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.
REFERENCES
3. “Increased prevalence of restless legs syndrome in patients with Crohn’s disease.” http://www.ncbi.nlm.nih.gov/pubmed/25951489
4. “Restless legs syndrome–theoretical roles of inflammatory and immune mechanisms.” http://www.ncbi.nlm.nih.gov/pubmed/22258033
5. “Elevated C-reactive protein is associated with severe periodic leg movements of sleep in patients with restless legs syndrome.” http://www.ncbi.nlm.nih.gov/pubmed/22750520
6. “Low-dose hydrocortisone in the evening modulates symptom severity in restless legs syndrome.” http://www.ncbi.nlm.nih.gov/pubmed/18443313
Chris Kresser, M.S., L.Ac is a globally recognized leader in the fields of ancestral health, Paleo nutrition, and functional and integrative medicine. He is the creator of ChrisKresser.com, one of the top 25 natural health sites in the world, and the author of the New York Times best seller, Your Personal Paleo Code (published in paperback in December 2014 as The Paleo Cure). You can read the full article here: http://chriskresser.com/4-little-known-causes-of-restless-legs-syndrome
The Restless Legs Blog (or how I tried to convince Big Pharma that my legs are better) 