Changes in Iron Absorption and Availability Before and After Weight Loss in Obese Pre-menopausal Women and Men.
Condition: Obesity
MeSH terms: Weight Loss
Study type: Observational

Summary: 
      The objective of this study is to investigate if weight loss, in particular due to adipose
      tissue loss, in obese patients will reverse the obesity-related reduction of iron absorption,
      and if this is due to a decrease in hepcidin concentrations. Additionally, the investigators
      will investigate changes in iron incorporation into erythrocytes due to a reduction of iron
      sequestration by the adipose tissue and reticuloendothelial system. The investigators expect
      that by decreasing adiposity, circulating hepcidin levels will decrease, iron absorption and
      incorporation into erythrocytes will increase and as a result iron status will be improved.
    

Detailed description: 
      Until now adiposity has been associated with low iron status and with higher hepcidin levels.
      Moreover, weight loss and thereby loss of fat mass, has been associated with decreased
      hepcidin levels and improved iron status. However, until now no direct measures of iron
      absorption or incorporation into erythrocytes have been assessed before and after losing
      weight/fat mass.

      We hypothesize that:

        -  body fat loss in obese women and men will improve iron absorption, corrected for iron
           status, from a labeled test meal measured by using a stable isotopes technique by on
           average 30%.

        -  body fat loss in obese women and men will decrease the related inflammatory state.

        -  greater subclinical inflammation in obese women and men will be correlated with a
           decreased incorporation of iron into erythrocytes, and that this will improve after loss
           of body fat.

      The study is a prospective cohort in which iron bioavailability will be assessed in obese
      women and men before and after weight loss and associated loss of body fat over a period of 6
      months.

      Iron absorption will be estimated using stable-isotope techniques where incorporation of 57Fe
      and 58Fe into erythrocytes is measured 14 days after administration. Preparation of
      isotopically labelled iron will be done at the Laboratory of Human Nutrition of the Swiss
      Federal Institute of Technology Zurich (ETH Zürich).

      A baseline venous blood sample will be drawn 6-8 weeks after the surgery when surgery-related
      inflammation has been resolved. The subjects will receive a test drink, containing 6 mg of
      57Fe labelled ferrous sulphate. One hour later, 2 ml of an aqueous solution containing 100 μg
      58Fe as iron citrate in 250 cc of normal saline will be infused over 50 min. This infusion
      protocol has been used safely and successfully to examine iron metabolism in both adults and
      infants. Fourteen days later, a second venous blood sample will be drawn. This procedure will
      be performed at baseline (6-8 weeks post-surgery) and at the end of the study (6 months post
      baseline).

      Our study could provide important information to establish the mechanism by which
      obesity-mediated inflammation could induce iron deficiency. This will be the first human
      trial that will evaluate if the obesity-related reduction of iron absorption is reversible in
      a context where obesity and iron deficiency are both highly prevalent.
    

Intervention name(s): Stable-isotope techniques
Intervention type(s): Other
Intervention description(s): Iron absorption will be estimated using stable-isotope techniques where incorporation of 57Fe and 58Fe into erythrocytes is measured 14 days after administration. The subjects will provide an initial blood sample (20ml) and then receive a test drink, containing 6 mg of 57Fe labeled ferrous sulphate. One hour later, 2 ml of an aqueous solution containing 100 μg 58Fe, as iron citrate in 250cc of normal saline will be infused over 50 min. Post infusion a 4ml blood sample will be taken. This procedure will be performed at baseline (6 weeks post-surgery) and at the end of the study (6-7 months post baseline).
Other intervention name(s): 57Fe ferrous sulphate; 58Fe iron citrate
Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Obese, premenopausal women and men aged 18 to 50 years after having undergone restrictive
        bariatric surgery.
      
Biospecimen description: 
      whole blood and serum