(P44-38-26) Diurnal Variation of Serum Hepcidin and Its Association With Non-Heme Iron Absorption in Healthy Adults

Objectives: Hepcidin is the central regulator of systemic iron homeostasis. Human studies have reported diurnal variation in serum hepcidin, but evidence has been limited by small sample sizes and heterogeneous study designs. We aimed to characterize diurnal variation in serum hepcidin and determine whether accounting for this variation improves prediction of non-heme iron absorption in healthy males and females of East Asian or North European ancestry.

Methods: Using data from 504 healthy adults in the FeGenes study, we assessed the distribution of serum hepcidin, measured by a commercially available ELISA, and its diurnal fold change across the daytime. Multivariable regression models were used to examine associations between ferritin and hepcidin in morning (7am to 12pm, n=283) and afternoon samples (12pm to 6pm, n=221) and to test whether inclusion of a hepcidin × time interaction improved prediction of stable isotope-measured non-heme iron absorption. All analyses were performed in the pooled cohort, then stratified by ancestry and sex.

Results: In the pooled cohort, serum hepcidin increased on average by 1.8-fold across the sampling window (7am to 6pm), with concentrations increasing linearly over time (p < 0.001) and the lowest values observed in the early morning. The association between ferritin and hepcidin did not significantly differ between morning and afternoon samples in the pooled cohort. When the hepcidin × sampling time interaction was added to the previously developed multivariable model predicting non-heme iron absorption, a significant interaction was only observed among Northern European females (n = 128, p = 0.02), where inclusion of time interaction increased the captured variance by 3.7%. No significant interaction was observed in other ancestry–sex groups.

Conclusions: This cross-sectional study represents the largest population-based assessments of diurnal hepcidin variation to date. Findings suggest serum hepcidin exhibits clear diurnal variation, but these changes have minimal influence on the relationship between hepcidin and iron absorption in healthy adults.

Funding Sources: NIH NIDDK