Restless legs syndrome (RLS) is a common sleep disorder that affects up to 10 percent of adults and up to 4 percent of children in the United States. This makes it the fourth leading cause of insomnia. With RLS, people have an uncontrollable urge to move their legs, along with uncomfortable sensations. This disrupts sleep and nightly rest for millions, significantly impairing quality of life.

Also known as Willis-Ekbom disease, RLS was first identified by Sir Thomas Willis in 1672, and then described in more detail and named by Karl-Axel Ekbom in 1944. Even though RLS was identified that long ago and has very peculiar symptoms, it often goes undiagnosed. Treating RLS can also be challenging, highlighting the need for greater awareness and understanding of this sleep disorder.

RLS manifests with distinct symptoms that can vary in intensity and presentation. Key symptoms and early signs of RLS include:

• Irresistible urge to move legs: The hallmark symptom of RLS is an uncontrollable urge to move the legs, often accompanied by uncomfortable sensations. The urges generally occur at night or when at rest and are relieved briefly by movement. These sensations, described as electric, itching, prickly, crawling, or painful, typically originate deep within the legs. Children may express these sensations as kicking, wiggly, or tingling legs.
• Periodic limb movements during sleep (PLMS): Around 90 percent of people with RLS also have PLMS, which are repeated leg movements during sleep that can vary in frequency.
• Disturbed sleep and insomnia: RLS can make it hard to fall asleep and stay asleep due to the strong urge to move the legs. This can lead to insomnia and not getting good sleep. It can also significantly affect daily function.

In addition to these key symptoms, RLS exhibits the following characteristics:

• Distribution of symptoms: RLS symptoms commonly affect the area below the knee in the back of the calf, but they can also extend to the arms and thighs. The sensations usually impact both legs but may alternate between them.
• Differentiating symptoms: It is important to distinguish RLS from leg cramps, muscle pain, arthritis discomfort, chronic foot tapping, or weakness. In children, RLS is often linked with growing pains and attention-deficit/hyperactivity disorder (ADHD), leading to potential misdiagnosis.
• Intermittent versus chronic RLS: RLS can present as intermittent or chronic. Intermittent RLS involves sporadic symptoms without a predictable pattern, while chronic RLS entails regular symptoms occurring more than twice a week.
• Severity and impact: The severity of RLS symptoms can range from mild discomfort to severe disruption that affects overall wellness by disrupting sleep, daily activities, and mental health.

RLS manifests in two types: primary idiopathic RLS and secondary RLS.

Secondary RLS is caused by other health problems or certain triggers. If you treat the root cause, the RLS symptoms often get better or go away completely. Common triggers for secondary RLS include:

• Certain health conditions
• Antihistamines
• Medications for mental health conditions
• Medications that help with nausea and vomiting

RLS is a complex puzzle with various pieces that scientists are still trying to put together. The causes depend on the type of RLS.

1. Primary Restless Legs Syndrome

Primary RLS, often termed idiopathic due to the absence of a direct cause, manifests through diverse pathways. Current research points to brain iron deficiency, genetic predispositions, and environmental factors as key contributors to the intricate physiology underlying RLS development.

Iron Deficiency

When the body is inflamed, as in RLS, more hepcidin is produced. This hormone plays a key role in managing iron, but an excess, as found in RLS, can prevent the proper distribution of iron. Researchers speculate this imbalance might lead to a relative iron deficiency in the brain that contributes to RLS symptoms. Consequently, reducing inflammation may be crucial for symptom relief and prevention.

Brain imaging studies have confirmed lower iron levels in the brain and cerebral spinal fluid in individuals with RLS, along with decreases in white matter and disruptions in the dopamine system. Brain iron deficiency impacts these neurotransmitters and myelin production. Insufficient iron for myelin production can result in slower or disrupted nerve signal transmission.

Iron is also required for oxygen transport in the blood. When the brain lacks sufficient iron, cells may not receive adequate oxygen, leading to lower oxygen levels (hypoxia).

Environmental Factors

Environmental factors, unique to each individual, can interact with genetic susceptibilities, potentially intensifying RLS symptoms. While studies vary in their findings, some suggest that factors such as obesity, smoking, sedentary lifestyle, evening sugar intake, and alcohol consumption may impact RLS. During pregnancy, hormonal shifts and increased nutrient demands can trigger or worsen RLS symptoms.

Genetic Factors

Genetic factors are estimated to contribute to 50 to 60 percent of RLS cases, with about one-third of the general population being genetically vulnerable if their iron levels decline. These factors influence the brain’s iron regulation, a critical mineral essential for oxygen transport and optimal brain function. Disruptions in iron acquisition can affect nerve signaling and the maintenance of nerve integrity, potentially leading to brain iron deficiency and neurological changes, even when standard blood tests show normal iron and ferritin levels.

Other Contributing Factors

Research also suggests a potential link between vitamin D deficiency and RLS. Vitamin D appears to play a role in regulating the brain’s dopamine pathways, and lower vitamin D levels have been associated with more severe RLS symptoms. Importantly, studies have shown that vitamin D therapy can improve RLS symptoms in those with a deficiency.

Additionally, hormonal factors may influence the onset and development of RLS. During the last trimester of pregnancy, when estrogen levels rise, the prevalence of RLS increases significantly. However, the relationship is not straightforward, since RLS often does not decrease after menopause, when estrogen levels decline.

Evidence also indicates that an imbalance between thyroid hormone levels and the dopamine system may contribute to the emergence of RLS symptoms. Deficient brain iron levels may impair both dopamine production and the normal metabolic breakdown of thyroid hormones. This results in low central nervous system dopamine and higher thyroid hormone levels. Case reports have shown that the administration of levothyroxine, a medication used to treat hypothyroidism, can trigger RLS symptoms, which are then resolved when the medication is withdrawn.

2. Secondary Restless Legs Syndrome

In secondary RLS, an underlying trigger such as a medical condition causes RLS. While many health problems are associated with RLS, not all of them directly cause it or make it more likely to happen. For example, although RLS occurs more frequently in people with multiple sclerosis (MS), it is unclear if MS can cause secondary RLS or if they just share the same mechanisms for development.

Based on consistent research findings, conditions known to trigger secondary RLS include:

• Iron deficiency or iron-deficient anemia
• Pregnancy
• Kidney disease
• Neuropathy
• Parkinson’s disease (treated, but not untreated)
• Stroke

Certain factors can make someone more likely to develop RLS, including:

• Age: RLS can occur at any age but is less frequent in children and more prevalent in older adults. Early-onset RLS starts before 45 years old, with a peak incidence between 20 and 40 years, typically running in families and progressing slowly. Late-onset RLS begins after age 45, is frequently linked to other health conditions, and tends to worsen more quickly.
• Sex: RLS occurs more in women, which may be attributed to RLS occurring frequently during pregnancy. Interestingly, women who have had no pregnancies have the same prevalence as men of the same age.
• Pregnancy: Women with a family history or prior history of RLS are more likely to get RLS during pregnancy, and conversely, women who had RLS during pregnancy are three to four times more likely to have it again.
• Ethnicity: Asian populations tend to have a lower prevalence of RLS, typically ranging from 1 to 3 percent. In contrast, the prevalence is considerably higher, between 5 and 13 percent, among populations in Europe and North America.
• Family history: Approximately 63 percent of those with RLS report having an immediate family member, such as a parent, sibling, or child, with RLS.
• Lifestyle: Lifestyle factors such as alcohol, tobacco, and smoking can increase the likelihood of developing RLS.

Understanding these risk factors can aid in prevention, early detection, and management.

There are no specific tests for diagnosing RLS. A sleep study, or polysomnogram, can help quantify leg movements during sleep, but it is not required for diagnosis. Diagnosis is based solely on the patient’s description of symptoms, without any objective or laboratory tests. This can make it difficult to diagnose children or people with cognitive issues, who may not be able to describe their symptoms.

The first diagnostic criterion is a compelling need to move the legs, often, but not always, with uncomfortable and unpleasant leg sensations. Then, the urge must meet all the following conditions:

• Starts or intensifies during rest or inactivity, like lying or sitting
• Eases partially or completely with movement, like walking or stretching, at least during the activity
• Happens or intensifies in the evening or night, more so than during the day

Additionally, the symptoms must not be attributed to another medical or behavioral condition. A rating scale may be used to assess severity.

The diagnostic criteria for children are more flexible due to their limited ability to describe their symptoms:

• Definite RLS: The child meets the adult criteria for RLS and can describe leg discomfort in their own words, consistent with the condition.
• Probable RLS: The child meets all the essential adult criteria for RLS, except the requirement that the urge to move or sensations are worse in the evening or at night. The child also has a biological parent or sibling with definite RLS.
• Possible RLS: The child has periodic limb movement disorder (PLMD) and a biological parent or sibling with definite RLS, but does not meet the full criteria for RLS.

If brain iron deficiency is not managed, it can worsen RLS, leading to more severe symptoms and complications. The main complications of RLS are related to how it progresses and affects your daily life, sleep, and mental health. These effects can cause serious health concerns that impact your overall well-being, including:

• Insomnia
• Anxiety
• Depression
• Social isolation
• Daytime fatigue
• Mood and behavior changes
• Difficulties at work or school
• Associated financial challenges
• Impaired concentration and thinking

Women who have had RLS during pregnancy are at a greater risk of pregnancy complications such as preeclampsia, gestational diabetes, perinatal and postpartum depression, and preterm birth.

Moreover, up to 31 percent of RLS patients feel compelled to eat at night, similar to the urge to move their legs. This habit of eating at night can get worse with sedative hypnotic drugs like benzodiazepines and may result in weight gain.

Treating RLS varies based on the severity of symptoms. Mild cases may not need to be treated, but some lifestyle changes may be beneficial. Intermittent RLS can be managed as needed. In cases of severe RLS where frequent symptoms impact your daily life, daily treatment is recommended, with medication doses as low as possible. With secondary RLS, addressing the underlying conditions should be prioritized because RLS can worsen if the other conditions are not treated.

Unfortunately, currently available conventional treatments—other than iron, if deficient—only address symptoms rather than modifying the disease.

Pharmacological Treatments

Some of the available pharmacological treatments are used off-label and come with significant risks including abuse, dependence, and augmentation. Augmentation, a critical concern, describes a paradoxical worsening of symptoms induced by a medication that initially provided relief. This progression can be mistaken for disease progression.

Pharmacological treatments for RLS include:

• Dopaminergic agents: Dopaminergic agents like ropinirole, levodopa, rotigotine, pramipexole, and cabergoline increase dopamine levels in the brain to alleviate symptoms. This can seem counterintuitive since RLS is linked to high dopamine levels. However, dopamine abundance during the day can lead to less responsive dopamine receptors over time, which is greatly aggravated at night when dopamine levels naturally decrease. Once considered first-line treatments, the significant risks associated with dopaminergic agents now limit their use to short-term, with gabapentinoids recommended for long-term management of RLS.
• Calcium channel alpha-2-delta ligands (gabapentinoids): Gabapentinoids like pregabalin, gabapentin, and gabapentin enacarbil regulate calcium channels in the brain, influencing neurotransmitter release and nerve cell activity. In RLS, these medications help improve sleep quality and reduce limb movements during sleep. Gabapentinoids can be especially beneficial for individuals with RLS who also suffer from nerve pain, chronic pain, insomnia, or anxiety, though there is a risk of serious side effects including breathing issues and hospitalization if taken with opioids or other sedating medications. Gabapentinoids should be used cautiously due to the potential for abuse, dependence, and the risk of cognitive impairment or dementia associated with long-term use.
• Opioids: Medications such as oxycodone, oxycodone/naloxone, tramadol, morphine, and methadone are used for severe treatment-resistant RLS or severe augmentation. Interestingly, tramadol is associated with augmentation, and opioid withdrawal can trigger RLS symptoms. The precise mechanism by which opioids alleviate RLS symptoms is unclear. Opioids should also be used cautiously due to their potential for abuse, dependence, and addiction.
• Benzodiazepines: Benzodiazepines, particularly clonazepam, have been prescribed off-label for RLS for years. Some small studies and case reports show benzodiazepines are effective at relieving symptoms and improving sleep. However, due to a lack of randomized control trials, a Cochrane review determined the effectiveness of clonazepam is unknown. The risks associated with long-term use of benzodiazepines should also be considered.
• Ketamine: Primarily used as an anesthetic, ketamine has shown promise when used off-label for the treatment of RLS. A 2002 case report described two patients with RLS who experienced significant improvement in their symptoms after taking oral ketamine for up to six months. However, it is important to note that the use of ketamine for RLS remains highly specialized and is primarily offered as infusion therapy by specialized centers, due to dose-dependent serious side effects.

Non-Pharmacological Treatments

Non-pharmacological treatments include:

• Iron therapy: Correcting an iron insufficiency may completely resolve symptoms for some with RLS. Iron supplementation is generally recommended if serum ferritin is below 75 milligrams per liter, and transferrin saturation is below 25 percent. With oral iron supplementation, such as ferrous sulfate, it is suggested to be taken daily with vitamin C to aid absorption.  This is the most practical method to supplement iron. If there are gastrointestinal or absorption issues, then intravenous ferric carboxymaltose infused over several hours can be given.
• Pneumatic compression devices (PCDs): Some, but not all studies, have shown PCDs to be effective in improving sleep quality, reducing daytime sleepiness, and enhancing overall quality of life for individuals with RLS. It is hypothesized that when these devices apply pressure to the legs, it stimulates the release of nitric oxide, leading to increased blood flow, and helping to reduce discomfort and restlessness.
• Acupuncture: A six-week study found acupuncture helped reduce nighttime restlessness and movement, symptom severity, and daytime sleepiness. Importantly, the acupuncture was well-tolerated, with no reported side effects.
• Repetitive transcranial magnetic stimulation (rTMS): rTMS involves placing an electromagnetic coil against the scalp, which generates magnetic pulses that stimulate nerve cells in the targeted brain region. It is approved by the FDA for the treatment of depression and other conditions. In two small studies, rTMS significantly improved RLS symptoms and anxiety.

Your mindset significantly shapes how you manage and experience RLS. Since RLS is a chronic and often progressive condition, it is easy to fall into negative thinking and feel overwhelmed, depressed, or anxious. These emotions aren’t just hard on your mind—they can actually worsen RLS symptoms. Stress triggers your body to release hormones that can increase inflammation, affecting your nervous system and exacerbating RLS.

The potential benefits of this approach have been demonstrated in research. In a small-scale study, individuals with moderate to severe RLS took part in eight 90-minute group therapy sessions. The participants reported notable improvements in their mental health and quality of life following the sessions. These positive effects were sustained for up to three months, highlighting the potential benefits of psychological support in managing RLS symptoms and enhancing overall well-being.

Exploring natural approaches for managing RLS offers a variety of options that can complement your overall treatment plan. While these methods may take more time to show results compared to pharmaceutical treatments, their benefits for your long-term health can be substantial. Patience and consistency are key as you find the right combination that works for you.

• Vitamins C and E: A small trial showed improvement in symptoms of RLS patients undergoing hemodialysis with vitamins C (at 200 milligrams) and E (at 400 milligrams) over the short term.
• Pycnogenol supplements: Research suggests Pycnogenol, a natural extract derived from the bark of the French maritime pine trees, may be effective for managing RLS. In a recent small study published in Panminerva Medica, subjects taking 150 milligrams of Pycnogenol daily for four weeks experienced improvements in their RLS symptoms compared to a control group, including decreases in crawling sensations, throbbing, aching, and sleep problems.
• Moderate aerobic and resistance exercise: Several studies have shown the effectiveness of moderate exercise in reducing RLS symptom severity, with the highest efficacy when aerobic and resistance training are combined. However, it is important to complete any exercise routine at least two to three hours before bedtime because physical activity can stimulate the body and exacerbate RLS symptoms.
• Near-infrared light (NIR): NIR has a high wavelength range that allows it to penetrate the skin deeply. The proposed mechanism explaining its efficacy in RLS is attributed to its ability to generate nitric oxide, which leads to an increase in blood flow and tissue oxygen. In most studies, NIR was used for 30 minutes, three times per week, for four weeks.

Maintaining good sleep habits, or sleep hygiene, can also be an important natural approach for managing RLS. This might include:

• Establishing a consistent sleep schedule by going to bed and waking up at the same time each day, even on weekends
• Creating a relaxing bedtime routine with calming activities like reading or meditation
• Taking a warm bath to help relax your muscles
• Keeping your legs cool once in bed
• Optimizing your sleep environment by keeping it cool, dark, quiet, and free of electronic devices
• Avoiding heavy meals, chocolate, caffeine, and alcohol before bedtime
• Taking magnesium supplements at bedtime to help with relaxation and potentially improve sleep quality

During an RLS episode, you may find relief simply by walking or stretching. Applying a hot or cool compress or massaging your legs may provide further relief.

While primary RLS may not be entirely preventable, there are proactive steps you can take to manage the condition and prevent the development of secondary RLS cases. Making lifestyle changes can be challenging, but having a positive mindset and focusing on what you can control, can take you a long way toward success. Preventive measures include lifestyle modifications, nutritional considerations, and addressing underlying causes.

• Avoid triggers: Steer clear of substances and activities that can exacerbate RLS symptoms, such as chocolate, caffeine, alcohol, tobacco, and activities that overstimulate the central nervous system.
• Manage stress and inflammation: Employ stress-reduction techniques and adopt an anti-inflammatory diet to help minimize the impact of these factors on RLS.
• Stay hydrated: Drink about half of your body weight in ounces daily. For example, if you weigh 150 pounds, drink 75 ounces of water, ideally filtered or pure spring water.
• Ensure adequate iron levels: Maintain proper iron stores with supplementation, if necessary. This is especially important in infants and toddlers during critical developmental stages.
• Optimize vitamin and mineral intake: Eat whole foods and consider supplementing with nutrients like vitamin D, magnesium, and folate, if dietary intake is insufficient. Work with a nutrition professional to determine your individual needs and the appropriate supplementation.
• Prevent underlying conditions: Take steps to prevent or properly manage underlying health issues that can trigger secondary RLS, such as kidney disease, stroke, neuropathy, and Parkinson’s disease. While genetics may predispose you to these conditions, adopting a healthy diet and lifestyle that minimizes toxic exposures can help prevent their onset and progression.
• Review medications: Go over any medications you may be taking that could worsen RLS symptoms and discuss alternative medications or dosage adjustments with your health care practitioner.

By implementing these preventive measures, you can take an active role in managing your risk of developing RLS or mitigating the severity of existing symptoms. Consulting with health care providers can help ensure a comprehensive and personalized approach to RLS prevention and management.