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

Federal Institute of Technology (ETH) Zurich

Status

Completed

Conditions

Obesity

Treatments

Drug: Ibuprofen

Study type

Interventional

Funder types

Other

Identifiers

NCT02745925

Fe_Abs_Ibu

Details and patient eligibility

About

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.

Full 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.

Enrollment

40 patients

Sex

Female

Ages

18 to 45 years old

Volunteers

No Healthy Volunteers

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