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Hazards associated with food fortification

Hazards associated with food fortification. Omar Obeid, PhD Department of Nutrition & Food Science American University of Beirut. Background. Food Fortification. Dietary Diversification. Supplementation. Micronutrient malnutrition : widespread problem throughout the world. Groups such as:

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Hazards associated with food fortification

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

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

  3. Advantages & Disadvantages of interventions Bell I., Fletcher R., and Lambert J. (2004). Proceedings of the Nutrition Society, 63, 605-614 Allen L. (2003) J. Nutr. 133: 3875S-3878S

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

  5. Definitions Bell I., Fletcher R., and Lambert J. (2004) Proceedings of the Nutrition Society, 63, 605-614

  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. Fortified Intake from food Dual curves of the dose-response relations between intake &risk of adverse effects UL EAR RDA 100 100 Risk of adverse effects (%) Safe range of intake Risk of inadequacy (%) Supplements 50 50 0 0 -2SD +2SD Observed Level of intake Kraemer K et al. (2008). Nutrition Reviews, 66(9): 517–525

  8. Dual curves of the dose-response relations between intake &risk of adverse effects UL EAR RDA 100 100 Risk of adverse effects (%) Introduction of Fortification Risk of inadequacy (%) x RDA 50 50 Vit C Vit E B6 Vit.A 0 0 0 25 50 75 -2SD +2SD 0 Observed Level of intake

  9. Risk of micronutrient over-consumption • 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. 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. Teratogenic Risk of High Prenatal Exposures to Performed Vitamin A Rothman, K. J., et al. (1995). N.Engl.J.Med.333, 1369-1373

  11. Vitamin A Recommended amounts: • Adult men 900 µg/day • Adult women 700 µg/day. • 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. Anderson J. Journal of Bone and Mineral Research 2002, 17 (8)

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

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

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

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

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

  17. Iron Fortification Infection Inflammation H. Pylori Folate Vitamin B12 Fe intake • Most cost-effective way to prevent iron deficiency Nutritional anemia Non-nutritional Anemia Sarker A et al. AJCN. 2004; 80:149-53.

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

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

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

  21. Effect of calcium on absorption & bioavailability of dietary iron 310 subjects 194 females 116 males • 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.

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

  23. Folate Fortification • 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

  24. Folate Fortification •  incidence of neural tube defects •  stroke associated mortality But also with •  incidence of colorectal cancer •  harm to population with low vitamin B-12 status • Cognitive decline in older persons 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

  25. Folate Fortification Kalmbach R D et al. (2008). American Journal of Clinical Nutrition 88 (3): 763-768 • 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. B12 deficiency. • May delay the diagnosis of B12 deficiency  irreversible neurologic damage Wyckoff K. & Ganji V.(2007). Am J Clin Nutr: 86:1187-92

  26. Mechanism • MS also responsible for the conversion of N5-Methyl THF to THF. • In B12 deficiency, folate is “trapped” as N5-Methyl THF . • Thus N5, N10-methylene THF needed for DNA synthesis is not produced which leads to macrocytosis • B12 necessary for the fxn of MS. • MS responsible for the remethylation of tHcy to methionine. • High dietary folic acid intake leads to bypassing the “trap”. • Macrocytosis associated with B12 deficiency is corrected. 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

  27. Mean corpuscular volume of subjects with low serum vit. B12 concentrations stratified by folic acid fortification period Higher proportion of individuals with low serum vit. B12 concentrations without macrocytosis in the postfortification period than in the prefortification period. Wyckoff K. & Ganji V. (2007). Am J Clin Nutr: 86:1187-92

  28. Folic acid fortification may have led to a correction of macrocytosis associated with vitamin B12 insufficiency Could be appropriate to add vitamin B12 to foods currently fortified with folic acid. Folic acid fortification Wyckoff K. & Ganji V. (2007). Am J Clin Nutr: 86:1187-92

  29. Interaction between Vitamin B12 status and serum folate in relation to anemia 1.0 0.6 (0.2-2.2) 2.0 (1.1-3.5) 5.2 (2.5-10.6) 1.0 5 10 0.1 0.5 Odds Ratio (OR) Morris MS et al. Am J Clin Nutr. 2007;85:193-200.

  30. Interaction between Vitamin B12 status and serum folate in relation to cognitive impairment 1.0 0.5 (0.2-0.9) 1.9 (1.1-3.1) 4.9 (2.6-9.2) 1.0 5 10 0.1 0.5 Odds Ratio (OR) Morris MS et al. Am J Clin Nutr. 2007;85:193-200.

  31. Folic acid fortification & Cancer • 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. 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

  32. Folic acid fortification & Cancer 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. 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. Overconsumption of nutrients Vitamin A Competition with other nutrients Zinc and iron ? Calcium and Iron Interaction with metabolism Folate and B12 Knowledge gap Causes of anemia Folic acid fortification & Cancer

  34. Thank You

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