In the last 20 years, there has been a substantial amount of
research into understanding the cause of RLS. From that research
there appears to be three factors which are pertinent to the
disease: brain concentrations of iron, brain dopamine
concentrations and genes. Role of Iron in RLS The single most
consistent finding and the strongest environmental risk factor
associated with RLS is iron insufficiency. Professor Nordlander
first recognized the association between iron deficiency and
RLS, and reported that treatment of the iron deficiency markedly
improved, if not eliminated, the RLS symptoms. Despite this
strong association between serum iron insufficiency and RLS,
only about 15% of the RLS clinical population appears to have
peripheral iron deficiency (serum ferritin < 50 mcg/l). To
account for this, Professor Nordlander in proposing his “iron
deficiency” hypothesis of RLS stated: “it is possible…that there
can exist an iron deficiency in the tissues in spite of normal
serum iron”. This hypothesis has led