What Causes Restless Leg Syndrome?

Restless Leg Syndrome

What Is Restless Leg Syndrome?

Restless leg syndrome (RLS) is a common sensorimotor disorder characterised by an urge to move, and associated with uncomfortable sensations in the legs (limbs).

Evidence from case reports and cross-sectional studies suggests that antidepressants may induce or worsen restless legs syndrome, and there is an association with migraines.

An association might be possible with cardiovascular disease, arterial hypertension, diabetes, migraine, and Parkinson disease, but the methodology of studies was poor.

What Causes Restless Leg Syndrome?

  • Brain iron deficiency
  • Dopamine neurotransmission abnormalities
  • Vitamin B12/folate deficiency
  • Kidney disease
  • Peripheral neuropathy (associated with diabetes)
  • Thyroid dysfunction
  • Immune activation (i.e inflammation)
  • Gut imbalances (e.g SIBO – small intestine bacterial overgrowth)
  • Vitamin D deficiency

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In one review the researches 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. 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.

In this situation, we need to investigate and understand the underlying cause of the inflammation – for example whether there is a gut infection.

To add strength to the argument that the gut might be involved one study found that 69% of RLS patients also had SIBO, compared with only 28% of controls. They also found that 28% of RLS patients had IBS, compared to only 4% of controls. And according to the 2012 review I mentioned in the previous section, 32% of the 38 conditions associated with RLS are also associated with SIBO.

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Treatment of Restless Leg Syndrome

It becomes clear then that to recover from restless leg syndrome requires restoring balance to the underlying cause. This may require functional testing to investigate SIBO or large intestine imbalances, nutrient status such as vitamin D, B12, folate and iron, inflammation such as high sensitivity CRP as well as kidney and thyroid function.

I have blogged extensively about SIBO: click here.


  • Restless legs syndrome associated with major diseases: A systematic review and new concept: click here.
  • RLS/Willis-Ekbom Disease Pathophysiology: click here.
  • RLS and nocturnal leg cramps: a review and guide to diagnosis and treatment: click here.
  • The influence of antidepressants on restless legs syndrome and periodic limb movements: A systematic review: click here.
  • RLS associated with major diseases: A systematic review and new concept: click here.
  • Can we now say that commonalities between restless leg syndrome and migraine exist?: click here.
  • Restless legs syndrome is associated with irritable bowel syndrome and small intestinal bacterial overgrowth: click here.
  • An evaluation of sleep quality and the prevalence of restless leg syndrome in vitamin D deficiency: click here.
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