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 the development of iron deficiency anemia, and I strongly recommend taking an oral iron supplement such as ferrous sulfate (325 mg) once or twice daily, as it is the most effective and efficient way to replenish iron stores, according to the British Society of Gastroenterology guidelines for the management of iron deficiency anaemia in adults 1. To address low iron saturation, it is essential to understand the underlying causes and the most effective treatment options. The British Society of Gastroenterology guidelines for the management of iron deficiency anaemia in adults provide a comprehensive approach to diagnosing and treating iron deficiency anaemia, including the use of oral iron supplements 1. Some key points to consider when taking oral iron supplements include:

• Take the supplement on an empty stomach with vitamin C (orange juice or a vitamin C supplement) to enhance absorption
• Avoid taking iron with calcium, dairy products, tea, coffee, or antacids, as these can reduce absorption
• Treatment typically continues for 3-6 months to replenish iron stores
• Common side effects include constipation, dark stools, and stomach upset
• If side effects are problematic, try taking the supplement with food or consider a lower dose It is also important to note that low iron saturation can lead to iron deficiency anemia if left untreated, causing fatigue, weakness, and reduced exercise capacity, as iron is essential for hemoglobin production, which carries oxygen throughout the body 1. In some cases, such as heart failure, intravenous iron replacement may be considered, as it has been shown to improve functional status and quality of life in patients with NYHA class II and III HF and iron deficiency, as recommended by the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Failure Society of America 1. However, the most recent and highest quality study, the British Society of Gastroenterology guidelines for the management of iron deficiency anaemia in adults, recommends oral iron supplements as the first line of treatment for iron deficiency anaemia, and I strongly recommend following this guideline to ensure the best possible outcome for patients with low iron saturation 1.

From the FDA Drug Label

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 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. Patients with PDD-CKD, stable erythropoietin for 8 weeks, hemoglobin of ≤ 11. 5 g/dL, TSAT ≤ 25%, ferritin ≤ 500 ng/mL were randomized to receive either no iron or Venofer (300 mg in 250 mL 0.9% NaCl over 1.5 hours on Day 1 and 15 and 400 mg in 250 mL 0.9% NaCl over 2.5 hours on Day 29).

Low iron saturation is addressed in the studies as patients with low transferrin saturation (TSAT) were included in the studies.

• The studies showed that Venofer treatment increased transferrin saturation in patients with low iron saturation.
• The target TSAT levels are not explicitly stated in the label, but the studies included patients with TSAT ≤ 25% and ≤ 20%.
• Treatment with Venofer resulted in increased TSAT levels, with mean increases ranging from 8.7% to 14% in different studies 2, 2, 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