Interactions that determine vitamin A, iron, and zinc status in humans

1
Interactions that determine vitamin A, iron, and
zinc status in humans Penelope Nestel
2
Important interactions

• Cooking and processing
• Bioavailability

3
Carotenoids, iron, zinc

• Carotenoids
• The colors of nature
• gt600 identified in nature
• 50 are provitamins A
• The major carotenoids found in people
  b-carotene, a-carotene, lycopene, b-cryptoxanthin
  lutein
• Provide 80 dietary vitamin A in developing
  countries

• Iron
• Heme
• Non-heme
• Plant ferritin
• Plant hemoglobin
• Zinc

4
Why study bioavailability?

• Iron, zinc, and vitamin A deficiency most common
  widespread deficiencies in developing countries
• Foods high in provitamin A, Fe, Zn not readily
  consumed by everybody, e.g. liver, eggs,
  fortified foods
• Bioavailability not an issue for
• Retinol (80-95 absorbed)
• Heme iron (25 absorbed)
• Bioavailability an issue for provitamin A,
  non-heme Fe, and Zn
• Need to know how to enhance bioavailability

5
Definitions

• Bioavailability the fraction of an ingested
  nutrient that is available for utilization in
  normal physiological functions or for storage
• 100 means that all of the ingested nutrient is
  absorbed and available

6
Determined bioavailabilities

• 20-50 of ingested b-carotene is absorbed and
  highly dependent on fat
• 5-15 Fe depending on type of diet
• 15-50 Zn depending on type of diet

7
Definitions unique to b-carotene

• Bioconversion the proportion of bioavailable
  carotene converted to retinol
• 100 all of bioavailable b-carotene is
  converted to retinol
• Bioefficacy the efficiency with which ingested
  carotenoids are absorbed and converted to retinol
• 100 1 mmol dietary b-carotene 2 mmol retinol

8
Assessing bioavailability

• Provitamins A
• Changes in serum retinol carotenoid
  concentrations
• Breast milk retinol carotenoid concentrations
• Change in modified relative dose response values
• Stable isotope techniques

• Fe Zn
• Changes in serum indicators of Fe or Zn status
• Hair Zn concentration
• Stable isotope techniques
• Hb incorporation
• whole body retention

9
Carotenoids SLAMENGHI

• 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

10
Species of carotenoids

• All-trans isomer - naturally occurring
  configuration
• Strong preferential absorption of the all-trans
  isomer demonstrated, except for lycopene (Boileau
  et al, Expl Biol Med 2002227 914-9.)
• Even when fed as the cis, shows up in the plasma
  as the trans isomer (You et al, AJCN 199664
  177-83)

11
Molecular Linkage

• Not well studied
• Esterification may enhance absorption (Bowen PE,
  J Nutr 2002132 3668-73)
• Evidence that lutein esters are more bioavailable
  than lutein not well studied with provitamin A
  carotenoids, e.g., b-cryptoxanthin.
• Esters are not absorbed by the enterocyte,
  therefore bioconversion to retinol is not affected

12
Amount of carotenoids consumed

• The kinetics of serum response to orally ingested
  b-carotene seems to be dose independent 60 vs
  210 mg b-carotene in lactating women (Canfield et
  al, AJCN 19966652-61)
• Given with or without a meal
• Other carotenoids present competition, e.g.
  zanthophylls in maize

13
Evidence of competition in humans

• b-carotene reduced lutein availability, but
  b-carotene response was not consistent between
  individuals (Kostic et al, AJCN 199562604-10)
• Lutein may inhibit the absorption of ß-carotene,
  particularly when lutein is the predominant
  carotenoid (Van den Berg, IJVNR 199868360-65
  Nutr Rev 1999571-10, Van den Berg and Van
  Vliet, AJCN 19986882-89)
• b-carotene reduced canthaxanthin availability
  but canthaxanthin did not reduce b-carotene
  appearance (White et al, JA Coll Nutr
  199413665-71 Paetau et al, AJCN
  1997661133-43)

14
Matrix in which the carotenoid is incorporated

• b-carotene dissolved in oil is more readily
  absorbed than that in foods
• Carotenoids can be entrapped and complexed to
  proteins in chloroplasts and cell structures
• Cooking can increase bioavailability of
  carotenoids can also destroy them

15
Bioconversion provitamin A carotenoids

• 131 sweetpotato
• 101 spinach
• 61 synthetic b-carotene
• (Haskell et al, AJCN 200480705-14)

16
Effectors of absorption and bioconversion
enhancers

• Protein stabilizes fat emulsions, enhances
  micelle formation, and carotenoid uptake
• Lecithin facilitates micelle formation and
  therefore carotenoid absorption
• Fat minimum amount necessary (5 g/meal)

17
Effectors of absorption and bioconversion
inhibitors

• Drugs some can decrease bioavailability
• Dietary fiber decrease absorption of
  carotenoids.
• Alcohol appears to affect carotenoid metabolism

18
Nutrient status of the host

• Bioavailability likely to be dependent on vitamin
  A status (Lee et al, J Nutr 1998128280-86)
• Current b-carotene intake and circulating
  b-carotene levels inhibit carotenoid
  bioconversion (West Castenmiller,
  IJVMR199868371-77)

19
Status of other nutrients

• Poor protein status or zinc deficiency affect
  b-carotene uptake subsequent bioconversion to
  retinol
• Poor protein diets or zinc deficiency may also
  interfere with the synthesis of retinol binding
  protein

20
Genetic factors

• Most inter-personal differences can be explained
  by the ingestion of supplements or dietary
  differences
• Lipid malabsorption syndromes reduce absorption
  of carotenoids
• Failure to split b-carotene in humans is rare,
  but can lead to carotenemia or vitamin A
  deficiency

21
Host-related factors

• Gender Serum response is higher in women than
  men, but may be due to differences in body weight
  composition
• Age inconclusive
• Disease where fat malabsorption or maldigestion
  is present

22
Mathematical Interactions

• The difference in effect observed when two
  factors play a role together compared with the
  product of the effects observed separately
• Area-under-the curve studies kinetic modeling
  involving a variety of compartments after
  ingestion of labeled b-carotene have been
  performed

23
Factors affecting bioavailability of minerals

• Iron (heme/non heme) or zinc intake
• Individual status
• Protein quantity quality
• Phytate
• Polyphenols (Fe)
• Organic acids (Fe)

24
Factors affecting bioavailability of iron

• Type of iron in meal
• Heme iron more bioavailable than non heme iron
• Iron status
• Low status enhances absorption

25

• Phytate
• Phytates form insoluble and/or indigestible
  complexes between iron, phytate, proteins
• Dose dependent inhibition of phytate (Hurrell et
  al, AJCN 199256573-76)
• Typically 1-2 phytate 2-5 Fe ab
• 0.10 phytate - 2-fold ?Fe ab
• 0.01 phytate - 5-fold ? Fe ab
• Require molar ratio PAFe lt11, preferably lt11
  0.41
• 30-40 mg/100 g in wheat flour (Hurrell, J Nutr
  20031332973S-77S)

26

• Polyphenols
• Form insoluble iron-tannate complexes
• 1 cup of tea ? Fe absorption 30 (Disler et al,
  Gut 197515193-200)
• Dose dependent (Derman et al, Br J Nutr
  197738261-9)
• 1 cup of coffee ? Fe absorption 30 (Morck et
  al, AJCN 197337416-20)
• Galloyl groups 3 adjacent hydroxyl groups are
  the main common structure in polyphenols that
  bind iron
• Coffee effect from chlorogenic acid

27

• Protein quantity quality
• Soy beans and nuts inhibit non-heme iron
  absorption
• Meat, fish, and poultry enhance iron absorption
• Organic acids
• Vitamin C molar ratio 41 vit CFe required
  (Hurrell et al, Nutr Rev 200260S7-15)
• Other organic acids citric acid, malic acid,
  tartaric acid, and lactic acid

28
Factors affecting bioavailability of zinc

• Amount of zinc in meal
• Fractional Zn absorption ? with ? amounts of Zn
  in meal
• Zinc status
• Low status enhances absorption
• 53 absorption of Zn from diet containing 5.5
  mg/d vs 25 when 16.5 mg/d fed (Wada et al J Nutr
  19951151345-1254)

29

• Protein quantity quality
• Fractional Zn absorption ? linearly with ?
  protein content
• Animal protein counteracts inhibitory effect of
  phytate
• Phytate
• Zn absorption inversely correlated with phytate
  content
• no threshold effect
• inhibition from IP5 IP6 but not IP4 IP3
  (Lonnerdal et al, 1989 J Nutr119211-14)

30

• Dose dependent inhibition of phytate (Hurrell et
  al AJCN 199256573-676)
• Typically 1-2 phytate 2-10 Zn absorption
• 0.10 phytate - 2-fold ? Zn absorption
• 0.01 phytate - gt2-fold ? Zn absorption

31
Summary of bioavailability factors

• Provitamins A
• Carotenoid species
• Molecular linkage
• Carotenoids in meal
• Matrix
• Absorption bioconversion effectors
• Interactions

• Minerals
• Phytate
• Polyphenols
• Organic acids
• Heme iron
• Cysteine-like AA
• Long-chain fatty acids (eg, palmitic acid)
• NDC (eg, inulin, resistant starch, etc.)

Host related Age, ethnicity, physiological
status, nutritional status, disease state,
genetic propensity