Skip to main content

Currently Skimming:

4 Vitamin A
Pages 82-161

The Chapter Skim interface presents what we've algorithmically identified as the most significant single chunk of text within every page in the chapter.
Select key terms on the right to highlight them within pages of the chapter.


From page 82...
... There are a number of sources of dietary vitamin A Preformed vitamin A is abundant in some animal-derived foods, whereas provitamin A carotenoids are abundant in darkly colored fruits and vegetables, as well as oily fruits and red palm oil.
From page 83...
... , carboxylic acid group (retinoic acid) , or ester group (retinyl ester)
From page 84...
... Preformed vitamin A is found only in animal-derived food products, whereas dietary carotenoicis are present primarily in oils, fruits, and vegetables. Function The 11-cis-retinaldehyde (retinal)
From page 85...
... Retinoic acid is important in maintaining an acloquate level of circulating natural killer cells that have antiviral and anti-tumor activity (Zhao and Ross, 1995~. Retinoic acid has been shown to increase phagocytic activity in murine macrophages (Katz et al., 1987)
From page 86...
... Intestinal absorption of preformed vitamin A occurs following the processing of retinyl esters in the lumen of the small intestine. Within the water-miscible micelles formed from bile salts, solubilizeci retinyl esters as well as triglycerides are hycirolyzeci to retinol and products of lipolysis by various hycirolases (Harrison, 1993~.
From page 87...
... Derived from clietary retinoicis, retinoic acid is absorbed via the portal system bounci to albumin (Blaner and Olson, 1994; Olson, 1991~. Vitamin A Activity of Provitamin A Carotenoids: Rationale for DevelopingRetinol Activity Equivalents.
From page 88...
... Only one study has compared the relative absorption of ,(-carotene in oil versus its absorption in a principally mixed vegetable diet in healthy and nutritionally adequate individuals (Van bet Hof et al., 1999~. This study conclucleci that the relative absorption of ,3-carotene from the mixed vegetable cliet compared to ,(-carotene in oil is only 14 percent, as assessed by the increase in plasma ,(-carotene concentration after dietary interven
From page 89...
... c of ,B-carotene; thus the retinal equivalency ratio is assumed to be 3.8:1 600 ~g/d retinal corrected dark adaptation; 1,200 ~g/d ,B-carotene corrected dark adaptation; therefore the retinal equivalency ratio was concluded to be 2:1 :O, 1950)
From page 90...
... Unfortunately, studies using a positive control group Preformed vitamin A) at a level equivalent to ,3-carotene from a mixed vegetable and fruit cliet using levels similar to the RAE have not been conclucteci in healthy and nutritionally acloquate inclivicluals.
From page 91...
... VITAMIN A rotary 91 Diet/Dose of ,B-Carotene Results ention, ention, Supplement, 30 mg/d Carrots, 30 mg/d Broccoli, 6 mg/d Vegetable diet, 3.5 mg/d Fruit diet, 2.3 mg/d Low carotenoid diet + Raw carrots, 12 mg/d + Supplement, 12 mg/d Fruit/squash diet, 509 1lg/d Dark green leafy vegetables + carrots, 684 ~g/d Low vitamin A/~-carotene diet, 44 1lg/d Increase of plasma p-carotene from carrots compared to supplemental p-carotene in gelatin beadlets was 18 % Increase of plasma p-carotene from broccoli compared to supplemental p-carotene in gelatin beadlets was 12 % Increase of serum p-carotene from fruit diet was .~-tS times higher than from vegetable diet Increase of serum p-carotene from raw carrots was 26% compared to that from supplemental p-carotene in a gelatin beadlet Increase of serum p-carotene from fruit/squash diet was 3.5-fold greater than that for the dark green leafy vegetables + carrots diet ention, Control diet, 0.5 mg/d Increase of serum p-carotene from spinach was Supplement diet, 9.8 mg/d 5% compared to that from supplemental Spinach diet, 10.4 mg/d p-carotene in oil ention, Supplement, 7.2 mg/day Increase of plasma p-carotene from high High vegetable diet, vegetable diet compared to supplemental 5.1 mg/d p-carotene in oil was 14% contained in chylomicrons, resulting in a carotene:retinol equivalency ratio of 13:1. One RAE for clietary provitamin A carotenoicis other than ,3-carotene is set at 24 ,ug on the basis of the observation that the vitamin A activity of ,3-cryptoxanthin anci oc-carotene is approximately half of that for ,3-carotene (Bauernfeinci, 1972; Deuel et al., 1949~.
From page 92...
... FIGURE 4-2 Absorption and bioconversion of ingested prov~tamin A carotenoids to retinol based on new equivalency factors (retinol activity equivalency ratio)
From page 93...
... Metabolism, Transport, and Excretion Retinyl esters and carotenoicis are transported to the liver in chylomicron remnants. Apoprotein E is required for the uptake of chylomicron remnants by the liver.
From page 94...
... Body Stores The hepatic vitamin A concentration can vary markocily clepenciing on dietary intake. When vitamin A intake is adequate, over 90 percent of total body vitamin A is located in the liver (Raica et al., 1972)
From page 95...
... The World Health Organization (WHO, 1982) classified various stages of xerophthalmia to include night blindness (impaireci dark adaptation clue to slowed regeneration of rhoclopsin)
From page 96...
... A generalized dysfunction of humoral and cell-mecliateci immunity is common in experimental animals and is likely to exist in humans. In aciclition to xerophthalmia, vitamin A deficiency has been associateci with increased risk of infectious morbidity and mortality in experimental animals and humans, especially in developing countries.
From page 97...
... . Before clinically apparent night blindness occurs, abnormal roci function may be cletecteci by dark adaptation testing.
From page 98...
... Uncler controlled fouling conditions, dark adaptation, objectively measured by dark adaptometry, is one of the most sensitive indicators of a change in vitamin A deficiency status (Figure 4-3~. Epiclemiological evidence suggests that host resistance to infection is impaired at lesser stages of vitamin A deficiency, prior to clinical onset of night blindness (Arroyave et al., 1979; Arthur et al., 1992; Barreto et al., 1994; Bloem et al., 1990; Ghana VAST Study Team, 1993; Loyci-Puryear et al., 1991; Salazar-Linclo et al., 1993)
From page 99...
... When liver vitamin A reserves fall below a critical concentration, thought to be approximately 20 ,ug/g of liver (Olson, 1987) , plasma retinol concentration declines.
From page 100...
... 100 DIETARY REFERENCE INTAKES TABLE 4-4 Correction of Abnormal Dark Aciaptation with Vitamin A Vitamin A Dark Intake Serum Adapta Reference Subject (Pg/d) Duration Retinol tiona ERGb Blanchard DA, man, 90-165 A and 20 y +450 3 d C Harper, +600 2 d SI 1940 JK, man, 90-165 A 23 y +300 4 d C +1,081 2 d C TH, man, 90-165 A 20 y +150 3 d PC +721 4 d N Batchelder GG, young 60 A and adult 600 A Ebbs, woman 1,201 N 1943 KY, young 60 A adult 600 A man 1,201 N MW, young 60 A adult 600 440 and 620 A woman IU/dL 1,200 6 d TC 1,200 17 d A 3,000 C Hume and Golding, 21 14 mo 22 IU/dL 2.81, A Krebs, man, 390 1 mo 50 IU/dL 2.38, A 1949 32 y, 2 mo 88 IU/dL 2.26, M vitamin A 6 mo 88 IU/dL 1.81, N depleted continued
From page 101...
... only subjects with intake gaps less than 600 ,ug/day were used and (2) the lowest corrected/ normal intake value was chosen as that level at which dark adaptation was corrected or normal and for which no abnormal ERG was recorded.
From page 102...
... FIGURE 4-3 Serum vitamin A concentrations and dark adaptation final thresholds. Upper limit of normal final threshold = -4.6 log candela/m2.
From page 103...
... Liver reserves of vitamin A can be correlated with known clietary intake levels of vitamin A An Estimated Average Requirement (EAR)
From page 104...
... With proper controls the RDR test is consiclereci a valid test to determine inacloquate vitamin A status. However, just as plasma retinol concentration is insensitive across a wicle range of "acloquate" liver vitamin A reserves, the RDR test floes not distinguish among different levels of acloquate vitamin A reserves (Solomons et al., 1990~.
From page 105...
... In spite of that, there is an association between the prevalence of conjunctival impression cytology (CIC) abnormality and serum retinal and RDR test results (Sommer and West, 1996~.
From page 106...
... Thus, for these reasons, immune function tests could not be used as an indicator for establishing the EAR for vitamin A FACTORS AFFECTING THE VITAMIN A REQUIREMENT Intestinal Absorption Dietary Fat Dietary vitamin A is cligesteci in mixed micelles and absorbed with fat.
From page 107...
... and mixed green leafy vegetables (cle Pee et al., 1995; Tang et al., 2000) as compared with a ,3-carotene supplement.
From page 108...
... Z He Zinc is required for protein synthesis, including the hepatic synthesis and secretion of retinal binding protein (RBP)
From page 109...
... reported that dark adaptation improved after the provision of 220 mg/ciay of zinc to zinc-cleficient patients. Carotenoids Competitive interactions among different carotenoicis have been observed.
From page 110...
... Using the method clescribeci in Chapter 2, the AI of vitamin A for infants ages 0 though 6 months is baseci on the average amount of vitamin A in human milk that is consumeci. After rounding, an AI of 400 ,ug retinal activity equivalents (RAE)
From page 111...
... The vitamin A intake for older infants can also be cletermineci by estimating the intake from human milk (concentration x 0.6 L/ clay) and complementary foocis (Chapter 2~.
From page 112...
... A computational method is used that includes an allowance for acloquate liver vitamin A stores to set the Estimateci Average Requirement (EAR) (see "Aclults Ages 19 Years and Older".
From page 113...
... 30Ollg RAE/day of vitamin A 400 fig RAE/day of vitamin A 600 fig RAE/day of vitamin A 900 fig RAE/day of vitamin A 6001lg RAE/day of vitamin A 700 fig RAE/day of vitamin A Adults Ages I 9 Years and Older Evidence Considered in Estimating the Average Requirement The calculation clescribeci below can be used for estimating the vitamin A requirement and is calculated on the basis of the amount of clietary vitamin A required to maintain a given bocly-pool size in well-nourisheci subjects. Olson (1987)
From page 114...
... suggest that the efficiency of storage is approximately 40 percent, rather than the 50 percent that was previously reported (Olson, 1987~. Based on these current estimations, the EAR of preformed vitamin A required to assure an adequate body reserve in an adult man is 0.005 x 20 ,ug/g x 0.03 x 76 kg x 1.1 x 2.5, or 627,ug RAE/day.
From page 115...
... The RDA is clefineci as equal to the EAR plus twice the CV to cover the neecis of 97 to 98 percent of the inclivicluals in the group (therefore, for vitamin A the RDA is 140 percent of the EAR)
From page 116...
... Vitamin A EAR and RDA Summary, Pregnancy EAR for Pregnancy 14-18 years 19-30 years 31-50 years 530 fig RAE/day of vitamin A 550 fig RAE/day of vitamin A 550 fig RAE/day of vitamin A The RDA for vitamin A is set by using a CV of 20 percent baseci on the calculated half-life values for liver vitamin A (see "Adults Ages 19 Years and Older". The RDA is defined as equal to the EAR plus twice the CV to cover the neecis of 97 to 98 percent of inclivicluals in the group (therefore, for vitamin A the RDA is 140 percent of the EAR)
From page 117...
... To set an EAR cluring pregnancy, 400 fig RAE/ciay is acicleci to the EAR for nonpregnant adolescent girls and women to assure acloquate bocly stores of vitamin A Vitamin A EAR and RDA Summary, Lactation EAR for Lactation 14-18 years 19-30 years 31-50 years 885 fig RAE/day of vitamin A 900 fig RAE/day of vitamin A 900 fig RAE/day of vitamin A The RDA for vitamin A is set by using a CV of 20 percent baseci on the calculated half-life values for liver vitamin A (see "Adults Ages 19 Years and Older".
From page 118...
... , inclivicluals who consume alcohol may be distinctly susceptible to the adverse effects of vitamin A and any increased intake to meet one's neecis should be in the context of maintaining health. Developing Countries and Vegetarian Diets A number of factors can influence the requirement for vitamin A, including iron status, the presence and severity of infection and parasites, the level of clietary fat, protein energy malnutrition, and the available sources for preformed vitamin A and provitamin A carotenoids.
From page 119...
... Vegetarianism. Preformed vitamin A is found only in animal-derived food products.
From page 120...
... . b RAE = retinal activity equivalents; 1 RAE = 1 fig retinal + 1/12(1lg ,B-carotene equivalents)
From page 121...
... Therefore, an EAR that floes not assure acloquate vitamin A stores has been cletermineci on the basis of the level of vitamin A for correction of abnormal dark adaptation in adults. This approach floes not assure acloquate stores of vitamin A because animal studies inclicate that vitamin A clepletion of the eye occurs after the clepletion of hepatic vitamin A reserves (Bankson et al., 1989; Lewis et al., 1942~.
From page 122...
... INTAKE OF VITAMIN A Food Sources Common clietary sources of preformed vitamin A in the United States and Canada include liver, dairy products, and fish. ChugAhuja et al.
From page 123...
... It should be recognized that this floes not represent a clinical deficiency state, such as abnormal dark adaptation. Because the level of vitamin A intake varies greatly (Beaton et al., 1983)
From page 124...
... . b RAE = retinal activity equivalents; 1 RAE = fig retinal + 1/12(pg ,B-carotene equivalents)
From page 125...
... The UL for provitamin A carotenoicis has been aciciresseci in the report Dietary Reference Intakes for Vitamin C, Vitamin E, Selenium, and Carotenoids (IOM, 2000~. Hazard Identification There are substantial ciata on the adverse effects of high vitamin A intakes.
From page 126...
... One two-part study (Melhus et al., 1998) suggests that a chronic intake of 1.5 mg/ciay of preformed vitamin A is associated with osteoporosis and increased risk of hip fracture.
From page 127...
... , which suggest that risk of bone mineral loss and hip fracture occurs at estimated intakes above 1.5 m/day, two U.S. studies provide no evidence of increased bone mineral loss in women with intakes of preformed vitamin A up to 1.5 to 2.0 mg/day (Freudenheim et al., 1986; Houtkooper et al.
From page 128...
... Epiclemiological ciata show the possibility of teratogenic effects with high intakes of preformed vitamin A (Table 4-8~. The critical period for susceptibility appears to be the first trimester of pregnancy and the primary birth defects associated with excess vitamin A intake are those derived from cranial neural crest (CNC)
From page 129...
... The wicle spectrum of vitamin A-incluceci liver abnormalities ranges from reversibly elevated liver enzymes to wiclespreaci fibrosis, cirrhosis, and sometimes cleath. Table 4-9 shows consistency and specificity of the following effects in liver pathology: spontaneous green fluorescence of sinusoidal cells, perisinusoicial fibrosis, hyperplasia, and hypertrophy of Ito cells.
From page 130...
... Martinez-Frias Case control 11,293 cases of NA and Salvador, study birth defects 1990 11,193 controls < 12,000 2 12,000 (supplemental forms) Dudas and Letter 1,203 exposed 1,800 -1 to 3 or Czeizel, 1992 1,510 nonexposed gestati Rothman et Cohort study 22,748 pregnant First al., 1995 women trimes 1,500 control 3,000 supplement 4,500 supplement + food Khoury et al., Case control 1,623 casesb < 2,400C -1 to 3 or 1996 study 3,029 controlsb gestati Shaw et al., Case control 925 cases of birth 2 3,000 (presumed)
From page 131...
... (p < 0.001) This suggests women of reproductive age may be at increased risk of teratogenicity at vitamin A exposures 2 12,000 1lg/day The comparison of the rate and pattern of congenital abnormalities in exposed and nonexposed groups did not indicate any teratogenic effect of vitamin A Vitamin A intakes > 3,000 1lg/d, significant increased risk of cranial neural crest defects No increased risks of defects from cranial neural crest among vitamin A and multivitamin users No increased risk of orofacial clefts at vitamin A intakes 2 3,000 1lg/d compared to controls No association between periconceptional vitamin A at doses > 2,400 or > 10,000 1lg/d and malformations in general and cranial neural crest defects Vitamin A doses < 3,000 1lg/d during the first trimester of pregnancy is not teratogenic continued
From page 132...
... Mastroiacovo Cohort study 311 infants Median: 15,000 0 to 9 wl et al., 1999 evaluated Range: 3,000-100,000 gestati a 3.5 = the ratio of the prevalence among babies born to women who consumed more than 4,500 ~g/d of preformed vitamin A/d from food and supplements to the prevalence among the babies whose mothers consumed 1,500 fig or less/d. For vitamin A from supplements alone, the ratio of the prevalence among the babies born to women who consumed more than 3,000 ~g/day to that among the babies whose mothers consumed 1,500 aged or less was 4.8.
From page 133...
... controls was 0.5 Daily intake of preformed vitamin A supplement 2 3,000 1lg/d does not seem to increase risk of serious anomalies of structures with a cranial neural crest cell contribution b Cases refer to mothers of infants with cranial neural crest-derived defects ascertained within the first year of life. Controls represent mothers of infants without birth defects, frequency-matched to cases by period of birth, race, and hospital of birth.
From page 134...
... I1 :) rosls; Increase In liver and serum vitamin A; headache, skin desquamation, hypercalcemia, and r confusion Severe hepatotoxicity Hepatiti' Hepatiti' Eaton, 1978 Woman, 8,300-10,600 30 Cirrhosis; portal Unknow 51 y (diet + hypertension; marked supplements)
From page 135...
... VITAMIN A an 135 Hepatitis Increased Alcohol Use Other Factors ~ portal 70 U/L)
From page 136...
... bilirubin; tests for IgM antibody to hepatitis A virus, HbsAg and anti-HBc were negative Zafrani 1984 et al Man, 15,000 from 36 y supplement 12 Increase in liver vitamin A concentration; spontaneous green fluorescence of sinusoidal cells; perisinusoidal fibrosis and hyperplasia; hypertrophy of Ito cells; portal and periportal fibrosis; lesions of hepatic sinusoids randomly distributed areas of sinusoidal dilation; RBCs present in Disse's spaces; sinusoidal barrier abnormalities mimicking peliosis hepatitis Negative antigehepati core a Zafrani et al., Woman, 26,000 8 Hepatic lesions; Negative 1984 25 y spontaneous green antige fluorescence of hepati sinusoidal cells; core a perisinusoidal fibrosis, hyperplasia, and hypertrophy of Ito cells; randomly distributed areas of sinusoidal dilation; RBCs present in Disse's spaces; sinusoidal barrier abnormalities mimicking peliosis hepatitis
From page 137...
... VITAMIN A 137 Hepatitis Hepatitis A virus infection 5 y earlier Increased Alcohol Use Other Factors Not excessive No meds ;/L) , tal ~ for IgM hepatitis A and vitamin Negative hepatitis B surface No No meds In; antigen; positive serum ,reen hepatitis B surface and if core antibodies .s; fibrosis via; If Ito ad ~OSiS; Attic lomly eas of lotion; in Disse's idal halite liosis Negative hepatitis B surface No None preen antigen; negative serum If hepatitis B surface and is; core antibodies fibrosis nd f Ito cells ributed Tidal ~ present -es; rier .
From page 138...
... showoci a significantly increased risk of birth defects at the cranial neural crest sites among women who consumed greater than 4,500 fig of preformed vitamin A/day from food and supplements cluring the first trimester compared to those who took 1,500 ~g/day or less. Most of the human data on teratogenicity of vitamin A involve closes equal to or greater than 7,800 ~g/ciay.
From page 139...
... The NOAEL of 4,500 ~g/ciay was clivicleci by the UF of 1.5 to obtain a UL value of 3,000 ~g/ciay for women of reproductive age.
From page 140...
... Therefore, 12,000 1lg/day (total preformed vitamin A intake)
From page 141...
... n oil s drops .qualsol A n oil Bulging fontanels Bulging fontanels, anorexia, hyperirritability, edema of occipital area, bone changes, skin lesions, desquamation Bulging fontanels, hyperirritability, anorexia, occipital edema, increased head circumference Anorexia, hyperirritability, edema of the occipital area, pronounced craniotabes, increased intracranial pressure, skin lesions, skin desquamation, x-ray findings: epiphyseal line changes 4 Bulging anterior fontanels, irritability, vomiting 4 Anorexia, hyperirritability, pronounced craniotabes, x-ray findings: cortical hyperostosis 1.5 Anorexia, hyperirritability, edema of the occipital area, pronounced craniotabes, increased intracranial pressure, skin lesions, skin desquamation, x-ray findings: epiphyseal line changes 2 Anorexia, hyperirritability, edema of the occipital area, pronounced craniotabes, increased intracranial pressure, skin lesions, skin desquamation, falling out of hair, x-ray findings: cortical hyperostosis 0.4 Hypercalcemia, metastatic calcification of the lungs, kidneys, stomach, soft tissue, and skin; peeling skin; erythematous rash; hyperphosphatemia, bleeding disorder; pulmonary insufficiency; and death after 2-week hospital stay 5.5 Anorexia, hyperirritability, edema of the occipital area, increased intracranial pressure, skin lesions, skin desquamation, x-ray findings: cortical hyperostosis ment containing 600 fig vitamin A, along with a mixed diet high in fruits and vegetables. When the use of the chicken livers was discontinued, the children recovered with no lingering effects.
From page 142...
... data must show grossly elevated liver vitamin A levels or hypertrophy of Ito cells, (2) no alcoholism, (3)
From page 143...
... UL = LOAEL = 14~000 1lg/day_ 3,000 1lg/day UF 5 Vitamin A UT Summary, Ages I 9 Years and Older, Excluding Women of Childbearing Age UL for Men 2 19 years 3,000 1lg/day of preformed vitamin A UL for Women 2 51 years 3,000 ~g/day of preformed vitamin A Infants, Children, and Adolescent Boys Data Selection. Case reports of hypervitaminosis A in infants were used to identify a LOAEL and derive a UL.
From page 144...
... Thus, the adult UL of 3,000 ~g/ciay of preformed vitamin A was acljusteci for children and adolescents on the basis of relative body weight as described in Chapter 2 with use of reference weights from Chapter 1 (Table 1-1~. Values have been rouncleci.
From page 145...
... Intake Assessment Baseci on ciata from the Third National Health and Nutrition Survey (NHANES III) , the highest meclian intake of preformed vitamin A for any gender and life stage group was 895 ~g/day (Appenclix Table Cob.
From page 146...
... 1987. Vitamin A relative dose response test: Validation by intravenous injection in children with liver disease.
From page 147...
... 1989. Effects of a vitamin-A-free diet on tissue vitamin A concentration and dark adaptation of aging rats.
From page 148...
... 1980. Correlation of dark adaptation test results with serum vitamin A levels in diseased adults.
From page 149...
... 1998a. Hyporetinolemia, illness symptoms, and acute phase protein response in pregnant women with and without night blindness.
From page 150...
... 1991. Influence of dose and pharmaceutical formulation of vitamin A on plasma levels of retinyl esters and retinal and metabolic generation of retinoic acid compounds and beta-glucuronides in the cynomolgus monkey.
From page 151...
... Gastroenterology 100:1701-1709. Ghana VAST Study Team.
From page 152...
... 1968. Survey of liver vitamin A stores of Canadians.
From page 153...
... 1980. Effect of dietary fat on absorption of pcarotene from green leafy vegetables in children.
From page 154...
... 1998. Excessive dietary intake of vitamin A is associated with reduced bone mineral density and increased risk for hip fracture.
From page 155...
... 1978. Zinc deficiency: A cause of abnormal dark adaptation in cirrhotics.
From page 156...
... 1979. Liver vitamin A reserves of neonates, preschool children and adults dying of various causes in Salvador, Brazil.
From page 157...
... 1999. Iron deficiency in young rats alters the distribution of vitamin A between plasma and liver and between hepatic retinal and retinyl esters.
From page 158...
... 1988. Size and composition of liver vitamin A reserves of human beings who died of various causes.
From page 159...
... 1985. Stimulation of interleukin 1 and 3 production by retinoic acid in vitro.
From page 160...
... 1982. Reversible hepatotoxicity associated with hepatic vitamin A accumulation in a proteindeficientpatient.
From page 161...
... 1995. Retinoic acid repletion restores the number of leukocytes and their subsets and stimulates natural cytotoxicity in vitamin A-deficient rats.


This material may be derived from roughly machine-read images, and so is provided only to facilitate research.
More information on Chapter Skim is available.