Restless Legs Syndrome Foundation Blog

October 21, 2020

Study: Hemoglobin Levels, Not Serum Ferritin, May Indicate a Better Response to Iron Intervention

Iron is fundamental to the healthy functioning of the body’s organs, including the brain. Its connection to the production of red blood cells is also a major determining factor in clinical practice when prescribing iron intervention. However, according to some scientists, the guidelines for iron replacement in neurological disorders, such as restless leg syndrome (RLS), are poorly defined.

“The current thinking, although not supported by all RLS physicians, is that serum ferritin levels are a measure of iron status and serve as a guidepost for iron replacement therapy," said RLS Foundation Scientific and Medical Advisory Board Member, Dr. James R. Connor. However, new research conducted by Connor and his team, and published in Fluids Barriers CNS, suggests that a patient’s hemoglobin levels may be a better indicator in determining the treatment guidelines for iron therapy.

The researchers conducted a preliminary research study to determine if the body’s iron status is communicated to the brain and they were able to show that iron transport does relate positively with hemoglobin (iron level measurement in the blood), but not with serum ferritin levels.

The team created a model to test their hypothesis. Using a cell culture model to mimic the blood vessels in the brain, they placed transferrin complexed with iron on one side of the cells (representing the blood side) and they put human cerebrospinal fluid on the other side of the cells which represented the brain side. The cerebrospinal fluid was randomly selected from more than 350 individuals enrolled in a study at Emory University for symptoms of excessive daytime sleepiness or other neurological disorders of excessive daytime sleepiness such as narcolepsy. Four additional samples came from an RLS study at Johns Hopkins University. Study samples were derived solely from females of northern European ancestry between the ages of 35 to 66 who were not considered anemic, a condition lacking healthy red blood cells.

The scientists said according to their findings, "the demand for iron for the production of blood cells in the bone marrow outweighs brain iron requirements. Thus, the study is showing that serum ferritin level, which is the traditional metric that is thought to reflect total body iron stores and relied upon to inform treatment decisions, may not be the preferred lab test when attempting to promote brain iron uptake.”

Connor said the data suggests that the hemoglobin levels may be a better indicator of which patients will respond to iron intervention and explains some of the individual differences in responders. "The data in this study supports physicians who consider serum ferritin levels an insufficient measure to determine which patients will respond to iron interventions. The next step would be to evaluate how hemoglobin levels impact response to iron treatment in RLS in a large population study."