The Iron Revolution 2021 Advocacy for IV Iron


Senior Member
The iron revolution: Keeping abreast of the developments in iron therapy (

1 Department of Medicine, Georgetown University School of Medicine, Washington, District of Columbia, USA
2 Department of Clinical Nephrology, King's College Hospital, London, UK
3 Department of Medicine, University of Utah Health Sciences Center, Salt Lake City, Utah, USA
4 Department of Medicine, Pathology and Pediatrics, Knight Cancer Center, Oregon Health Sciences University, Portland, Oregon, USA
5 Division of Surgery, Clinical Trials Unit, University of Western Australia, Perth, Western Australia, Australia

Here, we address several misconceptions which could be misinterpreted as harmful clinical recommendations, and which are contrary to recent clinical practice guidelines in a number of conditions, including heart failure, chronic kidney disease, and cancer.

1. “Oral iron is usually well tolerated.”
While oral iron is the first-line treatment of iron deficiency, the side-effect profile is significant.
Nearly 75% of patients experience side effects which ultimately result in one in four ceasing treatment, predominantly due to significant gastrointestinal perturbation.3

2. “Inappropriate use of intravenous iron in chronic conditions such as cancer and heart failure in the absence of clear iron deficiency can lead to unwanted side effects.”

3. Similarly in cancer and chemotherapy-induced anemia, at least 15 prospective trials, several of which compared oral to intravenous iron, reported clear benefits in energy, activity, and quality of-life with intravenous iron.10

Outcomes have reported increased hemoglobin levels, correction of anemia, reductions in the need for the more expensive erythropoiesis-stimulating agents, reduced need for blood transfusions, and improved patient outcomes in fatigue and quality-of-life.

4. “Intravenous iron should be considered only if oral iron cannot be tolerated.”

While the first-line use of oral iron is recommended, over half of healthy patients will experience side effects that are dose dependent which translate to poor adherence or underdosing.

Additionally, about 20% will not derive any clinical benefit, i.e. oral iron does not work. Indeed, healthy women often suffer for many years with iron deficiency.15

It is important to note that there are many clinical scenarios where oral iron may not be effective.

These include the common and often underdiagnosed symptom of heavy uterine bleeding which can affect one in three women. Blood loss in excess of 1 L per annum can lead to an imbalance in iron supply and demand where oral iron cannot keep up with the losses.16

In the setting of inflammatory bowel disease, oral iron can be toxic to the intestinal epithelium17,18 worsening the disease process itself, and independent of anemia, while causing an incommodious growth of intestinal bacteria negatively altering the microbiome.19

It is increasingly recognized that iron deficiency is very common following bariatric bypass surgery20 either where the duodenum (the location of DMT1 that facilitates iron absorption) is bypassed, or in gastric reduction surgery where oral iron cannot be conjugated to vitamin C, amino acids, and sugars to prevent its conversion to the unabsorbable ferric hydroxide in the proximal duodenum from the massive alkaline secretions from the pancreas.

6. “Iron is not specifically recommended for restless legs syndrome, but a trial of oral iron can be considered.”

Restless legs and muscle cramps are a common and disabling symptom of iron deficiency particularly with serum ferritin levels <15 ng/mL, but also present in conditions exhibiting functional iron deficiency.

Indeed, there are multiple randomized controlled studies supporting the recommendations of the World Sleep Society which recommends iron replacement, especially intravenous iron, when iron deficiency is present, as frontline therapy for restless legs syndrome.23
We propose that the modern intravenous iron formulations represent a revolution in healthcare, enabling one of the most common conditions in the world to be effectively treated, often in just one 20–30-min treatment.