Erythroferrone (ERFE) is the main erythroid regulator of hepcidin, the homeostatic hormone controlling plasma iron levels and total body iron. When the release of erythropoietin from the kidney stimulates the production of new red blood cells, it also increases the synthesis of ERFE in bone marrow erythroblasts. Increased ERFE then suppresses hepcidin synthesis, thereby mobilizing cellular iron stores for use in heme and hemoglobin synthesis. Recent mechanistic studies have shown that ERFE suppresses hepcidin transcription by inhibiting bone morphogenetic protein signaling in hepatocytes. In ineffective erythropoiesis, pathological overproduction of ERFE by an expanded population of erythroblasts suppresses hepcidin and causes iron overload, even in non-transfused patients. ERFE may be a useful biomarker of ineffective erythropoiesis and an attractive target for treating its systemic effects.

Erythroferrone structure, function, and physiology: Iron homeostasis and beyond.

Iron is an essential micronutrient for oxygen transport and mitochondrial metabolism and is critical for physical performance. Compromised iron stores are more commonly found among athletes, and females are especially at risk. Iron deficiency is generally treated using oral iron supplements. However, only a small proportion of ingested iron is absorbed, necessitating higher intakes, which may result in adverse side effects, reduced compliance, and inefficient repletion of iron stores. The probiotic strain Lactobacillus plantarum 299v (Lp299v) significantly increases intestinal iron absorption in meal studies. The present study was conducted to explore the effects of 20 mg of iron with or without Lp299v on iron status, mood state, and physical performance. Fifty-three healthy non-anemic female athletes with low iron stores (ferritin < 30 μg/L) were randomized, and 39 completed the study. Intake of Lp299v with iron for four weeks increased ferritin levels more than iron alone (13.6 vs. 8.2 µg/L), but the difference between the groups was not significant (p = 0.056). The mean reticulocyte hemoglobin content increased after intake of Lp299v compared to control (1.5 vs. 0.82 pg) after 12 weeks, but the difference between the group was not significant (p = 0.083). The Profile of Mood States (POMS) questionnaire showed increased vigor with Lp299v vs. iron alone after 12 weeks (3.5 vs. 0.1, p = 0.015). No conclusive effects on physical performance were observed. In conclusion, Lp299v, together with 20 mg of iron, could result in a more substantial and rapid improvement in iron status and improved vigor compared to 20 mg of iron alone. A larger clinical trial is needed to further explore these findings as well as the impact of Lp299v on physical performance.

The Effect of Lactobacillus plantarum 299v on Iron Status and Physical Performance in Female Iron-Deficient Athletes: A Randomized Controlled Trial.

As life expectancy has increased, particularly in developed countries, due to medical advances and increased prosperity, age-related neurological diseases and mental health disorders have become more prevalent health issues, reducing the well-being and quality of life of sufferers and their families. In recent decades, due to reduced work-related levels of physical activity, and key research insights, prescribing adequate exercise has become an innovative strategy to prevent or delay the onset of these pathologies and has been demonstrated to have therapeutic benefits when used as a sole or combination treatment. Recent evidence suggests that the beneficial effects of exercise on the brain are related to several underlying mechanisms related to muscle-brain, liver-brain and gut-brain crosstalk. Therefore, this review aims to summarize the most relevant current knowledge of the impact of exercise on mood disorders and neurodegenerative diseases, and to highlight the established and potential underlying mechanisms involved in exercise-brain communication and their benefits for physiology and brain function.

/pdf/molecular-mechanisms-underlying-the-beneficial-effects-of-399qejt1dm.pdf

Molecular Mechanisms Underlying the Beneficial Effects of Exercise on Brain Function and Neurological Disorders

Iron deficiency (ID) is a prevailing nutritional concern amongst the athletic population due to the increased iron demands of this group. Athletes’ ability to replenish taxed iron stores is challenging due to the low bioavailability of dietary sources, and the interaction between exercise and hepcidin, the primary iron-regulatory hormone. To date, copious research has explored the link between exercise and iron regulation, with a more recent focus on optimising iron treatment applications. Currently, oral iron supplementation is typically the first avenue of iron replacement therapy beyond nutritional intervention, for treatment of ID athletes. However, many athletes encounter associated gastrointestinal side-effects which can deter them from fulfilling a full-term oral iron treatment plan, generally resulting in sub-optimal treatment efficacy. Consequently, various strategies (e.g. dosage, composition, timing) of oral iron supplementation have been investigated with the goal of increasing fractional iron absorption, reducing gastric irritation, and ultimately improving the efficacy of oral iron therapy. This review explores the various treatment strategies pertinent to athletes and concludes a contemporary strategy of oral iron therapy entailing morning supplementation, ideally within the 30 min following morning exercise, and in athletes experiencing gut sensitivity, consumed on alternate days or at lower doses.

Refining treatment strategies for iron deficient athletes

Sports supplements are commonly used by elite athletes with the main goal of enhancing sport performance. Supplements use might be substantially different depending on the sport discipline, sex, and competitive level. To date, data about prevalence and the most-commonly used supplements in handball are scarce. Thus, the aim of this investigation was to determine the patterns of supplements use by handball players of both sexes and with different competitive levels: One hundred and eighty-seven handball players (112 men and 75 women) of different competitive levels (106 professional and 81 amateur) completed a validated self-administered questionnaire about supplements use. Supplements were classified according to the categorization of the Australian Institute of Sport (AIS). Overall, 59.9% of the handball players (n = 112) declared the use of at least one supplement and there were no significant differences between men and women (58.9% vs. 61.3%, p = 0.762) nor between professional vs. amateur handball players (67.1% vs. 53.8%, p = 0.074). The most prevalent supplements were sports drinks (42.2%), followed by energy bars (35.3%) and caffeine-containing products (31.6%). However, a greater consumption of group A supplements (those with strong scientific evidence; p = 0.029) and group B supplements (those with emerging scientific support, p = 0.012) was observed in male compared to female handball players. Supplements categorized as medical supplements were more commonly consumed in professional vs. amateur players (0.48 ± 0.80 vs. 0.21 ± 0.44, supplements p < 0.006). Additionally, a higher consumption of group B supplements was observed in professional compared to amateur players (0.58 ± 0.88 vs. 0.33 ± 0.72 supplements, p = 0.015). Handball players revealed a moderate use of supplements while sex and competitive level slighted changed the pattern of supplements use. A high portion of handball players use supplements as fuel during exercise and reported the use of caffeine-containing supplements to enhance performance.

Use of Sports Supplements in Competitive Handball Players: Sex and Competitive Level Differences.

Iron deficiency is a frequent and multifactorial disorder in the career of athletes, particularly in females. Exercise-induced disturbances in iron homeostasis produce deleterious effects on performance and adaptation to training; thus, the identification of strategies that restore or maintain iron homeostasis in athletes is required. Hepcidin is a liver-derived hormone that degrades the ferroportin transport channel, thus reducing the ability of macrophages to recycle damaged iron, and decreasing iron availability. Although it has been suggested that the circulating fraction of hepcidin increases during early post-exercise recovery (~3 h), it remains unknown how an acute exercise bout may modify the circulating expression of hepcidin. Therefore, the current review aims to determine the post-exercise expression of serum hepcidin in response to a single session of exercise. The review was carried out in the Dialnet, Elsevier, Medline, Pubmed, Scielo and SPORTDiscus databases, using hepcidin (and "exercise" or "sport" or "physical activity") as a strategy of search. A total of 19 articles were included in the review after the application of the inclusion/exclusion criteria. This search found that a single session of endurance exercise (intervallic or continuous) at moderate or vigorous intensity (60-90% VO2peak) stimulates an increase in the circulating levels of hepcidin between 0 h and 6 h after the end of the exercise bout, peaking at ~3 h post-exercise. The magnitude of the response of hepcidin to exercise seems to be dependent on the pre-exercise status of iron (ferritin) and inflammation (IL-6). Moreover, oxygen disturbances and the activation of a hypoxia-induced factor during or after exercise may stimulate a reduction of hepcidin expression. Meanwhile, cranberry flavonoids supplementation promotes an anti-oxidant effect that may facilitate the post-exercise expression of hepcidin. Further studies are required to explore the effect of resistance exercise on hepcidin expression.

https://www.mdpi.com/2072-6643/10/2/209/pdf

Adrián Feria-Madueño

Papers

Effects of an Acute Exercise Bout on Serum Hepcidin Levels