RLS and PLMD: Part III

Vitamin and mineral deficiencies have been implicated in RLS or PLMD with the most solid research conducted on the element of iron. Very recent research is showing a connection between low Vitamin D, and there has always been some concern about the impact of low magnesium levels.

Iron storage as measured by a lab variable known as serum ferritin is the standard technique for assessing whether or not low iron is likely to affect RLS/PLMD. Individuals with values less than 50 ng/ml often are at risk for both symptoms. One of the more interesting ways in which this relationship was discovered occurred when acute leg movement problems developed in those who had rapid blood loss, e.g. someone in a car accident. Following blood transfusions, the limb movement symptoms resolved. In one recent study, low ferritin patients were randomly assigned to iron treatment or a dopamine drug, Mirapex as described in Part I, and their results were of equal benefit, so clearly iron is a very big deal when considering ways to treat RLS/PLMD.(1)

Iron deficiency in general is associated with many problems in brain development in children, and the dopamine pathways in the brain seem to be especially susceptible to low iron levels . Remarkably, the lower the serum ferritin value, the less effective are the medications prescribed for RLS/PLMD. Also, just because the ferritin is low does not mean one also suffers from overall anemia or low blood counts. Most patients seeking treatment at sleep centers who show low ferritin do not show anemia.

Unfortunately, iron supplementation is not a straightforward matter. First, you absolutely must clarify that the serum ferritin level is below 50 ng/ml. Do not just start iron pills because you want to experiment. Next, if ferritin is low, discuss the use of iron supplements with your primary physician. Most doctors do not know about this connection, so they may be skeptical about recommending iron supplements if you suffer from other medical conditions. For example, patients who suffer from thickened blood volumes with conditions like polycythemia or those with iron storage conditions such as hemochromatosis can almost never use iron supplements. So, the biggest reason to work with your doctor is to insure your safety.

When starting iron supplements, there are two common and distressing side-effects: indigestion or constipation or both. Many people stop iron supplements within the first week because of these gastric symptoms, so you may need to explore different options to reduce or prevent these symptoms. There are liquid iron supplements that are more gentle on the stomach. You can find liquid iron in drugstores or vitamin stores, but they are also more expensive. Liquid iron is also more dangerous, so it is virtually axiomatic to never use liquid iron if you have children living in your home or kids who frequent your home. Ingestion of excess iron in a child may prove fatal.

Prescription iron pills are needed for someone who has difficulty absorbing iron. In some cases, you may need to see a hematologist to test why your ferritin level is low or why iron supplements do not raise the levels. In rare cases, a hematologist may put you on a program of iron infusions given intravenously, and this therapy may prove highly successful for some patients. Then again, it is important to know that some low levels of iron actually indicate covert blood loss, and colon cancer has been detected in patients who originally presented with RLS, whose ferritin level was low, which eventually led to a colonoscopy and the discovery of the cancer. (2)

Magnesium is another mineral that shows a small amount of evidence in the treatment of leg jerks. (3) Many alternative medicine publications or practitioners exclaim the value of magnesium in solving RLS or PLMD conditions, and yet actual confirmatory studies are missing from the scientific literature. In fact, when we have worked with patients making positive claims about their magnesium use, virtually all these individuals showed persistent leg movements when they were re-tested in the sleep lab. This finding does not preclude the possibility that magnesium was helpful to them or might work for you, but we would like to see more research in this area, albeit one other study with a very interesting result demonstrated improved RLS in a pregnant woman who received intravenous magnesium. (4) 

Turning to vitamins, folate and B12 deficiencies have been implicated in RLS/PLMD symptoms, but we rarely see such cases in a sleep clinic environment. One vitamin receiving recent attention is Vitamin D, where reports of deficiency are proving much more common than previously thought. Several studies have been published in just the past few years on Vitamin D and limb movement symptoms.

One study described the beneficial connection of Vitamin D with increased levels of dopamine in the brain, and in their comparison of two groups, the sample with RLS had both lower Vitamin D levels and worse sleep quality than a group with normal Vitamin D levels. (5) In another study, a small sample with RLS and low Vitamin D levels were treated with high dose or intramuscular injections of Vitamin D, and raising levels into the normal range clearly improved RLS symptoms. (6) Last, two additional studies showed the same effects of low Vitamin D levels in RLS patients, and again noted the likely connection between Vitamin D function and preserving dopamine, the neurotransmitter described in Parts I and II, which has very close connections to the problem of RLS/PLMD. (7,8)

 Summing up, all these vitamin and mineral interactions are worth exploring if you suffer RLS/PLMD symptoms. By addressing pertinent deficiencies, you may no longer need medications to treat RLS/PLMD, or your medications may prove more effective in resolving limb movement symptoms.



(1) Lee CS1, Lee SD, Kang SH, Park HY, Yoon IY. Comparison of the efficacies of oral iron and pramipexole for the treatment of restless legs syndrome patients with low serum ferritin. Eur J Neurol. 2014 Feb;21(2):260-6. doi: 10.1111/ene.12286. Epub 2013 Nov 23.

(2) Morcos Z. Restless legs syndrome, iron deficiency and colon cancer. J Clin Sleep Med. 2005;1(4):433.

(3) Hornyak M1, Voderholzer U, Hohagen F, Berger M, Riemann D. Magnesium therapy for periodic leg movements-related insomnia and restless legs syndrome: an open pilot study. Sleep. 1998 Aug 1;21(5):501-5.

(4) Bartell S1, Zallek S. Intravenous magnesium sulfate may relieve restless legs syndrome in pregnancy. J Clin Sleep Med. 2006 Apr 15;2(2):187-8.

(5) Çakır T, Doğan G, Subaşı V, Filiz MB, Ülker N, Doğan ŞK, Toraman NF. An evaluation of sleep quality and the prevalence of restless leg syndrome in vitamin D deficiency. Acta Neurol Belg. 2015 Apr 23. [Epub ahead of print] 

(6) Wali S, Shukr A, Boudal A, Alsaiari A, Krayem A. The effect of vitamin D supplements on the severity of restless legs syndrome. Sleep Breath. 2015 May;19(2):579-83. doi: 10.1007/s11325-014-1049-y. Epub 2014 Aug 23.

(7) Oran M, Unsal C, Albayrak Y, Tulubas F, Oguz K, Avci O, Turgut N, Alp R, Gurel A. Possible association between vitamin D deficiency and restless legs syndrome. Neuropsychiatr Dis Treat. 2014 May 21;10:953-8. doi: 10.2147/NDT.S63599. eCollection 2014.


(8) Balaban H, Yıldız ÖK, Çil G, Şentürk İA, Erselcan T, Bolayır E, Topaktaş S. Serum 25-hydroxyvitamin D levels in restless legs syndrome patients.   Sleep Med. 2012 Aug;13(7):953-7. doi: 10.1016/j.sleep.2012.04.009. Epub 2012 Jun 15.


Barry Krakow MD


Dr Krakow’s 27 years of sleep research have focused on the complex relationship between physiological and psychological sleep disorders. Dr Krakow currently operates private sleep medical center, Maimonides Sleep Arts & Sciences, Ltd., and serves as Classic SleepCare’s paid Medical Director.

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