Causes of the Restless Legs Syndrome (RLS)
Often there is no known cause for restless legs syndrome (RLS). In this case it is called idiopathic RLS.
Is the restless leg syndrome inhered?
RLS runs in families especially if the RLS begins before the age of 40. Researchers have identified a number of chromosomes that are associated with RLS. Genetics plays a massive role with 40% to 90% of individuals with RLS having at least one first-degree relative with the condition. Monozygotic twin concordance ranges between 54% and 83%.
A powerful landmark study, analyzing data from over 100,000 people with RLS, identifies 164 distinct genetic loci related to RLS. A number of genes (such as MEIS1, BTBD9, and PTPRD) found in RLS are involved in the embryonic development of the central nervous system (CNS). This finding has altered the view of researchers and clinicians from RLS being a random adult sleep issue to actually being a neurodevelopmental condition. It appears that the inherent vulnerabilities leading to RLS are genetically coded before birth although symptoms don't typically present until adulthood.
The MEIS1 gene is the single most strong genetic factor associated with RLS. MEIS1 is intrinsically linked to how the brain regulates iron and dopamine. Low iron (see "Iron" section below) and low dopamine (see "Dopamine" section below) increase the propensity for RLS.
Even though the genetic factor appears strong in RLS, it remains a polygenic disorder (a collection of genetic risks that add up). Whether the presence of risk factor genes actually trigger symptoms depends greatly on environmental and biological influencers.
Does age affect the restless legs syndrome?
RLS can occur at any age even in children. Approximately 2% to 4% of children and adolescents (age 0 to 17) are affected by RLS. However, RLS is more likely to occur as age increases. In early adult years (age 20 to 44) the prevalence of RLS increases to approximately 5.5% to 7.1%. Most people are diagnosed with RLS after age 40. Mature adults and seniors (age 45 to 79) have a RLS prevalence of approximately 7.5% to 8.7%. This is the age bracket where the gender gap widens significantly with RLS becoming more prevalent in females. In addition to the higher prevalence in the older population there is also an increase in the severity of RLS with symptoms becoming more severe and frequent.
Does gender influence the restless legs syndrome?
RLS is approximately twice as common in women. Prevalence of RLS in women is approximately 10% to 13% whilst in males the prevalence is approximately 5% to 8%. Higher RLS prevalence in women is often attributed to pregnancy. About 1 in 4 pregnant women experience RLS, particularly during the third trimester (For more information, see the Restless legs syndrome in pregnancy). The good news is that it normally subsides after delivery. It has been reported that the number of pregnancies is positively linked to long-term chronic RLS. Other factors leading to RLS in women include iron deficiency (due to menstruation) and hormonal fluctuations. Fluctuations in estrogen and progesterone are highly linked to symptom onset and severity. This explains why many women first notice symptoms during puberty or pregnancy.
The role of Dopamine in the restless legs syndrome
Researchers have identified that in people with RLS there is an imbalance of dopamine in the brain. Dopamine is involved in the transmission of messages from the basal ganglia (involved in smoothing and regulating movement) in the brain to controlling smooth muscle movement. Likely due to the endogenous circadian rhythm (body clock), RLS symptoms tend to worsen at night due to low dopamine. This is often exacerbated by low brain iron levels (see Iron section below), which are necessary for dopamine production. It is not always just a lack of dopamine, but also rather a complex dysfunction in the down regulation of dopamine receptors (D2R and D3) that causes the neurological urge to move. In RLS dopamine receptor reduction is reportedly caused by an excessive amount of presynaptic dopamine being produced during daytime. This elevated dopamine results in the downregulation of dopamine receptors.
In summary RLS is caused / worsened by low dopamine combined with a double whammy of low numbers of dopamine receptors. This crash in dopamine regulation then reduces the inhibition of sensory / motor signals to the extremities leading to the uncomfortable sensation and irresistible urge to move.
Did you know coffee is bad for the restless legs syndrome (RLS). Look at your coffee intake. Caffeine keeps people awake by acting as a molecular "mute button" for the brain’s fatigue signals. It does not actually provide the body with energy; rather, it prevents the brain from receiving the chemical message that you are tired. Throughout the day, as the brain neurons fire, they produce adenosine as a byproduct. Adenosine builds up over the course of the day and binds to specific receptors (A1 and A2A Receptors) in the brain, signaling to the body that it is time to slow down and rest. This is known as "sleep pressure." Because caffeine’s molecular structure is very similar to adenosine, it can "sneak" into the adenosine receptors. Caffeine stops adenosine from binding. Because caffeine does not trigger the same slowing-down effect as adenosine, the brain remains in an alert state, unaware of the mounting fatigue. This lack of sleep pressure makes it hard to fall asleep if there is caffeine in your system. Also the arousal state caused by caffeine stimulates the "irresistible urge" to move the legs and make the uncomfortable sensations associated with the RLS feel more pronounced.
Is low iron causing my RLS?
What is dopamine and how does it effect Restless Legs Syndrome (RLS)? Dopamine is a neurotransmitter that neurons (nerve cells) use to communicate with one another in the brain and the rest of the body. Dopamine's Core Function is with motivation and reward. It creates the anticipation and motivation to seek out rewarding experiences. It is involved in reinforcement: When you engage in a behavior that your brain deems beneficial (like eating, socializing, or achieving a goal), a surge of dopamine reinforces that pathway, making you more likely to repeat the action. Dopamine helps your brain decide what is "important" or worth paying attention to in your environment. While popularly referred to as the "pleasure chemical," its role is much more nuanced and fundamental to biology. Dopamine is essential for motor control. It is produced in several areas of the brain, including the substantia nigra. Within the basal ganglia (the brain's movement control center) dopamine acts as a regulator that helps ensure movements are smooth, coordinated, and properly initiated. In RLS there is a dysregulation of dopamine with low evening dopamine levels contributing to the "creepy crawly" leg sensations and the involuntary urges to move. The lack of dopamine inhibits the motor signals leading to RLS.
The relationship between low iron and RLS is one of the most critical factors in understanding the condition. Iron is a fundamental requirement for brain chemistry that regulates movement. Iron is a necessary "cofactor" for an enzyme called tyrosine hydroxylase. This enzyme is responsible for producing dopamine in the brain. So low iron leads to low tyrosine hydroxylase such that the result is a reduced amount of dopamine in turn leading to RLS. Since dopamine is the neurotransmitter that controls smooth, purposeful muscle movement, a lack of it leads to the "misfiring" signals yielding the crawling, tingling, and irresistible urge to move characterizing RLS.
As well as reducing the amount of available dopamine iron regulates dopamine transporters and receptors levels in the substantia nigra (modulates smooth physical movement). A low iron level downregulates dopamine receptor functionality destabilizing movement control loops causing / worsening RLS.
For the general population, a ferritin level of 30 ng/mL might be considered "normal." However, for someone with RLS, medical guidelines often suggest keeping ferritin levels above 75 ng/mL or even 100 ng/mL to manage symptoms. Although iron is an over-the-counter medication too much iron can be harmful. Getting an iron studies blood test is recommended.
What role does Glutamate play in the restless legs syndrome?
Glutamate is the principal excitatory neurotransmitter in the central nervous system (CNS) acting like the brain's accelerator pedal. Iron and dopamine have long been the key players in understanding RLS causes. However, glutamate is emerging as a key neurotransmitter regulating the severity of the symptoms, the nighttime restlessness, and the overall hyperarousal state in RLS. Genetic and neuroimaging studies indicate that persons with genetic predispositions for RLS have a presynaptic hyperglutamatergic state (the neurons produce too much glutamate, particularly at night). There is also reduced synaptic inhibition of glutamate further elevating glutamate. The increased excitation caused by excess glutamate overstimulates the cortico-striatal-thalamic-cortical circuit (the brain loop regulating movement, sensory processing, and sleep arousal), creating that disruptive, "creepy crawly" intense sensation with an urge to move. When glutamate levels are abnormally high the brain struggles to suppress minor physical sensations, leading to the crawling, itching, or pulling feelings in the legs. High glutamate drives the uncontrollable urge to move the limbs to relieve those sensations. Normally, glutamate levels drop at night to allow deep, restful sleep. In individuals with RLS, glutamate levels remain elevated throughout the night, causing persistent micro-arousals and a state of central hyperarousal where the brain remains alert even during rest. It is possible that this arousal state further disrupts sleep leading to daytime somnolence.
Glutamate doesn't act in isolation; it interacts directly with brain iron deficiency and dopamine signaling. Iron deficiency reduces dopamine receptor function. Dopamine normally helps to inhibit excessive glutamate release. When dopamine regulation fails, glutamate signaling goes into overdrive, causing sensorimotor hyperexcitability.
Did you know that the foods you eat may influence the Restless Legs Syndrome (RLS). Firstly, there are some foods to avoid namely drinks containing caffeine (e.g., coffee, energy drinks). Alcohol interferes with sleep cycles including the circadian rhythm. This worsens RLS. High-sugar diets and highly processed foods are linked to inflammation, which may negatively impact RLS symptoms. There are some foods that may help relieve some of the RLS leg discomfort and the urge to move. Iron is a critical factor in RLS. Red meat, poultry, seafood, beans, lentils, and iron-fortified cereals are all high in iron. Magnesium helps muscles relax and supports proper nerve function. Foods containing magnesium include almonds, cashews, peanuts, spinach, edamame, and black beans. Folate (B9) is essential for healthy nerve and cell function. Dark leafy greens (spinach), liver, and legumes are sources of Folate. Potassium aids in muscle contraction and nerve impulses. Foods containing potassium include Bananas, leafy greens, and various fruits/vegetables. So eat well and hopefully the RLS will reduce.
RLS during pregnancy
Yes, pregnancy can be associated with the onset of RLS. Up to 15% – 25% of pregnant women experience RLS, typically peaking in the third trimester before resolving after delivery. The number of pregnancies a woman has is also a predictor of having RLS. Because many standard medications for RLS are not recommended during pregnancy, the primary approach focuses on conservative, non-drug lifestyle changes under the guidance of a healthcare provider. Non Pharmacological strategies to treat RLS in pregnancy are outline in the "Prevention" page and "Getting relief" page.
Does smoking influence RLS? Like caffeine and alcohol, nicotine is a stimulant that can interfere with your ability to fall and stay asleep. Since fatigue and poor sleep quality are major triggers that worsen RLS symptoms, the use of nicotine (especially close to bedtime) can create a cycle where your RLS symptoms become more severe. Most healthcare providers include smoking cessation as a standard part of their lifestyle recommendations for RLS management. However, all that said some individuals reopt the smoking provides temporary relief from the "creepy crawly" feelings and the urge to move. Nicotine increases dopamine which is key in RLS modulation so it is understandable that smoking may actually improve RLS. Saying all that it has been reported that smoking is only a very temporary fix and in the long-term RLS symptoms will surface. In any event smoking cessation is beneficial on many levels.
Is restless legs a sign of nerve damage?
Peripheral neuropathy is a condition whereby there is damage to the nerves in the hands and / or feet felt as numbness or tingling in the extremeties. There is a connection between peripheral neuropathy and RLS. Studies show that anywhere from 5% to over 30% of people with peripheral neuropathy also suffer from RLS, a rate much higher than reported in the general population. The RLS from peripheral neuropathy results from damaged nerves in the extremities sending signals to the brain telling it to move the limbs to alleviate the uncomfortable sensation. RLS on the other hand originates in the brain sending signals down to the legs. It can be difficult to deduce the source of the RLS uncomfortable sensations.
Medications like gabapentin or pregabalin (see the "Treatments" page) are commonly prescribed for nerve pain. Because these medications calm down the overactive "misfiring" peripheral nerves, they frequently pull double-duty and significantly reduce RLS symptoms as well.
Parkinson's disease
Parkinson’s disease is a neurological disorder that elicits a drop in dopamine in the brain region called the substantia nigra effecting movement, balance and coordination. Both Parkinson's and RLS are dopaminergic disorders. People with Parkinson's are more likely to develop RLS and in some cases the RLS occurs prior to the Parkinson's disorder. It is reported that about 20% of Parkinson's patients have RLS. Although results from clinical prevalence studies show a wide variation from 0% to 52%.
What medications cause the restless legs syndrome?
Did you know that the Restless Legs Syndrome (RLS) has a significant and well-documented impact on mental health. While RLS is primarily a neurological condition, its effects often extend far beyond physical discomfort to emotional distress and mental health issues. Approximately 2 out of every 5 people with RLS also experience a psychiatric condition. The severity of RLS is directly correlated with the severity of mental health symptoms. There is a well documented correlation between RLS symptoms and mental health symptoms. As RLS symptoms worsen, scores for mental health, vitality, and social functioning often decrease. There's a bit of the chicken and the egg happening with mental health and RLS. RLS related sleep deprivation can trigger or worsen depression and anxiety, while people with existing mental health conditions are also more likely to experience RLS symptoms. RLS can lead to anxiety and stress about, when will you get to sleep and when will the uncomfortable feeling in the legs stop. Chronic sleep loss leads to daytime sleepiness in turn causing chronic fatigue and lethargy. Other daytime symptoms of RLS include irritability, feelings of hopelessness, and difficulty finding joy in daily activities. All of these feelings can over time contribute to the development of clinical depression. There are a wide range of medications available to treat depression. However, many of these antidepressants can actually worsen the RLS symptoms. Work with your healthcare provider to take "RLS safe" medications.
Some medications for other disorders may lead to RLS. These include some antidepressants, antipsychotic, antinausea, cold and allergy medications. These are further discussed in the page “Medications that worsen RLS”.
Varicose veins
Venous insufficiency has reportedly been found to occur in 22% of RLS patients. This has led some researchers to surmise that varicose veins play a role in causing RLS. Varicose veins / blood pooling is caused by damage to tiny valves in the veins that help stop blood pooling and direct the blood back to the heart. Action of the leg muscles, in particular the calf muscle, help the circulation of the blood out of the legs. Once a person with varicose veins becomes seated or supine there is no calf leg muscle activity to assist blood back to the heart and the blood pools in the calf causing build up of metabolic waste products and tissue inflammation. This build up in turn causes localized nerve irritation which manifests as an uncomfortable, creeping, or tingling sensation. Activating the calf muscles through movement results in the emptying of the stagnant blood out of your legs temporarily clearing the irritation. This leg discomfort-movement cycle is precisely the diagnostic criteria applied to RLS. However, in varicose veins the direction of restlessness is from the leg nerves to the CNS. Whereas in Primary RLS the direction of the restlessness is from the CNS to the legs (the opposite of varicose veins).
Treatment for varicose veins may alleviate RLS symptoms. Treatment modalities include compression stockings, laser treatments and sclerotherapy.
Sleep deprivation
RLS and sleep deprivation are a classic medical viscous cycle. RLS can cause chronic sleep loss leading to sleep deprivation from an inability to fall asleep and disruption of sleep architecture once asleep. Sleep deprivation elicits a downregulation of dopamine receptors in the brain causing the central nervous system to become more sensitive lowering your pain and discomfort thresholds, causing RLS symptoms to strike earlier in the evening and feel significantly more intense. (see "Dopamine" above)
Sleep deprivation caused by other mechanisms / disorders (e.g. sleep apnoea hypopnoea syndrome [SAHS] or poor sleep hygiene) can lead to worsening of RLS.
Kidney failure
The link between kidney failure (particularly End-Stage Renal Disease [ESRD]) and RLS is incredibly strong. While RLS affects roughly 5% to 10% of the general population, it skyrockets to affect 20% to 40% of patients on long-term dialysis.
One mechanism whereby kidney failure may cause RLS is Uremic Toxin Build up. This is elevated levels of toxins like urea, creatinine, and other metabolic by products. These circulating toxins are inherently neurotoxic. They irritate and damage peripheral nerves (causing peripheral neuropathy; see above) and alter brain chemistry, lowering the threshold for RLS symptoms to fire.
ESRD is related to severe iron deficiency and anemia. Kidneys produce a hormone called erythropoietin (EPO), which tells the body to make red blood cells. In kidney failure, EPO production plummets, leading to severe anemia. Dialysis itself also causes chronic iron loss, starving the central nervous system of the iron it needs to keep dopamine pathways functioning smoothly. (See "Iron" and "Dopamine" above). The low iron and dopamine increase the propensity of RLS. Intravenous (IV) iron infusions are often given during dialysis to bypass absorption issues and directly boost iron stores.
When kidneys fail, calcium levels often drop while phosphate levels spike. This imbalance, alongside fluctuations in potassium and magnesium, makes peripheral nerves hyper-excitable, leading directly to the classic twitching, crawling, and cramping sensations of RLS. With kidney transplant RLS resolves in days to weeks.
Spinal cord conditions
The prevalence of RLS is significantly higher in individuals with spinal disorders than in the general population. The spinal cord acts as the main superhighway for communication between the brain and the limbs. When the spinal cord is damaged it can trigger the classic RLS symptoms: The brain normally sends calming, "inhibitory" signals down the spinal cord to keep the limbs quiet during rest. Spinal cord damage can block these signals. Without that natural braking system, the spinal cord's reflex pathways become hyperexcitable, creating the typical RLS uncomfortable restless sensations that forces movement.
There is a specific pathway of dopamine-producing cells (the A11 group) that runs from the brain down the entire span of the spinal cord. Because RLS is closely tied to dopamine dysfunction, any physical lesion or compression along the cord can disrupt this pathway triggering RLS symptoms. There are five spinal cord disorders that can result in RLS.
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Spinal Cord Injury (SCI): Research indicates that roughly 18% to 19% of people with SCI experience RLS. RLS is more frequently associated with incomplete spinal cord injuries and lower (lumbosacral) lesions.
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Myelopathy & Spinal Stenosis: Cervical or thoracic spondylotic myelopathy (severe spinal cord compression due to wear-and-tear or narrowing of the spinal canal) can cause treatment-resistant RLS.
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Herniated Discs and Nerve Impingement: A severe slipped or herniated disc that pinches nerve roots or presses directly against the cord can alter sensory feedback generating lower-limb RLS.
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Multiple Sclerosis (MS): MS causes the immune system to attack the protective coating of nerves in the central nervous system. Lesions specifically located in the spinal cord are highly correlated with RLS.
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Spinal Vascular Issues: Though rare, sudden, acute flare-ups of RLS have occasionally been traced back to spinal cord ischemia (a temporary lack of blood flow to the cord).
Diabetes
There is a strong and well-documented link between diabetes and RLS. While about 10% of the general population experiences RLS, that number jumps significantly for people living with diabetes to approximately 20%. There are 3 potential mechanisms whereby diabetes may worsen RLS.
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Diabetic Neuropathy (Nerve Damage): Chronic high blood sugar can damage the tiny blood vessels that supply your nerves, especially in the legs and feet. This nerve damage can cause tingling, burning, or "creepy-crawly" sensations that mimic or directly trigger RLS symptoms.
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Iron Deficiency & Kidney Function: People with diabetes are at a higher risk for chronic kidney disease and anemia. Low iron levels and compromised kidney function are both major secondary causes of RLS.
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The Sleep-Sugar Vicious Cycle: RLS causes sleep deprivation. Poor sleep throws off the body's insulin sensitivity and glucose metabolism, making blood sugar even harder to control the next day worsening the diabetes leading to increased RLS symptoms.
Dogs may get restless legs syndrome (RLS), yes really. Signs that your pooch is having an episode of RLS are: 1. Dog frequently changing positions or appearing unable to settle while lying down. 2. Nighttime pacing such as getting up, moving around, lying down, and repeating this cycle frequently. 3. Kicking or twitching hind legs while resting. 4. Whining or barking, which may indicate physical discomfort during these periods of restlessness.
Multiple sclerosis (MS)
There is a strong, established connection between Multiple Sclerosis (MS) and RLS. Research shows that people with MS are up to 4 times more likely to develop RLS than the general public. There are several mechanisms whereby MS leads to RLS.
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Central Nervous System Lesions: MS causes the immune system to attack the protective coating (myelin) of nerves in the brain and spinal cord. When these lesions form in the spinal cord or specific brain regions (like the basal ganglia, which controls movement), it disrupts the normal signaling pathways to the legs resulting in RLS symptoms.
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Dopamine Disruption: The basal ganglia relies heavily on dopamine (see the "Dopamine" section above). MS lesions can disrupt how the brain processes dopamine, which is the exact underlying mechanism that triggers RLS.
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Increased Nerve Irritation: MS already causes sensory symptoms like numbness, tingling, and "pins and needles" (dysesthesia). At night, these sensations can blend with or intensify the classic urge to move your legs.
Fatigue is already one of the most debilitating symptoms of MS. When RLS prevents falling or staying asleep, it creates a brutal fatigue cycle. Chronic sleep deprivation directly worsens MS-related fatigue, makes brain fog more severe, and can even increase your sensitivity to daily MS pain.
For more information see the "Causes" section from Wikipedia.
Last reviewed 31/07/2026
Who would have thought, jellyfish, even having no brain, still seem to manage sleep. Scientists have observed that jellyfish meet the three critical criteria for sleep: 1. Reduced Activity (Quiescence): They experience periods of inactivity, such as a decrease in the frequency of their rhythmic pulsing. 2. While in this quiescent state, jellyfish are less responsive to external stimuli (like water pulses) and slower to react to their environment. 3. If disturbed or "kept awake" during their rest, jellyfish exhibit a "rebound" effect, showing an increased tendency to fall into that sleep-like state during periods when they would normally be active. Because jellyfish have no actual brain, but rather decentralized neural networks (nerve nets), implies that sleep is a fundamental process for cellular maintenance that likely predates the evolution of complex brains. It appears that sleep is hardwired into the DNA of the most simple of living organisms. Evolution has maintained sleep as an important factor in humans and other living organisms. This suggests that even very simple nervous systems to complex animals (e.g. humans) require downtime for repair and stability.