Publications by authors named "Coby Laarakkers"

The hormone hepcidin plays an important role in intestinal iron absorption and cellular release. Cord blood hepcidin values reflect fetal hepcidin status, at least at the time of delivery, but are not available for the Belgian population. Therefore, we aimed (1) to provide the first data on cord blood hepcidin levels in a Belgian cohort and (2) to determine variables associated with cord blood hepcidin concentrations.

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Purpose: Menstrual cycle phase affects resting hepcidin levels, but such effects on the hepcidin response to exercise are still unclear. Thus, we investigated the hepcidin response to running during three different menstrual cycle phases.

Methods: Twenty-one endurance-trained eumenorrheic women performed three identical interval running protocols during the early-follicular phase (EFP), late-follicular phase (LFP), and mid-luteal phase (MLP).

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Pathogenic variants impairing matriptase-2 function result in inappropriately high hepcidin levels relative to body iron status, leading to iron refractory iron deficiency anemia (IRIDA). As diagnosing IRIDA can be challenging due to its genotypical and phenotypical heterogeneity, we assessed the transferrin saturation (TSAT)/hepcidin ratio to distinguish IRIDA from multi-causal iron deficiency anemia (IDA). We included 20 IRIDA patients from a registry for rare inherited iron disorders and then enrolled 39 controls with IDA due to other causes.

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Article Synopsis
  • A patient had a specific genetic condition that caused high levels of hepcidin, a protein that regulates iron in the body.
  • Even though their iron levels were normal, they had a lot of inflammation in their body.
  • This situation showed that without a functioning HFE gene, inflammation can still increase hepcidin levels through a different pathway in the body.
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Phlebotomies are performed in hereditary hemochromatosis (HH) to maintain normal iron concentrations. Proton-pump inhibitors (PPIs) can reduce the number of phlebotomies in patients with HH. However, in patients without HH, the iron concentrations do not appear to be compromised when using PPIs.

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This study implemented a 2-week high carbohydrate (CHO) diet intended to maximize CHO oxidation rates and examined the iron-regulatory response to a 26-km race walking effort. Twenty international-level, male race walkers were assigned to either a novel high CHO diet (MAX = 10 g/kg body mass CHO daily) inclusive of gut-training strategies, or a moderate CHO control diet (CON = 6 g/kg body mass CHO daily) for a 2-week training period. The athletes completed a 26-km race walking test protocol before and after the dietary intervention.

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Menopause commonly presents the gradual accumulation of iron in the body over the years, which is a risk factor for diseases such as cancer, osteoporosis, or cardiovascular diseases. Running exercise is known to acutely increase hepcidin levels, which reduces iron absorption and recycling. As this fact has not been studied in postmenopausal women, this study investigated the hepcidin response to running exercise in this population.

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The use of oral contraceptives (OCs) by female athletes may lead to improved iron status, possibly through the regulation of hepcidin by sex hormones. The present work investigates the response of hepcidin and interleukin-6 (IL-6) to an interval exercise in both phases of the OC cycle. Sixteen endurance-trained OC users (age 25.

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Chronic low-grade inflammation in type 1 diabetes (T1D) might increase hepcidin synthesis, possibly resulting in functional iron deficiency (FID). We hypothesized that in T1D children with FID, hepcidin concentrations are increased compared to those with normal iron status and those with absolute iron deficiency (AID). We evaluated hepcidin concentrations in T1D children in relation to iron status, and investigated whether hepcidin is useful in assessing FID.

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Objectives: Hepcidin measurement advances insights in pathophysiology, diagnosis, and treatment of iron disorders, but requires analytically sound and standardized measurement procedures (MPs). Recent development of a two-level secondary reference material (sRM) for hepcidin assays allows worldwide standardization. However, no proficiency testing (PT) schemes to ensure external quality assurance (EQA) exist and the absence of a high calibrator in the sRM set precludes optimal standardization.

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Background: Use of serum hepcidin measurements in pediatrics would benefit from standardized age- and sex-specific reference ranges in children, in order to enable the establishment of clinical decision limits that are universally applicable.

Procedure: We measured serum hepcidin-25 levels in 266 healthy Dutch children aged 0.3-17 years, using an isotope dilution mass spectrometry assay, standardized with our commutable secondary reference material (RM), assigned by a candidate primary RM.

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Sleeping with low carbohydrate (CHO) availability is a dietary strategy that may enhance training adaptation. However, the impact on an athlete's health is unclear. This study quantified the effect of a short-term "sleep-low" dietary intervention on markers of iron regulation and immune function in athletes.

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Article Synopsis
  • Hepcidin is a peptide hormone that regulates iron metabolism and is variably reported to be bound to blood proteins like α2-macroglobulin and albumin.
  • This study investigated hepcidin protein binding in 14 patients with end-stage renal disease through peritoneal dialysis, finding that about 40% of hepcidin is protein-bound.
  • The results highlight significant individual variability in hepcidin clearance and emphasize the need for further research to understand hepcidin's biological behavior and measurement nuances.
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Purpose: This study examined postexercise inflammatory, hepcidin, and iron absorption responses to endurance exercise performed in the morning versus the afternoon.

Methods: Sixteen endurance-trained runners (10 male, 6 female) with serum ferritin (sFer) < 50 μg·L completed a 90-min running protocol (65% vV˙O2max) in the morning (AM), or the afternoon (PM), in a crossover design. An iron-fortified fluid labeled with stable iron isotopes (Fe or Fe) was administered with a standardized meal 30 min following the exercise and control conditions during each trial, serving as a breakfast and dinner meal.

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Objectives: Adhering to a low carbohydrate (CHO) high fat (LCHF) diet can alter markers of iron metabolism in endurance athletes. This investigation examined the re-introduction of CHO prior to, and during exercise on the iron-regulatory response to exercise in a homogenous (in regard to serum ferritin concentration) group of athletes adapted to a LCHF diet.

Design: Parallel groups design.

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Background Hepcidin concentrations measured by various methods differ considerably, complicating interpretation. Here, a previously identified plasma-based candidate secondary reference material (csRM) was modified into a serum-based two-leveled sRM. We validated its functionality to increase the equivalence between methods for international standardization.

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Purpose: The short-term restriction of carbohydrate (CHO) can potentially influence iron regulation via modification of postexercise interleukin-6 (IL-6) and hepcidin levels. This study examined the effect of a chronic ketogenic low-CHO high-fat (LCHF) diet on iron status and iron-regulatory markers in elite athletes.

Methods: International-level race walkers (n = 50) were allocated to one of three dietary interventions: (i) a high-CHO diet (n = 16), (ii) a periodized CHO availability (n = 17), or (iii) an LCHF diet (n = 17) while completing a periodized training program for 3 wk.

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Background And Purpose: Anaemia of chronic disease (ACD) has been linked to iron-restricted erythropoiesis imposed by high circulating levels of hepcidin, a 25 amino acid hepatocyte-derived peptide that controls systemic iron homeostasis. Here, we report the engineering of the human lipocalin-derived, small protein-based anticalin PRS-080 hepcidin antagonist with high affinity and selectivity.

Experimental Approach: Anticalin- and hepcidin-specific pharmacokinetic (PK)/pharmacodynamic modelling (PD) was used to design and select the suitable drug candidate based on t extension and duration of hepcidin suppression.

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Purpose: The extent to which hepcidin regulation after acute bouts of exercise is influenced by baseline (resting) concentrations of key iron parameters remains uncertain. This investigation explored the influence of selected iron parameters and 25-km race walk time on 3-h post-exercise hepcidin-25 levels in international-level race walkers.

Methods: Twenty-four male race walkers completed a graded exercise test and a 25-km race-walk trial.

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Purpose: This investigation examined if a high carbohydrate (CHO) diet, maintained across a seven-day training period, could attenuate post-exercise interleukin-6 (IL-6) and serum hepcidin levels.

Methods: Twelve endurance-trained male athletes completed two seven-day running training blocks whilst consuming either a high (8 g kg(-1)) versus a low (3 g kg(-1)) CHO isoenergetic diet. Each training block consisted of five running sessions performed on days 1, 2, 4, 5, and 7, with the intensity and duration of each session matched between training weeks.

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Background: Absolute plasma hepcidin concentrations measured by various procedures differ substantially, complicating interpretation of results and rendering reference intervals method dependent. We investigated the degree of equivalence achievable by harmonization and the identification of a commutable secondary reference material to accomplish this goal.

Methods: We applied technical procedures to achieve harmonization developed by the Consortium for Harmonization of Clinical Laboratory Results.

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Urinary hepcidin may have protective effects against AKI. However, renal handling and the potential protective mechanisms of hepcidin are not fully understood. By measuring hepcidin levels in plasma and urine using mass spectrometry and the kidney using immunohistochemistry after intraperitoneal administration of human hepcidin-25 (hhep25) in C57Bl/6N mice, we showed that circulating hepcidin is filtered by the glomerulus and degraded to smaller isoforms detected in urine but not plasma.

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