The Effect of Different Prebiotics on Iron Absorption From High Dose Iron Supplements
Condition: Iron-deficiency
MeSH terms: Anemia, Iron-Deficiency; Iron Deficiencies
Study type: Interventional

Summary: 
      Iron deficiency (ID) remains the most common global nutrient deficiency, with young women at
      high risk. Iron supplements are first line treatment for ID but absorption is often low.
      Dietary components that could increase iron absorption would be valuable.

      Prebiotics are among the potential enhancers of non-heme iron absorption.
      Galacto-oligosaccharides (GOS), fructo-oligosaccharides and acacia gum are safe and
      widely-used prebiotics.

      To our knowledge, no studies have assessed the effect of acacia gum on iron absorption in
      human or animal models. Evidence exists about the enhancement of iron absorption when given
      in combination with FOS in rats. However, an iron stable isotope study in infants reported
      that 7.5 g of GOS improved iron absorption from 5 mg iron from a mixture of ferrous fumarate
      and sodium iron EDTA. In a recent iron absorption study in adult women with low iron stores
      in our lab we found that 15 g of GOS given with FeFum (14 mg of elemental iron) acutely
      increased iron absorption when given with water (+61%) and a meal (+28%).

      For prevention of anemia among non-pregnant women, the WHO recommends intermittent (once,
      twice or three times a week) oral iron supplementation with 60 mg of elemental iron. This has
      been shown to be effective, safe and acceptable for improving hemoglobin concentrations in
      women and lowering their risk of anemia. If GOS improves iron absorption from a higher dose
      of iron, and if FOS and acacia gum might also enhance iron absorption from FeFum is unclear.
      With this study we therefore aim to investigate if consumption of a single oral dose of 15 g
      GOS, FOS or acacia gum increase iron absorption from single 100 mg oral iron doses, a common
      amount found in supplements on the market for treatment of iron deficiency, given as ferrous
      fumarate in otherwise healthy iron depleted women.
    

Detailed description: 
      Prebiotics are defined as "microbial food supplements that beneficially affect the host by
      selectively stimulating the growth and/or activity of one or a limited number of bacterial
      species already resident in the colon". Moreover, prebiotics are potential enhancers of iron
      absorption, via several mechanisms: a) increasing gastric residence time allowing for greater
      iron dissolution; b) stimulating enterocyte gene expression of proteins involved in iron
      absorption; c) stimulating enterocyte proliferation providing a greater surface for iron
      absorption; and d) stimulating SCFA production by gut commensal bacteria, decreasing distal
      gut luminal pH and increasing iron dissolution.

      Galacto-oligosaccharides (GOS), a safe and widely-used prebiotic, are a mixture of glucose-
      and galactose-based di- and oligosaccharides of varying structure and may be more selectively
      utilized by Bifidobacterium spp. than other prebiotics. Fructo-oligosaccharides (FOS) are
      composed by 4 to 9 units of fructose alone or in combination with one unit of glucose. FOS
      are widely used as food ingredients/nutritional supplements due to their bifidogenic
      properties. Acacia gum is composed by highly branched galactan polymers with galactose and/or
      arabinose side chains, possibly terminated by rhamnose or glucuronic acid residues. Both
      in-vitro and in-vivo studies have shown that acacia gum supports bifidobacterial growth and
      short-chain fatty acids (SCFA) production in the large intestine.

      GOS and FOS have received GRAS status in the USA. Acacia gum is extensively used in the food
      industry for various functions (emulsification, encapsulation, stabilization, etc.). It is
      affirmed as "GRAS" for use in various food items. Acacia gum in human subjects is well
      tolerated up to 50 g/day. The European Food Safety Authority stated that there is no safety
      concern for the use of Acacia Gum as a food supplement.

      To our knowledge, no studies have assessed the effect of acacia gum on iron absorption in
      human or animal models. Evidence exists about the enhancement of iron absorption when given
      in combination with FOS in rats. In humans, studies so far have failed in showing an effect
      of FOS on iron absorption. However, an iron stable isotope study in infants reported that 7.5
      g of GOS improved iron absorption from 5 mg iron from a mixture of ferrous fumarate and
      sodium iron EDTA. Moreover, in a recent iron absorption study in adult women with low iron
      stores in our lab we found that 15 g of GOS given with FeFum (14 mg of elemental iron)
      acutely increased iron absorption when given with water (+61%) and a meal (+28%). In another
      study in our lab (unpublished data) we found that 7 g of GOS given with FeFum (14 mg of
      elemental iron) acutely increased iron absorption when given with water (+26%), in iron
      depleted women. These effects were found to be iron compound specific and could not be shown
      for ferrous sulfate, the iron compound used in the existing human studies with FOS.

      For prevention of anemia among non-pregnant women, the WHO recommends intermittent (once,
      twice or three times a week) oral iron supplementation with 60 mg of elemental iron. This has
      been shown to be effective, safe and acceptable for improving hemoglobin concentrations in
      women and lowering their risk of anemia.

      If GOS improves iron absorption from a higher dose of iron, and if FOS and acacia gum might
      also enhance iron absorption from FeFum is unclear. With this study we therefore aim to
      investigate if consumption of a single oral dose of 15 g GOS, FOS or acacia gum increase iron
      absorption from single 100 mg oral iron doses, a common amount found in supplements on the
      market for treatment of iron deficiency, given as ferrous fumarate in otherwise healthy iron
      depleted women.
    

Intervention name(s): ferrous fumarate; ferrous fumarate + 15 g GOS; ferrous fumarate + 15 g FOS; labelled iron as ferrous fumarate + 15 g acacia gum
Intervention type(s): Dietary Supplement; Dietary Supplement; Dietary Supplement; Dietary Supplement
Intervention description(s): iron (100 mg) supplement in form of ferrous fumarate; iron (100 mg) supplement in form of ferrous fumarate with addition of prebiotics (15 g GOS); iron (100 mg) supplement in form of ferrous fumarate with addition of prebiotics (15 g FOS); iron (100 mg) supplement in form of ferrous fumarate with addition of prebiotics (15 g acacia gum)
Intervention MeSH terms: Ferrous fumarate
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Single (Participant)
Primary purpose: Prevention
Keywords: iron-deficiency; Prebiotics; galacto-oligosaccharides; fructo-oligosaccharides; acacia gum