Could hepcidin help in the identification of low energy availability? The implication of low energy availability on iron regulation
By Dr Claire Badenhorst and Dr Wendy O’Brien
Hepcidin and iron homeostasis
Iron homeostasis is controlled by the hormone, hepcidin, a peptide hormone produced in the liver. This hormone exerts its effect on the body’s primary iron export channel, ferroportin, located in the small intestine, white blood cells, liver and fat cells. Increases in hepcidin result in the breakdown and degradation of these channels, inhibiting the movement of iron into or out of cells. As such, elevations in hepcidin are associated with decreased dietary iron absorption, reduced iron movement from internal stores and ineffective recycling of iron (Figure 1). Within the athletic setting the impact of hepcidin on exercise-induced iron deficiency is well defined, with acute increases in hepcidin activity observed ~3-6 hours post-exercise, a consequence of exercise-induced inflammation. Research in this area has suggested a window of time following exercise in which iron metabolism is altered. Over the last decade research focussing on this window of altered iron metabolism has utilised interventions which, in theory, would mitigate the hepcidin effect on iron absorption in healthy athletes and, consequently, reduce their risk of developing iron deficiency.
Figure 1: Regulation of iron metabolism via hepcidin activity in the body.
Could hepcidin be an early onset marker of low energy availability?
Hepcidin research in sport has focused on single and repeated training blocks, and has suggested a cumulative effect in hepcidin activity over a regular and consistent training period (~7 days). The majority of dietary interventions pre- and post-exercise have focussed on manipulating dietary macronutrient (carbohydrate and fat) content among athletes in an attempt to determine the impact on iron status and health of adopting low carbohydrate or ketogenic diets. However, iron status may not be the only concern when focusing on dietary changes in athletes. Research indicates that whole body health may be compromised by overall low energy availability and inadequate energy intake, a syndrome known as Relative Energy Deficiency in Sport (RED-S). In instances where energy intake has been reduced (intentionally to lose weight, or unintentionally) an athlete’s current dietary intake may not meet daily iron requirements. While the impact of metabolic disturbances, such as RED-S, on iron metabolism has not been directly investigated, results from nutritional interventions over the last decade have provided incidental evidence to support the notion of hepcidin as an early-onset marker of low energy availability (LEA). In fact, when athletes present with overall LEA they may not initially demonstrate low iron stores but may instead display altered iron metabolism, a response that may be due to exaggerated hepcidin activity.
