From the Guidelines
High ferritin serum levels have been consistently associated with increased mortality and morbidity in hemodialysis patients, suggesting a negative correlation with longevity. The study by Kuragano and coworkers [@13@] found that high ferritin levels (consistently above 100 µg/L) were associated with an increased risk of acute cardiocerebrovascular disease, infections, and death. Similarly, the DOPPS study [@14@] found that higher adjusted mortality was associated with IV iron doses of 300-399 mg/month and 400 mg/month or more. These findings suggest that excessive iron stores, as reflected by high ferritin levels, may contribute to increased oxidative stress, inflammation, and disruption of homeostasis of iron-regulating hormones, ultimately leading to accelerated morbidity and mortality.
Key findings from the studies include:
- High ferritin levels (>100 µg/L) are associated with increased risk of acute cardiocerebrovascular disease, infections, and death [@13@]
- IV iron doses of 300-399 mg/month and 400 mg/month or more are associated with higher adjusted mortality [@14@]
- Excessive iron stores may contribute to increased oxidative stress, inflammation, and disruption of homeostasis of iron-regulating hormones 1
The mechanisms underlying the negative correlation between high ferritin serum levels and longevity are thought to involve:
- Elevated hepcidin levels, which may reflect a physiologic defense mechanism against iron overload [@83@]
- Increased oxidative stress, which can damage cells and tissues throughout the body [@16@, @88@]
- Arterial and cardiac structural changes, which can increase the risk of cardiovascular disease [@89@, @90@, @91@]
Overall, the evidence suggests that maintaining iron homeostasis is crucial for optimal health, and that high ferritin serum levels should be addressed through strategies such as reducing iron intake, avoiding vitamin C with meals, and consuming coffee or tea with meals to inhibit iron absorption. Regular monitoring of ferritin levels and adjustment of iron therapy as needed is essential to minimize the risks associated with iron overload and promote longevity.
From the Research
Studies on Ferritin Serum Levels and Longevity
- There are studies that suggest a negative correlation between ferritin serum levels and longevity 2.
- Elevated serum ferritin levels have been associated with increased mortality and reduced mortality at ferritin levels <100 ng mL-1 2.
- A study suggests that optimal ferritin levels for cardiovascular mortality reduction range from 20 to 100 ng mL-1, and that ferritin levels above 194 ng mL-1 associate with all-cause mortality in population cohorts 2.
Ferritin as a Measure of Iron Status
- Ferritin concentration is low in iron deficient individuals and high in iron-loaded individuals, regardless of confounding clinical conditions 3, 4.
- Current WHO thresholds for healthy populations appear valid, but the data is limited for different age groups or physiological conditions 4.
- Ferritin concentration is a common clinical practice for diagnosing iron deficiency and overload, but its levels can be elevated in inflammation and infection 3.
Comparison of Iron Supplements
- Ferrous gluconate (FG) and ferrous sulfate (FS) supplements are effective for prophylactic use in the prevention of iron deficiency anemia, but FG may be more effective than FS 5.
- Lactoferrin supplementation has been shown to have better effects on serum iron, ferritin, and hemoglobin concentration compared to ferrous sulfate, and may be a superior supplement for improving iron status and erythropoiesis 6.