Direct assessment of body iron balance in women with and without iron supplementation using a long-term isotope dilution method in Benin and Switzerland

Abstract

Background Long-term isotopic dilution measurements of body iron may allow quantification of basal body iron balance and iron gains during an iron intervention with higher precision and accuracy than conventional iron indices. Objectives We compared body iron balance before, during, and after oral iron supplementation in women in Benin and in Switzerland. Methods In prospective studies, Beninese (n = 11) and Swiss (n = 10) women previously labeled with stable iron isotopes were followed preintervention for 90–120 d, then received 50-mg iron daily for 90–120 d and were followed postintervention for 90–120 d. We used changes in blood isotopic composition to calculate iron absorption (Feabs), iron loss (Feloss), and net iron balance (Fegain). Results Compliance with supplementation was >90%. In Benin, during the preintervention, intervention, and postintervention periods, Fe means ± SDs were as follows: 1) Feabs: 0.92 ± 1.05, 3.75 ± 2.07, and 0.90 ± 0.93 mg/d; 2) Feloss: 1.46 ± 1.95, 1.58 ± 1.57, and 1.84 ± 1.61 mg/d; and 3) Fegain: −0.55 ± 1.56 mg/d, 2.17 ± 1.81 mg/d, and −0.94 ± 1.13 mg/d. In Switzerland, the corresponding values were: 1) 1.51 ± 0.37, 4.09 ± 1.52, and 0.97 ± 0.41 mg/d; 2) 0.76 ± 1.37, 2.54 ± 1.43, and 2.08 ± 1.05 mg/d; and 3) 0.75 ± 1.37, 1.55 ± 1.75, and −1.11 ± 1.06 mg/d. Inflammation was low in both settings, and isotopically calculated iron balance was comparable to that calculated from changes in conventional iron indices. Conclusion Without iron supplementation, Beninese women had lower long-term dietary iron absorption and higher iron losses in the preintervention period than Swiss women. During iron supplementation, both groups had high iron absorption and similar iron gains. However, there was a 3-fold increase in iron losses in the Swiss women during the supplementation and postintervention period compared with the preintervention period. Body iron isotope dilution is a promising new method for quantifying long-term body iron balance and for assessing the impact of iron interventions. The studies were registered at clinicaltrials.gov as NCT02979080 and NCT02979132, respectively.

Stable iron (58Fe) isotopic measurements in Kenyan toddlers during 3 months of iron supplementation demonstrate that half of the iron absorbed is lost

“…The study populations, the iron compound provided, the daily iron dose, the daily median iron absorbed and lost per kg BW from our study and all the other long-term isotopic studies with iron supplementation are listed in Table 4. 7,8 There was no significant difference in the distributions of individual daily iron losses between Kenyan and Gambian toddlers (p = 0.09). Expressed in terms of body weight, daily iron loss was correlated significantly with iron absorption (r = 0.66 [95% confidence interval 0.48-0.78]) but not with iron dose (r = 0.16 [95% CI −0.10 to 0.40]) in our study, in Gambian toddlers and in women in Benin and Switzerland.…”

“…We conducted the study between February and May 2021 in rural Kwale County, Kenya. To study children who had enriched and equilibrated body iron isotopic composition, 2,4,8 we recruited children who previously participated in stable iron isotope studies between July 2019 and January 2020. The designs of the two studies and details of the sample size calculation are provided in Supplemental Material (Data S1).…”

“…7 Subsequently, similar results were observed in iron-depleted Swiss women given iron supplements, in whom iron loss increased almost threefold during supplementation compared to the preintervention period. 8 In these studies, the source of the increased iron loss during supplementation was not identified. Body iron loss is not regulated and mainly results from cell desquamation; iron loss cannot be increased physiologically even in the presence of iron overload.…”

“…2 Episodic occult gastrointestinal blood loss caused by iron supplements was a potential source of the increased iron loss in the above studies. 7,8 Excess unabsorbed iron in the gut can cause iron-induced oxidative damage, mucosal irritation, inflammation and bleeding. [9][10][11] Therefore, the present study in Kenyan toddlers was designed to assess potential iron-induced gastrointestinal blood loss as the source of increased iron loss during supplementation.…”

Preparatory work for the update of the tolerable upper intake levels for iron

“…Under further detailed data extraction for Forest plot generation and further quantitative evaluation, three studies were excluded as two studies did not comprise an adequate control group. In one case, both groups received iron, one with ascorbic acid, the other received iron without ascorbic acid and in the other case, both groups received iron, just different by the place of intervention (Benin and Switzerland) (Speich et al, 2021). The third study excluded was identified to be an outlier under statistical evaluation, excluded by the responsible statistician.…”