Clinical trial NCT02745925: Mechanism of Decreased Iron Absorption in Obesity: Controlling Adiposity-related Inflammation
Official title: Mechanism of Decreased Iron Absorption in Obesity: Controlling Adiposity-related Inflammation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Obesity
Keywords: Iron bioavailability
Inflammation
Hepcidin
Iron absorption
Lead sponsor: Swiss Federal Institute of Technology
Sponsor class: OTHER
Collaborators: name: University of Monterrey, Mexico
First posted: 2016-04-20
Enrollment: 40
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: The main iron regulatory protein in the human metabolism is hepcidin. In normal weight, healthy subjects, hepcidin is regulated through the iron status of the body: low iron status results in low hepcidin concentrations, which facilitates dietary iron absorption. In obesity, which is an inflammatory state, hepcidin concentrations are increased and iron absorption is reduced despite low iron stores, leading to iron deficiency over time. Whether lowering the chronic low-grade inflammation during a limited treatment period and thereby lowering hepcidin concentration can improve iron absorption is uncertain.

Detailed description: In states of high hepcidin concentration, intestinal iron absorption (through enterocytes) and recycling of iron (through macrophages) is reduced. The extent to which non-heme iron is absorbed from the diet is influenced by the composition of the diet. Ascorbic acid is a potent enhancer of non-heme iron absorption. It's mechanism of action is luminal reduction of dietary ferric iron (Fe3+) to more soluble ferrous iron (Fe2+). A study in the inestigator's laboratory showed that the enhancing effect of ascorbic acid on non-heme iron absorption is reduced in overweight and obese individuals. Possible explanations for this fact are the different sites of action of ascorbic acid and serum hepcidin on the enterocytes in dietary iron absorption. Increased hepcidin reduces iron efflux into the circulation at the basolateral membrane of the enterocyte. Therefore the improved iron transport into enterocytes through ascorbic acid at the luminal side (via the divalent metal transporter (DMT)-1), by reducing Fe3+ to Fe2+ seems to be less successful. To improve iron absorption in obese subjects, an intervention at the basolateral membrane of the enterocyte would be needed.

Eligibility criteria: Inclusion Criteria:

* normal-weight (BMI18.5-24.9kg/m2) or obesity (BMI 29-40kg/m2)
* pre-menopausal
* no chronic illness and no significant medical conditions that could influence iron or inflammatory status other than obesity
* no-smoking

Exclusion Criteria:

* Diagnosed chronic disease or gastrointestinal disorders
* Metabolic disorders (e.g. diabetes)
* Regular use of medication (except oral contraceptives)
* Subject on a weight loss diet or planning to start a weight loss diet during the duration of the study
* Pregnancy or lactation

Primary outcomes:
measure: Fractional iron absorption
timeFrame: Days 15 and 45
Secondary outcomes:
measure: Plasma ferritin
timeFrame: Days 1, 15, 30, 45
measure: Hemoglobin
timeFrame: Days 1, 15, 30, 45
measure: Transferrin receptor
timeFrame: Days 1, 15, 30, 45
measure: Hepcidin
timeFrame: Days 1, 15, 30, 45
measure: c-reactive protein
timeFrame: Days 1, 15, 30, 45
measure: interleukin-6
timeFrame: Days 1, 15, 30, 45
measure: alpha-1-acid-glycoprotein
timeFrame: Days 1, 15, 30, 45
Other outcomes:
Locations:
city: Zurich
country: Switzerland
facility: Human Nutrition Laboratory ETH Zurich
Study officials:
affiliation: University of Zurich
name: Isabelle Herter-Aeberli, PhD
role: PRINCIPAL_INVESTIGATOR
References: