Iron deficiency has been reported to affect up to 36% of the athletic population. This condition has previously been attributed solely to exercise-induced iron losses (e.g. sweating, haematuria, gastrointestinal bleeding and haemolysis), often in combination with poor dietary intake. Recently, a new hormonal pathway has been discovered, involving the master iron regulatory hormone, hepcidin. Largely due to exercise- induced increases in interleukin-6 (IL-6), circulating hepcidin levels are subsequently increased, and have been shown to peak ~3-6 h post-exercise. When hepcidin levels are elevated above basal levels, iron recycling and absorption may be compromised. To date, most investigations studying these responses have used male participants where hormonal fluctuations in response to the menstrual cycle are not present. Additionally, these studies have also predominately been performed using weight-bearing exercise modalities (such as running) that are typically associated with increased haemolysis. Finally, it is also evident that these studies have generally been of an acute nature, thus ignoring the chronic influences of elevated hepcidin levels in athletic populations. Therefore, it was the aim of this thesis to examine if factors such as female hormonal fluctuations, weight-bearing vs. non-weight-bearing exercise, and exercise training conducted over an extended period of time might impact iron metabolism via hepcidin modulation.

Study One examined whether the different phases of an oral contraceptive cycle (OCC), regulated by exogenous oestradiol and progestogen from the monophasic oral contraceptive pill (OCP) affected post-exercise hepcidin responses in trained females (n=10). Here, a 40 min running trial was completed at 75% of peak oxygen uptake velocity (vVO_2peak) during two distinct phases of an OCC:​ (a) day 2-4, representing a hormone-free withdrawal period, and (b) day 12-14, representing the end of the first 4week of active hormone therapy. Results revealed that these different OCC phases did not appear to influence the post-exercise IL-6 and subsequent hepcidin response. Furthermore, no distinct changes in iron parameters were observed during the different OCC phases. Of importance, our results suggest that exercise undertaken during the different phases of an OCC do not appear to affect hepcidin regulation and iron metabolism. Finally, future studies seeking to explore similar variables may not need to control for different phases of an OCC, so long as participants are established monophasic OCP users.

Subsequently, Study Two compared the acute effects of weight-bearing (running) vs. non-weight-bearing (cycling) exercise performed at different intensities (high vs. low) on the post-exercise IL-6 and hepcidin response. Ten well trained male triathletes performed four 40 min exercise trials, which included:​ (a) low intensity continuous running at 65% v_2peak (L-R), (b) high intensity interval running at 85% vVO_2peak (H- R), (c) low intensity continuous cycling at 65% of the power output recorded at peak oxygen uptake (pVO_2peak) (L-C), (d) high intensity interval cycling at 85% pVO_2peak (H-C). The outcomes of this investigation showed that the levels of IL-6 were significantly elevated immediately post-exercise in all trials (p<0.05), and were not different between exercise modes. As a result, serum hepcidin levels were significantly elevated at 3 h post-exercise (p<0.05) in all trials, likely explained by the increases in IL-6. However, post-exercise serum iron levels were significantly elevated in all trials except for L-C, suggesting that low intensity non-weight-bearing exercise may reduce the degree of exercise-induced haemolysis. Regardless, despite any reductions in haemolysis associated with this form of low intensity activity, no effect on the iron parameters was apparent. Based on these findings, it would appear that the acute post-exercise hepcidin response remains similar after performing ~40 min of running or cycling at different 5intensities (high vs. low). These results highlight the potential for iron metabolism to be compromised in the acute post-exercise recovery period, potentially preventing individuals from replenishing any exercise-induced iron losses and ultimately causing a ̳negative iron balance‘.

Finally, Study Three compared the impact of weight-bearing vs. non-weight-bearing exercise sessions across a one-week period on hepcidin production and its potential impact on iron status. Ten active males performed a running (RTB) and cycling (CTB) training block that consisted of five exercise sessions within a seven day period. Corresponding RTB and CTB sessions were matched for both intensity and duration, and were constructed similarly to the typical exercise sessions that athletes might perform in their usual training environment. The exercise sessions were performed on day 1, 2, 4, 5, and 6, while days 3 and 7 were recovery days. For RTB, basal urinary hepcidin levels were significantly elevated at day 2 and on recovery days 3 and 7, as compared to day 1 (p<0.05). For CTB, although no statistical significance was recorded, moderate to large effect sizes suggested that basal hepcidin levels were higher on recovery days 3 and 7, as compared to day 1. These results highlight the potential for a series of exercise sessions to increase basal urinary hepcidin levels, especially if a weight-bearing activity is adopted (running). However, if non-weight-bearing exercise modalities are used, potentially longer duration and/or more exercise sessions might be required before any significant changes in basal hepcidin levels become apparent. Despite the trends for hepcidin levels to change during RTB and CTB, this did not appear to alter basal iron parameters (serum ferritin, iron, transferrin saturation) on recovery days 3 and 7 as compared to day 1. Nonetheless, such results may be due to the relatively short duration of this study (seven days) in comparison to the typical training calendar of athletes (e.g. over weeks/months), where decrements in iron status 6may be observed. Of importance, this study supports the proposition that a series of acute exercise sessions may have the ability to increase basal urinary hepcidin levels. Such events have the potential to alter iron metabolism, and may help explain the high incidence of iron deficiency in athletic populations.

In summary, the collective studies of this thesis examined the post-exercise hepcidin response under a variety of scenarios. These included the influence of exogenous OCP hormones, as well as performing weight-bearing vs. non-weight-bearing exercise, both acutely and over an extended training period. These studies have also highlighted potential mechanisms that might contribute towards exercise-induced iron deficiency in athletes. In summary, it is essential that service providers (such as physiologists, nutritionists and medical practitioners) and coaches remain vigilant in monitoring the iron status of their athletes (especially individuals with a history of iron deficiency), particularly during heavy training loads and the competitive season. This may help prevent iron status from falling to the critically low levels that are capable of compromising health and performance in athletes. Ultimately, these findings add to the limited information that currently exist regarding athletic-induced iron deficiency.