RESUMO
Iron deficiency is a widespread global health concern with varying prevalence rates across different regions. In developing countries, scarcity of food and chronic infections contribute to iron deficiency, while in industrialized nations, reduced food intake and dietary preferences affect iron status. Other causes that can lead to iron deficiency are conditions and diseases that result in reduced intestinal iron absorption and blood loss. In addition, iron absorption and its bioavailability are influenced by the composition of the diet. Individuals with increased iron needs, including infants, adolescents, and athletes, are particularly vulnerable to deficiency. Severe iron deficiency can lead to anemia with performance intolerance or shortness of breath. In addition, even without anemia, iron deficiency leads to mental and physical fatigue, which points to the fundamental biological importance of iron, especially in mitochondrial function and the respiratory chain. Standard oral iron supplementation often results in gastrointestinal side effects and poor compliance. Low-dose iron therapy seems to be a valid and reasonable therapeutic option due to reduced hepatic hepcidin formation, facilitating efficient iron resorption, replenishment of iron storage, and causing significantly fewer side effects. Elevated iron levels influence gut microbiota composition, favoring pathogenic bacteria and potentially disrupting metabolic and immune functions. Protective bacteria, such as bifidobacteria and lactobacilli, are particularly susceptible to increased iron levels. Dysbiosis resulting from iron supplementation may contribute to gastrointestinal disorders, inflammatory bowel disease, and metabolic disturbances. Furthermore, gut microbiota alterations have been linked to mental health issues. Future iron therapy should consider low-dose supplementation to mitigate adverse effects and the impact on the gut microbiome. A comprehensive understanding of the interplay between iron intake, gut microbiota, and human health is crucial for optimizing therapeutic approaches and minimizing potential risks associated with iron supplementation.
RESUMO
BACKGROUND: Iron deficiency without anaemia is a common health problem, especially in young menstruating women. The efficacy of the usually recommended oral iron supplementation is limited due to increased plasma hepcidin concentration, which reduces iron absorption and leads to side effects such as intestinal irritation. This observation raises the question of how low-dose iron therapy may affect plasma hepcidin levels and whether oral iron intake dose-dependently affects plasma hepcidin production. METHODS: Fifteen non-anaemic women with iron deficiency (serum ferritin ≤30 ng/ml) received a single dose of 0, 6, 30, or 60 mg of elemental oral iron as ferrous sulfate on different days. Plasma hepcidin was measured before and seven hours after each dose. RESULTS: Subjects had an average age of 23 (standard deviation = 3.0) years and serum ferritin of 24 ng/ml (interquartile range = 16-27). The highest mean change in plasma hepcidin levels was measured after ingesting 60 mg of iron, increasing from 2.1 ng/ml (interquartile range = 1.6-2.9) to 4.1 ng/ml (interquartile range = 2.5-6.9; p < 0.001). Iron had a significant dose-dependent effect on the absolute change in plasma hepcidin (p = 0.008), where lower iron dose supplementation resulted in lower plasma hepcidin levels. Serum ferritin levels were significantly correlated with fasting plasma hepcidin levels (R2 = 0.504, p = 0.003) and the change in plasma hepcidin concentration after iron intake (R2 = 0.529, p = 0.002). CONCLUSION: We found a dose-dependent effect of iron supplementation on plasma hepcidin levels. Lower iron dosage results in a smaller increase in hepcidin and might thus lead to more efficient intestinal iron absorption and fewer side effects. The effectiveness and side effects of low-dose iron treatment in women with iron deficiency should be further investigated. This study was registered at the Swiss National Clinical Trials Portal (2021-00312) and ClinicalTrials.gov (NCT04735848).