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

NCT ID: NCT02745925

Last Updated: 2019-10-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-04-30
• Study Completion Date: 2018-12-31

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.

Conditions

Obesity

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

normal-weight

normal-weight women

Group Type: EXPERIMENTAL

Ibuprofen

Intervention Type: DRUG

obesity

obese women

Group Type: EXPERIMENTAL

Ibuprofen

Intervention Type: DRUG

Interventions

Ibuprofen

Intervention Type: DRUG

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 45 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

University of Monterrey, Mexico

UNKNOWN

Sponsor Role: collaborator

Swiss Federal Institute of Technology

OTHER

Sponsor Role: lead

Responsible Party

Isabelle Herter-Aeberli

Dr.

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Isabelle Herter-Aeberli, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Zurich

Locations

Human Nutrition Laboratory ETH Zurich

Zurich, , Switzerland

Countries

Switzerland

Other Identifiers

Fe_Abs_Ibu

Identifier Type: -

Identifier Source: org_study_id