Magnesium Oxide for Nocturnal Leg Cramps

Is there a role for magnesium supplementation? After all, magnesium is important for many bodily functions. It is required for skeletal and smooth muscle relaxation. It is involved in many biochemical pathways including enzyme and protein synthesis. It is also thought that muscle cramp may be a sign of magnesium deficiency.  There have been many reported claims of the benefits with magnesium supplementation. But the evidence has been conflicting thus far.

A recently published study from JAMA Internal Medicine aimed to look at this question more closely. This study was a randomized clinical trial designed to determine if magnesium oxide supplement would be better than placebo for nocturnal leg cramp prophylaxis.

Below are the highlights of the study:

  • Potential subjects underwent a 2-week screening period. Those who met the inclusion criteria were randomized to receive either Magnesium oxide (865mg – providing 520mg elemental magnesium) or placebo once daily in the evening for the next 4 weeks.
  • Inclusion Criteria:
    • Community-dwelling individuals
    • Age older than 21 years
    • 4 or more documented episodes of nocturnal leg cramps during the 2 week screening phase
    • Insurance with Clalit Health Services
  • Exclusion Criteria:
    • Pregnancy
    • Current Treatment with Quinine
    • Concurrent Intake of Magnesium supplement
    • Renal Failure
    • Major neurological diseases (e.g. amyotrophic lateral sclerosis, multiple sclerosis, paraplegia, or quadriplegia)
  • The primary outcome was the difference in the mean number of nocturnal leg cramp per week between the screening phase (2 weeks) and the treatment phase (4 weeks)


  • Main Results:
    • Mean Number of Nocturnal Leg Cramps per Week:
      • Magnesium Oxide Group
        • Screening Phase = 7.84
        • Treatment Phase 4.44
        • Change -3.41
      • Placebo Group
        • Screening Phase = 8.51
        • Treatment Phase = 5.48
        • Change – 3.03
      • P value for change = 0.67 (in an intention-to-treat analysis)


  • Given the p-value was 0.67 in an intention-to-treat analysis, there was no statistically significant difference in the primary outcome. As such, the authors have concluded that oral magnesium oxide was not superior to placebo for treatment of nocturnal leg cramps.
  • The authors have also acknowledged few important limitations of the study including:
    • a grossly small sample size (the study initially estimated 110 participants from both groups to achieve 80% power to detect a treatment difference),
    • short duration (4 weeks),
    • self selection which may introduce selection bias as well as
    • self reporting of outcomes:

Here are my thoughts:

  • If nocturnal leg cramp is due to magnesium deficiency, why wasn’t there some attempt to look  at the baseline magnesium level before the study began.  This was also explained in the article – it was thought that magnesium serum level correlates poorly with the intracellular content of magnesium. Yet if we cannot quantify the extent of magnesium deficiency of the subjects, how can we possibly speak to anything to the effect of magnesium supplementation?
  • The study duration was very short and it seems unfair to compare the average results from the 2-week of screening phase to the average results of the 4-week treatment phase.
  • I am not a big fan of any supplementation. I do believe magnesium deficiency may play a role here in nocturnal leg cramps but oral supplement is not the most effective way to rectify the deficiency.
  • What about Epsom salt bath? Or eating magnesium-rich foods? I would be interested to see how the results pan out with either of these interventions.
  • Here are top foods that are high in magnesium:
    • Dark Leafy Greens (Raw spinach, Swiss chard, Kale)
    • Nuts and Seeds (Sesame seeds, Brazil nuts, Almonds)
    • Fish (Mackerel)
    • Beans and Lentils
    • Whole Grains (Brown rice, Quinoa, Millet)
    • Avocados
    • Low Fat Dairy (Yogurt)
    • Banana
    • Dry Fruits (Fig, Prune, Apricot, Date, Raisin)
    • Dark Chocolate
  • Unfortunately, the results of this study have not provided us with any new insight. We are still pretty confused if magnesium is helpful or not. I would rather invest in a healthy diet rich in magnesium (as well as other important minerals and vitamins), than to purchase a bottle of magnesium supplements that may cause diarrhea and other unwanted side effects.

Thank you for reading my post!


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My name is Cynthia Leung and I am a practicing pharmacist in Kingston Ontario, Canada. This blog is for me to share my ideas, opinions and perspectives on how medications are used in our health care system. Note that these posts are my own opinions and do not represent the opinions of my current or former employers and / or organizations that I may belong to. Any possible case scenarios described in my posts would be modified to maintain patient confidentiality. This blog is not a platform for professional advise for patients or health care providers and the content is not meant to support any clinical decisions or replace professional opinions. Also the images are either taken or created by the author, or adapted with permissions. I hope you will enjoy reading my posts!

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