Restless Legs Syndrome Foundation Blog

My Experience with Iron Infusion

I was 12 years old in the summer of 2002 when I began having trouble sleeping. I would wake up in the middle of the night with creepy, crawly feelings in my legs and an immediate urge to get up and move around. I would walk downstairs to my parents’ bedroom to explain what was happening, only to have the symptoms stop when I got to their room. These episodes occurred throughout the night and led to exhaustion, daytime sleepiness and poor grades at school.

I was evaluated by six doctors in six medical specialty areas who could not pinpoint what was causing my sleep problems – or even give it a name. I was told multiple times that I was experiencing “growing pains” that would eventually go away. Finally, I was diagnosed with restless legs syndrome (RLS), and my family’s primary focus became finding a treatment plan to manage my symptoms. When one person’s sleep is affected, the whole family feels the impact of nightly sleep disruptions.

I tried several conventional RLS treatments, however, none thoroughly relieved my symptoms. My ferritin level was tested and found to be considerably low. Because I was so young at the time, intravenous (IV) iron wasn’t an easily accessible option for me. So, I began a course of oral iron to see if I could raise my ferritin level. For about 14 years, I tried several different oral iron preparations, combinations of oral iron, and different dosages and times of administration, but tests confirmed that none of these treatment strategies was effective in raising my ferritin level above the 75–100 mcg/L target range for individuals with RLS.

My RLS doctor tracked and plotted my ferritin level with successive iron tests. Despite my adherence to oral iron administration guidelines, I eventually reached a point where the iron stores in my body would not meet or exceed mid-level values for ferritin. At that point, my RLS doctor discussed with me the risks and benefits of IV iron, coordinated my care with a hematologist, and provided instructions for IV iron administration for me as an RLS patient.

In 2016, I found a hematologist to administer IV iron as a way to increase my ferritin level. For my first iron infusion, I received low-molecular-weight iron dextran (INFeD). Other formulations of IV iron were used in subsequent infusions.

Iron infusions are relatively easy procedures that, from start to finish, take about two to six hours, depending on the type of iron formulation approved by your insurance company. First, the nurse checks your vital signs and sets up equipment to monitor your pulse and blood pressure. Second, an IV is started, and a test dose of the iron preparation is administered by IV. This is followed by an observation period of up to one hour. During the observation period, the nurse watches to make sure there aren’t any allergic reactions to the test dose. If you do not experience any allergic reactions, the nurse administers the full IV iron dose via a pump to ensure a controlled rate of infusion. Throughout the infusion period, the nurse continues to monitor your vital signs and check to see if you are having any unusual feelings that may indicate a side effect of the therapy. Once the iron infusion is complete, the IV cannula is removed, vital signs are checked for the last time and you are allowed to go home.

Since my first iron infusion, I’ve received this treatment about once every two years. I’ve noticed two main symptoms that usually indicate my ferritin levels are low: feeling more tired during the day and restless feelings in my legs. That means it’s time for another iron infusion.

For me, iron infusions have made a significant difference in helping to increase my ferritin levels, which in turn make my RLS more manageable. I still limit my caffeine intake, exercise daily, and maintain a normal sleep schedule by trying to go to bed and wake up around the same times each day. However, I know that my increased ferritin levels, resulting from iron infusion therapy, have led to a significant decrease in the restless sensations that would otherwise keep me awake at night and seriously affect my quality of life.

For more information see Evidence-based and consensus clinical practice guidelines for the iron treatment of restless legs syndrome/Willis-Ekbom disease in adults and children: an IRLSSG task force report.

Iron, Diet and Management of Iron Levels

The relationship between RLS and iron is complex, but research over the last two decades has increased the understanding of this relationship. It is now clear that brain iron deficiency plays a significant role in the development of RLS.

Dietary Iron

Iron intake from diet is essential for maintaining iron stores in the body. Unfortunately, the body absorbs only 10%–15% of dietary iron, and all ingested iron is not absorbed equally. Knowledge of iron sources in the diet will help people make choices that aid in the maintenance of iron stores in the body.

Dietary forms of iron are divided into two categories: heme iron and nonheme iron. Heme iron is only found in animal sources such as meat, poultry, fish and shellfish, and is easily absorbed in the gut. The body absorbs about 15%–35% of heme iron intake. To enhance the absorption of iron, foods rich in iron should be consumed with foods rich in vitamin C, such as orange juice, bell peppers and tomatoes. It is the acid environment in the stomach caused by vitamin C that helps iron absorption. Conversely, some items can impair the absorption of iron in foods. These items include the tannins found in tea and coffee, and the calcium in milk products and antacids.

Nonheme sources of iron include leafy greens, nuts, seeds, whole grains, legumes and fortified cereals. Although these foods are a source of iron, the iron they contain is not easily absorbed by the body. The percentage of nonheme iron absorbed is only 5%–12% because the human gastrointestinal tract does not readily absorb this type of iron.

Medical Conditions

Several medical conditions can further impair iron absorption in the gastrointestinal tract, leading to iron deficiency anemia, a state of low stores of iron in the body. Malabsorption of nutrients, including iron, occurs with medical conditions such as:

• Celiac disease
• Ulcerative colitis
• Crohn’s disease
• Small intestinal bacterial overgrowth
• Irritable bowel syndrome

Iron deficiency anemia is also common during pregnancy due to increased blood volume and the need for additional iron by the mother and fetus. In addition, blood loss resulting from heavy menstrual cycles, surgery, or chronic blood loss due to peptic ulcers, hiatal hernia, polyps or cancer can cause iron deficiency anemia.

Brain Iron Deficiency and Iron Supplementation

Lack of available iron affects the brain and the dopaminergic system. Brain iron deficiency and dysfunction of the dopaminergic system play a central role in the development of RLS. That is why every individual with RLS needs to monitor their iron status and the steps they need to take to maintain their iron stores at the recommended levels. Low stores of body iron, as measured by serum ferritin levels and low serum iron saturation levels, correlate with low iron in the brain and the worsening of RLS symptoms.

RLS researchers recommend a serum ferritin measurement of 100 mcg/L or above to minimize the severity of RLS symptoms. If dietary sources of iron are insufficient to maintain iron stores in RLS patients, oral iron supplementation is the next step to help keep serum ferritin in the acceptable range. Oral iron is recommended when serum ferritin is less than 75 mcg/L, with the goal of raising serum ferritin levels to 100 mcg/L within three months of initiating therapy.

Guidelines to achieve maximum absorption of supplementary oral iron include:

• Use ferrous sulfate 325 mg tablets with 60–65 mg elemental iron (check the bottle, as the amount varies), taken once daily with a beverage containing vitamin C or with a 250 mg tablet of vitamin C.
• Take the oral iron at night; iron redistribution in the brain is highest during the nighttime hours and studies suggest it may be better absorbed later in the day.
• Avoid consuming tea, coffee, products containing calcium (dairy products, antacids), and reflux medications within two hours of taking oral iron.
• Schedule oral iron four hours before or after taking thyroid medications to maintain the effectiveness of the thyroid medication.

Intravenous (IV) iron infusion should be considered if ferritin levels of 100 mcg/L or above are not achieved after three months of oral iron therapy. In two recent randomized, double-blind, placebo-controlled studies, RLS patients with a normal hemoglobin level, serum ferritin of less than 300 mcg/L, and transferrin saturation of less than 45% were administered 1,000 mg of iron intravenously and showed improvement in their RLS symptoms. After infusion, it takes six to eight weeks to evaluate iron status and symptom improvement.

Administering IV iron to RLS patients with low serum ferritin levels will quickly raise those levels above 100 mcg/L and improve their symptoms in less time than it takes to evaluate the effects of oral iron supplementation. For individuals with low serum ferritin and a high level of symptom severity, IV iron is an important treatment consideration to ensure adequate iron stores in the body, iron distribution in the brain and better management of RLS symptoms. In patients with falsely elevated ferritin levels due to inflammation or infection, a low serum iron saturation of less than 20% may be a better indication of the need for iron supplementation.

Conclusion

For people with RLS, maintaining iron stores at therapeutic levels requires a close working relationship with an RLS provider who understands the connection between the level of iron stores in the body and its impact on RLS symptoms. Revision of an RLS treatment plan based on a periodic evaluation of iron tests will ensure better management of RLS symptoms and an improved quality of life.

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."