What are the implications of low iron saturation, also known as Hypoferremia?

From the Guidelines

Low iron saturation is a condition that requires prompt attention to prevent fatigue, weakness, and other complications, and I strongly recommend taking an oral iron supplement such as ferrous sulfate (325 mg) once or twice daily, as indicated by the most recent guidelines 1. To address low iron saturation, it is essential to understand the underlying causes and symptoms. Low iron saturation can cause fatigue, weakness, pale skin, headaches, and difficulty concentrating due to reduced oxygen transport in the blood.

Key Considerations

• The British Society of Gastroenterology guidelines for the management of iron deficiency anaemia in adults recommend using serum ferritin as the most specific test for iron deficiency in the absence of inflammation 1.
• A serum ferritin level of <15 μg/L is indicative of absent iron stores, while levels of less than 30 μg/L are generally indicative of low body iron stores 1.
• An SF cut-off of 45 μg/L has been suggested as providing the optimal trade-off between sensitivity and specificity for iron deficiency in practice 1.

Treatment and Management

• Oral iron supplements, such as ferrous sulfate, are the first line of treatment for low iron saturation, and should be taken on an empty stomach with vitamin C to enhance absorption 1.
• Treatment typically continues for 3-6 months to replenish iron stores, even after symptoms improve.
• Increasing dietary iron by consuming lean red meat, beans, lentils, spinach, and fortified cereals can also help alleviate low iron saturation.
• Regular blood tests are crucial to monitor progress and adjust treatment as needed.

Special Considerations

• In patients with heart failure, intravenous iron replacement may be considered to improve functional status and quality of life, especially in those with iron deficiency and a transferrin saturation of <20% 1.
• However, the evidence base for oral iron repletion in the setting of anemia associated with heart failure is uncertain, and more research is needed to determine its effectiveness 1.

From the FDA Drug Label

Serum ferritin increased at endpoint of study from baseline in the Venofer-treated population (165.3 ± 24.2 ng/mL) compared to the historical control population (-27.6 ± 9. 5 ng/mL). Transferrin saturation also increased at endpoint of study from baseline in the Venofer-treated population (8.8 ± 1.6%) compared to this historical control population (-5.1 ± 4.3%). Increases in mean hemoglobin (1.1 ± 0.2 g/dL), hematocrit (3.6 ± 0.6%), serum ferritin (266.3 ± 30.3 ng/mL) and transferrin saturation (8.7 ± 2.0%) were observed from baseline to end of treatment. Increases from baseline in mean hemoglobin (1. 7 g/dL), hematocrit (5%), serum ferritin (434.6 ng/mL), and serum transferrin saturation (14%) were observed at week 2 of the observation period and these values remained increased at week 4 of the observation period.

Low iron saturation can be treated with iron (IV) as it increases transferrin saturation.

• The studies show an increase in transferrin saturation after treatment with iron (IV) 2.
• The increase in transferrin saturation is observed in different patient populations, including those with HDD-CKD and NDD-CKD 2.
• The treatment with iron (IV) also leads to an increase in hemoglobin and serum ferritin levels 2.

From the Research

Low Iron Saturation

• Low iron saturation can be treated with oral iron supplementation, which is usually the first line of treatment 3, 4, 5
• Oral iron supplementation can be effective in correcting iron-deficiency anemia and replenishing iron stores, but may cause gastrointestinal side effects that reduce compliance 3, 5
• The optimal dosage and frequency of oral iron supplementation are still being researched, with some studies suggesting that alternate-day schedules and morning single doses may increase iron absorption and reduce side effects 4
• Intravenous iron therapy can be used when oral iron supplementation is contraindicated or ineffective, and can rapidly achieve therapeutic targets without gastrointestinal complications 3, 6, 7
• The choice between oral and intravenous iron supplementation depends on various factors, including the presence of inflammation, the time available for iron replenishment, and the anticipated risk of side-effects or intolerance 6
• Markers of iron status, such as serum ferritin and transferrin saturation, can indicate a need for intravenous iron supplementation 7
• Different regimens are available for giving intravenous iron, including low-dose, medium-dose, and high-dose administration 7