Transcript Nutritional & Herbal Supplements What Do We Know?

Hazards associated with food
fortification
Omar Obeid, PhD
Department of Nutrition & Food Science
American University of Beirut
Background
Micronutrient malnutrition: widespread problem throughout the
world.
Groups such as:
– Children
– Women of childbearing age
– Elderly
Continuous risk of
deficiencies from one or
more nutrients
Three approaches currently employed to address micronutrient
deficiencies:
Food Fortification
Dietary Diversification
Supplementation
Bell I., Fletcher R., and Lambert J. (2004) Proceedings of the Nutrition Society, 63, 605-614
Advantages & Disadvantages of
interventions
Strategy
Advantages
Disadvantages
Dietary
Diversification
The best long-term
solution.
Factors affecting
food choices are
complex.
Supplementation
Food Fortification
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.
It often fails to supply all
necessary nutrients.
Risk of over-consumption in individuals outside the atrisk 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.
Increased risk of
overnutrition with
consumption of large
doses of micronutrients.
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.
Bell I., Fletcher R., and Lambert J. (2004). Proceedings of the Nutrition Society, 63, 605-614
Allen L. (2003) J. Nutr. 133: 3875S-3878S
Food Fortification
Continues to be one of the main
strategies employed to tackle
micronutrient deficiencies
Cost-effective & relatively
easy to deliver
However
Concerns about the risk of overconsumption in individuals outside the
at-risk groups.
Allen L. (2003) J. Nutr. 133: 3875S-3878S.
Definitions
Restoration
Nutritional
equivalence of
substitute foods
Fortification or
enrichment
Mandatory
fortification
Voluntary
fortification
• Full or partial
replacement of
nutrients lost
during some
stage of food
production or
distribution.
• Addition of one
or more
nutrients to a
food that is
intended as a
substitute for
another food.
• Addition of
nutrients to
levels above
those or not
normally present
in that food.
• Fortification
required by
national
legislation in
most countries.
• Fortification
practiced by food
producers.
• Ex: Addition of
thiamin or Fe to
white flour.
• Ex: Addition of
vit. A & D to
margarine &
other spreads
that replace
butter.
• Ex: Addition of
Iodine to salt.
• Ex: In UK,
addition of vit. A
& D to spreads
• Ex: Fortification
of breakfast
cereals.
Bell I., Fletcher R., and Lambert J. (2004) Proceedings of the Nutrition Society, 63, 605-614
• Addition of
calcium to
orange juice.
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
Dual curves of the dose-response relations
between intake &risk of adverse effects
EAR
UL
RDA
100
Safe range of intake
Intake from food
Fortified
Supplements
50
50
0
0
-2SD
+2SD
Observed Level of intake
Kraemer K et al. (2008). Nutrition Reviews, 66(9): 517–525
Risk of adverse effects (%)
Risk of inadequacy (%)
100
Dual curves of the dose-response relations
between intake &risk of adverse effects
EAR
UL
RDA
100
Introduction of Fortification
x RDA
50
Vit.
A
Vit
C
Vit
E
50
B6
0
0
0
+2SD
-2SD
0
25
50
75
Observed Level of intake
Risk of adverse effects (%)
Risk of inadequacy (%)
100
Risk of micronutrient overconsumption
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
Teratogenic Risk of High Prenatal Exposures to
Performed Vitamin A
Retinal intake Retinal intake
(µg/day)
(IU/day)
Pregnancies
Cranialneural 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%)
Rothman, K. J., et al. (1995). N.Engl.J.Med.333, 1369-1373
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)
Vitamin A Intake & Hip Fractures
Among Postmenopausal Women
Long-term consumption of high vitamin A diets may contribute to
osteoporosis & hip fracture.
P for trend
Quintiles of Vitamin A consumption
Food &
supplements µg/d
< 1250
1250-1699
1700-2249
2250-2999
≥3000
Multivariate RR
(95% CI)
1.00
0.92
(0.70-1.22)
1.13
(0.85-1.49)
1.24
(0.92-1.68)
1.48
(1.05-2.07)
Food only, µg/d
<1000
1000-1299
1300-1599
1600-1999
≥2000
Multivariate RR
(95% CI)
1.00
1.51
(0.86-2.66)
1.37
(0.74-2.51)
1.74
(0.96-3.14)
1.82
(0.97-3.40)
Feskanich D et al. JAMA. 2002;287(1):47-54.
0.003
0.24
Vitamin A Intake & Hip Fractures
Among Postmenopausal Women
P for trend
Quintiles of Retinol consumption
Food &
supplements µg/d
< 500
500-849
850-1299
1300-1999
≥2000
Multivariate RR
(95% CI)
1.00
1.25
(0.95-1.65)
1.18
(0.88-1.59)
1.43
(1.04-1.96)
1.89
(1.33-2.68)
Food only, µg/d
<400
400-549
5500-699
700-999
≥1000
Multivariate RR
(95% CI)
1.00
1.27
(0.77-2.07)
0.96
(0.57-1.63)
1.41
(0.86-2.32)
1.69
(1.05-2.74)
Feskanich D et al. JAMA. 2002;287(1):47-54.
<0.001
0.05
Vitamin A Intake & Hip Fractures
Among Postmenopausal Women
P for trend
Quintiles of Beta Carotene consumption
Food &
supplements µg/d
< 2550
2550-3549
3550-4649
4650-6299
≥6300
Multivariate RR
(95% CI)
1.00
1.18
(0.91-1.53)
1.03
(0.77-1.37
1.27
(0.96-1.69)
1.22
(0.90-1.66)
Food only, µg/d
<2500
2500-3449
3450-4549
4550-6099
≥6100
Multivariate RR
(95% CI)
1.00
1.06
(0.66-1.69)
1.36
(0.85-2.16)
1.12
(0.67-1.87)
1.36
(0.81-2.30)
Feskanich D et al. JAMA. 2002;287(1):47-54.
0.1
0.94
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
Feskanich D et al. JAMA. 2002;287(1):47-54.
Vitamin A Fortification
Vitamin A intakes accumulate from
Food
Fortified food
Supplements
Anderson J. Journal of Bone and Mineral Research 2002, 17 (8)
Can easily
exceed UL
safety
Iron Fortification
Most cost-effective way to prevent iron deficiency
Fe intake
Folate
Nutritional
anemia
Vitamin B12
Sarker A et al. AJCN. 2004; 80:149-53.
Infection
Non-nutritional
Anemia
Inflammation
H. Pylori
Iron Fortification
40
Anemia
H. Pylori
ID
IDA
Relative iron absorption (%)
35
Infected children with IDA
30
25
20
P = 0.34
15
10
5
0
Before treatment After treatment
Uninfected
children
Although associated with ID & IDA, H. Pylori eradication
does not significantly influence iron absorption.
Sarker A et al. AJCN. 2004; 80:149-53.
Iron Fortification
Additional exposure to dietary iron places some segments of
the population at increased risk of iron excess (Athletic males)
Frequent consumption of
red meat
Increased
Energy intake
Supplements
Fe-fortified foods
Iron overdose
18 mg
8 mg
Females
Males
RDA
45 mg
UL
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
Effect of calcium on absorption &
bioavailability of dietary iron
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).
310 subjects
194 females
Hallberg L,Hulthén L. Am J Clin Nutr 2000;71:1147–60.
116 males
Effect of calcium on absorption &
bioavailability of dietary iron
No inhibition when calcium
in a meal was < 50 mg
Inhibition maximum
when Ca 300-600 mg
Folate Fortification
1998: FDA made folic acid fortification of all cerealgrain 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
Associated with
 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
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
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
Kalmbach R D et al. (2008). American Journal of Clinical Nutrition 88 (3): 763-768
Wyckoff K. & Ganji V.(2007). Am J Clin Nutr: 86:1187-92
Mechanism
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 .
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
Thus N5, N10methylene THF needed
for DNA synthesis is
not produced which
leads to macrocytosis
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
Folic acid fortification
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.
Wyckoff K. & Ganji V. (2007). Am J Clin Nutr: 86:1187-92
Interaction between Vitamin B12 status and serum
folate in relation to anemia
Vitamin Status
B-12
Folate
Normal
Normal
Normal
High
0.6 (0.2-2.2)
Low
Normal
2.0 (1.1-3.5)
Low
High
5.2 (2.5-10.6)
1.0
0.1
0.5
1.0
Odds Ratio (OR)
Morris MS et al. Am J Clin Nutr. 2007;85:193-200.
5
10
Interaction between Vitamin B12 status and serum
folate in relation to cognitive impairment
Vitamin Status
B-12
Folate
Normal
Normal
1.0
Normal
High
0.5 (0.2-0.9)
Low
Normal
1.9 (1.1-3.1)
Low
High
4.9 (2.6-9.2)
0.1
0.5
1.0
Odds Ratio (OR)
Morris MS et al. Am J Clin Nutr. 2007;85:193-200.
5
10
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
Folic acid fortification & Cancer
Folate plays a dual role in carcinogenesis
Prevention of
early lesions.
Potential harm once
preneoplastic lesions
have developed.
Once established  small tumor may grow more
rapidly with folate supplementation
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
Folic acid fortification & Cancer
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
Thank You