Vitamine A

Wetenschappelijke naam

Vitamine A

Vitamine A

Vitamine A is een in vet oplosbare vitamine. Verschillende vitamine A-vormen omvatten retinol, retinaal, retinoïnezuur en retinylester. Deze verschillende vormen van vitamine A worden vaak gezamenlijk "retinoïden" genoemd. De meest krachtige vorm van vitamine A, all-trans retinol, is de vorm van retinol in de voeding (9191). Retinol is aanwezig in veresterde vorm in van dieren afgeleide producten, waaronder eieren, volle melk, boter, verrijkte margarine, vlees en olieachtige zeevis (7135). Dierlijke lever bevat de hoogste hoeveelheid retinol. Ongeveer tweederde van de vitamine A-inname komt van retinol via de voeding (9189). De vitamine A-familie bevat ook provitamine A-carotenoïden, die voorloper zijn van retinol. Ongeveer een derde van de vitamine A in de voeding is afkomstig van planten, die carotenoïden synthetiseren die in het lichaam worden omgezet in vitamine A (7135). Carotenoïde pigmenten (inclusief alfa-, bèta- en gamma-caroteen en cryptoxanthine) zijn aanwezig in granen, oliën, groene en gele groenten, en vooral in wortelen en fruit (8044). De hoeveelheid carotenoïden die worden geabsorbeerd en omgezet in vitamine A hangt af van de hoeveelheid ingenomen carotenoïden, de vitamine A-status van het individu en de carotenoïdencarrosserieën. Carotenoïden leveren ongeveer 50% van de vitamine A die nodig is in het Amerikaanse dieet (8044).

Gebruik

Oraal, vitamine A wordt gebruikt voor vitamine A-tekorten, verbetering van het gezichtsvermogen, leeftijdsgebonden maculaire degeneratie (AMD), glaucoom, cataract, retinitis pigmentosa, infectie en verbetering van de immuunfunctie. Het wordt ook oraal gebruikt voor huidaandoeningen zoals acne, eczeem, psoriasis, koortslippen, wonden, brandwonden, zonnebrand, keratosis follicularis (ziekte van Darier), ichthyosis (niet-inflammatoire huidschilfers), lichen planus pigmentosus en pityriasis rubra pilaris. Vitamine A wordt ook oraal gebruikt om vitamine A-tekort te voorkomen en te behandelen als gevolg van abnormale opslag en transport van vitamine A bij mensen met abetalipoproteïnemie, eiwitgebrek, diabetes mellitus, hyperthyreoïdie, koorts, leverziekte of cystische fibrose met leverbetrokkenheid. Het wordt ook oraal gebruikt voor zware menstruatie, premenstrueel syndroom (PMS), atrofische vaginitis, candidiasis, fibrocystische borstaandoeningen, verminderd aantal zaadcellen, maag-darmzweren, ziekte van Crohn, parodontitis, darmparasieten, diabetes, osteoartritis, tuberculose, luchtweginfecties, Hurler syndroom (mucopolysaccharidosis), sinusitis, allergische rhinitis en urineweginfecties (UTI's). Vitamine A wordt ook gebruikt voor het verminderen van complicaties van mazelen, shigellose, atrofische rhinitis, verlies van reukvermogen, astma, aanhoudende hoofdpijn, nierstenen, alcoholische hepatitis, autisme, de ziekte van Parkinson, complicaties van multiple sclerose (MS), hyperthyreoïdie, bloedarmoede, doofheid, tinnitus en leukoplakie. Andere orale toepassingen zijn het voorkomen en behandelen van kanker, non-Hodgkin-lymfoom en nadelige effecten op chemotherapie of radiotherapie, preventie van atopische aandoeningen, degeneratieve aandoeningen van het zenuwstelsel, bescherming van het hart en het cardiovasculaire systeem (antioxiderende effecten), genezing na fotoreactieve keratectomie en het verminderen van complicaties geassocieerd met bypass-kransslagader (CABG) en het vertragen van het verouderingsproces. Vitamine A wordt oraal gebruikt om de totale mortaliteit te verminderen, evenals de morbiditeit geassocieerd met malaria bij kinderen, en morbiditeit en mortaliteit door longontsteking en HIV bij kinderen met vitamine A-tekort. Vitamine A wordt ook oraal gebruikt om het risico op HIV-overdracht op de foetus tijdens de zwangerschap en overdracht op de pasgeborene tijdens de bevalling en vroege borstvoedingsperioden te verminderen en om zwangerschapsgerelateerde complicaties, evenals koorts en diarree na de bevalling, bij ondervoede vrouwen te verminderen. . Vitamine A wordt oraal gebruikt om de groei te verbeteren bij kinderen met een vitamine A-tekort en voor geestelijke en lichamelijke ontwikkeling bij zuigelingen.

In de praktijk wordt vitamine A gebruikt om wondgenezing te verbeteren, rimpels te verminderen en de huid te beschermen tegen UV-straling.

Intramusculair wordt vitamine A gebruikt voor het voorkomen en behandelen van de symptomen van een vitamine A-tekort, waaronder xeroftalmie en nachtblindheid, het voorkomen van vitamine A-tekort bij mensen met malabsorptie, het voorkomen van bronchopulmonale dysplasie bij premature baby's en het voorkomen van stresszweren bij ernstig zieke ziekenhuispatiënten.

Veiligheid

WAARSCHIJNLIJK VEILIG: wanneer oraal of intramusculair en op de juiste manier gebruikt. Vitamine A is veilig bij volwassenen wanneer het wordt ingenomen in doses lager dan het aanvaardbare bovenste inname niveau (UL) van 10.000 IE/dag (7135). Hogere doses verhogen het risico op bijwerkingen. Er is ook groeiende bezorgdheid dat het nemen van hoge doses antioxidanten zoals vitamine A meer kwaad dan goed kan doen. In een analyse van studies wordt het nemen van vitamine A-supplementen alleen of in combinatie met andere antioxidanten geassocieerd met een verhoogd risico op sterfte door allerlei oorzaken (15305, 90775).

MOGELIJK ONZEKER: bij oraal gebruik in hoge doses. Vitamine A 25.000 IE (als retinylpalmitaat) dagelijks gedurende 6 maanden gevolgd door 10.000 IE dagelijks gedurende 6 maanden, is met schijnbare veiligheid gebruikt in één klinische studie (95052). Langdurig gebruik van overmatige doses vitamine A kan echter significante bijwerkingen veroorzaken, zoals hypervitaminosis A. Het risico op het ontwikkelen van hypervitaminosis A is gerelateerd aan de totale cumulatieve dosis vitamine A in plaats van een specifieke dagelijkse dosis (1467, 1469). Er is ook bezorgdheid dat het innemen van hoge doses antioxidanten zoals vitamine A meer kwaad dan goed kan doen. In een analyse van studies wordt het nemen van vitamine A-supplementen alleen of in combinatie met andere antioxidanten geassocieerd met een verhoogd risico op sterfte door alle oorzaken (15305, 90775).

Er is onvoldoende betrouwbare informatie beschikbaar over de veiligheid van het gebruik van sublinguale of actuele formuleringen van vitamine A.

KINDEREN: WAARSCHIJNLIJK VEILIG: wanneer oraal of intramusculair en op de juiste manier gebruikt. De hoeveelheid vitamine A die veilig is, is afhankelijk van de leeftijd. Voor kinderen tot 3 jaar lijken doses van minder dan 2000 eenheden per dag veilig te zijn. Voor kinderen van 4 tot 8 jaar lijken doses van minder dan 3000 IE per dag veilig te zijn. Voor kinderen van 9 tot 13 jaar lijken doses van minder dan 5700 eenheden per dag veilig te zijn. Voor kinderen van 14 tot 18 jaar lijken doses van 9300 eenheden per dag veilig (7135). MOGELIJK ONVEILIG: bij oraal gebruik in hoge doses. Voor kinderen tot 3 jaar, vermijd doses hoger dan 2000 IE per dag. Voor kinderen van 4 tot 8 jaar, vermijd doses hoger dan 3000 IE per dag. Voor kinderen van 9 tot 13 jaar, vermijd doses hoger dan 5700 IE per dag. Voor kinderen van 14 tot 18 jaar, vermijd doses hoger dan 9300 IE per dag (7135). Hogere doses vitamine A-suppletie zijn in verband gebracht met een verhoogd risico op bijwerkingen zoals longontsteking, botpijn en diarree (319, 95051).

ZWANGERSCHAP EN LACTATIE: WAARSCHIJNLIJK VEILIG: wanneer oraal of intramusculair en op de juiste manier gebruikt. Vitamine A is veilig tijdens zwangerschap en borstvoeding wanneer het wordt gebruikt in doses van minder dan 10.000 IE per dag (7135, 16823). MOGELIJK ONVEILIG: bij oraal of intramusculair gebruik in hoge doses. Dagelijkse inname van meer dan 10.000 IE kan foetale misvormingen veroorzaken (3066, 7135). Overmatige inname van vitamine A via de voeding is ook in verband gebracht met teratogeniteit (11978). Het eerste trimester van de zwangerschap lijkt de kritieke periode te zijn voor gevoeligheid voor vitamine A-geassocieerde geboorteafwijkingen zoals craniofaciale afwijkingen en afwijkingen van het centrale zenuwstelsel (7135). Vormen van vitamine A zijn te vinden in verschillende voedingsmiddelen, waaronder dierlijke producten, voornamelijk lever, sommige verrijkte ontbijtgranen en voedingssupplementen (3066).

Effectiviteit

EFFECTIEF

Vitamine A-tekort: het mondeling innemen van vitamine A is effectief voor het voorkomen en verbeteren van symptomen van vitamine A-tekort, inclusief xeroftalmie, nachtblindheid en Bitots vlekken (82329, 82689, 82710, 90773). Vitamine A-tekort kan optreden als gevolg van abnormale opslag en transport van vitamine A bij mensen met abetalipoproteïnemie, eiwittekort, diabetes mellitus, hyperthyreoïdie, koorts, leverziekte en cystische fibrose (7135).

MOGELIJK EFFECTIEF

Borstkanker: epidemiologisch bewijs toont een verband aan tussen hoge inname van vitamine A en een verminderd risico op borstkanker bij premenopauzale vrouwen met een positieve familiegeschiedenis van borstkanker (1444, 34610). Het is echter niet bekend of supplementaire vitamine A een soortgelijk voordeel heeft.

Staar: een grootschalig bevolkingsonderzoek suggereert dat een hoge inname van vitamine A via de voeding geassocieerd is met een verminderd risico op nucleaire staar (6378). Uit analyse van populatieonderzoek blijkt ook dat de hoogste inname van vitamine A via de voeding geassocieerd is met een 17% lager risico op staar in vergelijking met de laagste inname (90786). Er is echter tegenstrijdig bewijs met betrekking tot de associatie tussen de bloedspiegels van vitamine A en het risico op cataract (90786, 90944). Het is niet bekend of aanvullende vitamine A een voordeel heeft.

Mazelen: analyses van klinisch onderzoek tonen aan dat het nemen van vitamine A de mortaliteit bij kinderen met mazelen niet vermindert wanneer alle leeftijden worden overwogen. Het oraal innemen van vitamine A 200.000 IE gedurende ten minste twee doses lijkt echter het risico op mortaliteit tot 83% te verminderen bij kinderen met mazelen die jonger zijn dan 2 jaar (82373, 82502).

Orale leukoplakie: klinisch onderzoek toont aan dat orale vitamine A 200.000-300.000 IE wekelijks gedurende 6-12 maanden de orale remissie van leukoplakie met maximaal 57% kan verbeteren (34674, 82617).

Algemene sterfte: er is enige discussie over de vraag of de programma's die hoge doses vitamine A leveren, veilig en effectief zijn voor het verminderen van kindersterfte in landen met een laag en middeninkomen waar vitamine A-tekort een probleem voor de volksgezondheid is. De meeste experts zijn het er echter over eens dat er redelijk bewijs is van klinisch betekenisvol voordeel (95055,95724, 97170).

Een meta-analyse van klinisch onderzoek gepubliceerd in april 2010, met 17 onderzoeken met meer dan 194.000 patiënten, toonde aan dat vitamine A-suppletie de mortaliteit door alle oorzaken vermindert met ongeveer 24% bij kinderen van 6 maanden tot 5 jaar (82559). Sommige onderzoeken die na deze meta-analyse zijn gepubliceerd, laten echter tegenstrijdige resultaten zien (90773, 90777). De grootste klinische studie die tot nu toe is uitgevoerd (Deworming and Enhanced Vitamine A; DEVTA), die na de analyse is gepubliceerd en waarbij een miljoen kleuters betrokken waren, suggereert dat een hoge dosis vitamine A-suppletie de mortaliteit door alle oorzaken niet significant vermindert bij kinderen van 6 maanden tot 5 jaar (90773). Deze grote studie had echter een aanzienlijk tekort aan middelen en werd bekritiseerd vanwege significante methodologische tekortkomingen, waaronder ontbrekende toestemming van de patiënt bij aanvang en gebrek aan therapietrouw (90773). Bovendien blijkt uit een meta-analyse die in 2017 is gepubliceerd, inclusief de DEVTA-studie, samen met 46 aanvullende studies waarbij meer dan 1,2 miljoen kleuters betrokken waren, dat vitamine A-suppletie de mortaliteit door alle oorzaken met 12% vermindert (95055). Op basis van deze bevindingen zijn de meeste experts het erover eens dat een hoge dosis vitamine A-suppletie voor kleuters in lage- en middeninkomenslanden het risico op sterfte door alle oorzaken vermindert met een klinisch betekenisvolle hoeveelheid en dat aanvullende onderzoeken deze conclusies waarschijnlijk niet zullen beïnvloeden (95055, 97170). De Wereldgezondheidsorganisatie blijft een hoge dosis vitamine A-suppletie aanbevelen voor kinderen van 6 maanden tot 5 jaar uit gebieden waar vitamine A-tekort een volksgezondheidsprobleem is (95724).

Postpartum diarree: klinisch onderzoek toont aan dat oraal innemen van vitamine A het optreden van postpartum diarree bij ondervoede vrouwen vermindert. Inname van vitamine A (als retinylpalmitaat) 23.000 IE wekelijks vóór, tijdens en na de zwangerschap vermindert het optreden van bloed en slijm in de ontlasting met 93% en vermindert het optreden van losse ontlasting met 88% tot 90% in vergelijking met placebo tijdens de eerste 6 maanden postpartum (2581).

Zwangerschapsgerelateerde sterfte: klinisch onderzoek toont aan dat het wekelijks gebruiken van vitamine A (als retinylpalmitaat) 23.000 IE vóór en tijdens de zwangerschap de zwangerschapsgerelateerde mortaliteit met 40% vermindert bij ondervoede vrouwen (6153).

Zwangerschap-gerelateerde nachtblindheid: klinisch onderzoek toont aan dat het nemen van vitamine A (als retinylpalmitaat) 23.000 IE wekelijks vóór en tijdens de zwangerschap zwangerschapsgerelateerde nachtblindheid met 37% vermindert bij ondervoede vrouwen (6154). Er zijn aanwijzingen dat zinksupplementen de effecten van vitamine A kunnen versterken bij het herstellen van het zicht bij zwangere vrouwen met een tekort aan zink die worden getroffen door nachtblindheid (8630).

Retinitis pigmentosa: observationeel en klinisch onderzoek toont aan dat het dagelijks nemen van vitamine A 15.000 IE of minder de achteruitgang van de retinale functie vertraagt ​​bij patiënten met retinitis pigmentosa (83, 97167).

Bronchopulmonale dysplasie: klinisch onderzoek toont aan dat suppletie met intramusculaire vitamine A de incidentie van bronchopulmonale dysplasie bij baby's met een zeer laag geboortegewicht niet vermindert (82331, 82613, 82731, 90778). Uit voorlopig klinisch onderzoek blijkt echter dat het intramusculair toedienen van vitamine A de incidentie van bronchopulmonale dysplasie in een subgroep van baby's met een laag geboortegewicht zou kunnen verminderen bij gebruik van stikstofmonoxide gedurende 21 dagen in vergelijking met alleen stikstofoxide (90778).

Anemie: sommige onderzoeken tonen aan dat het nemen van vitamine A, hemoglobine en ferritine, een eiwit in cellen die ijzer opslaan, verhoogt en het risico op bloedarmoede bij kinderen en zwangere vrouwen kan verminderen (9518, 34627). In ontwikkelingslanden met een hoge prevalentie van bloedarmoede lijkt het innemen van 3000 mcg retinol-equivalent van vitamine A in combinatie met ijzer en folaat oraal echter de concentraties hemoglobine en erytropoëtine niet meer te verbeteren dan alleen ijzer en folaat bij zwangere vrouwen (9188).

Autisme: kinderen met autisme hebben vaak een tekort aan vitamine A en vitamine A-niveaus zijn omgekeerd geassocieerd met autismesymptomen. Voorlopig klinisch onderzoek toont aan dat het nemen van een enkele dosis vitamine A 200.000 IE de emotionele respons, communicatie en andere symptomen enigszins verbetert in vergelijking met de uitgangssituatie bij kinderen met autismespectrumstoornissen (97168). Het ontbreken van een controlegroep beperkt de geldigheid van deze bevindingen.

Baarmoederhalskanker: analyse van klinisch onderzoek toont aan dat verhoogde vitamine A-waarden in het bloed of hogere vitamine A-innames geassocieerd zijn met een verminderd risico op baarmoederhalskanker. Dit effect wordt echter waargenomen wanneer beide vormen van vitamine A, retinol of carotenen, worden overwogen. Wanneer alleen de retinolvorm wordt overwogen, lijkt vitamine A-suppletie het risico op baarmoederhalskanker niet te verminderen (34613).

Kinderontwikkeling: Bij kinderen met vitamine A-tekort kan suppletie met vitamine A de groei verbeteren (82246).

Chronische straling proctitis: voorlopig klinisch onderzoek toont aan dat dagelijks 90 dagen retinolpalmitaat gedurende 90 dagen rectale symptomen kan verminderen in vergelijking met placebo bij patiënten met chronische stralingsproctopathie veroorzaakt door bekkenradiotherapie (82350).

Colorectaal adenoom: klinisch onderzoek toont aan dat het dagelijks nemen van een supplement met selenium, zink, vitamine A, vitamine C en vitamine E gedurende 5 jaar of tot het terugkeren van een adenoom het risico op recidiverende adenomen van de dikke darm met ongeveer 40% vermindert in vergelijking met placebo bij patiënten met adenomen van de dikke darm (92903). Het is niet duidelijk of dit voordeel te wijten is aan vitamine A of andere bestanddelen.

Coronaire bypass-operatie (CABG): voorlopig klinisch onderzoek toont aan dat het dagelijks innemen van vitamine A 5000 IE (als retinolpalmitaat) gedurende 21 dagen vanaf de dag van bypassoperaties van de kransslagader de tijd op de intensive care na chirurgie met 46% tot 69% verkort in vergelijking met een controlegroep die geen vitamine A kreeg (90783). Suppletie met vitamine A verbetert ook de totale ziekenhuisopname-tijd voor die patiënten met een adequate zinkstatus (90783).

HIV: een gepoolde analyse van klinische studies en populatieonderzoek toont aan dat vitamine A-suppletie bij moeders met een slechte vitamine A-status bij aanvang, geen invloed heeft op kinder- of moedersterfte, ziekenhuisopname of HIV-progressie. Pediatrische vitamine A-suppletie lijkt echter het sterftecijfer bij kinderen met HIV te verlagen in vergelijking met placebo (34529,95059).

HIV-gerelateerde diarree: een groot klinisch onderzoek toont aan dat het nemen van vitamine A de sterftecijferspecifieke mortaliteit tot 92% kan verlagen bij vitamine A-deficiënte kinderen met of zonder HIV (1465). Een analyse van klinisch onderzoek toont echter aan dat het nemen van vitamine A de diarree-specifieke mortaliteit niet significant vermindert wanneer alleen kinderen met HIV worden overwogen (82511). Maar vitamine A lijkt de algehele mortaliteit bij deze kinderen met 50% tot 63% te verminderen (1465, 82511).

Ontwikkeling van baby's: analyse van klinisch onderzoek toont aan dat het geven van intramusculaire vitamine A aan zuigelingen met een zeer laag geboortegewicht het risico op chronische longziekte op 36 weken na de menstruatie met ongeveer 13% vermindert in vergelijking met controle (95053). Voorlopig klinisch onderzoek toont ook aan dat het geven van intramusculaire vitamine A samen met ingeademd stikstofmonoxidegas gedurende 3 weken aan zuigelingen met een laag geboortegewicht op mechanische ventilatie de mentale ontwikkeling na een jaar bij sommige van deze patiënten zou kunnen verbeteren in vergelijking met alleen inhalatie van stikstofmonoxidegas (90778). Uit analyse van klinisch onderzoek blijkt echter dat intramusculaire vitamine A de neurologische ontwikkeling bij baby's met een zeer laag geboortegewicht niet verbetert (95053).

Longkanker: sommige klinische onderzoeken tonen aan dat een hoge dosis vitamine A 300.000 IE per dag na curatieve longkankerresectie het risico op nieuwe primaire tumoren vermindert bij patiënten die sterk worden blootgesteld aan tabak (7875).

Malaria: er zijn aanwijzingen dat vitamine A ten goede kan komen aan zuigelingen en jonge kinderen met malaria. Het oraal innemen van vitamine A lijkt de symptomen van malaria te helpen verminderen bij kinderen jonger dan 3 jaar die in endemische malariagebieden wonen (1464). Ander klinisch onderzoek toont echter aan dat enkele doses vitamine A 100.000 tot 200.000 IE de coma-resolutie, convulsies, koorts, parasitaire klaring of mortaliteit bij zuigelingen en kinderen jonger dan 5 jaar met cerebrale malaria niet verbeteren (90785).

Multiple sclerose-gerelateerde vermoeidheid: voorlopig klinisch onderzoek toont aan dat het dagelijks nemen van vitamine A 25.000 IE (als retinylpalmitaat) (Zahravi Farmaceutisch) gedurende 6 maanden gevolgd door 10.000 IE dagelijks gedurende 6 maanden, fysieke, cognitieve en psychosociale vermoeidheid verbetert in vergelijking met placebo bij patiënten met relapsing-remitting multiple sclerose die interferon beta-1a ontvangen (95052).

Non-Hodgkin lymfoom: populatieonderzoek suggereert dat mensen met een vitamine-inname van meer dan 2330 mcg per dag een 17% lager risico op non-Hodgkin-lymfoom hebben dan mensen met een dagelijkse vitamine-inname van minder dan 642 mcg per dag (90945).

Alvleesklierkanker: een analyse van observationeel onderzoek wees uit dat een hogere inname van vitamine A geassocieerd is met een verminderd risico op alvleesklierkanker; dit voordeel lijkt echter beperkt te zijn tot alleen ziekenhuisgevallen en onderzoeken uitgevoerd in Europa (95060). Analyse van klinisch onderzoek toont aan dat het nemen van vitamine A in combinatie met bètacaroteen het risico op alvleesklierkanker niet vermindert (12185).

Photoreactieve keratectomie: voorlopig klinisch onderzoek toont aan dat het nemen van een specifiek product (Evitex-capsules, Alcon) dat vitamine A bevat samen met vitamine E de genezing lijkt te verbeteren na fotoreactieve keratectomie. Hoge dosis (50.000 tot 75.000 IE) vitamine A in de vorm van retinolpalmitaat, dagelijks ingenomen met vitamine E (alfa-tocoferyl nicotinaat) 460-590 mg per dag lijkt re-epithelisatie te versnellen, de vorming van nevel te verminderen en de gezichtsscherpte te verbeteren bij patiënten die een laserchirurgie voor bijziendheid hebben ondergaan (348).

Dosering & gebruik

Volwassen

Oraal:

Algemeen: aanbevolen dagelijkse hoeveelheid (ADH) voor volwassenen: mannen van 19 jaar en ouder, 900 mcg / dag (3000 IE); vrouwen 19 jaar en ouder, 700 mcg / dag (2300 IE); zwangerschap 19 jaar en ouder, 770 mcg / dag (2600 IE); lactatie 19 jaar en ouder, 1300 mcg / dag (4300 IE) (7135). Vitamine A dosering wordt meestal uitgedrukt in IE, maar vermelding in microgram wordt soms gebruikt. Eén mcg vitamine A is gelijk aan 3,33 IE vitamine A. Vitamine A-aanbevelingen zijn voor retinol of voorgevormde vitamine A. Eerder werden vitamine A ADH-aanbevelingen uitgedrukt als retinolequivalenten (RE) om rekening te houden met de verschillen in bioconversie van de verschillende vitamine A vormt zich naar retinol. Retinol-activiteitsequivalenten (RAE) worden nu gebruikt: 1 mcg retinol is gelijk aan 1 RAE wat gelijk is aan 2 mcg aanvullend beta-caroteen, 12 mcg dieet beta-caroteen en 24 mcg dieet alfa-caroteen of beta-cryptoxanthine. Voorgevormde vitamine A uit dierlijke producten (retinol) of provitamine A-carotenoïden uit plantaardige producten zijn een aanvaardbare vitamine A-bron, hoewel provitamine A-carotenoïden in grotere hoeveelheden moeten worden geconsumeerd (7135). Consumptie van 5 porties fruit en groenten per dag levert 5-6 mg provitamine A carotenoïden, die ongeveer 50% tot 65% van de volwassen ADH voor vitamine A levert (7135).

Bloedarmoede: vitamine A 3333-10.000 IE is dagelijks gebruikt (34627).

Chronische stralingsproctitis: vitamine A 10.000 IE als retinolpalmitaat gedurende 90 dagen dagelijks (82350).

Colorectaal adenoom: een combinatiesupplement met selenium 200 mcg (als L-selenomethionine), zink 30 mg, vitamine A 2 mg (als retinol), vitamine C 180 mg en vitamine E 30 mg (als Da-tocoferolacetaat) dagelijks gedurende 5 jaar of tot het opnieuw optreden van een adenoom, is gebruikt (92903).

Coronaire bypass-operatie (CABG): vitamine A 5000 IE als retinolpalmitaat dagelijks gedurende 21 dagen (90783).

Longkanker: na een operatie is vitamine A 300.000 IE als retinolpalmitaat dagelijks gedurende 12 maanden gebruikt (7875).

Multiple sclerose-gerelateerde vermoeidheid: vitamine A 25.000 IE als retinylpalmitaat (Zahravi Pharmaceutical) dagelijks gedurende 6 maanden gevolgd door 10.000 IE dagelijks gedurende 6 maanden, is gebruikt (95052).

Orale leukoplakie: vitamine A 200.000 - 300.000 IE per week gedurende 6-12 maanden is gebruikt (34674. 82617).

Fotoreactieve keratectomie: vitamine A 75.000 IE dagelijks gedurende 30 dagen in drie verdeelde doses, gevolgd door 50.000 IE dagelijks gedurende 2 maanden in twee verdeelde doses, als retinolpalmitaat, met vitamine E 460-690 mg als alfa-tocoferyl nicotinaat, is gebruikt (348).

Post-partum diarree: Vitamine A 23.000 IE wekelijks vóór, tijdens en na de zwangerschap is gebruikt (2581).

Zwangerschapsgerelateerde mortaliteit: Vitamine A 23.300 IE wekelijks vóór en tijdens de zwangerschap is gebruikt (6153).

Zwangerschapgerelateerde nachtblindheid: Vitamine A 23.300 IE wekelijks vóór en tijdens de zwangerschap is gedurende 3 weken dagelijks gebruikt met of zonder 35 mg zink (6154, 8630).

Retinitis pigmentosa: Vitamine A 15.000 IE dagelijks, met of zonder vitamine E 400 IE dagelijks, gedurende 4-6 jaar is gebruikt (83).

Kinderen

Oraal:

Algemeen: Adequate inname (AI) niveaus van vitamine A voor zuigelingen zijn vastgesteld: geboorte tot 6 maanden, 400 mcg per dag (1300 IE); 7 tot 12 maanden, 500 mcg per dag (1700 IE). De aanbevolen dagelijkse hoeveelheid (ADH) voor kinderen is vastgesteld: kinderen 1 tot 3 jaar, 300 mcg per dag (1000 IE); 4 tot 8 jaar, 400 mcg per dag (1300 IE); 9 tot 13 jaar, 600 mcg dagelijks (2000 IE); jongens van 14 jaar en ouder, 900 mcg per dag (3000 IE); meisjes van 14 jaar en ouder, 700 mcg per dag (2300 IE); zwangerschap 14 tot 18 jaar, 750 mcg dagelijks (2500 IE); borstvoeding 14 tot 18 jaar, 1200 mcg per dag (4000 IE) (7135). Vitamine A dosering wordt meestal uitgedrukt in IE, maar dosering in microgram wordt soms gebruikt. Eén mcg vitamine A is gelijk aan 3,33 IE vitamine A. Vitamine A-aanbevelingen zijn voor retinol of voorgevormde vitamine A. Eerder werden vitamine A ADH-aanbevelingen uitgedrukt als retinolequivalenten (RE) om rekening te houden met de verschillen in bioconversie van de verschillende vitamine A vormt zich naar retinol. Retinol-activiteitsequivalenten (RAE) worden nu gebruikt: 1 mcg retinol is gelijk aan 1 RAE wat gelijk is aan 2 mcg aanvullend beta-caroteen, 12 mcg dieet beta-caroteen en 24 mcg dieet alfa-caroteen of beta-cryptoxanthine. Voorgevormde vitamine A uit dierlijke producten (retinol) of provitamine A-carotenoïden uit plantaardige producten is een aanvaardbare vitamine A-bron, hoewel provitamine A-carotenoïden in grotere hoeveelheden moeten worden geconsumeerd (7135). Consumptie van 5 porties fruit en groenten per dag levert 5-6 mg provitamine A carotenoïden, die ongeveer 50% tot 65% van de volwassen ADH voor vitamine A levert (7135).

Autisme: Vitamine A 200.000 IE is eenmaal gebruikt (97168).

HIV-gerelateerde diarree: vitamine A 400.000 IE als drie afzonderlijke doses met een tussenpoos van 4 maanden is gebruikt in combinatie met conventionele geneesmiddelen bij kinderen van 6 maanden tot 5 jaar (1465).

Malaria: vitamine A 100.000 IE bij zuigelingen <12 maanden of 200.000 IE bij zuigelingen van 12-24 maanden aan het begin en het einde van een periode van 6 maanden is gebruikt met of zonder zink 10 mg per dag gedurende 6 maanden (90771). Vitamine A 200.000 IE, in 200 mcL arachideolie met 10 mcg vitamine E als conserveermiddel, is om de 3 maanden gedurende 13 maanden gebruikt bij kinderen van 6-60 maanden (1464).

Mazelen: vitamine A 200.000 IE oraal voor ten minste twee enkele doses voor kinderen ouder dan een jaar en twee enkele doses van 100.000 IE voor zuigelingen zijn gebruikt (82373, 82502).

Algemene mortaliteit: een hoge dosis vitamine A-suppletie wordt aanbevolen voor kinderen in de leeftijd van 6-59 maanden in landen met een laag en gemiddeld inkomen waar vitamine A-tekort een volksgezondheidsprobleem is. Een enkele dosis vitamine A 100.000 IE wordt aanbevolen voor zuigelingen van 6-11 maanden oud, en vitamine A 200.000 IE elke 4-6 maanden wordt aanbevolen voor kinderen van 12-59 maanden oud (95724).

Vitamine A-tekort: bij kinderen van 6-72 maanden werd vitamine A als retinylacetaat in olie 200.000 IE om de 6 maanden gedurende 5 jaar gebruikt (90773).

Standaardisatie en formulering

Orale vitamine A wordt vaak geleverd in pinda-olie, plantaardige olie of sojaolie met vitamine E als conserveermiddel (2581, 90772, 90776, 90780, 90781, 90782, 90784). Het kan ook worden geleverd als een met water mengbare formulering (95057).

Supplementen bestaan ​​meestal uit voorgevormde vitamine A (95055). Vitamine A kan worden gemeten in internationale eenheden (IE) retinylpalmitaat (3,33 IE of 0,003491 micromol retinol = 1 microgram of retinol-equivalent RE) (95057).

Bijwerkingen

Algemeen: oraal, vitamine A wordt over het algemeen goed verdragen bij doses onder het aanvaardbare bovenste inname niveau (UL) en bijwerkingen in klinische onderzoeken ontbreken meestal of komen in dezelfde mate voor als in de placebogroep (82739, 90773, 90776,  90785). Hypervitaminosis A treedt echter soms op wanneer vitamine A wordt ingenomen in doses boven de UL. Acute hypervitaminose A kan optreden bij volwassenen en kinderen wanneer vitamine A wordt ingenomen in doses die respectievelijk 100 keer groter en 20 keer hoger zijn dan de ADH. Chronische hypervitaminose A kan optreden bij inname van vitamine A bij doses van> 25.000 IE dagelijks gedurende meer dan 6 jaar of 100.000 IE dagelijks gedurende meer dan 6 maanden (94644). De hoeveelheid vitamine A die chronische toxiciteit veroorzaakt, wordt echter beïnvloed door factoren zoals doseringsschema, vitaminevorm, gezondheidstoestand, voedingsfactoren zoals ethanol- en eiwitinname en interacties met vitamine C, D, E en K (10560). De lever is de belangrijkste opslagplaats van vitamine A. Hepatotoxiciteit geassocieerd met orale vitamine A heeft de dood tot gevolg gehad (6377, 7135). Er is bezorgdheid dat het nemen van hoge doses vitamine A het sterftekansrisico zou kunnen verhogen, maar deze associatie is in twijfel getrokken door andere onderzoekers (15305). Hypervitaminosis A kan verschillende dermatologische symptomen veroorzaken, waaronder een droge huid en lippen; scheurtjes, schilfers en jeukende huid; roodheid van de huid; hyperpigmentatie; en massale huidpeeling (7135,95051) en broze nagels, cheilitis, gingivitis en haarverlies (15, 95051). Andere symptomen zijn verhoogde leverenzymen, diarree, misselijkheid, anorexia, buikpijn en braken (7135, 82326, 82389, 82559, 95051, 95055). Hypervitaminosis A kan het risico op osteoporose en botbreuken, botpijn en longinfecties verhogen (319, 7712, 7712, 9190, 82288, 95051). Andere bijwerkingen zijn hoofdpijn, verhoogde druk in het hersenvocht, duizeligheid, wazig zien, prikkelbaarheid, slaperigheid, duizeligheid, delirium, coma, zwelling van de optische schijf, uitpuilende oogbollen, koorts, zweten, verzuim om gewicht te verliezen of gewichtsverlies en visuele stoornissen (15, 7135). Hypervitaminosis A kan spider angiomen, bloedarmoede, leukopenie, leukocytose en trombocytopenie (15, 95051) veroorzaken, evenals symptomen die een depressie of schizofrene stoornis nabootsen (7135). Bij zuigelingen werd spiercoördinatie en uitpuilende fontanel gemeld (7135, 95053, 95054). Het verhogen van de inname van vitamine A via de voeding gaat gepaard met een verhoogd risico op maagcarcinoom (9194). Intravaginaal kan all-trans-retinoïnezuur vaginale afscheiding, jeuk, irritatie en verbranding veroorzaken (9199). Intramusculair kunnen injecties met vitamine A pijnlijk zijn (95053). Een geval van intracraniële hypertensie is gemeld bij actueel vitamine A-gebruik (95056).

Interactie

Medicijnen

HEPATOTOXISCHE DRUGS

Het aanvaardbare bovenste inname niveau (UL) is het hoogste niveau van inname dat waarschijnlijk geen risico op bijwerkingen met zich meebrengt. Het is specifiek voor leeftijd en geslacht. Doses vitamine A boven de UL kunnen hepatotoxische effecten veroorzaken, variërend van verhoogde leverenzymen tot leverfalen (7135, 82554). Theoretisch kan het nemen van hoge doses vitamine A in combinatie met andere potentieel hepatotoxische geneesmiddelen het risico op leverziekte verhogen. Adviseer patiënten tegen het combineren van hoge doses vitamine A met andere hepatotoxische geneesmiddelen. Sommige geneesmiddelen die de lever nadelig kunnen beïnvloeden, zijn paracetamol (Tylenol), amiodaron (Cordarone), carbamazepine (Tegretol), isoniazide (INH), methotrexaat (Rheumatrex), methyldopa (Aldomet) en vele anderen.

RETINOÏDEN

Retinoïden, die vitamine A-derivaten zijn, kunnen additieve toxische effecten hebben wanneer ze worden ingenomen met vitamine A-supplementen (3046). Adviseer patiënten die retinoïden gebruiken om vitamine A-supplementen te vermijden. Sommige van deze retinoïden omvatten acitretine (Soriatane), bexaroteen (Targretin), etretinaat (Tegison) en isotretinoïne (Accutane), tretinoïne (Retin-A, Renova) en tazaroteen (Avage).

TETRACYCLINE ANTIBIOTICA

Goedaardige intracraniële hypertensie (pseudotumor cerebri) kan optreden met tetracyclines en met vitamine A-intoxicatie (een acute overdosis of chronische accumulatie van doses van 40.000 IE / dag of meer). Casusrapporten suggereren dat gelijktijdig gebruik van tetracyclines en vitamine A het risico op deze aandoening kan verhogen (10545, 10546, 10547). Vermijd hoge doses vitamine A bij mensen die chronisch tetracyclinen gebruiken. Tetracyclines omvatten demeclocycline (Declomycin), minocycline (Minocin) en tetracycline (Achromycin).

WARFARIN (Coumadin)

Vitamine A-toxiciteit wordt geassocieerd met bloeding en hypoprothrombinemie, mogelijk als gevolg van vitamine K-antagonisme (505). Hoge doses vitamine A kunnen het risico op bloedingen met warfarine verhogen. Adviseer patiënten die warfarine gebruiken om doses vitamine A boven de aanvaardbare bovenste inname van 10.000 IE / dag voor volwassenen te vermijden

Kruiden en supplementen

IJZER: Vitamine A kan de hemoglobinewaarden verbeteren bij mensen met bloedarmoede en lage serumretinolwaarden. Het is onwaarschijnlijk dat vitamine A-supplementen significante effecten hebben op de ijzerstatus bij mensen zonder vitamine A-tekort (9518, 9569, 9586, 95057).

Voedsel

VET: vet verhoogt de opname van vitamine A (7135).

Lab testen

BILIRUBIN: Vitamine A kan een valse toename van de resultaten van de bilirubinetest veroorzaken met behulp van het reagens van Ehrlich (15).

CHOLESTEROL: Er zijn niet-onderbouwde rapporten dat vitamine A valse verhogingen van de serumcholesteroltestresultaten kan veroorzaken, gemeten door de Zlatkis-Zak-reactie (15).

Ziektes

ALCOHOLISME: chronische alcoholinname kan de nadelige effecten van vitamine A versterken, met name hepatotoxiciteit (7135, 7139). Er zijn aanwijzingen dat chronische en overmatige inname van ethanol cytochroom P450 2E1 (CYP2E1) het metabolisme van vitamine A induceert, wat de productie van hepatotoxische en carcinogene vitamine A-metabolieten kan verhogen (1488, 7135, 7139).

ANEMIE: bloedarmoede wordt mogelijk niet voldoende behandeld met ijzersupplementen alleen bij patiënten met vitamine A-tekort. Vitamine A-tekort schaadt de mobilisatie van ijzer uit lichaamszaken. Het combineren van vitamine A met ijzersuppletie bij bloedarme patiënten met gelijktijdige vitamine A-tekort lijkt de hemoglobineconcentraties beter te verbeteren dan alleen ijzer (7135).

VET MALABSORPTIEZORGEN: de orale vitamine A-absorptie is verminderd in omstandigheden waarbij de vetabsorptie is verminderd, zoals coeliakie, kort darmsyndroom, obstructieve geelzucht, cystische fibrose, pancreasziekte en levercirrose (7135, 95054, 95058). Met water mengbare orale vitamine A-preparaten moeten worden gebruikt bij patiënten met vetmalabsorptiestoornissen.

HYPERLIPIDEMIA: type V hyperlipoproteïnemie verhoogt het risico op vitamine A hypervitaminosis (7135).

INTESTINELE INFECTIES EN INFESTATIES: ascariasis, giardiasis, haakworm, salmonellose, schistosomiasis en andere darminfecties en parasitaire aandoeningen kunnen de orale vitamine A-absorptie verminderen (7135, 95054).

IJZERDEFICIËNTIE: ijzergebrek kan het metabolisme van vitamine A beïnvloeden (95057).

LEVER ZIEKTE: patiënten met leverziekte kunnen een verhoogd risico op hypervitaminose en hepatotoxiciteit hebben, vooral als ze buitensporige doses vitamine A nemen (7135).

MALNUTRITION: bij ernstige ondervoeding van eiwitenergie (marasmus en kwashiorkor) is er een verminderde afgifte van retinol uit de lever. Totdat de voedingsstatus is genormaliseerd, is er een verhoogd risico op vitamine A-hypervitaminose (7135).

ZINKDEFICIËNTIE: zink is vereist bij hepatische synthese van retinol bindend eiwit. Zonder voldoende zink kunnen symptomen van vitamine A-tekort optreden, ondanks vitamine A-suppletie (8630, 95057). Zink in combinatie met vitamine A lijkt de maatstaven van vitamine A-toereikendheid bij ondervoede kinderen beter te verbeteren dan vitamine A of zink alleen (8636).

Werkingsmechanisme

Algemeen: vitamine A is een in vet oplosbare vitamine. Vitamine A omvat een familie van moleculen met een 20-koolstofstructuur met verschillende chemische groepen op de koolstofpositie 15. Variaties op de koolstofpositie 15 leveren verschillende vitamine A-vormen op, waaronder retinol, retinal, retinoïnezuur en retinylester. Deze verschillende vormen van vitamine A worden vaak gezamenlijk "retinoïden" genoemd. De meest krachtige vorm van vitamine A, all-trans retinol, is de vorm van retinol in het dieet. Het keert de tekenen en symptomen van vitamine A-tekort om en is de standaard voor vitamine A-activiteit (9191). De vitamine A-familie bevat ook provitamine A-carotenoïden, die voorloper zijn van retinol.

Vitamine A komt in verschillende vormen voor in voedingsmiddelen. Retinol, ook wel voorgevormde vitamine A genoemd, is aanwezig in veresterde vorm in van dieren afgeleide producten, waaronder eieren, volle melk, boter, verrijkte margarine, vlees en olieachtige zeevis (7135). Dierlijke lever bevat de hoogste hoeveelheid retinol via de voeding. Ongeveer twee derde van de vitamine A-inname komt van retinol via de voeding (9189). Zoetwatervis bevat een vorm van vitamine A genaamd 3-dehydroretinol, maar heeft slechts 30% tot 40% van de biologische activiteit van retinol (15). Ongeveer een derde van de vitamine A in de voeding is afkomstig van planten, die carotenoïden synthetiseren die in het lichaam worden omgezet in vitamine A (7135). Carotenoïde pigmenten (inclusief alfa-, bèta- en gamma-caroteen en cryptoxanthine) zijn aanwezig in granen, oliën, groene en gele groenten, en vooral in wortelen en fruit (8044). De hoeveelheid carotenoïden die worden geabsorbeerd en omgezet in vitamine A hangt af van de hoeveelheid ingenomen carotenoïden, de vitamine A-status van het individu en de carotenoïdencarrosserieën. Carotenoïden leveren ongeveer 50% van de vitamine A die nodig is in het Amerikaanse dieet (8044).

Vitamine A is vereist voor visie, groei en botontwikkeling, reproductie, celproliferatie en differentiatie, immuunfunctie en de integriteit van slijmvlies- en epitheeloppervlakken. All-trans retinol wordt door een onbekend mechanisme in het lichaam omgezet in all-trans retinoïnezuur. All-trans-retinoïnezuur is de actieve vorm van vitamine A in bijna alle biologische processen. Retinoïnezuur reguleert de expressie van verschillende genen die coderen voor structurele eiwitten, zoals keratine in de huid; enzymen, zoals alcoholdehydrogenase; extracellulaire matrixeiwitten, zoals het basismembraaneiwitlaminine; en retinol bindende eiwitten en receptoren (7135, 9189, 95051). Vitamine A reguleert ook genen, inclusief die van het dopaminerge systeem, in de hersenen en het centrale zenuwstelsel (91164). Vitamine A werkt als een cofactor bij de synthese van mucopolysachariden, cholesterolsynthese, het metabolisme van hydroxysteroïden en glycoproteïne glycosylatie (15).

Bovenstaande monografie is geschreven aan de hand van de onderstaande referenties.

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  • 82670 Meyskens, F. L., Jr., Liu, P. Y., Tuthill, R. J., Sondak, V. K., Fletcher, W. S., Jewell, W. R., Samlowski, W., Balcerzak, S. P., Rector, D. J., Noyes, R. D., and . Randomized trial of vitamin A versus observation as adjuvant therapy in high-risk primary malignant melanoma: a Southwest Oncology Group study. J Clin Oncol. 1994;12(10):2060-2065.
  • 82671 Alonso, P. L., Smith, T., Schellenberg, J. R., Masanja, H., Mwankusye, S., Urassa, H., Bastos, de Azevedo, I, Chongela, J., Kobero, S., Menendez, C., and . Randomised trial of efficacy of SPf66 vaccine against Plasmodium falciparum malaria in children in southern Tanzania. Lancet 10-29-1994;344(8931):1175-1181.
  • 82672 Landa, M. C., Frago, N., and Tres, A. Diet and the risk of breast cancer in Spain. Eur.J Cancer Prev. 1994;3(4):313-320.
  • 82673 Biswas, R., Biswas, A. B., Manna, B., Bhattacharya, S. K., Dey, R., and Sarkar, S. Effect of vitamin A supplementation on diarrhoea and acute respiratory tract infection in children. A double blind placebo controlled trial in a Calcutta slum community. Eur J Epidemiol 1994;10(1):57-61.
  • 82674 Lowe, P. M., Woods, J., Lewis, A., Davies, A., and Cooper, A. J. Topical tretinoin improves the appearance of photo damaged skin. Australas.J Dermatol 1994;35(1):1-9.
  • 82676 Underwood, B. A. Was the "anti-infective" vitamin misnamed? Nutr Rev 1994;52(4):140-143.
  • 82677 Schorah, C. J. Micronutrient provision in elderly subjects. Lancet 1-30-1993;341(8840):306-307.
  • 82678 No authors. Vitamin A supplementation in northern Ghana: effects on clinic attendances, hospital admissions, and child mortality. Ghana VAST Study Team. Lancet 7-3-1993;342(8862):7-12.
  • 82679 de Francisco, ., Chakraborty, J., Chowdhury, H. R., Yunus, M., Baqui, A. H., Siddique, A. K., and Sack, R. B. Acute toxicity of vitamin A given with vaccines in infancy. Lancet 8-28-1993;342(8870):526-527.
  • 82680 Stansfield, S. K., Pierre-Louis, M., Lerebours, G., and Augustin, A. Vitamin A supplementation and increased prevalence of childhood diarrhoea and acute respiratory infections. Lancet 9-4-1993;342(8871):578-582.
  • 82681 Ogaro, F. O., Orinda, V. A., Onyango, F. E., and Black, R. E. Effect of vitamin A on diarrhoeal and respiratory complications of measles. Trop.Geogr.Med 1993;45(6):283-286.
  • 82682 Werkman, S. H., Peeples, J. M., Cooke, R. J., Tolley, E. A., and Carlson, S. E. Effect of vitamin A supplementation of intravenous lipids on early vitamin A intake and status of premature infants. Am J Clin.Nutr 1994;59(3):586-592.
  • 82683 Mark, S. D., Liu, S. F., Li, J. Y., Gail, M. H., Shen, Q., Dawsey, S. M., Liu, F., Taylor, P. R., Li, B., and Blot, W. J. The effect of vitamin and mineral supplementation on esophageal cytology: results from the Linxian Dysplasia Trial. Int J Cancer 4-15-1994;57(2):162-166.
  • 82684 Sandler, D. L., Cooper, P. A., Bolton, K. D., Bental, R. Y., and Simchowitz, I. D. Periventricular-intraventricular haemorrhage in low-birth-weight infants at Baragwanath Hospital. S.Afr.Med.J 1994;84(1):26-29.
  • 82685 Kullavanijaya, P. and Kulthanan, K. Clinical efficacy and side effects of acitretin on the disorders of keratinization: a one-year study. J Dermatol. 1993;20(8):501-506.
  • 82686 Li, J. Y., Li, B., Blot, W. J., and Taylor, P. R. [Preliminary report on the results of nutrition prevention trials of cancer and other common diseases among residents in Linxian, China]. Zhonghua Zhong.Liu Za Zhi. 1993;15(3):165-181.
  • 82687 Butcher, G. P., Rhodes, J. M., Walker, R., Krasner, N., and Jackson, M. J. The effect of antioxidant supplementation on a serum marker of free radical activity and abnormal serum biochemistry in alcoholic patients admitted for detoxification. J Hepatol. 1993;19(1):105-109.
  • 82688 Finzi, A. F., Ippolito, F., Panconesi, E., Giannotti, B., and Rebora, A. Cyclosporin therapy in psoriasis: recommendations for treatment. Italian Multicenter Study Group on Cyclosporin in Psoriasis. Dermatology 1993;187 Suppl 1:38-40.
  • 82689 Gopaldas, T., Gujral, S., and Abbi, R. Prevalence of xerophthalmia and efficacy of vitamin A prophylaxis in preventing xerophthalmia co-existing with malnutrition in rural Indian children. J Trop.Pediatr 1993;39(4):205-208.
  • 82690 Rahman, M. M., Mahalanabis, D., Islam, M. A., and Biswas, E. Can infants and young children eat enough green leafy vegetables from a single traditional meal to meet their daily vitamin A requirements? Eur J Clin Nutr 1993;47(1):68-72.
  • 82691 Fawzi, W. W., Chalmers, T. C., Herrera, M. G., and Mosteller, F. Vitamin A supplementation and child mortality. A meta-analysis. JAMA 2-17-1993;269(7):898-903.
  • 82692 Lie, C., Ying, C., Wang, E. L., Brun, T., and Geissler, C. Impact of large-dose vitamin A supplementation on childhood diarrhoea, respiratory disease and growth. Eur J Clin Nutr 1993;47(2):88-96.
  • 82693 Andreano, J. M., Bergfeld, W. F., and Medendorp, S. V. Tretinoin emollient cream 0.01% for the treatment of photoaged skin. Cleve.Clin J Med 1993;60(1):49-55.
  • 82695 Glasziou, P. P. and Mackerras, D. E. Vitamin A supplementation in infectious diseases: a meta-analysis. BMJ 2-6-1993;306(6874):366-370.
  • 82696 Stoltzfus, R. J., Hakimi, M., Miller, K. W., Rasmussen, K. M., Dawiesah, S., Habicht, J. P., and Dibley, M. J. High dose vitamin A supplementation of breast-feeding Indonesian mothers: effects on the vitamin A status of mother and infant. J Nutr 1993;123(4):666-675.
  • 82697 Quinlan, K. P. and Hayani, K. C. Vitamin A and respiratory syncytial virus infection. Serum levels and supplementation trial. Arch Pediatr Adolesc.Med 1996;150(1):25-30.
  • 82698 Moon, T. E., Levine, N., Cartmel, B., Bangert, J., Rodney, S., Schreiber, M., Peng, Y. M., Ritenbaugh, C., Meyskens, F., and Alberts, D. Design and recruitment for retinoid skin cancer prevention (SKICAP) trials. The Southwest Skin Cancer Prevention Study Group. Cancer Epidemiol Biomarkers Prev. 1995;4(6):661-669.
  • 82699 Negri, E., La, Vecchia C., Franceschi, S., D'Avanzo, B., Talamini, R., Parpinel, M., Ferraroni, M., Filiberti, R., Montella, M., Falcini, F., Conti, E., and Decarli, A. Intake of selected micronutrients and the risk of breast cancer. Int J Cancer 1-17-1996;65(2):140-144.
  • 82700 Kartasasmita, C. B., Rosmayudi, O., Deville, W., and Demedts, M. Plasma retinol level, vitamin A supplementation and acute respiratory infections in children of 1-5 years old in a developing country. Respiratory Diseases Working Group. Tuber.Lung Dis 1995;76(6):563-569.
  • 82701 Rosales, F. J., Kjolhede, C., and Goodman, S. Efficacy of a single oral dose of 200,000 IU of oil-soluble vitamin A in measles-associated morbidity. Am J Epidemiol 3-1-1996;143(5):413-422.
  • 82702 Kirkwood, B. R., Ross, D. A., Arthur, P., Morris, S. S., Dollimore, N., Binka, F. N., Shier, R. P., Gyapong, J. O., Addy, H. A., and Smith, P. G. Effect of vitamin A supplementation on the growth of young children in northern Ghana. Am J Clin Nutr 1996;63(5):773-781.
  • 82703 Humphrey, J. H., Agoestina, T., Wu, L., Usman, A., Nurachim, M., Subardja, D., Hidayat, S., Tielsch, J., West, K. P., Jr., and Sommer, A. Impact of neonatal vitamin A supplementation on infant morbidity and mortality. J Pediatr 1996;128(4):489-496.
  • 82704 Dibley, M. J., Sadjimin, T., Kjolhede, C. L., and Moulton, L. H. Vitamin A supplementation fails to reduce incidence of acute respiratory illness and diarrhea in preschool-age Indonesian children. J Nutr 1996;126(2):434-442.
  • 82705 Chawla, P. K. and Puri, R. Impact of nutritional supplements on hematological profile of pregnant women. Indian Pediatr. 1995;32(8):876-880.
  • 82706 Nevill, C. G., Some, E. S., Mung'ala, V. O., Mutemi, W., New, L., Marsh, K., Lengeler, C., and Snow, R. W. Insecticide-treated bednets reduce mortality and severe morbidity from malaria among children on the Kenyan coast. Trop.Med Int Health 1996;1(2):139-146.
  • 82707 Binka, F. N., Kubaje, A., Adjuik, M., Williams, L. A., Lengeler, C., Maude, G. H., Armah, G. E., Kajihara, B., Adiamah, J. H., and Smith, P. G. Impact of permethrin impregnated bednets on child mortality in Kassena-Nankana district, Ghana: a randomized controlled trial. Trop.Med Int Health 1996;1(2):147-154.
  • 82708 Kushi, L. H., Fee, R. M., Sellers, T. A., Zheng, W., and Folsom, A. R. Intake of vitamins A, C, and E and postmenopausal breast cancer. The Iowa Women's Health Study. Am J Epidemiol 7-15-1996;144(2):165-174.
  • 82709 Wachnik-Swiecicka, A. and Rudzka-Kantoch, Z. [An evaluation of vitamin A status based on the measurement of retinol in the serum of children and infants]. Pediatr Pol 1995;70(4):303-306.
  • 82710 Shankar, A. V., West, K. P., Jr., Gittelsohn, J., Katz, J., and Pradhan, R. Chronic low intakes of vitamin A-rich foods in households with xerophthalmic children: a case-control study in Nepal. Am J Clin Nutr 1996;64(2):242-248.
  • 82711 Orfanos, C. E., Steigleder, G. K., Pullmann, H., and Bloch, P. H. Oral retinoid and UVB radiation: a new, alternative treatment for psoriasis on an out-patient basis. Acta Derm.Venereol. 1979;59(3):241-244.
  • 82712 Van Dooren-Greebe, R. J., Lemmens, J. A., De, Boo T., Hangx, N. M., Kuijpers, A. L., and van de Kerkhof, P. C. Prolonged treatment with oral retinoids in adults: no influence on the frequency and severity of spinal abnormalities. Br.J Dermatol. 1996;134(1):71-76.
  • 82713 Mork, N. J., Kolbenstvedt, A., and Austad, J. Skeletal side-effects of 5 years' acitretin treatment. Br.J Dermatol. 1996;134(6):1156-1157.
  • 82714 Venkatarao, T., Ramakrishnan, R., Nair, N. G., Radhakrishnan, S., Sundaramoorthy, L., Koya, P. K., and Kumar, S. K. Effect of vitamin A supplementation to mother and infant on morbidity in infancy. Indian Pediatr 1996;33(4):279-286.
  • 82715 Nosten, F., Luxemburger, C., Kyle, D. E., Ballou, W. R., Wittes, J., Wah, E., Chongsuphajaisiddhi, T., Gordon, D. M., White, N. J., Sadoff, J. C., and Heppner, D. G. Randomised double-blind placebo-controlled trial of SPf66 malaria vaccine in children in northwestern Thailand. Shoklo SPf66 Malaria Vaccine Trial Group. Lancet 9-14-1996;348(9029):701-707.
  • 82716 Frigg, M. Meta-analyses/meta-projects: a small but relevant contribution by Sight and Life to the prevention of vitamin A deficiency. Eur J Clin Nutr 1996;50 Suppl 3:S68-S69.
  • 82717 Potential interventions for the prevention of childhood pneumonia in developing countries: a meta-analysis of data from field trials to assess the impact of vitamin A supplementation on pneumonia morbidity and mortality. The Vitamin A and Pneumonia Working Group. Bull World Health Organ 1995;73(5):609-619.
  • 82718 Czeizel, A. E. Reduction of urinary tract and cardiovascular defects by periconceptional multivitamin supplementation. Am J Med Genet 3-15-1996;62(2):179-183.
  • 82719 Kirkwood, B. R., Gove, S., Rogers, S., Lob-Levyt, J., Arthur, P., and Campbell, H. Potential interventions for the prevention of childhood pneumonia in developing countries: a systematic review. Bull World Health Organ 1995;73(6):793-798.
  • 82720 Thorne, E. G., Lufrano, L., Boateng, F., and Sampson, A. R. Effect of tretinoin emollient cream on photodamaged skin: relationship between clinical improvement and skin irritation. Br J Dermatol 1996;135(4):655-656.
  • 82721 Verhoeven, D. T., Assen, N., Goldbohm, R. A., Dorant, E., van, 't, V, Sturmans, F., Hermus, R. J., and Van den Brandt, P. A. Vitamins C and E, retinol, beta-carotene and dietary fibre in relation to breast cancer risk: a prospective cohort study. Br.J Cancer 1997;75(1):149-155.
  • 82722 Pant, C. R., Pokharel, G. P., Curtale, F., Pokhrel, R. P., Grosse, R. N., Lepkowski, J., Muhilal, Bannister, M., Gorstein, J., Pak-Gorstein, S., Atmarita, and Tilden, R. L. Impact of nutrition education and mega-dose vitamin A supplementation on the health of children in Nepal. Bull World Health Organ 1996;74(5):533-545.
  • 82723 Hogarth, M. B., Marshall, P., Lovat, L. B., Palmer, A. J., Frost, C. G., Fletcher, A. E., Nicholl, C. G., and Bulpitt, C. J. Nutritional supplementation in elderly medical in-patients: a double-blind placebo-controlled trial. Age Ageing 1996;25(6):453-457.
  • 82724 Buajeeb, W., Kraivaphan, P., and Pobrurksa, C. Efficacy of topical retinoic acid compared with topical fluocinolone acetonide in the treatment of oral lichen planus. Oral Surg.Oral Med.Oral Pathol.Oral Radiol.Endod. 1997;83(1):21-25.
  • 82725 Bahl, R., Bhandari, N., Taneja, S., and Bhan, M. K. The impact of vitamin A supplementation on physical growth of children is dependent on season. Eur J Clin Nutr 1997;51(1):26-29.
  • 82726 Shann, F. Meta-analysis of trials of prophylactic antibiotics for children with measles: inadequate evidence. BMJ 2-1-1997;314(7077):334-336.
  • 82727 Lemnge, M. M., Msangeni, H. A., Ronn, A. M., Salum, F. M., Jakobsen, P. H., Mhina, J. I., Akida, J. A., and Bygbjerg, I. C. Maloprim malaria prophylaxis in children living in a holoendemic village in north-eastern Tanzania. Trans.R.Soc Trop.Med Hyg. 1997;91(1):68-73.
  • 82728 Moon, T. E., Levine, N., Cartmel, B., and Bangert, J. L. Retinoids in prevention of skin cancer. Cancer Lett. 3-19-1997;114(1-2):203-205.
  • 82729 Yu, S. Y., Zhu, Y. J., and Li, W. G. Protective role of selenium against hepatitis B virus and primary liver cancer in Qidong. Biol Trace Elem.Res 1997;56(1):117-124.
  • 82730 Roy, S. K., Islam, A., Molla, A., Akramuzzaman, S. M., Jahan, F., and Fuchs, G. Impact of a single megadose of vitamin A at delivery on breastmilk of mothers and morbidity of their infants. Eur J Clin Nutr 1997;51(5):302-307.
  • 82731 Kennedy, K. A., Stoll, B. J., Ehrenkranz, R. A., Oh, W., Wright, L. L., Stevenson, D. K., Lemons, J. A., Sowell, A., Mele, L., Tyson, J. E., and Verter, J. Vitamin A to prevent bronchopulmonary dysplasia in very-low-birth-weight infants: has the dose been too low? The NICHD Neonatal Research Network. Early Hum Dev. 7-24-1997;49(1):19-31.
  • 82732 Shatrugna, V., Raman, L., Uma, K., and Sujatha, T. Interaction between vitamin A and iron: effects of supplements in pregnancy. Int J Vitam.Nutr Res. 1997;67(3):145-148.
  • 82733 Giles, G. and Ireland, P. Diet, nutrition and prostate cancer. Int J Cancer 1997;Suppl 10:13-17.
  • 82734 Benn, C. S., Aaby, P., Bale, C., Olsen, J., Michaelsen, K. F., George, E., and Whittle, H. Randomised trial of effect of vitamin A supplementation on antibody response to measles vaccine in Guinea-Bissau, west Africa. Lancet 7-12-1997;350(9071):101-105.
  • 82735 Olsen, E. A., Katz, H. I., Levine, N., Nigra, T. P., Pochi, P. E., Savin, R. C., Shupack, J., Weinstein, G. D., Lufrano, L., and Perry, B. H. Tretinoin emollient cream for photodamaged skin: results of 48-week, multicenter, double-blind studies. J Am Acad Dermatol 1997;37(2 Pt 1):217-226.
  • 82736 Fawzi, W. W., Herrera, M. G., Willett, W. C., Nestel, P., el, Amin A., and Mohamed, K. A. The effect of vitamin A supplementation on the growth of preschool children in the Sudan. Am J Public Health 1997;87(8):1359-1362.
  • 82737 West, K. P., LeClerq, S. C., Shrestha, S. R., Wu, L. S., Pradhan, E. K., Khatry, S. K., Katz, J., Adhikari, R., and Sommer, A. Effects of vitamin A on growth of vitamin A-deficient children: field studies in Nepal. J Nutr 1997;127(10):1957-1965.
  • 82738 Habluetzel, A., Diallo, D. A., Esposito, F., Lamizana, L., Pagnoni, F., Lengeler, C., Traore, C., and Cousens, S. N. Do insecticide-treated curtains reduce all-cause child mortality in Burkina Faso? Trop.Med Int Health 1997;2(9):855-862.
  • 82739 Nacul, L. C., Kirkwood, B. R., Arthur, P., Morris, S. S., Magalhaes, M., and Fink, M. C. Randomised, double blind, placebo controlled clinical trial of efficacy of vitamin A treatment in non-measles childhood pneumonia. BMJ 8-30-1997;315(7107):505-510.
  • 82741 Dollimore, N., Cutts, F., Binka, F. N., Ross, D. A., Morris, S. S., and Smith, P. G. Measles incidence, case fatality, and delayed mortality in children with or without vitamin A supplementation in rural Ghana. Am J Epidemiol 10-15-1997;146(8):646-654.
  • 82742 Si, N. V., Grytter, C., Vy, N. N., Hue, N. B., and Pedersen, F. K. High dose vitamin A supplementation in the course of pneumonia in Vietnamese children. Acta Paediatr. 1997;86(10):1052-1055.
  • 82743 Longnecker, M. P., Newcomb, P. A., Mittendorf, R., Greenberg, E. R., and Willett, W. C. Intake of carrots, spinach, and supplements containing vitamin A in relation to risk of breast cancer. Cancer Epidemiol.Biomarkers Prev. 1997;6(11):887-892.
  • 82744 Moon, T. E., Levine, N., Cartmel, B., Bangert, J. L., Rodney, S., Dong, Q., Peng, Y. M., and Alberts, D. S. Effect of retinol in preventing squamous cell skin cancer in moderate-risk subjects: a randomized, double-blind, controlled trial. Southwest Skin Cancer Prevention Study Group. Cancer Epidemiol Biomarkers Prev. 1997;6(11):949-956.
  • 82745 Levine, N., Moon, T. E., Cartmel, B., Bangert, J. L., Rodney, S., Dong, Q., Peng, Y. M., and Alberts, D. S. Trial of retinol and isotretinoin in skin cancer prevention: a randomized, double-blind, controlled trial. Southwest Skin Cancer Prevention Study Group. Cancer Epidemiol Biomarkers Prev 1997;6(11):957-961.
  • 82747 Hanekom, W. A., Potgieter, S., Hughes, E. J., Malan, H., Kessow, G., and Hussey, G. D. Vitamin A status and therapy in childhood pulmonary tuberculosis. J Pediatr 1997;131(6):925-927.
  • 82748 von, Herbay A., Stahl, W., Niederau, C., and Sies, H. Vitamin E improves the aminotransferase status of patients suffering from viral hepatitis C: a randomized, double-blind, placebo-controlled study. Free Radic.Res 1997;27(6):599-605.
  • 82749 Semba, R. D., Lyles, C. M., Margolick, J. B., Caiaffa, W. T., Farzadegan, H., Cohn, S., and Vlahov, D. Vitamin A supplementation and human immunodeficiency virus load in injection drug users. J Infect.Dis 1998;177(3):611-616.
  • 82750 van de Kerkhof, P. C., Cambazard, F., Hutchinson, P. E., Haneke, E., Wong, E., Souteyrand, P., Damstra, R. J., Combemale, P., Neumann, M. H., Chalmers, R. J., Olsen, L., and Revuz, J. The effect of addition of calcipotriol ointment (50 micrograms/g) to acitretin therapy in psoriasis. Br.J Dermatol. 1998;138(1):84-89.
  • 82751 Wasantwisut, E. Nutrition and development: other micronutrients' effect on growth and cognition. Southeast Asian J Trop.Med Public Health 1997;28 Suppl 2:78-82.
  • 82752 Stephensen, C. B., Franchi, L. M., Hernandez, H., Campos, M., Gilman, R. H., and Alvarez, J. O. Adverse effects of high-dose vitamin A supplements in children hospitalized with pneumonia. Pediatrics 1998;101(5):E3.
  • 82753 Bojang, K. A., Obaro, S. K., D'Alessandro, U., Bennett, S., Langerock, P., Targett, G. A., and Greenwood, B. M. An efficacy trial of the malaria vaccine SPf66 in Gambian infants--second year of follow-up. Vaccine 1998;16(1):62-67.
  • 82755 Morcos, M. M., Gabr, A. A., Samuel, S., Kamel, M., el, Baz M., el, Beshry M., and Michail, R. R. Vitamin D administration to tuberculous children and its value. Boll.Chim.Farm. 1998;137(5):157-164.
  • 82756 Bhaskaram, P. and Balakrishna, N. Effect of administration of 200,000 IU of vitamin A to women within 24 hrs after delivery on response to PPV administered to the newborn. Indian Pediatr 1998;35(3):217-222.
  • 82757 Inder, T. E., Graham, P. J., Winterbourn, C. C., Austin, N. C., and Darlow, B. A. Plasma vitamin A levels in the very low birthweight infant--relationship to respiratory outcome. Early Hum Dev. 1998;52(2):155-168.
  • 82758 No author. Randomised trial to assess benefits and safety of vitamin A supplementation linked to immunisation in early infancy. WHO/CHD Immunisation-Linked Vitamin A Supplementation Study Group. Lancet 10-17-1998;352(9136):1257-1263.
  • 82759 Humphrey, J. H., Quinn, T., Fine, D., Lederman, H., Yamini-Roodsari, S., Wu, L. S., Moeller, S., and Ruff, A. J. Short-term effects of large-dose vitamin A supplementation on viral load and immune response in HIV-infected women. J Acquir.Immune.Defic.Syndr.Hum Retrovirol. 1-1-1999;20(1):44-51.
  • 82760 Cunliffe, W. J., Poncet, M., Loesche, C., and Verschoore, M. A comparison of the efficacy and tolerability of adapalene 0.1% gel versus tretinoin 0.025% gel in patients with acne vulgaris: a meta-analysis of five randomized trials. Br J Dermatol 1998;139 Suppl 52:48-56.
  • 82761 Papagaroufalis C, Cairis M, and Pantazatou E. A trial of vitamin A supplementation in infants susceptible to bronchopulmonary dysplasia. Pediatric Research 1988;23:518A.
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  • 82765 Bai XC, Ma Y Song GQ. The Combination treatment of arsenic trioxide and Alltrans-retinoic acid in patients with acute promyelocytic leukemia. Ning Xia Yi Xue Yuan Xue Bao 2007;29:502-504.
  • 82766 Su XL, XiaWL. Combined treatment of All-trans-retinoic acid and arsenic trioxide in patients with new-diagnosed acute promyelocytic leukemia. Lin Chuan Yu Shi Jian 2006;10:338-339.
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  • 82769 Beaton GH, Martorell R, Aronson KA, Edmonston B, McCabe G, and Ross AC. La suplementación con vitamina A y la morbilidad y mortalidad infantil en los países en desarrollo. Bol Oficina Sanit Panam 1994;117:506-518.
  • 82770 Agarwal DK, Pandey CM, and Agarwal KN. Vitamin A administration and preschool child mortality. Nutrition Research 1995;15(5):669-680.
  • 82771 Mahalanabis D, Rahman MR Wahed MA Islam MA Habte D. Vltamin A megadoses during early infancy on serum retinol concentration and acute side effects and residual effects on 6 month follow-up. Nutrition Research 1997;17(4):649-669.
  • 82774 Bental R.Y., Cooper PA, Cummins RR, Sandler DL, Wainer S, and Rotschild A. Vitamin A therapy - effects on the incidence of bronchopulmonary dysplasia. S.Afr.J.Food Sci.Nutr 1994;6:141-145.
  • 82775 Awasthi S, Peto R Bundy D et al. Six-monthly vitamin A supplementation from 1 to 6 years of age. Abstract of talk at ILSI Micronutrient Forum, Istanbul 2007;
  • 82776 Agarwal KN, Agarwal DK, and Pandey CM. Impact of vitamin A supplementation on morbidity pattern in rural pre-school children. Indian J Prev Soc Med 1998;29:14-24.
  • 82777 Barel AO, Delune M, Clarys P, and Gabard B. Treatment of photodamaged facial skin with topical tretinoin: a blinded, vehiclecontrolled half-side study. Nouvelles Dermatologiques 1995;14:585-591.
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