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Hepcidin and The Management of the Athlete’s Iron Status

Risk of low iron status, effect on performance and best practice guidelines for athletes

The major function of iron in the body is in the formation of haemoglobin and other compounds that are essential for the transport and utilization of oxygen. Iron is also an important requisite component of cytochromes and enzymes within the mitochondria, making iron an essential component for brain development and cognitive performance in athletes.

It is well known that athletes are at greater risk of iron deficiency than the general population. For the athlete, the reduction of iron stores could have effects on the capacity for oxygen transport, athlete motivation, concentration and hence decision making during play. Therefore, iron levels in athletes should be managed to ensure their performance is maximized. In the management of body iron levels, it is important to understand the role of the hormone hepcidin in iron metabolism.

The Role of Hepcidin in Iron Metabolism

Fairly recently, scientists have discovered the hormone Hepcidin, which regulates systemic iron homeostasis. Circulating high levels of this hormone:

…all with the aim to reduce iron stores to prevent overload, which has adverse effects on the body.

Hepcidin production is increased by:

Hepcidin production is reduced when:

It is well now that exercise causes an inflammatory response. One of the end results of this is increases in Interleukin-6 (IL-6), in turn increasing the production of hepcidin, which causes a reduction in iron absorption.

Hepcidin levels peak approximately 3–6 hours after exercise. Therefore, heavy and frequent exercise training bouts may put the athlete at further risk of iron deficiency.

athlete having a restAcute high intensity or endurance exercise increases Hepcidin production

Exercise Modality on Hepcidin Changes

All of the following papers showed significant elevation of hepcidin levels post-exercise with the listed exercise regimes:

The bottom line is: The longer the duration of exercise or the greater the intensity the greater the impact on the rise of hepcidin levels.

Current Iron Status on Hepcidin Changes

Baseline iron status appears to play a dominant role in the regulation of hepcidin. The greater the baseline iron stores the more magnified the post-exercise hepcidin response will be. Serum ferritin concentration has the largest effect (~47%), and serum iron levels (~39%) of the underlying variation (Peeling et al. 2017).

Low iron stores can cause a downregulation of hepcidin synthesis to encourage iron absorption and recycling, which is the body’s protective response to help to improve iron status. Athletes with sub-optimal iron stores (serum ferritin ~30–50 μg/L) may be at greatest risk, as they will generate post-exercise hepcidin elevation and compromise their ability to absorb dietary iron intake (Peeling et al. 2017).

Different Nutrient Influences on Hepcidin

There has been some previous evidence that Vitamin D supplementation can affect hepcidin levels in non-athletic populations. Recently though, Dahlquist et al. (2017) studied the effects of CHO, PTN, Vitamin D, and Vitamin K supplementation on hepcidin response in athletes.  Vitamin D did not affect hepcidin in this research, possibly due to the shorter supplementation period used, the lower dosage used than previous studies, as well as the fact that all the athletes in the study were Vitamin D sufficient, and not deficient as has been in previous studies. More research is required in this area, however the potential for a downstream effect on iron status is exciting (Pedlar et al 2018).

Post-exercise carbohydrate ingestion does not appear to impact post-exercise interleukin-6 and hepcidin responses (Badenhorst 2015).

Iron supplements acutely increase hepcidin production. Therefore, providing lower dosages (40-80 mg Fe) and avoiding twice-daily dosing can maximise fractional absorption. The duration of the hepcidin response supports alternate day supplementation, but longer-term effects of these schedules require further investigation (Moretti et al. 2015).

The Female Effect

Females are at particular risk of iron deficiency due to blood loss during menstruation, especially those with heavy bleeding.

The menstrual cycle influences the hepcidin response

The menstrual cycle influences cytokine production, causing inflammation at different times in the female athlete cycle (Pedlar 2018) influencing the hepcidin response.

Screening Recommendations

Sports Science and Sports Medicine disciplines working with athletes or a team of athletes need to be aware of an athletes’ iron status, to best manage health and performance, since both are affected with low iron stores. To achieve the best management of this situation, the following is a recommendation of what should be implemented:

Main Findings and Practical Consequences


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