trials conducted on the efficacy of magnesium for muscle cramps over the years. A Cochrane systematic review published in 2012 had reviewed seven studies, with four studies in older adults (total 322 participants) and three studies in pregnant women (202 participants) [7]. The review concluded that “magnesium is unlikely to provide a meaningful benefit in reducing the frequency or severity of cramps” in older adults. Whereas in pregnant women, the result is inconclusive, since “one study found benefit in reducing both cramp frequency and cramp pain while the other two found no benefit” [7]. Similarly, another systematic review published in 2014 also reached similar conclusion [8]. Therefore, at this stage, the use of magnesium supplementation for addressing muscle cramp is not supported by evidence. However, both systematic review recognised the need for further research as all the clinical trials conducted to date had limitations [8]. Furthermore, there were a wide variety of different magnesium treatment used in the trials with type, dose and length of magnesium therapy being very different from one trial to another.

Not all magnesium supplements are the same

It has been pointed out in the news article earlier that “There are differences in how well the body can use different forms of magnesium, such as citrate, aspartate, and oxide salts.

Crystal of magnesium oxide under microscope. This is a form of magnesium salt that is hard to be absorbed by the body. [Picture source: Flickr]

Bioavailabity is the scientific type referring to how well a substance can be used by the body. Magnesium salts come in many different forms, including magnesium citrate, magnesium citrate, magnesium oxide, magnesium bisglycinates, etc. It has long been recognised that different forms of magnesium salts have different levels of bioavailability with magnesium oxide being one of the worst in bioavailability [9].  Four general categories of magnesium forms are shown in the following table [10]. In general, inorganic insoluble salts are very difficult to be absorbed by the body, whereas organic soluble complexes are more easily dissolved in the blood and used by the body.

Table 1: Categories of magnesium salts and their bioavailability
Categories Magnesium Salts Bioavailability
Inorganic insoluble salts Oxides (MgO); Carbonates (MgCO3); Hydroxides (Mg (OH)2) Very low
Inorganic soluble salts Chlorides (MgCl2); Sulphates (MgSO4) Low
Organic soluble salts Citrates (Mg-Citrate); Lactates (Mg-Lactate); Gluconates Medium
Organic soluble complexes Bisglycinates (Mg-Bisglycinate;Zink-Histidine) High

Bioavailability of magnesium salts can explain why some trials did not manage to find an effect with magnesium supplementation for muscle cramps (such as in [2] with MgO), and some other trials showed effectiveness of  magnesium supplementation in relieving muscle cramps (e.g. [11] with Mg-Citrate & Mg-Lactate; [12] with Mg-Bisglycinate).

However, since organic soluble salts and complexes are more expensive to produce compared to inorganic mineral salts. Most of the commercially available magnesium supplements available off the shelves are formulated using inorganic mineral salts. As such, most of the clinical trials to date have been conducted using these more popular forms of magnesium. Moving forward, clinical trials should be conducted with magnesium salts that has high bioavailbity to confirm the efficacy of magnesium therapy against night cramp.

Conclusion

Not all magnesium supplements are the same.

Taking magnesium supplements that are commercially available off the shelf cannot help to relieve night cramps in older people, as confirmed by many clinical trials. This may be due to the low bioavailability of inorganic mineral salts such as magnesium oxide that is used in these inexpensive magnesium supplements. Several clinical trials that used organic forms of magnesium had demonstrated efficacy in reducing symptoms of muscle cramps. Hence, not all magnesium supplements are the same. You need to take the right ones!

 

References

[1]         Magnesium may not ease nighttime leg cramps – Channel NewsAsia, Channel News Asia. (2017). http://www.channelnewsasia.com/news/health/magnesium-may-not-ease-nighttime-leg-cramps/3554920.html (accessed March 8, 2017).

[2]         N. Roguin Maor, M. Alperin, E. Shturman, H. Khairaldeen, M. Friedman, K. Karkabi, U. Milman, Effect of Magnesium Oxide Supplementation on Nocturnal Leg Cramps, JAMA Intern. Med. 31 (2017) 7–19. doi:10.1001/jamainternmed.2016.9261.

[3]         B. Bonevski, A. Wilson, D.A. Henry, An analysis of news media coverage of complementary and alternative medicine., PLoS One. 3 (2008) e2406. doi:10.1371/journal.pone.0002406.

[4]         R.S. Monderer, W.P. Wu, M.J. Thorpy, Nocturnal Leg Cramps, Curr. Neurol. Neurosci. Rep. 10 (2010) 53–59. doi:10.1007/s11910-009-0079-5.

[5]         Nighttime Leg Cramps: What Causes Muscle Spasms and Late-Night Leg Cramps, (n.d.). http://www.webmd.com/sleep-disorders/tc/nighttime-leg-cramps-topic-overview#1 (accessed March 8, 2017).

[6]         D.L. Bilbey, V.M. Prabhakaran, Muscle cramps and magnesium deficiency: case reports., Can. Fam. Physician. 42 (1996) 1348–51. http://www.ncbi.nlm.nih.gov/pubmed/8754704 (accessed March 8, 2017).

[7]         S.R. Garrison, G.M. Allan, R.K. Sekhon, V.M. Musini, K.M. Khan, Magnesium for skeletal muscle cramps, in: S.R. Garrison (Ed.), Cochrane Database Syst. Rev., John Wiley & Sons, Ltd, Chichester, UK, 2012: p. CD009402. doi:10.1002/14651858.CD009402.pub2.

[8]         P. Sebo, B. Cerutti, D.M. Haller, Effect of magnesium therapy on nocturnal leg cramps: a systematic review of randomized controlled trials with meta-analysis using simulations, Fam. Pract. 31 (2014) 7–19. doi:10.1093/fampra/cmt065.

[9]         M. Firoz, M. Graber, Bioavailability of US commercial magnesium preparations., Magnes. Res. 14 (2001) 257–62. http://www.ncbi.nlm.nih.gov/pubmed/11794633 (accessed March 8, 2017).

[10]      S. Siebrecht, Magnesium Bisglycinate as safe form for mineral supplementation in human nutrition, Int. J. Orthomol. Relat. Med. 144 (2013). http://www.omundernaehrung.com/media/documents/en/Siebrecht_Dr_Stefan_Magnesium_bisglycinate.pdf.

[11]      L.O. Dahle, G. Berg, M. Hammar, M. Hurtig, L. Larsson, The effect of oral magnesium substitution on pregnancy-induced leg cramps., Am. J. Obstet. Gynecol. 173 (1995) 175–80. http://www.ncbi.nlm.nih.gov/pubmed/7631676 (accessed March 8, 2017).

[12]      C. Supakatisant, V. Phupong, Oral magnesium for relief in pregnancy-induced leg cramps: a randomised controlled trial, Matern. Child Nutr. 11 (2015) 139–145. doi:10.1111/j.1740-8709.2012.00440.x.

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