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Top Labs To Run Bi-Annually On Your Patients Who Suffer From Restless Legs Syndrome

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Top Labs To Run Bi-Annually On Your Patients Who Suffer From Restless Legs Syndrome

Restless legs syndrome is a chronic movement and sleep disorder in which patients experience an overwhelming urge to move their legs in a diurnal pattern. Restless legs syndrome affects 5-15% of the population and can occur at any age, from childhood to older than 90 years old. (8

The symptoms of restless legs syndrome cause significant distress and impairment in social and other important areas of functioning by impacting sleep, energy, daily activities, and mood. A root-cause medicine approach to treating restless legs syndrome aims to target underlying factors leading to the development of the disease to provide symptomatic relief and improve quality of life. This article will discuss top functional medicine labs that can help in the functional medicine evaluation of a patient with restless legs syndrome. 


What is Restless Legs Syndrome?

Restless legs syndrome (RLS), or Willis-Ekbom disease, is a neurological disorder that primarily affects the legs and can cause discomfort, tingling, itching, and an irresistible urge to move them. Individuals with RLS often experience these sensations during rest or inactivity, particularly in the evening or at night. The symptoms worsen at night, leading to sleep disturbances and insomnia. RLS is considered both a sleep disorder and a movement disorder due to its characteristic symptoms of discomfort and irresistible leg movements that primarily occur during periods of rest or inactivity, leading to disrupted sleep patterns (9).

Up to 10% of the American population is estimated to have RLS. RLS can begin at any age, affecting both men and women; however, risk factors that increase the likelihood of experiencing the condition include female sex, Caucasian race, pregnancy, and end-stage kidney disease (8).  

There is no known cure for RLS, but conventional medicine utilizes medications and lifestyle changes to manage symptoms and improve quality of life. Lifestyle changes, such as regular exercise, maintaining a healthy and regular sleep routine, and avoiding triggers like caffeine and alcohol, can help alleviate symptoms. Pharmacologic options for symptom management include dopamine agonists, anti-seizure medications, benzodiazepines, and opioids. Addressing underlying medical conditions or iron deficiencies may provide relief in some cases. (9

What Causes Restless Legs Syndrome?  

The exact cause of RLS is not fully understood, but it is thought to involve a combination of genetic and environmental factors. Some potential factors that may contribute to RLS include:


Research has indicated a tendency for RLS to run in some families, suggesting a genetic component to the disorder. Up to 92% of people with RLS have a first-degree relative with the condition. Studies have identified specific genetic variants associated with an increased risk of RLS. These variants are often related to the function of dopamine pathways, described in more detail below. However, genetic risk factors do not guarantee that a person will develop RLS, highlighting the importance of epigenetics in disease development that is yet to be understood entirely.

Dopamine Imbalance 

Dopamine is a neurotransmitter that plays a crucial role in controlling muscle movements and sensations. Changes in dopamine levels in the brain have been linked to RLS. An imbalance in dopamine levels or its receptor activity can lead to abnormal signaling, contributing to the symptoms of RLS. One of the primary treatments for RLS involves using dopamine agonists, medications that help regulate the dopamine signaling pathways and reduce sensations and movements associated with RLS. (1, 6)

Iron is essential for the production of dopamine in the brain. In individuals with RLS, there may be alterations in iron metabolism or storage, leading to reduced dopamine production or disrupted dopamine function. Iron deficiency, even without anemia, has been linked to RLS symptoms. (1, 6)

Medications and Substance Use

Certain medications and substances, such as antihistamines, antidepressants, anti-nausea drugs, caffeine, nicotine, and alcohol, can exacerbate RLS symptoms (11). 

Underlying Medical Conditions

RLS is sometimes associated with other medical conditions, including peripheral neuropathy, diabetes, kidney disease, spinal cord conditions, Parkinson's disease, thyroid disease, pregnancy, and micronutrient imbalances (3).  

Restless Legs Syndrome Symptoms

The chief symptom of RLS is the urge to move the legs, predominantly at night, and may be accompanied by nighttime leg twitches. The unpleasant sensations in the legs and feet are often described as crawling, creeping, pulling, throbbing, aching, itching, and electric. Symptoms of RLS can vary in severity, ranging from mild discomfort to significant disruption of daily life and sleep patterns. (10

Diagnosis is typically based on the presence of specific criteria outlined by medical organizations, including the International Restless Legs Syndrome Study Group (IRLSSG), which has outlined five essential diagnostic criteria for diagnosis:

  • An urge to move the legs, which is usually, but not always, accompanied by or felt to be caused by uncomfortable and unpleasant sensations in the legs
  • The urge to move the legs and any accompanying unpleasant sensations begin or worsen during periods of rest or inactivity
  • The urge to move the legs and any accompanying unpleasant sensations are partially or totally relieved by continued movement
  • The urge to move the legs and any accompanying unpleasant sensations during rest or inactivity only occur or are worse in the evening or night 
  • The occurrence of the above features is not solely accounted for as symptoms primary to another medical or behavioral condition

What Are the Benefits of Regular Lab Testing for Patients With Restless Legs Syndrome?

Regular lab testing for patients with RLS can provide valuable insights and benefits in understanding and managing the condition. While lab testing alone cannot diagnose RLS, it can help identify underlying factors contributing to or exacerbating RLS symptoms, such as iron deficiency, kidney disease, diabetes, and thyroid disorders. Lab testing can help healthcare providers tailor treatment approaches to each patient's needs. Additionally, regular testing can help track changes over time, assess the effectiveness of treatment strategies, and support making necessary adjustments based on the patient's response to medical interventions.

Top Labs to Run Bi-Annually on Patients With Restless Legs Syndrome

Functional medicine offers a variety of tests that helps to rule out underlying medical conditions and contributing factors to RLS and helps tailor treatment options to patients' individual needs. Here are a few tests to consider ordering bi-annually for patients with RLS.

Anemia Panel

Given the association of iron deficiency, with or without anemia, to RLS and the similar symptoms that can present with all conditions, a complete blood count (CBC) and complete iron panel, including ferritin, serum iron, total iron binding capacity, and transferrin saturation, screens for anemia and details a full picture of iron status, metabolism, and distribution throughout the body.

Comprehensive Metabolic Panel

A comprehensive metabolic panel (CMP) measures a variety of biomarkers helpful in diagnosing diabetes, kidney disease, and electrolyte imbalance.

Thyroid Panel

A comprehensive thyroid panel, including at minimum TSH, free T4, and free T3, screens for thyroid disorders, which, if present, can promote uncomfortable muscle sensations and unwanted movements and disrupt sleep patterns. 

Organic Acid Test (OAT)

An OAT is a specialty urine test that provides a comprehensive screening and snapshot into a person's metabolic health and function. By measuring a variety of organic acids in the urine, this test can screen for gastrointestinal dysbiosis, nutrient deficiencies, neurotransmitter imbalances, and dysfunctional energy production pathways.

Gut Health Testing

Ongoing research is being performed to evaluate the connection between RLS and gastrointestinal disorders, including celiac disease, irritable bowel syndrome (IBS), small intestinal bacterial overgrowth (SIBO), and Crohn's disease (3). Tests that can aid in the diagnostic process of these conditions include a serum celiac, IBS, and Crohn's Assay (CICA), comprehensive stool test, and SIBO breath test. For patients in whom you have a strong clinical suspicion of celiac disease or inflammatory bowel disease, refer for a colonoscopy for a definitive diagnosis.



RLS can be a debilitating condition that negatively impacts the quality of life and disrupts healthy sleep patterns. The conventional algorithm for treatment offers palliative treatment options focused on symptomatic management that come with the risk of many undesirable side effects. Functional medicine treatment options emphasizing lifestyle modifications, therapeutic dietary interventions, and nutrient therapy offer great promise in providing RLS relief. The labs discussed in this article should be considered part of any functional medicine evaluation to guide targeted treatment recommendations and monitor treatment progress.

The information provided is not intended to be a substitute for professional medical advice. Always consult with your doctor or other qualified healthcare provider before taking any dietary supplement or making any changes to your diet or exercise routine.
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Lab Tests in This Article


1. Allen, R. (2004). Dopamine and iron in the pathophysiology of restless legs syndrome (RLS). Sleep Medicine, 5(4), 385–391.

2. Cloyd, J. (2023, February 2). Top Lab Test to Run on Your Iron Deficiency Anemia Patients. Rupa Health.

3. DePorto, T. (2022, November 30). Restless Leg Syndrome: Causes, Symptoms, and Treatment. Rupa Health.

4. Dhawan, V., Ali, M., & Chaudhuri, K. R. (2006). Genetic aspects of restless legs syndrome. Postgraduate Medical Journal, 82(972), 626–629.

5. Diagnostic Criteria. International Restless Legs Syndrome Study Group.

6. Dichtl, S., Haschka, D., Nairz, M., et al. (2018). Dopamine promotes cellular iron accumulation and oxidative stress responses in macrophages. Biochemical Pharmacology, 148, 193–201.

7. Diorio, B. (2022, September 23). How to Regulate Your Dopamine Levels Naturally. Rupa Health.

8. Mansur, A., Castillo, P. R., Rocha Cabrero, F., et al. (2020). Restless Leg Syndrome. PubMed; StatPearls Publishing.

9. Restless Legs Syndrome. (2023, August 1). National Institute of Neurological Disorders and Stroke.

10. Restless legs syndrome. (2018). Mayo Clinic.

11. Restless Legs Syndrome (RLS): Causes, Symptoms & Diagnosis. (2020, January 24). Cleveland Clinic.

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