Micronutrient Enhancement. Sherry A. Tanumihardjo Department of Nutritional Sciences University of Wisconsin-Madison, Wisconsin, USA
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1 Micronutrient Enhancement through Biofortification Sherry A. Tanumihardjo Department of Nutritional Sciences University of Wisconsin-Madison, Wisconsin, USA
2 Distribution of 10.9 million deaths among children less than 5 years old in all developing countries, 2000 Diarrhoea 12% HIV 4% Malaria 8% Measles 5% Perinatal 22% Malnutrition 60% ARI 20% Other 29%
3 Current dimensions of major forms of malnutrition Intra-uterine growth retardation 30 million/year (23.8% of all births) Low birth weight Brain damage Protein-energy malnutrition 159 million under-5 children Iodine deficiency disorders 740 million Vitamin A deficiency 250 million under-5 children Anaemia including iron deficiency 2 billion Obesity >300 million people Increased morbidity & mortality Brain damage Blindness Increased morbidity & mortality Increased morbidity & mortality Impaired motor development Reduced physical activity CVD & Diabetes WHO/NHD
4 Functional and storage iron Hemoglobin (85%) - iron containing pigment in RBCs Myoglobin (5%) - holds oxygen in muscle tissue Cytochromes - enzymes important in cellular respiration Iron sulfur proteins - important in electron transport Transferrin - iron carrying protein in the blood Serum ferritin - iron storing protein also found in liver, spleen and bone marrow Hemosiderin derived from hemoglobin and can be reused Enzyme cofactor - peroxidase, catalase DNA synthesis - ribonucleotide reductase
5 Symptoms of iron deficiency anemia Pallor Weakness Fatigue Dyspnea Palpitations Reduced work capacity Short attention span
6 Functions of vitamin A Ross et al. (2000) Physiol. Rev. 80:
7 Xerophthalmia classification XN X1A XB X1B X2 X3A X3B XF XS Nightblindness Conjunctival xerosis Bitot s spot Bitot s spot with conjunctival xerosis Corneal xerosis Corneal ulceration with xerosis Keratomalacia Xerophthalmia fundus Corneal scars CAN LEAD TO BLINDNESS!
8 Examples of eye signs Bitot s spots Blindness
9 The Interim High Dose Supplements
10 Why are we supplementing women and children? Vitamin A status is compromised for both mothers and infants in many developing countries. Most sources of vitamin A are derived from fruits and vegetables and the β-carotene is perceived to not be available.
11 Effects of vitamin A supplementation in populations with vitamin A-deficiency Reduced mortality in children <5 years by 23% (meta-analysis of 7 studies) Reduced mortality in pregnant women by 40% Reduced severity but not incidence of much respiratory and gastrointestinal disease Reduced incidence of malarial attacks by 30% Beaton et al. Geneva: ACC/SCN, Shankar et al. Lancet 1999;354: West et al. BMJ 1999;318:
12 Supplements alone are not enough! Tanumihardjo, et al., EJCN 2004
13 Dietary diversification Teach them how to garden!
14 Food β-c total β-c freed Tanumihardjo, IJVNR 72: 41, 2002 Intestinal wall Bioaccessibility = β-c freed /β-c total Bioavailability = β-c absorbed / β-c total β-c absorbed Retinal Cleaved Bioconversion = Retinol / β-c absorbed Reduced Retinol Bioefficacy = Retinol / β-c total
15 The bottom line All things in moderation except vegetables!
16 Fortification Addition of minerals or preformed vitamin A to commonly consumed foods, such as salt, sugar, maize flour, rice and wheat.
17 Worldwide: Costs of Interventions to Reduce Micronutrient Malnutrition 500 million vitamin A capsules distributed annually cost of $500 million $200 million public investments in salt iodine fortification leveraged $1.5 billion in private industry contributions over a decade $2 per person per year for iron fortification of rice x 500 million people x 10 years = $10 billion
18 Nicaraguan sugar fortification Evaluation of baseline liver retinol reserves were 0.57 µmol/g liver, well above deficient (0.07 µmol/g liver). One year after sugar fortification was implemented, liver reserves increased to 1.2 µmol/g liver. In 9 of 21 children, liver vitamin A concentrations were >1.05 µmol/g liver.
19 Biofortification Greek word bios means life Latin word fortificare means make strong MAKE LIFE STRONG!
20 A new methodology? 1000 years ago 400 years ago <400 years ago <30 years ago 2007!!!
21 Poverty as it relates to hidden hunger Poverty Hunger Food insecurity Overnutrition? Nutrient deficiencies Hidden hunger Obesity Diets high in staple foods!!! Tanumihardjo et al., JADA, 2007
22 Advantages of Biofortification Targets the poor: eat high levels of food staples Rural-based: complements fortification and supplementation Cost-effective: research at a central location can be multiplied across countries and time Sustainable: investments are front-loaded, low recurrent costs
23 Interdisciplinary Communication and Cooperation is Essential Plant Breeders Molecular Biologists Food Technologists Human Nutritionists Extensionists Experts in Food Product Development/Marketing Communications Economists
24 Orange-fleshed sweet potato Vitamin A equivalency factors: Sweet potato: ~13:1 Indian spinach: ~10:1 Haskell et al. Am J Clin Nutr β-carotene: ~6:1 2004
25 South African Trial Supervised feeding with 1 mg RAE OFSP versus 0 RAE WFSP
26 Change in liver stores of vitamin A Intervention Control Intervention effect: (-0.015, ) P =
27 Infants eating sweet potato 0.8 Liver vitamin A accum mulation (µmol/g) ? Sweet potato Sweet potato Tablets or sachets Age of child (mo) Sachets or tablets Tanumihardjo, Comp. Rev. Food Sci. & Food Safety, 2008;7:
28 Sweet potato in Mozambique Effectiveness study using an integrated agricultural and nutrition intervention 2 year intervention covering 2 agricultural cycles 90% of intervention households produced sweet potato Intervention children (n = 498) ate more sweet potato and had higher serum retinol than controls (n = 243) Low et al. J Nutr. 2007;137:
29 Towards Sustainable Nutrition Improvement in Rural Mozambique. Taste tests are conducted at every adaptive trial harvest to determine preferences of local consumers.
30 Towards Sustainable Nutrition Improvement in Rural Mozambique. Sweet potato bread maker making bread at home and selling it at the market under the name of Golden Bread.
31 Orange Sweetpotato in Africa a Success Story Active behavior change Agronomic equality crucial Assistance to understanding and overcoming constraints to adoption crucial Farmer participation in breeding and varietal selection Seeds systems development Product and market development
32 Moving on to pumpkin nshima
33 Bioefficacy of biofortified maize on vitamin A status To determine the bioefficacy of maize with enhanced β-carotene To determine the effect of β-carotene and maize levels on vitamin A status
34 Results: Liver vitamin A was the same between the β-carotene and high-β-carotene maize group. Bioconversion : ~3 µg β-carotene to 1 µg retinol. 2.0 a Liver VA (µm mol) c b b 0.0 Control Maize BC VA Treatment
35 Partnerships and tasks ZamSeed grew the maize National Food and Nutrition Commission Lusaka coordinating and mobilizing the community Tropical Research and Development Center Ndola anthropology and biochemistry University of Wisconsin Madison randomization, field coordination, oversight, unique biochemical markers
36 Sensitization Provincial health office: 2008 Vitamin A status survey Follow-up with efficacy study Survey study in 2009 Identify six study sites Provincial health office: 2009 Provincial permanent secretary office District health office District developing coordinating committee (Jan 2010)
37 Engaging the community Facilitator Emily Ngulube retired nurse-midwife Meetings with the community, headmen, church leaders and volunteers. Social mobilization activities including drama and open discussions Listed villages within the 6 study sites Confirm potential child participants in the villages by household
38 Hiring nutritionists
39 Grinding the maize
40 Setting up kitchens
41 Cooking the maize
42 Stirring and stirring.
43 Cleaning up the mess
44 Can the maize change vitamin A status? Predictions from animal and human data.
45 A male child eating maize Liver vitamin A accumulation (µm mol/g) Sugar Age of child (y) Bioconversion slows Maize Supplements Tanumihardjo, Comp. Rev. Food Sci. & Food Safety, 2008;7:
46 5 4 Adolescent girl eating maize Liver vitamin A accumulation (µmol/g) Fortified sugar (high intake) Biofortified maize (high intake) Biofortified maize (low intake) ? Fortified sugar (low intake) Age of girl (y) Tanumihardjo, Comp Rev Food Sci & Food Safety, 2008;7:373-81
47 Visible traits Nutrition education becomes important Focus on children and expectant mothers Social marketing Convincing local farmers to grow biofortified crops
48 Invisible traits Iron in rice in the Philippines Zinc in wheat in Pakistan
49 Milled Dry Rice As consumed: 400 grams per day x +10 mg/kg Fe = +4.0 mg/day Fe Absorbed (10% bioavailability): +0.4 mg/day = 30% of the Mean physiological requirement for absorbed Fe 90% retention after boiling: Requires +11 mg/kg Fe as purchased Target for Breeders: 2 mg/kg (current average) + 11mg/kg = 13 mg/kg
50 The Subjects Religious sisters from 10 convents
51 Total body iron after nine months of consuming high-iron (+1.7 mg Fe/dy) or control rice stratified by 3 levels of baseline body iron Final body iro on (mg/kg) Control High-iron p = NS p = Body iron at baseline (mg/kg) Least square means controlling for baseline body iron and amount of rice consumed over 9 months. Yellow numbers inside bars reflect changes from baseline value
52 Pakistan, Zinc in Peshawar wheat Inquilab 91 Advanced Line
53 Zinc biofortification High Zn Rice (increases in Fe as well) How much extra zinc per day? Example: Adult women, rural areas Intake of 400 g milled, dry rice x +8 mg/kg Zn = +3.2 mg Zn/day 40% of the Estimated Average Requirement
54 Multinutrient approaches What if one could add high provitamin A and zinc to maize? Not only would zinc and vitamin A status be improved but overall function. Zinc is involved in vitamin A metabolism.
55 Synergism between vitamin A and zinc dehydrogenase Vision retinol retinal Zn monooxygenase Digestion β-carotene 2 retinol Zn Protein synthesis Zn retinol binding protein (RBP) retinol:rbp in blood
56 Time! 600 years
57 Thank you for your attention! Any questions or discussion points?
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