(P44-04-26) Energy Deficit Suppresses the Diurnal Increase in Serum Hepcidin: A Secondary Analysis of a Randomized Longitudinal Parallel Arm Trial

Objectives: Hepcidin is a diurnally regulated hepatic hormone that restricts iron absorption and availability. Declines in iron status in military personnel may result from hepcidin induction during energy deficits (energy intake < expenditure) experienced in training and operations characterized by high energy expenditures (≥3500 kcal/d). This study aimed to assess the effects of graded energy deficit severity (20, 40, 60%) on serum hepcidin and its diurnal rhythm. We hypothesized stepwise increases in hepcidin with deficit severity, independent of time of day.

Methods: In a secondary analysis of a randomized longitudinal parallel arm trial (NCT04910724), participants (n = 2F/28M, serum ferritin = 52.1 ± 43.8 ng/mL) representative of US Army Soldiers (age = 22.3 ± 4.7 y, BMI = 24.6 ± 2.5 kg/m², VO₂peak = 38.4 ± 4.6 mL/kg/min) completed 4 d of energy balance (BAL) via controlled energy intake (2690 ± 380 kcal/d) and exercise (560 ± 70 kcal/d), followed by 6 d of energy deficit (DEF) via reduced energy intake (20, 40, 60%; n = 10/group) and similar exercise to BAL. Dietary iron intakes during BAL and 20, 40, and 60% DEF were 20.2 ± 3.2, 15.7 ± 2.0, 11.6 ± 1.6, and 9.5 ± 1.4 mg/d, respectively (p-adj. ≤ 0.03 for all). Serum hepcidin was measured in the morning (AM) and 9 h later (PM) on BAL day 3 and DEF day 5. Linear mixed models assessed effects of treatment (BAL, DEF), group (20, 40, 60%), time (AM, PM), and their interactions. Data are means±SDs and α=0.05.

Results: Serum hepcidin was lower during DEF than BAL (p-treatment = 0.009) and did not differ by DEF severity (p-group = 0.60). Hepcidin increased diurnally during both BAL (29.5 ± 10.8 to 56.9 ± 31.8 ng/mL) and DEF (24.4 ± 14.0 to 38.3 ± 24 ng/mL, p-time < 0.001). A treatment×time effect was observed (p = 0.02) whereby the diurnal increase in hepcidin was 2-fold lower during DEF (+13.8 ± 12.6 ng/mL) than BAL (+27.4 ± 26.7, p-adj. < 0.001 for both).

Conclusions: Counter to the initial hypothesis, energy deficit suppressed hepcidin similarly between 20, 40 and 60% deficit. Unexpected findings may be attributable to relatively lower exercise energy expenditures compared to those observed in training and operations.

Funding Sources: Funded by the Military Operational Medicine Research Program. Views are not necessarily those of the US DoW, Army, or ARIEM.