Restless Legs Syndrome - 4 Less-Known Causes | Chris Kresser

4 Little-Known Causes of Restless Legs Syndrome

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Restless legs syndrome is a seemingly simple condition, but the cause is often difficult to pinpoint. Find out four potential contributing factors and how to address them.

dietary causes of rls
Can certain dietary choices cause RLS? Stockbyte/Stockbyte/Thinkstock

Few things are more frustrating than lying in bed at night exhausted, but not being able to fall asleep because of an uncontrollable urge to move your legs. This phenomenon, known as restless legs syndrome (RLS), affects between 4% and 29% of adults in Western populations, and is a major contributor to sleep loss. (1, 2)

Pinpointing the cause of RLS has been an active research topic for years, but the condition is still not fully understood. The symptoms have been convincingly linked to impaired dopamine function in the brain, but the cause of this dysfunction is still being explored.

In this article, I’ll review four factors that could contribute to RLS, as well as steps you can take for improving your symptoms.

1. Systemic Inflammation and Immune Dysregulation

Restless legs syndrome has been associated with numerous conditions involving systemic inflammation and immune dysregulation. (3) One review paper published in 2012 investigated health conditions that were reported to cause or exacerbate RLS symptoms, and found that 95% of the 38 different health conditions that were strongly associated with RLS have an inflammation or immune component. (4) These conditions include Parkinson’s disease, multiple sclerosis, ADHD, Alzheimer’s disease, Celiac disease, Crohn’s disease, rheumatoid arthritis, sleep apnea, diabetes, and depression.

As further evidence, an elevated blood level of C-reactive protein (a marker of systemic inflammation) has been associated with increased RLS severity. (5) A small crossover trial found that a hydrocortisone infusion, which reduces systemic inflammation, reduced RLS symptoms. (6)

Researchers have proposed three potential mechanisms to explain the association between RLS and inflammatory or autoimmune states: direct autoimmune attack on the nervous system; genetic factors that could predispose an individual to RLS and be triggered by inflammation or autoimmunity; and iron deficiency caused by inflammation, which I’ll talk more about below.

 

What to do: If your RLS is a symptom of underlying systemic inflammation or immune dysregulation, the goal should be to find and treat the root cause. As I’ve mentioned many times in the past, gut infections are often the culprit—even if you don’t have noticeable digestive symptoms—so get your gut tested.

If you already have a diagnosed inflammatory or immune condition such as those I mentioned above, the best first step you can take is to adopt a “low-inflammatory” diet and lifestyle. This means eating a nutrient-rich, low-toxin diet based on whole foods; getting enough sleep every night; prioritizing stress management; and incorporating regular movement into your day.

You can also check out the bonus chapter about autoimmune disease from my book, as well as explore other information on my site about reversing autoimmune disease, the autoimmune protocol, the role of the microbiome, and alternative therapies such as LDN.

Do you have restless legs syndrome? Find out what might be causing it, and what to do.

2. Small Intestinal Bacterial Overgrowth (SIBO) and IBS

Some of the more recent research on restless legs syndrome has focused on a connection with small intestinal bacterial overgrowth (SIBO) and IBS, which is often caused by SIBO. One study found that 69% of RLS patients also had SIBO, compared with only 28% of controls. (7) They also found that 28% of RLS patients had IBS, compared to only 4% of controls. And according to the 2012 review I mentioned in the previous section, 32% of the 38 conditions associated with RLS are also associated with SIBO. (8)

A strong association between SIBO and RLS doesn’t mean that SIBO is causing RLS in these patients. But a few trials have found that in patients with both SIBO and RLS, their RLS symptoms improve after being treated for SIBO. (9)

For example, one double-blind, placebo-controlled study reported that treatment with the antibiotic rifaximin—the standard treatment for SIBO—significantly improved RLS symptoms in patients with both conditions. (10) This, of course, does suggest a causal link between SIBO and RLS.

What to do: If you have both RLS and SIBO, the best option would be to find a functional medicine practitioner who has experience dealing with SIBO and get treated. That said, two steps you can try on your own are a low-FODMAP diet and probiotics. Low-FODMAP diets reduce the amount of fermentable carbohydrates that “feed” bacteria in the small intestine, and a couple studies have shown that probiotics can be as effective as antibiotics for treating SIBO. (11, 12) I’ve found the probiotics S. boulardii (a beneficial yeast), and MegaSporeBiotic to be helpful.

One important note about low-FODMAP diets, however, is that it’s generally not a good idea to stay on one indefinitely. Low-FODMAP diets eliminate sources of prebiotics, which can improve symptoms by starving pathogenic bacteria, but can also starve your beneficial bacteria. The best approach is to follow a low-FODMAP diet until symptoms subside (and your SIBO breath test is normal), and then gradually re-introduce prebiotic foods (or supplements) to support your gut microbiome.

3. Vitamin D Deficiency

As I mentioned in the introduction, one of the most-researched theories about the cause of restless legs syndrome is impaired dopamine signaling, which has led to the conventional treatment of RLS by dopamine agonists (i.e. chemicals that can bind to and activate dopamine receptors). Unfortunately, these treatments can become less effective over time, and can even result in a worsening of symptoms.

And while replacing neurotransmitters might be an effective way to manage symptoms in the short term, the goal should be to figure out why dopamine signaling is impaired in the first place.

This is where vitamin D comes into play.

The role of vitamin D in dopamine signaling is only beginning to be investigated, but some evidence indicates that vitamin D could play an important role by increasing levels of dopamine and its metabolites in the brain, as well as protecting dopamine-associated neurons from toxins. (13)

RLS has been associated with vitamin D deficiency in several studies, and disease severity has been inversely correlated with vitamin D levels. (14, 15, 16) One study has also found that vitamin D supplementation improved the severity of RLS symptoms. (17)

What to do: If you have RLS, one of the easiest first steps you can take is to get your vitamin D levels tested. A good range to shoot for is typically between 25-50 ng/mL, but if you have an autoimmune disease or another chronic health condition, I prefer to bring vitamin D levels up to 35-60 ng/mL. One way to supplement vitamin D is cod liver oil; I recommend extra-virgin cod liver oil. You can also take a D3 supplement, such as this one that contains both vitamin D and vitamin K2. And of course, you should get regular sun exposure to bring your vitamin D levels up naturally.

4. Iron Deficiency

Iron deficiency isn’t exactly a “little-known” cause of restless legs syndrome; in fact, it’s probably one of the most well-researched areas relating to RLS. Iron is required for proper dopamine signaling, but its role is much better established than that of vitamin D, and it’s pretty clear that iron deficiency in the CNS can cause RLS symptoms by impairing dopamine function. (18)

Several studies have found that low iron levels in the cerebrospinal fluid and in the brain occur more frequently in patients with RLS compared with matched controls. (19, 20) And this difference isn’t always reflected in serum ferritin levels.

Other abnormalities in iron metabolism have also been observed in RLS patients, and many conditions that increase the risk of RLS (including pregnancy and end-stage kidney disease) are known to cause iron insufficiency. (21, 22)

Further, iron supplementation significantly improves or even eliminates the symptoms of RLS in many patients. For example, RLS patients with low-normal serum ferritin experienced significant improvements in their RLS symptoms after 12 weeks of iron supplementation. (23) And oral iron was as effective for treating RLS as pramiprexole, a dopamine agonist, although the response rate for both treatments was relatively low (46.7%). (24)

The tricky thing about iron deficiency is that the solution is often not as simple as taking an iron supplement. Iron deficiency is frequently secondary to SIBO, gut infections, or other inflammatory states, which explains at least in part the association between RLS and these conditions. Iron deficiency caused by infection or inflammation is mediated primarily by the hormone hepcidin, which at high levels can decrease serum iron and reduce iron absorption from the GI tract. (25)

One cause of increased hepcidin levels is the production of IL-6, an inflammatory cytokine present in most inflammatory diseases. Another cause of increased hepcidin levels is the presence of lipopolysaccharides (LPS), which are components of gram-negative bacteria that can enter circulation as a result of SIBO or other gut infections. Thus, increased levels of circulating IL-6 or LPS can result in iron deficiency, and subsequently, RLS.

What to do: If you have RLS and iron deficiency, the first step is to identify why you’re iron deficient. If the cause is blood loss (such as from heavy menstruation in women) or dietary insufficiency (such as in vegetarian or vegan diets), increase your consumption of iron-rich foods such as liver and red meat. You can also consider an iron supplement; I recommend Proferrin ES and bovine ferritin, because they are better absorbed and better tolerated than plant-based iron supplements. 

However, if the cause is SIBO or a gut infection, increasing iron intake can often make matters worse by creating an environment that promotes pathogen growth and inflammation. (26, 27, 28) For this reason, it’s best to address the gut before (or at least concurrently with) adding iron supplements.

As you can see, restless legs syndrome is complex, and several factors could come into play when trying to figure out the cause. As with many other health conditions, RLS is best seen as a symptom which signals that something else is amiss, and it’s necessary to dig deeper to find out the root cause, and how to treat it.

If you suffer from restless legs syndrome, I hope this article helped clarify what might be causing it.

293 Comments

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  1. Hi Chris,

    I wonder if anybody has ever looked into the link between RLS and the sympathetic nervous system – more specifically the fight or flight response. It’s been my personal experience that I will have RLS when I am more stressed out or overwhelmed. Most telling, however, is the fact that every time I fly I will have severe RLS the following night. I believe that is because I really hate flying. When I fly everything in my body is telling me to run away from there – meaning my sympathetic nervous system is highly activated, but I am powerless to take action.
    I guess it is worth mentioning that I am a psychotherapist who is very interested and invested in working with trauma through the body and this alternate cause for RLS seems very plausible to me.
    By the way, I have found that rolling my leg, or vigorously massaging my thighs up and down with a tubular object (I often use my deodorant container) 100 times gets rid of my symptoms most of the time if not always!
    Thank you for your wonderful work and for sharing your wisdom and knowledge with the rest of us!
    Take care,

    Anyella

    • Have yourself checked out for Obstructive Sleep apnea OSA which is associated with increased adrenergic activity . This may be contributing to your RLS .. OSA causes major inflammation

    • I’ve massage my legs on a foam roller and it works like magic. I’ve often stressed over not being able to travel with my foam roller — I love your idea of an empty deodorant container in a pinch. Thanks for the excellent tip!

  2. I would like you to comment on the latest study on brain aging.
    I read that the “Mind or Mediterranean Diet” slows brain aging by adding whole grains and beans to what we eat. This seems to be contrary to the Paleo approach to health.
    What’s your take on this?
    thanks
    Mel

  3. Chris – Very interesting article – you’ve identified several areas that may be causing my RLS. I’ve had a history of bowel obstruction for the last 8 years and been on Pramiprexole for quite some time and it’s less and less effective each day. My PCP has never mentioned it may be linked to my intestinal issues. I’ve been experiencing more frequent episodes of RLS, even at work now which was not an issue before. I am going to see a gastroenterolist (SP?) because I’ve been having more and more pain in my gut – now that I feel more informed I will definitely be able to explain my symptoms and the possibility of the connection between RLS and my gut! Thanks again

    • Do look into something called augmentation. It’s when pramipexole (a dopamine agonist) causes the symptoms to occur earlier or with more severity.

  4. I have something called periodic limb movement disorder, which was diagnosed at a sleep clinic. It doesn’t wake me up but it wakes my partner up. What happens is my leg (usually just one) jerks periodically about every 30 seconds, not all night, but quite a bit. I’ve taken magnesium which didn’t help. Does anyone have any advice for this malady? Thanks!

    • I was told I had a PLMD index of 93 at my sleep lab. According to my sleep specialist I was low in B12.(kind of odd since I had been trying to convince my doctor of this with no luck). I went to a naturopath and began an elimination diet soon after that and found that a change in diet helped tremendously.

        • I started taking B12 and iron tablets and magnesium about 6 months ago. So far, no change. I do think it is related to something I am eating though. About 10-12 minutes after consuming any kind of food, it begins. Not so much in the morning and afternoon but in the evening……..Drives me CRAZY. I am also taking Ropinirole and it is NOT working for me. Before he Ropinerole I took Sinemet and that stopped working also. So very frustrating.

  5. Thank you for the great article. I am wondering which is the best type of Magnesium for RLS? Thank you!

    • For the sake of not being redundant, Nadine, please read the responses I have already posted to Amy, and others here in comments.

    • Nicole, many forms of magnesium are poorly absorbed and some can have a laxative effect, which also interferes with absorption.

      Of the oral forms, magnesium glycinate and magnesium taurinate are well absorbed and do not have a laxative effect. But I prefer magnesium chloride hexahydrate applied topically to the problem area. Both as a preventative and as a treatment for symptoms.

  6. From the comments posted here, as well as what Chris says, it is clear that there may be multiple causes of RLS. I strongly suspect that ultimately the cause is the presence of a particular toxin in the body, and which flows into the brain case with interstitial fluid flow, causing damage to the meninges and then the brain itself. It may be at the root of all the problems with all those different parts of the body mentioned by Chris, as well.

    The cause may be a group of toxins, so that if one has more than one of them inside then the symptoms are more widespread. I used to have problems with restless legs, but once I got rid of a lot of the toxins in me, it stopped completely. Since I was exposed to these toxins as a baby, they have had a lifetime to get sequestered into the bones of the body, and thus take a very long time to be eliminated.

    I use a completely different method of detoxification than most speak about, not concentrating on the gut as much, but on the acupuncture meridians, hypodermal fluid flow and mind-body techniques, along with careful control of the chemistry in that fluid (not just that in blood and lymph vessels) by limiting activity, controlling diet for each meal, use of spices, as well as teaching my brain what to do about specific problems. When I first learned how to do the latter, the brain started to release all toxins at once from the bones, causing a serious problem. I had to teach the brain to make repairs to all transport pathways after each toxin release before starting another, and how to find where they were stored by searching through memories of when I was exposed to them.

      • Yeah it does, but the biology is very accurate. When you spend the time thinking out how it all works, as I have, intensively, for the past 10 years, it is very logical. It explains why removing toxins can be so slow and difficult (you have to use simple diffusion). Ask anyone who has undergone chelation therapy.

        Dr. Getoff discussed a lot of this stuff in an Aug 2, 2015 interview on Natural Health 365 radio show (http://www.naturalhealth365.com/category/podcast but it is not archived there yet). He didn’t get at the steps between blood flow and the cells, as I have, but he tells us how the usual methods for determining presence of toxins are not helpful. However, he concentrates on detoxifying the gut epithelium in much of what he does, ignoring what goes on INSIDE the gut (not in the lumen, which is technically outside the body because nothing has crossed an epithelial membrane yet).

        When you get your own brain trained to do the steps, it is much like training your brain to making a 3 point basketball shot. It takes practice, practice, practice in as many different places and activities as you can. We have seen how some of these techniques can achieve a lot of healing in psychotherapy, but only if the patient does the homework. Since the body and mind are so interlaced in the brain, it stands to reason that what we can train our minds to do, can affect our bodies, and vice versa.

  7. Yes Vitamin-D and Iron deficiency can also cause RLS, I consulted to a Doctor about my RLS syndrome so he ran some basic test and found out that I Had Iron deficiency , So i took Iron pills for about a month and then it was like gone for some time, But I don’t think that there is a permanent solution to RLS, I am still Suffering from the problem.

  8. I used to have RLS very bad every night. When I started taking gingko biloba it went away. I have no idea what that did, perhaps it lowered some inflammation going on in my body from poor diet. Back then I didn’t eat very healthy – alot of sugary processed foods, fast foods and eating out. Now I eat mostly organic paleo w/ some legumes, rice, quinoa and oats. I don’t take the gingko anymore and don’t have RLS either.

  9. This article, and many others, mention getting your gut tested for infections of various types. How does one go about doing that – what type of doctor (gastroenterologist?), and which tests would one specifically request? Thanks.

  10. According to Alan Gaby and Jonathan Wright (MDs), familial RLS can be due to folate deficiency. I had a client with RLS as did his mother and his organic acid results showed FIGLU (metabolite that rises with folate deficiency). The recommended dose of folate (Gaby/Wright) is 5-30 mg/day! This cause of RLS appears to affect 10% of the population. Interestingly, RLS can present during pregnancy for this reason too. I suggest, though, that folate be provided with vitamin B12.

  11. Great article. I definitely agree with so many who have already mentioned… magnesium!! If I have eaten too many nuts that were not soaked, then the twitching is present again. I realize that I am very low on magnesium all the time, so use an awesome spray that really helps. The other things that so helped me… raw milk kefir!!! and lots of filtered water!!! If I am low on enough fluids, I will feel it in my legs.

  12. My RLS is caused by tight glutes. When I feel my legs begin to twitch I use a foam roller for my glutes. This works every time.

  13. It certainly is a complex issue and may be difficult finding the cause of many ailments. Makes me realize how important our gut health is and to focus there for many different health issues. Health begins in the gut, right?

  14. I have had RLS as long as I can remember. My mom had it, my daughter has it and her 18-year-old son. So…is it familial? I have thyroid issues (hypo) and so did my mom. I would do Anything to not have RLS. Doctors only treat the symptoms and not the cause. What do you suggest I begin in terms of my gut? inflammation, etc.? I have none of the diseases you mention in your opening comments. Is my issue inflammation? IBS? SIBO? And for a lifetime? Help! I regard your articles on health highly. Thanks Billie

  15. I have suffered with restless legs for nearly 40 years. It is definitely genetic but I am by far the worst in my family. I also get restless arms. My doctor is very dismissive of this condition (i’m from the uk and we don’t have functional doctors in most parts) so everything has been trial and error on my part. Magnesium doesn’t work but has been brilliant for my migraines .I have ‘normal’ vitamin b and iron levels but I definitely find the iron supplements help. I use Spatone sachets by Nelsons which is natural iron water collected from the streams of the Lake District and so doesn’t cause stomach upsets. It takes a couple of weeks to work and I daren’t miss a day. I have idiopathic insomnia and rarely sleep more than 2 or 3 hours per night. I can’t get to sleep and I can’t stay asleep and I have tried everything including sleeping pills and nothing works so this is where I think the connection with dopamine comes in, its a problem in the brain. Sometimes I get up in the morning and feel like I have run a marathon with the sleepless nights and the kicking and thrashing and I have aches and pains in my leg and thigh muscles most days. I think it’s all connected.

    • Chris, I had the same problem with sleep. I didn’t have any problems going to sleep I simply couldn’t stay asleep. After much research I learnt that if your Adrenal’s aren’t working properly it effects your sleep. Adrenal’s produce cortisol, cortisol regulates sleep. Once I got my Adrenal’s where they need to be my sleep became much better. I no longer take a sleep aid.
      I was also kicking during the night. Which kept me from having a restful night sleep. I asked for blood test and the results were I was severely anemic with a very low white blood cell count. I was put on a high dose of iron and the kicking stopped. Your iron may not be working for you. Try upping the dosage. It’s possible the brand your taking is not compatible to your body.
      All my best to you….

  16. Hi Chris,

    I’m just curious if you could share why you recommend Extra-virgin cod liver oil instead of fermented cod liver oil? Thanks!

  17. I started having RLS last year and appreciate how it feels to suffer from this condition.

    One night, I had a dream, this dream said that the reason I was having this RLS was because I was getting too hot in bed. The next evening I took action to make sure I did not get too hot, and sure enough my RSL stopped. Never to return again.

    • Thank you for sharing Sarah. I too have always suffered with excessive heat during the night . It has never occurred to me that that could be a contributary factor of my RLS .

      I have suffered periodically with an ache, deep in the bones of my left ankle and wrist for over 20 years which is so severe that I have to thrash my arm and leg about to get any relief. It only occurs at night time when I am lying in bed and I didn’t realise until now that it is a recognised condition called RLS.
      Johnny

    • I wonder if the heat you felt was due to internal inflammation that might still be present? It might now be going noticed due to the room temperature cooling your body enough (and stopping the RLS symptoms) in a superficial way. It’s just a thought, as I noticed in my experience as well that right before an RLS episode would happen at night, I would always feel too hot. It would happen unless the room was cold enough to need several blankets. I eventually found that the primary culprits were a couple of foods I had a strong sensitivity to (ones that I loved and would eat every day and often) that were creating inflammation. Once I cut them out of my diet, the RLS episodes stopped entirely within 24 hrs.

      • Well, Grace, would you be so gracious as to elaborate on what foods you “cut out of” your diet? It might be helpful to some of us here.

        • Hi, This sounds too simple to be true, but foods you are sensitive to are often foods that you hunger for or crave, in much the same way as an alcoholic craves alcohol? although obviously not as severely, there is a negative response by your body to the food. I have a child that craved milkshakes and ice cream, and it took a while to work out that the milkshake that she craved and begged for would result in her becoming whiney and weepy almost immediately, and getting sick three days later. If you have a child that insists on a favorite food and that behaves badly afterwards, ie orange juice at school and then disturbs the class after lunch break, it may be a food that is causing a negative reaction. Look for the foods that cause you to be drowsy, or overactive, or unable to concentrate. Good luck

    • This shows what the purpose of dreaming is to being with. I think it tests out pathways that have been repaired in the brain. It also clearly tells you what is being worked on in the brain, and it was telling you that heat seems to have a lot to do with your symptoms. The dream state is a few steps above and closer to consciousness than deep sleep is. By going there, the brain wants your conscious brain involved in analysis of information the brainstem has figured out is a problem. If you remember your dream upon awakening, it wants you to have fully conscious parts of the brain involved with the solution. It clearly worked for you. If you can’t remember the dream, it has worked out a solution.

  18. You may want to try what works or me: Do a couple of dozen sit-ups while lying on a soft surface like a bed.
    This completely takes away the symptom for me — I think it may have something to do with stretching the muscles of back and legs.
    Good luck!

  19. I used to have RLS almost every night when I got in bed. I had been taking a good multivitamin (for women) and a Vitamin D3, daily. I started adding fish oil, 3 times per day (from Aldi’s) because my eye doctor told me I have dry eye. When I added the fish oil, I was able to quit using eye drops, and I noticed my RLS was gone. For the last week and a half, I have been out of fish oil, so I wasn’t taking them, and the RLS came back. I am convinced the fish oil in conjunction to the other vitamins helped.

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