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Hepcidin is a Better Predictor of Iron Stores in Premenopausal Women than Blood Loss or Dietary Intake

View Article: PubMed Central - PubMed

ABSTRACT

The relationship between dietary intake, circulating hepcidin and iron status in free-living premenopausal women has not been explored. This cross-sectional study aimed to identify dietary determinants of iron stores after accounting for blood loss and to determine whether iron intake predicts iron stores independently of hepcidin in a sample of Australian women. Three hundred thirty eight women aged 18–50 years were recruited. Total intake and food sources of iron were determined via food frequency questionnaire; the magnitude of menstrual losses was estimated by self-report; and blood donation volume was quantified using blood donation records and self-reported donation frequency. Serum samples were analysed for ferritin, hepcidin and C-reactive protein concentrations. Linear regression was used to investigate associations. Accounting for blood loss, each 1 mg/day increase in dietary iron was associated with a 3% increase in iron stores (p = 0.027); this association was not independent of hepcidin. Hepcidin was a more influential determinant of iron stores than blood loss and dietary factors combined (R2 of model including hepcidin = 0.65; R2 of model excluding hepcidin = 0.17, p for difference <0.001), and increased hepcidin diminished the positive association between iron intake and iron stores. Despite not being the biggest contributor to dietary iron intake, unprocessed meat was positively associated with iron stores, and each 10% increase in consumption was associated with a 1% increase in iron stores (p = 0.006). No other dietary factors were associated with iron stores. Interventions that reduce hepcidin production combined with dietary strategies to increase iron intake may be important means of improving iron status in women with depleted iron stores.

No MeSH data available.


Effect of serum hepcidin on the relationship between dietary iron intake and natural log-transformed serum ferritin concentration, holding CRP, blood donation and menstrual losses at their mean values (CRP 0.67 mg/L, blood donation 400 mL/year, menstrual loss 104 arbitrary units, blood sampling at 11:15). The association between dietary iron intake and natural log-transformed serum ferritin is non-significant at 7.39 and 11.02 ng/mL (hepcidin concentrations > 11.02 ng/mL not depicted).
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nutrients-08-00540-f002: Effect of serum hepcidin on the relationship between dietary iron intake and natural log-transformed serum ferritin concentration, holding CRP, blood donation and menstrual losses at their mean values (CRP 0.67 mg/L, blood donation 400 mL/year, menstrual loss 104 arbitrary units, blood sampling at 11:15). The association between dietary iron intake and natural log-transformed serum ferritin is non-significant at 7.39 and 11.02 ng/mL (hepcidin concentrations > 11.02 ng/mL not depicted).

Mentions: Hepcidin data were available for 265 women. When the multivariate analyses were repeated in only these 265 women, no differences were observed in outcomes compared with the analyses that included 313 women (data not shown). There was a positive correlation between hepcidin and serum ferritin, with Spearman’s r = 0.67, p < 0.001. Including natural log-transformed hepcidin concentration in models increased the amount of explained variance in serum ferritin from 20% (Table 3) to 65% (Table 4). The relationship between log-transformed serum ferritin and hepcidin also remained when repeating the analysis (Table 4, Model A) in only the women who provided fasting morning samples (β for log-transformed serum hepcidin 0.86 (95% CI 0.72, 1.01)). Furthermore, dietary iron intake was no longer associated with iron stores when hepcidin was included as a covariate, although the positive association with total iron intake remained. We also explored interactions between dietary iron intake or total iron intake and circulating hepcidin in these models. Including an interaction of dietary iron intake (mg/day) × log-transformed hepcidin was found to be negative and statistically significant (β-0.030 (95% CI −0.053, −0.007)) and indicated that a positive association between dietary iron intake and iron stores was strongest when circulating hepcidin concentrations were low. This association remained when a variable indicating the location of recruitment (Sydney/Melbourne) was added to the model. Figure 2 displays this interaction at different levels of hepcidin concentration. The change in the slope of natural log-transformed serum ferritin on dietary iron intakes was predicted across the sample’s range of natural log-transformed hepcidin values from 0–3.2 (1–24.54 ng/mL) at intervals of 0.4, holding blood loss covariates at their mean. The positive association between dietary iron intake and log-transformed serum ferritin was strongest at 1 ng/mL hepcidin (i.e., greatest changes in slope), progressively weakening as the intervals of hepcidin concentrations increased. At 7.39, 11.02, 16.44 and 24.53 ng/mL hepcidin, there was no association between dietary iron intake and iron stores.


Hepcidin is a Better Predictor of Iron Stores in Premenopausal Women than Blood Loss or Dietary Intake
Effect of serum hepcidin on the relationship between dietary iron intake and natural log-transformed serum ferritin concentration, holding CRP, blood donation and menstrual losses at their mean values (CRP 0.67 mg/L, blood donation 400 mL/year, menstrual loss 104 arbitrary units, blood sampling at 11:15). The association between dietary iron intake and natural log-transformed serum ferritin is non-significant at 7.39 and 11.02 ng/mL (hepcidin concentrations > 11.02 ng/mL not depicted).
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC5037527&req=5

nutrients-08-00540-f002: Effect of serum hepcidin on the relationship between dietary iron intake and natural log-transformed serum ferritin concentration, holding CRP, blood donation and menstrual losses at their mean values (CRP 0.67 mg/L, blood donation 400 mL/year, menstrual loss 104 arbitrary units, blood sampling at 11:15). The association between dietary iron intake and natural log-transformed serum ferritin is non-significant at 7.39 and 11.02 ng/mL (hepcidin concentrations > 11.02 ng/mL not depicted).
Mentions: Hepcidin data were available for 265 women. When the multivariate analyses were repeated in only these 265 women, no differences were observed in outcomes compared with the analyses that included 313 women (data not shown). There was a positive correlation between hepcidin and serum ferritin, with Spearman’s r = 0.67, p < 0.001. Including natural log-transformed hepcidin concentration in models increased the amount of explained variance in serum ferritin from 20% (Table 3) to 65% (Table 4). The relationship between log-transformed serum ferritin and hepcidin also remained when repeating the analysis (Table 4, Model A) in only the women who provided fasting morning samples (β for log-transformed serum hepcidin 0.86 (95% CI 0.72, 1.01)). Furthermore, dietary iron intake was no longer associated with iron stores when hepcidin was included as a covariate, although the positive association with total iron intake remained. We also explored interactions between dietary iron intake or total iron intake and circulating hepcidin in these models. Including an interaction of dietary iron intake (mg/day) × log-transformed hepcidin was found to be negative and statistically significant (β-0.030 (95% CI −0.053, −0.007)) and indicated that a positive association between dietary iron intake and iron stores was strongest when circulating hepcidin concentrations were low. This association remained when a variable indicating the location of recruitment (Sydney/Melbourne) was added to the model. Figure 2 displays this interaction at different levels of hepcidin concentration. The change in the slope of natural log-transformed serum ferritin on dietary iron intakes was predicted across the sample’s range of natural log-transformed hepcidin values from 0–3.2 (1–24.54 ng/mL) at intervals of 0.4, holding blood loss covariates at their mean. The positive association between dietary iron intake and log-transformed serum ferritin was strongest at 1 ng/mL hepcidin (i.e., greatest changes in slope), progressively weakening as the intervals of hepcidin concentrations increased. At 7.39, 11.02, 16.44 and 24.53 ng/mL hepcidin, there was no association between dietary iron intake and iron stores.

View Article: PubMed Central - PubMed

ABSTRACT

The relationship between dietary intake, circulating hepcidin and iron status in free-living premenopausal women has not been explored. This cross-sectional study aimed to identify dietary determinants of iron stores after accounting for blood loss and to determine whether iron intake predicts iron stores independently of hepcidin in a sample of Australian women. Three hundred thirty eight women aged 18&ndash;50 years were recruited. Total intake and food sources of iron were determined via food frequency questionnaire; the magnitude of menstrual losses was estimated by self-report; and blood donation volume was quantified using blood donation records and self-reported donation frequency. Serum samples were analysed for ferritin, hepcidin and C-reactive protein concentrations. Linear regression was used to investigate associations. Accounting for blood loss, each 1 mg/day increase in dietary iron was associated with a 3% increase in iron stores (p = 0.027); this association was not independent of hepcidin. Hepcidin was a more influential determinant of iron stores than blood loss and dietary factors combined (R2 of model including hepcidin = 0.65; R2 of model excluding hepcidin = 0.17, p for difference &lt;0.001), and increased hepcidin diminished the positive association between iron intake and iron stores. Despite not being the biggest contributor to dietary iron intake, unprocessed meat was positively associated with iron stores, and each 10% increase in consumption was associated with a 1% increase in iron stores (p = 0.006). No other dietary factors were associated with iron stores. Interventions that reduce hepcidin production combined with dietary strategies to increase iron intake may be important means of improving iron status in women with depleted iron stores.

No MeSH data available.