Iron supplementation in affective disorders and / or post-traumatic stress disorder (PTSD) and / or serotonin-dependent diseases

Abstract

Subject matter of the present invention is iron supplementation for treatment and / or prophylaxis of an affective disorder and / or post-traumatic stress disorder (PTSD) and / or serotonin-dependent diseases in a human patient in need thereof. Subject matter of the present invention is in particular iron supplementation for treatment and / or prophylaxis of depression, in particular of a major depressive disorder (MDD) in a human patient in need thereof.

Description

[0001] M75416WO BOEHMERT & BOEHMERTIron supplementation in affective disorders and / or post-traumatic stress disorder (PTSD) and / or serotonin-dependent diseases Subject matter of the present invention is iron supplementation for treatment and / or prophylaxis of an affective disorder and / or post-traumatic stress disorder (PTSD) and / or serotonin-dependent diseases in a human patient in need thereof. Subject matter of the present invention is in particular iron supplementation for treatment and / or prophylaxis of depression, in particular of a major depressive disorder (MDD) in a human patient in need thereof. Introduction The incidence of depression is increasing, making it a leading cause of disability around the world and a relevant contributor to the global burden of disease (Kendrick T et al., Patient-reported outcome measures for monitoring primary care patients with depression (PROMDEP): study protocol for a randomized controlled trial, BMC Trials 2020;21(1):441). According to 2020 data, the economic burden of major depressive disorder (MDD) among US adults increased from $US 236 billion in 2010 to $US 326 billion in 2018 (Greenberg PE et al., The economic burden of adults with major depressive disorder in the United States (2010 and 2018), Pharmacoeconomics 2021;39(6):653-65.). The search for new therapeutic concepts remains at utmost importance: Despite the availability of numerous antidepressant medications, around 50% of patients with MDD do not respond to treatment, and even more do not achieve remission. While relapse is common, mid- and long-term adverse events include weight changes, sexual dysfunction, and insomnia, which often affect patient compliance. While iron is known to be essential for oxygen utilization and mitochondrial function, the treatment of concomitant iron deficiency in heart failure has now emerged as a guideline‐endorsed therapy, which improves exercise capabilities while reducing inflammation (Von Haehling S, et al, Iron deficiency and cardiovascular disease. Nat Rev Cardiol 2015;12(11):659-69, McDonagh TA, et al, 2021 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J 2021;42(36):3599-726). Meanwhile, an increasing body of evidence indicates that iron also has an important role in neurologic function and development, since it is involved in brain development, neurotransmitter synthesis and myelination of neurons (Hare D, et al., A delicate balance: Iron metabolism and diseases of the brain. Front Aging Neurosci 2013;5:34). Iron deficiency causes reduced myelination in the brain and impairs monoamine metabolism (Lee HS et al., Psychiatric disorders risk in patients with iron deficiency anemia and association with iron supplementation medications: a nationwide database analysis. BMC Psychiatry 2020;20(1):216, and Todorich B et al., Oligodendrocytes and myelination: the role of iron. Glia 2009;57(5):467–78). The present invention provides for iron supplementation for treatment and / or prophylaxis of an affective disorder and / or post-traumatic stress disorder (PTSD) and / or serotonin-dependent diseases in a human patient in need thereof. Subject matter of the present invention Subject matter of the present invention is iron supplementation for treatment and / or prophylaxis of an affective disorder and / or post-traumatic stress disorder (PTSD) and / or serotonin-dependent diseases in a human patient in need thereof. The treatment and / or prophylaxis involving iron supplementation according to the present invention is in particular directed at alleviating depression by correcting the biochemical disturbances in neurotransmitter synthesis that result from impaired iron homeostasis. In this context, the iron supplementation of the present invention serves to enhance iron availability in the brain, thereby supporting the production of neurotransmitters essential for mood regulation and cognitive processes. This approach is mainly biochemical, aiming to restore normal iron balance within the body. As a result, iron levels are increased systemically, including within the brain. The described treatment and / or prophylaxis is straightforward and non-invasive with respect to brain tissue, and does not require the use of specialized equipment.Subject matter of the present invention is in particular iron supplementation for treatment and / or prophylaxis of an affective disorder and / or post-traumatic stress disorder (PTSD) and / or serotonin-dependent disease in a human patient in need thereof, wherein said disorder or disease is depression, more particularly a major depressive disorder (MDD). Subject matter of the present invention is in particular iron supplementation for treatment and / or prophylaxis of an affective disorder. Subject matter of the present invention is in particular iron supplementation for treatment and / or prophylaxis of post-traumatic stress disorder (PTSD). One embodiment of the present invention is iron supplementation for treatment and / or prophylaxis of an affective disorder and / or post-traumatic stress disorder (PTSD) and / or serotonin-dependent diseases in a human patient in need thereof, wherein said patient has a ferritin level equal or above 0 µg / L, equal or above 15 µg / L, preferably equal or above 20 µg / L, preferably equal or above 30 µg / L, more preferably equal or above 40 µg / L, more preferably equal or above 50 µg / L, more preferably equal or above 60 µg / L, more preferably equal or above 70 µg / L, more preferably equal or above 80 µg / L, more preferably equal or above 90 µg / L, most preferably equal or above 100 µg / L. One particular embodiment of the present invention is iron supplementation for treatment and / or prophylaxis of an affective disorder and / or post-traumatic stress disorder (PTSD) and / or serotonin- dependent diseases in a human patient in need thereof, wherein said patient has a ferritin level equal or above 15 µg / L, preferably equal or above 20 µg / L, preferably equal or above 30 µg / L, more preferably equal or above 40 µg / L, more preferably equal or above 50 µg / L, more preferably equal or above 60 µg / L, more preferably equal or above 70 µg / L, more preferably equal or above 80 µg / L, more preferably equal or above 90 µg / L, most preferably equal or above 100 µg / L. One embodiment of the present invention is iron supplementation for treatment and / or prophylaxis of an affective disorder and / or post-traumatic stress disorder (PTSD) and / or serotonin-dependent diseases in a human patient in need thereof, wherein said patient has a ferritin level in a range of 0 µg / L to 600 µg / L, preferably in a range of 15 µg / L to 500 µg / L, preferably in a range of 20 µg / L to 400 µg / L, more preferably in a range of 30 µg / L to 300 µg / L, more preferably in a range of 40 µg / L to 200 µg / L, more preferably in a range of 50 µg / L to 150 µg / L and most preferably in a range of 60 µg / L to 100 µg / L. One particular embodiment of the present invention is iron supplementation for treatment and / or prophylaxis of an affective disorder and / or post-traumatic stress disorder (PTSD) and / or serotonin- dependent diseases in a human patient in need thereof, wherein said patient has a ferritin level in a range of 15 µg / L to 600 µg / L, preferably in a range of 15 µg / L to 500 µg / L, preferably in a range of 20 µg / L to 400 µg / L, more preferably in a range of 30 µg / L to 300 µg / L, more preferably in a range of 40 µg / L to 200 µg / L, more preferably in a range of 50 µg / L to 150 µg / L and most preferably in a range of 60 µg / L to 100 µg / L. One embodiment of the present invention is is iron supplementation for treatment and / or prophylaxis of an affective disorder and / or post-traumatic stress disorder (PTSD) and / or serotonin-dependent diseases in a human patient in need thereof, wherein said patient does not suffer from an iron defiency and wherein iron deficiency is defined as ferritin levels of < 15 µg / L . In another embodiment said ferritin levels are serum ferritin levels of < 15 µg / L. In another embodiment said ferritin levels are whole blood or serum and / or serum ferritin levels of < 15 µg / L. In case of doubt, if the measured ferritin values differ between whole blood, plasma, and serum samples, the ferritin value determined in the serum sample is to be used as the definitive value. In particular embodiments, the patient has a ferritin level of < 300 μg per liter, more particularly 15 to < 300 µg per liter. Ferritin levels (or concentrations) are determined in a sample obtained from said subject, particularly a sample selected from the group comprising whole blood, serum, or plasma, more particularly serum. According to WHO criteria, Ferritin levels between 0 and <15 µg / L define iron deficiency in apparently healthy individuals (i.e. without known infection or inflammation, without known chronic internal disease), while ferritin levels between 15 and <300 µg / L in individuals without infection or inflammation define appropriate iron status. In particular embodiments, iron supplementation is not administered in subjects with known infection or inflammation. Ferritin is usually determined by quantitative and / or qualitative methods, by immunoassay and / or clinical chemistry, and / or immunologic, and / or photometric, and / or chromatographic and / or mass spectrometric methods. In one embodiment of the present invention, ferritin is measured in serum and / or plasma, preferably in serum. In one embodiment ferritin is measured to determine the iron status of a patient. Particular assays for the determination of ferritin level or concentration in the present invention are based on an immunoassay principle, for example an enzyme-linked immunosorbent assay (ELISA) or a chemiluminescence immunoassay (CLIA). The assay uses specific binders, e.g. antibodies that bind to ferritin and enable a quantitative determination. Other particular assays for the determination of ferritin level or concentration use one or more of the following techniques: Immunoturbidimetric assays; clinical chemistry methods, including photometric assays measuring ferritin based on its interaction with specific reagents, resulting in a detectable colorimetric or spectrophotometric signal; chromatographic methods, such as high-performance liquid chromatography (HPLC), which can separate and quantify ferritin based on its physicochemical properties; mass spectrometric methods, including liquid chromatography-tandem mass spectrometry (LC-MS / MS), which can provide highly specific and sensitive detection of ferritin through its mass-to- charge ratio and fragmentation patterns. In one embodiment, the measurement of ferritin is utilized to assess the iron status of a patient. Specifically, ferritin levels are correlated with iron storage levels in the body, where low ferritin concentrations indicate iron deficiency and elevated ferritin levels may suggest iron overload or other pathological conditions, such as inflammation or liver disease. The method of the present invention is particularly advantageous for diagnosing and monitoring iron-related disorders, including but not limited to iron deficiency anemia, hemochromatosis, and chronic disease-related anemia. Particular assays to determine the ferritin level in the present invention comprise:- a ferritin capture binder, e.g. an anti-ferritin antibody, particularly a monoclonal anti-ferritinantibody, which is immobilized on a solid support, e.g. a microtiter plate; -adding the sample obtained from the subject, e.g. serum or plasma to the aforementioned solidsupport with immobilized capture binder; -incubate so that ferritin from the sample binds to the capture binder;- adding a second, labeled, e.g. enzyme-labeled, ferritin binder, e.g. a labeled anti-ferritinantibody; -optionally washing to remove unbound labeled binder;- optionally adding a substrate (e.g. TMB);- measuring the signal from the labeled binder, determining therefreom the amount of boundferritin and calculating the level or concentration of ferritin in said sample; said signal may be a variety of signals, depending on the label, such as e.g. a fluorescence signal from a fluorophore label or more preferably the conversion of a substrate by an enzyme label, which produces a colored or luminescent signal. The intensity of the signal is measured photometrically or luminescence-based and can be compared with a standard curve to determine the ferritin concentration. In more particularl mebodiments of the invention, an assay for the determination of ferritin level or concentration in a sample, such as serum or plasma, from said subject, is based on a sandwich enzyme- linked immunosorbent assay (ELISA) methodology. This assay is typically prepared by immobilizing a capture antibody specific to human ferritin on a solid support, typically a microtiter plate, typically made of polystyrene; whrein the antibody is a polyclonal or monoclonal anti-ferritin antibody previously raised in a host species (e.g., rabbit or mouse) and diluted in a coating buffer (e.g., carbonate-bicarbonate buffer, pH 9.6) to a concentration of approximately 1–10 µg / mL; incubating the solid support with this solution (e.g., 100 µL per well in case of a microtiter plate), e.g. overnight at 4°C or for 2 hours at room temperature (25°C) to allow the antibody to adsorb onto the surface of the solid support; washing with a washing buffer (e.g., phosphate-buffered saline with 0.05% Tween-20, pH 7.4) to remove unbound antibody, and blocking the solid support with a protein-containing solution (e.g., 1% bovine serum albumin in phosphate-buffered saline), e.g. for 1–2 hours at room temperature, to prevent non-specific binding. The assay can be conducted by a method comprising: -providing a first ferritin antibody (capture antibody) immobilized on a solid support, which maybe prepared as described above; -adding a sample, e.g., serum or plasma, obtained from the subject, which in particular is dilutedappropriately to ensure the ferritin concentration falls within the assay’s dynamic range, e.g., 1:10 or 1:100, in a diluent such as phosphate-buffered saline with 0.1% bovine serum albumin; optionally adding multiple aliquots of the diluted sample to batches or wells of the solid support in duplicate or triplicate; -optionally adding samples of known ferritin concentrations (e.g., purified human ferritinranging from 0.5 to 500 ng / mL) and / or a blank (i.e. a control sample, comprising diluent only) to separate wells or batches of the solid support (allowing generating a standard curve); -incubating the solid support with added samples, e.g. for 1–2 hours at 37°C or room temperature,allowing the ferritin in the sample to bind to the capture antibody; -washing the solid support, e.g. three times, with a washing buffer to remove unbound material,- adding a second anti-ferritin antibody (detection antibody), e.g. a monoclonal antibodyrecognizing a different epitope of ferritin than the first antibody, conjugated to an enzyme, such as horseradish peroxidase (HRP) or alkaline phosphatase (AP), wherein typically the detection antibody is diluted, e.g., 1:1000 to 1:5000, in a buffer, e.g., phosphate-buffered saline with 0.1% bovine serum albumin, and wherein e.g., 100 µL of said diluted detection antibody are added to each well or batch of the solid support; -incubating the solid support, e.g. for 1–2 hours at 37°C or room temperature (allowing thedetection antibody to bind to ferritin in the sample); -washing the solid support, e.g. three to five times; with a washing buffer to remove unbounddetection antibody; -adding a solution of a substrate specific to the detection antibody-enzyme conjugate, e.g.,tetramethylbenzidine (TMB) for HRP or p-nitrophenyl phosphate for AP; -incubating the solid support, e.g. for 10–30 minutes at room temperature in the dark (duringwhich the enzyme catalyzes a colorimetric reaction proportional to the amount of bound ferritin); -stopping the reaction by adding a stop solution, e.g., 1 M sulfuric acid for TMB (this alsoenhances the color change for HRP-based systems); -measuring the absorbance of each well using a reader, e.g. a microtiter plate reader, at awavelength specific to the substrate (e.g., 450 nm for TMB after stopping, or 405 nm for p- nitrophenyl phosphate); -determining the ferritin concentration in the sample by comparing the absorbance valuesdetermined for the (diluted) sample to a standard curve, typically using a logarithmic or four- parameter logistic regression fit. Such an assay offers a detection range of approximately 0.5–500 ng / mL, with a sensitivity of around 0.5 ng / mL, depending on the antibodies and enzyme system used. The intra-assay and inter-assay coefficients of variation are generally less than 10%, ensuring reproducibility. The method can be adapted by adjusting incubation times, antibody concentrations, or sample dilutions to suit specific needs, and it is compatible with automated systems for higher throughput if desired. Another embodiment of the present invention is iron supplementation for treatment and / or prophylaxis of an affective disorder and / or post-traumatic stress disorder (PTSD) and / or serotonin-dependent diseases in a human patient in need thereof, wherein said iron supplementation is administered independent of iron deficiency and / or anemia of a patient and wherein iron deficiency is defined as ferritin levels of < 15 µg / L, preferably ferritin levels of ≤ 12 µg / L, more preferably ferritin levels of ≤ 10 µg / L. In another embodiment ferritin levels are whole blood or serum and / or plasma ferritin levels. In case of doubt, if the measured ferritin values differ between whole blood, plasma, and serum samples, the ferritin value determined in the serum sample is to be used as the definitive value. In another embodiment ferritin levels are serum and / or plasma ferritin levels of < 15 µg / L.Here, in a further embodiment of the present invention, iron supplementation for treatment of the affective disorder and / or post-traumatic stress disorder (PTSD) and / or serotonin-dependent diseases in a human patient is performed irrespective of the iron status of the patient. In further embodiments, ferritin is usually determined by quantitative methods, by immunoassay and / or clinical chemistry, and / or immunologic, and / or photometric, and / or chromatographic and / or mass spectrometric methods as detailed herein. In other embodiments ferritin is determined by quantitative methods, by immunoassay and / or clinical chemistry, and / or immunologic, and / or photometric, and / or chromatographic and / or mass spectrometric methods. Particular assays for the determination of ferritin level or concentration in the present invention are in certain embodiments based on an immunoassay principle, for example an enzyme-linked immunosorbent assay (ELISA) or a chemiluminescence immunoassay (CLIA). The assay uses in particular embodiments specific binders, e.g. antibodies that bind to ferritin and enable a quantitative determination. Iron deficiency according to the present invention is a condition characterized by a reduction in the body’s iron stores, which may occur with or without the development of anemia. Iron is an essential micronutrient required for numerous physiological processes, including oxygen transport, DNA synthesis, and cellular respiration. The primary storage form of iron in the body is ferritin, and the assessment of serum ferritin concentration is widely recognized as a reliable indicator of total body iron stores. Iron deficiency typically develops in stages. In the initial stage, iron stores become depleted, as reflected by a reduction in serum ferritin levels, while hemoglobin concentrations remain within the normal range. This stage is referred to as iron deficiency without anemia. The key distinction between iron deficiency and iron deficiency anemia lies in the presence or absence of anemia. Iron deficiency refers to depleted iron stores, as evidenced by low serum ferritin, but with preserved hemoglobin levels. In contrast, iron deficiency anemia is characterized by both depleted iron stores and reduced hemoglobin concentration, signifying impaired erythropoiesis due to insufficient iron availability. Some embodiments of the present invention relate to an iron supplementation for treatment and / or prophylaxis of an affective disorder and / or post-traumatic stress disorder (PTSD) and / or serotonin- dependent diseases in a human patient in need thereof, wherein said patient does not suffer from an iron deficiency and wherein iron deficiency is defined as whole blood or plasma and / or serum or whole blood ferritin level of less than 15 µg / L in said patient. Particular embodiments of the present invention relate to an iron supplementation for treatment and / or prophylaxis of an affective disorder and / or post-traumatic stress disorder (PTSD) and / or serotonin- dependent diseases in a human patient in need thereof, wherein said patient does not suffer from an iron deficiency, wherein iron deficiency is defined as whole blood or plasma and / or serum or whole blood ferritin level of less than 15 µg / L in said patient and wherein ferritin is determined by methods according to the state of the art selected from the group comprising quantitative and / or qualitative methods, an immunoassay and / or clinical chemistry, and / or immunologic, and / or photometric, and / or chromatographic and / or mass spectrometric methods. In case of doubt, if the measured ferritin values differ between whole blood, plasma, and serum samples, the ferritin value determined in the serum sample is to be used as the definitive value. Anemia is a blood disorder in which the blood has a reduced ability to carry oxygen. This can be due to a lower than normal number of red blood cells, a reduction in the amount of hemoglobin available for oxygen transport, or abnormalities in hemoglobin that impair its function. Anemia can be caused e.g. by decreased red blood cell production, which may be caused by iron deficiency, folate deficiency, vitamin B12 deficiency, thalassemia and a number of bone marrow tumors. Anemia can be classified based on the amount of hemoglobin in each cell. The diagnosis of anemia in men is based on a hemoglobin of less than 130 to 140 g / L (13 to 14 g / dL); in women, it is less than 120 to 130 g / L (12 to 13 g / dL).In other embodiments, the diagnosis of anemia is based on hemoglobin level of less than 12 g / dL in females and 13 g / dL in males. Further embodiments of the present invention relate to iron supplementation for treatment and / or prophylaxis of an affective disorder and / or post-traumatic stress disorder (PTSD) and / or serotonin- dependent diseases in a human patient in need thereof, wherein said patient does not suffer from anemia and wherein anemia is defined as a whole blood hemoglobin level of less than 12 g / dL in females and a whole blood hemoglobin level less than 13 g / dL in males. Further embodiments of the present invention relate to iron supplementation for treatment and / or prophylaxis of affective disorder and / or post-traumatic stress disorder (PTSD) and / or serotonin- dependent diseases in a human patient in need thereof, wherein said patient is a non-anemic patient, a mild anemic patient or a subclinical anemic patient. Further embodiments of the present invention relate to iron supplementation for treatment and / or prophylaxis of affective disorder and / or post-traumatic stress disorder (PTSD) and / or serotonin- dependent diseases in a human patient in need thereof, wherein said patient is a non-anemic female and has a whole blood hemoglobin level of greater than or equal to 12 g / dL or said patient is a non-anemic male and has a whole blood hemoglobin level of greater than or equal to 13 g / dL. Further embodiments of the present invention relate to iron supplementation for treatment and / or prophylaxis of affective disorder and / or post-traumatic stress disorder (PTSD) and / or serotonin- dependent diseases in a human patient in need thereof, wherein said patient is a non-anemic female or mild anemic female and has a whole blood hemoglobin level of greater than 11 g / dL or said patient is a non-anemic male or a mild anemic male and has a whole blood hemoglobin level of greater than 12 g / d L. Further embodiments of the present invention relate to iron supplementation for treatment and / or prophylaxis of affective disorder and / or post-traumatic stress disorder (PTSD) and / or serotonin- dependent diseases in a human patient in need thereof, wherein said patient is a non-anemic female or a mild anemic female or a subclinical anemic female and has a whole blood hemoglobin level of greater than 10 g / dL or said patient is a non-anemic male or a mild anemic male or a subclinical anemic male and has a whole blood hemoglobin level of greater than 11 g / d L. Further embodiments of the present invention relate to iron supplementation for treatment and / or prophylaxis of affective disorder and / or post-traumatic stress disorder (PTSD) and / or serotonin- dependent diseases in a human patient in need thereof, wherein said patient is a mild anemic female and has a whole blood hemoglobin level of 11 g / dL to less than 12 g / dL or said patient is a mild anemic male and has a whole blood hemoglobin level of 12 g / dL to less than 13 g / dL. Further embodiments of the present invention relate to iron supplementation for treatment and / or prophylaxis of affective disorder and / or post-traumatic stress disorder (PTSD) and / or serotonin- dependent diseases in a human patient in need thereof, wherein said patient is a subclinical anemic female and has a whole blood hemoglobin level of 10 g / dL to less than 11 g / dL or said patient is a subclinical anemic male and has a whole blood hemoglobin level of 11 g / d L to less than 12 g / dL. Further embodiments of the present invention relate to iron supplementation for treatment and / or prophylaxis of affective disorder and / or post-traumatic stress disorder (PTSD) and / or serotonin- dependent diseases in a human patient in need thereof, wherein said patient does not suffer from an iron deficiency and wherein iron deficiency is defined as whole blood or plasma and / or serum ferritin level of less than 15 µg / L in said patient. Further embodiments of the present invention relate to iron supplementation for treatment and / or prophylaxis of an affective disorder and / or post-traumatic stress disorder (PTSD) and / or serotonin- dependent diseases in a human patient in need thereof, wherein said patient does not suffer from iron deficiency anemia and wherein iron deficiency anemia is defined as whole blood hemoglobin level of less than 12 g / dL in females and a whole blood hemoglobin level less than 13 g / dL in males and concomitant whole blood or plasma and / or serum ferritin level of less than 15 µg / L. In case of doubt, if the measured ferritin values differ between whole blood, plasma, and serum samples, the ferritin value determined in the serum sample is to be used as the definitive value. Further embodiments of the present invention relate to iron supplementation for treatment and / or prophylaxis of affective disorder and / or post-traumatic stress disorder (PTSD) and / or serotonin- dependent diseases in a human patient in need thereof, wherein said patient is female and wherein said female is a non-pregnant female. Further embodiments of the present invention relate to iron supplementation for treatment and / or prophylaxis of affective disorder and / or post-traumatic stress disorder (PTSD) and / or serotonin- dependent diseases in a human patient in need thereof, wherein said patient is female and wherein said female is a pregnant female. Further embodiments of the present invention relate to iron supplementation for treatment and / or prophylaxis of affective disorder and / or post-traumatic stress disorder (PTSD) and / or serotonin- dependent diseases in a human patient in need thereof, wherein said patient is 18 years or above, preferably 15 years or above. Further embodiments of the present invention relate to iron supplementation for treatment and / or prophylaxis of affective disorder and / or post-traumatic stress disorder (PTSD) and / or serotonin- dependent diseases in a human patient in need thereof, wherein said patient is below 15 years old, preferably below 12 years old, more preferably below 5 years old. In certain embodiments of the present invention, the patient as detailed herein does not suffer from anemia, preferably not from anemia or subclinical anemia, more preferably not from mild anemia or subclinical anemia or anemia. Throughout the application, it is mentioned “plasma and / or serum or whole blood in a patient” in the context of ferritin or hemoglobin level This may be substituted by “ferritin and / or hemoglobin level in a sample of said patient, wherein the sample is selected from the group comprising plasma and / or serum or whole blood.” In certain embodiments of the present invention, this may be substituted by “ferritin and / or hemoglobin level in a sample taken from said patient, wherein the sample is selected from the group comprising plasma and / or serum or whole blood.” In certain embodiments of the present invention, this may be substituted by “ferritin and / or hemoglobin level are determined in a sample taken from said patient, wherein the sample is selected from the group comprising plasma and / or serum or whole blood.” In particular embodiments, hemoglobin is measured using the cyanmethemoglobin method, which is knonwn to the skilled person and is the gold standard (recommended by the ICSH (International Council for Standardization in Haematology)) for hemoglobin measurement due to its accuracy, reliability, and standardization. Automated hematology analyzers are widely used in clinical laboratories for routine hemoglobin testing as part of a complete blood count. In said method, hemoglobin is oxidized to hemiglobin with potassium hexacyanoferrate(III). In a subsequent reaction, the hemiglobin formed reacts with potassium cyanide to form hemiglobin cyanide. Hemiglobin cyanide can be determined photometrically at a avelength has of 546 (where it has an absorption maximum). The alternative Sysmex SLS hemoglobin method uses cyanide-free sodium lauryl sulfate (SLS). As iron depletion progresses, the body’s capacity to produce hemoglobin is compromised, ultimately resulting in a reduction of hemoglobin concentration below established reference values. This advanced stage is termed iron deficiency anemia. In one embodiment of the present invention, anemia is iron-deficiency anemia. Iron deficiency anemia is thus defined as a condition in which both iron stores (as indicated by serum ferritin) are depleted and hemoglobin concentration falls below the lower limit of normal, as defined by population-specific reference ranges. According to World Health Organization (WHO) criteria, anemia is present when hemoglobin concentration is less than 13.0 g / dL in men aged 15 years and above, less than 12.0 g / dL in non-pregnant women aged 15 years and above, and less than 11.0 g / dL in pregnant women or children aged 6–59 months. Iron deficiency is generally indicated by a serum ferritin concentration of less than 15 µg / L in adults or less than 12 ng / mL in children under 5 years. In particular embodiments of the present invention, iron deficiency anemia is defined as haemoglobin concentrations of less than 13.0 g / dL in men aged 15 years and above, less than 12.0 g / dL in non- pregnant women aged 15 years and above, less than 11.0 g / dL in pregnant women or children aged 6– 59 months and / or serum ferritin concentration of less than 15 µg / L in adults or less than 12 ng / mL in children under 5 years. In other embodiments, the treatment according to the present invention is performed in non- iron deficient non-anemic patients, wherein said patients are characterized by haemoglobin concentrations of at least 13.0 g / dL in men aged 15 years and above, at least 12.0 g / dL in non-pregnant women aged 15 years and above, at least 11.0 g / dL in pregnant women or children aged 6–59 months and comcomitant whole blood or plasma and / or serum ferritin concentration of at least 15 µg / L in adults or at least 12 ng / mL in children under 5 years. Iron-deficiency anemia is anemia caused by a lack of iron and may be caused by blood loss, insufficient dietary intake, or poor absorption of iron from food. Ferritin levels between 0 and <15 µg / L define iron deficiency in apparently healthy individuals (i.e. without known infection or inflammation, without known chronic internal disease), while ferritin levels are between 15 and <300 µg / L in individuals without infection or inflammation (according to WHO criteria). According to the World Health Organization (WHO), anemia is defined as hemoglobin (Hb) levels <12.0 g / dL in women and <13.0 g / dL in men. (see e.g. Cappellini & Motta; Semin Hematol. 2015 Oct;52(4):261-9. doi: 10.1053 / j.seminhematol.2015.07.006). In particular, a hemoglobin concentration <12 g / dL in nonpregnant women beyond 15 years, and a hemoglobin concentration <13 g / dL in men beyond the age of 15 is defined as anemia (according to WHO criteria). Sources of blood loss can include heavy periods, childbirth, uterine fibroids, stomach ulcers, colon cancer, and urinary tract bleeding, poor absorption of iron from food may occur as a result of an intestinal disorder such as inflammatory bowel disease or celiac disease, or surgery such as a gastric bypass. If symptoms present, patients may present with the sign of pallor, feeling tired, weak, dizziness, lightheadedness, poor physical exertion, headaches, decreased ability to concentrate, cold hands and feet, cold sensitivity, increased thirst and confusion. In severe cases, shortness of breath can occur. Other possible symptoms and signs of iron-deficiency anemia include Koilonychia, Irritability, Angina, Palpitations, Tingling, numbness, or burning sensations, Glossitis, Angular cheilitis, Poor appetite, Dysphagia, Periorbital hyperpigmentation and Restless legs syndrome. External symptoms of anemia may also include tiredness, paleness, and decreased attention capacity. The clinical symptoms of anemia include low serum iron levels (hypoferremia), low hemoglobin levels, low hematocrit levels, reduced red blood cell count, reduced reticulocytes, and elevated levels of soluble transferrin receptors. Typically, treatment of iron-deficiency anemia includes dietary changes to incorporate iron-rich foods into regular oral intake and oral iron supplementation. The substitution with iron takes place either by the oral route or by intravenous iron administration, preferred by intravenous iron administration. In addition, erythropoetine and other erythropoietin-stimulating substances may also be used in the treatment of anemias to stimulate red blood cell production. Subject matter of the present invention is in particular iron supplementation for treatment and / or prophylaxis of serotonin-dependent diseases in a human patient in need thereof. Specific embodiments of the present invention relate to an iron supplementation for treatment and / or prophylaxis of serotonin- dependent diseases in a human patient in need thereof, wherein said serotonin-dependent diseases are selected from the group comprising serotonin-dependent diseases depression, carcinoid syndrome, irritable bowel syndrome, dementia, pulmonary fibrosis, asthma and pulmonary arterial hypertension. Just like depression, carcinoid syndrome, irritable bowel syndrome, dementia, pulmonary fibrosis, asthma, and pulmonary arterial hypertension are clinically recognized conditions with established serotonin dysregulation. In oncology, pathologically high serotonin levels contribute to tumor growth and metastasis in colorectal cancer, as well as severe gastrointestinal and cardiac symptoms in NET tumor patients (carcinoid syndrome). Serotonin is synthesized by the two tryptophan hydroxylases, TPH1 in enterochromaffin cells of the gut and TPH2 in hindbrain raphe nuclei. Telotristat ethyl is the first TPH inhibitor with FDA approval for the treatment of carcinoid syndrome. In gastroenterology, serotonin acts as paracrine signaling molecule in the whole gastrointestinal tract. Its release from enterochromaffin cells initiates peristaltic, secretory, vasodilatory, vagal and nociceptive reflexes. Altered serotonin signaling leads to both intestinal and extraintestinal symptoms in inflammatory bowel syndrome. In neurology, neuropathological and neuroimaging studies have consistently demonstrated degeneration of monoamine systems, especially the serotonin system, in dementia / Alzheimer's disease. In pneumology, increased peripheral serotonin levels contribute to pulmonary vessel remodeling and aggravate the disease progression in pulmonary arterial hypertension and PH-LHD (pulmonary hypertension due to left heart disease) subtypes of pulmonary hypertension. Moreover, in pneumology, the plasma level of serotonin are increased in symptomatic asthmatic patients and the use of anti-depressants, known to reduce serotonin levels, provokes a decrease in asthma symptoms and an increase in pulmonary function. Furthermore, in pneumology, enhanced activation of serotonergic signaling is associated with pulmonary fibrosis, and serotonin (5-HT)2 receptors have been implicated to have important roles in observed profibrotic actions. Subject matter of the present invention is in particular for treatment and / or prophylaxis of an affective disorder and / or post-traumatic stress disorder (PTSD) and / or serotonin-dependent diseases in a human patient in need thereof, wherein said patient suffers from internal diseases and medical conditions caused, mediated or aggravated by (in particular increased) circulating serotonin levels, like pulmonary arterial hypertension, tumor growth and metastasis in Colorectal Cancer, asthma, inflammatory bowel disease, and fibrotic diseases in the lungs, liver, skin, or kidneys. Other embodiments of the present invention relate to treatment and / or prophylaxis of an affective disorder and / or post-traumatic stress disorder (PTSD) and / or serotonin-dependent diseases in a human patient in need thereof, wherein said patient suffers from medical conditions caused, mediated or aggravated by circulating serotonin levels, like pulmonary arterial hypertension, tumor growth and metastasis in Colorectal Cancer, asthma, inflammatory bowel disease, and fibrotic diseases in the lungs, liver, skin or kidneys. Particular embodiments of the present invention relate to iron supplementation for treatment and / or prophylaxis of post-traumatic stress disorder (PTSD) in a human patient in need thereof, wherein said patient does not suffer from an iron deficiency and wherein iron deficiency is defined as whole blood or plasma and / or serum ferritin level of less than 15 µg / L in said patient. Particular embodiments of the present invention relate to iron supplementation for treatment and / or prophylaxis of post-traumatic stress disorder (PTSD) in a human patient in need thereof, wherein said patient does not suffer from anemia and wherein anemia is defined as a whole blood hemoglobin level of less than 12 g / dL in females and a whole blood hemoglobin level less than 13 g / dL in males. Particular embodiments of the present invention relate to iron supplementation for treatment and / or prophylaxis of affective disorder and / or post-traumatic stress disorder (PTSD) and / or serotonin- dependent diseases in a human patient in need thereof, wherein said patient is a non-anemic patient, a mild anemic patient or a subclinical anemic patient. Particular embodiments of the present invention relate to iron supplementation for treatment and / or prophylaxis of post-traumatic stress disorder (PTSD) s in a human patient in need thereof, wherein said patient is a non-anemic female and has a whole blood hemoglobin level of greater than or equal to 12 g / dL or said patient is a non-anemic male and has a whole blood hemoglobin level of greater than or equal to 13 g / dL. Particular embodiments of the present invention relate to iron supplementation for treatment and / or prophylaxis of post-traumatic stress disorder (PTSD) in a human patient in need thereof, wherein said patient is a non-anemic female or mild anemic female and has a whole blood hemoglobin level of greater than 11 g / dL or said patient is a non-anemic male or a mild anemic male and has a whole blood hemoglobin level of greater than 12 g / d L. Particular embodiments of the present invention relate to iron supplementation for treatment and / or prophylaxis of post-traumatic stress disorder (PTSD) in a human patient in need thereof, wherein said patient is a non-anemic female or a mild anemic female or a subclinical anemic female and has a whole blood hemoglobin level of greater than 10 g / dL or said patient is a non-anemic male or a mild anemic male or a subclinical anemic male and has a whole blood hemoglobin level of greater than 11 g / d L. Particular embodiments of the present invention relate to iron supplementation for treatment and / or prophylaxis of post-traumatic stress disorder (PTSD) in a human patient in need thereof, wherein said patient is a mild anemic female and has a whole blood hemoglobin level of 11 g / dL to less than 12 g / dL or said patient is a mild anemic male and has a whole blood hemoglobin level of 12 g / dL to less than 13 g / dL. Particular embodiments of the present invention relate to iron supplementation for treatment and / or prophylaxis of post-traumatic stress disorder (PTSD) in a human patient in need thereof, wherein said patient is a subclinical anemic female and has a whole blood hemoglobin level of 10 g / dL to less than 11 g / dL or said patient is a subclinical anemic male and has a whole blood hemoglobin level of 11 g / d L to less than 12 g / dL. Particular embodiments of the present invention relate to iron supplementation for treatment and / or prophylaxis of post-traumatic stress disorder (PTSD) in a human patient in need thereof, wherein said patient does not suffer from iron deficiency anemia and wherein iron deficiency anemia is defined as whole blood hemoglobin levels of less than 12 g / dL in females and a whole blood hemoglobin level less than 13 g / dL in males and comcomitant whole blood or plasma and / or serum ferritin level of less than 15 µg / L. In case of doubt, if the measured ferritin values differ between whole blood, plasma, and serum samples, the ferritin value determined in the serum sample is to be used as the definitive value. Particular embodiments of the present invention relate to iron supplementation for treatment and / or prophylaxis of post-traumatic stress disorder (PTSD) in a human patient in need thereof, wherein said patient is 18 years or above, preferably 15 years or above. Particular embodiments of the present invention relate to iron supplementation for treatment and / or prophylaxis of post-traumatic stress disorder (PTSD) in a human patient in need thereof, wherein said patient is below 18 years old, preferably below 12 years old, more preferably below 5 years old. In certain embodiments of the present invention, the patient suffering from post-traumatic stress disorder (PTSD) as detailed herein does not suffer from anemia, preferably not from anemia or subclinical anemia, more preferably not from mild anemia or subclinical anemia or anemia. Throughout the application, it is mentioned “plasma and / or serum or whole blood in a patient” in the context of ferritin or hemoglobin level This may be substituted by “ferritin and / or hemoglobin level in a sample of said patient, wherein the sample is selected from the group comprising plasma and / or serum or whole blood.” In certain embodiments of the present invention, this may be substituted by “ferritin and / or hemoglobin level in a sample taken from said patient, wherein the sample is selected from the group comprising plasma and / or serum or whole blood.” In certain embodiments of the present invention, this may be substituted by “ferritin and / or hemoglobin level are determined in a sample taken from said patient, wherein the sample is selected from the group comprising plasma and / or serum or whole blood.” According to a subject of the present invention said disorder or disease is a mental illness. In one embodiment according to the present invention said disorder or disease is depression, in particular major depressive disorder (MDD). Particular embodiments of the present invention relate to iron supplementation for treatment and / or prophylaxis of depression, in particular major depressive disorder (MDD) in a human patient in need thereof, wherein said patient does not suffer from an iron deficiency and wherein iron deficiency is defined as whole blood or plasma and / or serum ferritin level of less than 15 µg / L in said patient. Particular embodiments of the present invention relate to iron supplementation for treatment and / or prophylaxis of depression, in particular major depressive disorder (MDD) in a human patient in need thereof, wherein said patient does not suffer from anemia and wherein anemia is defined as a whole blood hemoglobin level of less than 12 g / dL in females and a whole blood hemoglobin level less than 13 g / dL in males. Particular embodiments of the present invention relate to iron supplementation for treatment and / or prophylaxis of affective disorder and / or depression, in particular major depressive disorder (MDD) and / or serotonin-dependent diseases in a human patient in need thereof, wherein said patient is a non- anemic patient, a mild anemic patient or a subclinical anemic patient. Particular embodiments of the present invention relate to iron supplementation for treatment and / or prophylaxis of depression, in particular major depressive disorder (MDD) s in a human patient in need thereof, wherein said patient is a non-anemic female and has a whole blood hemoglobin level of greater than or equal to 12 g / dL or said patient is a non-anemic male and has a whole blood hemoglobin level of greater than or equal to 13 g / dL. Particular embodiments of the present invention relate to iron supplementation for treatment and / or prophylaxis of depression, in particular major depressive disorder (MDD) in a human patient in need thereof, wherein said patient is a non-anemic female or mild anemic female and has a whole blood hemoglobin level of greater than 11 g / dL or said patient is a non-anemic male or a mild anemic male and has a whole blood hemoglobin level of greater than 12 g / d L. Particular embodiments of the present invention relate to iron supplementation for treatment and / or prophylaxis of depression, in particular major depressive disorder (MDD) in a human patient in need thereof, wherein said patient is a non-anemic female or a mild anemic female or a subclinical anemic female and has a whole blood hemoglobin level of greater than 10 g / dL or said patient is a non-anemic male or a mild anemic male or a subclinical anemic male and has a whole blood hemoglobin level of greater than 11 g / d L. Particular embodiments of the present invention relate to iron supplementation for treatment and / or prophylaxis of depression, in particular major depressive disorder (MDD) in a human patient in need thereof, wherein said patient is a mild anemic female and has a whole blood hemoglobin level of 11 g / dL to less than 12 g / dL or said patient is a mild anemic male and has a whole blood hemoglobin level of 12 g / dL to less than 13 g / dL. Particular embodiments of the present invention relate to iron supplementation for treatment and / or prophylaxis of depression, in particular major depressive disorder (MDD) in a human patient in need thereof, wherein said patient is a subclinical anemic female and has a whole blood hemoglobin level of 10 g / dL to less than 11 g / dL or said patient is a subclinical anemic male and has a whole blood hemoglobin level of 11 g / d L to less than 12 g / dL. Particular embodiments of the present invention relate to iron supplementation for treatment and / or prophylaxis of depression, in particular major depressive disorder (MDD) in a human patient in need thereof, wherein said patient does not suffer from iron deficiency anemia and wherein iron deficiency anemia is defined as whole blood hemoglobin levels of less than 11 g / dL in females and a whole blood hemoglobin level less than 12 g / dL in males and comcomitant whole blood or plasma and / or serum ferritin level of less than 15 µg / L. In case of doubt, if the measured ferritin values differ between whole blood, plasma, and serum samples, the ferritin value determined in the serum sample is to be used as the definitive value. Particular embodiments of the present invention relate to iron supplementation for treatment and / or prophylaxis of depression, in particular major depressive disorder (MDD) in a human patient in need thereof, wherein said patient is 18 years or above, preferably 15 years or above. The treatment of MDD with iron supplementation for treatment and / or prophylaxis is in one embodiment a First-Line Therapy in the Treatment of Children and Adult Patients with Major Depressive Disorder. In one embodiment said Patient meets one or more of the following criteria:1. The start of the current major depressive episode (MDE) is at least 12 weeks but not more than 12months prior to Screening;2. Has at least moderate severity of illness based on rater-administered MADRS total score ≥ 24 atScreening and at Baseline;3. Has sufficient history and medical record confirmation verifying the anti-depressive therapy (ADT)and the current major depressive episode (MDE) is causing clinically significant distress or impairment in social, occupational, or other important areas of functioning.4. ferritin level <300 μg per liter.In one embodiment the patient meets all of the above-mentioned criteria 1-4. In one embodiment the patient meetis at least the following four criteria:1. The start of the current major depressive episode (MDE) is at least 12 weeks but not more than12 months prior to Screening;2. Has at least moderate severity of illness based on rater-administered MADRS total score ≥ 24 atScreening and at Baseline;3. Has sufficient history and medical record confirmation verifying the anti-depressive therapy(ADT) and the current major depressive episode (MDE) is causing clinically significant distress or impairment in social, occupational, or other important areas of functioning.4. ferritin level <300 μg per literIn one embodiment the patient meets all of the above-mentioned criteria 1-4. In one embodiment the patient receives a treatment with single-dose intravenous iron, preferably a fixed- dose of 300-600 mg, preferably 400-500 mg, preferably 423 mg, preferably in one embodiment an intravenous iron was administered as ferric carboxymaltose solution [e.g. Ferinject® / Injectafer® ).In one embodiment the patient is currently not under treatment with one or more antidepressants, in particular but not limited to the following compounds: 1. citalopram / escitalopram2. fluoxetine3. paroxetine4. sertraline5. duloxetine6. levomilnacipran / milnacipran (if locally approved for MDD)7. venlafaxine / desvenlafaxine8. bupropion9. vilazodone10. vortioxetineIn one embodiment the patients is currently and has been previously not under treatment with one or more antidepressants, including the above-mentioned compunds. Sollten wir hier auch die Exclusion criteria aufnehmen? The treatment of MDD with iron supplementation for treatment and / or prophylaxis is in one embodiment a Adjunctive Therapy in the Treatment of Patients With Major Depressive Disorder In one embodiment said Patient meets one or more of the following criteria:1. The start of the current major depressive episode (MDE) is at least 12 weeks but not more than36 months prior to Screening;2. Has at least moderate severity of illness based on rater-administered MADRS total score ≥ 24 atScreening and at Baseline;3. Has sufficient history and medical record confirmation verifying the anti-depressive therapy(ADT) and the current major depressive episode (MDE) is causing clinically significant distress or impairment in social, occupational, or other important areas of functioning.4. ferritin level <300 μg per liter.In one embodiment the patient meetis at least the following four criteria:1. The start of the current major depressive episode (MDE) is at least 12 weeks but not more than36 months prior to Screening;2. Has at least moderate severity of illness based on rater-administered MADRS total score ≥ 24 atScreening and at Baseline;3. Has sufficient history and medical record confirmation verifying the anti-depressive therapy(ADT) and the current major depressive episode (MDE) is causing clinically significant distress or impairment in social, occupational, or other important areas of functioning.4. ferritin level <300 μg per literIn one embodiment the patient meets all of the above-mentioned criteria 1-4. In one embodiment the patient receives a treatment with single-dose intravenous iron, preferably a fixed- dose of 300-600 mg, preferably 400-500 mg, preferably 423 mg, preferably in one embodiment an intravenous iron is administered as ferric carboxymaltose solution (e.g. Ferinject® / Injectafer® ). Particular iron supplementations in the present invention are Ferinject®, ferric derisomaltose solution (e.g. Monoferric®), or „iron sucrose (e.g. Venofer®). Adjunctive Therapy means that the patient is having an inadequate response (that may mean less than 50% improvement) to ADT (antidepressive therapy) in the current MDE (major depressive episode) as confirmed by the Investigator using the Antidepressant Treatment Response Questionnaire (ATRQ) and taking at least the minimum effective dose (per package insert) of one of the following antidepressants as monotherapy treatment for at least 6 weeks duration: 1. citalopram / escitalopram2. fluoxetine3. paroxetine4. sertraline5. duloxetine6. levomilnacipran / milnacipran (if locally approved for MDD)7. venlafaxine / desvenlafaxine8. bupropion9. vilazodone10. vortioxetineThe treatment of MDD with iron supplementation for treatment and / or prophylaxis is in one embodiment a replacement of Pharmacological Antidepressive Therapies in the Treatment of Chronic Major Depressive Disorder Patients. In one embodiment said patient meets at least one of the following criteria:1. Male or female patients between the ages of 12 and 75 years, inclusive;2. Meets DSM-5 criteria for MDD (MDD with psychotic features will be acceptable) as confirmed bythe Investigator or Sponsor-approved rater using the modified Structured Clinical Interview for DSM-5, Clinical Trials Version (SCID-5-CT) and meets all of the following criteria: 1. The start of the current major depressive episode (MDE) is at least 12 weeks but notmore than 36 months prior to Screening; 2. Mild to moderate severity of illness based on rater-administered MADRS total score atScreening and at Baseline; 3. Is on stable dose of ADT for at least 3 months, and a dose change is not intended atScreening or Baseline; 4. ferritin level <300 μg per liter.3. Currently having an adequate or inadequate response (less than 50% improvement) to ADT in thecurrent MDE as confirmed by the Investigator using e.g. the Antidepressant Treatment Response Questionnaire (ATRQ) and taking at least the minimum effective dose (per package insert) of one antidepressants, in particular one of the following antidepressants (e.g. as monotherapy treatment) for at least 6 weeks duration: 1. citalopram / escitalopram2. fluoxetine3. paroxetine4. sertraline5. duloxetine6. levomilnacipran / milnacipran (if locally approved for MDD)7. venlafaxine / desvenlafaxine8. bupropion9. vilazodone10. vortioxetineIn one embodiment said patient meets at least the following criteria:1. Male or female patients between the ages of 12 and 75 years, inclusive;2. Meets DSM-5 criteria for MDD (MDD with psychotic features will be acceptable) as confirmed bythe Investigator or Sponsor-approved rater using the modified Structured Clinical Interview for DSM-5, Clinical Trials Version (SCID-5-CT) and meets all of the following criteria: 1. The start of the current major depressive episode (MDE) is at least 12 weeks but notmore than 36 months prior to Screening; 2. Mild to moderate severity of illness based on rater-administered MADRS total score atScreening and at Baseline; 3. Is on stable dose of ADT for at least 3 months, and a dose change is not intended atScreening or Baseline; 4. ferritin level <300 μg per liter3. Currently having an adequate or inadequate response (less than 50% improvement) to ADT in thecurrent MDE as confirmed by the Investigator using e.g. the Antidepressant Treatment Response Questionnaire (ATRQ) and taking at least the minimum effective dose (per package insert) of one antidepressants, in particular one of the following antidepressants (e.g. as monotherapy treatment) for at least 6 weeks duration: 1. citalopram / escitalopram2. fluoxetine3. paroxetine4. sertraline5. duloxetine6. levomilnacipran / milnacipran (if locally approved for MDD)7. venlafaxine / desvenlafaxine8. bupropion9. vilazodone10. vortioxetine In one embodiment the patient receives a treatment with single-dose intravenous iron, preferably a fixed- dose of 300-600 mg, preferably 400-500 mg, preferably 423 mg, preferably in one embodiment an intravenous iron was administered as ferric carboxymaltose solution [e.g. Ferinject® / Injectafer® ). The treatment of MDD with iron supplementation for treatment and / or prophylaxis is in one embodiment a treatment of a patient with mild depression. In one embodiment mild depression is defined in accordance to the classification in diagnostic questionnaires, which mental health professionals use to measure the severity of depressive episodes in patients with mood disorders, such as Montgomery- Åsberg Depression Rating Scale (MADRS), the Hamilton Rating Scale for Depression (HRSD), the Beck Depression Inventory (BDI), or the Patient Health Questionnaire (PHQ-9); in these diagnostic questionnaires “mild or subclinical depression” is defined as having a low score classifying said subject as suffering from mild depression. The treatment of MDD with iron supplementation for treatment and / or prophylaxis is in one embodiment a treatment of a patient with a mild or depression but no major depressive disorder but that patient has another primary disease. Said primary disease maybe cancer, maybe a cardiovascular disease. In one embodiment said patient has a primary disease that is heart failure, in particular systolic heart failure. In one embodiment said patient has a stable ambulatory HF patients in New York Heart Association class 2 or 3, with left ventricular ejection fraction (LVEF) ≤45%, and serum ferritin level <300 ng / mL. In one embodiment said patient receives a treatment with single-dose intravenous iron, preferably a fixed-dose of 300-600 mg, preferably 400-500 mg, preferably 423 mg, preferably in one embodiment an intravenous iron was administered as ferric carboxymaltose solution [e.g. Ferinject® / Injectafer® ). Said medication i.e. iron supplementation may be administered to the subject as diluted i.v. solution in up to 100 mL saline in an amount equivalent to 500 to 2000mg of iron, in particular in the form of FCM, administered over at least 10 min, or over at least 15 min. In one embodiment according to the present invention said disorder or disease is an affective disorder. In one embodiment according to the present invention said disorder or disease is a serotonin-dependent disease. In one embodiment of the present invention, said patient does not suffer from an iron deficiency or iron deficiency anemia. In a further embodiment of the present invention, said patient does not suffer from fibromyalgia or fibromyalgic syndrome. One embodiment of the present invention is iron supplementation for treatment and / or prophylaxis of depression, wherein depression is selected from the group comprising Disruptive Mood Dysregulation Disorder, Major Depressive Disorder—Single and Recurrent Episodes, Persistent Depressive Disorder, Premenstrual Dysphoric Disorder, Substance / Medication-Induced Depressive Disorder, Depressive Disorder Due to Another Medical Condition, Other Specified Depressive Disorder, and Unspecified Depressive Disorder. Depressive disorders are generally characterized by a cluster of symptoms including sadness or low mood, crying, loss of interest in once-enjoyed activities, decreased energy, and sleeping and eating changes. While these symptoms can be present in youth and adults, in adolescence, depression may manifest in slightly diverse ways. For example, over 60% of depressed teenagers reported severe impairment in functioning related to school / work, family, chores, and social roles (Avenevoli et al., 2015). Recent research has shown that typical presentations of youth depressive illness may include fatigue, irritability, and anger with behavioral correlates including poor school performance, negative acting out, and poor interpersonal and peer relationships (Jaycox et al., 2009). Disruptive mood dysregulation disorder (DMDD) is a mental disorder in children and adolescents characterized by a persistently irritable or angry mood and frequent temper outbursts that are disproportionate to the situation and significantly more severe than the typical reaction of same-aged peers. DMDD was added to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-V) as a type of depressive disorder diagnosis for youths. The symptoms of DMDD resemble many other disorders, thus a differential includes attention-deficit / hyperactivity disorder (ADHD), oppositional defiant disorder (ODD), anxiety disorders, and childhood bipolar disorder, intermittent explosive disorder (IED), major depressive disorder (MDD), and conduct disorder (Diagnostic and statistical manual of mental disorders (5th ed.). Washington, DC: American Psychiatric Association. 2013-05-22). DMDD is classified as a mood disorder. Diagnosis requires meeting criteria set by the DSM-V, which includes frequent and severe temper outbursts several times a week for over a year that are observed in multiple settings. Treatments include medication to manage mood symptoms as well as individual and family therapy to address emotion-regulation skills.[4] Children with DMDD are at risk for developing depression and anxiety later in life.[3][6] Major depressive disorder is characterized by a depressed mood (or irritability in children) or loss of pleasure or interest for at least 2 weeks (American Psychiatric Association, 2013). It is also accompanied by at least three (for a total of at least five) of the following symptoms present most days: weight loss or change in appetite, insomnia or hypersomnia, psychomotor retardation or agitation, fatigue or loss of energy, excessive / inappropriate guilt or feelings of worthlessness, indecisiveness or diminished ability to concentrate or think, and recurrent thoughts of death or suicidal ideation or suicide plan or attempt (American Psychiatric Association, 2013). The diagnosis of major depressive disorder is based on the person's reported experiences, behavior reported by relatives or friends, and a mental status examination. So far, there is no laboratory test for the diagnosis of the disorder, but testing may be done to rule out physical conditions that can cause similar symptoms. The most common time of onset is in a person's 20s, with females affected about twice as often as males (Kessler RC, Bromet EJ (2013). "The epidemiology of depression across cultures". Annual Review of Public Health.34: 119–38). The course of the disorder varies widely, from one episode lasting months to a lifelong disorder with recurrent major depressive episodes. Treatment of major depressive disorder comprises psychotherapy and antidepressant medication. Hospitalization may be necessary in cases with associated self-neglect or a significant risk of harm to self or others. Major depressive disorder can negatively affect a person's personal life, work life, or education, and cause issues with a person's sleeping habits, eating habits, and general health. Another depressive disorder, persistent depressive disorder (formerly called dysthymia) in the Diagnostic and Statistical Manual of Mental Disorders (5th ed.; DSM-5; American Psychiatric Association, 2013), is characterized by a depressed mood most of the time for at least 2 years, along with at least two of the following symptoms: feeling hopeless, insomnia or hypersomnia, overeating or poor appetite, fatigue or low energy, low self-esteem, and indecisiveness or poor concentration (American Psychiatric Association, 2013). In children and adolescents, the mood can be irritable, and the duration of persistent depressive disorder is at least 1 year. Moreover, there cannot be a gap in these symptoms for more than 2 months, a hypomanic or manic episode during this time period, nor criteria met for cyclothymic disorder, and symptoms are not better explained by another disorder, cause significant impairment in functioning or distress, and are not due to a different medical condition or a substance use disorder (American Psychiatric Association, 2013). Persistent depressive disorder is treated with psychotherapy and pharmacotherapy, whereas a combination of psychotherapy and pharmacotherapy shows best results. Premenstrual dysphoric disorder (PMDD) is a mood disorder characterized by emotional, cognitive, and physical symptoms. PMDD causes significant distress or impairment in menstruating women during the luteal phase of the menstrual cycle. The symptoms occur in the luteal phase (between ovulation and menstruation), improve within a few days after the onset of menses, and are minimal or absent in the week after menses. Clinicians consider mood symptoms, physical symptoms and impact on the patient's life when diagnosing PMDD. Mood symptoms include emotional lability (rapidly changing emotions, sensitivity to rejection, etc.), irritability and anger that may lead to conflict, anxiety, feeling on edge, hopelessness, difficulty concentrating, appetite changes, sleeping more or less than usual, or feeling out of control. The physical symptoms are similar to the symptoms of Premenstrual Syndrome (PMS). These include breast tenderness or swelling, joint pain, muscle pain, gaining weight, or feeling bloated. Several medications have been shown to effectively reduce the physical and emotional symptoms of PMDD including antidepressant treatment such as Selective serotonin reuptake inhibitors (SSRIs) and Serotonin norepinephrine reuptake inhibitors (SNRIs)), anxiolytics such as alprazolam (Xanax) and buspirone, psychotherapy / cognitive behavioral therapy, hormonal treatment such as oral contraceptives with e.g. ethinylestradiol and drospirenone (progestin) and surgical menopause. Other proposed treatments include dietary modification, herbal remedies including St John's Wort and chasteberry, acupuncture, and exercise. Substance / medication-induced mental disorders refer to depressive, anxiety, psychotic, or manic symptoms that occur as a physiological consequence of the use of substances of abuse or medications. Substance-induced disorders may develop in the context of either intoxication or withdrawal. Of the depressive episodes occurring in the general population, nearly half precipitate in the context of heavy alcohol use. The next most frequently associated substances are cocaine and opioids, especially heroin. Iatrogenic substances can also induce pathological affective states. Examples of such medications include interferon (IFN), corticosteroids, digoxin, and antiepileptic drugs. Either class - substance or medication - can induce states of mania or depression. Thus, patients may endorse sad mood, insomnia, feelings of guilt, suicidal ideation, psychomotor retardation, distractibility, hopelessness, helplessness, irritability, decreased libido, anergy, or anorexia if depressed. In the setting of mania, the patient will endorse grandiosity, distractibility, impulsivity, pressured speech, racing thoughts, sexual promiscuity, irritability, insomnia, and increased energy. Here, it is crucial that the treatment emphasizes on abstinence from the inciting substance. In some cases, antidepressants and / or antipsychotics may be applied. Depressive Disorder Due to Another Medical Condition Depressive disorder due to another medical condition according to the present invention may be selected form the group comprising substance / medication-induced depressive disorder, dysthymia, cyclothymia, bereavement, adjustment disorder with depressed mood, bipolar disorder, schizoaffective disorder, schizophrenia, anxiety disorders, and eating disorders for the appropriate management. Depressive symptoms can be secondary to the following causes: ^Neurological causes such as cerebrovascular accident, multiple sclerosis, subdural hematoma,epilepsy, Parkinson disease, Alzheimer disease ^Endocrinopathies such as diabetes, thyroid disorders, adrenal disorders^ Metabolic disturbances such as hypercalcemia, hyponatremia^ Medications / substances of abuse: steroids, antihypertensives, anticonvulsants, antibiotics,sedatives, hypnotics, alcohol, stimulant withdrawal ^Nutritional deficiencies such as vitamin D, B12, B6 deficiency, iron or folate deficiency^ Infectious diseases such as HIV and syphilis^ MalignanciesIn other embodiments, depressive symptoms can be secondary to the following causes: ^Neurological causes such as cerebrovascular accident, multiple sclerosis, subdural hematoma,epilepsy, Parkinson disease, Alzheimer disease ^Endocrinopathies such as diabetes, thyroid disorders, adrenal disorders^ Metabolic disturbances such as hypercalcemia, hyponatremia^ Medications / substances of abuse: steroids, antihypertensives, anticonvulsants, antibiotics,sedatives, hypnotics, alcohol, stimulant withdrawal ^Nutritional deficiencies such as vitamin D, B12, B6 deficiency, iron or folate deficiency^ Infectious diseases such as HIV and syphilis^ Malignancies^ Cancer^ Cardiovascular Diseases like e.g. Heart FailureOther Specified Depressive Disorders Other Specified Depressive Disorders is a category of DSM-5 diagnoses that applies to individuals who have symptoms characteristic of a depressive disorder (e.g. - major depressive disorder), but do not meet the full criteria for any of them. “Other Specified” diagnoses are not limited to these disorders and are used throughout the DSM-5 to capture presentations where individuals have significant clinical impairment but do not meet standard criteria. The other specified depressive disorder category is used in situations in which the clinician chooses to communicate the specific reason that the presentation does not meet the criteria for any specific depressive disorder. This is done by recording “other specified depressive disorder” followed by the specific reason (e.g., “short-duration depressive episode”). Examples of presentations that can be specified using the “other specified” designation include the following: 1. Recurrent brief depression: Concurrent presence of depressed mood and at least four other symptoms of depression for 2-13 days at least once per month (not associated with the menstrual cycle) for at least 12 consecutive months in an individual whose presentation has never met criteria for any other depressive or bipolar disorder and does not currently meet active or residual criteria for any psychotic disorder. 2. Short-duration depressive episode (4-13 days): Depressed affect and at least four of the other eight symptoms of a major depressive episode associated with clinically significant distress or impairment that persists for more than 4 days, but less than 14 days, in an individual whose presentation has never met criteria for any other depressive or bipolar disorder, does not currently meet active or residual criteria for any psychotic disorder, and does not meet criteria for recurrent brief depression. 3. Depressive episode with insufficient symptoms: Depressed affect and at least one of the other eight symptoms of a major depressive episode associated with clinically significant distress or impairment that persist for at least 2 weeks in an individual whose presentation has never met criteria for any other depressive or bipolar disorder, does not currently meet active or residual criteria for any psychotic disorder, and does not meet criteria for mixed anxiety and depressive disorder symptoms. For patients that do not meet full criteria for the aforementioned depressive disorders (depressive episode with insufficient symptoms) but either experience recurrent episodes of depressed mood and at least four other symptoms of depression for 2–13 days (recurrent brief depression) or experience a depressive episode for 4–13 days (short-duration depressive episode), the DSM-5 presents this as Other Specified Depressive Disorder (American Psychiatric Association, 2013). Different instruments can be used to assess whether a patient is suffering from depression. Initial assessments of depressive symptoms can help determine possible treatment options, and periodic assessment throughout care can guide treatment and gauge progress. These instruments include both interview and self-report measures and may be used to screen, diagnose and / or track treatment outcomes. Each instrument has been demonstrated to be valid and reliable, and most are available at no cost. These instruments are well known to the person skilled in the art and comprise but are not limited to Across the Lifespan- Beck Depression Inventory The Beck Depression Inventory (BDI) is widely used to screen for depression and to measure behavioral manifestations and severity of depression. The BDI can be used for ages 13 to 80. The inventory contains 21 self-report items which individuals complete using multiple choice response formats. Validity and reliability of the BDI has been tested across populations, worldwide (see e.g. Beck, A.T., Ward, C.H., Mendelson, M., Mock, J., & Erbaugh, J. (1961). An inventory for measuring depression. Archives of General Psychiatry, 4(6), 561-571.) Center for Epidemiologic Studies Depression Scale The Center for Epidemiologic Studies Depression Scale (CES-D) was designed for use in the general population and is now used as a screener for depression in primary care settings. It includes 20 self- report items, scored on a 4-point scale, which measure major dimensions of depression experienced in the past week. The CES-D can be used for children as young as 6 and through older adulthood. It has been tested across gender and cultural populations and maintains consistent validity and reliability (see e.g. Radloff, L.S. (1977). The CES-D Scale: A self-report report depression scale for research in the general population. Applied Psychological Measurement, 1(3), 385-401.) Hamilton Depression Rating Scale The Hamilton Rating Scale for Depression, abbreviated HDRS, HRSD or HAM-D, measures depression in individuals before, during and after treatment. The scale is administered by a health care professionals and contains 21 items, but is scored based on the first 17 items, which are measured either on 5-point or 3-point scales (see e.g. Hamilton, M. (1960). A rating scale for depression. Journal of Neurology, Neurosurgery & Psychiatry, 23, 56-61). Montgomery-Åsberg Depression Rating Scale The 10-item Montgomery-Åsberg Depression Rating Scale (MADRS) measures severity of depression in individuals 18 years and older. Each item is rated on a 7-point scale. The scale is an adaptation of the Hamilton Depression Rating Scale and has a greater sensitivity to change over time (see e.g. Montgomery, S.A., & Åsberg, M. (1979). A new depression scale designed to be sensitive to change. The British Journal of Psychiatry, 134, 382-389). PHQ-9 The nine-item Patient Health Questionnaire (PHQ-9) is a depressive symptom scale and diagnostic tool to screen adult patients in primary care settings. The instrument assesses for the presence and severity of depressive symptoms and a possible depressive disorder. A patient may take the PHQ-9 in written form or be presented the survey items in interview form. The PHQ-9 questions reflect the diagnostic criteria for major depressive disorder (MDD) found in the DSM- 5. The items ask about the patient's experience in the last two weeks. Questions are about the level of interest / pleasure in doing things (anhedonia), feeling down or depressed, sleep-related problems (sleeping too much / difficulty falling or staying asleep), low energy or fatigue, eating problems (poor appetite or eating too much), self-worth (feeling like a failure), ability to concentrate, psychomotor problems (speaking / moving slowly or fidgety / restless), and thoughts of suicide. Responses range from “0” (Not at all) to “3” (nearly every day). A tenth question asks about the extent to which the previously mentioned symptoms make functioning in daily life difficult (see e.g. Kroenke K, Spitzer RL, Williams JB (September 2001). "The PHQ-9: validity of a brief depression severity measure". Journal of General Internal Medicine.16 (9): 606–613). In one embodiment of the present invention, instruments for assessing depression in Children and Adolescents comprise Behavior Assessment System for Children (BASC), Child Behavior Checklist, Children’s Depression Inventory and Children’s Depression Rating Scale. In a further embodiment of the present invention, instruments for assessing depression in a general Adult Population comprise Beck Hopelessness Scale, Quick Inventory of Depressive Symptomatology-Self- Report (QIDS-SR), Patient Health Questionnaire, Reminiscence Functions Scale, Short Form Health Survey, Social Adjustment Scale-Self Report and Social Functioning Questionnaire. In another embodiment of the present invention, instruments for assessing depression in older adults comprise Geriatric Depression Scale and Life Satisfaction Index. The person skilled in the art would be aware which instrument is to be used to assess depression in a given patient. An affective disorder, also known as an mood disorder, may refer to any of a group of conditions of mental and behavioral disorder where a disturbance in the person's mood is the main underlying feature. The classification is in the Diagnostic and Statistical Manual of Mental Disorders (DSM) and International Classification of Diseases (ICD). The affective disorders fall into seven groups, including abnormally elevated mood, such as mania or hypomania; depressed mood such as major depressive disorder (MDD) and moods which cycle between mania and depression, known as bipolar disorder (BD). There are several sub-types of depressive disorders or psychiatric syndromes featuring less severe symptoms such as dysthymic disorder and cyclothymic disorder. One embodiment of the present invention is iron supplementation for treatment and / or prophylaxis of depression, in particular major depressive disorder (MDD) in a human patient in need thereof, wherein more than one mood disorder is present in a patient. In one embodiment bipolar disorder and depressive disorder or depressive disorder and PTSD are present in a patient. In a further embodiment of the present invention, a mood disorder and schizophrenia are both present in a patient. Said is known as schizoaffective disorder. Mood disorders according to the present invention may also be substance induced or occur in response to a medical condition. In one embodiment according to the present invention said disorder or disease is a post-traumatic stress disorder (PTSD). Posttraumatic stress disorder (PTSD) is a psychiatric disorder that may occur in people who have experienced or witnessed a traumatic event, series of events or set of circumstances. An individual may experience this as emotionally or physically harmful or life-threatening and may affect mental, physical, social, and / or spiritual well-being. Examples include natural disasters, serious accidents, terrorist acts, war / combat, rape / sexual assault, historical trauma, intimate partner violence and bullying. Symptoms of PTSD fall into the following four categories. 1- Intrusion: Intrusive thoughts such as repeated, involuntary memories; distressing dreams; or flashbacks of the traumatic event. Flashbacks may be so vivid that people feel they are reliving the traumatic experience or seeing it before their eyes. 2- Avoidance: Avoiding reminders of the traumatic event may include avoiding people, places, activities, objects and situations that may trigger distressing memories. People may try to avoid remembering or thinking about the traumatic event. They may resist talking about what happened or how they feel about it. 3- Alterations in cognition and mood: Inability to remember important aspects of the traumatic event, negative thoughts and feelings leading to ongoing and distorted beliefs about oneself or others; distorted thoughts about the cause or consequences of the event leading to wrongly blaming self or other; ongoing fear, horror, anger, guilt or shame; much less interest in activities previously enjoyed; feeling detached or estranged from others; or being unable to experience positive emotions. 4- Alterations in arousal and reactivity: Arousal and reactive symptoms may include being irritable and having angry outbursts; behaving recklessly or in a self-destructive way; being overly watchful of one's surroundings in a suspecting way; being easily startled; or having problems concentrating or sleeping. Specific symptoms can vary in severity. Many people who are exposed to a traumatic event experience symptoms similar to those described above in the days following the event. For a person to be diagnosed with PTSD, however, symptoms may last for more than a month and must cause significant distress or problems in the individual's daily functioning. Many individuals develop symptoms within three months of the trauma, but symptoms may appear later and often persist for months and sometimes years. PTSD often occurs with other related conditions, such as depression, substance use, memory problems and other physical and mental health problems. One category of psychotherapy, cognitive behavior therapies (CBT), is very effective in treating PTSD. Cognitive processing therapy, prolonged exposure therapy, Trauma Focused Cognitive Behavioral Therapy, Eye Movement Desensitization, Group therapy and Reprocessing for PTSD and stress inoculation therapy are among the types of CBT used to treat PTSD. Other psychotherapies such as interpersonal, supportive and psychodynamic therapies focus on the emotional and interpersonal aspects of PTSD. Moreover, medication can help to control the symptoms of PTSD. Typically, antidepressants such as SSRIs and SNRIs (selective serotonin re-uptake inhibitors and serotonin-norepinephrine re-uptake inhibitors), are used to treat the core symptoms of PTSD. They are used either alone or in combination with psychotherapy or other treatments. Other medications may be used to lower anxiety and physical agitation, or treat the nightmares and sleep problems that trouble many people with PTSD. Also, treatments including complementary and alternative therapies are also being used to help people with PTSD. These approaches provide treatment outside the conventional mental health clinic and may require less talking and disclosure than psychotherapy. Examples include acupuncture, yoga and animal- assisted therapy. Subject matter of the present invention is in particular iron supplementation for treatment and / or prophylaxis of a human patient in need thereof as detailed herein, wherein said disorder or disease is a Serotonin-dependent diseases or Serotonin syndrome. Serotonin syndrome (SS) is a group of symptoms that may occur with the use of certain serotonergic medications or drugs. The symptoms range from mild to severe, and may potentially be fatal. Symptoms in mild cases include high blood pressure and a fast heart rate; usually without a fever. Symptoms in moderate cases include high body temperature, agitation, increased reflexes, tremor, sweating, dilated pupils, and diarrhea. In severe cases, body temperature can increase to greater than 41.1 °C. Complications may include seizures and extensive muscle breakdown. Serotonin syndrome is typically caused by the use of two or more serotonergic medications or drugs. This includes selective serotonin reuptake inhibitor (SSRI), serotonin norepinephrine reuptake inhibitor (SNRI), monoamine oxidase inhibitor (MAOI), tricyclic antidepressants (TCAs), amphetamines, pethidine (meperidine), tramadol, dextromethorphan, buspirone, L-tryptophan, 5-hydroxytryptophan, St. John's wort, triptans, MDMA, metoclopramide, or cocaine. Diagnosis is based on a person's symptoms and history of medication use. However, no laboratory tests can confirm the diagnosis. The most important symptoms for diagnosing SS are tremor, extreme aggressiveness, akathisia, or clonus (spontaneous, inducible and ocular). Physical examination of the patient should include assessment of deep tendon reflexes and muscle rigidity, the dryness of the mucosa of the mouth, the size and reactivity of the pupils, the intensity of bowel sounds, skin color, and the presence or absence of sweating. To fulfill the Hunter Criteria, a patient must have taken a serotonergic agent and meet one of the following conditions: Spontaneous clonus, or Inducible clonus plus agitation or diaphoresis, or Ocular clonus plus agitation or diaphoresis, or Tremor plus hyperreflexia, or Hypertonism plus temperature > 38 °C (100 °F) plus ocular clonus or inducible clonus. Initial treatment consists of discontinuing medications which may be contributing. In some cases benzodiazepines may be used. If this is not sufficient, a serotonin antagonist such as cyproheptadine may be used. In those with a high body temperature, active cooling measures may be needed. Subject matter of the present invention is iron supplementation for treatment and / or prophylaxis of an affective disorder and / or post-traumatic stress disorder (PTSD) and / or serotonin-dependent diseases in a human patient in need thereof, wherein said disorder or disease is depression and wherein depression comprises mild, moderate and severe depression. The person skilled in the art is aware on how to determine the severity of depression. In one embodiment of the present invention mild, moderate and severe depression are classified using established questionnaires selected from the group comprising PHQ-9, MADRS, BDI and HAM-D. In a further embodiment of the present invention mild, moderate and severe depression are classified using thresholds of the biomarkers Serotonin, Norepinephrine and / or Dopamine. The person skilled in the art is aware how to measure the aforementioned biomarkers and how to determine the severity of depression based on the respective threshold of the biomarkers. In particular embodiments relating to a patient receiving therapy with one or more antidepressants or scheduled to receive therapy with one or more antidepressants, the antidepressants are administered or scheduled to be administered to said patient at least at the minimum effective dose. e.g. as per the package insert of said antidepressant. In particular embodiments relating to a patient receiving therapy with antidepressants or scheduled to receive therapy with antidepressants, the antidepressants are selected from the group comprising citalopram / escitalopram, fluoxetine, paroxetine, sertraline, duloxetine, levomilnacipran / milnacipran, venlafaxine / desvenlafaxine, bupropion, vilazodone and vortioxetine. In other particular embodiments relating to a patient receiving therapy with one or more antidepressants or scheduled to receive therapy with one or more antidepressants, the antidepressants are administered or scheduled to be administered to said patient at least at the minimum effective dose. e.g. as per the package insert of said antidepressant. Certain embodiments relate to an iron supplementation for treatment and / or prophylaxis of a human patient in need thereof as detailed herein, wherein said patient is not treated with an dopamine D2 receptor antagonist. Other embodiments, relate to an iron supplementation for treatment and / or prophylaxis of a human patient in need thereof, wherein said patient is suffering from post-traumatic stress disorder (PTSD) as detailed herein and wherein said patient is not treated with an dopamine D2 receptor antagonist. Other embodiments, relate to an iron supplementation for treatment and / or prophylaxis of a human patient in need thereof, wherein said patient is suffering from depression, in particular from a major depressive disorder (MDD) as detailed herein and wherein said patient is not treated with an dopamine D2 receptor antagonist. Other embodiments, relate to an iron supplementation for treatment and / or prophylaxis of a human patient in need thereof, wherein said patient is suffering from post-traumatic stress disorder (PTSD), wherein said patient is non-anemic or mild anemic or subclinical anemic as detailed herein and wherein said patient is not treated with an dopamine D2 receptor antagonist. Other embodiments, relate to an iron supplementation for treatment and / or prophylaxis of a human patient in need thereof, wherein said patient is suffering from depression, in particular from a major depressive disorder (MDD) as detailed herein and wherein said patient is not treated with an dopamine D2 receptor antagonist. Other embodiments, relate to an iron supplementation for treatment and / or prophylaxis of a human patient in need thereof, wherein said patient is suffering from depression, in particular from a major depressive disorder (MDD), wherein said patient is non-anemic or mild anemic or subclinical anemic as detailed herein and wherein said patient is not treated with an dopamine D2 receptor antagonist. In particular embodiments, the patient has a primary diagnosis of MDD according to criteria of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), and more particularly has an inadequate response to ongoing ADT. In particular embodiments, the patient has an age of 18 to 75 years. In other particular embodiments, the patient has an age of 12 to 75 years. In particular embodiments, the patient has suffered from a major depressive episode (MDE) at least 12 weeks, more particularly 12 weeks to 36 months, prior to the start of treatment with the iron supplementation. In particular embodiments, the patient is suffering from an MDE and is characterized by one or more of the following: a) at least moderate severity of illness based on rater-administered MADRS total score ≥ 24, b) sufficient history and medical record confirmation verifying the MDE, and / or an anti-depressive therapy (ADT) administered to the patient is causing clinically significant distress or impairment in social, occupational, or other important areas of functioning. In particular embodiments, the patient has suffered from a major depressive episode (MDE) at least 12 weeks, more particularly 12 weeks to 36 months, prior to the start of treatment with the iron supplementation. In other particular embodiments, the patient is suffering from an MDE and is characterized by one or more of the following: a) mild to moderate severity of illness based on rater-administered MADRS total score ≥ 24, b) has been on a stable dose of anti-depressive therapy (ADT) for at least 3 months before the first administration of iron supplementation. In particular embodiments, the patient is suffering from an MDE and has never suffered from a disorder selected from the group comprising Schizophrenia, Schizoaffective Disorder, Schizophreniform Disorder or other psychotic disorder, and Bipolar Disorder. In particular embodiments, the patient is suffering from an MDE and, within 6 months prior to administration of the iron supplementation, has not suffered from a disorder selected from the group comprising 1) Anxiety disorders such as Panic Disorder or Generalized Anxiety Disorder requiring concurrent treatment to the iron supplementation, Obsessive-compulsive Disorder, and Posttraumatic Stress Disorder as primary diagnoses; 2) Eating disorder; 3) Substance use disorders excluding nicotine use; and 4) Personality disorder of sufficient severity to have a major impact on the patient's psychiatric status, meaning in particular a personality disorder of sufficient severity to require psychiatric treatment. In particular embodiments, the patient is suffering from an MDE and, within 12 months prior to administration of the iron supplementation, has not had any other clinically relevant psychiatric diagnosis or suffered from a clinically relevant psychiatric condition other than MDD. Clinically relevant means a psychiatric diagnosis or condition that has been the main focus of treatment for said patient. In particular embodiments, the patient is suffering from an MDE and, according to a qualified opinion of a physician or psychiatrist, does not have a significant risk for suicidal behavior, wherein in particular the patient 1) does not score "yes" on Suicidal Ideation Items 4 or 5 of the Columbia-Suicide Severity Rating Scale (C-SSRS), 2) has not had suicide attempts within 2 years prior to administration of the iron supplementation, 3) scores < 5 on MADRS Item 10 (Suicidal Thoughts); and / or 4) is considered by a physician / psychiatrist to not be in imminent danger to him / herself or others. In particular embodiments, the patient is suffering from an MDE, wherein said MDE is the patient’s first MDE and the patient is younger than 60 years of age. In particular embodiments, patient has a mild or moderate depression, or a subclinical depression, or mild-to-moderate characteristic attitudes or symptoms of depression, or a depressive disorder not otherwises specified, such as minor depressive disorder and recurrent brief depression. In more particular embodiments, symptoms of the disorder may arise due to reasons including other medical conditions, such as heart failure or any other acute or chronic non-psychiatric disease, like cancer or inflammatory bowel disease. In certain particular embodiments, the iron supplementation is administered to said patient to reduce the levels of serotonin and / or norepinephrine in said patient. In a specific embodiment of the invention said iron supplementation is selected from the group comprising an intravenous iron supplementation, parenteral iron supplementation, oral iron supplementation, intraaerterial iron supplementation or intramuscular iron supplementation. In one particular embodiment of the invention said iron supplementation is intravenous iron supplementation or oral iron supplementation. In a further particular embodiment said iron supplementation is intravenous iron supplementation. “Intravenous iron supplementation, parenteral iron supplementation, intraarterial iron supplementation , oral iron supplementation or intramuscular iron supplementation” means in particular that the supplementations are confectioned for intravenous, parenteral, intraarterial, oral or intramuscular administration, and / or to be administered intravenously, parenterally, intraarterially, orally or intramuscularly, respectively. In one embodiment of the present invention, iron is administered to the patient in a concentration of 0,0001 g / L to 20 g / L, preferably 0,001 g / L to 2 g / L, preferably 0,02 g / L to 1,5 g / L, more preferably 0,05 g / L to 1,2 g / L, more preferably 0,1 g / L to 1 g / L and most preferably 0,5 g / L. A particular embodiment of the present invention relates to Ferinject® 50mg / m Las iron supplementation; this may be used as 10 mL-ampulle comprising an equivalent of 500 mg elementarey, trivalent iron as ferric carboxymaltose, which is comprised in the medicament ni a concentration of 50 mg / mL; further components are sodium hydroxide (for adjusting the pH), hydrochloric acid (for adjusting the pH) and water for injections. The 50mg / mL solution can be diluted in physiological saline, or can be administered to the subject directly; particularly, a solution comprising 500 mg ironequivalents are diluted in 100 mL physiological saline beforeadministeration to the subject. In one embodiment of the present invention, iron is administered intravenously to the patient in an amount of 10 mg to 2000 mg, preferably 50 mg to 1500 mg, preferably 100 mg to 1000 mg, and most preferably 500 mg. In one embodiment of the present invention, iron is administered orally in an amount of 1 mg to 1000 mg, preferably 20 mg to 800 mg, preferably 50 mg to 600 mg, and most preferably 500 mg. In a further embodiment iron is administered once per day. For the avoidance of doubt, where iron concentrations are detailed herein, iron is in particular present in an iron-containting compound, e.g. a complex comprising iron, an iron salt, or the like, and the concentrations refer to iron equivalents (i.e. disregarding the remainder of the compound). In one embodiment of the present invention, iron is administered in a dose of 1 mg / Kg body weight to 30 mg / Kg body weight, preferably of 2 mg / Kg body weight to 25 mg / Kg body weight, more preferably of 5 mg / Kg body weight to 15 mg / Kg body weight, and most preferably of 10 mg / Kg body weight. In one embodiment of the present invention, the iron supplementation comprises iron in a concentration of 0,0001 g / L to 20 g / L, preferably 0,001 g / L to 2 g / L, preferably 0,02 g / L to 1,5 g / L, more preferably 0,05 g / L to 1,2 g / L, more preferably 0,1 g / L to 1 g / L and most preferably 0,5 g / L. In one embodiment of the present invention, the iron supplementation is an intravenous supplementation, comprising iron in an amount of 10 mg to 2000 mg, preferably 50 mg to 1500 mg, preferably 100 mg to 1000 mg, and most preferably 500 mg. In one embodiment of the present invention, the iron supplementation is an oral supplementation, comprising iron in an amount of 1 mg to 1000 mg, preferably 20 mg to 800 mg, preferably 50 mg to 600 mg, and most preferably 500 mg. In a further embodiment said oral supplementation is administered once per day. For the avoidance of doubt, where iron concentrations are detailed herein, iron is in particular present in an iron-containting compound, e.g. a complex comprising iron, an iron salt, or the like, and the concentrations refer to iron equivalents (i.e. disregarding the remainder of the compound). In one embodiment of the present invention, the iron supplementation is an intravenous supplementation, comprising iron in a dose of 1 mg / Kg body weight to 30 mg / Kg body weight, preferably of 2 mg / Kg body weight to 25 mg / Kg body weight, more preferably of 5 mg / Kg body weight to 15 mg / Kg body weight, and most preferably of 10 mg / Kg body weight. In one embodiment the iron supplementation according to the present invention is a pharmaceutical formulation comprising iron, or an iron-containing compound and optionally at least one pharmaceutically acceptable excipient. In one embodiment of the present invention, the pharmaceutical formulation is an intravenous formulation, parenteral formulation, intraarterial formulation, oral formulation or intramuscular formulation. “Intravenous formulation, parenteral formulation, intraarterial formulation, oral formulation or intramuscular formulation” means in particular that the formulations are confectioned for intravenous, parenteral, intraarterial, oral or intramuscular administration, and / or to be administered intravenously, parenterally, intraarterially, orally or intramuscularly, respectively. In particular embodiments, said pharmaceutical formulation is in form of a solution, preferably a ready-to-use solution. In other particular embodiments, said pharmaceutical formulation is in a freeze-dried state. In other particular embodiments, said pharmaceutical formulation is to be administered orally, intramuscularly, intraarterially or intravenously. In one embodiment said pharmaceutical formulation is to be administered intramuscularly or intraaerterially or intravenously. In a further embodiment, said pharmaceutical formulation is to be administered intravenously. In further embodiments, the pharmaceutical formulation according to the present invention is not administered intranasally. In certain embodiments, the iron supplementation or pharmaceutical formulation are in the form of an infusion, which means in particular that the iron supplementation or pharmaceutical formulation are confectioned for infusion and / or to be administered as an infusion, respectively. In one embodiment of the present invention, the pharmaceutical formulation comprises iron in a concentration of 0,0001 g / L to 20 g / L, preferably 0,001 g / L to 2 g / L, preferably 0,02 g / L to 1,5 g / L, more preferably 0,05 g / L to 1,2 g / L, more preferably 0,1 g / L to 1 g / L and most preferably 0,5 g / L. In one embodiment of the present invention, the pharmaceutical formulation is an intravenous formulation, comprising iron in an amount of 10 mg to 2000 mg, preferably 50 mg to 1500 mg, preferably 100 mg to 1000 mg, and most preferably 500 mg. In one embodiment of the present invention, the pharmaceutical formulation is an oral formulation, comprising iron in an amount of 1 mg to 1000 mg, preferably 20 mg to 800 mg, preferably 50 mg to 600 mg, and most preferably 500 mg. In a further embodiment said oral formulation is administered once per day. For the avoidance of doubt, where iron concentrations are detailed herein, iron is in particular present in an iron-containting compound, e.g. a complex comprising iron, an iron salt, or the like, and the concentrations refer to iron equivalents (i.e. disregarding the remainder of the compound). In one embodiment of the present invention, the pharmaceutical formulation is an intravenous formulation, comprising iron in a dose of 1 mg / Kg body weight to 30 mg / Kg body weight, preferably of 2 mg / Kg body weight to 25 mg / Kg body weight, more preferably of 5 mg / Kg body weight to 15 mg / Kg body weight, and most preferably of 10 mg / Kg body weight. One embodiment of the present invention is an iron supplementation for treatment and / or prophylaxis of an affective disorder and / or post-traumatic stress disorder (PTSD) and / or serotonin-dependent diseases in a human patient in need thereof, wherein said iron supplematation comprises iron in the form of iron(III) or iron(II), e.g. an Iron(III) or Iron(II) compound, wherein, for the avoidance of doubt, iron compounds include all forms wherein iron is present in a composition of matter comprising iron and other atoms, e.g. iron complexes or salts of iron. In one embodiment, said iron supplematation is selected from the group comprising ferrous bisglycinate chelate, Iron(II) glycine sulphate complex (Ferro sanol duodenal®), Iron(III) derisomaltose (MonoFer®, Iron isomaltoside, ferric derisomaltose, Monoferric), Iron(III) hydroxide-dextran complex (Cosmofer®), Iron(III) sodium D-gluconate complex (Ferlixit® ; Ferrlecit®), Iron-II- gluconate / iron(III)-sodium-gluconate complex (Ferrlecit®), Iron(III) hydroxide sucrose complex (Venofer®, PA21, Velforo), Iron(III) hydroxide sucrose complex (Fermed®), Iron carboxymaltose (Ferinject®), Ferric maltol (ST10; ST10-021) and / or ferric citrate (KRX-0502; auryxia). In an embodiment, said iron supplematation is Iron(III) derisomaltose (MonoFer®, Iron isomaltoside, ferric derisomaltose, Monoferric) or Iron(III) hydroxide-dextran complex (Cosmofer®). Further particular embodiments of the iron supplementation of the present invention are detailed in the following. Embodiments describing processes also relate to the products obtainable and / or obtained by such processes. The iron supplementation according to embodiments of the present invention comprises suitable soluble iron salts such as ferric hypophosphite, ferric albuminate, ferric chloride, ferric citrate, ferric oxide saccharate, ferric ammonium citrate, ferrous chloride, ferrous gluconate, ferrous iodide, ferrous sulfate, ferrous lactate, ferrous fumarate, heme, ferric trisglycinate, ferrous bisglycinate, ferrous asparto glycinate, ferric nitrate, ferrous hydroxide saccharate, ferric sulfate, ferric gluconate, ferric aspartate, ferrous sulfate heptahydrate, ferrous phosphate, ferric ascorbate, ferrous formate, ferrous acetate, ferrous malate, ferrous glutamate, ferroglycine sulfate, ferric oxide hydrate, ferric pyrophosphate soluble, ferric hydroxide saccharate, ferric manganese saccharate, ferric subsulfate, ferric ammonium sulfate, ferrous ammonium sulfate, ferric sesquichloride, ferric manganese citrate, ferric quinine citrate, ferric sodium citrate, ferric sodium edetate, ferric formate, ferric ammonium oxalate, ferric potassium oxalate, ferric sodium oxalate, ferric peptonate, ferric manganese peptonate, ferrous cholinisocitrate, ferric choline citrate, other pharmaceutically acceptable iron salts, and combinations thereof. Particular embodiments relate to ferroglycine sulfate complex, i.e. ferrous glycine sulfate complex (Fe(II) glycine sulfate complex, commercially available for instance as ferro sanol® duodenal. This embodiment further comprises in other embodiments examples of suitable slightly soluble iron salts such as ferric acetate, ferric fluoride, ferric phosphate, ferric pyrophosphate, ferrous pyrophosphate, ferrous carbonate saccharated, ferrous carbonate mass, ferrous succinate, ferrous citrate, ferrous tartrate, ferric fumarate, ferric succinate, ferrous hydroxide, ferrous nitrate, ferrous carbonate, ferric sodium pyrophosphate, ferric tartrate, ferric potassium tartrate, ferric subcarbonate, ferric glycerophosphate, ferric saccharate, ferric hydroxide saccharate, ferric manganese saccharate, ferrous ammonium sulfate, other pharmaceutically acceptable iron salts, and combinations thereof. Further embodiments of the present invention comprise examples of suitable insoluble iron salts such as ferric sodium pyrophosphate, ferrous carbonate, ferric hydroxide, ferrous oxide, ferric oxyhydroxide, ferrous oxalate, other pharmaceutically acceptable iron salts and combinations thereof. Moreover, other embodiments of the present invention comprise examples of suitable iron complexes such as polysaccharide-iron complex, methylidine-iron complex, ethylenediaminetetraacetic acid (EDTA)-iron complex, phenanthrolene iron complex, p-toluidine iron complex, ferrous saccharate complex, ferrlecit®, ferrous gluconate complex, ferrum vitis, ferrous hydroxide saccharate complex, iron-arene sandwich complexes, acetylacetone iron complex salt, iron-dextran complex, iron-dextrin complex, iron-sorbitol-citric acid complex, saccharated iron oxide, ferrous fumarate complex, iron porphyrin complex, iron phtalocyamine complex, iron cyclam complex, dithiocarboxy-iron complex, desferrioxamine-iron complex, bleomycin-iron complex, ferrozine-iron complex, iron perhaloporphyrin complex, alkylenediamine-N,N-disuccinic acid iron(lll) complex, hydroxypyridone-iron(lll) complex, aminoglycoside-iron complex, transferrin-iron complex, iron thiocyanate complex, iron complex cyanides, porphyrinato iron(lll) complex, polyaminopolycarbonate iron complexes, dithiocarbamate iron complex, adriamycin iron complex, anthracycline-iron complex, N-methyl-D-glucamine dithiocarbamate (MGD)-iron complex, ferrioxamine B, ferrous citrate complex, ferrous sulfate complex, ferric gluconate complex, ferrous succinate complex, polyglucopyranosyl iron complex, polyaminodisuccinic acid iron complex, biliverdin-iron complex, deferiprone iron complex, ferric oxyhydride-dextran complex, dinitrosyl dithiolato iron complex, iron lactoferrin complexes, 1,3- ethylenediaminetetraacetic acid (EDTA) ferric complex salts, diethylenetriaminepentaacetic acid iron complex salts, cyclohexanediaminetetraacetic acid iron complex salts, methyliminodiacetic acid iron complex salts, glycol ether diaminetetraacetic acid iron complex salts, ferric hydroxypyrone complexes, ferric succinate complex, ferric chloride complex, ferrous glycine sulfate complex, ferric aspartate complex, sodium ferrous gluconate complex, ferrous hydroxide polymaltose complex, other pharmaceutically acceptable iron complexes and combinations thereof. Further embodiments comprise iron amino acid chelates, which include products resulting from the reaction of protein hydrolysates such as polypeptides, dipeptides and naturally occurring alpha amino acids with the iron ion, as well as amino acid chelates with ethylenediaminetetraacetic acid (EDTA), monohydroxyethylethylenediaminetriacetic acid, diethylenetriaminepentaacetic acid, monohydroxyethyldiglycine and dihydroxyethylglycine. Specific examples of iron amino acid chelates include ferrous aspartate, ferrous asparto glycinate, ferrous bisglycinate and ferrous histidinate. Other embodiments of the present invention comprise examples of elemental iron in the ferric form, such as ferric oxide-hydroxide, ferric acetate, ferric bromide, ferric chloride, ferric citrate, ferric ammonium citrate, ferric fluoride, ferric hydroxide, ferric nitrate, ferric polymaltose, ferric phosphate, ferric pyrophosphate, ferric oxalate, ferric ammonium oxalate, ferric sulfate, ferroglycine sulfate, ferric sulfide, ferric glycinate and EDTA ferric sodium salt, in particular ferric glycinate. In particular embodiments, the iron is present in the form of ferrous asparto glycinate (e.g. Sumalate® of Albion Laboratories, Inc. or a product technically equivalent thereto), in the form of ferrous bisglycinate (e.g. Ferrochel® of Albion Laboratories, Inc. or a product technically equivalent thereto), or in the form of ferric glycinate (e.g. Iron Taste-Free® of Albion Laboratories, Inc. or a product technically equivalent thereto). Further details thereof are disclosed in WO2017165287. A further embodiment in particular relates to oral supplementation. Although the oral route is the most convenient route of delivery for iron, in many cases it has serious limitations due to limited intestinal absorption of the iron and non-compliance. Almost all commercial oral preparations today use ferrous iron (Fe2+), although ferric iron (Fe3+) is the form of iron that binds to transferrin within the blood plasma, and this is the form of iron that the body can metabolize and use. However, ferric iron does not pass through the intestinal wall via the specific ferrous iron receptors. Ferrous iron passes through the intestinal wall via a receptor-mediated transcellular pathway and it is then converted to the ferric form whereby it is taken up by the protein transferrin in the bloodstream. Therefore, most oral iron supplements contain ferrous iron. Ferrous iron when given orally, has very low bioavailability. Because only small amounts are absorbed, large doses are necessary most of which is left non-absorbed in the intestine leading to side effects, which include digestive intolerance, causing nausea, heartburn, flatulence, abdominal pain, diarrhea or constipation, and black or tarry stools. Thus non-compliance of patients is very common because of this intolerance related to gastrointestinal adverse events. The present embodiment relates to formulations of ferric iron-compounds for oral delivery, including a bioavailability enhancer to allow paracellular absorption of iron so that the iron does not need to be absorbed via specific iron receptors. The ferric iron compound according to the present embodiment includes ferric iron in ferric salts and / or complexes including the following: (a) ferric salts of carboxylic acids, e.g. ferric citrate, ferric tribasic citrate, ferric ammonium citrate, ferric tartrate, ferric acetylacetonate, ferric ammonium oxalate, ethylenediaminetetraacetate ferric sodium salt, ferric salts of monocarboxylic acids (short, medium and long chains); preferred are ferric ammonium citrate, ethylenediaminetetraacetate ferric sodium salt (ferric sodium EDTA); (b) ferric salts comprising an heterocyclic structure, e.g. ferric trimaltol and ferric hydroxy pyrones e.g. iron complexes of 3-hydroxy-4-pyrones; and (c) other ferric derivatives, e.g. ferric inorganic salts such as ferric ammonium sulfate; ferric organic salts such as ferric dextrans, ferric trimaltose, ferrichydroxide polymaltose, ferric acetyl-hydroxamate and ferric salts of amino acids; preferred is ferric acetyl-hydroxamate. Preferred bioavailability enhancers include medium chain fatty acid salts and derivatives thereof, bile salts, none-ionic surfactants, ionic surfactants, water soluble phospholipids, medium-chain glycerides, ethylene-diaminetetraacetic acid, fatty acid derivatives pf polyethylene glycol, alkylsaccharides or salicylates. Further details thereof are disclosed in WO2012097155. Another embodiment relates to an iron supplementationcomprising ferrous L-threonate, which may be prepared as follows: 1. Prepared by neutralization reaction of L-threonic acid with ferrous oxides or ferrous hydroxides, for example, with ferrous oxide (FeO) and ferrous hydroxide (Fe(OH)2); 2. Prepared by replacement reaction of L-threonic acid or calcium L-threonate with inorganic ferrous salts, such as ferrous sulfate (FeSO4), ferrous chloride (FeCI2) and ferrous nitrate (Fe(NO3)2), wherein L-threonic acid can be obtained by oxidizing vitamin C or by removing calcium from calcium L- threonate. Further details thereof are disclosed in EP1038524A1. Further embodiments concerne an iron supplementation which are lipid-based dispersions comprising iron (II) or iron (II) supplements, such as ferrous sulfate, ferric chloride, ferrous gluconate, ferrous lactate, ferrous tartrate, iron-sugar-carboxylate complexes, ferrous fumarate, ferrous succinate, ferrous glutamate, ferric citrate, ferrous citrate, ferrous pyrophosphate, ferrous cholinisocitrate, and ferrous carbonate, and the like. In one embodiment the iron is ferric citrate. Thereby, the lipid-based dispersion includes a lipid layer, including liposome forming lipids. Typically, the lipid includes at least one phosphatidyl choline which provides the primary packing / entrapment / structural element of the liposome. Typically, the phosphatidyl choline includes mainly C16 or longer fatty-acid chains. Chain length provides for both liposomal structure, integrity, and stability. Optionally, the fatty-acid chains can have at least one double bond. Optionally, the lipid further includes a phospholipid not being a phosphatidyl choline. Cholesterol typically provides stability to the liposome. Further details thereof are disclosed in WO2006031857. The iron supplementation according to further embodiments of the present invention relates to nanonized iron compositions. Thereby, any appropriate method can be used to make the nanonized iron composition, including for example, the Rapid Expansion of Supercritical Solutions (RESS) process, the Supercritical Anti-Solvent (SAS) method, and the Particles from Gas Saturated Solutions (PGSS) method. These methods are known to the skilled person in the art. Embodiments of the nanonized iron composition can by in any appropriate drug delivery form, including an oral dosage, a transdermal patch, an intravenous solution or a dialysate, as well as other forms known in the pharmaceutical drug delivery arts. Various embodiments relate to nanonized iron compositions wherein the iron-containing nanoparticles have a diameter of 1000 nm or less, or 500 nm or less, or 250 nm or less, or 100 nm or less, or 50 nm or less. Additional embodiments provide nanonized compositions in which 50% or more of the particles have a diameter within 1 to 1000 nm, or within 1 to 500 nm, or within 1 to 250 nm, or within 1 to 100 nm, or within 1 to 50 nm, or within 10 to 1000 nm, or within 10 to 500 nm, or within 10 to 250 nm, or within 10 to 100 nm, or within 10 to 50 nm, or within 50 to 1000 nm, or within 50 to 500 nm, or within 50 to 250 nm, or within 100 to 1000 nm, or within 100 to 500 nm, or within 100 to 250 nm. One or more these particle sizes can be selected such that when the particles are added to a parenteral or other solution for administration to the patient the nanonized compositions dissolve sufficiently in the solution so that no filtering of the solution is needed to prevent an immune response such as a pyrogenic reaction due to any un-dissolved particles. Embodiments of the present invention relate to minimizing adverse GI reactions associated with oral delivery on iron-containing compounds and / or improving absorption in the small intestine, wherein the diameter (or other particle size dimension) of the iron-containing nanoparticles can be 1000 nm or less, or 500 nm or less, or 250 nm or less, or 100 nm or less, or 50 nm or less, or 20 nm or less, or 10 nm or less. Related embodiments for achieving this result provide nanonized iron compositions in which 50% or more of the particles have a diameter within 1 to 1000 nm, or within 1 to 500 nm, or within 1 to 250 nm, or within 1 to 100 nm, or within 1 to 50 nm, or within 10 to 1000 nm, or within 10 to 500 nm, or within 10 to 250 nm, or within 10 to 100 nm, or within 10 to 50 nm, or within 50 to 1000 nm, or within 50 to 500 nm, or within 50 to 250 nm, or within 100 to 1000 nm, or within 100 to 500 nm, or within 100 to 250 nm. The same range of sizes apply to parenteral or other solutions for administration to the patient to prevent an immune response such as a pyrogenic reaction due to any un-dissolved particles, as well as for the parenteral or other solution delivered to a patient receiving treatment for iron deficiency. Still, additional embodiments relate to nanonized iron compositions wherein the iron-containing nanoparticles have a diameter of 50,000 nm or less, or 25,000 nm or less, or 10,000 nm or less, or 5000 nm or less, or 2500 nm or less. Further embodiments provide nanonized compositions in which 50% or more of the particles have a diameter within 100 to 50,000 nm, or within 100 to 25,000 nm, or within 100 to 10,000 nm, or within 100 to 5000 nm, or within 1000 to 50,000 nm, or within 1000 to 25,000 nm, or within 1000 to 10,000 nm, or within 1000 to 5000 nm, or within 5000 to 50,000 nm, or within 5000 to 25,000 nm, or within 5000 to 10,000 nm, or within 10,000 to 50,000 nm, or within 10,000 to 25,000 nm. Particular embodiments relate to intravenous and dialysate embodiments, wherein the particle sizes (as determined by diameter or other particle dimension) of the iron-containing nanoparticles comprising the nanonized iron composition can be chosen to be in the 100 to 5000 nm range, the 500 to 10,000 nm range, the 1000 to 25,000 nm range, the 5000 to 50,000 nm range or the 10,000 to 100,000 nm range. Also, the particle size and particle size distribution can be optimized for other factors separately or in combination with rate of dissolution and / or solubility, such as stability, bioavailability and the presence of other compounds such as erythropoietin (or other red blood cell stimulating glycoprotein) or various preservatives such as citric acid. Yet additional embodiments provide nanonized iron compositions wherein the iron-containing nanoparticles have a diameter of 500,000 nm or less, or 250,000 nm or less, or 100,000 nm or less, or 50,000 nm or less, or 25,000 nm or less. Still further embodiments provide nanonized compositions in which 50% or more of the particles have a diameter within 1000 to 500,000 nm, or within 1000 to 250,000 nm, or within 1000 to 100,000 nm, or within 1000 to 50,000 nm, or within 10,000 to 500,000 nm, or within 10,000 to 250,000 nm, or within 10,000 to 100,000 nm, or within 10,000 to 50,000 nm, or within 50,000 to 500,000 nm, or within 50,000 to 250,000 nm, or within 50,000 to 100,000 nm, or within 100,000 to 500,000 nm, or within 100,000 to 250,000 nm. In other embodiments of the present invention, the nanoparticles are nanonized iron compositions that are sized or otherwise configured to minimize an adverse reaction of the patient to administration of an iron compound included in the nanonized iron composition. Suitable iron compounds for use in nanonized iron-containing compositions can include, for example, ferric pyrophosphate, and related iron salts. Other suitable iron compounds can include without limitation, ferrous or ferric complexes comprising edetate, ethylenediamineedetate, ethylenediaminesuccinate, ferric citrate, ferric pyrophosphate citrate chelate, ferric ammonium citrate, ferric choline citrate, ferric manganese citrate, ferric quinine citrate, ferric sodium citrate, ferric formate, ferric gluconate, ferric ammonium sulfate, ferric ammonium oxalate, ferric potassium oxalate, ferric sodium oxalate, ferric trisglycinate, ferric bislycinate, ferrous saccharate, ferrlecit®, ferrous gluconate, ferrum vitis, ferrous hydroxide saccharate, iron-arene sandwich, acetylacetone iron salt, iron-dextran complex, iron-dextrin, iron-sorbitol-citric acid, saccharated iron oxide, ferrous fumarate, iron porphyrin, iron phtalocyamine, iron cyclam, dithiocarboxy-iron, desferrioxamine-iron, bleomycin-iron, ferrozine-iron, iron perhaloporphyrin, alkylenediamine-N,N'-disuccinic acid iron(III), hydroxypyridone-iron(III), aminoglycoside iron, transferrin-iron, iron thiocyanate, iron complex cyanides, porphyrinato iron(III), polyaminopolycarbonate iron, dithiocarbamate iron, adriamycin iron, anthracycline-iron, MGD-lron, ferrioxamine B, ferrous citrate, ferrous sulfate, ferric gluconate complex, ferrous succinate, polyglcopyranosyl iron, polyaminodisuccinic acid iron, biliverdin-iron, deferiprone iron, ferric oxyhydride-dextran, dinitrosyl dithiolato iron, iron lactoferrin, 1,3-PDTA ferric complex salts, diethylenetriaminepentaacetic acid iron salts, cyclohexanediaminetetraacetic acid iron salts, methyliminodiacetic acid iron salts, glycol ether diaminetetraacetic acid iron complex, ferric hydroxypyrone, ferric succinate, ferric chloride, ferrous glycine sulfate, ferric aspartate, sodium ferrous gluconate, ferrous hydroxide polymaltose, other pharmaceutically acceptable chelated iron complexes, blends, mixtures and / or combinations thereof. Further details thereof are disclosed in WO2012092305. The iron supplementation according to further embodiments comprises an iron carbohydrate complex which is any complex of iron ions or iron particles comprising Fe3+and / or Fe2+and a carbohydrate. In particular, the carbohydrate complex is selected from the group comprising iron carboxymaltose, iron polyglucose sorbitol carboxymethyl ether complex, iron mannitol complex, iron dextran, iron hydrogenated dextran, carboxyalkylated reduced oligo- and poly saccharides, iron sucrose, iron gluconate, iron dextrin, iron hydrogenated dextrin, iron polymaltose, iron hydrogenated polymaltose, iron polyisomaltose, iron hydrogenated polyisomaltose, iron saccharide complex, iron pyrophosphate, iron sorbitol, glycoheptanoic acid, oxidised dextrin, oxidised dextran, oxidised oligo and polysaccharides or mixtures thereof. In a certain embodiment the iron is complexed with dextran glucoheptonic acid. This iron carbohydrate complex is also known as Gleptoferron and is obtainable as eg. Gleptosil (Alstoe Limited Animal Health, York, GB), Ursoferran (Serumwerk Bernburg AG, Bernburg, D). In another embodiment, the iron is complexed to hydrogenated dextran. Commercial iron hydrogenated dextran complexes are Uniferon, CosmoFer, MonoFer, and DiaFer obtainable from Pharmacosmos A / S, Holbaek, Denmark. The carbohydrate component of the iron carbohydrate complex may have any suitable molecular weight. It is generally preferred to use a carbohydrate component with a molecular weight in which weight average molecular weight (MW) of the carbohydrate component of the iron carbohydrate complex is 800 to 80,000 Dalton, preferably 800 to 10,000 In preferred embodiments, the apparent molecular weight of the iron carbohydrate complex is 500.000 Dalton or less, such as an apparent molecular weight of 400.000 Dalton or less. Further details thereof are disclosed in WO2016066172. The iron supplementation according to further embodiments of the present invention comprises a method of preparing an iron hydroxide product. The method includes the steps of: (1) adding a first base solution to a solution of a ferric salt to obtain Mixture A having a pH value of 2.7-2.8, (2) adding a second base solution to Mixture A to prepare a crude iron hydroxide suspension having a pH value of 2.8-3.8, and (3) adding a third base solution to adjust the pH of the crude iron hydroxide suspension to 4.5-9.5 (e.g., 5-9), followed by purification and concentration, thereby obtaining a purified polynuclear iron hydroxide suspension containing polynuclear iron hydroxide or wet cake as an exemplary product. Purification methods are those known in the art. The first, second and the third base solution, independently, can be an aqueous solution of a carbonate salt, e.g., NaHCO3, Na2CO3, (NH4)CO3, and K2CO3. The preferred solution is an aqueous Na2CO3solution having a mass percentage of 1% to 25% (e.g., 3% to 20%, 5% to 15%, and 10%). Further, the first, second, and third base solutions can be the same or different. Suitable ferric salts include Fe2(SO4)3,Fe(NO3)3, FeCl3, and their hydrates. A preferred ferric salt is FeCl3(e.g., FeCl3*6H2O) having a mass percentage of 5% to 60%, preferably 15% to 25%. In some embodiments, the method further contains the steps of: (i) mixing the purified polynuclear iron hydroxide suspension and a carbohydrate to obtain a carbohydrate mixture, (ii) adjusting the pH value of the carbohydrate mixture to 7.5-13 or 9.5-13.5 (e.g., 10-13.5), and (iii) heating the pH-adjusted carbohydrate mixture to a temperature of 60°C - 125°C (preferably 75-95°C and more preferably 80- 95°C), thereby producing an iron hydroxide-carbohydrate complex suspension, in which the mass ratio between iron and carbohydrate is (1-1100) : 100, and the iron hydroxide product is the iron hydroxide carbohydrate complex. Exemplary carbohydrates include monosaccharides, disaccharides, oligosaccharides, polysaccharides, hydrolyzed polysaccharides, and any combinations thereof. In a preferred embodiment, the carbohydrate is sucrose and the mass ratio between Fe3+and sucrose is 1 : (10-20), e.g., 1 : (13-17). The term “carbohydrate” refers to aldehyde or ketone compounds substituted with multiple hydroxyl groups, of the general formula (CH2O)n, in which n is 3-300. Carbohydrates include monosaccharide (n=3-10), disaccharide (n=8-14, e.g., 12, having two monosaccharide units), oligosaccharide (n=15-59, i.e., having 3-9 monosaccharide units), as well as polysaccharide (i.e., having 10 or more monosaccharide units). Examples include glyceraldehyde, dihydroxyacetone, erythrose, threose, arabinose, ribose, xylose, ribulose, xylulose, glucose (dextrose), fructose, galactose, ribose, allose, altrose, gulose, idose, mannose, talose, psicose, sorbose, tagatose, mannoheptulose, sedoheptulose, 2- keto-3-deoxy-manno-octonate, and sialose. Examples of a disaccharide include sucrose, maltose, isomaltose, lactose, trehalose, cellobiose, chitobiose, rutinose, and rutinulose. The term “carboxylated carbohydrate” refers to a carbohydrate containing a carboxyl group (-COOH or -COO-). They can be prepared by oxidizing a corresponding original carbohydrate. In other embodiments, the method further includes the steps of: (i) mixing the purified polynuclear iron hydroxide suspension with citric acid, a citrate salt, or combination thereof to obtain a citrate mixture, and (ii) heating the citrate mixture at a temperature of 40°C - 105°C (e.g., 45-95°C and 55-65°C) for 2 minutes to 10 hours (e.g., 2-180 minutes and 5-30 minutes) thereby producing an ferric citrate complex suspension containing iron hydroxide-citrate complex, in which the molar ratio between iron and citrate being 1 : (0.3 - 5), preferable 1: (0.6 - 1.5), and the iron hydroxide product is an iron hydroxide-citrate complex. The iron hydroxide-citrate complex has a water solubility of 20 wt% or greater (e.g., 50 wt% or greater), a high iron content (e.g., by dry weight 5% - 35% and 12% - 25%), and absence of free ferric ions. In still other embodiments, the method further includes the steps of: (a) mixing the purified polynuclear iron hydroxide suspension and a solution containing (i) citric acid or a citrate salt and (ii) pyrophosphoric acid or a pyrophosphate salt to obtain a pyrophosphate mixture, and (b) heating the pyrophosphate mixture at a temperature of 40°C - 105°C (e.g., 55-65°C) for 5 minutes to 10 hours (e.g., 25-55 minutes), thereby producing a ferric citrate pyrophosphate suspension, in which the molar ratio of iron : citrate : pyrophosphate is 1 : (0.3 -3) : (0.3 - 3) and the iron hydroxide product is an iron hydroxide-citrate- pyrophosphate complex that has a water solubility of 20 wt% or greater (e.g., 50 wt% or greater) and contains by dry weight iron 3% - 35% (e.g., 5-20 %). In yet other embodiments, the method further includes the steps of: (a) mixing the purified polynuclear iron hydroxide suspension with a carboxylated carbohydrate to obtain a carboxylated carbohydrate mixture, and (b) heating the carboxylated carbohydrate mixture at a temperature of 50 °C - 125 °C (e.g., 65-125°C, 55-75°C, and 65-75°C) for 5 minutes to 10 hours (e.g., 25-55 minutes), thereby producing a ferric carboxylated carbohydrate suspension, in which the molar ratio between iron and the carboxylated carbohydrate is 1 : (0.3 - 5), preferably 1: (0.5 - 1.5), and the iron hydroxide product is an iron hydroxide-carboxylated carbohydrate complex. Exemplary carboxylated carbohydrates are gluconate and other carboxylated disaccharides, oligosaccharides, and polysaccharides. Gluconic acid or any water-soluble gluconate salt (e.g., alkali-D-gluconate such as sodium-D-gluconate) can be used in the preparation. Further, the method includes the additional steps of: (a) mixing the purified polynuclear iron hydroxide suspension with a multivalent anion to obtain a multivalent anion mixture, (b) adjusting the pH value of the multivalent anion mixture to 2-13, preferably 3-9, and (c) heating the pH-adjusted multivalent anion mixture to a temperature of 40°C - 125°C, preferably 50°C - 95°C, thereby producing a nano ferric complex suspension, in which the mass ratio between iron and the multivalent anion is (1-1100) : 100 and the iron hydroxide product is the nano ferric complex. Suitable multivalent anions include citric acid, tartaric acid, succinic acid, fumaric acid, malic acid, glyceryl phosphoric acid, any salt thereof, and any combination thereof. These multivariant anions can be used in combination with pyrophosphate. Also within the scope are iron hydroxide products prepared from any method described above. Further details thereof are disclosed in WO2022072439. The iron supplementation according to the present invention comprises stable injectable iron compositions including iron, a carbohydrate, a stabilizing agent and water. In a first embodiment, the injectable iron composition comprises iron, a carbohydrate, a stabilizing agent and water. In further embodiments, the iron is elemental iron. In further embodiments, the carbohydrate comprises (i) a monosaccharide, a disaccharide, an oligosaccharide or a polysaccharide; or (ii) a modified monosaccharide, a modified disaccharide, a modified oligosaccharide or a modified polysaccharide. In further embodiments, the elemental iron and the carbohydrate form a colloidal iron (III) carbohydrate complex. In other embodiments, the composition comprises iron carboxymaltose, iron sucrose, iron polyisomaltose, iron dextrin, iron gluconate, iron sorbitol, iron hydrogenated dextran, iron derisomaltose, derived carbohydrate-coated, superparamagnetic iron oxide or isomers thereof or mixtures thereof. In further embodiments, (i) the monosaccharide comprises glucose, galactose, fructose, isomers thereof or mixtures thereof; (ii) the disaccharide comprises sucrose, lactose, maltose or isomers thereof or mixtures thereof; (iii) the oligosaccharide comprises raffinose, stachyose, verbascose or isomers thereof or mixtures thereof; or (iv) the polysaccharides comprise starch, a starch derivative, dextran, cellulose, glycogen or isomers thereof or mixtures thereof. In further embodiments, (i) the monosaccharide comprises dihydroxyacetone, glyceraldehyde, erythrose, ribose, ribulose, sorbose, xylose, arabinose, fructose, glucose, galactose, mannose, or isomers thereof or mixtures thereof; or (ii) the disaccharide comprises sucrose, maltose, cellobiose, gentiobiose, isomaltose, melibiose, primeverose, rutinose, trehalose, lactose or isomers thereof or mixtures thereof. In further embodiments, the starch derivative comprises a dextrin comprising a maltodextrin, a maltose syrup, a glucose syrup or mixtures thereof. In further embodiments, the stabilizing agent comprises an alkalinizing agent, a buffering agent or sucrose. In further embodiments, the iron comprises elemental iron, the carbohydrate comprises sucrose, and the stabilizing agent comprises at least one of a sodium compound, L-histidine, sucrose, or a combination thereof. In further embodiments, the alkalinizing agent comprises sodium hydroxide, potassium hydroxide, calcium hydroxide or a combination thereof. In further embodiments, the buffering agent comprises sodium carbonate, sodium bicarbonate, potassium carbonate, potassium bicarbonate, calcium carbonate, calcium bicarbonate or a mixture thereof. In further embodiments, the buffering agent comprises L-histidine, glycine, arginine, tyrosine, lysine or a mixture thereof. In further embodiments, the sodium compound is sodium hydroxide, sodium chloride, sodium gluconate or a combination thereof. In further embodiments, (i) the iron (III) carbohydrate complex comprises an iron monosaccharide complex, an iron disaccharide complex, an iron oligosaccharide complex, an iron polysaccharide complex or combinations thereof; or (ii) wherein the iron polysaccharide complex comprises iron carboxymaltose, iron sucrose, iron polyisomaltose, iron polymaltose, iron gluconate, iron sorbitol, iron hydrogenated dextran, iron derisomaltose or mixtures thereof. Further embodiments relate to an injectable iron composition comprising a colloidal iron- carbohydrate complex, a stabilizing agent and water, preferably wherein the carbohydrate is a sugar comprising glucose and fructose. The stable iron composition of the present application can be prepared using a commercially available iron-carbohydrate complex or iron-carbohydrate colloid that water, and a stabilizing agent can be mixed with to form the stable ready-to-use or ready-to-administer iron compositions of the current application. Such commercially available iron-carbohydrate complexes or iron-carbohydrate colloids are listed in Table A. These compounds are encompassed for the use of the present invention as such, i.e. also without further preparing a stable iron composition according to the present invention. Table A: The commercially available iron-carbohydrate complexes or iron-carbohydrate colloids listed in Table A are available from the following manufacturers listed in Table B below.

[0002] Table B: The commercially available iron-carbohydrate complexes or iron-carbohydrate colloids listed in Table A have the following iron-carbohydrate content and pH listed in Table C. Table C Tire commercially available iron-carbohydrate complexes or iron-carbohydrate colloids listed in Table A have the following physico-chemical properties listed in Table D below. Table D In some embodiments of the present invention, iron ferumoxytol also known as derived carbohydrate- coated, superparamagnetic iron oxide relates to an iron complex where ferumoxitol includes a polyglucose sorbitol carboxymethyl ether-coated non-stoichiomctric magnetite. In certain embodiments of the present invention is an iron sucrose injectable solution comprising Venofer® (Iron Sucrose Injection, USP), which is 20 mg / mL composed of the active pharmaceutical ingredient (API) polynuclear iron (Ill)-hydroxide in sucrose having a molecular weight of approximately 34.000 to 60,000 Daltons (Da) and a proposed structural formula of: [Na2Fe5O8(OH) x 3(H2O)]n x m(C12H22O11), where n is the degree of iron polymerization and m is the number of sucrose molecules associated with the polymerized iron (Ill)-hydroxide and are in the range of providing said molecular weight. In particular embodiments, the sucrose in the polynuclear iron (III)-hydroxide complex can be in a range from about 0.5 mg / mL, 1, 1.5, 2, 2.5, 3, 4, 5.6, 7, 8.9, 10, 11, 12.13, 14, 15.16, 17, 18,19, 20.21, 22, 23, 24.25, 26.27, 28.29.30 to about 31 mg / mL. In another embodiments, the stabilizing agent sodium hydroxide can be present in the iron composition in an amount from about 0.07, or about 0.08 to about 28.3 mg / mL or to about 0.96 mg / mL. In addition to Venofer®, other parenteral iron compositions approved in the United States include iron dextran (e.g., InFed®, Dexferrum®), sodium ferric gluconate complex in sucrose (Ferrlecit®), and ferric carboxymaltose injection (Injectafer®). Those approved in the UK also includes iron sucrose (Sucrofcr®, UK Claris). Ferric dcrisomaltose (e.g., ferric derisomaltose or iron isomaltoside) is another form of iron compound used in the treatment of iron deficiency. This drug is a complex of iron (III) hydroxide and derisomaltose. The latter is an iron carbohydrate oligosaccharide that works to release iron. The molecular formula of this iron carbohydrate complex is Ci 8H34FeOi6+3- Specifically, ferric derisomaltose is an iron carbohydrate complex with a matrix structure composed of interchanging layers of ferric hydroxide and the carbohydrate derisomaltose. Derisomaltose contains linear, hydrogenated isomaltooligosaccharides with an average molecular weight of 1000 Da. Ferric derisomaltose has an average molecular weight of 155,000 Da and has the following empirical formula: {FeO(1-3X) (OH) (1+3X) (C6H5O73-)X], (H2O)T, (C6H1006)R(-C6H10O5-)Z(C6H13O5)R, (NaCl)Y wherein X= 0.0311; T = 0.25; R = 0.14; Z = 0.49; Y = 0.14. Further details of the iron supplementation are disclosed in WO2023028252. The iron supplementation according to further embodiments of the present invention comprises iron complex compounds, which is a complex of iron ions or iron particles comprising Fe3+and / or Fe2+and one or more ligands. The iron atoms are bound in a coordination complex through ionic and coordinate covalent bonds with the ligand(s) or as part of a poly-nuclear iron ligand nanomolecule, preferably an iron carbohydrate nanomolecule. According to embodiments of the present invention, the ligand in the iron complex compound is a carbohydrate. The term “carbohydrate" as used herein is not limited to compounds having the empirical formula Cm(H2O)n, wherein m and n are integers which may be the same or different from each other, but also includes carbohydrates which are reduced, oxidised, or derivatised, e.g. by the formation of ethers, amides, esters and amines with the hydroxyl groups of the carbohydrates or by the conversion of aldehyde groups of the carbohydrates to glycolic groups so as to form heptonic acids. Carbohydrates which may be used as ligands in iron carbohydrate complexes include, for example, monosaccharides; disaccharides, e.g. sucrose, maltose or isomaltose; oligosaccharides and polysaccharides, e.g. maltodextrin, polyglucose, dextran, oligomaltose, oligoisomaltose; sugar alcohols, e.g. sorbitol and mannitol; sugar acids and salts thereof, e.g. gluconic acid, gluconate, dextran glucoheptonic acid, dextrin glucoheptonic acid, dextran glucoheptonate and dextrin glucoheptonate, as well as reduced and / or oxidised and / or derivatised variants thereof, e.g. carboxymaltose, polyglucose sorbitol carboxymethyl ether, hydrogenated dextran, oxidised dextran, carboxyalkylated oligo- and polysaccharides, oxidised oligo- and polysaccharides, hydrogenated dextrin, oxidised dextrin, hydrogenated oligomaltose, hydrogenated oligoisomaltose, hydrogenated oligomaltose, hydroxyethyl starch, hydroxyethyl starch carrying heptonic acid moieties, or a mixture of two or more thereof. When oligo- and polysaccharides are used, these typically comprise mixtures of oligo- and polysaccharides having varying chain lengths. Therefore, these oligo- and polysaccharides can conveniently be characterised by weight or number average molecular weights and the distribution of these molecules across a range of molecular weights. For the sake of simplicity, reference to an oligo- or polysaccharide is meant to refer to such mixtures. Such carbohydrates will typically have a weight average molecular weight (Mw) of from 500 to 80,000 Da, such as from 800 to 40,000 Da or from 800 to 10,000 Da and in particular from 800 to 3,000 Da. In particular embodiments, the carbohydrate is a polysaccharide or oligosaccharide or mixture thereof having a weight average molecular weight (Mw) of from 500 to 7,000 Da, such as from 500 to 3,000 Da, from 700 to 1,400 Da and in particular of from 850 to 1,150 Da, e.g., of about 1,000 Da, or from 1,150 to 1,350 Da, e.g., of about 1,250 Da. The term “oligosaccharide” comprises typically 3-10 monosaccharide units, their derivatives described above, and mixtures, wherein the majority (e.g. at least 60%, at least 70%, or at least 80%) has the length of 3-10 monosaccharides. Preferably, the content of reducing aldehyde groups in the carbohydrate is at least partially reduced. This can be achieved by hydrogenation, oxidation, glycosylation, or a combination thereof. Iron carbohydrate complex compounds comprising carbohydrates which are hydrogenated and / or oxidised can be prepared as described, for example, in WO 99 / 48533 A1; WO 2010 / 108493 A1 or WO 2019 / 048674 A1, all of which is incorporated by reference. The amount of reducing carbohydrate can be determined using Somogyi’s reagent. Alternatively or additionally to hydrogenation, aldehyde groups can be oxidised in embodiments of the present invention, for example by oxidation of the carbohydrate using an aqueous solution of hypochlorite, chlorite or hypobromite at a pH within the alkaline range, e.g. within the range of from pH 8 to pH 12, in particular from pH 9 to pH 11. Particularly preferred carbohydrate ligands according to the present invention are: - Oligoisomaltose, in particular hydrogenated oligoisomaltose (i.e. oligoisomaltoside). In particular embodiments, the oligoisomaltos(id)e has a weight average molecular weight (Mw) of from 700 to 1,500 Da. Oligoisomaltos(id)e having a weight average molecular weight (Mw) of from 850 to 1,150 Da; preferably 950 to 1,050 Da, most preferably from 975 to 1025 Da, e.g., of about 1000 Da, represents one particular embodiment. Oligoisomaltos(id)e having a weight average molecular weight (Mw) of from 1,150 to 1,350 Da; preferably from 1,200 to 1,300 Da, most preferably from 1,225 to 1275 Da; e.g., of about 1250 Da (also referred to herein as “octasaccharide”), represents another particular embodiment. - Gluconic acid derivatives of carbohydrates, such as dextran or dextrin, including bepectate or dextran glucoheptonic acid. The term “bepectate” as used herein refer to a hydroxyethyl-amylopectin (starch) derivative. Bepectate has also been referred to as polyglucoferron (FeramylTM). Bepectate is disclosed, for instance, in WO 2012 / 175608 A1. Such hydroxyethyl-amylopectin (starch) derivative may carry a number of heptonic acid residues per molecule, depending on the number of terminal glucosyl residues being present in the starch molecule. More generally, hydroxyethyl starch (HES) is a starch in which some of the hydroxyl groups of the single glucosyl residues are substituted by a hydroxyethyl residue. The modification by the heptonic acid residue takes place by converting the terminal glucosyl residue of the hydroxyethyl starch into a heptonic acid residue. Preferably, the hydroxyethyl starch used in the method has a weight average molecular weight (Mw) of less than 200,000 g / mol, in particular of less than 130,000 g / mol, in particular of less than 100,000 g / mol, in particular of less than 90,000 g / mol, in particular of less than 80000 g / mol and very particular of less than 75,000 g / mol. A very well suited molecular weight is in the range of 55,000 g / mol to 85,000 g / mol. Such a hydroxyethyl starch with a molecular weight of 70,000 g / mol ± 15,000 g / mol and an average degree of molar substitution of 0.5 ± 0.05 can also be referred to as HES 70 / 0.5. According to other embodiments, the ligand is a ligand suitable for ligand-substituted oxohydroxy iron complex compounds. Suitable ligands include, for example, carboxylic acids, such as adipic acid, glutaric acid, tartaric acid, malic acid, succinic acid, aspartic acid, pimelic acid, citric acid, gluconic acid, lactic acid and benzoic acid; food additives such as maltol, ethyl maltol and vanillin; anions with ligand properties such as bicarbonate, sulphate and phosphate; mineral ligands such as silicate, borate, molybdate and selenate; amino acids, in particular proteinogenic amino acids, such as tryptophan, glutamine, proline, valine and histidine; and nutrient-based ligands such as folate, ascorbate, pyridoxine and niacin; as well as a mixtures of two or more thereof. A particular example of suitable polymeric ligands are the biocompatible polyethylene glycol-based polymers described in US 8,741,615 B2, i.e., a biocompatible polymer of general formula (I), wherein R1is alkyl, aryl, carboxyl, or amino, R2is alkyl or aryl, n is an integer from 5 to 1000, and m is an integer from 1 to 10. Suitable alkyl groups for R1and R2include C1-C20straight chain or branched alkyl groups. In one embodiment, each of R1and R2independently, is a C1-C6straight chain or branched alkyl such as methyl, ethyl, propyl, isopropyl, n-butyl, sec-butyl, tert-butyl, n-pentyl, isopentyl, tert- pentyl, n-hexyl, and isohexyl. Suitable aryl groups for R1and R2include C6-C12substituted or unsubstituted aryl groups such as phenyl, biphenyl, and naphthyl, and examples of substituents thereof include hydroxyl, haloalkyl, alkoxyl, cyano, nitro, amino, or alkylamino. The number of methylene units m is preferably an integer from 1 to 10. The number of oxyethylene units n is preferably an integer from 5 to 1000, equivalent to a molecular weight of 200-50000 g / mole of the PEG. In one embodiment, m is about 3, and n is about 15. The biocompatible polymer is useful in that it can chemically modify the surface of iron oxide nanoparticles to give a biocompatible magnetic material comprising a magnetic nanoparticle and the biocompatible polymer. For iron ions to be suitable for parenteral administration, they have to be complexed with ligands so that the amount of free iron ions is low, and the iron is released in a controlled manner after being administered. Expediently, the total amount of free iron that comes with the iron complex compound prior to administration is in certain embodiments 0.01% w / v or less and preferably less than 0.003% w / v (for an iron complex compound being presented as a 100 mg / mL solution). Put differently, in another embodiments, the total amount of free iron relative to the total iron content is 0.1% or less and preferably less than 0.03% of free iron by weight of total iron content (for an iron complex compound being presented as a 100 mg / mL solution). This requires the iron complex compound to have a physical stability that sufficient for the complex to be processed into the final drug product and stored until it is used. Iron carbohydrate complex compounds according to the present invention include complexes with the carbohydrate ligands disclosed herein, for example, iron carboxymaltose, iron polyglucose sorbitol carboxymethyl ether complex, iron mannitol complex, iron dextran, iron hydrogenated dextran, iron oxidised dextran, iron carboxyalkylated reduced oligo- and polysaccharides, iron sucrose, iron gluconate, iron dextrin, iron hydrogenated dextrin, iron oxidised dextrin, iron oligomaltose, hydrogenated iron oligomaltose, iron hydrogenated oligosaccharides such as iron hydrogenated oligoisomaltose, iron hydroxyethyl starch, iron sorbitol, iron dextran glucoheptonic acid (e.g., gleptoferron) and a mixture of two or more thereof. According to particular embodiments, the iron carbohydrate complex compound is selected from iron carboxymaltose, iron polyglucose sorbitol carboxymethyl ether complex, iron mannitol complex, iron dextran, iron hydrogenated dextran, iron sucrose, iron gluconate, iron dextrin, iron hydrogenated oligoisomaltose and a mixture of two or more thereof. In more preferred embodiments, the iron carbohydrate complex is iron hydrogenated oligoisomaltose (iron oligoisomaltoside). The amount of iron in the iron carbohydrate complex compound, determined for dry matter, is in embodiments of the present invention typically in the range of from 10 to 50%, preferably 15 to 35%, most preferably 20 to 30%, e.g., from 20 to 25%, of iron by weight of the carbohydrate complex. Accordingly, the weight ratio of elemental iron to carbohydrate in the complex is typically 10:90 to 50:50, preferably 15:85 to 45:55, most preferably 20:80 to 40:60, e.g., about 70:30. The “apparent” peak molecular weight (MP) of the iron carbohydrate complexes is typically in the range of from 800 to 800,000 Da, such as from 10,000 to 500,000 Da or from 20,000 to 400,000 Da or from 50,000 to 300,000 Da and in particular from 90,000 to 200,000 Da. The “apparent” peak molecular weight MP can be determined by gel-permeation chromatography using, e.g., dextran standards. See, for example, the method described in Jahn et al., Eur J Pharm Biopharm 2011, 78, 480-491. For iron oligoisomaltos(id)e complexes disclosed herein the “apparent” peak molecular weight (MP) is typically in the range of from 120,000 to 190,000 Da, in particular from 125.000 to 185.000 Da or from 130,000 to 180,000 Da. An “apparent” peak molecular weight (MP) in the range of 135,000 to 175,000 Da and especially in the range from 140,000 to 155,000 Da has proven to be advantageous, especially in connection the ferric octasaccharide disclosed herein. Preferably, the “apparent” peak molecular weight (MP) is in the range of 145,000 to 155,000 Da, especially in connection the ferric octasaccharide disclosed herein. The iron oligoisomaltos(id)es preferably have a relatively narrow molecular weight distribution with a dispersity (Mw / Mn) in the range of 1.0 to 1.5, preferably 1.05 to 1.4, more preferably 1.1 to 1.3; e.g., at about 1.2. In some embodiments, the iron carbohydrate complexes can comprise stabilizers such as organic acids. Preferably, the organic acid is an organic hydroxy acid. Suitable examples of organic hydroxy acids are gluconic acid and citric acid. Citric acid is an expedient example. If present, the amount of citric acid is typically in the range of 3 to 20% by weight of total quantity of elemental iron. Particularly suitable iron carbohydrate complexes are oligoisomaltos(id)es, such as iron isomaltoside 1000 (INN name: ferric derisomaltose) or ferric octasaccharide. The term “iron oligoisomaltosides” refers to colloidal complexes comprising iron, e.g., as iron oxide hydroxide, and oligoisomaltoside in a matrix-like structure. An example of another iron oligoisomaltoside is commercially available in many countries under the tradename Monofer®, Monoferric® or Diafer®. The iron oligoisomaltoside complexes have been found to have properties which turn out to be advantageous when it comes to their medical use. In particular embodiments, total amount of free iron was found to be less than 0.01% w / v and in particular preferably less than 0.003% w / v for a 100 mg / mL solution of the iron oligoisomaltoside complex. In another particular embodiment, iron carbohydrate complex is ferric bepectate (FBP). Ferric bepectate is disclosed, for instance, in WO 2012 / 175608 A1. These are also known as gleptoferron, as disclosed e.g. in US 3,639,588. Another embodiment relates to ferric octasaccharide complexes, which comprise iron complexed with an octasacchairde. Preferably, the ferric octasaccharaide comprises an iron oxide hydroxide in stable association with an octasaccharide. Further details thereof are disclosed in WO2023012242. The iron supplementation according to further embodiments comprises ferrous bisglycinate chelate having the following structure formula This compound, and its structure, have been known for some time (Ashmed S.D. The chemistry of ferrous bisglycinate chelate, Arch. Latino Am. De Nutr., 2001, 51(1), 7-12; Atkins P.W., Berau J.A. 1992 General Chemistry 2nd ed. Scientific American Books, WH Freeman New York; Coplin et al. Tolerability of Iron: a comparison of bis-glycino iron II and ferrous sulphate, Clinical Therapeutics, vol. 13, n. 5, 606-612 , 1991). Ferrous bisglycinate chelate is commercially available as e.g. Ferrochel® of Albion Laboratories, Inc.. Further details thereof are disclosed in EP2047854A1. The iron supplementation according to a further embodiment comprises the preferred iron composition bis-glycine chelate of iron (FerrochelTM, Albion International, Inc., USA), due to its gentleness to the stomach or tolerability profile. Further embodiments generally relate to amino acid chelates which are products resulting from the reaction of a polypeptide, dipeptide or naturally occurring alpha amino acid with a metal ion having a valence of two or more. Although the term amino acid as used herein refers only to products obtainable through protein hydrolysis, synthetically produced amino acids are not to be excluded provided they are the same as those obtained through protein hydrolysis. Accordingly, protein hydrolysates such as polypeptides, dipeptides and naturally occurring alpha amino acids are collectively referred to as amino acids. Additional suitable amino acid chelates include for example but are not limited to ethylenediaminetetraacetic acid (EDTA), monohydroxyethylethylenediaminetriacetic, acid, diethylenetriaminepentaacetic, monohydroxyethyldiglycine and dihydroxyethylglycine. Other suitable forms of iron include for example but are not limited to soluble iron salts, slightly soluble iron salts, insoluble iron salts, chelated iron, iron complexes, non-reactive iron such as carbonyl iron and reduced iron, and combinations thereof. Suitable iron absorption promoters include for example but are not limited to ascorbic acid, salts of ascorbic acid, derivatives of ascorbic acid, compounds having VitaminC activity, carbohydrates such as but not limited to mannitol, sorbitol, xylose, inositol, fructose, sucrose, lactose, and glucose, calcium, copper, sodium molybdate, amino acids and combinations thereof. Further details thereof are disclosed in US2006134227A1. The iron supplementation according to further s comprises iron carbohydrate complexes that do not induce significant increases in iFGF23 (intact FG23). While in particular ferric carboxymaltose (FCM) significantly increases iFGF23 (see, for instance, WO 2013 / 134273 A1), results from clinical trials provide evidence that the risk for increasing iFGF23 and thus triggering iFGF23-mediated effects is low with iron isomaltoside 1000 (Monofer®). Accordingly, the preferred iron carbohydrate complex is iron isomaltoside (IIM).The term “iron isomaltoside” as used herein refers to colloidal complexes comprising iron, e.g., as iron oxide hydroxide, and isomaltoside in a matrix-like structure. The term “isomaltoside” as used herein refers to a hydrogenated oligoisomaltose (oligoisomaltoside). In particular embodiments, the isomaltoside is a mixture of hydrogenated poly- / oligosaccharides having a weight average molecular weight Mw of from 500 to 7,000 Da, such as from 500 to 3,000 Da, from 700 to 1,400 Da and in particular of about 1,000 Da. The number average molecular weight (Mn) of such hydrogenated poly- / oligosaccharide is preferably in the range of from 400 to 1,400 Da, and 90 wt- % of these molecules have molecular weights of less than 3,500 Da, in particular less than 2,700 Da, and the molecular weights of the remaining 10% of the molecules are below 4,500 Da, in particular below 3,200 Da. For example, said hydrogenated poly- / oligosaccharide is a hydrogenated polyglucose, oligoglucose or a mixture thereof, such as a hydrogenated dextran, hydrogenated dextrin or hydrogenated oligoisomaltose (oligoisomaltoside) or a mixture thereof, with hydrogenated oligoisomaltose, particularly hydrogenated oligoisomaltose wherein the majority (such as at least 60%, e g. from 70 to 80%) of the molecules has 3-6 monosaccharide units, being preferred. Accordingly, in preferred embodiments, the iron carbohydrate complex is an iron hydrogenated oligoisomaltose, in particular an iron(III) hydrogenated oligoisomaltose, wherein the majority (such as at least 60%, eg. from 70 to 80%) of the oligoisomaltoside molecules has 3-6 monosaccharide units, such as iron(III) isomaltoside 1000 (INN name: ferric derisomaltose). Iron isomaltosides are typically characterized by a strong colloidal complex of iron oxide-hydroxide and hydrogenated isomaltose (isomaltoside) chains resulting in a gradual release of iron. In the particular embodiments, the content of dimer saccharide of the hydrogenated poly- / oligosaccharide is preferably 2.9 wt-% or less, 2.5 wt-% or less, or 2.3 wt-% or less, in particular 2.1 wt-% or less or 1.5 wt-% or less, and most preferably 1.0 wt-% or less, based on the total weight of the hydrogenated poly- / oligosaccharide. Preferably, preparations of the hydrogenated poly- / oligosaccharide used for preparing iron carbohydrate complexes have a content of monomer saccharide of 0.5 wt-% or less. Iron hydrogenated dextran complexes prepared from such hydrogenated poly- / oligosaccharide preparations typically have an apparent molecular weight (Mp) in the range of from 120,000 to 180,000 Da, in particular from 130,000 to 160,000 Da. Before the hydrogenated poly- / oligosaccharide preparation is contacted with the iron preparation, the preparation can be purified by membrane processes so as to remove high molecular weight hydrogenated polysaccharides and / or low molecular weight hydrogenated oligosaccharides. In particular embodiments, the hydrogenated poly- / oligosaccharide preparation has been purified by one or more membrane processes having a cut-off value between 340 and 800 Da. In even more particular embodiments, the hydrogenated poly- / oligosaccharide preparation has been purified by one or more membrane processes using a membrane having a cut-off value that allows for holding back polysaccharides having a molecular weight above 2,700 Da, optionally followed by further hydrolysis, and followed by one or more membrane processes using a membrane having a cut-off value between 340 and 800 Da. Alternatively, the purification by said membrane processes takes place prior to the hydrogenation. In particularly preferred embodiments, the iron isomaltoside is a compound having the formula

[0003] In further particularly preferred embodiments, the iron complex compound is a compound having the formula In particular embodiments, the iron complex has an iron content (determined for dry matter) of from 23 to 39 wt-% and is optionally present in the form of an injectable solution having about 100 mg / ml. Iron isomaltosides are obtainable as described, for instance, in WO2010 / 108493 A1 and WO2019 / 048674 A1. A preferred example of iron isomaltoside is commercially available in many countries under the tradename Monofer®, Monoferric® or Diafer®. Another particular iron carbohydrate complex is ferric bepectate (FBP). The term “ferric bepectate” as used herein refers to colloidal complexes comprising an iron core, e.g., as iron oxide hydroxide, coated with a hydroxyethylamylopectin derivative. Ferric bepectate has also been referred to as polyglucoferron. Ferric bepectate and its manufacture are disclosed, for instance, in WO2012175608 A1. Iron isomaltosides are the preferred iron carbohydrate complex. Particularly preferably, the iron isomaltoside is ferric derisomaltose. Further details thereof are disclosed in WO2020249712. The iron supplementation according to further embodiments comprises an injectable medicinal preparation to prevent and treat iron deficiency anemia. This injectable medicinal preparation is also suitable for the treatment of the diseases of the present invention. The preparations use as active substances iron (III) dextran heptonic acid, iron (III) oligomaltoside, isomaltoside 1000 (an oligosaccharide with a mean molecular weight of 1,000 Da, which consists predominantly of chains corresponding to 3-5 glucose units), or iron (III) dextran complex. The iron (III) complexes additionally comprise one or more vitamins selected from the group consisting of folic acid (vitamin B9), cyanocobalamin or hydroxocobalamin (vitamin B12), niacin niacinamide or nicotinamide (vitamin B3), and vitamin E (tocopherol acetate or a-tocopherol; to reduce toxicity due to neutralization of the oxidative action of iron ions). Further details thereof are disclosed in EP3459550A1. The iron supplementation according to a further embodiment encompasses iron hydrogenated dextran complexes having a carbohydrate component comprising a backbone of glucose units linked by alpha- 1,6 glycosidic linkages and optionally branches of glucose units linked to the backbone through alpha- 1,3 glycosidic linkages, wherein the proportion of alpha-1,3 glycosidic linkages to alpha-1,6 glycosidic linkages is less than 5:100, such as less than 1:100. The low amount of branches of glucose units linked to the backbone through alpha-1,3glycosidic linkages may have less tendency to provoke an immunological response to the treatment. In a preferred embodiment, the carbohydrate component does not comprise detectable branches of glucose units linked by alpha-1,3 glycosidic linkages to the backbone. One embodiment relates to an (1—>6)-alpha-D-glucopyranan-(1—>6)-D-glucitol iron(lll) complex. The weight average molecular weight (MW) of the carbohydrate component of the iron carbohydrate complex is 800 to 40,000 Dalton, such as 800 to 10,000, and preferably 800 to 2,000 Dalton, more preferably around 1,000 Dalton. Generally, the apparent molecular weight of the iron carbohydrate complex measured relative to dextran standards, is 400.000 Dalton or less, such as 300.000 Dalton or less, and preferably 200.000 Dalton or less. Generally, the apparent molecular weight of the iron carbohydrate complex is above 20.000 Daltons, such as above 50.000 Daltons, and preferably above 100.000 Daltons. The method of determining the apparent molecular weight using dextran standards is disclosed in Jahn MR, et al, European Journal of Pharmaceutics and Biopharmaceutics 78 (2011) 480-491. The iron carbohydrate complex generally comprises one or more iron cores and a plurality of carbohydrates. The mean iron core size is suitably not greater than about 15 nm and usually in the range of at least about 1 nm to no greater than about 15 nm, such as at least about 3 nm but no greater than about 10 nm, and preferably at least about 5 nm but not greater than about 8 nm. The complex may contain any appropriate number of iron molecules per one carbohydrate, such as between 1 to 100 iron molecules per carbohydrate molecule, such as 5 to 50 or preferably 7 to 20 iron molecules per carbohydrate molecule. In a preferred embdoiment the iron carbohydrate complex comprises about 10 ± 5 iron molecules per one carbohydrate. Preferred is the iron carbohydrate complex Monofer®, an iron hydrogenated oligoisomaltoside having an apparent molecular weight of around 150,000 Daltons, an iron core of 5-8 nm, a shell diameter of around 10 nm, and about 8 iron atoms per carbohydrate molecule. The carbohydrate component has a weight average molecular weight of around 1,000 MW and comprises glucose units linked by a-1,6 glycosidic linkages without detectable branches of a-1,3 glucose units with a reduced end group. Further details thereof are disclosed in WO2016206699. The iron supplementation according to further embodiments relates to high dosage application of iron carbohydrate complexes. Preferably, such iron carbohydrate complexes have one or more of the following characteristics: a nearly neutral pH (e.g., about 5 to about 7); physiological osmolarity; stable carbohydrate component; an iron core size no greater than about 9 nm; mean diameter particle size no greater than about 35 nm, preferably about 25 nm to about 30 nm; slow or competitive delivery of the complexed iron to endogenous iron binding sites; serum half-life of over about 7 hours; low toxicity;nonimmunogenic carbohydrate component; or low risk of anaphylactoid I hypersensitivity reactions.Such iron carbohydrate complexes comprise (a) iron carboxy-maltose complexes such as ferric carboxymaltose (CAS-No. 9007-72-1, VIT-45, polynuclear iron (lll)-hydroxide 4(R)-(poly-(1—>4)-O-a-glucopyranosyl)-oxy-2(R),3(S),5(R),6- tetrahydroxy-hexanoate, "Injectafer®"), (b) carboxyalkylated reduced polysaccharide iron oxide complexes such as polyglucose sorbitol carboxymethyl ether-coated non-stoichiometric magnetite (e.g. “ferumoxytol”, see Spinowitz 2005 Kidney Inti 68, 1801-1807,described in U.S. Patent No.6,599,498), and (c) iron polyisomaltose complexes such as iron polyisomaltose, e.g. iron isomaltoside 1000 (MonoferTM). Further details thereof are disclosed in WO2016196274. The iron supplementation according to further embodiments of the present invention comprises iron- dextran compounds having an extremely low frequency of non-desired side effects and being satisfactory stable, also during sterilization and storage as aqueous solutions, which iron-dextran compound can be used as component in a therapeutical composition for prophylaxis or treatment of iron-deficiency in animal or human subjects by parenteral administration, the iron-dextran compound being characterized in that it comprises hydrogenated dextran having a weight average molecular weight (Mw) between 700 and 1,400 Daltons, preferably approximately 1,000 Daltons, a number average molecular weight (Mn) of 400 to 1,400 Daltons and wherein 90% by weight of the dextran has molecular weights less than 2,700 Daltons and the Mw of the 10% by weight fraction of the dextran having the highest molecular weights is below 3,200 Daltons, said hydrogenated dextran having been subjected to purification by membrane processes having a cut-off value between 340 and 800 Daltons, in stable association with ferric oxyhydroxide. In some embodiments, the iron-dextran compound has an apparent peak molecular weight (Mp) of 50,000-150,000 Da, preferably 70,000-130,000 Da, more preferably 80,000-120,000 Da, and its iron content is 15-45% b.w. The compounds can be synthesized as disclosed in WO0030657 and WO9948533. The iron supplementation according to further embodiments relates to an iron oligosaccharide compound , which compound comprises a hydrogenated oligosaccharide in stable association with ferric oxyhydroxide, the hydrogenated oligosaccharide having a weight average molecular weight (Mw) of less than 3,000 Daltons, preferably approximately 1,000 Daltons, the content of dimer saccharide in said hydrogenated oligosaccharide being 2.9% by weight or less, based on the total weight of the hydrogenated oligosaccharide. The amount of dimer in the oligosaccharide entering into stable association with iron(III)-oxyhydroxide is a key factor with regard to the stability of the final compound, and that the effect is exerted in a highly non-linear manner. Thus, by controlling the amount of dimer in the oligosaccharide before reacting with iron, a stable iron oligosaccharide compound is provided in an effective and cost-efficient way. In the case of dextran or dextrin, which are both glucose polymers comprising a 1,6-bonds as well as a 1,4-bonds, the dimers in question are isomaltose (two glucose monomers joined by an a 1,6-bond) and maltose (two glucose monomers joined by an a 1,4-bond). The hydrogenated oligosaccharide may be Dextran 1, which satisfies the Ruopean Pharmacopeia, entry 01 / 2009:1506. Usually, iron(III)-oxyhydroxid is the sole component used in the iron saccharide composition. The employed hydrogenated oligosaccharide being dextran or dextrin, has weight average molecular weight (Mw) between 500 and 3000 Daltons, a number average molecular weight (Mn) above 500 Daltons, wherein 90% by weight of said hydrogenated oligosaccharide has molecular weights less than 3500 Daltons, and the Mw of the 10% by weight fraction of the hydrogenated oligosaccharide having the highest molecular weights is below 4500 Daltons. Preferably, the hydrogenated oligosaccharide has been subjected to membrane processes having a cut-off value of between 340 and 800 Daltons. Suitably, the iron oligosaccharide compound has an apparent molecular weight (MP) of 120 to 180 kD. Preferably, the an apparent molecular weight (MP) is between 130 and 160 kD. The amount of iron in the iron oligosaccharide compound may vary in accordance to the intended use of the final composition. Generally, the amount of iron in the iron oligosaccharide compound is 50 % by weight or less. Suitably, the amount of iron oligosaccharide is above 10 % by weight. The compounds as mentioned above may be synthesized as disclosed in WO2010108493. Further embodiments relate to iron(III)hydroxide / dextran complexes which give stable sterile solutions for injection purposes having a high iron content of more than 20% W / V, which can be produced as disclosed in US4599405A. The iron supplementation according to further embodiments relates to therapeutically useful parenteral preparations of iron comprising readily absorbed complexes of trivalent iron with a mixture of sorbitol, gluconic acid and certain oligosaccharides as the complex forming agents and which complexes of trivalent iron are nonionic, have a uniform composition and a low toxicity while at the same time the rate of absorption and effectiveness of the iron administered to the human of animal body is improved. The disclosure thereof may be found in WO2023285979. The complex forming agent consist of sorbitol, gluconic acid and, as third component, a dextrin of dextran having an average intrinsic viscosity of about 0.01 to about 0.025 at 25° C. and an average molecular weight of from about 500 to about 1,200; or a hydrogenated dextrin or dextran having said average intrinsic viscosity and said average molecular weight and being substantially nonreducing to the Somogyi reagent; or mixtures thereof, in a molar ratio of about 0.4 mol of sorbitol : about 0.3 mol of gluconic acid : 0.3 mol of the above polyglucose calculated as anhydroglucose CeH Og. About 1 mol of said complex forming agent is present in the iron preparation per each mol of trivalent iron or ferric hydroxide. The iron supplementation according to further embodiments relates to ferric saccharide complexes having an absolute weight average molecular weight of about 25,000 or more and especially 100,000 Daltons or more, and preferably exclude polysaccharides. The highest useful molecular weight of an iron-saccharidic complex is limited by that which is no longer dispersed in colloidal form in a carrier liquid such as water. Furthermore, the high molecular weight products can be produced without the need to include sucrose or another sugar if, for example, the iron-composition is based on a sugar acid derivative such as sodium gluconate. Consequently, the product produced under such circumstances may be preferred for treating patients with a sensitivity to the presence of additional sugar in the parenteral composition, e.g., diabetic patients. Such ferric saccharide complexes may be used to prepare parenteral iron pharmaceutical compositions useful for treating human subjects. Such iron-saccharidic complex is, or contains, an active hematinic species (AHS). These complexes also contain iron in the form of Fe(III) and saccharide, usually in the form of anions. Such iron-saccharidiccomplexes exclude the iron-dextrans of the art. Examples of iron-saccharidic complexes include suchspecies as sodium ferric gluconate complex in sucrose (SFGCS) and ferric hydroxidesucrose complex (FHSC), but are not limited to these. Fe(III) and (OH)- as "ions" includes these entities individually as well as their presence in larger ionic species, e.g., Fe(OH)2+or FeOH2+or Fe(OH)4- etc. The iron present in the iron-saccharidic complexes is in the form of Fe(III) or ferric, and not ferrous (Fe(II)). The “saccharide” includes a sugar or sugar derivative. Typical monosaccharides include dihydroxyacetone, glyceraldehyde, erythrose, ribose, ribulose, sorbose, xylose, and arabinose, as well as the more common sugars such as fructose (also known as levulose) and glucose (also known as dextrose), and also galactose, and mannose. Typical disaccharides include sucrose, maltose, cellobiose, gentiobiose, isomaltose, melibiose, primeverose, rutinose, trehalose and lactose. Sugar derivatives are saccharides including acids such as gluconic acid; glucaric acid; the hydroxy acid of fructose; alpha- methylcaproic acid; aldonic acids; aldaric acids; mannaric acid; uronic acids; galacturonic acid; glucuronic acids; mannuronic acids; xylaric acid; tartaric acid; mucic acid; glyceric acid; lactic acid; tartaric acid; dicarboxylic acids of arabinose, glucose and mannose; maltobionic acid; and lactobionic acid. Further sugar derivatives are saccharides including the alkali metals and alkaline-earth metals of sugar acids, including metals selected from the group consisting of lithium, sodium, potassium, calcium, barium, strontium and magnesium. A particularly useful salt is sodium gluconate. Further sugar derivatives are saccharides including fucosamine (also known as 2-amino-2,6-dideoxygalactose), galactosamine (or 2-amino-2-deoxyglactose), acosamine (or 3-amino-2,3,6-trideoxy-L-xylo-hexose), bacillosamine (or 2,4-diamino-2,4,6-trideoxy-D-glucose), glucosamine (or CH2OH(CH2O)3CHNH2CHO), etc. Specific compounds according to the present invention useful as sources of Fe(III) include ferric chloride, ferric nitrate, ferric hydroxide, ferric sulfate, ferric acetate, ferric carbonate, and ferric citrate; ferric hydroxide is especially useful. The formula of ferric hydroxide can be represented as Fe(OH)3or Fe2O3x3H2O. Ferric salts, such as those just named as well as any others that can be useful in this process, are typically used as a means of generating ferric hydroxide in situ. Preferably, the ferric salt is at least partially soluble in water and capable of being converted to the hydroxide under the conditions of the process. Especially useful is ferric hydroxide in a colloidally dispersed form. The compounds mentioned above and their synthesis is disclosed in WO2005000210. The iron supplementation according to further embodiments relates to a process for the production of organic ferric compounds, characterized in that reactants comprising an iron (III) compound, glycerin and a hydroxycarboxylic acid, are mixed in an aqueous medium, and the pH of the reaction mixture is adjusted to a value of at least 5. Optionally, inulin may be added to delay resorption. Specifically, an iron (III) compound is dissolved or suspended in water at a temperature between 20° and 100° C., preferably at room temperature (20-30° C), and amounts of glycerin and a hydroxycarboxylic acid are added to the resulting solution or suspension so that the mol ratio of the components, i.e. the iron (III) compound to glycerin and to hydroxycarboxylic acid amounts to 1:1 / 2- 10:1 / 3-3, preferably, 1:1 / 2-3:1 / 3-2. The mixture is subsequently heated to a temperature of 20-100°C, preferably 50-80° C, and is brought to a pH value of at least 5, preferably, 5-8, by the addition of a base. Isolation and purification of the resulting organic iron (III) -complexes may be effected by precipitation with a partially or wholly water-miscible precipitant, decantation of the supernatant liquid, solution of the syrupy or amorphous precipitate in water and repetition of this operation until the desired degree of purity is obtained. It is also possible to use other methods of purification. All inorganic iron (III) compounds which are soluble or suspendible in water, e.g. ferric chloride, nitrate or sulphate, as well as freshly precipitated ferric hydroxide are suitable. Aside from these inorganic salts it is also possible to use organic iron (III) compounds which are soluble or suspendible in water, e.g. salts of organic hydroxycarboxylic acids; the addition of the latter has the advantage that the iron (III) component and the hydroxycarboxylic acid component are added simultaneously. A further addition of the hydroxycarboxylic acid component may be effected up to the ratio indicated above. Examples of hydroxycarboxylic acids, which may be used either in their free form or in the form of their iron (III) compounds, are; tartaric acid, citric acid, malic acid and gluconic acid. In cases where a too rapid resorption is not desired, the organic complex ferric compounds may be modified with inulin in order to delay resorption. Reactants comprising an iron (III) compound, glycerin and a hydroxycarboxylic acid, are mixed in an aqueous medium, the pH of the reaction mixture is adjusted to a value of about 5 to 6, natural or depolymerized inulin is added to the reaction mixture, and the pH of the reaction mixture is then adjusted to a value of about 7 to 8. Apart from the adjustment of the pH values as indicated, the process is identical to that already described. The natural or depolymerized inulin which is added may be in the form of an aqueous solution, at a temperature of 70 to 100°C. The depolymerized inulin may be obtained by acid depolymerization of natural inulin, e.g. using the process described by Holzer et al. in Monatshefte für Chemie 88, 11-24 (1957). Further details thereof are disclosed in US3591616A. The iron supplementation according to the present invention relates to iron oxyhydroxide nanoparticles, which are surface-modified nanoparticles coated with organic molecules such as biocompatible organic molecules, surfactants, and biomacromolecules. The biocompatible coating surrounding the iron oxyhydroxide nanoparticle plays crucial roles in stabilizing the iron core, slowing down the release of iron, protecting the particles from further aggregation, as well as sustaining the particles in a colloidal suspension that can be intravenously injected. The coating may partially or completely cover the surface of the iron oxyhydroxide core to which it is bound. When the coating completely covers the iron oxyhydroxide core, a homogeneous monolayer of the biocompatible molecule is surrounding the spherical or quasi-spherical iron oxide core. Alternatively, more than one layer can cover the iron oxyhydroxide particle core by hydrophobic and / or hydrophilic interactions between the organic molecules of the coating. The term "iron oxyhydroxide" is used to denote a chemical compound composed of iron, oxygen and hydrogen having general formula FeO(OH). The iron oxyhydroxide is either antiferromagnetic when the saturation magnetisation (Ms) is below 10 A m2 / kg at room temperature or weakly ferromagnetic and the iron may be as one or both of ferric iron (Fe3+) and ferrous iron (Fe2+). Non-limiting examples of iron oxyhydroxides include ferric minerals like Fe3+OOH (goethite or a-polymorph), hydrated forms of iron oxyhydroxide with different degree of hydratation, such as ferrihydrite or (Fe3+)2O3 x 0.5H2O, Fe5O7.5 x 4H2O or FeO(OH) x 1.8H2O, sulphate-containing iron oxyhydroxide, such as schwertmannite or Fe8O8(OH)5.5(SO4)1.25 or Fe8O8(OH)6(SO4) x nH2O or (Fe3+)16O16(OH)9.6(SO4)3.2 x 10H2O, anhydrous iron oxyhydroxyde, chloride-containing iron oxyhydroxyde, such as akagaenite or Fe6O5(OH)7CI or FeO0.833(OH)1.167 Cl0.167 , and mixtures thereof. A preferred iron oxyhydroxide is goethite, ferrihydrite or akagaenite. In particular embodiments, the size of the coated iron oxyhydroxide nanoparticle is comprised between 1 and 50 nm. In a preferred embodiment, the size of the coated iron oxyhydroxide nanoparticle is comprised between 2 and 20 nm. Preferably, the size of the coated iron oxyhydroxide nanoparticle is about 3 nm. The particle size can be determined by different techniques that are known in the art such as transmission electron microscopy (TEM) or, if a crystalline phase is present, X-ray diffraction (XRD). The values of particle size obtained by the techniques known in the art are in agreement within the experimental error. In another particular embodiments, the hydrodynamic size of the coated iron oxyhydroxide nanoparticle is comprised between 25 and 100 nm, preferably between 35 and 55 nm. More preferably, the size of the coated iron oxyhydroxide nanoparticle is about 45 nm. In this context, hydrodynamic size and hydrodynamic diameter will be used interchangeably. In contrast to the particle size, the hydrodynamic size or diameter relates to the behaviour of the nanoparticle in a fluid and it represents the diameter of a hard sphere that diffuses at the same speed as the nanoparticle being measured. In particular embodiments, the coating of the iron oxyhydroxide nanoparticle is a neutrally charged organic molecule selected from the group consisting of biocompatible organic molecules, surfactants and biomacromolecules. A "biocompatible organic molecule" is defined as an organic compound with low molecular weight, usually up to 1000 Dalton and size on the order of 1 nm that can display a biological function by binding to a biological macromolecule to alter its native activity or function. Biocompatible organic molecules may include without being limited thereto, amino acids, mono-, di- or oligo-saccharides, citric acids, succinic acids, carboxylic acids, amines, silanes, vitamins, and cyclodextrins. A "surfactant" is defined as an organic compound that is amphiphilic, namely it contains both hydrophobic and hydrophilic groups. Example of surfactants include long fatty carbon chains with a hydrophilic head such as fatty acids, polyols, petroleum sulphonate, alkylbenzenesulphonates, naphthalene sulphonates, olefin sulphonates, alkyl sulphates, carboxylates, sulphonates, sulphated natural oils, sulphated esters, sulphated alkanolamides, ethoxylated and sulphated alkylphenols (linear or branched), ethoxylated aliphatic alcohols, polyoxyethylene surfactants, carboxylic esters, polyethylene glycol esters, anhydrosorbitol ester, glycol esters of fatty acids (oleic acid and lauric acid), carboxylic amides, monoalkanolamine condensates, polyoxyethylene fatty acid amides, quaternary ammonium salts, alkyl phosphonates such as dodecyl phosphonate, hexadecyl phosphonate, dihexadecyl phosphonate. A "biomacromolecule" is defined as an organic compound with high molecular weight (>1000 Dalton) and a diameter ranging from about 100 to 10,000 angstroms that plays a functional role (structural, metabolic, signalling, etc.) within living cells and organisms. Examples of biomacromolecules may include natural polymers such as dextran, starch, PEGylated starch, gelatin, chitosan, proteins, polypeptides, sugars and antibodies. In other embodiments, the above referred neutrally charged organic molecule coating the iron oxyhydroxide nanoparticle contains hydroxyl groups (-OH) that can bind to the surface of the particle core. Examples include carboxylic acids such as citric acids, cyclodextrins, monosaccharides, di- saccharides, oligo- and poly-saccharides, glycoconjugates, glycopeptides, polyethyleneglycol, dextran, carboxydextran, alginate (e g. sodium alginate, calcium alginate, alginate sulfate). The presence of hydroxyl groups, particularly those in sugars, has a beneficial effect to the stability of iron oxyhydroxide nanoparticles additionally allowing for a narrow size distribution or polydispersity as the hydroxyl- containing ligands strongly bind to the nanoparticle surface avoiding aggregation of small particles and selectively blocking metal sites that might otherwise engage in side reactions. In one embodiment, the neutrally charged organic molecule used for coating the iron oxyhydroxide nanoparticle has a molecular weight between 100 and 300000 Dalton, preferably between 150 and 275000 Dalton. In a preferred embodiment, the iron oxyhydroxide nanoparticle is coated with a sugar that has a molecular weight between 180 and 300000 Dalton. In preferred embodiments, the sugar is sorbitol, sucrose or dextran. In some embodiments, the iron oxyhydroxide nanoparticle comprises a particle core covered with sorbitol molecules, the coated nanoparticle having a size between 1-5 nm, preferably about 3 nm. In other preferred embodiments, the iron oxyhydroxide nanoparticles coated with sorbitol are commercially available under the brand Yectofer®. In further embodiments, the iron oxyhydroxide nanoparticle comprises a particle core covered with sucrose molecules, the coated nanoparticle having a size between 1-5 nm and a hydrodynamic size between 40 and 50 nm. In preferred embodiments, the iron oxyhydroxide nanoparticles coated with sucrose are commercially available under the trademark Venofer®. Venofer® consists of an iron sucrose colloidal solution. The nanoparticles in the colloidal solution comprise a core of iron oxyhydroxide, more particularly a ferrihydrite, coated with sucrose. In other embodiments, the iron oxyhydroxide nanoparticle comprises a particle core covered with dextran, the coated nanoparticle having a size between 1 and 30 nm, preferably between 4 and 20 nm. In a preferred embodiment, the iron oxyhydroxide nanoparticles coated with dextran are commercially available under the brands Imferon® and Dexferrum®. Further details thereof are disclosed in EP4173627A1. The iron supplementation according to further embodiments relates to ferric carboxymaltose (FCM), of which Ferinject® is a commercially available example. Ferric carboxymaltose has been designed to provide high iron utilisation and to have a better benefit to risk profile than iron dextran and iron sucrose therapy. In the case of iron dextran, a key risk is the reaction with anti-dextran antibodies leading to the well known dextran induced anaphylactic reactions. In the case of iron sucrose, the negative characteristics include high pH, high osmolarity, low dosage limits and the long duration of administration. Ferric carboxymaltose allows for controlled delivery of iron within the cells of the reticuloendothelial system and subsequent delivery to the iron-binding proteins ferritin and transferrin, with minimal risk of release of large amounts of ionic iron in the serum. Further details thereof of this embodiment, in particular regarding the synthesis of (FMC), are disclosed in WO2016181195. Further processes for the preparation of Iron (III) carboxymaltose complexes are described in WO2011055374. The iron supplementation according to the present invention relates to an iron hydroxypyrone compound, more specifically to iron (III) maltol (i.e. ferric trimaltol, ferric maltol, ST10, CAS Registry- No. 33725-54-1, sold e.g. under the name AccruferTM(US)), which is a chemically stable complex formed between ferric iron (Fe3+) and maltol (3-hydroxy-2-methyl-4-pyrone). Formulations and preparations of iron (III) maltol are well known in the art (e.g. WO2015101971). Moreover, ferric trimaltol may be formulated as amorphous solid dispersion, which is also known in the art. Processes to prepare ferric maltol and polymorphs thereof are known in the art. Ferric trimaltol may be administered orally. Iron (III) maltol may be applied in amorphous form, for instance in an amorphous solid dispersion as wee as in crystalline forms. The term “amorphous solid dispersion” is a physically uniform mixture of two or more ingredients containing at least one ingredient in amorphous form and at least one further polymer; in particular, the ingredient in amorphous form is kinetically trapped (otherwise called “dispersed”) in the polymer in a non-crystalline high-energy state (Chavan R. B. et al., Asian J. Pharm, Sei. 2019, 14, 248-264). Such amorphous solid dispersions are described in WO2023285979. Polymorphs, i.e. crystalline forms of iron (III) maltol are described in WO2023047195. Iron (III) maltol is an iron hydroxypyrone compound. Processes to produce iron hydroxypyrones, in particular iron trihydroxypyrones such as ferric trimaltol or ferric triethylmaltol as well as compositions thereof are disclosed in WO2012101442. The iron supplementation according to further embodiments relates to ferric citrate with a molar ratio of ferric ion and citric acid of 1:0.80 to 1:0.92, having a specific surface area of 20 to 45 m2 / g, which can be measured, for example, by a measurement method of BET surface area by a nitrogen gas adsorption method (relative pressure: 0.05 to 0.3). The ferric citrate is used in embodiments in an amount of 500 mg / to 1000 mg / day, and can be in the form of a tablet. Ferric citrate can be produced by a method known per se, for example, the method described in Examples of WO 2012 / 091139, or a method analogous thereto. Highly pure ferric citrate is described for instance in EP3685831. In this embodiment, the ferric citrate is substantially free of beta-iron hydroxide oxide, the content of beta-iron hydroxide oxide is in the range of preferably less than 6% by weight, especially preferably 0 to 1% by weight. In embodiments of the present invention, the ferric citrate is ferric citrate hydrate represented by a complex represented by the molecular formula Fe*x(C6H8O7)*y(H2O). In the above-mentioned molecular formula, x is preferably 0.75 to 1.10, more preferably 0.78 to 0.95, particularly preferably 0.80 to 0.92, especially preferably 0.81 to 0.91. Further details thereof are disclosed in EP3685831A1. The iron supplementation according to further embodiments relates to an iron preparation of iron(III) citrate comprising an iron complex that is prepared by oxidation of iron(II) citrate dibasic in the presence of dihydrogen pyrophosphate in water. The complex comprises ferric iron cations surrounded by and joined by electrostatic bonds to both citrate and pyrophosphate in a manner that prevents polymerization. The complex comprises stable, unpolymerized iron(III) citrate comprises, by weight, about 9% to about 14% iron, from about 30% to about 60% citrate, from about 5% to about 20% pyrophosphate, and from about 1% to about 15% sodium. The method for the preparation of said iron preparation comprises combining ferrous citrate dibasic and disodium dihydrogen pyrophosphate in water, exposing the resulting mixture to oxygen in a volume sufficient to oxidize the ferrous iron to ferric iron and at a rate sufficiently slow to allow complex formation between iron(III), citrate, and pyrophosphate as oxidation occurs, thus preventing polymerization of ferric citrate, and isolating a stable, unpolymerized iron(III) citrate complex therefrom by removing water. The reaction mixture may be exposed to oxygen by known means including, by way of example, bubbling, aerating, or sparging. Further details thereof are disclosed in US2011021629. The iron supplementation according to further embodiments of the present invention relates to ferric citrate-containing pharmaceutical compositions (e.g., solid oral dosage forms) comprising intragranular components (e.g., ferric citrate, binders, disintegrants, fillers or lubricants) and extragranular components (e.g., glidants or lubricants). Some embodiments relate to a pharmaceutical composition formulated as a solid oral dosage form, comprising: an intragranular component comprising ferric citrate present in an amount that is about 60-80 weight%; one or more binders present in a total amount that is about 1-10 weight%; one or more disintegrants present in a total amount that is about 1-5 weight%; one or more fillers present in a total amount that is about 10-30 weight%; and one or more lubricants present in a total amount that is about 0.1-2 weight%; andan extragranular component comprising one or more glidants present in a total amount that is about 0.1-2 weight%; and one or more lubricants present in a total amount that is about.0.1-2 weight%; wherein the weight% is determined based on the total weight of the tablet. In some embodiments, one or more binders of the intragranular component are selected from the group consisting of hydroxypropyl cellulose (HPC), hydroxypropyimethyl cellulose (HPMC), sodium alginate, alginic acid, guar gum, acacia gum, xanthan gum, carbolpol, cellulose gum (carboxy methyl cellulose), ethyl cellulose, maltodextrin, PVP / VA, povidone, microcrystalline cellulose, starch (partially or fully pregelatinized starch), methyl cellulose, and copovidone. Preferable binders are copovidone and hydroxypropylmethyl cellulose (HPMC). In some embodiments, one or more disintegrants of the intragranular component are selected from the group consisting of croscarmellose sodium, crospovidone, sodium starch glycolate, starch, and microcrystalline cellulose. In some embodiments, one or more fillers of the intragranular component are selected from microcrystalline cellulose, starches, partially pregelatinized starches, sorbitol powder, mannitol powder, lactose, hydroxypropyl methyl cellulose, hydroxypropyl cellulose, maltodextrins, dried glucose syrup, and dextrose mono & anhydrous. In embodiments, one or more lubricants of the intragranular and / or extragranular components are selected from the group consisting of magnesium stearate, calcium stearate, sodium stearyl fumarate, polyethylene glycol, sodium lauryl sulfate, talc, mineral oil, leucine, and poloxamer. Preferred is magnesium stearate and calcium stearate. In some embodiments, one or more glidants of the extragranular component are selected from the group consisting of hydrophilic fumed silica, colloidal silicon dioxide, starch, talc, and magnesium stearate. A preferred glidant is hydrophilic fumed silica and colloidal silicon dioxide. Ferric citrate is commercially available or may be prepared according to WO2004 / 074444; WO2007 / 022435; WO2011 / 011541; and / or US20120121703, each of which is incorporated in its entirety. In particular, the ferric citrate is known chemically as iron (+3),x(1,2,3-propanetricarboxylic acid, 2-hydroxy-),y(H2O) with x=0.70 - 0.87, and y = 1.9 - 3.3. Further details on the iron supplementation are disclosed in WO2022251563. Moreover, formulations of ferric citrated are disclosed in WO2019135155. In certain embodiments, the commercially available ferric citrate is AuryxiaTM(Keryx Biopharmaceuticals), a tablet comprising 210 mg ferric iron tablets for oral administration, equivalent to 1g ferric citrate, are film-coated, peach-colored, and oval-shaped tablets debossed with “KX52.” The inactive ingredients are pregelatinized starch and calcium stearate. In addition, the film-coating contains the following inactive ingredients: hypromellose, titanium dioxide, triacetin, and FD&C Yellow #6 / Sunset Yellow FCF Aluminum Lake, FD&C Red #40 / Allura Red AC Aluminum Lake, and FD&C Blue #2 / Indigo Carmine Aluminum Lak. The iron supplementation according to further embodiments of the present invention relates to a combination therapy comprising an iron compound and a citrate compound, i.e. for co-administration. The terms “co-administering” and “combination therapy” mean that an iron compound and a citrate compound are administered in a manner that permits both to exert physiological effects during an overlapping period of time. In combination therapy comprising an iron compound and a citrate compound, the compounds may be administered in the same pharmaceutical composition (e.g., an admixture) or in separate compositions, via the same or different routes of administration. An iron compound and a citrate compound may be co-administered concurrently, i.e., simultaneously, or at different times, as long as both exert physiological effects during an overlapping period of time. The term “iron compound” refers to a compound containing iron (e.g., ferric or ferrous) that is suitable for administration to a subject, e.g., an orally active therapeutic compound. Examples of iron compounds according to the present invention include, but are not limited to, ferrous sulfate, ferrous fumarate, ferrous gluconate, ferrous succinate, ferric citrate, ferric pyrophosphate, soluble ferric pyrophosphate (SFP), ferric hydroxide, ferric pyrophosphate citrate, iron polymaltose, iron ascorbate, ferric (tri)maltol, heme iron polypeptide, iron EDTA, iron polysaccharide complex, and combinations thereof. The term “soluble ferric pyrophosphate” or “SFP” refers to a soluble composition comprising a mixture of iron complexed to pyrophosphate and citrate with other excipients. For example, SFP can be a mixture of iron pyrophosphate citrate and sodium sulfate. In certain embodiments, SFP refers to FPC and comprises a mixed-ligand iron compound comprising iron chelated with citrate and pyrophosphate, optionally having the following formula Fe4(C6H4O7)3(H2P2O7)2(P2O7) (relative MW 1313 daltons) Examples of SFP are described in U.S. Patent Nos.7,816,404 and 8,178,709. The term “citrate compound” refers to a compound suitable for administering to a subject, e.g., a mammal such as a human, that yields a citrate anion (C6H5O73-) at physiological pH. Examples of citrate compounds include, but are not limited to, citric acid and salts of citrate such as sodium citrate, potassium citrate, calcium citrate, magnesium citrate, ammonium citrate, ferric citrate, and combinations of any of the foregoing. A citrate compound may solid, semi-solid, or a liquid (e.g., an aqueous solution such as Shohl’s solution). Further details thereof are disclosed in WO2017120311. The iron supplementation according to further embodiments relate to an iron(III)dextrin compound. The dextrin compound is prepared by hydrolysis of starch. Dextrins are saccharides composed of glucose units linked together predominantly by alphy-1,4-glucosidic bonds. It is preferred that the starch is hydrolysed until it does not form strong coloured complexes with iodine. Solutions of starch hydrolysed to that extend comprise high amounts of dextrins in the desired molecular size range, and has a viscosity that is sufficient low to allow the handling of the solutions to be easy and accurate. The dextrin is hydrolysed to a suitable low molecular weight, and is fractioned to a narrow range of molecular weights avoiding high molecular weight dextrins and low molecular saccharides. The 10% fraction of the dextrins having the highest molecular weight has an average molecular weight of less than 4500 Daltons, and that 90% of the dextrins are having molecular weights of less than 3000 Daltons. It is further important that the 10% fraction having the lowest molecular weight has a weight average molecular weight of 340 Daltons or more. Before being combined with iron the reducing capability of the dextrins is removed. This may be done by hydrogenation of the terminal aldehyde groups of the dextrins to alcohols. This reduction may be performed using well known procedures, the reducing capability of the dextrins should be less than 3.0% determined by cupric oxidation method. Hydrogenation using sodium borohydride is preferred. In preferred embodiments, the process comprises the following: (i) preparing an aqueous solution comprising the purified hydrogenated dextrin and at least one water- soluble ferric salt; (ii) adjusting the pH of said aqueous solution to a value above 7 by addition of a base, preferably to a value above 8.5; (iii) heating the mixture to a temperature above 85°C until it turns to a black or dark brown coloidal solution which can be filtered through a 0.45 µm filter; and (iv) further purification and stabilization using filtration, heating and membrane processes and addition of one or more stabilizers, and optionally drying the solution to obtain the desired iron-dextrin compound as a stable powder. The stabilization suitably takes place by addition of a salt of an organic hydroxy acid, preferably a citrate. Preferred embodiments relate to an iron dextrin compound being a water soluble powder comprising up to 50% (w / w) iron. Preferably the iron content of the powder is in the range of 10-50% (w / w), more preferred in the range of 20-45% (w / w), and even more preferred in the range of 30-42% (w / w). Further details thereof are disclosed in US2003191090A1. The iron supplementation according to further embodiments of the present invention relates to a process for the preparation of complexes of iron (III) hydroxide and activated glucose syrup comprising, preferably consisting of, the steps: (i) providing an aqueous solution of glucose syrup, having a dextrose equivalent (DE) of at least 21, as determined by gravimetrical analysis at a temperature in the range of from 25°C to 80°C and at a pH in the range of from 6 to 13; (ii) adding one or more oxidizing bleaching agents, and optionally a catalytic amount of an oxidation catalyst, to the solution of (i), while maintaining the pH and temperature within the range as defined in step (i), allowing the solution to cool down to a temperature in the range of from 10°C to 45°C, keeping the solution at this temperature for 5 min to 24 hours, thereby obtaining the activated glucose syrup; (iii) converting said activated glucose syrup into a complex with iron (III) hydroxide; and (iv) obtaining a complex of iron (III) hydroxide and activated glucose syrup, wherein the oxidizing bleaching agent(s) is / are used in an total amount of 0.0005-0.01 mol / g (glucose syrup) multiplied with the correction factor: (dextrose equivalent of the glucose syrup) / 21, wherein the complex has an iron content in the range of from 27 to 35 wt.%, based on the weight of the complex; and wherein the obtained complex of iron (III) hydroxide and activated glucose syrup has more than two -COOH groups per glucose molecule which indicates that the glucose syrup is activated and wherein the glucose syrup of step (i) does not have any -COOH group per / at the glucose molecule. Further details thereof are disclosed in EP2997968A1. The iron supplementation according to further embodiments of the present invention relates to iron(III) complex compounds with carbohydrates including those wherein carbohydrates are selected from the group consisting of dextrans and derivatives thereof, dextrins and derivatives thereof and also pullulan, oligomers and / or derivatives thereof. Particular preference is given to iron(III) complex compounds with dextrins or oxidation products thereof. Examples of the preparation of the iron(III) complex compounds are found, for example, in patent specifications DE 14679800, WO04037865 A1, U.S. Pat. No. 3,076,798, WO03 / 087164 and WO02 / 46241, the totality of the disclosures of which, in particular in respect of the preparation processes, is to be incorporated herein. The term “dextrins” is a collective term for various lower and higher polymers of D-glucose units, which form during the incomplete hydrolysis of starch. They can also be prepared by polymerisation of sugars (e.g. WO02083739A2, US20030044513Al, U.S. Pat. No.3,766,165). The dextrins include the maltodextrins, or polymaltoses, which are prepared by enzymatic cleavage of maize or potato starch with alpha-amylase and which are characterised by the degree of hydrolysis, expressed by the DE value (dextrose equivalent). Polymaltose can also be obtained by acid hydrolysis of dextrins. The resulting iron(III) complexes have, for example, an iron content of from 10 to 40% wt. / wt., in particular from 20 to 35% wt. / wt. They are generally readily soluble in water. It is possible to prepare therefrom neutral aqueous solutions having an iron content of, for example, from 1% wt. / vol. to 10% wt. / vol. Such solutions can be thermally sterilised. Regarding the preparation of iron(III)-polymaltose complex compounds, reference may be made to U.S. Pat. No.3,076,798. In preferred embodiments, an iron(III) hydroxide-polymaltose complex compound is used. The iron (Ill)-polymaltose complex compound preferably has a molecular weight in the range from 20,000 to 500,000 daltons, in a preferred embodiment from 30,000 to 80,000 daltons (determined by means of gel permeation chromatography, for example as described by Geisser et al. in Arzneim. Forsch / Drug Res. 42(11), 12, 1439-1452 (1992), paragraph 2.2.5).A particularly preferred iron(III) hydroxide-polymaltose complex compound according tot he present invention is Maltofer® from Vifor AG, Switzerland, which is available commercially. In a further preferred embodiment, an iron(III) complex compound with an oxidation product of one or more maltodextrins is used. This is obtainable, for example, from an aqueous iron(III) salt solution and an aqueous solution of the product of the oxidation of one or more maltodextrins with an aqueous hypochlorite solution at a pH value in the alkaline range, wherein when a maltodextrin whose dextrose equivalent is from 5 to 37 is used and when a mixture of a plurality of maltodextrins is used, the dextrose equivalent of the mixture is from 5 to 37 and the dextrose equivalent of the individual maltodextrins contained in the mixture is from 2 to 40. The weight-average molecular weight Mw of the complexes so obtained is, for example, from 30 kDa to 500 kDa, preferably from 80 to 350 kDa, particularly preferably up to 300 kDa (determined by means of gel permeation chromatography, for example as described by Geisser et al. in Arzneim. Forsch / Drug Res. 42(11), 12, 1439-1452 (1992), paragraph 2.2.5). Reference may be made in this connection to WO 2004037865 A1, for example, the totality of the disclosure of which is to be incorporated in the present application. Regarding the preparation of iron complex compounds with hydrogenated dextrins, reference may be made to WO03 / 087164. Regarding the preparation of iron(III)-pullulan complex compounds, reference may be made to WO 02 / 46241. Further details thereof are disclosed in US8722101B2. Further water-soluble iron carbohydrate derivative complexes, the preparation thereof and medicaments comprising them are disclosed in US8263577B2. The iron supplementation according to further embodiments of the present invention relates to so-called “mixed-valence” iron carbohydrate complex compounds, in which the iron is present in the oxidation levels 2+ and 3+ side by side. The iron-carbohydrate complex compounds are characterize by their content of iron (II), the remaining iron is present practically exclusively as iron (III). The content of iron (II) in the total iron content is at least 2 wt. %, preferably more than 3 wt. %, based on the total amount of iron in the iron-carbohydrate complex compound. Preferably, the content of iron(II) in the total iron content is 3 to 50 wt. %, more preferably 5 to 40 wt. %, particularly preferably 7 to 35 wt. %, in each case based on the total amount of iron in the iron-carbohydrate complex compound. The iron(II) content can be determined, in particular, by a titrimetric determination (see, for example: Jander Jahr, Maßanalyse [Volumetric Analysis] 15th edition, Verlag Walter de Gruyter, 1989). The content of total iron in the weight of the iron-carbohydrate complex compound is preferably 5 to 40 wt. %, preferably 10 to 30 wt. %. In a preferred embodiment, the content of carbohydrate (or carbohydrates) in the weight of the complex compound is 10 to 80 wt. %, preferably 20 to 70 wt. %, particularly preferably 35 to 65 wt. %. The amounts data based, on the weight of the iron-carbohydrate complex compound always relate to the total weight of the iron-carbohydrate complex compound, including, for example, the water content which may result from the preparation process. In addition to iron(III), iron(II) and one or more carbohydrates, the iron-carbohydrate complex compound contains hydroxyl groups (in general designated OH-), oxo groups (in general designated O2-), optionally further anions and water. In addition to the carbohydrates, the iron-carbohydrate complex compounds can also contain other ligands, for example carboxylic acids, such as gluconic acid, lactic acid etc.. The content of water in the iron-carbohydrate complex compound in this context can expediently be up to 10 wt. %, depending on the drying conditions. Preferably, the water content is 2 to 8 wt. %. An iron-carbohydrate complex compound has, for example, the following composition: 5 to 40 wt. % of iron (preferably 10 to 30 wt. %), of which preferably 3 to 50 wt. %, more preferably 5 to 40 wt. % (preferably , based on the total amount of iron, is present in the form of iron(II), 10 to 80 wt. %, preferably 20 to 70 wt. %, particularly preferably 35 to 65 wt.% of one or more carbohydrates, remainder: oxygen and hydrogen in bonded form (apart from in the carbohydrate) and optionally further elements. Further elements, in addition to iron, carbon, oxygen, hydrogen and nitrogen, can result, for example, from introduction from the iron(III) salt used during the preparation and, where appropriate, acids and / or bases used during the preparation. They are thus, for example, chlorine (for example from Cl-), sulfur, for example from sulfate (SO42-), nitrogen, for example from nitrate (NO3-) and alkali metals and alkaline earth metals from the bases used, such as alkali metal and alkaline earth metal hydroxides, carbonates or bicarbonates etc. The content of further elements is in general less than 15, more preferably less than 10 wt. %, based on the weight of the iron-carbohydrate complex compound. In particular embodiments, the weight average molecular weight of the iron-carbohydrate complex compound is 10 to 80 kDa, preferably 12 to 65 kDa, particularly preferably 15 to 60 kDa. The weight- average molecular weight is determined in this context by gel permeation chromatography against pullulan as the standard (for example as described by Geisser et al. in Arzneim. Forsch. / Drug Res. 42 (II), 12, 1439-1452 (1992), paragraph 2.2.5). The iron-carbohydrate complex compound contains one or more carbohydrates which are present, for example, in the compounds bonded as a complex and / or via hydrogen bridge bonds to iron or iron- containing partial structures. The iron-carbohydrate complex compound contains at least one carbohydrate, for example chosen from natural carbohydrates or synthetic carbohydrate derivatives, such as starch, hydrolyzed starches, such as dextrins (in particular maltodextrin, maltose syrup, glucose syrup), cyclodextrins, dextrans, saccharides. Preferred are dextrins, such as maltodextrin and maltose syrup as well as glucose syrup, and incompletely hydrolyzed starch which has a DE value of between 0 and 100. the carbohydrates employed during the preparation of the iron-carbohydrate complex compound are preferably those which have the ability to reduce iron(III) to iron(II). Further details thereof are disclosed in US8263564B2. The iron supplementation according to further embodiments of the present invention comprises a process to obtain the iron(III) carbohydrate complex compounds. Such iron the iron(III) carbohydrate complexes are obtainable from an aqueous solution of an iron (III) salt and an aqueous solution of the oxidation product of one or more maltodextrins, using an aqueous hypochlorite solution at an alkaline pH-value of e.g. 8 to 12 where, when one maltodextrin is applied, its dextrose equivalent lies between 5 and 20, and when a mixture of several maltodextrins is applied, the dextrose equivalent of the mixture lies between 5 and 20 and the dextrose equivalent of each individual maltodextrin contained in the mixture lies between 2 and 40. In order to prepare the ligands of the complexes, the maltodextrins are oxidized in an aqueous solution with a hypochlorite solution. Suitable examples are solutions of alkali hypochlorites such as a solution of sodium hypochlorite. Commercially available solutions can be used. The concentration of the hypochlorite solution is, e.g. at least 13% by weight, preferably in the order of 13 to 16% by weight, calculated as active chlorine. Preferably the solutions are used in such an amount that about 80 to 100%, preferably about 90% of one aldehyde group per molecule of maltodextrin is oxidized. In this manner, the reactivity caused by the glucose content of the maltodextrin molecules is lowered to 20% or less, preferably to 10% or less. The oxidation is carried out in an alkaline solution, e.g. at a pH of 8 to 12, for example 9 to 11. As an example, oxidation can be carried out at temperatures in the order of 15 to 40° C., preferably of 25 to 35° C. The reaction times are, e.g. in the order of 10 minutes to 4 hours, e.g.1 to 1.5 hours. By this procedure the degree of depolymerisation of the starting maltodextrins is kept at a minimum. Only theoretically it is assumed that the oxidation occurs mainly at the terminal aldehyde group (acetal or semi-acetal group respectively) of the maltodextrin molecules. It is also possible to catalyse the oxidation reaction of the maltodextrins for instance by addition of bromide ions, as well as other oxidation systems such as the known ternary oxidation system hypochlorite / alkali bromide / 2,2,6,6,-tetramethypiperidine-1-oxyl (TEMPO) for the oxidation of the maltodextrins. The process to oxidize maltodextrins catalytically with alkali bromides or with the ternary TEMPO system is described e.g. by Thaburet et al in Carbohydrate Research 330 (2001), 21-29. In order to prepare the complexes the obtained oxidized maltodextrins are reacted with an iron (III) salt in an aqueous solution. Water soluble salts of inorganic or organic acids, or mixtures thereof, such as halides, e.g. chloride and bromide or sulfates can be used as iron (III) salts. It is preferred to use physiologically acceptable salts. It is especially preferred to use an aqueous solution of iron (III) chloride. It has been found that the presence of chloride ions favours the formation of the complexes. The chloride ions can be used in the form of water soluble chlorides such as alkali metal chlorides, e.g. sodium chloride, potassium chloride or ammonium chloride. As stated, the iron (III) is preferably used in the form of the chloride. Further details thereof are disclosed in US2021054105A1. The iron supplementation according to further embodiments of the present invention comprises a process for the preparation of an iron(III) pullulan complex and the preparation obtained in such process. Such preparation comprise aqueous colloidal suspensions or complex iron(III)-hydroxide solutions with pullulan oligosaccharides with average molar mass in range of 2000-20000 g / mol primarily 7000-12000 g / mol. The pullulan complex with iron(III)-hydroxide is an aqueous dark red solution, stable at temperatures in range 4-50°C, during period of 5 years, stable concerning air oxygen and light, with time of complex hydrolytic decomposition in range 5 to 7 seconds. Some pullulan derivatives, such as hydrogenated oligomers and oxidized oligomers, can form stable colloidal complexes with iron(III)- hydroxide. It was found that stated ligands, with low intrinsic viscosity (mostly in range of 0,02-0,08 dl / g), produce important injection solutions. The resulting complex with iron content is in certain embodiments in a range of 50-75 mg Fe3+ / ml in the preparation, is not toxic, but it possesses high degree of iron resorption from the location of i.m. application (13,5 mg Fe3+ / 100ml of serum after 24 hours). The synthesis of the complex with pullulan oligomers requires the iron(III)hydroxide β2-polymorphous modification of iron(III)hydroxide. Further details thereof are disclosed in WO0246241. The iron supplementation according to further embodiments comprises a method for preparing an iron complex with hydroxyethyl starch (HES). A starch manufactured by this method is characterized in that it carries a heptonic acid residue on at least one of its termini. Thus, such starch may carry a number of heptonic acid residues per molecule, depending on the number of terminal glucosyl residues being present in the starch molecule. This heptonic acid residue increases the hydrophilicity of the hydroxyethyl starch and increases the stability of complexes formed by this hydroxyethyl starch with ligands, like for example metal ions such as iron ions. Hydroxyethyl starch (HES) is a starch in which some of the hydroxyl groups of the single glucosyl residues are substituted by a hydroxyethyl residue. Terminal glucosyl residues of the HES may be converted into heptonic acid residues via reaction with a cyanide group of a cyanide compound to form a novel C-C single bond. By reducing the pH value, a saponification of the nitrile group takes place. The result of this reaction is the introduction of a carboxyl group into the existing molecule, i.e. forming a heptonic acid. In further embodiments, the metal ions are present in the complex in an amount of 1 % (w / w) to 20% (w / w), in particular of 2% (w / w) to 15% (w / w), in particular of 3% (w / w) to 10% (w / w), in particular of 4 % (w / w) to 6 % (w / w), in particular around 5 % (w / w), in each case with respect to the total weight of the complex of hydroxyethyl starch and metal ions. In further preferred embodiments, the complex of hydroxyethyl starch and iron ions has a radius of gyration in the range of approximately 30 to 70 nm, in particular of approximately 40 to 60 nm, in particular of approximately 45 to 55 nm, and very particular of around 50 nm. Thus, the complex has a size which is comparable to that of viruses. The size (or radius of gyration) of the complex can for example be determined by the field-flow fractionation (FFF), in particular if carried out as asymmetric flow FFF. This method is per se known to a person skilled in the art and will not be described here in detail. A final solution of the complex of hydroxyethyl starch and iron ions has preferably a dark brown colour and exhibits a viscosity of less or equal 25 mm2 / s, a density of 1.050 to 1.150 g / ml, a pH value of 5.0 to 7.5, a cyanide content of less than 0.5 ppm, a free iron content of less than 0.1 g / 100 ml, a chloride content of less than 0.5 g / 100 ml, a total iron content of 4.750 to 5.250 g / 100 ml, an HES content of 5 to 15 g / 100 ml and / or a dry matter content of 10 to 25 g / 100 ml. Further details of the process to prepare the iron supplementation are disclosed in WO2021204705A1. The iron supplementation according to further embodiments of the present invention relates to carboxylate ligand modified ferric iron oxo-hydroxide having a three dimensional polymeric structure in which the carboxylate ligands are nonstoichiometrically substituted for the oxo or hydroxy groups of the ferric iron oxo-hydroxide so that some of the ligand integrates into the solid phase by formal metal- ligand bonding and / or wherein the three dimensional polymeric structure of the carboxylate ligand modified ferric iron oxo-hydroxide is such that the substitution of the oxo or hydroxy groups by the carboxylate ligands is substantially random. Such carboxylate ligand modified ferric iron oxo- hydroxides may be produced using the methods disclosed in W02008096130 or W02017060441. In such carboxylate-ligand-modified iron oxo-hydroxides, the presence of formal metal ion-ligand bonding is one feature that distinguishes the materials from other products such as "iron polymaltose" (Maltofer) in which particulate crystal line iron hydroxide is surrounded by a sugar shell formed from maltose and thus is simply a mixture of iron oxo-hydroxide and sugar at the nano-level (Heinrich (1975);Geisser and Muller (1987);Nielsen et al (1994; US Patent No: 3,076,798); US2006 / 0205691).In addition, the carboxylate-ligand modified ferric iron hydroxides are solid phase metal poly oxo- hydroxides modified by non-stoichiometric ligand incorporation. This distinguishes them from the numerous metal-ligand classical coordination complexes that are well reported in the art (W003 / 092674,W005 / 037449) which are stoichiometric. In the carboxylate ligand modified iron hydroxides of this embodiment, which are described and can be produced as disclosed in WO2021204705A1, the carboxylate ligands may be one, two, three or four or more carboxylate ligands in the form of the carboxylate ion or the corresponding carboxylic acid. Generally, the ligand is a dicarboxylic acid ligand, and may be represented by the formula HOOC-R1- COOH (or an ionised form thereof), where R1is an optionally substituted C1-10alkyl, C1-10alkenyl or C1-10 alkynyl group. The use of ligands in which R1 is a C1-10 alkyl group, and more preferably is a C1-6 alkyl group, is preferred. Preferred optional substituents of the R1group include one or more hydroxyl groups, for example as present in malic acid. These ligands include carboxylic acids such as adipate / adipic acid, tartrate / tartaric acid, glutarate / glutaric acid, malate / malic acid, succinate / succinic acid, aspartate / aspartic acid, pimelate / pimelic acid, citrate / citric acid, lactate / lactic acid or benzoate / benzoic acid. In the production of some preferred materials, such as IHAT, two different ligands are used, such as adipate / adipic acid and tartrate / tartaric acid. Other examples of preferred combinations of ligands include tartrate / tartaric acid and succinate / succinic acid. Particularly preferred materials are formed using the following molar ratios of ligands and Fe(lll), see table E: Table E: Materials are formed using the following molar ratios of ligands and Fe(lll). It is assumed that in the class of materials referred to herein as "IHAT", it is the tartrate / tartaric acid ligands that are mostly responsible for the disruption of the iron hydroxide structure of the primary particles (Nanomedicine,10(8):1877-1886, 2014). In view of this observation, in further embodiments, the carboxylate ligand modified iron hydroxides may be modified by tartrate / tartaric acid as the sole carboxylate ligand. The ratio of the ferric iron ion(s) to the carboxylate ligands can be varied according to the methods disclosed herein and may vary one or more properties of the materials. Generally, the useful ratios of M:L will be between 10:1, 5:1, 4:1, 3:1, 2:1 and 1:1 and 1:2, 1:3, 1:4, 1:5 or 1:10, and preferably between 4:1 and 1:1. By way of example, in the preferred class of IHAT materials, the concentration of ferric iron ions may be between 20 mM and 80 mM, the concentration of adipate is between 10 mM and 40 mM and the concentration of tartrate is between 10 mM and 40 mM. In the synthesis of IHAT, a concentration of ferric iron of about 40 mM was used with 20 mM adipic acid and 20 mM tartaric acid. Alternatively, and in particular where different ratios of the components are used, the concentration of ferric iron may be between 20 mM and 500 or 1000 mM, the concentration of adipate may be between 10 mM and 150 mM and the concentration of tartrate may be between 10 mM and 250 mM or 500 mM. In some embodiments, the at least one carbohydrate is soluble and includes at least one mono-, di- or polysaccharide, such as agarose, dextran, dextrin, dextran derivatives, cellulose and cellulose derivatives, saccharose (sucrose), maltose or lactose preferably saccharose (sucrose),dextrin or starch. The term "starch" as used herein includes any conventionally used starch products (such as potato starch, corn starch, rice starch, tapioca starch) in native, pregelatinized, degraded, modified, and derivatized forms, preferably suitable for direct compression, and mixtures thereof. Preferred products include native and pregelatinized starch, such as in a mixture having a ratio (native: pregelatinized) in the range of 10:1 to 0.5:1, preferably in the range of 3:1 to 0.5:1 more preferably In the range of 2:1 to 1:1. The use of a mixture of native and pregelatinized starch has turned out be particularly advantageous in the manufacture of a tablet with high iron loading, since it allows the preparation of a stabilized pre-mixture which can be compressed to a suitable tablet either directly or with a very small amount of further excipients. In specific embodiments, the stabilization agent of choice may be present in an amount of 1.0 to 50% (w / w), preferably 5.0 to 30% (w / w). All % weights (w / w) throughout this description are expressed in relation to the total weight of the pharmaceutical composition, if not indicated otherwise. In one embodiment, the iron supplementation according to the present invention may be administered in an acute or chronic therapy. The term therapy further includes initial, short- and long-term therapy. Acute therapy includes iron supplementation according to the present invention in alternating doses and up to a duration of 12 months. In one embodiment, the alternating doses may be selected from the doses specified in the above embodiments. Chronic therapy also includes all forms of iron administration and doses of 1 to 2000 mg per application at different intervals - from daily administration (especially oral / enteral / intravenous administration) to (1-, or 2-, or 3-, or 4-, or 5-, or 6-, or 7-, or 8-, or 9-, or 10-, or 11- or 12-) weekly, quarterly, monthly or yearly administration. The dose and frequency of therapy can also be guided according to diagnosis, symptom severity and iron status (usually determined by quantitative and / or qualitative determination of ferritin, and / or iron, and / or transferrin, and / or transferrin saturation, and / or soluble transferrin receptor - in each case determined in serum and / or plasma, by immunoassay and / or clinical chemistry, and / or immunology, and / or photometry, and / or chromatographic and mass spectrometric methods). In one embodiment of the present invention, the iron supplementation is administered to patients with a Ferritin level in a range of 0 to14 µg / L. In a further embodiment of the present invention, the iron supplementation is administered to patients with a Ferritin level of > 15 µg / L. In one embodiment, the iron supplementation is administered to patients with a Ferritin level in a range of 15 µg / L to 500 µg / L, preferably in a range of 20 µg / L to 400 µg / L, more preferably in a range of 30 µg / L to 300 µg / L, more preferably in a range of 40 µg / L to 200 µg / L, more preferably in a range of 50 µg / L to 150 µg / L and most preferably in a range of 60 µg / L to 100 µg / L. In another embodiment, said patients do not suffer from inflammatory conditions or infections. Patients suffering from depression typically do not suffer from internal diseases that may lead to (subclinical) inflammation. However, in patient groups with pre-existing internal diseases such as patients with heart failure, the serum ferritin may be well above 100 µg / L (false-positively), as well as for patients with inflammatory bowel disease or dialysis patients. In these conditions, ferritin is an acute- phase protein, which is elevated due to inflammation, not reflecting increased iron stores, but an (often chronical) subclinical low-grade inflammation (see in this regard e.g. vanDalen et al. Acute heart failure and iron deficiency: a prospective, multicentre, observational study. ESC Heart Fail. 2022 Feb; 9(1): 398–407.The interpretation of indicators of iron status during an acute phase response. Christine A.Northrop-Clewes. https: / / cdn.who.int / media / docs / default-source / micronutrients / 9789241596107-annex4.pdf?sfvrsn=3485bae5_2#:~:text=Normally%20the%20synthesis%20of%20ferritin,cytokines% 2C%20independently%20of%20intracellular%20iron and Wang et al. Serum Ferritin: Past, Present and Future. Biochim Biophys Acta.2010 Aug; 1800(8): 760–769.) In the following items, specific embodiments of the invention are detailed: 1. Iron supplementation for treatment and / or prophylaxis of affective disorder and / or post-traumaticstress disorder (PTSD) and / or serotonin-dependent diseases in a human patient in need thereof. 2. Iron supplementation for treatment and / or prophylaxis of depression and / or affective disorderand / or post-traumatic stress disorder (PTSD) and / or serotonin-dependent disease in a human patient in need thereof according to item 1 wherein said disorder or disease is depression, in particular a major depressive disorder (MDD) or a mild depression, or depression secondary to a) neurological causes such as a cerebrovascular accident, multiple sclerosis, subdural hematoma, epilepsy, Parkinson disease or Alzheimer disease, b) endocrinopathies such as diabetes, thyroid disorders or adrenal disorders, c) metabolic disturbances such as hypercalcemia or hyponatremia, d) medication / substance abuse, e.g. of steroids, antihypertensives, anticonvulsants, antibiotics, sedatives, hypnotics, alcohol or stimulants and / or withdrawal thereof; e) nutritional deficiencies such as vitamin D, B12, B6, iron or folate deficiency, f) infectious diseases such as HIV or syphilis, g) malignancies, h) cancer, or i) cardiovascular diseases like e.g. heart failure, j) inflammatory bowel disease. 3. Iron supplementation for treatment and / or prophylaxis of depression and / or affective disorderand / or post-traumatic stress disorder (PTSD) and / or serotonin-dependent disease in a human patient in need thereof according to item 1, wherein said disorder or disease is an affective disorder. 4. Iron supplementation for treatment and / or prophylaxis of depression and / or affective disorderand / or post-traumatic stress disorder (PTSD) and / or serotonin-dependent disease in a human patient in need thereof according to item 1, wherein said disorder or disease is a post-traumatic stress disorder (PTSD).Iron supplementation for treatment and / or prophylaxis of depression and / or affective disorderand / or post-traumatic stress disorder (PTSD) and / or serotonin-dependent disease in a human patient in need thereof according to item 1, wherein said disorder or disease is a serotonin- dependent disease.Iron supplementation for treatment and / or prophylaxis of an affective disorder and / or post-traumatic stress disorder (PTSD) and / or serotonin-dependent diseases in a human patient in need thereof according to item 5, wherein said patient suffers from internal diseases and medical conditions caused, mediated or aggravated by (elevated or not elevated) circulating serotonin levels, like pulmonary arterial hypertension, tumor growth and metastasis in Colorectal Cancer, asthma, inflammatory bowel disease, and fibrotic diseases in the lungs, liver, skin, and kidneys.Iron supplementation for treatment and / or prophylaxis of an affective disorder and / or post-traumatic stress disorder (PTSD) and / or serotonin-dependent diseases in a human patient in need thereof according to any of items 1 to 6, wherein said patient does not suffer from an iron deficiency and wherein iron deficiency is defined as ferritin levels of < 15 µg / L.Iron supplementation for treatment and / or prophylaxis of an affective disorder and / or post-traumatic stress disorder (PTSD) and / or serotonin-dependent diseases in a human patient in need thereof according to any of items 1 to 7, wherein said patient is receiving therapy with one or more antidepressants or is scheduled to receive therapy with one or more antidepressants, and wherein preferably the patient is suffering from a Major Depressive Disorder.Iron supplementation for treatment and / or prophylaxis of an affective disorder and / or post-traumatic stress disorder (PTSD) and / or serotonin-dependent diseases in a human patient in need thereof according to item 8, wherein said iron supplementation is administered as adjunctive therapy to said therapy with one or more antidepressants.Iron supplementation for treatment and / or prophylaxis of an affective disorder and / or post-traumatic stress disorder (PTSD) and / or serotonin-dependent diseases in a human patient in need thereof according to item 8, wherein said iron supplementation is administered as replacement of said therapy with one or more antidepressants.Iron supplementation for treatment and / or prophylaxis of an affective disorder and / or post-traumatic stress disorder (PTSD) and / or serotonin-dependent diseases in a human patient in need thereof according to any of items 1 to 10, wherein said patient is not receiving treatment antidepressants, preferably has never received treatment with antidepressants, and wherein preferably the patient is suffering from a Major Depressive Disorder.Iron supplementation for treatment and / or prophylaxis of an affective disorder and / or post-traumatic stress disorder (PTSD) and / or serotonin-dependent diseases in a human patient in need thereof according to any of items 1 to 11, wherein the iron supplementation is selected from the group comprising an intravenous iron supplementation, parenteral iron supplementation, intraaerterially iron supplementation, oral iron supplementation or intramuscular iron supplementation, preferably an intravenous iron supplementation or an oral iron supplementation, more preferably an intravenous iron supplementation.Iron supplementation for treatment and / or prophylaxis of depression and / or affective disorderand / or post-traumatic stress disorder (PTSD) and / or serotonin-dependent disease in a human patient in need thereof according to any of items 1 to 12, wherein iron supplementation comprises the administration of an Iron(III) or Iron(II) compound, in particular selected from the group comprising ferrous bisglycinate chelate, Iron(II) glycine sulphate complex (Ferro sanol duodenal®), Iron(III) derisomaltose (MonoFer®, Iron isomaltoside, ferric derisomaltose, Monoferric), Iron(III) hydroxide-dextran complex (Cosmofer®), Iron(III) sodium D-gluconate complex (Ferlixit® ; Ferrlecit®), Iron-II- gluconate / iron(III)-sodium-gluconate complex (Ferrlecit®), Iron(III) hydroxide sucrose complex (Venofer®, PA21, Velforo), Iron(III) hydroxide sucrose complex (Fermed®), Iron carboxymaltose (Ferinject®), Ferric maltol (ST10; ST10-021) and / or ferric citrate (KRX-0502; auryxia), more particularly, said iron supplematation is Iron(III) derisomaltose (MonoFer®, Iron isomaltoside, ferric derisomaltose, Monoferric) and Iron(III) hydroxide-dextran complex (Cosmofer®).Iron supplementation for treatment and / or prophylaxis of depression and / or an affective disorderand / or post-traumatic stress disorder (PTSD) and / or serotonin-dependent disease in a human patient in need thereof according to any of items 1 to 13, wherein said iron supplementation is administered in form of a pharmaceutical formulation.Iron supplementation for treatment and / or prophylaxis of depression and / or an affective disorderand / or post-traumatic stress disorder (PTSD) and / or serotonin-dependent disease in a human patient in need thereof according to any of items 1 to 14, wherein said iron supplementation is in form of a solution, preferably a ready-to-use solution.Iron supplementation for treatment and / or prophylaxis of depression and / or an affective disorderand / or post-traumatic stress disorder (PTSD) and / or serotonin-dependent disease in a human patient in need thereof according to any of items 1 to 14, wherein said iron supplementation is in a freeze-dried state.Iron supplementation for treatment and / or prophylaxis of depression and / or an affective disorderand / or post-traumatic stress disorder (PTSD) and / or serotonin-dependent disease in a human patient in need thereof according to any of items 1 to 16, wherein the iron supplementation is selected from the group comprising an intravenous iron supplementation, parenteral iron supplementation, intraaerterial iron supplementation, oral iron supplementation or intramuscular iron supplementation, wherein said iron supplementation comprises iron in a concentration of 0,0001 g / L to 20 g / L, preferably 0,001 g / L to 2 g / L, preferably 0,02 g / L to 1,5 g / L, more preferably 0,05 g / L to 1,2 g / L, more preferably 0,1 g / L to 1 g / L and most preferably 0,5 g / L.Iron supplementation for treatment and / or prophylaxis of depression and / or an affective disorderand / or post-traumatic stress disorder (PTSD) and / or serotonin-dependent diseases in a human patient in need thereof according to any of items 1 to 17, wherein the iron supplementation is selected from the group comprising an intravenous iron supplementation, intraaerterial iron supplementation, parenteral iron supplementation, oral iron supplementation or intramuscular iron supplementation, wherein said iron supplementation comprises iron in a dose of 1 mg / Kg body weight to 30 mg / Kg body weight, preferably of 2 mg / Kg body weight to 25 mg / Kg body weight, more preferably of 5 mg / Kg body weight to 15 mg / Kg body weight, and most preferably of 10 mg / Kg body weight.Iron supplementation for treatment and / or prophylaxis of depression and / or an affective disorderand / or post-traumatic stress disorder (PTSD) and / or serotonin-dependent disease in a human patient in need thereof according to any of items 1 to 18, wherein the iron supplementation is selected from the group comprising an intravenous iron supplementation, parenteral iron supplementation, intraaerterial iron supplementation, oral iron supplementation or intramuscular iron supplementation, wherein said iron supplementation comprises iron in a fixed dose of 400 to 450 mg, more particularly 423 mg.Iron supplementation for treatment and / or prophylaxis of depression and / or an affective disorderand / or post-traumatic stress disorder (PTSD) and / or serotonin-dependent disease in a human patient in need thereof according to any of items 1 to 19, wherein the iron supplementation is administered to said patient in repeated doses in a 12 week interval.21. Iron supplementation for treatment and / or prophylaxis of depression and / or an affective disorderand / or post-traumatic stress disorder (PTSD) and / or serotonin-dependent disease in a human patient in need thereof according to any of items 1 to 19, wherein the iron supplementation is an intravenous iron supplementation, preferably a ferric carboxymaltose solution, which is administered in a dose equivalent to 500 to 2000mg of iron, more preferably administered over at least 15 min. The following embodiments form also part of the present invention: 1. Iron supplementation for treatment and / or prophylaxis of affective disorder and / or post-traumaticstress disorder (PTSD) and / or serotonin-dependent diseases in a human patient in need thereof. 2. Iron supplementation for treatment and / or prophylaxis of an affective disorder and / or post-traumatic stress disorder (PTSD) and / or serotonin-dependent diseases in a human patient in need thereof according to embodiment 1, wherein said patient does not suffer from an iron deficiency and wherein iron deficiency is defined as plasma and / or serum or whole blood ferritin level of less than 15 µg / L in said patient. 3. Iron supplementation for treatment and / or prophylaxis of an affective disorder and / or post-traumatic stress disorder (PTSD) and / or serotonin-dependent diseases in a human patient in need thereof according to embodiment 1, wherein said patient does not suffer from anemia and wherein anemia is defined as a whole blood hemoglobin level of less than 12 g / dL in females and a whole blood hemoglobin level less than 13 g / dL in males. 4. Iron supplementation for treatment and / or prophylaxis of affective disorder and / or post-traumaticstress disorder (PTSD) and / or serotonin-dependent diseases in a human patient in need thereof according to embodiment 1, wherein said patient is a non-anemic patient, a mild anemic patient or a subclinical anemic patient. 5. Iron supplementation for treatment and / or prophylaxis of affective disorder and / or post-traumaticstress disorder (PTSD) and / or serotonin-dependent diseases in a human patient in need thereof according to embodiment 4, wherein said patient is a non-anemic female and has a whole blood hemoglobin level of greater than or equal to 12 g / dL or said patient is a non-anemic male and has a whole blood hemoglobin level of greater than or equal to 13 g / dL. 6. Iron supplementation for treatment and / or prophylaxis of affective disorder and / or post-traumaticstress disorder (PTSD) and / or serotonin-dependent diseases in a human patient in need thereof according to embodiment 4, wherein said patient is a non-anemic female or mild anemic female and has a whole blood hemoglobin level of greater than 11 g / dL or said patient is a non-anemic male or a mild anemic male and has a whole blood hemoglobin level of greater than 12 g / d L.Iron supplementation for treatment and / or prophylaxis of affective disorder and / or post-traumaticstress disorder (PTSD) and / or serotonin-dependent diseases in a human patient in need thereof according to embodiment 4, wherein said patient is a non-anemic female or a mild anemic female or a subclinical anemic female and has a whole blood hemoglobin level of greater than 10 g / dL or said patient is a non-anemic male or a mild anemic male or a subclinical anemic male and has a whole blood hemoglobin level of greater than 11 g / d L.Iron supplementation for treatment and / or prophylaxis of affective disorder and / or post-traumaticstress disorder (PTSD) and / or serotonin-dependent diseases in a human patient in need thereof according to embodiment 4, wherein said patient is a mild anemic female and has a whole blood hemoglobin level of 11 g / dL to less than 12 g / dL or said patient is a mild anemic male and has a whole blood hemoglobin level of 12 g / dL to less than 13 g / dL.Iron supplementation for treatment and / or prophylaxis of affective disorder and / or post-traumaticstress disorder (PTSD) and / or serotonin-dependent diseases in a human patient in need thereof according to embodiment 4, wherein said patient is a subclinical anemic female and has a whole blood hemoglobin level of 10 g / dL to less than 11 g / dL or said patient is a subclinical anemic male and has a whole blood hemoglobin level of 11 g / d L to less than 12 g / dL.Iron supplementation for treatment and / or prophylaxis of affective disorder and / or post-traumatic stress disorder (PTSD) and / or serotonin-dependent diseases in a human patient in need thereof according to embodiments 4 to 9, wherein said patient does not suffer from an iron deficiency and wherein iron deficiency is defined as whole blood or plasma and / or serum ferritin level of less than 15 µg / L in said patient.Iron supplementation for treatment and / or prophylaxis of an affective disorder and / or post-traumatic stress disorder (PTSD) and / or serotonin-dependent diseases in a human patient in need thereof according to any of embodiments 1 to 10, wherein said patient does not suffer from iron deficiency anemia and wherein iron deficiency anemia is defined as whole blood hemoglobin level of less than 12 g / dL in females and whole blood hemoglobin level less than 13 g / dL in males and concomitant whole blood or plasma and / or serum ferritin level of less than 15 µg / L.Iron supplementation for treatment and / or prophylaxis of affective disorder and / or post-traumaticstress disorder (PTSD) and / or serotonin-dependent diseases in a human patient in need thereof according to embodiments 1 to 11, wherein said patient is female and wherein said female is a non-pregnant female.Iron supplementation for treatment and / or prophylaxis of affective disorder and / or post-traumaticstress disorder (PTSD) and / or serotonin-dependent diseases in a human patient in need thereof according to embodiments 1 to 12, wherein said patient is 18 years or above., preferably 15 years or aboveIron supplementation for treatment and / or prophylaxis of depression and / or affective disorderand / or post-traumatic stress disorder (PTSD) and / or serotonin-dependent disease in a human patient in need thereof according to embodiment 1 to 13, wherein said disorder or disease is depression, in particular a major depressive disorder (MDD) or a mild depression or depression secondary to neurological causes, endocrinopathies, metabolic disturbances, medication / substance abuse, nutritional deficiencies, infectious diseases, malignancies, cancer, inflammatory bowel disease or cardiovascular diseases.Iron supplementation for treatment and / or prophylaxis of depression and / or affective disorderand / or post-traumatic stress disorder (PTSD) and / or serotonin-dependent disease in a human patient in need thereof according to embodiment 1 to 14, wherein said disorder or disease is an affective disorder.Iron supplementation for treatment and / or prophylaxis of depression and / or affective disorderand / or post-traumatic stress disorder (PTSD) and / or serotonin-dependent disease in a human patient in need thereof according to embodiment 1 to 14, wherein said disorder or disease is a post-traumatic stress disorder (PTSD).Iron supplementation for treatment and / or prophylaxis of depression and / or affective disorderand / or post-traumatic stress disorder (PTSD) and / or serotonin-dependent disease in a human patient in need thereof according to embodiment 1 to 14, wherein said disorder or disease is a serotonin-dependent disease.Iron supplementation for treatment and / or prophylaxis of an affective disorder and / or post-traumatic stress disorder (PTSD) and / or serotonin-dependent diseases in a human patient in need thereof according to embodiment 1 to 17, wherein said patient suffers from internal diseases and medical conditions caused, mediated or aggravated by circulating serotonin level, like pulmonary arterial hypertension, tumor growth and metastasis in Colorectal Cancer, asthma, inflammatory bowel disease, and fibrotic diseases in the lungs, liver, skin, and kidneys.Iron supplementation for treatment and / or prophylaxis of depression and / or affective disorderand / or post-traumatic stress disorder (PTSD) and / or serotonin-dependent disease in a human patient in need thereof according to embodiment 1 to 18, wherein said disorder or disease is a Major Depressive Disorder (MDD).Iron supplementation for treatment and / or prophylaxis of an affective disorder and / or post-traumatic stress disorder (PTSD) and / or serotonin-dependent diseases in a human patient in need thereof according to any of embodiments 1 to 19, wherein said patient is receiving therapy with one or more antidepressants or is scheduled to receive therapy with one or more antidepressants, and wherein preferably the patient is suffering from a Major Depressive Disorder.Iron supplementation for treatment and / or prophylaxis of an affective disorder and / or post-traumatic stress disorder (PTSD) and / or serotonin-dependent diseases in a human patient in need thereof according to embodiment 20, wherein said iron supplementation is administered as adjunctive therapy to said therapy with one or more antidepressants.Iron supplementation for treatment and / or prophylaxis of an affective disorder and / or post-traumatic stress disorder (PTSD) and / or serotonin-dependent diseases in a human patient in need thereof according to embodiment 20, wherein said iron supplementation is administered as replacement of said therapy with one or more antidepressants.Iron supplementation for treatment and / or prophylaxis of an affective disorder and / or post-traumatic stress disorder (PTSD) and / or serotonin-dependent diseases in a human patient in need thereof according to any of embodiments 1 to 22, wherein said patient is not receiving treatment antidepressants, preferably has never received treatment with antidepressants, and wherein preferably the patient is suffering from a Major Depressive Disorder.Iron supplementation for treatment and / or prophylaxis of an affective disorder and / or post-traumatic stress disorder (PTSD) and / or serotonin-dependent diseases in a human patient in need thereof according to any of embodiments 1 to 20 and embodiment 23, wherein the iron supplementation is selected from the group comprising an intravenous iron supplementation, parenteral iron supplementation, intraaerterial iron supplementation, oral iron supplementation or intramuscular iron supplementation, preferably an intravenous iron supplementation or an oral iron supplementation, more preferably an intravenous iron supplementation.Iron supplementation for treatment and / or prophylaxis of depression and / or affective disorderand / or post-traumatic stress disorder (PTSD) and / or serotonin-dependent disease in a human patient in need thereof according to any of embodiments 1 to 24, wherein iron supplementation comprises the administration of an Iron(III) or Iron(II) compound, in particular selected from the group comprising ferrous bisglycinate chelate, Iron(II) glycine sulphate complex (Ferro sanol duodenal®), Iron(III) derisomaltose (MonoFer®, Iron isomaltoside, ferric derisomaltose, Monoferric), Iron(III) hydroxide-dextran complex (Cosmofer®), Iron(III) sodium D-gluconate complex (Ferlixit® ; Ferrlecit®), Iron-II-gluconate / iron(III)-sodium-gluconate complex (Ferrlecit®), Iron(III) hydroxide sucrose complex (Venofer®, PA21, Velforo), Iron(III) hydroxide sucrose complex (Fermed®), Iron carboxymaltose (Ferinject®), Ferric maltol (ST10; ST10-021) and / or ferric citrate (KRX-0502; auryxia), more particularly, said iron supplematation is Iron(III) derisomaltose (MonoFer®, Iron isomaltoside, ferric derisomaltose, Monoferric) and Iron(III) hydroxide-dextran complex (Cosmofer®).Iron supplementation for treatment and / or prophylaxis of depression and / or an affective disorderand / or post-traumatic stress disorder (PTSD) and / or serotonin-dependent disease in a human patient in need thereof according to any of embodiments 1 to 25, wherein said iron supplementation is administered in form of a pharmaceutical formulation.Iron Supplementation for treatment and / or prophylaxis of depression and / or an affective disorderand / or post-traumatic stress disorder (PTSD) and / or serotonin-dependent disease in a human patient in need thereof according to any of embodiments 1 to 26, wherein said iron supplementation is in form of a solution, preferably a ready-to-use solution.Iron supplementation for treatment and / or prophylaxis of depression and / or an affective disorderand / or post-traumatic stress disorder (PTSD) and / or serotonin-dependent disease in a human patient in need thereof according to any of embodiments 1 to 27, wherein said iron supplementation is in a freeze-dried state.Iron supplementation for treatment and / or prophylaxis of depression and / or an affective disorderand / or post-traumatic stress disorder (PTSD) and / or serotonin-dependent disease in a human patient in need thereof according to any of embodiments 1 to 28, wherein the iron supplementation is selected from the group comprising an intravenous iron supplementation, parenteral iron supplementation, intraaerterial iron supplementation, oral iron supplementation or intramuscular iron supplementation, wherein said iron supplementation comprises iron in a concentration of 0,0001 g / L to 20 g / L, preferably 0,001 g / L to 2 g / L, preferably 0,02 g / L to 1,5 g / L, more preferably 0,05 g / L to 1,2 g / L, more preferably 0,1 g / L to 1 g / L and most preferably 0,5 g / L. 30. Iron supplementation for treatment and / or prophylaxis of depression and / or an affective disorderand / or post-traumatic stress disorder (PTSD) and / or serotonin-dependent diseases in a human patient in need thereof according to any of embodiments 1 to 29, wherein the iron supplementation is selected from the group comprising an intravenous iron supplementation, intraaerterial iron supplementation, parenteral iron supplementation, oral iron supplementation or intramuscular iron supplementation, wherein said iron supplementation comprises iron in a dose of 1 mg / Kg body weight to 30 mg / Kg body weight, preferably of 2 mg / Kg body weight to 25 mg / Kg body weight, more preferably of 5 mg / Kg body weight to 15 mg / Kg body weight, and most preferably of 10 mg / Kg body weight. 31. Iron supplementation for treatment and / or prophylaxis of depression and / or an affective disorderand / or post-traumatic stress disorder (PTSD) and / or serotonin-dependent disease in a human patient in need thereof according to any of embodiments 1 to 30, wherein the iron supplementation is selected from the group comprising an intravenous iron supplementation, parenteral iron supplementation, intraaerterial iron supplementation, oral iron supplementation or intramuscular iron supplementation, wherein said iron supplementation comprises iron in a fixed dose of 400 to 450 mg, more particularly 423 mg. 32. Iron supplementation for treatment and / or prophylaxis of depression and / or an affective disorderand / or post-traumatic stress disorder (PTSD) and / or serotonin-dependent disease in a human patient in need thereof according to any of embodiments 1 to 31, wherein the iron supplementation is administered to said patient in repeated doses in a 12 week interval. 33. Iron supplementation for treatment and / or prophylaxis of depression and / or an affective disorderand / or post-traumatic stress disorder (PTSD) and / or serotonin-dependent disease in a human patient in need thereof according to any of embodiments 1 to 32, wherein the iron supplementation is an intravenous iron supplementation, preferably a ferric carboxymaltose solution, which is administered in a dose equivalent to 500 to 2000mg of iron, more preferably administered over at least 15 min. Figure description Figure 1: Study schedule in the PSIRON-2 study Figures 2 A and B: Course of HAM-D score in control and intervention groups (visit 1 to visit 2) Figures 3 A and B: Course of HAM-D score within the control group after crossover (visit 2 to visit 3) Figures 4 A and B: Disease severity reclassification upon iron supplementation within the HAM-D and MADRS scores Figure 5: Change of BDI score between baseline and week 12 Figure 6: Change of BDI score between baseline and week 12: biometrical short report Examples Example 1 Administration of iron in patients suffering from depression Study Design The PSIRON-2 study is a non-randomized, observer-blinded, crossover study, recruiting patients at a university hospital in Germany. Patients and study interventionThe study schedule is shown in Figure 1. A total of 34 adults were recruited. All patients had beendiagnosed with depression (first or recurrent episode) at least 3 months ago and were treated according to standard of care, including interpersonal psychotherapy and antidepressant medication. All patients had a baseline ferritin concentration ≤100 µg / L. Exclusion criteria included any iron medication in clinical routine and lacking the capacity to consent. Two clinician-assessed depression assessment scales and two self-reported depression assessment scales were performed at baseline in all 34 patients. Fourteen patients out of 34 were then directly supplemented with intravenous iron (intervention group), while the remaining 20 patients received Saline (control group) as a therapeutic measure for the beneficiary of the placebo effect and for volume repletion after blood draw. After 10 weeks the depression assessment scales were repeated in all 34 patients, and the control group was treated with intravenous iron. Depression scales were re-assessed in the control group at a third visit 10 weeks thereafter. The Hamilton Rating Scale for Depression (HAM-D) was the primary read-out of the cross-over analysis. The overall analysis compared all patients immediately before and 10 weeks after iron supplementation and assessed the effect of iron supplementation in two clinician-administered (HAM-D and Montgomery-Asberg Depression Rating Scale (MADRS)) and two self-reported depression assessment scales (9-question Patient Health Questionnaire (PHQ-9) and Beck Depression Inventory-II (BDI-II)). Blood draw was performed at all visits and before eventual iron supplementation. Patients were instructed to having fasted since the night before, admitted to blood draw around 08 and 12 a.m., and all samples were immediately labelled, processed, and stored at -80°C until further analysis. All laboratory analyses were performed within 3 months after blood draw. Analyses, outcomes, blinding and intravenous treatment All routine laboratory parameters, including the iron parameters, were measured using Siemens Vista Dimension assays. The neurotransmitter concentrations were measured using commercially available ELISA assays. In order to assess the severity of depression, the two clinician-administered scales HAM- D and MADRS, and the two self-reported depression assessment scales PHQ-9 and BDI-II were serially assessed. The outcome was assessed in blinded manner: personnel administering the treatment was different from those assessing the 4 treatment scales. For iron infusion, 500 mg ferric carboxymaltose (10 mL) was not injected directly, but diluted in 90 mL Saline and administered over 15 minutes. Patients in the control group received 100 mL Saline, which was not given as active comparator or placebo, but rather as therapeutic measure for the placebo effect and as fluid balance measure for the blood draw. Statistical analysis Data are presented as absolute and relative frequency for categorical variables and as mean and standard deviation. A p-value <0.05 was the criterion for statistical significance. Logistic regression was used, in order to evaluate the effect of iron supplementation on disease severity. In accordance with the national guidelines, an improvement (i.e. decrease) ≥3 points in the HAM-D questionnaire, a decrease ≥5 points in the PHQ-9 questionnaire, a decrease ≥2 points in the MADRS questionnaire, and a decrease ≥5 points in the BDI-II questionnaire, between intervention and follow-up assessment were determined as clinically relevant improvement. The therapeutic effect is given as odds ratio [OR] with respective confidence interval. Pearson correlation coefficients were calculated. Statistical analyses were conducted using R project for statistical computing, version 4.0.1. Results Fourteen patients out of 34 were directly supplemented with intravenous iron (intervention group), while the remaining 20 patients served as controls (control group) and were only treated at a second visit (see table 1). The treatment was well tolerated in all patients, and no patient reported any side effects or intolerabilities. Moreover, no patient evolved iron overload, as evidenced by ferritin controls during follow-up. The baseline characteristics were well balanced between the two groups, including neurotransmitter levels. A total of 26 patients were female, and the mean age was 43 years. While mean (standard deviation, SD) hemoglobin levels were within normal range, 14.1 (1.0) g / dL in the control group and 13.6 (0.7) g / dL in the intervention group, mean ferritin concentrations were 47.1 (29.5) µg / L in the control group, and 39.1 (33.0) µg / L in the intervention group. Only 7 patients (20.6%) had ferritin levels below 15 µg / L and thereby were classified as iron-deficient according to the updated 2020 WHO guideline on use of ferritin concentrations to assess iron status in individuals and populations. No patient had a hemoglobin level below 12.3 g / dL (data not shown). Baseline score of HAM-D (mean 17.2 (7.8) in the control group, and 15.9 (7.9) in the intervention group) indicated an intermediate disease severity with light to moderate symptoms. Table 1: Characteristics of the study patients at baseline.

[0004] Age, years (SD) 44.0 (14.5) 41.6 (14.6)Weight, kg (SD) 74.1 (14.5) 72.1 (14.2)Current or former smoker, no (%) 14 (70) 7 (50)Size, cm (SD) 171.1 (8.3) 170.1 (7.3)Hb, g / dL (Q1, Q3) 14.2 (13.4; 14.7) 13.6 (13.3; 13.9)hsCRP, mg / dL (SD) <0.5 (0.1) <0.5 (0.0)TSH, mU / L (SD) 1.3 (0.7) 1.3 (0.6)Free T3, pg / dL (SD) 4.2 (0.6) 4.2 (0.5)Free T4, ng / dL(SD) 15.9 (2.0) 15.4 (2.6)Ferritin, µg / L (SD) 47.1 (29.5) 39.1 (33.0)TSAT, % (SD) 21.4 (6.2) 27.4 (8.4)Transferrin, g / L (SD) 2.8 (0.3) 2.7 (0.4)Iron, µmol / L (SD) 14.9 (4.3) 18.2 (4.9)HAM-D Score (SD) 17.2 (7.8) 15.9 (7.9)Escitalopram, no (%) 5 (25) 1 (7.1)Quetiapine, no (%) 3 (15) 0 (0)Opipramol, no (%) 1 (5) 1 (7.1)Venlafaxine, no (%) 2 (10) 1 (7.1)Trimipramine, no (%) 1 (5) 0 (0)Duloxetin, no (%) 1 (5) 2 (14.3)Fluoxetin, no (%) 0 (0) 2 (14.3)Bupropion, no (%) 4 (20) 1 (7.1)Citalopram, no (%) 0 (0) 2 (14.3)Mirtazapine (%) 1 (5) 3 (21.4)Vortioxetine, no (%) 0 (0) 1 (7.1)Sertralin, no (%) 2 (10) 1 (7.1)No antidepressant medication 4 (20) 0 (0)Interpersonal psychotherapy 20 14SD= standard deviation; N= number, HAM-D= Hamilton Rating Scale for Depression; q= quartile; TSAT= transferrin saturation; medication includes multiple ingestion; hsCRP= high-sensitivity C- reactive protein While the HAM-D score in the control group virtually did not change between visit 1 and visit 2 (17.2 (7.8) and 17.1 (8.1)), the score decreased by a mean of 3.9 points (15.9 (7.9) to 12.1 (6.1) upon iron supplementation in the intervention group, resulting in only 4 (20% of the control group) versus 9 (64.3% of the intervention group) with an clinically relevant improvement of depressive symptomsaccording to HAM-D score. The course of the HAM-D score in both patient groups is shown in Figures2a and 2b. The crossover results of the control group regarding the HAM-D questionnaire are displayedin Figures 3a and 3b. Remarkably, the therapeutic effect of intravenous iron is again at the same extentas in the immediate intervention group: upon iron supplementation at visit 2, the mean absolute decrease of the HAM-D score is at an astounding 6.6 (7.2) points, with a beneficial therapeutic effect (improvement by 3 or more points) in 13 (68.4%) out of 20 patients in the control group. The disease severity reclassification upon iron supplementation within the HAM-D and MADRS scoresare shown in Figures 4a and 4b. Ten weeks after iron treatment, 76% (HAM-D) and 73% (MADRS)of the patients were classified as not / mildly depressed, as compared with 48% and 42% of patients immediately before iron supplementation. Data were available for 33 out of 34 patients (1 dropout during follow-up) and indicate a strong and statistically significant therapeutic effect of intravenous iron (see table 2). All four depression scales tested were improved during 10 weeks of follow-up (HAM-D p<0.001, PHQ-9 p=0.043, BDI-II p=0.005, MADRS p<0.001). Table 2: Pooled depression questionnaire analysis of all patients immediately before and 10 weeks after iron supplementation, Mean score Mean score Mean absolute Patients (%) p-value (SD) before (SD) after difference with clinically intervention intervention (SD) relevant (N= 33) (N= 33) improvement HAM-D 17.0 (7.5) 11.5 (6.5) 5.5 (5.7) 66.7 <0.0001PHQ-9 12.2 (6.2) 10.3 (5.9) 1.6 (4.3) 27.3 0.0428BDI-II 21.3 (12.1) 17.3 (12.1) 3.9 (6.5) 48.5 0.0051MADRS 20.3 (10.9) 14.0 (10.7) 6.3 (8.7) 60.6 0.0002SD= standard deviation; N= number; HAM-D= Hamilton Rating Scale for Depression; PHQ-9= 9- question Patient Health Questionnaire; BDI-II= Beck Depression Inventory II; MADRS= Montgomery– Åsberg Depression Rating Scale Biomarker analyses revealed a strong therapeutic effect of iron supplementation on serotonin (80.8 ng / mL before and 64.2 ng / mL after iron; p=0.027) and norepinephrine (404.3 pg / mL before and 323.1 pg / mL after iron; p=0.014), but not dopamine (p=0.392), see table 3. Table 3: Pooled neurotransmitter analysis of all patients immediately before and 10 weeks after iron supplementation (N = 33). Mean Mean concentrationChange p-valueconcentration (SD) after (SD) before intervention intervention (N= 33) (N= 33)Serotonin, ng / mL 80,8 (75,6) 64,2 (62,4) -20.5% 0.0272Norepinephrine,404,3 (167,1) 323,1 (155,0) -20.1% 0.0138pg / mLDopamine, pg / mL 28.9 (14.6) 25,9 (16.9) -10.4% 0.3918Correlation of neurotransmitter concentrations before versus 10 weeks after iron supplementationSerotonin 0.8438 (p <0.0001)Norepinephrine 0.4024 (p =0.2026)Dopamine 0.2513 (p =0.1583)SD= standard deviation; N= number, HAM-D= Hamilton Rating Scale for Depression; q= quartile; TSAT= transferrin saturation; medication includes multiple ingestion While the change in Norepinephrine levels was correlated to the change in HAM-D score (0.4181; p=0.016), other correlations only reached borderline statistical significance or were non-significant (see table 4). Table 4: Correlation between the change in the significantly altered neurotransmitters norepinephrine and serotonin and the change in depression scores after iron supplementation. Deltap-value Deltap-value Norepinephrine Serotonin Delta HAM-D 0.4181 0.0155 -0.0231 0.8985Delta PHQ-9 0.2831 0.1104 0.1243 0.4907Delta BDI-II 0.0477 0.7921 -0.1823 0.3099Delta MADRS 0.2578 0.1475 0.0090 0.9604N= Number; HAM-D= Hamilton Rating Scale for Depression; PHQ-9= 9-question Patient Health Questionnaire; BDI-II= Beck Depression Inventory II; MADRS= Montgomery–Åsberg Depression Rating Scale. However, there was no correlation of baseline iron parameters and change in depression scores after iron supplementation (see Table 5). Table 5: Correlation of baseline iron parameter levels and the change in depression score (before versus after iron supplementation) is given. HAM-D= Hamilton Rating Scale for Depression; PHQ-9= 9-question Patient Health Questionnaire; BDI-II= Beck Depression Inventory II; MADRS= Montgomery–Åsberg Depression Rating Scale; TSAT= transferrin saturation. Accurate determination of iron status is crucial for diagnostic and screening purposes in the clinical setting and to guide therapeutic interventions. Since MDD is a non-inflammatory disease, the regular WHO recommended cut-off values (apparently healthy subjects) of ferritin to define iron deficiency apply here. This is underlined by the data disclosed in the present application: As it can be seen in the baseline characteristics of the 34 patients with MDD, mean concentration of the inflammation marker hsCRP (high-sensitivity C-reactive protein) was below the limit of detection <0.5mg / dL (standard deviation 0.0). This definitively proves that inflammation is not an issue in patients with MDD. For this reason, the ferritin cutoffs for apparently healthy subjectsapply for these patients: Iron deficiency: serum ferritin concentration 0-14 µg / L [www.WHO.int; WHO Guideline: Use of ferritin concentrations to assess iron status in individuals and populations]. Example 2 Administration of iron in patients suffering from PTSD Study Design The study was conducted as a non-randomized, observer-blinded, before / after study, recruiting patients at a university hospital in Germany. Patients and study intervention A total of 13 adults were recruited, for patient characteristics see table 6. All patients had been diagnosed with PTSD followed by depression at least 3 months ago and were treated according to standard of care, including interpersonal psychotherapy and antidepressant medication. All patients had a baseline ferritin concentration ≤100 µg / L. Exclusion criteria included any iron medication in clinical routine and lacking the capacity to consent. One clinician-assessed depression using assessment questionnaire (MADRS) at baseline in all 13 patients. The patients were then directly supplemented with intravenous iron. After 10 weeks the depression assessment scale was repeated. Analyses, outcomes, and intravenous treatment All routine laboratory parameters, including the iron parameters, were measured using Siemens Vista Dimension assays. In order to assess the severity of PTSD, the clinician-assessed the scale of the MADRS. For iron infusion, 500 mg ferric carboxymaltose (10 mL) was not injected directly, but diluted in 90 mL Saline and administered over 15 minutes. Statistical analysis Data are presented as absolute and relative frequency for categorical variables and as mean and standard deviation. A p-value <0.05 was the criterion for statistical significance. Logistic regression was used, in order to evaluate the effect of iron supplementation on disease severity. In accordance with the national guidelines, an improvement a decrease ≥2 points in the MADRS questionnaire, between intervention and follow-up assessment were determined as clinically relevant improvement. Statistical analyses were conducted using R project for statistical computing, version 4.0.1. Results The treatment was well tolerated in all 14 patients, and no patient reported any relevant side effects or intolerabilities. Moreover, no patient evolved iron overload, as evidenced by ferritin controls during follow-up.85% of the patients were female. The mean ferritin concentration was 39.2 (22.7), evidencing normal iron status in the cohort. Table 6: Characteristics of the study patients at baseline. Upon supplementation of iron the MADRS score significantly improved in the patients, with 53.8% of the patients achieving a clinically relevant improvement (see table 7). Table 7: Efficacy analysis using the outcome MADRS: Note: a decrease in ≥2 points between intervention and follow-up assessment is accepted as clinically relevant improvement in the guidelines] SD= standard deviation and iv= intravenous Example 3 Multicenter, randomized, double-blind, placebo-controlled parallel-group, fixed-dose study in adult patients with a primary diagnosis of MDD according to criteria of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) who have an inadequate response to ongoing anti- depressive therapy (ADT). Detailed Description The study comprises three periods: ^Screening Period (up to 2 weeks) during which patient eligibility will be assessed.^ Double-blind Treatment Period (IMP only to be given at baseline) in which all patients will berandomized to receive a single-dose of intravenous placebo or intravenous iron (423 mg) in 1:1 ratio. ^Follow-up Period (12 weeks) in which all patients will return to the clinic for efficacy and safetyfollow-up visits. Inclusion Criteria 1. Male or female patients between the ages of 18 and 75 years, inclusive;2. Meets DSM-5 criteria for MDD (MDD with psychotic features will be acceptable) as confirmedby the Investigator or Sponsor-approved rater using the modified Structured Clinical Interview for DSM-5, Clinical Trials Version (SCID-5-CT) and meets all of the following criteria: 1. The start of the current major depressive episode (MDE) is at least 12 weeks but notmore than 36 months prior to Screening; 2. Has at least moderate severity of illness based on rater-administered MADRS total score≥ 24 at Screening and at Baseline; 3. Has sufficient history and medical record confirmation verifying the anti-depressivetherapy (ADT) and the current major depressive episode (MDE) is causing clinically significant distress or impairment in social, occupational, or other important areas of functioning. 4. ferritin level <300 μg per liter;3. Currently having an inadequate response (less than 50% improvement) to ADT in the currentMDE as confirmed by the Investigator using the Antidepressant Treatment Response Questionnaire (ATRQ) and taking at least the minimum effective dose (per package insert) of one of the following antidepressants as monotherapy treatment for at least 6 weeks duration: citalopram / escitalopram, Fluoxetine, paroxetine, sertraline, duloxetine,levomilnacipran / milnacipran (if locally approved for MDD), venlafaxine / desvenlafaxine, bupropion, vilazodone, vortioxetine. Exclusion Criteria 1. Within the patient's lifetime, has a confirmed DSM-5 psychiatric diagnosis other than MDD,including: 1. Schizophrenia, Schizoaffective Disorder, Schizophreniform Disorder or other psychoticdisorder; 2. Bipolar Disorder;2. Within 6 months of Screening, has a confirmed DSM-5 psychiatric diagnosis other than MDDincluding: 1. Anxiety disorders such as Panic Disorder or Generalized Anxiety Disorder; Obsessive-compulsive Disorder; Posttraumatic Stress Disorder as primary diagnoses. Note: Anxiety symptoms may be allowed if secondary to MDD, provided these symptoms do not require concurrent treatment; 2. Eating disorder;3. Substance use disorders (excluding nicotine);4. Personality disorder of sufficient severity to have a major impact on the patient'spsychiatric status; 5. Within 12 months of Screening, has had any other psychiatric condition (other thanMDD) that has been the main focus of treatment; 3. The patient experiences a ≥ 25% decrease in the MADRS total score between Screening andBaseline; 4. In the opinion of the Investigator, the patient has a significant risk for suicidal behavior duringparticipation in the study or: 1. At Screening, the patient scores "yes" on Suicidal Ideation Items 4 or 5 of the Columbia-Suicide Severity Rating Scale (C-SSRS) within 6 months prior to Screening, or at Baseline, the patient scores "yes" on Suicidal Ideation Items 4 or 5 since the Screening Visit; 2. At Screening, the patient has had 1 or more suicide attempts within 2 years prior toScreening; 3. At Screening or Baseline, the patient scores ≥ 5 on MADRS Item 10 (SuicidalThoughts), or 4. The patient is considered to be in imminent danger to him / herself or others.5. The patient has a first MDE at age 60 years or older.Outcome Measures ^Primary outcome measure:Montgomery-Asberg Depression Rating Scale; MADRS is a clinician-rated 10 item scale to assess depressive symptoms. Each item is rated on a 7-point scale from 0-6. The total score ranges from 0 to 60 with a higher score indicating increased severity of depressive symptoms. ^Secondary outcome measures:Hamilton Depression Scale; HAM-D, is a multiple-item questionnaire used to provide an indication of depression, and as a guide to evaluate recovery. The administration of intravenous iron should result in an improvement of the patient’s mental state, in addition to ADT, or potentially replacing ADT altogether. Example 4 Multicenter, randomized, double-blind, placebo-controlled parallel-group, fixed-dose study in children and adult patients with a primary diagnosis of MDD according to criteria of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), who are not yet on anti-depressive therapy (ADT). Detailed Description The study comprises three periods: ^Screening Period (up to 2 weeks) during which patient eligibility will be assessed.^ Double-blind Treatment Period (IMP only to be given at baseline) in which all patients will berandomized to receive a single-dose of intravenous placebo or intravenous iron (423 mg) in 1:1 ratio. ^Follow-up Period (12 weeks) in which all patients will return to the clinic for efficacy and safetyfollow-up visits. Inclusion Criteria 1. Male or female patients between the ages of 12 and 75 years, inclusive;2. Meets DSM-5 criteria for MDD (MDD with psychotic features will be acceptable) as confirmedby the Investigator or Sponsor-approved rater using the modified Structured Clinical Interview for DSM-5, Clinical Trials Version (SCID-5-CT) and meets all of the following criteria: 1. The start of the current major depressive episode (MDE) is at least 12 weeks but notmore than 12 months prior to Screening; 2. Has at least moderate severity of illness based on rater-administered MADRS total score≥ 24 at Screening and at Baseline; 3. Has sufficient history and medical record confirmation verifying the anti-depressivetherapy (ADT) and the current major depressive episode (MDE) is causing clinically significant distress or impairment in social, occupational, or other important areas of functioning. 4. ferritin level <300 μg per liter3. Currently and previously not under treatment with one or more antidepressants, including thefollowing compounds: citalopram / escitalopram, Fluoxetine, paroxetine, sertraline, duloxetine, levomilnacipran / milnacipran (if locally approved for MDD), venlafaxine / desvenlafaxine, bupropion, vilazodone, vortioxetine. Exclusion Criteria 1. Within the patient's lifetime, has a confirmed DSM-5 psychiatric diagnosis other than MDD,including: 1. Schizophrenia, Schizoaffective Disorder, Schizophreniform Disorder or other psychoticdisorder; 2. Bipolar Disorder;2. Within 6 months of Screening, has a confirmed DSM-5 psychiatric diagnosis other than MDDincluding: 1. Anxiety disorders such as Panic Disorder or Generalized Anxiety Disorder; Obsessive-compulsive Disorder; Posttraumatic Stress Disorder as primary diagnoses. Note: Anxiety symptoms may be allowed if secondary to MDD, provided these symptoms do not require concurrent treatment; 2. Eating disorder;3. Substance use disorders (excluding nicotine);4. Personality disorder of sufficient severity to have a major impact on the patient'spsychiatric status; 5. Within 12 months of Screening, has had any other psychiatric condition (other thanMDD) that has been the main focus of treatment; 3. The patient experiences a ≥ 25% decrease in the MADRS total score between Screening andBaseline; 4. In the opinion of the Investigator, the patient has a significant risk for suicidal behavior duringparticipation in the study or: 1. At Screening, the patient scores "yes" on Suicidal Ideation Items 4 or 5 of the Columbia-Suicide Severity Rating Scale (C-SSRS) within 6 months prior to Screening, or at Baseline, the patient scores "yes" on Suicidal Ideation Items 4 or 5 since the Screening Visit; 2. At Screening, the patient has had 1 or more suicide attempts within 2 years prior toScreening; 3. At Screening or Baseline, the patient scores ≥ 5 on MADRS Item 10 (SuicidalThoughts), or 4. The patient is considered to be in imminent danger to him / herself or others.5. The patient has a first MDE at age 60 years or older. Outcome Measures ^Primary outcome measure:Montgomery-Asberg Depression Rating Scale; MADRS is a clinician-rated 10 item scale to assess depressive symptoms. Each item is rated on a 7-point scale from 0-6. The total score ranges from 0 to 60 with a higher score indicating increased severity of depressive symptoms. ^Secondary outcome measures:Hamilton Depression Scale; HAM-D, is a multiple-item questionnaire used to provide an indication of depression, and as a guide to evaluate recovery. The administration of intravenous iron should result in an improvement of the patient’s mental state, in addition to ADT, or potentially replacing ADT altogether. Example 5 Multicenter, randomized, double-blind, placebo-controlled parallel-group, fixed-dose, non-inferiority study in children and adult patients with a primary diagnosis of MDD according to criteria of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) who are on a stable dose of ongoing anti-depressive therapy (ADT). The therapeutic intervention comprises the replacement of the chronic ADT therapy by intravenous iron. Detailed Description The study will be conducted in three periods: ^Screening Period (up to 2 weeks) during which patient eligibility will be assessed.^ Observer-blind Treatment Period (IMP only to be given at baseline) in which all patients willbe randomized to discontinue their established ADT and receive a single-dose of intravenous iron (423 mg) or to continue their ADT in 1:1 ratio. ^Follow-up Period (12 weeks) in which all patients will return to the clinic for efficacy and safetyfollow-up visits. Inclusion Criteria 1. Male or female patients between the ages of 12 and 75 years, inclusive;2. Meets DSM-5 criteria for MDD (MDD with psychotic features will be acceptable) as confirmedby the Investigator or Sponsor-approved rater using the modified Structured Clinical Interview for DSM-5, Clinical Trials Version (SCID-5-CT) and meets all of the following criteria: 1. The start of the current major depressive episode (MDE) is at least 12 weeks but notmore than 36 months prior to Screening; 2. Mild to moderate severity of illness based on rater-administered MADRS total score atScreening and at Baseline; 3. Is on stable dose of ADT for at least 3 months, and a dose change is not intended atScreening or Baseline; 4. ferritin level <300 μg per liter3. Currently having an adequate or inadequate response (less than 50% improvement) to ADT inthe current MDE as confirmed by the Investigator using the Antidepressant Treatment Response Questionnaire (ATRQ) and taking at least the minimum effective dose (per package insert) of one of the following antidepressants as monotherapy treatment for at least 6 weeks duration: citalopram / escitalopram, Fluoxetine, paroxetine, sertraline, duloxetine, levomilnacipran / milnacipran (if locally approved for MDD), venlafaxine / desvenlafaxine, bupropion, vilazodone, vortioxetine. Exclusion Criteria 1. Within the patient's lifetime, has a confirmed DSM-5 psychiatric diagnosis other than MDD,including: 1. Schizophrenia, Schizoaffective Disorder, Schizophreniform Disorder or other psychoticdisorder; 2. Bipolar Disorder;2. Within 6 months of Screening, has a confirmed DSM-5 psychiatric diagnosis other than MDDincluding: 1. Anxiety disorders such as Panic Disorder or Generalized Anxiety Disorder; Obsessive-compulsive Disorder; Posttraumatic Stress Disorder as primary diagnoses. Note: Anxiety symptoms may be allowed if secondary to MDD, provided these symptoms do not require concurrent treatment; 2. Eating disorder;3. Substance use disorders (excluding nicotine);4. Personality disorder of sufficient severity to have a major impact on the patient'spsychiatric status; 5. Within 12 months of Screening, has had any other psychiatric condition (other thanMDD) that has been the main focus of treatment; 3. The patient experiences a ≥ 25% decrease in the MADRS total score between Screening andBaseline; 4. In the opinion of the Investigator, the patient has a significant risk for suicidal behavior duringparticipation in the study or: 1. At Screening, the patient scores "yes" on Suicidal Ideation Items 4 or 5 of the Columbia-Suicide Severity Rating Scale (C-SSRS) within 6 months prior to Screening, or at Baseline, the patient scores "yes" on Suicidal Ideation Items 4 or 5 since the Screening Visit; 2. At Screening, the patient has had 1 or more suicide attempts within 2 years prior toScreening; 3. At Screening or Baseline, the patient scores ≥ 5 on MADRS Item 10 (SuicidalThoughts), or 4. The patient is considered to be in imminent danger to him / herself or others.5. The patient has a first MDE at age 60 years or older.Outcome Measures ^Statistical test will be for non-inferiority of replacement of an established ADT by intravenousiron ^Primary outcome measure:Montgomery-Asberg Depression Rating Scale; MADRS is a clinician-rated 10 item scale to assess depressive symptoms. Each item is rated on a 7-point scale from 0-6. The total score ranges from 0 to 60 with a higher score indicating increased severity of depressive symptoms. ^Secondary outcome measures:Hamilton Depression Scale; HAM-D, is a multiple-item questionnaire used to provide an indication of depression, and as a guide to evaluate recovery. The replacement of ADT by intravenous iron should result in a more favorable side effect profile for the patients, while at least maintaining beneficial effects on the patient’s mental state. Example 6 Therapy and blinding Intravenous iron was administered as ferric carboxymaltose solution [Ferinject® / Injectafer® Vifor Pharma]. Study medication was given as diluted i.v. solutions in up to 100 mL saline (which is the amount of FCM that is equivalent to 500 to 2000 mg of iron, respectively) administered over at least 15 min (up to 2000 mg in patients with hemoglobin <10 g / dL and / or weight of ≥70 kg). Normal saline [0.9% weight / volume (w / v) NaCl] was administered as placebo as per the instructions for active therapy. Each administration of study drug occurred after completion of the study-related assessment of BDI questionnaire. Ferric carboxymaltose is a dark brown liquid solution and cannot easily be masked from placebo (0.9% saline). Therefore, unblinded pharmacy personnel not involved in any study assessments for efficacy or safety were responsible for preparing the study treatment injections in black infusion bags. Patients with systolic heart failure (HF), who had no known diagnosis of major depressive disorder, were studied in a clinical study. Patients were randomized 1:1 to treatment with a single dose of ferric carboxymaltose or placebo (saline). Treatment covered correction of iron deficiency during first 4 weeks. The pre-specified secondary endpoint was change in severity of depression as measured by the Becks Depression Inventory (BDI). Participants Eligible patients included stable ambulatory HF patients in New York Heart Association class 2 or 3, with left ventricular ejection fraction (LVEF) ≤45%, and serum ferritin level <300 ng / mL. Patients with active infection, clinical evidence of current malignancy, chronic liver disease and / or screening alanine transaminase or aspartate transaminase above three times the upper limit of the normal range, and patients on renal dialysis were excluded. Randomisation 18 Patients meeting the eligibility criteria were randomized 1:1 to treatment with ferric carboxymaltose or placebo (saline) in the order they qualified. Block randomization with random block size (4,6,8) was done. Therapy and blinding Intravenous iron was administered as ferric carboxymaltose solution [Ferinject® / Injectafer® Vifor Pharma; FCM]. Study medication was given as diluted i.v. solutions in up to 100 mL saline (which is the amount of FCM that is equivalent to 500 to 2000 mg of iron, respectively) administered over at least 15 min. Normal saline [0.9% weight / volume (w / v) NaCl] was administered as placebo as per the instructions for active therapy. Each administration of study drug occurred after completion of the study- related assessment of BDI questionnaire. Ferric carboxymaltose is a dark brown liquid solution and cannot easily be masked from placebo (0.9% saline). Therefore, unblinded pharmacy personnel not involved in any study assessments for efficacy or safety were responsible for preparing the study treatment injections in black infusion bags. Evaluation Due to the limited sample size, only a single outcome was assessed - Change of score in the Beck Depression Inventory (BDI) from baseline to 12 weeks. The BDI is a self-report rating inventory that measures characteristic attitudes and symptoms of depression. Results A total of 18 patients were randomized. Of the 18 subjects, 10 were randomized to FCM, and 8 to saline. One patient in the FCM group did not complete the follow-up visits and was excluded from further efficacy analysis. A second patient in the FCM group did not complete BDI questionnaire at month 3. Table 8 shows the baseline characteristics of all 18 patients. In general, patients in both treatment groups were comparable, while patients in the placebo group were slightly older and had more comorbidities. Figure 5 and Figure 6 show the results regarding the effects of intravenous iron supplementation on BDI disease severity score. Mean BDI score at baseline was 10.0 in the placebo group and 11.3 in the FCM group, indicating mild symptoms of depression across the study population. At month 3 there was a decrease (i.e. improvement) of 5.9 points (one patient did not complete BDI assessment at follow-up) in BDI score within the FCM group, in contrast to an increase of 1.4 point in the saline group (mean difference between groups: 5.5% ± 3.8%; p = 0.027) during the same period. When corrected for placebo, there was a striking improvement of 7.3 points in the treated group, which translates to an unprecedented decrease in BDI score of 65%. Safety analyses: Regarding safety, all adverse events were judged as "not related" to application of verum / placebo. Conclusion Iron supplementation with intravenous ferric carboxymaltose in patients with mild to moderate symptoms of depression strongly improves characteristic attitudes and symptoms of depression as assessed by the 21-question multiple-choice self-report inventory BDI. These results prove that IV iron is highly effective compared with placebo, even at low severity scores of depression questionnaires. Moreover, it implies potential use of intravenous iron for prevention of clinically manifest major depressive disorder in patients with chronic internal diseases. Furthermore, it implies potential use of intravenous iron in patients with mild or moderate depression, or a subclinical depression, or mild-to-moderate characteristic attitudes or symptoms of depression, or a depressive disorder not otherwises specified, such as minor depressive disorder and recurrent brief depression. Whereas symptoms of the disorder may arise due to several reasons. These include: Distress due to medical conditions (like heart failure or any other acute or chronic non-psychiatric disease), or environmental effects and situations. Table 8. Baseline characteristics Example 7: Precision Medicine Effect of Iron in MDD A) To investigate the effects of iron on patients with MDD (major depressive disorder), patients in the PSIRON-2 study were administered intravenous iron supplementation. Study description: Nonrandomized, observer-blinded crossover study in an academic out-patient clinic, involving 33 adults with MDD, all treated according to standard of care, including interpersonal psychotherapy and antidepressant medication. Intervention: Single intravenous administration of 500 mg of intravenous iron (ferric carboxymaltose). Endpoint Assessment: Serial assessment of MDD disease severity questionnaires and circulating neurotransmitter concentrations. Results Table 9: Pooled neurotransmitter analysis of all patients immediately before and 10 weeks after iron supplementation (N= 33). Mean concentration (SD) before intervention after intervention Change p-value (N= 33) (N= 33) Serotonin, ng / mL 80.8 (75,6) 64.2 (62.4) -20.5% 0.0272Norepinephrine, pg / mL 404.3 (167.1) 323.1 (155.0) -20.1% 0.0138Dopamine, pg / mL 28.9 (14.6) 25.9 (16.9) -10.4% 0.3918N= Number; SD= standard deviation. Table 10: Correlation of change in the significantly altered neurotransmitter levels and change in depression score after iron supplementation (N= 33). Delta Norepinephrine p-value Delta p-value Serotonin Delta HAM-D 0.4181 0.0155 -0.0231 0.8985N= Number; HAM-D= Hamilton Rating Scale for Depression. It was documented that iron supplementation in MDD patients results in reduced peripheral concentrations of norepinephrine and serotonin: 10 weeks after supplementation, circulating concentrations of both neurotransmitters were reduced by 20%, and the decrease in serotonin concentrations was significantly correlated to the overall improvement in the HAM-D assessment. This is similar to what was previously reported for selective serotonin reuptake inhibitors (SSRIs) (1, 2). Various studies investigating circulating serotonin levels pre- and post-SSRI treatment in MDD showed significantly decreased plasma serotonin levels within 4 to 8 weeks (1, 2). Holck and coworkers proofed the decrease being correlated to therapeutic response as assessed with HAM-D, just as in our study (2). Regarding norepinephrine, one study evaluating SSRI in 18 patients with psychiatric disease, found exactly the same extent of decrease as in our study upon treatment, 20.1%, although the change in that study was borderline statistically non-significant (p=0.06) (3). The fact that (already decreased) serotonin and norepinephrine concentrations further decrease upon iron supplementation on top of existing antidepressant medication, underlines the efficacy of iron in MDD. References : 1. Holck A et al., J Affect Disord 2019;250:65-70 ; 2. Gupta M et al., Mol Psychiatry 2016;21(12):1717-25 ; 3. Oh JY et al., Psychiatry Res 2015;225(3):471-5. B) Study description: Randomized, double-blinded, placebo-controlled study, involving 80 adults with chronic heart failure, all treated according to standard of care. Intervention: Serial intravenous iron supplementation (ferric carboxymaltose); 500 to 2000 mg, depending on hemoglobin values and body weight, 4 (500 mg) and 8 (500 mg) months. Endpoint Assessment: Circulating serotonin and norepinephrine concentrations. Results: Table 11: Pooled neurotransmitter analysis of all patients immediately before and 12 months after iron supplementation (N= 80). Mean concentration (SD) before intervention after intervention Change p-value (N= 80) (N= 80) Serotonin, ng / mL 124.6 (98.7) 122.5 (86.7) -1.7% (p= 0.79)Norepinephrine, pg / mL 994.3 (500.0) 1101.2 (537.7) +10.7% (p= 0.15)N= Number; SD= standard deviation. Results: Intravenous iron supplementation in MDD emerges as targeted personalized therapy tailored to individual needs. In contrast to patients with MDD, intravenous iron supplementation has no significant effect on circulating concentrations of the neurotransmitters serotonin and norepinephrine in heart failure patients. It should be noted that, if anything, the shown results underestimate the neurotransmitter-lowering effects of iron in MDD, since it is apparent that higher and longer exposition to ferric carboxymaltose, as in the patienst with heart failure, would even increase the effect. Example 8: Ferric carboxymaltose supplementation in PTSD Administration of intravenous iron in patients suffering from PTSD Study Design The study was conducted as a non-randomized before / after study. Patients and study intervention A total of 6 adults were recruited. All patients were treated according to standard of care, including interpersonal psychotherapy and antidepressant medication. All patients had a baseline ferritin concentration ≤100 µg / L. Exclusion criteria included any iron medication in clinical routine and lacking the capacity to consent. For iron infusion, 500 mg ferric carboxymaltose (10 mL) was not injected directly, but diluted in 90 mL Saline and administered over 15 minutes. Analyses, outcomes, and intravenous treatment All laboratory parameters were measured using conventional laboratory assays. Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) total severity score was assessed at baseline in all 6 patients. The patients were then directly supplemented with intravenous iron. After 6-8 weeks the CAPS-5 assessment scale was repeated. The clinical efficacy of iron administration on PTSD severity was assessed by the delta in the CAPS-5 score. Statistical analysis The statistical analyses were exploratory due to the limited sample size. Results The treatment was well tolerated in all 6 patients. One patient reported headaches and mild gastrointestinal discomfort. Both issues resolved after one day. 5 out of 6 patients were female. None patient had iron deficiency at baseline (Ferritin <15 ng / mL). Upon supplementation of iron, the CAPS-5 score significantly improved (as measured by a reduction in CAPS-5 total severity score) in the patients, with 3 out of 6 (50%) of the patients achieving a clinically relevant improvement (see table below). Table 12: Efficacy analysis using the outcome CAPS-5: SD= standard deviation; ; N= number Note: a decrease of ≥10 points in CAPS-5 score between intervention and follow-up assessment is defined as clinically relevant improvement in the guidelines Example 9: Ferric derisomaltose supplementation in MDD Administration of intravenous iron in patients suffering from MDD Study Design The study was conducted as a non-randomized before / after study. Patients and study intervention A total of 7 adults were recruited. Patients had various measures of standard of care, including interpersonal psychotherapy in the past, as well as antidepressant medication. All patients had a baseline ferritin concentration ≤100 µg / L. Exclusion criteria included any iron medication in clinical routine and lacking the capacity to consent. For iron infusion, 500 mg ferric derisomaltose (5 mL) was not injected directly, but diluted in 95 mL Saline and administered over 15 minutes. Analyses, outcomes, and intravenous treatment All laboratory parameters were measured using conventional laboratory assays. Severity of symptoms of depression was assessed by Physician-Administered MADRS (Montgomery– Åsberg Depression Rating Scale) questionnaire before treatment in all 7 patients. The patients were then directly supplemented with intravenous iron. After 8-12 weeks the questionnaire was repeated. The clinical efficacy of iron administration was assessed by the delta in the MADRS score. Statistical analysis The statistical analyses were exploratory due to the limited sample size. Results The treatment was well tolerated in all 7 patients. One patient reported headaches, which resolved within 1-2 days.4 patients were female. One patient had iron deficiency at baseline (Ferritin <15 ng / mL). Upon supplementation of iron, depression improved (as measured by a reduction in MADRS total severity score) in the patients, with 4 out of 7 (57%) of the patients achieving a clinically relevant improvement (see table below). Table 13: Efficacy analysis using the outcome MADRS: Mean score Mean score Mean absolute Patients (%) with (SD) before (SD) after difference clinically relevant intervention intervention improvement (N= 7) (N= 7) MADRS 22.7 (5.3) 17.1 (2.4) 5.6 57.1 %[≥6 points] SD= standard deviation; N= number; MADRS= Montgomery–Åsberg Depression Rating Scale Note: a decrease of ≥6 points in MADRS score between intervention and follow-up assessment is defined as clinically relevant improvement. When comparing treatment groups, a 2-point difference in MADRS scores between groups is considered clinically meaningful. Example 10: Oral iron (Ferro Sanol®) in MDD Administration of oral iron in patients suffering from MDD Study Design The study was conducted as a non-randomized before / after study. Patients and study intervention A total of 6 adults were recruited. Patients had various measures of standard of care, including interpersonal psychotherapy in the past, as well as antidepressant medication. Baseline ferritin concentrations were not available. Exclusion criteria included any iron medication in clinical routine and lacking the capacity to consent. Ferro Sanol® was recommended once to twice (in case of acceptable tolerability with regard to gastroenteric side effects) daily for a period of 3 months. Analyses, outcomes, and intravenous treatment No laboratory parameters were measured. Severity of symptoms of depression was assessed by Physician-Administered MADRS (Montgomery– Åsberg Depression Rating Scale) questionnaire before treatment in all 6 patients. The patients were then supplemented for 3 months. After approximately 3 months the questionnaire was repeated. The clinical efficacy of iron administration was assessed by the delta in the MADRS score. Statistical analysis The statistical analyses were exploratory due to the limited sample size and uncontrolled therapeutic compliance. Results The tolerability was acceptable.5 patients reported history of gastroenteric side effects during the course of 3 months.4 patients were female. Upon supplementation of iron, depression improved (as measured by a reduction in MADRS total severity score) in the patients, with 2 out of 6 (33%) of the patients achieving a clinically relevant improvement (see table below). Table 14: Efficacy analysis using the outcome MADRS: Mean score (SD) Mean score (SD) Mean absolute Patients (%) with before after difference clinically relevant intervention intervention improvement (N= 6) (N= 6) MADRS 19.0 (8.1) 16.8 (6.1) 2.2 33.3 %[≥6 points]...

Claims

M75416WO BOEHMERT & BOEHMERTClaims1. Iron supplementation for treatment and / or prophylaxis of affective disorder and / or post-traumatic stress disorder (PTSD) and / or serotonin-dependent diseases in a human patient in need thereof.

2. Iron supplementation for treatment and / or prophylaxis of an affective disorder and / orpost-traumatic stress disorder (PTSD) and / or serotonin-dependent diseases in a human patient in need thereof according to claim 1, wherein said patient does not suffer from an iron deficiency and wherein iron deficiency is defined as plasma and / or serum or whole blood ferritin level of less than 15 µg / L in said patient.

3. Iron supplementation for treatment and / or prophylaxis of an affective disorder and / orpost-traumatic stress disorder (PTSD) and / or serotonin-dependent diseases in a human patient in need thereof according to claim 1, wherein said patient does not suffer from anemia and wherein anemia is defined as a whole blood hemoglobin level of less than 12 g / dL in females and a whole blood hemoglobin level less than 13 g / dL in males.

4. Iron supplementation for treatment and / or prophylaxis of affective disorder and / or post-traumatic stress disorder (PTSD) and / or serotonin-dependent diseases in a human patient in need thereof according to claim 1, wherein said patient is a non-anemic patient, a mild anemic patient or a subclinical anemic patient.

5. Iron supplementation for treatment and / or prophylaxis of affective disorder and / or post-traumatic stress disorder (PTSD) and / or serotonin-dependent diseases in a human patient in need thereof according to claim 4, wherein said patient is a non-anemic female and has a whole blood hemoglobin level of greater than or equal to 12 g / dL or said patient is a non-anemic male and has a whole blood hemoglobin level of greater than or equal to 13 g / dL.

6. Iron supplementation for treatment and / or prophylaxis of affective disorder and / or post-traumatic stress disorder (PTSD) and / or serotonin-dependent diseases in a human patient in need thereof according to claim 4, wherein said patient is a non-anemic female or mild anemic female and has a whole blood hemoglobin level of greater than 11 g / dL or saidpatient is a non-anemic male or a mild anemic male and has a whole blood hemoglobin level of greater than 12 g / d L.

7. Iron supplementation for treatment and / or prophylaxis of affective disorder and / or post-traumatic stress disorder (PTSD) and / or serotonin-dependent diseases in a human patient in need thereof according to claim 4, wherein said patient is a non-anemic female or a mild anemic female or a subclinical anemic female and has a whole blood hemoglobin level of greater than 10 g / dL or said patient is a non-anemic male or a mild anemic male or a subclinical anemic male and has a whole blood hemoglobin level of greater than 11 g / d L.

8. Iron supplementation for treatment and / or prophylaxis of affective disorder and / or post-traumatic stress disorder (PTSD) and / or serotonin-dependent diseases in a human patient in need thereof according to claim 4, wherein said patient is a mild anemic female and has a whole blood hemoglobin level of 11 g / dL to less than 12 g / dL or said patient is a mild anemic male and has a whole blood hemoglobin level of 12 g / dL to less than 13 g / dL.

9. Iron supplementation for treatment and / or prophylaxis of affective disorder and / or post-traumatic stress disorder (PTSD) and / or serotonin-dependent diseases in a human patient in need thereof according to claim 4, wherein said patient is a subclinical anemic female and has a whole blood hemoglobin level of 10 g / dL to less than 11 g / dL or said patient is a subclinical anemic male and has a whole blood hemoglobin level of 11 g / d L to less than 12 g / dL.

10. Iron supplementation for treatment and / or prophylaxis of affective disorder and / or post-traumatic stress disorder (PTSD) and / or serotonin-dependent diseases in a human patient in need thereof according to claims 4 to 9, wherein said patient does not suffer from an iron deficiency and wherein iron deficiency is defined as whole blood or plasma and / or serum ferritin level of less than 15 µg / L in said patient.

11. Iron supplementation for treatment and / or prophylaxis of an affective disorder and / orpost-traumatic stress disorder (PTSD) and / or serotonin-dependent diseases in a human patient in need thereof according to any of claims 1 to 10, wherein said patient does not suffer from iron deficiency anemia and wherein iron deficiency anemia is defined aswhole blood hemoglobin level of less than 12 g / dL in females and a whole blood hemoglobin level less than 13 g / dL in males and concomitant whole blood and / or plasma and serum ferritin level of less than 15 µg / L.

12. Iron supplementation for treatment and / or prophylaxis of affective disorder and / or post-traumatic stress disorder (PTSD) and / or serotonin-dependent diseases in a human patient in need thereof according to claims 1 to 11, wherein said patient is female and wherein said female is a non-pregnant female.

13. Iron supplementation for treatment and / or prophylaxis of affective disorder and / or post-traumatic stress disorder (PTSD) and / or serotonin-dependent diseases in a human patient in need thereof according to claims 1 to 12, wherein said patient is 18 years or above, preferably 15 years or above.

14. Iron supplementation for treatment and / or prophylaxis of depression and / or affectivedisorder and / or post-traumatic stress disorder (PTSD) and / or serotonin-dependent disease in a human patient in need thereof according to claim 1 to 13, wherein said disorder or disease is depression, in particular a major depressive disorder (MDD) or a mild depression or depression secondary to neurological causes, endocrinopathies, metabolic disturbances, medication / substance abuse, nutritional deficiencies, infectious diseases, malignancies, cancer, inflammatory bowel disease or cardiovascular diseases.

15. Iron supplementation for treatment and / or prophylaxis of depression and / or affectivedisorder and / or post-traumatic stress disorder (PTSD) and / or serotonin-dependent disease in a human patient in need thereof according to claim 1 to 14, wherein said disorder or disease is an affective disorder.

16. Iron supplementation for treatment and / or prophylaxis of depression and / or affectivedisorder and / or post-traumatic stress disorder (PTSD) and / or serotonin-dependent disease in a human patient in need thereof according to claim 1 to 14, wherein said disorder or disease is a post-traumatic stress disorder (PTSD).

17. Iron supplementation for treatment and / or prophylaxis of depression and / or affectivedisorder and / or post-traumatic stress disorder (PTSD) and / or serotonin-dependentdisease in a human patient in need thereof according to claim 1 to 14, wherein said disorder or disease is a serotonin-dependent disease.

18. Iron supplementation for treatment and / or prophylaxis of an affective disorder and / orpost-traumatic stress disorder (PTSD) and / or serotonin-dependent diseases in a human patient in need thereof according to claim 1 to 17, wherein said patient suffers from internal diseases and medical conditions caused, mediated or aggravated by circulating serotonin level, like pulmonary arterial hypertension, tumor growth and metastasis in Colorectal Cancer, asthma, inflammatory bowel disease, and fibrotic diseases in the lungs, liver, skin, and kidneys.

19. Iron supplementation for treatment and / or prophylaxis of depression and / or affectivedisorder and / or post-traumatic stress disorder (PTSD) and / or serotonin-dependent disease in a human patient in need thereof according to claim 1 to 18, wherein said disorder or disease is a Major Depressive Disorder (MDD).

20. Iron supplementation for treatment and / or prophylaxis of an affective disorder and / orpost-traumatic stress disorder (PTSD) and / or serotonin-dependent diseases in a human patient in need thereof according to any of claims 1 to 19, wherein said patient is receiving therapy with one or more antidepressants or is scheduled to receive therapy with one or more antidepressants, and wherein preferably the patient is suffering from a Major Depressive Disorder.

21. Iron supplementation for treatment and / or prophylaxis of an affective disorder and / orpost-traumatic stress disorder (PTSD) and / or serotonin-dependent diseases in a human patient in need thereof according to claim 20, wherein said iron supplementation is administered as adjunctive therapy to said therapy with one or more antidepressants.

22. Iron supplementation for treatment and / or prophylaxis of an affective disorder and / orpost-traumatic stress disorder (PTSD) and / or serotonin-dependent diseases in a human patient in need thereof according to claim 20, wherein said iron supplementation is administered as replacement of said therapy with one or more antidepressants.

23. Iron supplementation for treatment and / or prophylaxis of an affective disorder and / orpost-traumatic stress disorder (PTSD) and / or serotonin-dependent diseases in a human patient in need thereof according to any of claims 1 to 22, wherein said patient is not receiving treatment antidepressants, preferably has never received treatment with antidepressants, and wherein preferably the patient is suffering from a Major Depressive Disorder.

24. Iron supplementation for treatment and / or prophylaxis of an affective disorder and / orpost-traumatic stress disorder (PTSD) and / or serotonin-dependent diseases in a human patient in need thereof according to any of claims 1 to 20 and claim 23, wherein the iron supplementation is selected from the group comprising an intravenous iron supplementation, parenteral iron supplementation, intraaerterial iron supplementation, oral iron supplementation or intramuscular iron supplementation, preferably an intravenous iron supplementation or an oral iron supplementation, more preferably an intravenous iron supplementation.

25. Iron supplementation for treatment and / or prophylaxis of depression and / or affectivedisorder and / or post-traumatic stress disorder (PTSD) and / or serotonin-dependent disease in a human patient in need thereof according to any of claims 1 to 24, wherein iron supplementation comprises the administration of an Iron(III) or Iron(II) compound, in particular selected from the group comprising ferrous bisglycinate chelate, Iron(II) glycine sulphate complex (Ferro sanol duodenal®), Iron(III) derisomaltose (MonoFer®, Iron isomaltoside, ferric derisomaltose, Monoferric), Iron(III) hydroxide-dextran complex (Cosmofer®), Iron(III) sodium D-gluconate complex (Ferlixit® ; Ferrlecit®), Iron-II-gluconate / iron(III)-sodium-gluconate complex (Ferrlecit®), Iron(III) hydroxide sucrose complex (Venofer®, PA21, Velforo), Iron(III) hydroxide sucrose complex (Fermed®), Iron carboxymaltose (Ferinject®), Ferric maltol (ST10; ST10-021) and / or ferric citrate (KRX-0502; auryxia), more particularly, said iron supplematation is Iron(III) derisomaltose (MonoFer®, Iron isomaltoside, ferric derisomaltose, Monoferric) and Iron(III) hydroxide-dextran complex (Cosmofer®).

26. Iron supplementation for treatment and / or prophylaxis of depression and / or an affectivedisorder and / or post-traumatic stress disorder (PTSD) and / or serotonin-dependentdisease in a human patient in need thereof according to any of claims 1 to 25, wherein said iron supplementation is administered in form of a pharmaceutical formulation.

27. Iron Supplementation for treatment and / or prophylaxis of depression and / or an affectivedisorder and / or post-traumatic stress disorder (PTSD) and / or serotonin-dependent disease in a human patient in need thereof according to any of claims 1 to 26, wherein said iron supplementation is in form of a solution, preferably a ready-to-use solution.

28. Iron supplementation for treatment and / or prophylaxis of depression and / or an affectivedisorder and / or post-traumatic stress disorder (PTSD) and / or serotonin-dependent disease in a human patient in need thereof according to any of claims 1 to 27, wherein said iron supplementation is in a freeze-dried state.

29. Iron supplementation for treatment and / or prophylaxis of depression and / or an affectivedisorder and / or post-traumatic stress disorder (PTSD) and / or serotonin-dependent disease in a human patient in need thereof according to any of claims 1 to 28, wherein the iron supplementation is selected from the group comprising an intravenous iron supplementation, parenteral iron supplementation, intraaerterial iron supplementation, oral iron supplementation or intramuscular iron supplementation, wherein said iron supplementation comprises iron in a concentration of 0,0001 g / L to 20 g / L, preferably 0,001 g / L to 2 g / L, preferably 0,02 g / L to 1,5 g / L, more preferably 0,05 g / L to 1,2 g / L, more preferably 0,1 g / L to 1 g / L and most preferably 0,5 g / L.

30. Iron supplementation for treatment and / or prophylaxis of depression and / or an affectivedisorder and / or post-traumatic stress disorder (PTSD) and / or serotonin-dependent diseases in a human patient in need thereof according to any of claims 1 to 29, wherein the iron supplementation is selected from the group comprising an intravenous iron supplementation, intraaerterial iron supplementation, parenteral iron supplementation, oral iron supplementation or intramuscular iron supplementation, wherein said iron supplementation comprises iron in a dose of 1 mg / Kg body weight to 30 mg / Kg body weight, preferably of 2 mg / Kg body weight to 25 mg / Kg body weight, more preferably of 5 mg / Kg body weight to 15 mg / Kg body weight, and most preferably of 10 mg / Kg body weight.

31. Iron supplementation for treatment and / or prophylaxis of depression and / or an affectivedisorder and / or post-traumatic stress disorder (PTSD) and / or serotonin-dependent disease in a human patient in need thereof according to any of claims 1 to 30, wherein the iron supplementation is selected from the group comprising an intravenous iron supplementation, parenteral iron supplementation, intraaerterial iron supplementation, oral iron supplementation or intramuscular iron supplementation, wherein said iron supplementation comprises iron in a fixed dose of 400 to 450 mg, more particularly 423 mg.

32. Iron supplementation for treatment and / or prophylaxis of depression and / or an affectivedisorder and / or post-traumatic stress disorder (PTSD) and / or serotonin-dependent disease in a human patient in need thereof according to any of claims 1 to 31, wherein the iron supplementation is administered to said patient in repeated doses in a 12 week interval.

33. Iron supplementation for treatment and / or prophylaxis of depression and / or an affectivedisorder and / or post-traumatic stress disorder (PTSD) and / or serotonin-dependent disease in a human patient in need thereof according to any of claims 1 to 32, wherein the iron supplementation is an intravenous iron supplementation, preferably a ferric carboxymaltose solution, which is administered in a dose equivalent to 500 to 2000mg of iron, more preferably administered over at least 15 min.

Images