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Tanumihardjo nutrition vit a
Tanumihardjo nutrition vit a
Tanumihardjo nutrition vit a
Tanumihardjo nutrition vit a
Tanumihardjo nutrition vit a
Tanumihardjo nutrition vit a
Tanumihardjo nutrition vit a
Tanumihardjo nutrition vit a
Tanumihardjo nutrition vit a
Tanumihardjo nutrition vit a
Tanumihardjo nutrition vit a
Tanumihardjo nutrition vit a
Tanumihardjo nutrition vit a
Tanumihardjo nutrition vit a
Tanumihardjo nutrition vit a
Tanumihardjo nutrition vit a
Tanumihardjo nutrition vit a
Tanumihardjo nutrition vit a
Tanumihardjo nutrition vit a
Tanumihardjo nutrition vit a
Tanumihardjo nutrition vit a
Tanumihardjo nutrition vit a
Tanumihardjo nutrition vit a
Tanumihardjo nutrition vit a
Tanumihardjo nutrition vit a
Tanumihardjo nutrition vit a
Tanumihardjo nutrition vit a
Tanumihardjo nutrition vit a
Tanumihardjo nutrition vit a
Tanumihardjo nutrition vit a
Tanumihardjo nutrition vit a
Tanumihardjo nutrition vit a
Tanumihardjo nutrition vit a
Tanumihardjo nutrition vit a
Tanumihardjo nutrition vit a
Tanumihardjo nutrition vit a
Tanumihardjo nutrition vit a
Tanumihardjo nutrition vit a
Tanumihardjo nutrition vit a
Tanumihardjo nutrition vit a
Tanumihardjo nutrition vit a
Tanumihardjo nutrition vit a
Tanumihardjo nutrition vit a
Tanumihardjo nutrition vit a
Tanumihardjo nutrition vit a
Tanumihardjo nutrition vit a
Tanumihardjo nutrition vit a
Tanumihardjo nutrition vit a
Tanumihardjo nutrition vit a
Tanumihardjo nutrition vit a
Tanumihardjo nutrition vit a
Tanumihardjo nutrition vit a
Tanumihardjo nutrition vit a
Tanumihardjo nutrition vit a
Tanumihardjo nutrition vit a
Tanumihardjo nutrition vit a
Tanumihardjo nutrition vit a
Tanumihardjo nutrition vit a
Tanumihardjo nutrition vit a
Tanumihardjo nutrition vit a
Tanumihardjo nutrition vit a
Tanumihardjo nutrition vit a
Tanumihardjo nutrition vit a
Tanumihardjo nutrition vit a
Tanumihardjo nutrition vit a
Tanumihardjo nutrition vit a
Tanumihardjo nutrition vit a
Tanumihardjo nutrition vit a
Tanumihardjo nutrition vit a
Tanumihardjo nutrition vit a
Tanumihardjo nutrition vit a
Tanumihardjo nutrition vit a
Tanumihardjo nutrition vit a
Tanumihardjo nutrition vit a
Tanumihardjo nutrition vit a
Tanumihardjo nutrition vit a
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Tanumihardjo nutrition vit a

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  • 1. Taking Stock of the Evidence on Biofortification of Food Crops with Provitamin A Carotenoids: Situation Analysis of What We Know Sherry A. Tanumihardjo Associate Professor University of Wisconsin-Madison, USA Department of Nutritional Sciences
  • 2. Parker, FASEB J 10:543, 1996
  • 3. Definitions  Bioaccessibility: how much carotenoid is released from the food matrix and available for absorption.  Bioavailability: fraction of ingested nutrient available for utilization or storage.  Bioconversion: proportion of bioavailable carotene converted to retinol.  Bioefficacy: efficiency ingested carotenoids are absorbed and converted to retinol.
  • 4. Intestinal wall b-Cabsorbed Cleaved Retinal Reduced Retinol Food b-Ctotal b-Cfreed Bioaccessibility = b-Cfreed / b-Ctotal Bioavailability = b-Cabsorbed / b-Ctotal Bioconversion = Retinol / b-Cabsorbed Bioefficacy = Retinol / b-Ctotal Tanumihardjo, IJVNR 72: 41, 2002
  • 5. SLAMENGHI - 1996  Species of carotenoids  molecular Linkage  Amount of carotenoids consumed in a meal  Matrix in which the carotenoid is incorporated  Effectors of absorption and bioconversion  Nutrient status of the host  Genetic factors  Host-related factors  mathematical Interactions
  • 6. Advantages of Biofortification: Enhancing micronutrients in crops  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
  • 7. The Sherry Factors!!!  S – Species of carotenoid  H – Host related factors  E – Effectors of absorption  R – Relative amounts of carotenoids  R – Resistant starch  Y – Yet to be determined
  • 8. S – Species of carotenoid Hydrocarbon or not…
  • 9. S – Species of carotenoid OH OH -carotene b-carotene b-cryptoxanthin retinol
  • 10. -Carotene equivalents 5.5 mg:1 mg Treatment group n Serum retinol (mmol/L) Liver retinyl palmitate (mmol/g) Liver total retinol2 (mmol/g) Baseline3 6 1.30 + 0.35 0.123 + 0.024b 0.170 + 0.027b Vitamin A 9 1.44 + 0.21 0.198 + 0.051a 0.267 + 0.071a -Carotene 9 1.39 + 0.09 0.110 + 0.026b 0.155 + 0.033b b-Carotene 9 1.40 + 0.17 0.109 + 0.051b 0.153 + 0.066b Oil control 5 1.57 + 0.38 0.061 + 0.029c 0.091 + 0.041c Tanumihardjo & Howe. J. Nutr. 135: 2622–6, 2005
  • 11.  Bioconversion for b-cryptoxanthin was 2.8 mg to 1 mg retinol and almost identical to b- carotene. a ab bc c ab 0.00 0.05 0.10 0.15 0.20 0.25 0.30 0.35 Base Ctl bC bCX VA µmolRE/gliver ab c bc a a 0.0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 Base Ctl bC bCX VA µmolRE/liver Davis et al., BJN, 2008
  • 12. Biofortified b-cryptoxanthin maize 0 0.2 0.4 0.6 0.8 1 1.2 1.4 1.6 mmolRE/liver Base Control bC Maize VA bc bc c b a Davis et al., BJN, 2008
  • 13. Bioefficacy of biofortified b-carotene maize  High-b-carotene maize did not differ from b-carotene . Bioconversion: ~3 mg b-carotene to 1 mg retinol. 0.0 0.5 1.0 1.5 2.0 Control Maize BC VA Treatment LiverVA(mmol) a bb c
  • 14. What about bioconversion factors in human studies?  Li et al. Am J Clin Nutr 2010 • 6.48 ± 3.51 mg bC:1 mg retinol in 6 young women in Iowa  Muzhingi et al. FASEB J. 2009 • 3.0 ± 1.5 mg bC:1 mg retinol in 9 healthy Zimbabwean men
  • 15. S – Species of carotenoid Cis or trans
  • 16. Cassava: Comparable to b-carotene supplement even with substantial cis-b-carotene a bb c bc 0 0∙2 0∙4 0∙6 0∙8 1 1∙2 1∙4 1∙6 1∙8 Base Control BC Cassava VA Treatments mmolVitaminA/liver A a bcb c bc 0 0∙1 0∙2 0∙3 0∙4 0∙5 0∙6 0∙7 0∙8 Base Control BC Cassava VA Treatments mmolVitaminA/gliver B c c c a b b b a a b 0 1 2 3 4 5 6 7 8 9 Base Control BC Cassava VA Treatments nmolb-Carotene/liver trans cis C
  • 17. Erdman’s group  All-trans b-carotene appears to be more bioavailable than 9-cis or 13-cis b-carotene in gerbils given single oral doses of each isomer • Deming et al., J. Nutr. 132: 2700-8, 2002.  The relative vitamin A value of 9-cis b-carotene is less and that of 13-cis b-carotene may be greater than the accepted 50% that of all trans- b-carotene in gerbils  Deming et al., J. Nutr. 132: 2709-12, 2002.
  • 18. Cis/trans b-carotene Bresnahan et al. FASEB J 2011 a c bc bc b b
  • 19. H – Host related factors
  • 20. Polymorphisms  Single nucleotide polymorphisms in the human BCMO1 gene have been discovered causing observably reduced BCMO1 activity.  We do not know how this will influence biofortification efforts at the population level.  Lietz et al., Arch Biochem Biophys, 2010
  • 21. R = 0.885 0 5 10 15 20 25 0 0.5 1 1.5 2 Conversionfactor(mg:mg) Total vitamin A liver reserves (mmol) Vitamin A status of the host High b-carotene orange carrots Orange and purple carrots Kale, spinach, and brussels sprouts Sweet Potato Red carrots and Cassava Maize Total vitamin A liver reserves (mmol) Conversionfactor(mg:mg)
  • 22. H – Host related factors Other nutrient status
  • 23. How are iron and vitamin A related?  Hematopoiesis and erythropoiesis: formation of red blood cells  Modulation in the anemia of infection  Iron absorption and metabolism: iron mobilization and transport  Immune modulation: Reduced morbidity and mortality of some infectious diseases
  • 24. Vision retinol retinal Zn monooxygenase Digestion b-carotene 2 retinal Zn Protein synthesis Zn retinol binding protein retinol:RBP in blood (RBP) Synergism between vitamin A and Zn dehydrogenase
  • 25. E – Effectors of absorption Fat
  • 26. Ribaya-Mercado et al. AJCN 2007;85:1041-9  Schoolchildren fed 4.2 mg provitamin A carotenoids in the form of vegetables for 9 weeks with 2.4, 5 or 10 g fat/meal.  Low liver reserves (< 0.07 mmol/g) fell from 35% to 7% and the amount of fat did not influence the results.
  • 27. Influence of fat on bioconversion Mills et al. J. Nutr. 139: 44-50, 2009 mgb-carotenetoretinol
  • 28. Emerging data: Type of fat  Dietary fats with increased unsaturated to saturated fat enhance absorption of carotenoids by increasing efficiency of micellarization and lipoprotein secretion  Unsaturated fat enhances carotenoid bioavailability • Chitchumroonchokchai et al., FASEB J. 2010; Abstract 539.3.
  • 29. R – Relative amounts of carotenoids
  • 30.  Conversion factors ranged from 9 to 11 mg b-carotene to 1 mg retinol for typical orange and 23 mg b- carotene to 1 mg retinol for biofortified carrots. 0 50 100 150 200 250 300 350 high orange orange purple white Totalliverb-carotene(nmol) a b b c (A) 0 0.2 0.4 0.6 0.8 1 1.2 1.4 1.6 1.8 2 high orange orange purple white TotallivervitaminA(mmol) a b b c (B) Dosti et al., BJN. 2006
  • 31. Cassava: Varying the level of cassava a abab b a a 0 0∙3 0∙6 0∙9 Base Control 15% #2 17% #1 35% #2 40% #1Treatments mmolVitaminA/liver A abab ab b ab a 0 0∙1 0∙2 0∙3 Base Control 15% #2 17% #1 35% #2 40% #1Treatments mmolVitaminA/gliver B b b a bb a a b b cc a 0 1 2 3 4 5 6 7 8 Base Control 15% #2 17% #1 35% #2 40% #1 Treatments nmolb-Carotene/liver trans cis C
  • 32. b-Carotene assessment 0 10 20 30 40 Control Maize BC VA Treatment Liverb-carotene(nmol) a b Liver bC is ~100% greater in maize treatment group
  • 33. VA status with increasing b-carotene. Liver VA from orange maize was greater than yellow, regardless of % (P < 0.05). 0 0.2 0.4 0.6 0.8 30% typical 60% typical 30% high BC 60% high BC Maize Treatment LiverVA(mmol) ab bc c a
  • 34. Provitamin A from cassava, maize, or supplements of vitamin A, β-carotene, and β-cryptoxanthin
  • 35. Conclusions:  Not all provitamin A carotenoids are equivalent, one conversion factor does not fit all foods and is related to vitamin A status.  Biofortified maize not only maintained vitamin A status, but was as efficacious as b-carotene supplements.  In populations consuming maize, using orange instead of white maize may impact vitamin A status.
  • 36. A male child eating maize 0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1 0.5 1 1.5 2 2.5 3 3.5 4 4.5 Age of child (y) LivervitaminAaccumulation mmol/g) Sugar Maize Supplements Bioconversion slows Tanumihardjo, Comp. Rev. Food Sci. & Food Safety, 2008;7:373-81.
  • 37. Setting up kitchens
  • 38. Grinding the maize
  • 39. Food Details Standardized recipes with a rotating menu
  • 40. Cooking the maize
  • 41. Stirring and stirring….
  • 42. Food Details Serving sizes weighed for each menu item
  • 43. Food Details Children Eating! All uneaten food weighed for each subject
  • 44. Cleaning up the mess And the data!
  • 45. * * A B C D
  • 46. R – Resistant starch Sweet potato, Golden Rice and banana
  • 47. Orange Fleshed Sweetpotato
  • 48. • Using the paired isotope dilution test, final vitamin A was higher in the spinach, vitamin A and b-carotene groups compared to the control group. • Vitamin A equivalency factors were estimated: ~13:1 for sweet potato ~10:1 for Indian spinach ~6:1 for b-carotene Vitamin A provided with meals Haskell et al. Am J Clin Nutr. 2004;80:705-14
  • 49. Mills et al. J. Nutr. 139: 44-50, 2009 Influence of dry matter on bioconversion mgb-carotenetoretinol
  • 50. South African Trial Supervised feeding; 125 g x 5 d/wk for 10.5 wk; 1030 mg RAE OFSP vs 0 mg RAE WFSP; 90% compliance; 250% RDA
  • 51. Infants eating sweet potato Sweet potato Sachets or tablets ? 0 0.2 0.4 0.6 0.8 6 7 8 10 11 12 13 Age of child (mo) LivervitaminAaccumulation (mmol/g) Sweet potato Tablets or sachets Tanumihardjo, Comp. Rev. Food Sci. & Food Safety, 2008;7:373-81.
  • 52. -0.004 0.004 -0.006 -0.005 -0.004 -0.003 -0.002 -0.001 0.000 0.001 0.002 0.003 0.004 0.005 0.006 Intervention effect: -0.008 (-0.015, -0.001) P = 0.0203 Change in liver stores of vitamin A Intervention Control
  • 53. 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;137:1320-7.
  • 54. . Towards Sustainable Nutrition Improvement in Rural Mozambique Taste tests were conducted at every adaptive trial harvest to determine preferences of local consumers.
  • 55. . Towards Sustainable Nutrition Improvement in Rural Mozambique Sweet potato bread maker making his bread at home and selling it in the nearby market of Lualua. Bread is marketed under the name of Golden Bread.
  • 56. Orange sweet potato 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, product, and market development
  • 57. Progress with Golden Rice
  • 58. Ready for golden rice?
  • 59. Bioconversion factor:  The conversion factor for Golden Rice was 3.8 + 1.7 mg to 1 mg with a range of 1.9–6.4:1 in 5 healthy adults • Tang et al. Am J Clin Nutr 2009;89:1776–83  Pure βC, GR βC, and spinach βC to retinol were 2.0, 2.1, and 7.3 mg to 1 mg, respectively • Tang et al. FASEB J 2010 Abstract
  • 60. Do favorable bioconversion factors result in efficacy to improve vitamin A status?
  • 61. No change in serum retinol
  • 62. Both groups lost liver stores as predicted by the numbers
  • 63. What do the numbers predict?  6 mg/g X 0.75 retention factor  4.5 mg/g X158 g/day  711 mg with an optimistic 3:1 conversion  237 mg with a 275 mg/d EAR = - 38 mg  Potential loss during the trial is 28 mg/g liver with maize feeding
  • 64. MRDR versus liver reserves Liver reserves in mg/g liver MRDRvalue
  • 65. BN MN OR TN PP VA VitaminA(μmol/liver)VitaminA(μmol/gliver) Values are means + SD; n = 10. Means with different letters are different, P < 0.05. ND, not detected VA Concentration Total Liver VA  All fruits maintained baseline liver VA concentrations.  All fruits prevented VA depletion as compared to control, except banana.  Liver carotenoids present in respective groups. Arscott et al., Exp. Biol. Med, 2009 Fruit – Banana?
  • 66. r = 0.88 Banana r = 0.44 with banana Dark orange carrot Orange and purple carrots Kale, spinach brussels Red carrots sprouts Maize Mango, orange, tangerine, papaya Conversion efficiency improves as VA status declines
  • 67. Interesting Observations Daily Diet and VA Intake Diet Daily Diet Intake (g) VA Intake (nmol) VA- 6.77 0.00 VA+ 6.64 19.11 VA+ Banana 8.12 30.38 60CG 9.16 32.47 60CR 8.99 37.50 60LG 8.28 29.72 60LR 7.67 48.84 15KBG 7.55 56.16 30KBG 7.61 103.70
  • 68. More studies with banana All gerbils vitamin A deficient!
  • 69. Study 2: Total liver vitamin A (nmol)
  • 70. Y – Yet to be determined
  • 71. Another reason to feed whole foods! Mills et al. J. Nutr. 2008.;138:1692-8 c a ababab bc d 0 2 4 6 8 10 12 B aselineC ontrol PO O O R PO R VA mmolTEAC/g Hydrophilic Extracts Lipophilic Extracts b a a a a a a 0 1 2 3 4 5 6 B aselineC ontrol PO O O R PO R VA mmolTEAC/L
  • 72. Vision retinol retinal Zn monooxygenase Digestion b-carotene 2 retinal Zn Protein synthesis Zn retinol binding protein retinol:RBP in blood (RBP) Biofortification: vitamin A and Zn dehydrogenase
  • 73. LET’S FEED PEOPLE: Jejunal Morphology ORAL TPN Peterson, C.A. et al. Am J Physiol 272:G1100, 1997 Supports biofortification efforts!
  • 74. Situation analysis of what we know
  • 75. The Current VAAL Team  Sara Arscott  Kara Bresnahan  Ashley Valentine  Emily Nuss  Chris Davis  Harold Furr  David Liu  Napaporn Riabroy  Margertha McLean  Sammie Schmalzle  Jacob Tanumihardjo Collaborators:  Philipp Simon  Torbert Rocheford  Kevin Pixley  Natalia Palacios Past members whose work was cited:  Mandy Porter Dosti  Hua Jing  Julie Howe  Jordan Mills
  • 76. Thanks for your attention

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