Iron Absorption and Losses in Young South African Women Living Without and With Overweight and Obesity

Linda Malan70 enrolled

Overview

Young women living with obesity (OB) have a greater risk of developing iron deficiency. Plus, the risk of anemia and/or ID in young women living with overweight (OW) and obesity (OB) is further increased by inadequate dietary intake and/or poor bioavailability of iron, as well as gastrointestinal and menstrual iron losses. It is not certain whether women living with OW/OB can meet their iron requirements from their day-to-day diet. The aim of this study is to compare iron absorption and losses over a long period between women living with and without OW and OB. Secondary outcomes include iron and inflammation status, as well as dietary iron intake.

Adiposity-related inflammation stimulates an increase in secretion of hepcidin hormone thus limiting the absorption of iron and increasing the risk for iron deficiency (ID). In addition, the risk of anemia and/or ID in young women living with overweight (OW) or obesity (OB) is further increased by inadequate dietary intake and/or poor bioavailability of iron, as well as gastrointestinal and menstrual iron losses. Although one study quantified iron losses and absorption in young African women using the stable isotope dilution method the focus was on normal-weight women. Thus, whether women living with OW/OB can meet their iron requirements from their habitual diet remains uncertain. This is a longitudinal study including an iron absorption study (Phase 1) and a follow-up period (Phase 2) in women living with and without OW and OB. In phase 1, 70 healthy, mildly- and non-anemic young women living with and without OW or OB will receive a test drink labelled with 15 mg of labelled ferrous sulfate (57Fe) (Visit 1). Fractional iron absorption from the test drink will be determined by measuring the incorporation of the isotopic label into red blood cells 14 days after administration (Visit 2), and will be compared between the two groups. Participants will then undergo a one-year equilibration period. During this time, they will be contacted monthly for an electronically completed, telephonic or in-person health check, chronic medication and supplement use,, blood donation or transfusion, and whether they have fallen pregnant. In addition, they will be asked if they are on a weight-loss diet, a urine pregnancy test done and weight and haemoglobin measured once every 3-4 months. Halfway through the equilibration period we will ask participants not taking hormonal contraceptives (and not intending to do so in phase 2 of the study), to track their menstrual cycle by providing them with a monthly paper- or electronic calendar. About 1 year after isotope administration, participants will be contacted again and screened (Visit 3) for phase 2 of the study. During this visit, a health and medical history check including the use of proton pump inhibitors,antacids, H2 blockers or iron supplements, contraceptive use and menstruation intensity will be conducted. Then, anthropometric measurements will be performed to determine BMI, and a urine sample collected for pregnancy test. If the participant qualifies to proceed with phase 2, they will be required to consume an antihelminthic dose. Phase 2 of the study will involve 4 visits (Visits 4 to 7), where they will be followed up for 6 months. During this time, blood samples will be drawn every 8 weeks for the determination of isotopic composition. In addition, iron and inflammation status will be assessed. Dietary intake will be assessed using three 24-hour recalls conducted within visits 4, 6 and 7. Additionally, for willing participants not using hormonal contraceptives and having a regular cycle (26 to 30 days), Visit 4 (or subsequent convenient visit) will be planned to coincide with day 2 of their menstrual phase where 6 ml of blood will be drawn to quantify sex hormones, hepcidin, iron and inflammation status and IL-6. These participants will be invited again during the follicular phase (day 7), early luteal phase (day 18) and late luteal phase (day 23) for additional blood samples. For each of these sampling points, a window period of +/- 1 day will be allowed.

Eligibility

Sex: FEMALEMin age: 18 YearsMax age: 35 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: * Of African descent * BMI of 18.5 to 24.9 kg/m2 for participants living without OW/OB and BMI ≥ 28 kg/m2 for participants living with OW/OB * Having low to moderate inflammation-adjusted iron stores (ferritin ≤50 µg/L) * Absence of low-grade inflammation (CRP\<2 mg/l) for participants living without OW/OB and presence of low-grade inflammation CRP 2-20 mg/l) for participants living with OW/OB * Planning to reside in the study area for at least 2 years Exclusion Criteria: * Hemoglobin \< 11 g/dl * Treated or self-reported chronic or malabsorptive disorder * Current use of chronic anti-inflammatory medication, like corticosteroids or non-steroidal anti-inflammatory medication * Pregnancy or planning to become pregnant in the next 2 years * Lactation * Fear of needles or experiencing vaso-vagal episodes when exposed to blood * Difficulty drawing blood due to poor quality veins * Blood donation in the past 4 months or plans to donate blood during the study * On a weight-loss diet or program or planning to start the same during the study * Smoking * Unwillingness to stop taking iron and /or vitamin C-containing supplements during phase 1 of the study * Regular use of antacids, proton pump inhibitors or H2 blockers Additional inclusion criteria applicable to phase 2 of the study * Labelled with stable iron isotope (tracer) for a minimum of one year * Willingness not to start or stop contraceptive use during the 6 months * BMI ≥ 18.5 to 24.9 kg/m2 for participants living without OW/OB and BMI ≥ 28 kg/m2 for participants living with OW/OB Additional exclusion criteria applicable to phase 2 of the study \- Blood transfusion, intravenous iron infusion, blood donation or significant blood loss during the equilibration period

Outcomes

Primary Outcomes

Iron absorption

Long-term iron absorption will be determined in, and compared between women living without and with OW/OB in Phase 2 of the study and will be proportional to the change in the concentration of iron isotope 57 in the erythrocyte over time.

Time frame: Visits 4 (day 373), 5 (day 429), 6 (day 485) and 7 (day 541)

Secondary Outcomes

Iron losses

Long-term iron losses will be determined in, and compared between women living without and with OW/OB in Phase 2 of the study and will be proportional to the change in the absolute amount of iron isotope 57 in the erythrocyte over time.

Time frame: Visits 4 (day 373), 5 (day 429), 6 (day 485) and 7 (day 541)

Iron balance

Iron balance will be calculated in and compared between women living without and with OW/OB as the difference between iron absorption and iron losses.

Time frame: Visits 4 (day 373), 5 (day 429), 6 (day 485) and 7 (day 541)

Fractional iron absorption

Fractional iron absorption from a single dose of 15 mg of isotopically-labeled iron will be compared between women living without and with OW/OB.

Time frame: Visit 2 (day 15)

Iron status

Iron status will be determined by measuring plasma ferritin and soluble transferrin receptor.

Time frame: Screening (Ferritin only), Visits 1 (day 1), 4 (day 373), day 378, day 389 and day 394], 5 (day 429), 6 (day 485) and 7 (day 541)

Inflammation status

Inflammation status will be determined by measuring plasma C-reactive protein (CRP) and alpha-1-acid glycoprotein. CRP will also be used to assess the absence or presence of low-grade inflammation at screening for phase 1 and visit 3, using a cut-off of \<2 mg/l and 2-20 mg/l, respectively.

Time frame: Screening (CRP only), Visit 1 (day 1), 3 (day 366;CRP only), day 378, day 389 and day 394] 4 (day 373), 5 (day 429), 6 (day 485) and 7 (day 541)

Dietary iron intake

Dietary iron intake will be assessed using 3 x 24 hr recalls within visits 4, 6 and 7.

Time frame: Visits 4 (day 373), 5 (day 429), 6 (day 485) and 7 (day 541)

Laboratory comparison of measurement of red blood cell isotope concentrations

Iron isotope concentration measurements will be compared between the laboratories at North-West University and the Swiss Federal Institute of Technology Zurich.

Time frame: Visit 2 (day 15), 4 (day 373), 5 (day 429), 6 (day 485) and 7 (day 541)

Dietary intake of iron absorption enhancers

Dietary intake of iron absorption enhancers like vitamin C will be determined using 3 x 24-h recalls questionnaire conducted within the scheduled visit

Time frame: Visits 4 (day 373), 6 (day 485) and 7 (day 541)

Dietary intake of iron absorption inhibitors

Dietary intake of iron absorption inhibitors like phytic acid will be determined using 3 x 24-h recalls questionnaire conducted within the scheduled visit

Time frame: Visits 4 (day 373), 6 (day 485) and 7 (day 541)

Body fat percentage

Body fat percentage will be assessed using the deuterium dilution technique and/or bioelectrical impedance analysis or the bodpod

Time frame: Screening, Visits 4 (day 373), 5 (day 429), 6 (day 485) and 7 (day 541)

Waist circumference

Waist circumference will be measured as an indicator of body fat distribution.

Time frame: Screening, Visits 4 (day 373), 5 (day 429), 6 (day 485) and 7 (day 541)

Hip circumference

Hip circumference will be measured as an indicator of body fat distribution.

Time frame: Screening, Visits 4 (day 373), 5 (day 429), 6 (day 485) and 7 (day 541)

Liver function

Liver function will be assessed by measuring alanine transaminase and aspartate transaminase enzymes.

Time frame: Screening

Gut inflammation

Gut inflammation will be assessed by measuring gut integrity and inflammation biomarkers namely Intestinal fatty acid-binding protein (IFABP) and soluble cluster of differentiation 14 (sCD14).

Time frame: Screening

Menstruation intensity

Menstruation intensity will be assessed using a self-administered health diary

Time frame: Day 373 to day 541

Haemoglobin

Haemoglobin measurement will be compared between a point-of-care device (Hemocue) and an automated haematology analyser

Time frame: Screening

Oestradiol

17-beta oestradiol will be measured on days 2, 7, 18 and 23 of the menstrual cycle. The day 2 sample will align with visit 4 or the next convenient scheduled visit.

Time frame: Visit 4 (day 373), day 378, day 389 and day 394

Progesterone

Progesterone will be measured on days 2, 7, 18 and 23 of the menstrual cycle. The day 2 sample will align with visit 4 or the next convenient scheduled visit.

Time frame: Visit 4 (day 373), day 378, day 389 and day 394

Iron Absorption and Losses in Young South African Women Living Without and With Overweight and Obesity

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts