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Background: Excess body iron (Fe) accrual is linked to chronic diseases. East Asian (EA) adults (median age 50 y) were reported to have higher Fe stores compared to other populations despite lacking the mutation that causes Fe overload in Northern European (NE) adults. It is unknown if these differences are evident in a healthy population under 50 y of age., Objectives: This cross-sectional study aims to compare Fe-related markers in young adults of EA and NE ancestry and identify determinants of Fe status., Methods: Participants were healthy United States males and premenopausal/nonpregnant females of genetically confirmed EA (n = 251) or NE (n = 253) ancestry, aged 18-50 y and without obesity. A complete blood count was obtained. Serum ferritin (SF; μg/L), c-reactive protein, and interleukin-6 were measured by immunoassay, and serum soluble transferrin receptor (mg/L) and transferrin by quantitative immunoturbidimetry. Total body Fe (mg/kg) was calculated. Elevated Fe stores were defined as SF >200 (females) or >300 (males) and c-reactive protein <5 mg/L. Results are shown as the geometric mean 95% confidence interval (CI) or mean ± standard deviation., Results: The mean age of the population was (26.3 y; 25.6, 26.9 y), with 69.2% of participants aged under 30 y. SF was higher in EA (172; 152, 194) compared with NE (85.3; 76.8, 94.8) males (P < 0.001), and in EA (42.6; 36.7, 49.5) compared with NE (31.9; 27.8, 36.5) females (P = 0.004). The prevalence of elevated Fe stores was 16.7% in EA compared with 0.8% in NE males (P < 0.001) and 1.6% in EA compared with 0% in NE females (P = 0.47). Total body Fe was higher in EA (11.7 ± 2.7) compared with NE (9.1 ± 2.6) males (P < 0.001) and in EA (6.7 ± 3.6) compared with NE (5.6 ± 3.4) females (P = 0.01). All differences persisted after adjustment for confounders (all P < 0.05)., Conclusions: Individuals of EA ancestry had a significantly greater body Fe burden compared to NE individuals. Of concern, these differences were evident in a cohort primarily consisting of young individuals aged 18-29 y. This trial was registered at clinicaltrials.gov as NCT04198545., Competing Interests: Conflict of interest The authors report no conflicts of interest., (Copyright © 2024 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)

Background: Individuals of East Asian (EA) ancestry have greater risk of elevated iron (Fe) stores compared with individuals of Northern European (NE) ancestry, but no studies have assessed differences in Fe regulatory hormones between these populations., Objectives: This study aimed to evaluate hepcidin, erythropoietin, and erythroferrone as a function of ancestry and examine their associations with Fe status markers in United States adults of genetically confirmed EA or NE ancestry., Methods: Participants in this cross-sectional study were healthy EA (n = 251) or NE (n = 253) males and premenopausal, nonpregnant females, aged 18-50 y, and without obesity. Serum hepcidin, erythropoietin, and erythroferrone concentrations were measured using ELISAs. Fe status [serum ferritin (SF), soluble transferrin receptor, total body iron, and transferrin], hematologic (complete blood count), and inflammatory (C-reactive protein and IL-6) markers were measured. Results are shown as the geometric mean (95% CI)., Results: Hepcidin (ng/mL) was significantly higher in EA (43.9; 95% CI: 39.6, 48.7) compared with NE (31.3; 95% CI: 28.4, 34.5) males (P < 0.001) but did not differ between EA (21.8; 95% CI: 19.4, 24.6) and NE (21.3; 95% CI: 19.0, 23.8) females (P = 0.66). Interestingly, the hepcidin:SF ratio was lower in EA males (0.26; 95% CI: 0.23, 0.28) and females (0.51; 95% CI: 0.46, 0.57) compared with NE males (0.37; 95% CI: 0.33, 0.40; P < 0.001) and females (0.65; 95% CI: 0.57, 0.73; P = 0.01), respectively. These differences remained significant after adjustment for C-reactive protein (males: P-adjusted < 0.001; females: P-adjusted = 0.008) or IL-6 (males: P-adjusted < 0.001; females: P-adjusted = 0.006). Erythropoietin did not differ between ancestry groups in males (P = 0.11) or females (P = 0.96). Lastly, erythroferrone (ng/mL) was higher in EA (1.3; 95% CI: 0.8, 1.9) compared with NE (0.6; 95% CI: 0.4, 0.9; P = 0.009) males but did not differ between females (EA: 0.7; 95% CI: 0.5, 1.1; NE: 0.5; 95% CI: 0.3, 0.7; P = 0.11)., Conclusions: A lower hepcidin:SF ratio in EA compared with NE participants suggests that among EAs, hepcidin concentrations are lower relative to the load of Fe present. Further studies are needed to elucidate the mechanisms underlying the observed differences. This study was registered at clinicaltrials.gov as NCT04198545., Competing Interests: Conflict of interest The authors report no conflicts of interest., (Copyright © 2024 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)

Background: Because humans lack mechanisms for excreting excess iron (Fe), dietary Fe absorption must be tightly regulated to ensure optimal Fe levels. We previously showed that East Asian (EA) individuals have higher Fe stores compared with Northern European (NE) individuals, but the physiological basis for this difference is unknown., Objectives: Our aim is to compare nonheme Fe absorption and its regulation in healthy participants of genetically confirmed EA or NE ancestry., Methods: Participants of this cross-sectional study were males and premenopausal, nonpregnant females of EA (n = 253) or NE (n = 251) ancestry, aged 18-50 y, and without obesity. Participants ingested a stable 57 Fe isotope as a FeSO 4 solution mixed with syrup. Percent Fe absorption was calculated based on erythrocyte 57 Fe enrichment 2 wk postdosing measured using magnetic sector thermal ionization mass spectrometry and normalized to a fixed serum ferritin (SF) level. Fe status traits (SF, soluble transferrin receptor, total body Fe), hormones (hepcidin, erythropoietin, erythroferrone), and inflammatory markers were evaluated., Results: SF-corrected % Fe absorption was higher in EA females [27.4 (95% confidence interval (CI): 23.4, 32.0)] and males [19.8 (95% CI: 14.9, 26.4)] compared with NE females [14.8 (95% CI: 11.8, 18.2)] and males [14.9 (95% CI: 11.8, 18.9)], respectively (both P < 0.001). Percent Fe absorption was consistently associated with hepcidin in EA males [β = -0.64; standard error (SE) = 0.24; P = 0.008] and females (β = -0.61; SE = 0.12; P < 0.001), and in NE males (β = -0.63; SE = 0.22; P = 0.005) and females (β = -0.71; SE = 0.14; P < 0.001). Percent Fe absorption was linearly associated with SF in EA females (β = -0.57; SE = 0.09; P < 0.001) and NE males (β = -0.73; SE = 0.21; P < 0.001) and females (β = -0.68; SE = 0.12; P < 0.001), but in EA males, a U-shaped relationship was observed (P = 0.003)., Conclusions: EA individuals have a greater SF-corrected Fe absorption compared with NE individuals. Increased Fe absorption and resulting excess Fe accumulation suggests that EA individuals may be at greater risk of Fe overload-related diseases. Further studies are needed to evaluate the long-term implications of these findings. This trial was registered at clinicaltrials.gov as NCT04198545., Competing Interests: Conflict of interest The authors report no conflicts of interest., (Copyright © 2024 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)