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Better\tabsorbed\nFewer\tside\teffects\nLeast\tconstipating\nMore\texpensive\nHealth\tprofessionals\tusually\tprescribe\toral\tiron\tthree\ttimes\tdaily\tfor\t3-6\tmonths\tto\ttreat\tiron\ndeficiency.\tDepending\ton\tthe\tseverity\tof\tthe\tanemia\tand\tthe\tpatient’s\ttolerance,\tthe\tdaily\tdose\tof
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elemental\tiron\trecommended\tis\t50\tto\t100\tmg\tthree\ttimes\tdaily\tfor\tadults\tand\t2-6\tmg/kg\tof\tbody\nweight\tdivided\tinto\tthree\tdoses\tper\tday\tfor\tchildren\t(\nShort\tand\tDomagalski,\t2013\n;\t\nWang,\t2016\n).\nVitamin\tC\tgiven\twith\tthe\tiron\tgreatly\tincreases\tiron\tabsorption,\tbut\tat\thigher\tdoses\tit\tmay\talso
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increase\tgastric\tirritation\tby\tintensifying\toxidative\tstress\tin\tthe\tgastrointestinal\ttract.\tTaking\tit\twith\na\thigh\tvitamin\tC\tfood\tsuch\tas\torange\tjuice\tmay\tbe\tbetter\ttolerated.\nAbsorption\tof\t10\tto\t20\tmg\tof\tiron\tper\tday\tpermits\tRBC\tproduction\tto\tincrease\tto\tapproximately\nthree\ttimes\tthe\tnormal\trate
|
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improvements\tin\tmood\tand\tappetite\tsooner.\tThe\themoglobin\tlevel\twill\tbegin\tto\tincrease\tby\tday\t4.\nIron\ttherapy\tshould\tbe\tcontinued\tfor\t4-6\n\tmonths,\teven\tafter\trestoration\tof\tnormal\themoglobin\tlevels,\nto\tallow\tfor\trepletion\tof\tbody\tiron\treserves.\tCoordination\tof\tcare\twith\ta\tphysician\tis\tessential\twith\ntherapeutic\tiron\tsupplementation.
|
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] |
therapeutic\tiron\tsupplementation.\nParenteral\tiron\tadministration.\nIf\tiron\tsupplementation\tfails\tto\tcorrect\tthe\tanemia,\t(1)\tthe\tpatient\tmay\tnot\tbe\ttaking\tthe\nsupplemental\tiron\tas\tprescribed\tdue\tto\tgastric\tdistress,\t(2)\tbleeding\tmay\n\tbe\tcontinuing\tat\ta\trate
|
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be\tcontinuing\tat\ta\trate\nfaster\tthan\tthe\terythroid\tmarrow\tcan\treplace\tblood\tcells,\tor\t(3)\tthe\tsupplemental\tiron\tis\tnot\tbeing\nabsorbed,\tpossibly\tas\ta\tresult\tof\tmalabsorption\tsecondary\tto\tsteatorrhea,\tceliac\tdisease,\tor\nhemodialysis.\tParenteral\tadminstration\tis\talso\tused\tfor\tpatients\twho\tare\treceiving\terythropoietin,\ta
|
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hormone\tthat\tstimulates\tblood\tcell\tproduction.\tIt\tis\tmost\toften\tgiven\tas\tiron\tdextran\n\tbut\tcan\talso\tbe\ngiven\tas\tiron\tsucrose\tor\tferric\tgluconate.\tAlthough\treplenishment\tof\tiron\tstores\tby\tthis\troute\tis\nfaster,\tit\tis\tmore\texpensive\tand\tintravenous\ttherapy\tcarries\tadditional\trisk.\nMedical\tnutrition\ttherapy
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0.10019321739673615,
-0.04925960674881935
] |
Medical\tnutrition\ttherapy\nNutrition\tassessments\tand\tinterventions\tshould\tconsider\tthe\tamount\tof\tabsorbable\tdietary\tiron\nconsumed.\tA\tgood\tsource\tof\tiron\tcontains\ta\tsubstantial\tamount\tof\tiron\tin\trelation\n\tto\tits\tcalorie\ncontent\tand\tcontributes\tat\tleast\t10%\tof\tthe\trecommended\tdietary\tallowance\t(RDA)\tfor\tiron.\tLiver;
|
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] |
kidney;\tbeef;\tdried\tfruits;\tdried\tpeas\tand\tbeans;\tnuts;\tdark\tgreen\tleafy\tvegetables;\tand\tfortified\nwhole-grain\tbreads,\tmuffins,\tcereals,\tand\tnutrition\tbars\tare\tamong\tthe\tfoods\tthat\trank\thighest\tin\niron\tcontent\t(see\t\nAppendix\t42\n).\tIt\tis\testimated\tthat\t1.8\tmg\tof\tiron\tmust\tbe\tabsorbed\tdaily\n\tto\tmeet
|
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] |
to\tmeet\nthe\tneeds\tof\t80%\tto\t90%\tof\tadult\twomen\tand\tadolescent\tboys\tand\tgirls.\nForm\tof\tiron.\nHeme\tiron\n\t(approximately\t15%\tof\twhich\tis\tabsorbable)\tis\tthe\torganic\tform\tin\tmeat,\tfish,\tand\npoultry,\tand\tis\tknown\tas\tthe\t\nmeat-fish-poultry\t(MFP)\tfactor\n.\tIt\tis\tmuch\tbetter\tabsorbed\tthan\nnonheme\tiron.\t\nNonheme\tiron
|
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] |
.\tIt\tis\tmuch\tbetter\tabsorbed\tthan\nnonheme\tiron.\t\nNonheme\tiron\n\tcan\talso\tbe\tfound\tin\tMFP,\tas\twell\tas\tin\tlegumes,\tgrains,\tvegetables,\nherbs\tand\tfruits,\tbut\n\tit\tis\tnot\tpart\tof\tthe\theme\tmolecule.\tThe\tabsorption\trate\tof\tnonheme\tiron\tvaries\nbetween\t3%\tand\t8%\tdepending\ton\tthe\tpresence\tof\tdietary\tenhancing\tfactors,\tspecifically\tvitamin\tC
|
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and\tmeat,\tfish,\tand\tpoultry.\tVitamin\tC\tnot\tonly\tis\ta\tpowerful\treducing\tagent,\tbut\talso\tbinds\tiron\tto
|
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form\ta\treadily\tabsorbed\tcomplex.\tThe\tmechanism\tby\twhich\tthe\tMFP\tfactor\tpotentiates\tthe\nabsorption\tof\tnonheme\tiron\tin\tother\n\tfoodstuffs\tis\tunknown.\nInhibitors.\nIron\tabsorption\tcan\tbe\tinhibited\tto\tvarying\tdegrees\tby\tfactors\tin\tfoods\tthat\tbind\tiron,\tincluding\ncarbonates,\toxalates,\tphosphates,\tand\tphytates\t(whole\tgrain\tbreads\tand\tcereals\tand\tlegumes
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[beans]).\tFactors\tin\tvegetable\tfiber\tmay\tinhibit\tnonheme\tiron\tabsorption.\tIf\ttaken\twith\tmeals,\ttea\nand\tcoffee\tcan\treduce\tiron\tabsorption\tby\t50%\tthrough\tthe\tformation\tof\n\tinsoluble\tiron\tcompounds\nwith\ttannin.\tIron\tin\tegg\tyolk\tis\tpoorly\tabsorbed\tbecause\tof\tthe\tpresence\tof\tphosvitin.\nBioavailability\tof\tdietary\tiron.
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Bioavailability\tof\tdietary\tiron.\nBecause\ttypical\tWestern\tdiets\tgenerally\tcontain\t6\tmg/1000\tkcal\tof\tiron,\tthe\tbioavailability\tof\tiron\tin\nthe\tdiet\tis\tmore\timportant\tin\tcorrecting\tor\tpreventing\tiron\tdeficiency\tthan\tthe\ttotal\tamount\tof\ndietary\tiron\tconsumed.\tThe\trate\tof\tabsorption\tdepends\n\ton\tthe\tiron\tstatus\tof\tthe\tindividual,\tas
|
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0.03564809262752533,
0.08238004893064499,
0.06324385851621628,
0.10162244737148285,
-0.00900957453995943
] |
on\tthe\tiron\tstatus\tof\tthe\tindividual,\tas\nreflected\tin\tthe\tlevel\tof\tiron\tstores.\tThe\tlower\tthe\tiron\tstores,\tthe\tgreater\tthe\trate\tof\tiron\tabsorption.\nIndividuals\twith\tiron\tdeficiency\tanemia\tabsorb\tapproximately\t20%\tto\t30%\tof\tdietary\tiron\tcompared\nwith\tthe\t5%\tto\t10%\tabsorbed\tby\tthose\twithout\tiron\tdeficiency.\nIron\toverload
|
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0.01190268062055111
] |
Iron\toverload\nExcess\tiron\tis\tstored\tas\tferritin\tand\themosiderin\tin\tthe\tmacrophages\n\tof\tthe\tliver,\tspleen,\tand\tbone\nmarrow.\tThe\tbody\thas\ta\tlimited\tcapacity\tto\texcrete\tiron\tand\tis\tefficient\tat\trecycling\tit.\tApproximately\n1\tmg\tof\tiron\tis\texcreted\tdaily\tthrough\tthe\tgastrointestinal\ttract,\turinary\ttract,\tand\tskin.\tWhen\tred
|
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] |
blood\tcells\tare\tno\tlonger\tfunctional\t(after\tabout\t120\tdays),\tthey\tare\tre-absorbed\tby\tthe\tspleen.\tIron\nfrom\tthese\tcells\tcan\tbe\trecycled\tby\tthe\tbody.\tTo\tmaintain\ta\tnormal\n\tiron\tbalance,\tthe\tdaily\tobligatory\nloss\tmust\tbe\treplaced\tby\tthe\tabsorption\tof\theme\tand\tnonheme\tfood\tiron.\tPersons\twith\tiron\toverload
|
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] |
excrete\tincreased\tamounts\tof\tiron,\tespecially\tin\tthe\tfeces,\tto\tcompensate\tpartially\tfor\tthe\tincreased\nabsorption\tand\thigher\tstores.\nExcessive\tiron\tintake\tusually\tstems\tfrom\taccidental\tincorporation\tof\tiron\tinto\tthe\tdiet\tfrom\nenvironmental\tsources.\tIn\tthe\tUnited\n\tStates\tiron-containing\tsupplements\tremain\ta\tcommon\tsource
|
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] |
States\tiron-containing\tsupplements\tremain\ta\tcommon\tsource\nof\texcessive\tiron\tingestion,\tespecially\tamong\tchildren\t(\nChang\tand\tRangan,\t2011\n).\tIn\tother\tparts\tof\nthe\tworld,\texcessive\tiron\tintake\tmay\tresult\tfrom\tconsumption\tof\tbeverages\tor\tfoods\tprepared\tin\tiron-\ncontaining\tcooking\tvessels\t(\nNational\tLibrary\tof\tMedicine,\t2019\n).
|
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0.07076316326856613,
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0.02568688429892063
] |
containing\tcooking\tvessels\t(\nNational\tLibrary\tof\tMedicine,\t2019\n).\nUncommon\tdisorders\tassociated\twith\tiron\toverload\tinclude\themochromatosis,\n\tthalassemias,\nsideroblastic\tanemia,\tchronic\themolytic\tanemia,\tineffective\terythropoiesis,\ttransfusional\tiron\noverload\t(secondary\tto\tmultiple\tblood\ttransfusions),\tporphyria\tcutanea\ttarda,\taplastic\tanemia,\tand
|
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] |
alcoholic\tcirrhosis.\t\nAplastic\tanemia\n\tis\ta\tnormochromic-normocytic\tanemia\taccompanied\tby\ta\ndeficiency\tof\tall\tthe\tformed\telements\tin\tthe\tblood;\tit\tcan\tbe\tcaused\tby\texposure\tto\ttoxic\tchemicals,\nionizing\tradiation,\tand\tmedications,\talthough\tthe\tcause\tis\toften\tunknown.
|
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] |
Brain\tiron\tincreases\twith\tage\tand\tis\tabnormally\televated\tin\tneurodegenerative\tdiseases,\tincluding\nAlzheimer’s\tdisease\tand\tParkinson’s\tdisease\t(\nWard\tet\tal,\t2014\n).\tSeveral\tgene\tvariants\taffect\tiron\nmetabolism\tand\tmay\tcontribute\tto\tearly\tonset\tof\tthese\tconditions.\nHemochromatosis\nHereditary\themochromatosis\n\tis\ta\tgeneral
|
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0.11233357340097427,
0.10207275301218033,
0.13088011741638184,
0.004304502159357071
] |
Hemochromatosis\nHereditary\themochromatosis\n\tis\ta\tgeneral\n\tterm\tfor\ta\tgroup\tof\trare\tgenetic\tdisorders\tthat\tare\ncharacterized\tby\tthe\taccumulation\tof\tiron\tin\tbody\torgans,\ttypically\tthe\tliver,\tpancreas,\tand\theart.\nOver\ttime\tthis\taccumulation\tis\tassociated\twith\torgan\tdamage,\torgan\tfailure,\tand\tsometimes
|
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] |
premature\tdeath.\tThe\tmost\tcommon\tform\tof\themochromatosis\tgoes\tby\tseveral\tnames\tincluding\nhereditary\tiron\toverload\t(HFE-related)\themochromatosis,\ttype\tI\tor\tclassic\n\themochromatosis,\tor\nhereditary\themochromatosis.\tThe\tdisease\tgenerally\tdoes\tnot\tbecome\tapparent\tuntil\t20\tto\t40\tyears\tof
|
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] |
age.\tMen\tare\tusually\tdiagnosed\tearlier\tthan\twomen\tbecause\tthey\thave\tno\tphysiologic\tmechanisms\nfor\tlosing\tiron\tsuch\tas\tmenstruation,\tpregnancy,\tor\tlactation.\tSymptoms\tinclude\tfatigue,\tjoint\tpain,\nand\tenlarged\tliver\tand\tspleen.\tThe\texact\tprevalence\tof\tthis\tdisorder\tis\tunknown,\n\tbut\tit\tis\tthought\tto
|
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] |
but\tit\tis\tthought\tto\nbe\tthe\tmost\tcommon\tautosomal\trecessive\tdisorder\tin\tCaucasian\tpopulations.\tIn\tindividuals\tof\nNorthern\tEuropean\tdescent,\tit\tis\testimated\tto\thave\tan\tincidence\tof\t1\tin\t227\tpeople.\tPeople\twith\tthis\ncondition\tabsorb\tthree\ttimes\tmore\tiron\tfrom\ttheir\tfood\tthan\tthose\twithout\themochromatosis.\tThose
|
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who\thave\ttwo\taffected\tgenes\t(homozygous)\twill\tlikely\tdie\tof\tiron\toverload\tunless\tthey\tdonate\n\tblood\nfrequently.\tOtherwise,\tthe\texcessive\tiron\tabsorption\tcontinues\tunabated.\nThe\tHemochromatosis\tand\tIron\tOverload\tScreening\tStudy\t(HEIRS)\tnotes\tthat\tnon-Hispanic\twhites
|
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] |
have\tthe\thighest\tprevalence\tof\tthe\tC282Y\tmutation\tof\tthe\thereditary\tiron\t(HFE)\tgene\tand\tthus\nhemochromatosis,\tfollowed\tby\tNative\tAmericans,\tHispanics,\tAfrican\tAmericans,\tPacific\tIslanders,\nand\tAsians\t(\nAdams,\t2015\n).\tAsians\tand\n\tPacific\tIslanders\thave\tthe\thighest\tlevels\tof\tiron\tin\ttheir\tblood
|
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] |
Pacific\tIslanders\thave\tthe\thighest\tlevels\tof\tiron\tin\ttheir\tblood\nof\tall\tracial\tand\tethnic\tgroups,\tbut\tthey\thave\tthe\tlowest\tprevalence\tof\tthe\tgene\tmutation\tfound\twith\nthe\ttypical\tform\tof\themochromatosis.\tResults\tfrom\tthe\tHEIRS\tstudy\tsuggest\tthat\tincreased\tiron\nvalues\tin\tnon-Caucasian\tpopulations\tmay\tbe\tassociated\twith\tnon-HFE\themochromatosis\tand
|
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secondary\tiron\toverload.\nPathophysiology\nHepcidin\n\tis\ta\tpeptide\tsynthesized\tin\tthe\tliver\tthat\tfunctions\tas\tthe\tprincipal\tregulator\tof\tsystemic\niron\thomeostasis.\tIt\tregulates\tiron\ttransport\tfrom\tiron-exporting\ttissues\tinto\tplasma.\tHepcidin\ndeficiency\tunderlies\tmost\tknown\tforms\tof\thereditary\themochromatosis.\tHepcidin\tinhibits\tthe\tcellular
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efflux\tof\tiron\tby\tbinding\tto\tand\tinducing\tthe\tdegradation\tof\t\nferroprotein\n,\tthe\tsole\tiron\texporter\tin\niron-transporting\n\tcells.\tHepcidin\tcontrols\tplasma\tiron\tconcentration\tand\ttissue\tdistribution\tof\tiron\tby\ninhibiting\tintestinal\tiron\tabsorption,\tiron\trecycling\tby\tmacrophages,\tand\tiron\tmobilization\tfrom
|
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] |
hepatic\tstores\t(\nGanz,\t2011\n).\nHepcidin\tsynthesis\tis\tincreased\tby\tiron\tloading\tand\tdecreased\tby\tanemia\tand\thypoxia.\tIts\nsynthesis\tis\talso\tgreatly\tincreased\tduring\tinflammation,\ttrapping\tiron\tin\tmacrophages,\tdecreasing\nplasma\tiron\tconcentrations,\tand\tcausing\tiron-restricted\terythropoiesis\tthat\tis\tcharacteristic\tof
|
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] |
anemia\tof\tchronic\tdisease.\tThere\tis\tevidence\tthat\tthe\tmutation\tof\tthe\tHFE\tgene\tleading\tto\nhemochromatosis\tis\talso\tassociated\twith\tincreased\tlevels\tof\tgastrin\tin\tthe\tstomach,\tleading\tto\nincreased\tlevels\tof\tgastric\tacid\tand\tthus\tincreased\tabsorption\tof\tiron\t(\nGanz,\t2011\n).\tIn\nhemochromatosis\tiron\tabsorption
|
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] |
Ganz,\t2011\n).\tIn\nhemochromatosis\tiron\tabsorption\n\tis\tenhanced,\tresulting\tin\ta\tgradual,\tprogressive\taccumulation\tof\niron.\tMost\taffected\tpersons\tdo\tnot\tknow\tthey\thave\tit.\nA\tprogressive,\tpositive\tiron\tbalance\tmay\tresult\tin\ta\tvariety\tof\tserious\tproblems,\tincluding
|
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] |
hepatomegaly,\tskin\tpigmentation,\tarthritis,\theart\tdisease,\thypogonadism,\tdiabetes\tmellitus,\tand\ncancer.\tIndividuals\twith\tabnormally\thigh\tiron\tlevels\tare\tmore\tlikely\tto\tdevelop\tcancer\tof\n\tthe\tcolon.\nIron\tis\ta\tprooxidant\tthat\tcan\tbe\tused\tfor\ttumor\tcell\tgrowth\tand\tproliferation.\tThere\talso\tseems\tto\tbe
|
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0.0947575643658638,
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] |
increased\trisk\tfor\tage-related\tmacular\tdegeneration,\tAlzheimer’s\tdisease,\tand\tParkinson’s\tdisease\nbecause\tof\tthe\toxidative\tdamage\tassociated\twith\tiron\toverload\t(\nBelaidi\tand\tBush,\t2016\n;\t\nFleming\tand\nPonka,\t2012\n).\nAssessment\nIf\tan\tiron\toverload\tis\tsuspected,\tserum\tferritin\tlevel\t(storage\n\tiron)\tand\tpercent\tof\ttransferrin
|
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0.012734808959066868
] |
iron)\tand\tpercent\tof\ttransferrin\nsaturation\t([serum\tiron/TIBC]\t×\t100)\tshould\tbe\tperformed\t(\nBacon\tet\tal,\t2011\n).\tIron\toverload\tmay\tbe\npresent\tif\tthe\ttransferrin\tsaturation\tis\tgreater\tthan\tor\tequal\tto\t45%\tand\tif\tthe\tserum\tferritin\tlevel\tis\nelevated.\tIf\ttransferrin\tsaturation\tand\tferritin\tlevels\tare\televated,\tHFE\tmutation\tanalysis\tis\nrecommended.
|
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] |
recommended.\nMedical\tmanagement\nThe\tpatient\twith\tiron\toverload\n\tmay\tsimultaneously\tbe\tanemic\tas\ta\tresult\tof\tdamage\tto\tthe\tbone\nmarrow,\tan\tinflammatory\tdisorder,\tcancer,\tinternal\tbleeding,\tor\tchronic\tinfection.\tIron\tsupplements\nshould\tnot\tbe\ttaken\tuntil\tthe\tcause\tis\tknown.
|
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0.06913348287343979,
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0.016905194148421288
] |
should\tnot\tbe\ttaken\tuntil\tthe\tcause\tis\tknown.\nFor\tpatients\twith\tsignificant\tiron\toverload,\tweekly\tphlebotomy\tfor\t2\tto\t3\tyears\tmay\tbe\trequired\tto\neliminate\tall\texcess\tiron\t(\nBacon\tet\tal,\t2011\n).\tTreatment\tfor\tnoninherited\tforms\tof\tsecondary\n\tiron\noverload\talso\tmay\tinvolve\tiron\tdepletion\twith\tintravenous\tdeferoxamine\tor\toral\tdeferasirox,
|
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] |
chelating\tagents\tthat\tare\texcreted\tby\tthe\tkidneys,\tor\twith\tcalcium\tdisodium\nethylenediaminetetraacetic\tacid\t(EDTA).\tMorbidity\tand\tmortality\tare\treduced\tif\texcess\tbody\tiron\tis\nremoved\tby\tphlebotomy\ttherapy\tbefore\thepatic\tcirrhosis\tor\tdiabetes\tdevelops.\nMedical\tnutrition\ttherapy\nIndividuals\twith
|
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] |
Medical\tnutrition\ttherapy\nIndividuals\twith\n\tiron\toverload\tshould\treduce\tmeat,\tfish\tand\tpoultry\tand\tconsume\tmore\tof\ta\tplant\nbased\tor\tvegetarian\tdiet.\tReduced\tvitamin\tC\tis\trecommended\tas\twell\tas\tavoidance\tof\tvitamin\tC\nsupplements,\tas\tthis\tcan\tincrease\tabsorption\tof\tiron.
|
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] |
supplements,\tas\tthis\tcan\tincrease\tabsorption\tof\tiron.\nAffected\tpersons\tshould\tavoid\tfoods\tthat\tare\tfortified\twith\tiron\t(i.e.,\tbreakfast\tcereals,\tenergy\tor\nsports\tbars,\tand\tmeal-replacement\tdrinks\tor\tshakes).\tThey\tshould\talso\n\tavoid\tiron\tsupplements\tor\nmultiple\tvitamin\tand\tmineral\tsupplements\tthat\tcontain\tiron.\tThe\tRDA\tfor\tiron\tshould\tnot\tbe
|
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exceeded,\tand\tfor\tsome,\tlower\tintakes\tare\trecommended\t(see\tRDA\ttables\tat\tthe\tbeginning\tof\tthe\nbook).\nMegaloblastic\tanemias\nMegaloblastic\tanemia\n\treflects\ta\tdisturbed\tsynthesis\tof\tDNA,\twhich\tresults\tin\tmorphologic\tand\nfunctional\tchanges\tin\terythrocytes,\tleukocytes,\tand\tplatelets\n\tand\ttheir\tprecursors\tin\tthe\tblood\tand
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] |
and\ttheir\tprecursors\tin\tthe\tblood\tand\nbone\tmarrow.\tThis\tanemia\tis\tcharacterized\tby\tthe\tpresence\tof\tlarge,\timmature,\tabnormal,\tRBC\nprogenitors\tin\tthe\tbone\tmarrow;\t95%\tof\tcases\tare\tattributable\tto\tfolate\tor\tvitamin\tB\n12\n\tdeficiency.\nTwo\tdisorders\tof\tcobalamin\tmetabolism\tarise\tfrom\tmutations\tof\tthe\tmethionine\tsynthase\tand
|
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] |
methionine\tsynthase\treductase\tgenes;\tthese\tdisorders\tfeature\tmegaloblastic\tanemia\n\tand\tneurologic\nmanifestations\t(see\t\nChapter\t6\n).\nBoth\tvitamins\tare\tessential\tto\tthe\tsynthesis\tof\tnucleoproteins.\tHematologic\tchanges\tare\tthe\tsame\nfor\tboth;\thowever,\tthe\tfolic\tacid\tdeficiency\tis\tthe\tfirst\tto\tappear.\tNormal\tbody\tfolate\tstores\tare
|
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] |
depleted\twithin\t2\tto\t4\tmonths\tin\tindividuals\tconsuming\tfolate-deficient\tdiets.\tBy\tcontrast,\tvitamin\nB\n12\n\tstores\tare\tdepleted\tonly\tafter\tseveral\tyears\tof\n\ta\tvitamin\tB\n12\n–deficient\tdiet.\tIn\tpersons\twith\nvitamin\tB\n12\n\tdeficiency,\tfolic\tacid\tsupplementation\tcan\tmask\tB\n12\n\tdeficiency\t(\nFig.\t31.3\n).
|
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] |
FIG.\t31.3\nSequential\tstages\tof\tvitamin\tB\n12\n\tstatus.\n\tSource:\t(From\tHerbert\tV:\tStaging\tvitamin\tB\n12\n.\tIn\tZiegler\tEE,\tFiler\tLJ,\neditors:\t\nPresent\tknowledge\tin\tnutrition,\n\ted\t7,\tWashington,\tDC,\t1996,\tInternational\tLife\tSciences\tInstitute\tPress.)\nIn\tcorrecting\tthe\tanemia,\tthe\tvitamin\tB\n12\n\tdeficiency\tmay\tremain\tundetected,\tleading\tto\tthe
|
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] |
12\n\tdeficiency\tmay\tremain\tundetected,\tleading\tto\tthe\nirreversible\tneuropsychiatric\tdamage\tthat\tis\tcorrected\tonly\twith\n\tB\n12\n\tsupplementation\t(see\t\nChapter\n41\n).\nFolate-deficiency\tanemia\nEtiology\nFolate\tis\ta\tnaturally\toccurring\tB\tvitamin\tfound\tin\tfoods\tin\tthe\ttetrahydrofolate\t(THF)\tform.\tFolic\tacid
|
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is\tthe\tsynthetic\tversion\tof\tthe\tvitamin\tfound\tin\tthe\tfully\toxidized\tmonoglutamate\tform,\twhich\tmay\tbe\nfound\tin\tfortified\tfoods\tand\tsupplements.\tFolate-deficiency\tanemia\tis\tassociated\twith\tprolonged\ninadequate\tdiets,\n\tinadequate\tabsorption,\tinadequate\tuse\tof\tfolic\tacid\tcaused\tby\tgenetic\taberrations,
|
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] |
and\tincreased\trequirements\tresulting\tfrom\tpregnancy\tor\tgrowth.\tFolate-deficiency\tanemia\tcan\taffect\npregnant\twomen\tand\toccurs\tin\tinfants\tborn\tto\tmothers\twith\tfolate\tdeficiency.\tFolate\tdeficiency\tin\nearly\tpregnancy\tcan\tresult\tin\tan\tinfant\tborn\twith\ta\tneural\ttube\tdefect\t(see\t\nChapter\t14\n).\tOther\ncauses\tare\tintestinal
|
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] |
Chapter\t14\n).\tOther\ncauses\tare\tintestinal\n\tdisorders\tresulting\tin\tmalabsorption\t(celiac\tdisease,\ttropical\tsprue,\tand\ninflammatory\tbowel\tdisease),\tuse\tof\tcertain\tdrugs\t(anticonvulsants,\tbarbiturates,\tcycloserine,\nsulfasalazine,\tcholestyramine,\tand\tmetformin),\tamino\tacid\texcess\t(glycine\tand\tmethionine),\tand\nalcohol.
|
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] |
alcohol.\nBecause\talcohol\tinterferes\twith\tthe\tfolate\tenterohepatic\tcycle,\tmost\tpeople\twith\talcoholism\thave\ta\nnegative\tfolate\tbalance\n\tor\ta\tfolate\tdeficiency.\tAlcoholics\tconstitute\tthe\tonly\tgroup\tthat\tgenerally\thas\nall\tsix\tcauses\tof\tfolate\tdeficiency\tsimultaneously:\tinadequate\tingestion,\tabsorption,\tand\tuse,\tand
|
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] |
increased\texcretion,\trequirement,\tand\tdestruction\tof\tfolate\t(see\t\nChapter\t28\n).\t\nBox\t31.2\n\tdescribes\tthe\ncauses\tof\tfolate\tdeficiency.\nBOX\t31.2\nCauses\tof\tFolate\tDeficiency
|
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] |
Inadequate\nIngestion\nPoor\tdiet\t(lack\tof\n\tor\tovercooked\tfruits\tand\tvegetables),\tvitamin\tB\n12\n\tor\tvitamin\tC\ndeficiency,\tchronic\talcoholism\nInadequate\nAbsorption\nCeliac\tdisease,\ttropical\tsprue,\tdrug\tinteractions,\tcongenital\tdefects\nInadequate\nUtilization\nAntagonists,\tanticonvulsants,\tenzyme\tdeficiency,\tvitamin\tB\n12\n\tand\tvitamin\tC\tdeficiency,
|
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] |
12\n\tand\tvitamin\tC\tdeficiency,\nchronic\talcoholism,\texcess\tglycine\tand\tmethionine\nIncreased\nRequireme\nnt\nExtra\ttissue\tdemand,\tinfancy,\n\tincreased\thematopoiesis,\tincreased\tmetabolic\tactivity,\nLesch-Nyhan\tsyndrome,\tdrugs\nIncreased\nExcretion\nVitamin\tB\n12\n\tdeficiency,\tliver\tdisease,\tkidney\tdialysis,\tchronic\texfoliative\tdermatitis\nIncreased\nDestruction
|
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0.019593169912695885
] |
Increased\nDestruction\nDietary\toxidants\nModified\tfrom\tHerbert\tV,\tDas\tKC:\tFolic\tacid\tand\tvitamin\tB\n12\n.\tIn\tShils\tME\tet\tal,\teditors:\t\nModern\tnutrition\nin\thealth\tand\tdisease\n,\ted\t8,\tvol\t1,\tPhiladelphia,\n\t1994,\tLea\t&\tFebiger.\nBOX\t31.3\nCauses\tof\tVitamin\tB\n12\n\t\nDeficiency\nInadequate\ningestion
|
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0.016960350796580315
] |
BOX\t31.3\nCauses\tof\tVitamin\tB\n12\n\t\nDeficiency\nInadequate\ningestion\nPoor\tdiet\tresulting\tfrom\ta\tvegan\tdiet\tand\tlack\tof\tsupplementation,\tchronic\talcoholism,\npoverty\nInadequate\nabsorption\nGastric\tdisorders,\tsmall\tintestinal\tdisorders,\tcompetition\tfor\tabsorption\tsites,\tpancreatic\ndisease,\tHIV,\tor\tAIDS,\tgastritis,\tgastric\tsurgery\nInadequate\nuse\nVitamin\tB
|
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] |
Inadequate\nuse\nVitamin\tB\n12\n\tantagonists,\n\tcongenital\tor\tacquired\tenzyme\tdeficiency,\tabnormal\tbinding\nproteins\nIncreased\nrequiremen\nt\nHyperthyroidism,\tincreased\thematopoiesis\nIncreased\nexcretion\nInadequate\tvitamin\tB\n12\n\tbinding\tprotein,\tliver\tdisease,\trenal\tdisease\nIncreased\ndestruction
|
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] |
binding\tprotein,\tliver\tdisease,\trenal\tdisease\nIncreased\ndestruction\nPharmacologic\tdoses\tof\tascorbic\tacid\twhen\tit\tfunctions\tas\ta\tprooxidant\nMedication\ninduced\nDrugs\tthat\tsuppress\tgastric\tacid\tand\tmetformin\thave\tbeen\n\tassociated\twith\tB\n12\ndeficiency\nAIDS,\n\tAcquired\timmune\tdeficiency\tsyndrome;\t\nHIV,\n\thuman\timmunodeficiency\tvirus.
|
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] |
HIV,\n\thuman\timmunodeficiency\tvirus.\nFolate\tabsorption\ttakes\tplace\tin\tthe\tsmall\tintestine.\tEnzyme\tconjugases\t(e.g.,\tpteroylpolyglutamate\nhydrolase,\tthe\tfolate\tconjugase),\tfound\tin\tthe\tbrush\tborder\tof\tthe\tsmall\tintestine,\thydrolyze\tthe\npolyglutamates\tto\tmonoglutamates\tand\treduce\tthem\tto\tdihydrofolate\tand\ttetrahydrofolic\n\tacid
|
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] |
acid\n(THFA)\tin\tthe\tsmall\tintestinal\tepithelial\tcells\t(enterocytes).\tFrom\tthe\tenterocytes\tthese\tforms\tare\ntransported\tto\tthe\tcirculation,\twhere\tthey\tare\tbound\tto\tprotein\tand\ttransported\tas\tmethyl\tTHFA\tinto\nthe\tcells\tof\tthe\tbody.\nIn\tthe\tabsence\tof\tvitamin\tB\n12\n,\t5-methyl\tTHFA,\tthe\tmajor\tcirculating\tand\tstorage\tform\tof\tfolic\tacid,
|
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0.1645655483007431,
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] |
deoxyuridylate\tto\tthymidylate,\twhich\tis\tnecessary\tfor\tDNA\tsynthesis.\nMTHFR\tallele.\nA\tgenetic\tdefect\tfound\tin\t25%\tof\tHispanics,\t10%\tof\tCaucasians\tand\tAsians,\tand\t1%\tof\tAfrican\nAmericans\n\tis\tthe\tmethylenetetrahydrofolate\treductase\t(MTHFR)\tdeficiency\t(National\tInstitutes\tof\nHealth,\tOffice\tof\tDietary\tSupplements,\t2018)\t(see\t\nChapter\t6
|
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] |
Health,\tOffice\tof\tDietary\tSupplements,\t2018)\t(see\t\nChapter\t6\n).\tThe\tallele\tis\tproblematic\tin\tpregnancy\nand\tmay\tcontribute\tto\tmiscarriages,\tanencephaly,\tor\tneural\tdefects\t(see\t\nChapter\t14\n).\tBecause\nMTHFR\tirreversibly\treduces\t5,10-methylenetetrahydrofolate\tto\t5-methyltetrahydrofolate,\tits\ndeficiency\tmay\tresult\tin
|
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] |
deficiency\tmay\tresult\tin\n\tdevelopmental\tdelay,\tmotor\tand\tgait\tdysfunction,\tseizures,\tneurologic\nimpairment,\textremely\thigh\tlevels\tof\thomocysteine,\tclotting\tdisorders,\tand\tother\tconditions.\nMethylfolate\ttrap.\nVitamin\tB\n12\n\tdeficiency\tcan\tresult\tin\ta\tfolate\tdeficiency\tby\tcausing\tfolate\tentrapment\tin\tthe\nmetabolically\tuseless\tform\tof\t5-methyl\tTHFA\t(
|
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] |
metabolically\tuseless\tform\tof\t5-methyl\tTHFA\t(\nFig.\t31.4\n).\tThe\tlack\tof\tvitamin\tB\n12\n\tto\tremove\tthe\t5-\nmethyl\tunit\tmeans\tthat\n\tmetabolically\tinactive\tmethyl\tTHFA\tis\ttrapped.\tIt\tcannot\trelease\tits\t1-carbon
|
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] |
12\n\tcan\tresult\tin\ta\tdeficiency\tof\tfolic\tacid\tbecause\tfolate\tis\ntrapped\tin\tthe\tform\tof\t5-methyltetrahydrofolate\t(5-methyl\tTHFA),\twhich\tcannot\tbe\tconverted\tto\tTHFA\tand\nmethyl\tgroups\tdonated\tby\tthe\tvitamin\tB\n12\n–dependent\tpathway.\t\nDNA,\n\tDeoxyribonucleic\tacid;\t\nTHFA\n,\ntetrahydrofolic\tacid.\nPathophysiology\nFolate\tdeficiency\tdevelops\tin\tfour\tstages:
|
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] |
Pathophysiology\nFolate\tdeficiency\tdevelops\tin\tfour\tstages:\n\ttwo\tthat\tinvolve\tdepletion,\tfollowed\tby\ttwo\tmarked\tby\ndeficiency\t(\nFig.\t31.5\n):\nStage\t1:\tCharacterized\tby\tearly\tnegative\tfolate\tbalance\t(serum\tdepletion\tto\tless\tthan\t3\tng/mL)\nStage\t2:\tCharacterized\tby\tnegative\tfolate\tbalance\t(cell\tdepletion),\twith\ta\tdecrease\tin
|
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erythrocyte\tfolate\tlevels\tto\tless\tthan\t160\tng/mL\nStage\t3:\tCharacterized\tby\tdamaged\tfolate\tmetabolism,\twith\tfolate-deficient\terythropoiesis.\nThis\tstage\tis\tcharacterized\tby\tslowed\tDNA\tsynthesis,\tmanifested\tby\tan\tabnormal\tdiagnostic\ndeoxyuridine\t(dU)\tsuppression\ttest\tcorrectable\tin\tvitro\tby\tfolates,\tgranulocyte\tnuclear
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] |
hypersegmentation,\tand\tmacroovalocytic\tred\tcells.\nStage\t4:\tCharacterized\tby\tclinical\tfolate-deficiency\tanemia,\twith\tan\televated\tMCV\tand\nanemia.
|
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] |
FIG.\t31.5\nSequential\tstages\tof\tfolate\tstatus.\t\ndU,\n\tDeoxyuridine;\t\nMCV\n,\tmean\tcorpuscular\tvolume;\t\nRBC,\n\tred\nblood\tcell.\n\tSource:\t(From\tHerbert\tV:\tFolic\tacid.\tIn\tShils\tME\tet\tal,\teditors:\t\nModern\tnutrition\tin\thealth\tand\tdisease\n,\ted\t9,\nPhiladelphia\t1998,\tLea\t&\tFebiger.)
|
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] |
,\ted\t9,\nPhiladelphia\t1998,\tLea\t&\tFebiger.)\nBecause\tof\ttheir\tinterrelated\troles\tin\tthe\tsynthesis\tof\tthymidylate\tin\tDNA\tformation,\ta\tdeficiency\tof\neither\tvitamin\tB\n12\n\tor\tfolate\n\tresults\tin\ta\tmegaloblastic\tanemia.\tThe\timmature\tnuclei\tdo\tnot\tmature\nproperly\tin\tthe\tdeficient\tstate;\tand\tlarge\t(macrocytic),\timmature\t(megaloblastic)\tRBCs\tare\tthe
|
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] |
result.\tThe\tcommon\tclinical\tsigns\tof\tfolate\tdeficiency\tinclude\tfatigue,\tdyspnea,\tsore\ttongue,\ndiarrhea,\tirritability,\tforgetfulness,\tanorexia,\tglossitis,\tand\tweight\tloss.\nNormal\tbody\tfolate\tstores\tare\tdepleted\twithin\t2\tto\t4\tmonths\n\ton\ta\tfolate-deficient\tdiet,\tresulting\tin
|
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on\ta\tfolate-deficient\tdiet,\tresulting\tin\na\tmacrocytic,\tmegaloblastic\tanemia\twith\ta\tdecreased\tnumber\tof\terythrocytes,\tleukocytes,\tand\nplatelets.\tFolate-deficiency\tanemia\tis\tmanifested\tby\tvery\tlow\tserum\tfolate\t(<3\tng/mL)\tand\tRBC\nfolate\tlevels\tof\tless\tthan\t140\tto\t160\tng/mL.\tWhereas\ta\tlow\tserum\tfolate\tlevel\tmerely\tdiagnoses\ta
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] |
negative\tbalance\tat\tthe\ttime\tthe\tblood\tis\tdrawn,\ta\tred\tcell\tfolate\t(RCF)\tlevel\n\tmeasures\tactual\tbody\nfolate\tstores,\tand\tthus\tis\tthe\tsuperior\tmeasurement\tfor\tdetermining\tfolate\tnutriture.\tTo\tdifferentiate\nfolate\tdeficiency\tfrom\tvitamin\tB\n12\n\tdeficiency,\tlevels\tof\tserum\tfolate,\tRCF,\tserum\tvitamin\tB\n12\n,\tand\nvitamin\tB\n12
|
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] |
12\n,\tand\nvitamin\tB\n12\n\tbound\tto\ttranscobalamin\tII\t(TCII)\tcan\tbe\tmeasured\tsimultaneously\tusing\ta\tradioassay\nkit.\tAlso\tdiagnostic\tfor\tfolate\tdeficiency\tis\tan\televated\tlevel\tof\tformiminoglutamic\n\tacid\tin\tthe\turine,\nas\twell\tas\tthe\tdU\tsuppression\ttest\tin\tbone\tmarrow\tcells\tor\tperipheral\tblood\tlymphocytes\t(see\nChapter\t5\n\tand\t\nAppendix\t12\n).
|
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] |
Chapter\t5\n\tand\t\nAppendix\t12\n).\nMedical\tmanagement\nBefore\ttreatment\tis\tinitiated,\tit\tis\timportant\tto\tdiagnose\tthe\tcause\tof\tthe\tmegaloblastosis\tcorrectly.\nAdministration\tof\tfolate\tcorrects\tmegaloblastosis\tfrom\teither\tfolate\tor\tvitamin\tB\n12\n\tdeficiency,\tbut\tit\ncan\tmask\tthe\tneurologic\tdamage\n\tof\tvitamin\tB\n12
|
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deficiency,\tbut\tit\ncan\tmask\tthe\tneurologic\tdamage\n\tof\tvitamin\tB\n12\n\tdeficiency,\tallowing\tthe\tnerve\tdamage\tto\tprogress\tto\nthe\tpoint\tof\tirreversibility.\nA\tdosage\tof\t1\tmg\tof\tfolate\ttaken\torally\tevery\tday\tfor\t2\tto\t3\tweeks\treplenishes\tfolate\tstores.\nMaintaining\trepleted\tstores\trequires\tan\tabsolute\tminimum\toral\tintake\tof\t50\tto\t100\tmicrograms\tof
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folate\tfrom\tfood\tand\tor\tdietary\tsupplements\tdaily.\tWhen\tfolate\tdeficiency\tis\tcomplicated\tby\nalcoholism,\tgenetic\n\taberrations,\tor\tother\tconditions\tthat\tsuppress\thematopoiesis,\tincrease\tfolate\nrequirements,\tor\treduce\tfolate\tabsorption,\ttherapy\tshould\tremain\tat\t500\tto\t1000\tmicrograms\tdaily.
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Symptomatic\timprovement,\tas\tevidenced\tby\tincreased\talertness,\tand\tappetite,\tmay\tbe\tapparent\nwithin\t24\tto\t48\thours,\tlong\tbefore\thematologic\tvalues\trevert\tto\tnormal,\ta\tgradual\tprocess\tthat\ttakes\napproximately\ta\tmonth.\nMedical\tnutrition\ttherapy\nAfter\tthe\tanemia\tis\tcorrected,\tthe\tpatient\tshould\tbe\teducated\tto\teat\tmultiple\tservings\tof\tfolate-rich
|
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fresh\tfruit\tor\tdark\tgreen\tvegetables\tor\tto\tdrink\ta\tglass\tof\tvegetable\tor\tfruit\tand\tvegetable\tjuice\tdaily\n(see\t\nAppendix\t31\n\tfor\ta\tlist\tof\tfolate-containing\tfoods).\tFresh,\tuncooked\tfruits\tand\tvegetables\tare\ngood\tsources\tof\tfolate\tbecause\tfolate\tcan\teasily\tbe\tdestroyed\tby\n\theat.\tIn\t1998\tthe\tFood\tand\tDrug
|
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] |
heat.\tIn\t1998\tthe\tFood\tand\tDrug\nAdministration\trequired\tthat\tgrains\tbe\tfortified\twith\tfolic\tacid.\tThe\tRDAs\tfor\tfolate\tare\tsummarized\non\tthe\tinside\tcover\tof\tthis\ttext.\tThe\tRDA\tfor\tadults\tis\t400\tmcg\tdaily.\tThe\tDietary\tGuidelines\tfor\nAmericans\trecommend\tthat\twomen\tof\tchildbearing\tage\twho\tmay\tbecome\tpregnant\tand\tthose\tin\ttheir
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] |
first\ttrimester\tof\tpregnancy\tconsume\tadequate\tsynthetic\tfolic\tacid\t(400\tmcg/day\n\tand\t600\tmcg/day,\nrespectively)\tfrom\tfortified\tfoods\tand\tsupplements\tin\taddition\tto\tconsuming\ta\tvariety\tof\tfoods\ncontaining\tfolate\t(see\t\nChapter\t14\n\tand\t\nAppendix\t31\n).\nVitamin\tB\n12\n\tdeficiency\tand\tpernicious\tanemias\nIntrinsic\tfactor\t(IF)
|
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] |
Vitamin\tB\n12\n\tdeficiency\tand\tpernicious\tanemias\nIntrinsic\tfactor\t(IF)\n\tis\ta\tglycoprotein\tsecreted\tby\tparietal\tcells\tof\tthe\tgastric\tmucosa\tin\tthe\tgastric
|
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juice\tthat\tis\tnecessary\tfor\tthe\tabsorption\tof\tdietary\tvitamin\tB\n12\n.\tIngested\tvitamin\n\tB\n12\n\tis\tfreed\tfrom\nprotein\tby\tgastric\tacid\tand\tgastric\tand\tintestinal\tenzymes.\tThe\tfree\tvitamin\tB\n12\n\tattaches\tto\tsalivary\nR-binder,\twhich\thas\ta\thigher\taffinity\tfor\tthe\tvitamin\tthan\tdoes\tIF.\tAn\tacid\tpH\t(2.3)\tis\tneeded,\tsuch\tas\nthat\tfound\tin\tthe\thealthy\tstomach.
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] |
that\tfound\tin\tthe\thealthy\tstomach.\nEtiology\nThe\trelease\tof\tpancreatic\ttrypsin\tinto\tthe\tproximal\tsmall\tintestine\tdestroys\tR-binder\tand\treleases\nvitamin\tB\n12\n\tfrom\tits\tcomplex\n\twith\tR-protein.\tWith\tan\talkaline\tpH\t(6.8)\tin\tthe\tintestine,\tIF\tbinds\tthe\nvitamin\tB\n12\n.\tThe\tvitamin\tB\n12
|
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] |
vitamin\tB\n12\n.\tThe\tvitamin\tB\n12\n–IF\tcomplex\tis\tthen\tcarried\tto\tthe\tileum.\tIn\tthe\tileum,\twith\tthe\tpresence\nof\tionic\tcalcium\t(Ca\n2\n+)\tand\ta\tpH\t(>6),\tthe\tcomplex\tattaches\tto\tthe\tsurface\tvitamin\tB\n12\n–IF\treceptors\non\tthe\tileal\tcell\tbrush\tborder.\tHere,\tthe\tvitamin\tB\n12\n\tis\treleased\tand\tattaches\tto\t\nholotranscobalamin\nII\t(holo\tTCII)\n.\tHolo
|
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] |
holotranscobalamin\nII\t(holo\tTCII)\n.\tHolo\n\tTCII\tis\tvitamin\tB\n12\n\tattached\tto\tthe\tbeta-globulin,\tthe\tmajor\tcirculating\tvitamin\nB\n12\n\tdelivery\tprotein.\tLike\tIF,\tholo\tTCII\tplays\tan\tactive\trole\tin\tbinding\tand\ttransporting\tvitamin\tB\n12\n.\nThe\tTCII–vitamin\tB\n12\n\tcomplex\tthen\tenters\tthe\tportal\tvenous\tblood.
|
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-0.04492820426821709,
0.04334448277950287,
0.04476107656955719,
-0.01220216229557991,
-0.03143526241183281,
0.016997944563627243,
0.052707239985466,
0.07892825454473495,
0.047625768929719925,
-0.04294290021061897
] |
.\nThe\tTCII–vitamin\tB\n12\n\tcomplex\tthen\tenters\tthe\tportal\tvenous\tblood.\nOther\tbinding\tproteins\tin\tthe\tblood\tinclude\thaptocorrin,\talso\tknown\tas\ttranscobalamin\tI\t(TCI)\tand\ntranscobalamin\tIII\t(TCIII).\tThese\tare\talpha-globulins,\n\tlarger\tmacromolecular-weight\tglycoproteins
|
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0.07294442504644394,
-0.011415446177124977
] |
larger\tmacromolecular-weight\tglycoproteins\nthat\tmake\tup\tthe\tR-binder\tcomponent\tof\tthe\tblood.\tUnlike\tIF,\tthe\tR-proteins\tare\tcapable\tof\tbinding\nnot\tonly\tvitamin\tB\n12\n\tbut\talso\tmany\tof\tits\tbiologically\tinactive\tanalogs.\tAlthough\tapproximately\t75%\nof\tthe\tvitamin\tB\n12\n\tin\thuman\tserum\tis\tbound\tto\thaptocorrin\tand\troughly\t25%\tis\tbound\tto\tTCII,\tonly
|
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] |
TCII\tis\timportant\tin\tdelivering\tvitamin\tB\n12\n\tto\tall\tthe\tcells\n\tthat\tneed\tit.\tAfter\ttransport\tthrough\tthe\nbloodstream,\tTCII\tis\trecognized\tby\treceptors\ton\tcell\tsurfaces.\tPatients\twith\thaptocorrin\nabnormalities\thave\tno\tsymptoms\tof\tvitamin\tB\n12\n\tdeficiency.\tThose\tlacking\tTCII\trapidly\tdevelop\nmegaloblastic\tanemia.\tVitamin\tB\n12\n\tis\texcreted\tin\turine.
|
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] |
megaloblastic\tanemia.\tVitamin\tB\n12\n\tis\texcreted\tin\turine.\nPathophysiology\nPernicious\tanemia\n\tis\ta\tmegaloblastic,\tmacrocytic\tanemia\tcaused\tby\ta\tdeficiency\tof\tvitamin\tB\n12\n,\nmost\n\tcommonly\tfrom\ta\tlack\tof\tIF.\tRarely,\tvitamin\tB\n12\n\tdeficiency\tanemia\toccurs\tin\tstrict\tvegetarians\nwhose\tdiet\tcontains\tno\tvitamin\tB\n12
|
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whose\tdiet\tcontains\tno\tvitamin\tB\n12\n\texcept\tfor\ttraces\tfound\tin\tplants\tcontaminated\tby\nmicroorganisms\tcapable\tof\tsynthesizing\tvitamin\tB\n12\n.\tOther\tcauses\tinclude\tautoimmune\tdisorders\nthat\tdestroy\tgastric\tparietal\tcells;\tantibody\tto\tIF;\tbariatric\tor\tintestinal\tsurgery;\tbacterial\novergrowth\tin\tthe\tsmall\tintestine;
|
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] |
overgrowth\tin\tthe\tsmall\tintestine;\n\tmalabsorption\tin\tthe\tsmall\tintestine\tdue\tto\tceliac\tdisease,\tCrohn’s\ndisease,\tHIV,\ttropical\tsprue,\tand\tcancers\tinvolving\tthe\tsmall\tintestine;\tdrugs\t(paraaminosalicylic\nacid,\tcolchicine,\tneomycin,\tmetformin,\tantiretrovirals);\tand\tlong-term\tingestion\tof\talcohol\tor\ncalcium-chelating\tagents\t(\nBox\t31.3\n).
|
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] |
calcium-chelating\tagents\t(\nBox\t31.3\n).\nAging\tis\tassociated\twith\tB\n12\n\tdeficiency\tfor\tvarious\treasons\tas\tdiscussed\tin\t\nChapter\t19\n.\nApproximately\n\t1%\tto\t2%\tof\tthe\tU.S.\tpopulation\tover\tthe\tage\tof\t51\tyears\thas\tclinical\tB\n12\n\tdeficiency,\nand\tit\tis\tthought\tthat\t10%\tto\t20%\thave\tsubclinical\tdeficiency\t(\nCarmel,\t2011\n).\tThe\tincidence\tof\tB\n12
|
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] |
Carmel,\t2011\n).\tThe\tincidence\tof\tB\n12\ndeficiency\tin\tolder\tindividuals\tmay\tbe\trelated\tto\tmedications\tcommonly\tused\tin\tthis\tpopulation\tsuch\nas\tH\n2\n\tantagonists\t(see\t\nAppendix\t13\n)\tand\tmetformin\tused\tto\ttreat\ttype-2\tdiabetes\t(\nHerbert\t2019\n).\nStages\tof\tdeficiency\nAs\ta\tresult\tof\tnormal\tenterohepatic\tcirculation\t(i.e.,\texcretion\tof\tvitamin\tB\n12
|
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12\n\tand\tanalogs\tin\tbile\tand\nresorption\tof\tvitamin\tB\n12\n\tin\tthe\tileum),\tit\tmay\ttake\tup\tto\ta\tyear\tor\ttwo\tfor\tstrict\tvegetarians\twho\tare\nnot\treceiving\tvitamin\tB\n12\n\tsupplementation\tto\tdevelop\ta\tvitamin\tB\n12\n\tdeficiency.\tSerum\tB\n12\n,\nhomocysteine,\tand\tmethylmalonic\tacid\tlevels\tare\tnot\tas\teffective\tas\tpredictors\tof\tB\n12\n-responsive\nneurologic
|
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