Abstract
Ferrous sulfate is a commonly used iron supplement for the correction of iron-deficiency anemia but with frequent gastrointestinal side effects. Milk-derived iron-binding glycoprotein lactoferrin possesses well gastrointestinal tolerance and fewer side effects caused by the intake of high-dose iron. However, the underlying mechanism of the iron-enhancing effect of lactoferrin remains unclear. In addition, the comparative efficacies between lactoferrin and ferrous sulfate are also remained to be determined. We conducted a systematic review and meta-analysis on published intervention studies to investigate how lactoferrin modulate iron metabolism and evaluate the comparative effects between lactoferrin and ferrous sulfate supplementation on iron absorption, iron storage, erythropoiesis and inflammation. Lactoferrin supplementation had better effects on serum iron (WMD: 41.44 ug/dL; p < 0.00001), ferritin (WMD: 13.60 ng/mL; p = 0.003) and hemoglobin concentration (11.80 g/dL; p < 0.00001), but a reducing effect on fractional iron absorption (WMD: −2.08%; p = 0.02) and IL-6 levels (WMD: −45.59 pg/mL; p < 0.00001) compared with ferrous sulfate. In conclusion, this study supports lactoferrin as a superior supplement to ferrous sulfate regarding the improvement in serum iron parameters and hemoglobin levels. Considering the weak influence of lactoferrin on iron absorption, the anti-inflammation effect of lactoferrin may be the potential mechanism to explain its efficacy on iron status and erythropoiesis.
Highlights
Iron is a necessary trace element for all mammals and involved in many essential metabolic processes such as oxygen transport, mitochondrial respiration and enzymatic activities [1]
Following criteria were used in literature evaluation: (1) clinical trials conducted in Iron deficiency (ID)/iron-deficiency anemia (IDA) or healthy individuals; (2) study reporting baseline and post-intervention results on iron status (including at least one of the following outcomes: hemoglobin concentration; total serum iron (SI); serum ferritin (SF); and fractional iron absorption (FIA); (3) the intervention substance was lactoferrin or bovine lactoferrin, and ferrous sulfate must be used in control groups
Literature searching and selection process are presented in IDA [31,32,33,34,35,36]; 6 studies were performed in pregnant women [31,32,33,34,35,36] and 4 studies in nonpregnant women [34,36,37]
Summary
Iron is a necessary trace element for all mammals and involved in many essential metabolic processes such as oxygen transport, mitochondrial respiration and enzymatic activities [1]. The deficiency of iron will lead to the metabolic abnormality in all parts of human bodies. The most common manifestations of iron deficiency are fatigue, headache and paleness [2]. Iron deficiency (ID) impairs cardiac function in the elderly and neurocognitive development in infants [1]. Children suffering from severe iron deficiency are associated with cognitive dysplasia, delayed body development, and low productivity [3,4]. The depletion of iron will restrict hemoglobin synthesis and result in iron-deficiency anemia (IDA) [5,6]. IDA is the unique preventable and theorical easier treatable of the main and more frequent years lived with disabilities (YLDs) in the whole world [7]
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