Hazards associated with food fortification Omar Obeid, PhD Department of Nutrition & Food Science...
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Transcript of Hazards associated with food fortification Omar Obeid, PhD Department of Nutrition & Food Science...
Hazards associated with food fortification
Omar Obeid, PhDOmar Obeid, PhDDepartment of Nutrition & Food ScienceDepartment of Nutrition & Food Science
American University of BeirutAmerican University of Beirut
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, 605-614Bell 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
Continuous risk of deficiencies from one or
more nutrients
StrategyDietary
Diversification Supplementation Food Fortification
AdvantagesThe 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.
DisadvantagesFactors 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, 605-614Allen L. (2003) J. Nutr. 133: 3875S-3878S
Advantages & Disadvantages of interventions
Continues to be one of the main strategies employed to tackle
micronutrient deficiencies
Food Fortification
Allen L. (2003) J. Nutr. 133: 3875S-3878S.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
Bell I., Fletcher R., and Lambert J. (2004) Proceedings of the Nutrition Society, 63, 605-614
Definitions
Food Fortification
Estimating the prevalence of inadequate nutrient intakes Tolerable upper intake levels (UL)Bioavailability of nutrients from food vehiclesEfficacy trialsEffectiveness trials
Allen, L. H. (2006) J. Nutr. 136: 1055–1058Allen, L. H. (2006) J. Nutr. 136: 1055–1058
Observed Level of intakeObserved Level of intake
00
5050
100100 100100
5050
00
Risk
of adverse effects
Risk
of adverse effects
(%)
(%)
Ris
k o
f in
adeq
uac
y (%
)R
isk
of
inad
equ
acy
(%)
EAREAR RDA RDA ULUL
+2SD-2SD
Dual curves of the dose-response relations between intake &risk of adverse effects
Kraemer K et al. (2008). Nutrition Reviews, 66(9): 517–525Kraemer K et al. (2008). Nutrition Reviews, 66(9): 517–525
Supplements
Safe range of intake
Intake from food Fortified
Observed Level of intakeObserved Level of intake
00
5050
100100 100100
5050
00
Risk
of adverse effects
Risk
of adverse effects
(%)
(%)
Ris
k o
f in
adeq
uac
y (%
)R
isk
of
inad
equ
acy
(%)
EAREAR RDA RDA ULUL
0 +2SD-2SD 0 25 50 75
B6Vit C
Vit E
x RDA x RDA
Vit.A
Dual curves of the dose-response relations between intake &risk of adverse effects
Introduction of Fortification
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
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
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)
Pregnancies Cranial-neural crest
defects
Total defects
0-1500 0-5,000 6,410 33(0.51%) 86(1.3%)
1,500-3,000 5,001-10,000 12,688 59(0.47%) 196(1.5%)
3,000-4,500 10,001-15,000 3,150 20(0.63%) 42(1.3%)
>4,500 >15,000 500 9(1.80%) 15(3.0%)
Recommended amounts:Adult men 900 µg/day
Adult women 700 µg/day.
Recommended amounts:Adult men 900 µg/day
Adult women 700 µg/day.
Anderson J. Journal of Bone and Mineral Research 2002, 17 (8)
Vitamin A
Tolerable upper limit (UL): 2800–3000 µg/day for adult
women & men.
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.
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.
Feskanich D et al. JAMA. 2002;287(1):47-54.
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.
Vitamin A Intake & Hip FracturesAmong Postmenopausal Women
Feskanich D et al. JAMA. 2002;287(1):47-54.
Vitamin A Intake & Hip FracturesAmong Postmenopausal Women
Feskanich D et al. JAMA. 2002;287(1):47-54.
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
Vitamin A intakes accumulate from
Anderson J. Journal of Bone and Mineral Research 2002, 17 (8)
Food
Fortified food
SupplementsCan easily exceed UL
safety
Vitamin A Fortification
Iron Fortification
Sarker A et al. AJCN. 2004; 80:149-53.
Most cost-effective way to prevent iron deficiency
Non-nutritional Anemia
Infection
Inflammation
H. PyloriNutritional
anemia Folate
Vitamin B12
Fe intake
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 = 0.34P = 0.34
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
8 mg Males
18 mg
Females
18 mg
Females
45 mg
UL
45 mg
UL
Supplements Fe-fortified foods
RDARDA
Increased Energy intake
Frequent consumption of red meat
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 Walker CF et al. Am J Clin Nutr 2005; 82:5–12
No firm conclusionson the existence of interactions
between iron and zinc
However However
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
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
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: 86:1187-92Conley M., et al (2003). Am J Clin Nutr; 77:1474-7
Folate Fortification
Associated with
Ganji V. & Wyckoff K. (2007). Am J Clin Nutr: 86:1187-92Conley M., et al (2003). Am J Clin Nutr; 77:1474-7
incidence of neural tube defects stroke associated mortality
incidence of colorectal cancer harm to population with low vitamin B-12 statusCognitive decline in older persons
But also withBut also with
Folate Fortification
Folate Fortification
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
Kalmbach R D et al. (2008). American Journal of Clinical Nutrition 88 (3): 763-768Kalmbach R D et al. (2008). American Journal of Clinical Nutrition 88 (3): 763-768
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
B12 necessary for the fxn of MS.
MS responsible for the remethylation of tHcy to methionine.
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
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
High dietary folic acid intake leads to bypassing the “trap”.
Macrocytosis associated with B12 deficiency is corrected.
High dietary folic acid intake leads to bypassing the “trap”.
Macrocytosis associated with B12 deficiency is corrected.
Mechanism
Mean corpuscular volume of subjects with low serum vit. B12 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. B12 concentrations without macrocytosis in the postfortification
period than in the prefortification period.
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
Morris MS et al. Am J Clin Nutr. 2007;85:193-200.Morris MS et al. Am J Clin Nutr. 2007;85:193-200.
Odds Ratio (OR)Odds Ratio (OR)
0.10.1 0.50.5 1.01.0 55 1010
1.01.0
0.6 (0.2-2.2)0.6 (0.2-2.2)
2.0 (1.1-3.5)2.0 (1.1-3.5)
5.2 (2.5-10.6)5.2 (2.5-10.6)
Interaction between Vitamin B12 status and serum folate in relation to anemia
Vitamin Status
B-12 Folate
Normal Normal
Normal High
Low Normal
Low High
Morris MS et al. Am J Clin Nutr. 2007;85:193-200.Morris MS et al. Am J Clin Nutr. 2007;85:193-200.
Odds Ratio (OR)Odds Ratio (OR)
0.10.1 0.50.5 1.01.0 55 1010
1.01.0
0.5 (0.2-0.9)0.5 (0.2-0.9)
1.9 (1.1-3.1)1.9 (1.1-3.1)
4.9 (2.6-9.2)4.9 (2.6-9.2)
Interaction between Vitamin B12 status and serum folate in relation to cognitive impairment
Vitamin Status
B-12 Folate
Normal Normal
Normal High
Low Normal
Low High
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): 189-93Kim Y. et al (2008) Am J Clin Nutr; 87:517-33Potter J. & Ulrich C. (2006) Cancer Epidemiol Biomarkers Prev; 15(2): 189-93Kim Y. et al (2008) Am J Clin Nutr; 87:517-33
Folate plays a dual role in carcinogenesis
Once established small tumor may grow more rapidly with folate supplementation
Prevention of early lesions.
Prevention of early lesions.
Potential harm once
preneoplastic lesions have developed.
Potential harm once
preneoplastic lesions have developed.
Folic acid fortification & Cancer
Potter J. & Ulrich C. (2006) Cancer Epidemiol Biomarkers Prev; 15(2): 189-93Kim Y. et al (2008) Am J Clin Nutr; 87:517-33Potter J. & Ulrich C. (2006) Cancer Epidemiol Biomarkers Prev; 15(2): 189-93Kim Y. et al (2008) Am J Clin Nutr; 87:517-33
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
Thank You