Nutrients Bioavailability from FoodSourc

Bioavailability of nutrients from food

1. Nutrient
Bioavailability
(What weget from what we have taken in)
Dereje Tsegaye(MPH,Assiss.Prof.PhD fellow)
1

2. Topics
•Definition
•Whatmakesitup
•Criticalphase
•Howitsmeasured
2

3. First basic law of nutrition:
No nutrient is absorbed and
utilized to the full extent that
it is fed
Steven Blezinger
3

4. Define Bioavailability
•Bioavailabilityisthefractionofaningestednutrient
thatisavailableforutilizationinnormalphysiologic
functionsandforstorage.
–Thatwhichbecomesbioavailable
–Thefraction(orpercentage)ofnutrientabsorbedthat
isusefultothebody
–Thedegreetowhichanabsorbednutrientisavailable
tothesystem
4

5. Biological Availability
(Bioavailability)
•Definitioncanbebasedoneitherthepercentageofa
nutrientingestedorthepercentageofanutrient
absorbedthatbecomesusefultotheorganism
•Thepercentageingestedispreferredbysomebecause
thepercentageabsorbedisdifficulttodetermineand
reliesonanindirectanalysis
•Thepercentageabsorbedis,nonetheless,amore
accurateappraisalofbioavailability
5

6. •Bioavailabilityisapost-absorptionassessmentofhow
muchofanutrientthathasbeenabsorbedbecomes
functionaltothesystem
Nutritional Definition
•Bioavailabilityisaassessmentofhowmuchofa
nutrientisretainedinthefoodproductafter
processingfortheconsumer
Food Science Definition
6

7. •Assimilationmaybeamajorpartofamineral’s
bioavailabilityandneedstobeassessedseparatelye.g.
75Se as selenite
75Se as selenomethionine
Absorption %
92
96
Retention %
a
<50
>80
a
Arbitrary units
•2-picolinicacidenhanceszincabsorptioninratsby
nearly60%.
•But,alsoincreaseszincexcretionsothereisnonet
effectonretentionandhencenoincreasein
bioavailability
Why Not Absorption Alone as an index of
Bioavailability?
7

8. Different terms used in bioavailability
•Bioavailabilityisthefractionofaningestednutrient
thatisavailableforutilizationinnormalphysiologic
functionsandforstorage.
•Bioconversionisthefractionofabioavailablenutrient
(e.g.,absorbedprovitaminAcarotenoids)thatis
convertedtotheactiveformofanutrient(retinol).
8

9. Terms…
•Bioefficacyisthefractionofaningestednutrient(e.g.,
dietaryprovitaminAcarotenoids)thatisabsorbedand
convertedtotheactiveformofthenutrient(retinol)in
thebody.
•Functionalbioefficacyisthefractionofaningested
nutrientthatperformsacertainmetabolicfunction,such
astheabilityofingestedprovitaminAcarotenoidsto
reverseorpreventabnormaldarkadaptation. 9

10. •WithrespecttoprovitaminAcarotenoids,theterm
bioefficacyisdefinedastheproductofthefractionofthe
ingestedamountthatisabsorbed(bioavailability)and
thefractionofthatwhichisconvertedtoretinolinthe
body(bioconversion).
*Bioefficay=bioavailabilityXbioconversion
10

11. Components of Bioavailability
•Digestion
•Absorption
•Liver surveillance
•Transport
•Trans membrane
movement
•Intracellular movement
•Target binding
Assimilation
Phase
Absorptive
Phase
11

12. Bioavailability in toto
Raw Food Product (100%)
Processed Food
Digestion
Absorption
Cellular uptake
Functional Nutrient
Total (proximate analysis)
Chemically available
Biologically available
12

13. The fraction of the total amount absorbed that
performs a function
Digestion
Absorption
Functional Site
Blood Transport
Membrane transport
Losses
along
the way
Which is the
most critical
phase for
Nutrients ?
Intracellular movement
Liver and kidney excretion
13

14. Note that
A nutrient is considered outside the
bodyuntil it passes through the
intestinal barrier
14

15. The amount that gets absorbed depends on:
•Digestibility of the food source
•Solubility of the nutrient
•Elements in the food source that hinder or facilitate
absorption (enhancers and inhibitors)
With a focus on the organism, bioavailability
depends on:
Extrinsic Factors
•Age
•Health
•Nutritional state
•Physiological state
•Genetic predisposition
•Gender
•Developmental stage
•Species
Intrinsic
Factors
15

16. Bioavailability of
Macronutrients
16

17. Absorption & Transport
End-products of digestion:
1. CHO >>> Monosaccharides
2. Fats >>> Glycerol + fatty acids
3. Proteins >>> Amino acids
4. Vitamins, minerals & water –no
digestion
17

18. Absorption
18

19. Absorption & Transport
•Absorptionoccursinthesmallintestine
–Wallofsmallintestinecoveredwith100soffolds
–Eachfoldcoveredwith1000sofvilli
–Eachvillicontains100sofmicrovilli
19

20. The Small Intestine Villa
20

21. Absorption & Transport
•Absorbednutrientsentereitherthe:
1.Vascularsystem–water-solublenutrients
(monosaccharides,aminoacids,water-solublevitamins,
minerals,water,shortchainfattyacids)entertheblood
viatheportalveinfortransporttotheliver
2.Lymphsystem–fat-solublenutrients(lipids,fat-soluble
vitamins)enterhere,eventuallyenteringthebloodnear
theheart
21

22. Absorption & Transport
3.Transportoflipidsandlipidsolublevitamins–sincefats
areinsolubleinwater,theymustbepackagedfor
transportaslipoproteins(triglyceride,phospholipid,
protein,cholesterol)
22

23. Absorption of Carbohydrates
a)Starch and other discharides
23

24. a)Starch & other disaccharides …
24

25. 25
They get fermented in the
colon by anaerobic bacteria
Oligosaccharides (eg. Raffinose, Stachyose)
and non-starch polysaccharides resistant
starch
Escape digestion in the
upper gut (small intestine
Increased faecal Biomass
resulting in increased
peristalsis
Production of
short chain fatty
acids (SCFA)
 Acetate
 Propionate
 Butyrate

Production of
gases likes co2,
methane and
hydrogen
sulphide
b)Digestion of oligosaccharides, resistant starch and non-
starch polysaccharides (Dietary Fiber)

26. 26
Dietary fiber
•Fiberreferstocertaintypesofcarbohydratesthatour
bodycannotdigest(oligosaccharidesandnon-starch
polysaccharides).
•Thesecarbohydratespassthroughtheintestinaltract
intactandhelptomovewasteoutofthebody.
•Dietsthatarelowinfiberhavebeenshowntocause
problemssuchasconstipationandhemorrhoidsandto
increasetheriskforcertaintypesofcancerssuchascolon
cancer.

27. 27
Cont…
•Dietshighinfiber;however,havebeenshownto
decreaserisksforheartdisease,obesity,andthey
helplowercholesterol.
•Foodshighinfiberincludefruits,vegetables,and
wholegrainproducts.

28. 28
How does fiber prevent different health
problems?
Cancer(Colonic,breast..)
•Preventssecondarybileacidcirculation
•Decreaseintestinaltransittime
•Decreasecontactofcarcinogenswithintestinal
cells
•Fermentationproductbutyratehasapoptotic
effect
•Decreasesabsorptionfatsandsugars

29. 29
Cont…
DietaryFiberpreventsConstipation,Hemorrhoids&
Diversticulosisby:
•Increasingperystalsismakingstoolbulk
•Decreasingstrainingtopassstool

30. Carbohydrate malabsorption
Lactose intolerance
•Mostmammalsnormallyceasetoproducelactase,
becominglactoseintolerant,afterweaning
•Itisestimatedthat75%ofadultsworldwideshowsome
decreaseinlactaseactivityduringadulthood
•Thefrequencyofdecreasedlactaseactivityrangesfrom
5%innorthernEuropethrough71%forSicilytomorethan
90%insomeAfricanandAsiancountries
•Thisdistributionisnowthoughttohavebeencausedby
recentnaturalselectionfavoringlactase-persistent
individualsinculturesinwhichdairyproductsareavailable
asafoodsource.
30

31. Mechanism of Lactose-Induced Diarrhea
and Flatus
Lactase-sufficient
people absorb
>80% of lactose
Lactase-deficient
people absorb
<50% of lactose
6-20 grams malabsorbed
lactose = flatus
(1 g = 44 ml H
2)
>20 grams malabsorbed
lactose = flatus+diarrhea
Small
bowel
Colon
Lactose
Glucose
Galactose
Lactose
CO
2+H
2
SCFA
lactose
glucose
galactose
FLATUS OSMOTIC DIARRHEA31

32. Glycaemic Index
•Theglycemicindexorglycaemicindex(GI)isameasure
ofhowquicklybloodglucoselevels(i.e.,bloodsugar)
riseaftereatingaparticulartypeoffood.
•Glucose(thedefiningstandard)hasaglycemicindexof
100
32

33. Classification
Glycaemic
index range
Examples of foods
Low GI 55 or less
beans(white, black, pink, kidney, lentil, soy,
almond, peanut, walnut, chickpea); small seeds
(sunflower, flax, pumpkin, poppy, sesame); most
whole intact grains(durum/spelt/kamutwheat,
millet, oat, rye, rice, barley); most vegetables, most
sweet fruits(peaches, strawberries, mangos);
tagatose; fructose
Medium GI56–69
not intact whole wheator enriched wheat, pita
bread, basmati rice, unpeeled boiled potato, grape
juice, raisins, prunes, pumpernickel bread,
cranberry juice, regular ice cream, sucrose, banana
High GI 70 and above
white bread(only wheat endosperm), most white
rice(only rice endosperm), corn flakes, extruded
breakfast cereals, glucose, maltose, maltodextrins,
potato, pretzels, parsnip, bagels
Glycaemic index...
33

34. Absorption of Lipids
•Abnormaltofindmorethan6or7%ofingestedlipidsstill
intactinthefeces(Digestibility=93-94%).
•Mostfatabsorptiontakesplaceintheduodenumor
jejunum–micellescarrymonoglyceridesandfreefatty
acidstothebrushborderwheretheydiffuseinto
enterocytes.
•Cholesterolandothersterolsarepoorlyabsorbed.
•Overall,about50%ofdietarycholesterolisabsorbed.
•Fiber(especiallysolublefiber)decreasecholesterol
absorption 34

35. ABSORPTION…
•Bilesaltsareabsorbedintheileum(enterohepatic
circulation)
•Short-chainfattyacids(<12carbon)andglycerol
areabsorbeddirectlyintobloodstream.
•Theydonotenterthelymphsystem
•Onceintheenterocytes,Largerchainfatty
acids(>=12carbon),monoglyceridesandfreefatty
acidsarereformedintotriglycerides
35

36. ABSORPTION…
•Thetriglycerides,andcholesterolwillbeesterfiedinto
cholestrolesterandthesewillbecoatedwith
phospholipids,andproteintoformaLipoproteincalled
Chylomicron
•CHYLOMICRONSenterthelymphaticsystemthroughthe
lacteals
•ChilomicronsVLDLLDLHDL
Lipoproteinlipaselysescontents!
36

37. triglycerides
Absorption of Lipids…
37

38. 38

39. Absorption & Transport
4basictypesoflipoprotein:
1.Chylomicrons–very,verylowdensity(85%
triglyceride);absorbedfromsmallintestineinto
lymph&circulatedtocellswheresomeoflipid
materialispickedoff&remnantsreturntoliver
2.VLDL–verylowdensitylipoprotein(50%
triglyceride);madebyliver&travelstocells
39

40. Absorption & Transport
3.LDL–lowdensitylipoprotein(50%cholesterol);
remainsofVLDL;highlevelsincreaseriskof
heartattack
4.HDL–highdensitylipoprotein(50%protein);
removescholesterolfrombloodforreturnto
liver;highlevelsdecreaseriskofheartattack
40

41. Malabsorption due to
Luminal Maldigestion of Fat (Steatorrhea)
:Common causes
Pancreatic insufficiency:Chronic pancreatitis
Bile salt deficiency: Loss of terminal ileum:
loss of bile salts in stool
insufficient bile salts
Bacterial overgrowth: Deconjugation and loss
of bile acids
Gastric hypersecretion:Acid inactivation of
pancreatic enzymes
41

42. 0
20
40
60
80
100
0 20 40 60 80 100
Relationship between Pancreatic
Function and Steatorrhea
Fecal Fat (g/day)
Pancreatic Function (%) This leads to deficiency of
Lipid soluble vitamins
42

43. ABSORPTION OF PROTEINS
•Mostproteinabsorptiontakesplaceintheduodenum
andjejunum
•Mostaminoacidsareabsorbedintothebloodstream,
butsomeremainintheenterocytesandareusedto
synthesizeenzymesandnewcells
•>99%ofproteinentersthebloodstreamasaminoacids
•Absorptionofwholeproteincancauseasevereallergic
reaction
43

44. ABSORPTION OF PROTEINS…
•Intheenterocyte,otherpeptidasesimmediatelydigest
everythingintosingleaminoacidswhichareabsorbed
intothebloodstream
•Someaminoacidssharethesametransportsystem,so
ifyoutakeinalargeamountofoneparticularamino
acid,youmaybeinhibitingtheabsorptionofothers
44

45. Free Amino Acid Absorption
•Free amino acids
–Carrier systems
•Basic AA
•Neutral AA
•Acidic AA
•Iminoacids
–Entrance of some AA is
via active transport
•Requires energy
Na
+
Na
+
45

46. Peptide Absorption
•Form in which the majority
of protein is absorbed
•More rapid than
absorption of free amino
acids
•Active transport
–Energy required
•Metabolized into free
amino acids in enterocyte
•Only free amino acids
absorbed into blood
46

47. Absorption of Intact Proteins
•Newborns
–First 24 hours after birth
–Immuno globulins
•Passive immunity
•Adults
–Paracellular routes
•Tight junctions between cells
–Intracellular routes
•Endocytosis
•Pinocytosis
•Of little nutritionalsignificance...
–Affects health (allergies and passive immunity)
47

48. Groff & Gropper, 2000
*Whole proteins are nutritionally insignificant...
Basolateral Membrane
•Transport of
free amino acids
only*
–Peptides are
hydrolyzed
within the
enterocyte
•Transport mainly by
diffusion and
Na-independent
carriers
48

49. Protein Malabsorption
Celiac Sprue I
•Immune-mediateddestructionofenterocytesinresponse
toingestionoftheproteinglutenfoundinwheatand
certainothergrains.
•Afractiontermedgliadincontainstheimmunogenic
material(gluteninducedeteropathy)
•Smallintestinalvilliaredamagedordestroyed-"flatgut"
appearance.
•Maturedigestingandtransportingenterocytesare
virtuallyabsent.
49

50. Celiac Sprue -II
•Patchydisease-usuallyaffectsproximalintestinemore
thandistalintestine.
•Mucosaldigestionandabsorptionarebothseverely
impaired.
•Characteristicantibodiesusedindiagnosis:IgA
antibodiestotissuetransglutaminaseorgliadin.
50

51. Clinical Manifestations of Sprue
•Weightloss,oftenwithincreasedappetite
•Bulky,oilystools–steatorrhea-fatmalabsorption
•Flatus/frothystools–carbohydratemalabsorption
•Anemia–deficienciesofiron,folate
•Osteopenicbonedisease–VitaminDandcalcium
malabsorption
•Edema/hypoproteinemia–proteindeficiencyand
malnutrition
•Cheilosisandglossitis–Bvitamindeficiencies
•TheonlyknowneffectivetreatmentisalifelongGluten
FreeDiet
51

52. Absorption of
Minerals
(Unifying principles that apply to all minerals)
52

53. Digestion
•Preparingforabsorption
•Liberatingmineralsfromaboundstatetoanaqueous
phase
•Digestiveenzymes
•Bileacidsandsaltsthatworkwithdigestiveenzymes
(e.g.,lipases)
53

54. Purpose of digestion to mineral nutrition
•Mineralsinafoodsourcearelockedwithinamatrix
composedprimarilyofproteins,complex
carbohydratesandfats
•Thepurposeofdigestionistorenderlargecomposite
moleculesintosmallermanageableunits…mineralsare
liberatedduringthisprocess
•Digestiveprocessesconsistsmainlyofhydrolytic
enzymesthatbreakchemicalbondsbetweenmodular
unitswithouttotaldestruction(metabolism)ofthe
liberatedcomponents
54

55. Digestive Enzymes (hydrolases)
Enzyme Location Target Action
Pepsin gastric juiceproteins breaks peptide bonds
Trypsin and
chymotrypsin
duodenum proteins breaks peptide bonds
Amylases saliva and
duodenum
starch and
glycogen
breaks glycosidic bonds
Lipases duodenum complex
lipids
breaks ester bonds
Glycosidasesmicrovilli di-and tri-
saccharides
breaks glycosidic bonds
Peptidases microvilli small
peptides
breaks peptide bonds
I
II
Phase I is primarily salivary and pancreatic secretions
Phase II involves enzymes on the surface of absorbing cells
55

56. Critical factors in Mineral Absorption
•Absorptiontendstobeselectiveforthemineral(makes
findingaunifiedmechanismmoredifficult)
•Adeficiencyincreasesthefractionofthatmineral
absorbed(absorptionistunedtointernalbodilyneeds)
•Certainfoodchemicals(e.g.,phytate,oxalate)lower
absorptionbytyingupthemineral
•Thereiscompetitionforabsorptionmachinery
56

57. Critical factors…
•Metalionsantagonism(Cu-Zn;Zn-Fe;etc.)occursation
channelsduringthetransmuralpassagephaseof
absorption
•VitamindependencyisseenwithVitaminDandCthat
regulatebodyloadofCa
+2
andFe
2+
respectively
•Absorptivecellsexcretefactorsthataidinthesolubility
ofmetalions
•Sometransportproteinsareinvesiclesthatfusewiththe
membraneandmovevectoriallywithinthecell
57

58. Steps in mineral absorption
1.Transportthroughtheluminal(apical)cellmembrane,
i.e.,startoftranscellular
2.Handlingwithintheenterocyte,i.e.,mediate
transcellular
3.Transportthroughtheantiluminalbasolateralmembrane
intothecirculation,i.e.,endoftranscellular.
4.Transportbetweenthecells,i.e.,paracellular
*Onlymetalsinanaqueousphasecanbetransportedinto
theenterocyte
58

59. Two categories of ingested metal Ions
1. Solubility not dependent on pH
2. Solubility pH dependent
Examples: Na+, K+, Mg2+, Ca2+
Examples: Cu2+, Fe2+, Mn2+, Zn2+
Category 2 metal ions are soluble in acid, but form insoluble
hydroxy-polymersat neutral or alkaline pH.
Category 1 metal ions are soluble throughout
the gastrointestinal pH range (1-8)
Solubility and Metal Ion Absorption
59

60. Secretions of Digestion
60

61. Mucosal Side
Serosal Side
Basolateral
Surface
(antiluminal
surface)
Apical
surface
Microvilli
Ca
Ca
Ca
Enterocyte
To access the serosal
side, the mineral must
pass either through the
enterocyte (transcellular
99%) or the junction
between enterocytes
(paracellular <1%))
Fe
Fe
Fe
A large fraction of the
iron can be trapped
(sequestered) within
the cytosol of the
enterocyte)
61

62. Role of Vesicles in the Regulation of
Mineral Absorption
Vesicles are internal membrane compartments that move between the cytosol
and membranes. This movement is regulated by external factors
Vesicles contain the transport proteins that absorb the mineral into the lumen of
the vesicle and bring it into the cell
Vesicles that have fused with the membrane are positioned to absorb minerals.
Absorption thus depends on the number of vesicles that fused
with the membrane.
Resting Cell Absorbing Cell
62

63. MACROMINERALS
•Monovalent cations, Na
+
, K
+
•Monovalent anions,Cl
-
•Divalent cations, Ca
2+
, Mg
2+
•Complexes, HPO
4
=
, HCO
3
-
63

64. Rule1:Macromineralsingeneralenterintestinalcells
throughtransportportalsdesignatedforthemineral
(major)orbetweencells(minor).
Rule2:Theenergyforentryisprovidedbyaconcentration
gradientacrossthemembraneorbyhydrolysisofATP
(activetransport)
Rule3:Electro-neutralityissoughtintheoperationof
membraneco-transporters
Rules that apply to the absorption of Macrominerals
64

65. Macrominerals
Na
+
, K
+
, Cl
-
, HPO
4
-
, Mg
2+
, Ca
2+
•Themacro-mineralsforthemostpartrelyondiffusion
controlledmechanismscombinedwithspecificchannel
proteinstopassintothesystem.
•Gradientsacrossthemembranecanbedrivenby
unidirectionalandbidirectionalATPaseenzymes
Example
Na
+
/K
+
ATPase
Ca
2+
/H+ ATPase
65

66. Properties of Macro-minerals Relative to
Absorption
1.Monovalentionsexistmostlyasfreeions
2.Monovalentionsareunabletoformstablecomplexes
3.Divalentionsexistpartiallyasfreeions
4.Divalentionsaremoreapttoformcomplexeswith
proteinsandorganics
5.Complexesexistmainlyasfreeions
66

67. Absorption of Sodium and Chloride
Na
+
Na
+
Glucose
Amino acids
H
+
Cl
-
HCO
3
-
Apical (lumen) side
Glucose cotransporter
Amino acid transporter
Na+/H+ antitporter
CO
2 CO
2
H
2CO
3
H
+
H
+
+ HCO
3
-
H
2O
2K
+
3Na
+
Anion antiporter
Blood
Intestinal Enterocyte
Carbonic anhydrase
ATP
ase
Na+/K+ ATPase
67

68. Calcium and Magnesium
68

69. 50
100
0
0
100 200
Dietary Calcium
Calcium
Absorbed
50
100
0
0
100 200
Dietary Calcium
No Vit D Vit D ( 1,25-(OH)
2-D
3)
Saturable
Non-Saturable
Duodenum
Vitamin D deficient rats
69

70. 0
0
100 200
50
100
0
0
100 200
Saturable
0
0
100 200
Saturable
Non-saturable
Duodenum Jejunum
Ileum
Calcium Instilled, mM
Uptake in ileum is by diffusion only; it is, therefore, not regulated
by vitamin D. Thus, most of the Ca2+ is absorbed in the
duodenum.
70

71. •CaT1,aCachannelproteininthebrushborderofhuman
enterocyte,isregulatedby1,25-dihydroxyvitaminD.
•ThevitaminappearstomediatechangesinCaT1-mRNA
levels.CaT1,therefore,couldbetheprimarygatekeeper
regulatinghomeostaticmodulationofintestinalcalcium
absorptionefficiency.
•Ourbestunderstandingisthatcalciumentersthe
duodenalcellthroughcalciumchannelswhichmay
containavitaminDresponsiveCa-bindingcomponent.
Entryisdownanelectrochemicalgradient(Bonner,1999)
71

72. Ca
2+
Ca
2+
Calbindin
ATP
ase
ATP
ase
Ca
2+
CAT1
Mg2+
(Na+)
Ca
2+
Calcium ATPase
Enterocyte
Paracellular
Ca
2+
Ca bound to
fiber, phytate,
oxalate, fatty
acids
Calcium ATPase
antiporter
Lumen Blood
Ca
2+
Calcium Absorption
Albumin
Vitamin D
responsive
CAT1 is a Ca
2+
channel protein located in the brush border of mucosal cells
Calbindin is a small (9 kD) protein in the cytosol of mucosal cells
72

73. Magnesium
1. Absorption depends on concentration
2. Absorption is saturable and non-saturable (7-10%)
3. Fully saturable in ileum but not jejunum (contrast with calcium)
4. Absorption in the colon significant
Human Study
Fed Fractional Absorption
7 mg 65-75%
36 mg 11-14%
73

74. Magnesium
Enterocyte
Mg
2+
TRPM6
Distal jejunum and ileum
Cation channel protein
(transient receptor
protein TRP)
Mg
2+
Since TRPM6 operates by
diffusion without co-
transporters, Mg
2+
absorption efficiency
depends on the amount
of Mg
2+
in the diet and
within the cell
ATP
ase
ATP
ADP
Mg
2+
Mg
2+
-bound to
phytate, fiber,
fatty acids
74

75. Microminerals
Becauseoftheirverylowcellularconcentrations,the
micronutrientsrelyonspecifichighaffinitytransporters
andbindingproteinsformovement.Somecollectin
vesiclesandusethevesicleasthetransportfactor.
Fe
2+
, Cu
2+
, Mn
2+
,
Zn
2+
Redox-sensitivemetals(Fe
2+
/Fe
3+
,Cu
+
/Cu
2+
)relyon
valencestatechangestobesequesteredortransported
fromthecell.
75

76. MetalssuchasFe
3+
andZn
2+
aremoresolublein
acidsolutionsduetoashiftintheequilibrium
towardsthefreeion
Fe(OH)
3(s) Fe
3+
(aq) + 3OH
-
(aq)
H
+
Zn(OH)
2(s) Zn
2+
(aq) + 2OH
-
(aq)
Pulls equilibria
pH
1.02.03.04.05.06.07.08.09.0
Solubility
Fe(OH)
3solubility
Zn(OH)
2solubility
76

77. Elements of Micromineral Absorption
•Insolubilityorironandzincispartiallyovercomeby
mucinssecretedfromthecells
•Fe
3+
andCu
+
canengagetheirrespectivetransporters
•Cytosolicsequesteringandregulatoryfactorshavethe
potentialtolockthemineralwithinthecellandblockits
release
•InternalmovementofZn
2+
,Cu
+
andFe
3+
isprimarilyvia
vesicles
•BasolateralsurfacereleaseisredoxsensitiveforFeandCu
77

78. Iron regulation
78

79. Iron metabolism
79

80. •Mucinsarecomplexpolysaccharidessecretedinto
thelumenthatassistinstabilizingthesolubilityof
metalions
•Mucinspreventalkaline-inducedpolymerizationof
category2metalionsandmakethemetalionavailable
totransportersontheenterocytesurface
Mucins
80

81. Mineral Bioavailability
81

82. Methods of
Assessing
Bioavailability
82

83. 1. Depletion-Repletion Techniques
•Inthe“Sheffieldexperiment”conductedinthe1940s,in
whichmaleparticipantswereconscientiousobjectorsto
militaryservice,16(2womenand14men)subjects
consumedavitaminA–deficientdietand7control
subjects(1womanand6men)consumedthesamediet
butwithadditionalsupplementsofretinolorB-carotene
fromvarioussourcesforperiodsrangingfrom8.5to25
mo.
83

84. Depletion-Repletion…
•Darkadaptationwasusedasafunctionalindicatorof
bioefficacy.
•Inthecontrolgroup,either750µgretinol/d(n=2)or
3000µgB-carotene/dinoil(n=4)orinmargarine(n=
2)preventedimpaireddarkadaptation.
•Inthe16subjectsfedthedeficientdiet,only3men,
whoalsohadthelowestplasmaretinolconcentrations,
developedimpaireddarkadaptation(depletionphase
ofthestudy).
84

85. Depletion-repletion…
•Either390µgretinol/d(n=1)or1500µgB-carotene/d
inoil(n=2)wasrequiredtoreversethisimpaireddark
adaptation(repletionphase).
•Otherdepletion-repletionstudiesconductedbyBooher
etal(15;n=5)andbyWagner(16;n=10)shortlybefore
WorldWarIIreachedsimilarconclusions.
•Whereasinthe1970sSauberlichetal(17;n=8)
concludedthat,onaweightbasis,onlytwiceasmuchB-
caroteneasretinolwasrequiredtoreverseimpaired
darkadaptation.
85

86. 2. Balance studies
•Inoral-fecalbalancetechniques,thedifferencebetween
theamountof-caroteneinfoodconsumedandthat
excretedinfecesisassumedtorepresenttheamountof
nutrientabsorbed(eg.B-cartotene).
•Withthesetechniques,gastricorbacterialdegradation
ofunabsorbedcarotenoidsmaycontributeto
overestimationofabsorption.
•RaoandRaofoundindicationsthatsuchbacterial
degradationoccurs.
86

87. Balance study…
•Ontheotherhand,endogenouslysecretedbetacarotene
mightbeexcretedinfeces,thusleadingtoan
underestimateofbioavailability.
•Thus,dataonthebioavailabilityofcarotenoidsobtained
withbalancetechniquesshouldbeinterpretedwithcare.
87

88. 3. Radioisotopes
•Nearlyalloftheearlyworkcharacterizingbodyironpools
andironbioavailabilitywasundertakenusingiron
radioisotopesspecifically55Feand59Fe
•Radioactiveisotopeshavesomeadvantagesinhuman
studiesinthatthey
–requireaverysmall,essentially‘massfree’,
–amountofironlabelandtheinstrumentationneeded
formeasurementofironradioisotopesinbiological
samplesisfoundinmanyresearchfacilities.
–Anadditionaladvantageofthegammaemitting59Fe
radioactiveisotopeisthatwholebodycountingcanbe
usedtomeasurethefractionofironisotopethatis
retainedinthebodyafteringestion.
88

89. Radioisotopes…
•Disadvantagestotheuseofradioisotopesinclude
thefactthattheyhavefinitehalf-lives.
–Thismayintroducetimelimitationsforshippingisotopesto
isolatedsettings,storingisotopesbeforethestudyis
implemented
–andcollectingandanalyzingthebiologicalsamplespost-dosing
•Typicalradiationexposuresfromradioactiveiron
isotopes
89

90. 4. Stable Isotopes
•Thepotentialriskandincreasedreluctancetouse
radioisotopeshasstimulatedtheuseofstableisotopes.
•Thus,inrecentyears,stableisotopesandcompounds
labeledwithstableisotopeshavebecomeincreasingly
available.
•Basically,themethodologytoassessironbioavailability
involvestheadministrationofsingleormultipleoral
stableironisotope(s).
•Ironabsorptionisthenestimatedusingoneofthree
approaches
90

91. •Ametabolicbalancestudycanbeundertakentorecover
theamountoforalstableironisotope(s)excretedin
faeces(faecalrecoverymethod).
•(b)Aplasmasamplecanbeobtainedseveralhourspost-
dosingtoassessplasmaappearancekinetics(plasma
appearancemethod).
•(c)Abloodsamplecanbecollected2weekspost-dosing
toassesstheamountofstableironisotope(s)
incorporatedintoRBCs(erythrocyteironincorporation
method). 91

92. •Administrationofstableironisotopesdoesnothaveany
knownadverserisksatthedosestypicallyusedinhuman
studies.
•Allthreeminorabundancestableironisotopescanbe
giventothesamesubjecttocomparebioavailabilityof
variousfoodsortoallowforsimultaneousadministration
oforalandintravenousisotopes.
•Multiplestableisotopesofdifferentmineralscanalsobe
giventothesameindividualtoexamineinteractionsof
ironwithothernutrientssuchascalciumorzinc
92

93. •Stable-isotope-tracertechniquesweresuccessfully
developedforstudyingthemetabolismofminerals,such
asiron,magnesium,andzinc,andofvitaminsandtheir
precursors,suchasfolateandprovitaminAcarotenoids.
•Becauseofthelimitedavailabilityoforganicnutrients
labeledwithstableisotopesandthedifficultyintheir
quantification,fewstudieshavebeencarriedoutsofar.
93

94. 5. Algorithm Method
•Thealgorithmmaybeusedtotranslatedatafromdietary
surveysintoamountsofanutrientexpectedtobe
absorbed.
•Themainrequirementforsuchcalculationsisthat
detailedinformationisavailableaboutthemeal
compositionanditsvariationoverarepresentativeand
sufficientlylongperiodoftime.
•A7-drecord,forexample,maynotrepresenttheiron
absorptionfromthehabitualdiet.
94

95. •Animportantuseofthealgorithmwouldbetotranslate
physiologicrequirementsintodietaryrequirements
underdifferentdietaryconditionsknowntoprevailina
certainpopulation.
•IntheFAOrecommendations,3levelsofbioavailability
(5%,10%,and15%)wereusedarbitrarilyforthis
translation.
•Thevalidityofchoicesofrepresentativebioavailability
valuescanbetestedbyusingthealgorithm.
95

96. •Thealgorithmmaybeusefulinthefuturesearchfor
realisticrecommendationstobeusedinfoodbased
strategiestoimproveironnutritionindeveloping
countries.
•Challenges
–EstimationofPhytate
–EstimationofvitaminC
96

97. 97

98. 98

99. Thank you!
99