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Hazards associated with food fortification Omar Obeid, PhD Department of Nutrition & Food Science American University of Beirut.

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Presentation on theme: "Hazards associated with food fortification Omar Obeid, PhD Department of Nutrition & Food Science American University of Beirut."— Presentation transcript:

1 Hazards associated with food fortification Omar Obeid, PhD Department of Nutrition & Food Science American University of Beirut

2 Micronutrient malnutrition: widespread problem throughout the world. Groups such as: – Children – Women of childbearing age – Elderly Three approaches currently employed to address micronutrient deficiencies: Dietary Diversification Supplementation Food Fortification Bell I., Fletcher R., and Lambert J. (2004) Proceedings of the Nutrition Society, 63, 605-614 Background Continuous risk of deficiencies from one or more nutrients

3 Strategy Dietary DiversificationSupplementationFood Fortification Advantages The best long-term solution. Targets specific risk groups very quickly with larger micronutrients doses. Provides rapid solutions to address low micronutrient intakes at a population level while maintaining traditional dietary patterns. Disadvantages Factors affecting food choices are complex. It often fails to supply all necessary nutrients. Risk of over-consumption in individuals outside the at- risk groups or those who consume high amounts of fortified foods. Individuals in non targeted groups are usually neglected.May not reach the most needy population groups. compliance is poor.Substantial technical barriers to fortification: The right dose of fortificant should be found so that it is effective but not toxic. Adverse effects on the sensory qualities of foods. Nutrient-nutrient interaction. Poor bioavailability of some fortificants. Difficulty of fortifying some foods such as rice. Increased risk of overnutrition with consumption of large doses of micronutrients. Bell I., Fletcher R., and Lambert J. (2004). Proceedings of the Nutrition Society, 63, 605-614 Allen L. (2003) J. Nutr. 133: 3875S-3878S Advantages & Disadvantages of interventions

4 Continues to be one of the main strategies employed to tackle micronutrient deficiencies Food Fortification Allen L. (2003) J. Nutr. 133: 3875S-3878S. Cost-effective & relatively easy to deliver Concerns about the risk of over- consumption in individuals outside the at-risk groups. However

5 Bell I., Fletcher R., and Lambert J. (2004) Proceedings of the Nutrition Society, 63, 605-614 Definitions Restoration Full or partial replacement of nutrients lost during some stage of food production or distribution. Ex: Addition of thiamin or Fe to white flour. Nutritional equivalence of substitute foods Addition of one or more nutrients to a food that is intended as a substitute for another food. Ex: Addition of vit. A & D to margarine & other spreads that replace butter. Fortification or enrichment Addition of nutrients to levels above those or not normally present in that food. Ex: Addition of Iodine to salt. Mandatory fortification Fortification required by national legislation in most countries. Ex: In UK, addition of vit. A & D to spreads Voluntary fortification Fortification practiced by food producers. Ex: Fortification of breakfast cereals. Addition of calcium to orange juice.

6 Food Fortification Estimating the prevalence of inadequate nutrient intakes Tolerable upper intake levels (UL) Bioavailability of nutrients from food vehicles Efficacy trials Effectiveness trials Allen, L. H. (2006) J. Nutr. 136: 1055–1058

7 Observed Level of intake 0 50 100100 50 0 Risk of adverse effects (%) Risk of inadequacy (%) EAR RDA UL +2SD-2SD Dual curves of the dose-response relations between intake &risk of adverse effects Kraemer K et al. (2008). Nutrition Reviews, 66(9): 517–525 Supplements Safe range of intake Intake from food Fortified

8 Observed Level of intake 0 50 100100 50 0 Risk of adverse effects (%) Risk of inadequacy (%) EARRDA UL 0 +2SD-2SD 0255075 B6B6 Vit C Vit E x RDA Vit. A Dual curves of the dose-response relations between intake &risk of adverse effects Introduction of Fortification

9 The cumulative effects of supplementation & fortification have raised safety concerns about exceeding the tolerable upper intake levels (ULs). Actual amount of folic acid being added to food is 50% more than the FDA regulations. Individuals at greatest risk: – Those who consume large amounts of fortified foods & take dietary supplements. Risk of micronutrient over- consumption Bell I., Fletcher R., and Lambert J. (2004) Proceedings of the Nutrition Society, 63, 605-614 NIH State-of-the-Science Conference statement on Multivitamin/Mineral Supplements and Chronic Disease Prevention (2006). NIH Consensus and State-of-the-Science Statements. Volume 23, Number 2. Conley M., et al. (2003). Am J Clin Nutr; 77:1474-7

10 Rothman, K. J., et al. (1995). N.Engl.J.Med.333, 1369-1373 Teratogenic Risk of High Prenatal Exposures to Performed Vitamin A Retinal intake (µg/day) Retinal intake (IU/day) PregnanciesCranial- neural crest defects Total defects 0-15000-5,0006,41033(0.51%)86(1.3%) 1,500-3,0005,001-10,00012,68859(0.47%)196(1.5%) 3,000-4,50010,001-15,0003,15020(0.63%)42(1.3%) >4,500>15,0005009(1.80%)15(3.0%)

11 Recommended amounts: Adult men 900 µg/day Adult women 700 µg/day. Anderson J. Journal of Bone and Mineral Research 2002, 17 (8) Tolerable upper limit (UL): 2800–3000 µg/day for adult women & men. Standard dose of vitamin A in multi-mineral/vitamin supplement: 1500 µg/day, whether in the retinol form (retinyl palmitate) or combination of retinol & β-carotene.

12 Toxicity might happen in elderly more than younger adults since: – Storage of vitamin A in the liver & fat tissue as body fat accumulates with advancing age. – circulating retinol has a longer half-life. – Intake of multivitamins and minerals adding to it the amounts from food sources and food fortification. Anderson J. Journal of Bone and Mineral Research 2002, 17 (8)

13 Feskanich D et al. JAMA. 2002;287(1):47-54. Vitamin A Intake & Hip Fractures Among Postmenopausal Women Long-term consumption of high vitamin A diets may contribute to osteoporosis & hip fracture.

14 Feskanich D et al. JAMA. 2002;287(1):47-54. Vitamin A Intake & Hip Fractures Among Postmenopausal Women

15 Feskanich D et al. JAMA. 2002;287(1):47-54. Vitamin A Intake & Hip Fractures Among Postmenopausal Women

16 Feskanich D et al. JAMA. 2002;287(1):47-54. Vitamin A Intake & Hip Fractures Among Postmenopausal Women Thus, long-term intake of a diet high in retinol may promote the development of osteoporotic hip fractures in women

17 Vitamin A intakes accumulate from Anderson J. Journal of Bone and Mineral Research 2002, 17 (8) Food Fortified food Supplements Can easily exceed UL safety Vitamin A Fortification

18 Iron Fortification Sarker A et al. AJCN. 2004; 80:149-53. Most cost-effective way to prevent iron deficiency Non-nutritional Anemia InfectionInflammation H. Pylori Nutritional anemia FolateVitamin B 12 Fe intake

19 Iron Fortification H. Pylori Anemia ID Sarker A et al. AJCN. 2004; 80:149-53. IDA Although associated with ID & IDA, H. Pylori eradication does not significantly influence iron absorption. Infected children with IDA P = 0.34

20 Iron overdose Iron Fortification Additional exposure to dietary iron places some segments of the population at increased risk of iron excess (Athletic males) 8 mg Males 18 mg Females 45 mg UL Supplements Fe-fortified foods RDA Increased Energy intake Frequent consumption of red meat

21 Iron Zinc interaction Iron & Zinc Similar absorption & transport mechanisms compete for absorptive pathways Walker CF et al. Am J Clin Nutr 2005; 82:5–12 No firm conclusions on the existence of interactions between iron and zinc No firm conclusions on the existence of interactions between iron and zinc However

22 Basal meal: Wheat rolls served with margarine and water on 2 mornings. (iron content of the rolls was adjusted to 4.1 mg by adding ferrous sulfate to the dough). Hallberg L,Hulthén L. Am J Clin Nutr 2000;71:1147–60. Effect of calcium on absorption & bioavailability of dietary iron 310 subjects 194 females 116 males

23 No inhibition when calcium in a meal was < 50 mg Inhibition maximum when Ca 300-600 mg Effect of calcium on absorption & bioavailability of dietary iron

24 1998: FDA made folic acid fortification of all cereal- grain products mandatory in the U.S. Rationale: reduce the risk of a women having a child with neural tube defect (NTD). Ganji V. & Wyckoff K. (2007). Am J Clin Nutr: 86:1187-92 Conley M., et al (2003). Am J Clin Nutr; 77:1474-7 Folate Fortification

25 Associated with Ganji V. & Wyckoff K. (2007). Am J Clin Nutr: 86:1187-92 Conley M., et al (2003). Am J Clin Nutr; 77:1474-7 incidence of neural tube defects stroke associated mortality incidence of neural tube defects stroke associated mortality incidence of colorectal cancer harm to population with low vitamin B-12 status Cognitive decline in older persons incidence of colorectal cancer harm to population with low vitamin B-12 status Cognitive decline in older persons But also with Folate Fortification

26 Amount of fortification in the U. S set at 140 µg/100 g of cereal grain product Expected to the average folic acid intake attributable to fortification by 100 µg/d. High folic acid intakes may lead to the correction of hematological abnormalities associated with vit. B 12 deficiency. May delay the diagnosis of B 12 deficiency irreversible neurologic damage Wyckoff K. & Ganji V.(2007). Am J Clin Nutr: 86:1187-92 Kalmbach R D et al. (2008). American Journal of Clinical Nutrition 88 (3): 763-768

27 Potter J. and Ulrich C. (2006) Epidemiol Biomarkers Prev; 15(2): 189-93 Wyckoff K. & Ganji V. (2007). Am J Clin Nutr: 86:1187-92 B 12 necessary for the fxn of MS. MS responsible for the remethylation of tHcy to methionine. MS also responsible for the conversion of N 5 -Methyl THF to THF. In B 12 deficiency, folate is trapped as N5-Methyl THF. Thus N 5, N 10 - methylene THF needed for DNA synthesis is not produced which leads to macrocytosis High dietary folic acid intake leads to bypassing the trap. Macrocytosis associated with B 12 deficiency is corrected. Mechanism

28 Mean corpuscular volume of subjects with low serum vit. B 12 concentrations stratified by folic acid fortification period Wyckoff K. & Ganji V. (2007). Am J Clin Nutr: 86:1187-92 Higher proportion of individuals with low serum vit. B 12 concentrations without macrocytosis in the postfortification period than in the prefortification period.

29 Folic acid fortification may have led to a correction of macrocytosis associated with vitamin B 12 insufficiency Could be appropriate to add vitamin B 12 to foods currently fortified with folic acid. Folic acid fortification Wyckoff K. & Ganji V. (2007). Am J Clin Nutr: 86:1187-92

30 Morris MS et al. Am J Clin Nutr. 2007;85:193-200. Odds Ratio (OR) 0.10.5 1.0510 1.0 0.6 (0.2-2.2) 2.0 (1.1-3.5) 5.2 (2.5-10.6) Interaction between Vitamin B 12 status and serum folate in relation to anemia Vitamin Status B-12Folate Normal High LowNormal LowHigh

31 Morris MS et al. Am J Clin Nutr. 2007;85:193-200. Odds Ratio (OR) 0.10.5 1.0510 1.0 0.5 (0.2-0.9) 1.9 (1.1-3.1) 4.9 (2.6-9.2) Interaction between Vitamin B 12 status and serum folate in relation to cognitive impairment Vitamin Status B-12Folate Normal High LowNormal LowHigh

32 Important role of folate in nucleotide synthesis – Deficiency affects primarily rapidly dividing tissues. The administration of folate enhanced the growth of existing tumors. Folate antagonists (methotrexate) became a basis of cancer chemotherapy. Poorer clinical response to methotrexate were related to higher blood folate concentrations due to induced multiple drug resistance. Folic acid fortification & Cancer Potter J. & Ulrich C. (2006) Cancer Epidemiol Biomarkers Prev; 15(2): 189-93 Kim Y. et al (2008) Am J Clin Nutr; 87:517-33

33 Folate plays a dual role in carcinogenesis Once established small tumor may grow more rapidly with folate supplementation Prevention of early lesions. Potential harm once preneoplastic lesions have developed. Folic acid fortification & Cancer Potter J. & Ulrich C. (2006) Cancer Epidemiol Biomarkers Prev; 15(2): 189-93 Kim Y. et al (2008) Am J Clin Nutr; 87:517-33

34 Overconsumption of nutrients – Vitamin A Competition with other nutrients – Zinc and iron ? – Calcium and Iron Interaction with metabolism – Folate and B 12 Knowledge gap – Causes of anemia Folic acid fortification & Cancer

35 Thank You


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