Understanding dietary and fortificant iron: The devil is in the detail Sylvaine Bruggraber Nutritionist In Industry London, 4 th November 2010 Structure 1. Dietary Iron: 2. Fortificant 3. Bioavailability 4. Biofortification Iron in the UK diet Haem & non-haem Where are they? What are they? Problems Tools for bioavailability Inhibitors and enhancers Definition New findings 1
1. Dietary Iron 1. Dietary Iron - UK diet Main contributors to the average household intake of iron in the UK in 2007, DEFRA Dairy & eggs 4% vegetables 15% Beverage 5% others 7% cereals 48% fruits 5% meat & fish 16% 2
1. Dietary Iron - Haem iron Main contributors to the average household intake of iron in the UK in 2007, DEFRA Dairy & eggs 4% vegetables 15% Beverage 5% others 7% cereals 48% fruits 5% meat & fish 16% Haem iron Haemoglobin (blood) Myoglobin (muscle) 1. Dietary Iron - Haem iron Apical (lumen) Haem HCP1 Basolateral (plasma) 3
1. Dietary Iron Non-haem iron Main contributors to the average household intake of iron in the UK in 2007, DEFRA Dairy & eggs 4% vegetables 15% Beverage 5% others 7% cereals 48% Non-haem iron Fe complexes fruits 5% meat & fish 16% Haem iron Haemoglobin (blood) Myoglobin (muscle) 1. Dietary Iron Non-haem iron Compiled from Briat et al, Curr Opin Plant Biol, 2007 4
1. Dietary Iron Non-haem iron Apical (lumen) I Iron deficiency (4 billion) Dcytb DMT1 Haem 6.6 billion HCP1 Basolateral (plasma) 1. Dietary Iron Contains ~ 4500 Fe atoms Ferrous sulphate Kalgaonkar S et al. 2009, J N Biochem;20:304-11 5
1. Dietary Iron Breakdown Breakdown Incomplete breakdown Dissolution Uptake Uptake Uptake Bo Lönnerdale, Am J Clin Nutr 2009;89(Suppl):1680S-5S 1. Dietary Iron > > 69% 62% 52% Lentils Yellow peas Green peas > 38% > > 29% 15% Soybeans Pinto beans Red kidney beans Hoppler et al. Analytical Chemistry, published online 2009 6
2. Fortificants Top 20 contributors of iron Food Name Iron (mg) BREAD WHITE SLICED 5281.554 WEETABIX & OTHER WHOLEWHEAT BISKS 3970.292 IRON TABLET 500mg 3500 WINE RED NOT CANNED 2845.269 BREAD WHITE TOASTED 2790.149 BREAD WHOLEMEAL 2757.71 IRON TABLET/CAPSULE 200mg 2600 FERROUS SULPHATE TABLETS 200MG 2580 CORN FLAKES KELLOGGS ONLY 2566.592 BEANS BAKED CANNED 2367.511 POTATOES NEW BOILED SKINS EATEN 2330.998 BRANFLAKES KELLOGGS ONLY 1711.133 ROLLS WHITE SOFT 1632.434 ASDA MULTIVITAMINS AND IRON 1344 SPECIAL K KELLOGGS 1232.5 POTATOES OLD BAKED FLESH & SKIN 1230.256 MUESLI EG. ALPEN WITH ADDED SUGAR 1095.102 CRUNCHY NUT CORNFLAKES KELLOGGS & 1025.145 COFFEE INSTANT POWDER OR GRANULES 1007.17 7
Changes in Iron content of breakfast cereals 150 % change in iron content (2000-1980s) 125 100 75 50 25 0-25 -50-75 -100-125 -150 Bran flakes Rice cereal, toasted and crisped Cornflakes, honey and nut-coated Cornflakes Wheat and rice cereal flakes High-fibre wheat bran cereal Porridge, instant Rice cereal, chocolate-covered Muesli, Swiss-style Shredded wholegrain wheat cereal biscuits Unpublished in preparation 2. What is fortification iron? Elemental iron (reduced, electrolytic, carbonyl) Iron chelates: bis-glycinates FeNa 2 EDTA Pyrophosphate 8
2. Fortificant absorption Apical (lumen) I Iron deficiency (4 billion) Dcytb DMT1 Haem 6.6 billion HCP1 Basolateral (plasma) 2. Fortificant absorption formation Wortley et al. British Journal of Nutrition (2005), 93, 65 9
2. Fortificant absorption Iron availability Wortley et al. British Journal of Nutrition (2005), 93, 65 Iron deficiency (4 billion) 6.6 billion 3. Bioavailability 10
3. Bioavailability Apical (lumen) Basolateral (plasma) Ferroportin (IREG1) Hephaestin I 3. Bioavailability - How? Predictability Human Animal in vitro (digestion/caco2) Algorithm High-throughput 11
3. Bioavailability - Host factors Ascorbic acid I Low luminal ph (5.5) Dcytb + DMT1 Iron status Infection Inflammation Hepcidin Ferroportin (IREG1) - Hephaestin I 3. Bioavailability - Food factors I Dcytb DMT1 A- Multi-nutrient interactions B- Nutrient-gene interactions Ferroportin (IREG1) Hephaestin I 12
A- Multi-nutrient interactions (luminal) lumen I Food/ diet Dcytb DMT1 Iron Bioavailability (absorption) A- Multi-nutrient interactions (luminal) Vit C Tannin More Fe absorption Less Fe absorption Promoters: Meat (meat effect) Citric acid inhibitors: Polyphenol Phytic acids (fibres) 13
A- Multi-nutrient interactions (luminal) Inhibitors I Dcytb DMT1 A- Multi-nutrient interactions (luminal) I Enhancers Dcytb DMT1 14
A- Multi-nutrient interactions - Ferrous sulphate (Fe 2+ ) Kalgaonkar S and Lönnerdal B, J Nutr Biochem 2008;19:33-39 B- Nutrient-gene interactions (intracellular) I Dcytb DMT1 - Fe (DMT1/Dcytb mrna) - Ca (ferritin formation) Ferroportin (IREG1) Hephaestin I + Ascorbic acid (short term) - Ascorbic acid (long term) 15
3. Bioavailability - Fortificant Low reactivity with food Low bioavailabiltiy Staple cereal flours High phytate (inhibitors) 3. Bioavailability - Fortificant Elemental iron (reduced, electrolytic, carbonyl) Iron chelates: bis-glycinates FeNa 2 EDTA Encapsulated (e.g. Lecithin) Pyrophosphate Nano-sized 16
4. Biofortification 4. Biofortification Increasing available iron in staple crops: selection of naturally iron rich cultivars, genetic modification fertilization Increase ferritin / decrease phytate Obtain concentration with biological impact 17
4. Biofortification Predictability Human Animal in vitro (digestion/caco2) Algorithm High-throughput Screening of foods for Fe bioavailability Caco-2 cell model predict direction of response BUT not magnitude 4. Biofortification Bioavailability2010, Pacific grove CA, USA September Increased iron is not ferritin iron (beans) Increased iron is not iron-phytate (beans and lentils) Iron polyphenols Fe speciation in plant to develop biofortification strategies 18
Summary Iron bioavailability is dictated by its chemical speciation in the food but also in the gut lumen may be an important iron source in our diet and may not be absorbed through the previously described pathways Biofortification strategies rely on understanding natural non-haem iron. What are the nutritionally relevant iron compounds in our diet? Should we be building fortificant and supplemental iron with more relevance to dietary iron? 19