What causes Restless Legs Syndrome (RLS), and how can you reduce or eliminate your symptoms?

Restless legs syndrome (RLS; also called Willis-Ekbom Disease) is a condition that causes uncomfortable or unpleasant sensations in the legs, often described as creeping, crawling, itching, tingling, pulling, throbbing, or painful. People with RLS feel an irresistible urge to move their legs in order to relieve these sensations. For this reason, RLS can be classified as a movement disorder. It can also be classified as a sleep disorder because the symptoms are made worse by resting and trying to sleep. However, RLS is most appropriately classified as a neurological sensorimotor disorder, because the symptoms are produced within the brain.

Restless legs syndrome is fairly common, occurring in between 3.9% and 15% of the world population. Rates of RLS are higher among Caucasians and in western countries than in Asian and Indian populations. Symptoms of RLS may begin at any age, and tend to get worse with age. Women get RLS about twice as often as men, and researchers suggest that this could be due to childbearing and differences in hormones and social roles.

RLS can have a significant negative effect on quality of life, mainly due to disrupted, shortened, and low-quality sleep. RLS symptoms typically occur in the evening and overnight; this is likely because natural melatonin production inhibits dopamine, causing symptoms to worsen at night when we produce melatonin. Lack of sleep can for many people lead to difficulty concentrating, impaired memory, poor performance at work and school, and mood disorders including depression and anxiety.

Across the board, scientists agree that more research needs to be done in order to fully understand RLS. So far, studies show that iron deficiency and dopaminergic (DA) system dysfunction are the two factors most often present in RLS sufferers, and the two are related. There are a number of things you can do to find out what might be causing your RLS and to reduce your symptoms, and I’ll discuss these in the last section of the post.

Diagnosing Restless Legs Syndrome

There is currently no test for RLS, so the condition is diagnosed by a doctor’s evaluation on the following five criteria:

  • A strong or overwhelming urge to move the legs, often associated with uncomfortable sensations described as creeping, crawling, itching, tingling, pulling, throbbing, or painful
  • Uncomfortable sensations and urge to move the legs begins or gets worse during rest or inactivity
  • Moving relieves the uncomfortable sensations in the legs (at least partially or temporarily)
  • Uncomfortable sensations and urge to move the legs begins or gets worse in the evening or at night
  • The above features are not due to any other medical or behavioral condition

It’s common for symptoms to be experienced very mildly or intermittently at first, and to follow a gradual progression. Many years may pass before symptoms are experienced regularly. People most often feel symptoms in both legs, but they can occur on just one side or alternate sides. Some people develop symptoms in their arms as well, and in rare cases, the chest or head. More than 80% of people with RLS also experience periodic limb movement of sleep (PLMS), which involves involuntary leg and/or arm movements during sleep.

If you’re trying to figure out whether or not you have RLS, it’s good to be aware that the following conditions can mimic and be misdiagnosed as RLS:

  • leg cramps
  • positional discomfort
  • local leg injury
  • arthritis
  • leg edema
  • venous stasis
  • peripheral neuropathy
  • radiculopathy (sciatica)
  • habitual foot tapping/leg rocking
  • anxiety
  • myalgia
  • drug-induced akathisia

RLS can be related to or caused by the following factors and conditions:

    • End-stage renal disease and hemodialysis

    • Iron deficiency

    • Vitamin D deficiency

    • A condition involving inflammation or immune system changes, including Parkinson’s disease, multiple sclerosis, ADHD, Alzheimer’s disease, Celiac disease, Crohn’s disease, rheumatoid arthritis, sleep apnea, diabetes, and depression

    • Certain medications, such as antinausea drugs, antipsychotic drugs, antidepressants that increase serotonin, and some cold and allergy medications that contain antihistamines

    • Use of alcohol, nicotine, and caffeine

    • Pregnancy, especially in the last trimester (symptoms typically disappear within 4 weeks after delivery)

    • Neuropathy (nerve damage)

    • Sleep deprivation or sleep apnea

Iron deficiency and dopaminergic (DA) system dysfunction in restless legs syndrome

Since 1953, research has consistently shown that people with RLS are often deficient in iron. Ultrasound, MRI, and autopsy studies show that a part of the brain called the substantia nigra in particular tends to have decreased levels of iron. Other parts of the brain including the putamen, thalamus, red nucleus, and pallidum have also been found to have lower than normal concentrations of iron in RLS patients.

Logically, iron supplementation has been tested and used as treatment for RLS. Some people’s symptoms are improved or eliminated completely with iron supplementation, and others’ are not. The blood-brain barrier poses a problem when it comes to iron; blood serum levels of iron (iron circulating throughout the body) and levels of iron in the brain are different. People can have normal or higher than normal blood iron levels, while their brain remains iron deficient. Research suggests that in RLS, brain iron uptake is dysregulated, leading to brain iron deficiency.

A 2011 in vitro study in rats found that iron deficiency can cause death of dopaminergic cells in the substantia nigra. When these dopamine-secreting neurons die, it leads to dysfunction of mesolimbic and nigrostriatal dopaminergic pathways. These pathways regulate movement as well as motivation and desire for reward. Researchers hypothesize that the dysfunction of these pathways in turn leads to dysregulation of limbic and sensorimotor networks, resulting in the symptoms of RLS.

Death of dopaminergic neurons in the substantia nigra and disruption of dopamine pathways also occurs in Parkinson’s disease. And while rates of RLS are higher among Parkinson’s disease patients than controls and the two conditions have overlapping clinical symptoms, scientists believe that the underlying pathological processes that cause RLS versus RLS associated with Parkinson’s disease are different. In RLS, iron deficiency causes death of dopamine-secreting neurons. But in Parkinson’s disease, it has been found that too much iron in the substantia nigra causes oxidative stress, leading to the death of dopamine-secreting neurons.

Dopamine medications, which are largely used to treat Parkinson’s disease, can prevent the breakdown of dopamine, mimic dopamine, or convert into dopamine when they reach the brain. These drugs can reduce the symptoms of RLS, and some have been approved to treat RLS. However, long-term use is typically not recommended because it can lead to worsening of symptoms. This occurs because over time, the brain adapts to the increased levels of dopamine or dopamine-like substances in the brain, and gradually makes less of its own dopamine. The initial dose can become less effective, and people may begin to experience symptoms earlier in the day or all day. Other side effects of dopamine medications include sleepiness and compulsive behavior. Taking into consideration the potential side effects, natural ways of stimulating dopamine production (which I’ll discuss in the next section) are far preferable for the long term.

Figuring out the cause and reducing or eliminating your symptoms of RLS

There are a number of things you can do to figure out what’s causing your restless legs syndrome, alleviate your symptoms, and potentially eliminate them altogether. In addition to the actions listed below, doctors recommend eliminating caffeine, tobacco, and alcohol. Researchers suggest that lifestyle changes should be tried before taking medications due to their efficacy and lack of side effects.

Consider iron supplementation: As a first step, you should get a blood test to find out the level of ferritin in your blood. Dr. John Winkelman, an RLS specialist at Harvard-affiliated Massachusetts General Hospital, recommends treating RLS with a pill form of iron when the ferritin level is 50 mcg/L or lower. He reports that this relieves RLS symptoms substantially in about half of people with ferritin at these levels. As mentioned earlier, levels of iron in the blood and brain are different, so taking an iron supplement may not have a direct or immediate effect on levels of iron in your brain. If you are considering taking an iron supplement, consult your doctor (or ideally, an RLS specialist) to get a blood test and for advice on the correct dosage.

Increasing iron in your diet is also an option, but don’t attempt to do it by increasing consumption of animal products. The iron in animal products is heme iron, which is linked to many serious medical conditions including metabolic syndrome, coronary heart disease, atherosclerosis, stroke, type 2 diabetes, Alzheimer’s disease, Parkinson’s disease, arthritis, and cancer. It is far healthier to obtain dietary iron from whole grains, legumes, dried fruits, nuts, seeds, and dark green leafy vegetables.

Consider vitamin D supplementation: A 2015 study of RLS sufferers who were also vitamin D deficient found that increasing their vitamin D levels through supplementation resulted in a significant reduction in RLS symptoms. Another study done in 2018 found a significant association between vitamin D deficiency and developing RLS. The study authors suggest that “vitamin D may play a role in the pathophysiology of RLS by modulating the dopaminergic system.” If you are considering taking a vitamin D supplement, consult your doctor (or ideally, an RLS specialist) to get a blood test and for advice on the correct dosage. You can also increase your vitamin D levels with sun exposure (in moderation!) and dietary sources including mushrooms and cereals, plant milks, and juices that are fortified with vitamin D.

Address immune system function and inflammation: A 2012 review found that 95% of 38 conditions that are highly associated with RLS are also associated with inflammation and immune system changes. It has also been found that an elevated blood level of C-reactive protein (a marker of systemic inflammation) is associated with increased RLS symptom severity. A small 2008 study found improvements of RLS symptoms with hydrocortisone injections, which decrease inflammation. To learn more about the level of inflammation that could be occurring in your body, talk to your doctor about your current health conditions, get any necessary blood tests done, and consider dietary changes to reduce inflammation.

Address small intestinal bacterial overgrowth (SIBO) and irritable bowel syndrome (IBS): A small 2019 study found that 100% of RLS sufferers tested had SIBO, compared to 6-15% of the general population. Another study found that 69% of RLS patients tested positive for SIBO (compared to 10% of healthy controls), and 28% tested positive for IBS (compared to general population controls). While at first it may sound strange that gut health could be related to RLS, study authors discuss how research has linked gut bacteria to iron deficiency, inflammation, and sleep problems.

Reduce stress: Research consistently shows that chronic stress lowers dopamine levels and has a negative effect on dopamine signaling in the brain. The stress-related disorders of anxiety and depression (both of which involve dysregulation of the dopamine system) are significantly higher among people with RLS. Researchers note this is likely due in part to sleep deprivation in RLS sufferers (see below). RLS sufferers can experience increased symptoms in times of stress, and reduced symptoms when stress is alleviated. Reducing your stress level can be a complex task, but the next five items will help.

Address sleep habits and disorders: Sleep deprivation resulting from RLS symptoms increases risk of anxiety and depression. And, sleep deprivation due to poor sleep habits, sleep apnea, or other sleep disorders can lead to anxiety and depression which in turn can increase the risk of developing RLS. Researchers note that any factors that cause sleep deprivation should be addressed before pharmacological treatment. This includes reducing or eliminating caffeine and alcohol, going to bed and waking at regular times, sleeping in a restful environment, and treating any other sleep disorders like sleep apnea.

Get regular exercise: Exercise has been shown to significantly reduce the severity of RLS symptoms, and lack of exercise is a strong predictor of and risk factor for developing RLS. Researchers suggest that there are several likely reasons why exercise is beneficial for RLS sufferers: increased blood flow (lasting beyond the exercise session), the release of exercise-induced endorphins, and increased release of dopamine. Research also consistently shows that regular exercise improves sleep quality.

Practice yoga: A 2013 study tested the effects of practicing Iyengar yoga for 8 weeks on symptoms of RLS. The participants experienced remarkable reductions in RLS symptoms and severity, and the more often the participants practiced yoga per week, the more their symptoms improved. Their sleep quality, stress level, and mood improved as well. This is not surprising, as research has shown how yoga reduces stress hormones and increases dopamine. And like any form of physical exercise, yoga increases blood flow, releases endorphins, and improves sleep.

Practice meditation and mindfulness: A study of Yoga Nidra meditation found that meditation increased dopamine release by 65%. A small proof-of-concept trial found mindfulness-based stress reduction (MSBR) to be effective for reducing RLS symptom severity, RLS-specific quality of life, sleep quality, and daytime sleepiness. While it doesn’t seem that much other research has been done to directly test the effects of meditation and mindfulness on RLS symptoms, enough research has been done on the effects of meditation on brain function and stress level that it can be considered a worthwhile treatment option for RLS sufferers.

Do anything that reduces your stress, increases dopamine, and improves sleep naturally: This includes spending time outdoors, practicing forms of meditative movement like tai chi and qigong, becoming aware of unnecessary worry and negative thought patterns, and doing anything that brings you joy.

Taking the next step

Research shows us more and more each day how all the systems and functions of our body and brain interact. We may be aware of just one or a few specific symptoms, but they can be indicative of many, sometimes seemingly unrelated imbalances occurring inside us. If you have restless legs syndrome, don’t be resigned to live with it—take the time to investigate all of the possible causes and see what you discover!