Mechanism of Decreased Iron Absorption in Obesity: Controlling Adiposity-related Inflammation

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.

Study Overview

• Status: Completed
• Conditions: Obesity
• Intervention / Treatment: Drug: Ibuprofen

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.

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Switzerland
  • Zurich, Switzerland, 8092
    • Human Nutrition Laboratory ETH Zurich

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: NON_RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: normal-weight; normal-weight women	Drug: Ibuprofen
EXPERIMENTAL: obesity; obese women	Drug: Ibuprofen

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fractional iron absorption	The fractional iron absorption from four test meals will be calculated based on the shift of the iron isotopic ratios in the collected blood samples 14 days after administration of the isotopically labeled meals. Calculation of fractional iron absorption will take into account the principles of isotope dilution and the fact that iron isotopic labels are not mono-isotopic. The investigators assumed iron incorporation into erythrocytes to be constant. Blood volume, needed for the calculation of fractional iron absorption will be estimated based on available data on blood volume estimations in obese women.	Days 15 and 45

Secondary Outcome Measures

Outcome Measure	Time Frame
Plasma ferritin	Days 1, 15, 30, 45
Hemoglobin	Days 1, 15, 30, 45
Transferrin receptor	Days 1, 15, 30, 45
Hepcidin	Days 1, 15, 30, 45
c-reactive protein	Days 1, 15, 30, 45
interleukin-6	Days 1, 15, 30, 45
alpha-1-acid-glycoprotein	Days 1, 15, 30, 45

Collaborators and Investigators

• Sponsor: Swiss Federal Institute of Technology
• Collaborators: University of Monterrey, Mexico
• Investigators: Principal Investigator: Isabelle Herter-Aeberli, PhD, University of Zurich

Study record dates

Study Major Dates

• Study Start (ACTUAL): April 1, 2016
• Primary Completion (ACTUAL): December 1, 2018
• Study Completion (ACTUAL): December 1, 2018

Study Registration Dates

• First Submitted: April 18, 2016
• First Submitted That Met QC Criteria: April 18, 2016
• First Posted (ESTIMATE): April 20, 2016

Study Record Updates

• Last Update Posted (ACTUAL): October 4, 2019
• Last Update Submitted That Met QC Criteria: October 3, 2019
• Last Verified: October 1, 2019

More Information

Terms related to this study

• Keywords: Inflammation; Hepcidin; Iron absorption; Iron bioavailability
• Additional Relevant MeSH Terms: Pathologic Processes; Overnutrition; Nutrition Disorders; Overweight; Body Weight; Obesity; Inflammation; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Ibuprofen
• Other Study ID Numbers: Fe_Abs_Ibu