VITAMIN A DEFICIENCY AND HYPERVITAMINOSIS A

By Dr. Pankaj Yadav DNB (1st yr)

Introduction
Vitamin A deficiency (VAD) is a major

nutritional concern in poor societies, especially in lower income countries like INDIA. Vitamin A is an essential nutrient needed in small amounts for the normal functioning of the visual system, and maintenance of cell function for growth, epithelial integrity, red blood cell production, immunity and reproduction.

 Active forms are retinol, retinaldehyde, and retinoic acid Plants synthesize the more complex carotenoids which are cleaved to retinol by most animals and stored in the liver as retinyl palmitate N retinol plasma values: 15-30 mcg/dl in infants & 30-90 mcg/dl in adults Retinal is the prosthetic group of photosensitive pigment in both rods (rhodopsin) & cones (iodopsin), major difference lies in the nature of protein bound Needed in lysosomal membrane stability Plays a role in keratinization, cornification, bone development & cell growth & reproduction

Absorption of Vitamin A
Retinoids
Retinyl esters broken down to free retinol in small

intestine - requires bile, digestive enzymes, integration into micelles Once absorbed, retinyl esters reformed in intestinal cells 90% of retinoids can be absorbed

Carotenoids
Absorbed intact, absorption rate much lower

Intestinal cells can convert carotenoids to retinoids

Transport and Storage of Vitamin A

Liver stores 90% of vitamin A in the body Reserve is adequate for several months Transported via chylomicrons from intestinal

cells to the liver Transported from the liver to target tissue as retinol via retinol-binding protein, which is bound to transthyretin

Excretion of Vitamin A
Not readily excreted Some lost in urine Kidney disease and aging increase risk of

toxicity because excretion is impaired

Functions of vitamin A
Vision (night, day, colour) Epithelial cell integrity against infections Immune response Haematopoiesis Skeletal growth Fertility (male and female) Embryogenesis

Functions of Vitamin A: Growth and Differentiation of Cells acid is necessary for cellular Retinoic
differentiation Important for embryo development, gene expression Retinoic acid influences production, structure, and function of epithelial cells that line the outside (skin) and external passages (mucus forming cells) within the body

Functions of Vitamin A: Immunity

Deficiency leads to decreased resistance to

infections Supplementation may decrease severity of infections in deficient person

The Visual Cycle

 Prevention of cardiovascular disease

Antioxidant capabilities 5 servings/day of fruits and vegetables

Cancer prevention
Antioxidant capabilities Lung, oral, and prostate cancers Studies indicate that vitamin A-containing foods are more

protective than supplements

Age-related macular degeneration

Cataracts Acne AML

Source of vitamin A
Colostrum foods containing either preformed vitamin A

esters - liver, milk,cheese,eggs or food products fortified with vitamin A or carotenoid precursors (mainly betacarotene), such as green leaves, carrots, ripe mangoes,eggs, and other orange-yellow vegetables and fruits.

Source of vitamin A
fruit carotenoid

sources(micrograms/100gm) Mango (golden) 307 Papaya (solo) 124 Cucurbita (mature pulp) 862 Buriti palm (pulp) 3,000 Red palm oil 30,000 Carrot 2,000 Dark green leafy vegetables 685 Tomato 100 Apricot 250 Sweet potato, red and yellow 670

Animal (micrograms/100gm) Fatty fish liver oils Halibut 900,000 Cod 18,000 Shark 180,000 Dairy produce Butter 830 Margarine, vitaminized 900 Eggs 140 Milk 40 Cheese, fatty type 320 Liver of sheep and ox 15,000 Beef, mutton, pork 04

Vitamin A requirement

Units of measuring vitamin A

Each g RAE corresponds to 1 g retinol, 2 g of -carotene in oil, 12 g of "dietary" beta-carotene, One International Unit (I.U.) = 0.3 mcg. of retinol = 0.6 mcg. of beta-carotene

= 1.2 mcg. of other total mixed carotenoids

Prevalence of vitamin A deficiency in South Asia (%)

Country Afghanistan Bangladesh Bhutan INDIA Nepal Pakistan

sub clinical VAD (%) 53 28 32 57 33 35

clinical VAD (%) 0.7 0.7 0.7 1

7.11.2.1 Indias Undernourished Children: A Call For Reform and Action, World Bank Report:http://siteresources.worldbank.org/HEALTHNUTRITIONANDPOPULATION/Resources/2816271095698140167/IndiaUndernourishedChildrenFinal.pdf; last accessed on 24/09/07

Infancy Childhood Pregnancy Lactation Urban poor Older adults Alcoholism Liver disease (limits storage) Fat malabsorption Increased excretion as in cancer & UTI Low protein intake resulting in deficient carriers

High risk group

 Usually, VAD develops in an environment of ecological social and economical deprivation Synergism between deficient dietary intake of vitamin A coexists with severe infections, such as measles, and frequent infections causing

diarrhoea and respiratory diseases that can lower intake through depressed appetite and absorption, and deplete body stores of vitamin A through excessive metabolism and excretion

Health consequences
Xerophthalmia is the most specific VADD,and

is the leading preventable cause of blindness in children throughout the world Night blindness Anaemia can result from VAD in children and women,likely due to multiple apparent roles of vitamin A in supporting iron mobilization and transport, and hematopoiesis

VITAMIN A DEFICIENCY

Assessing vitamin A status and deficiency

Two sets of indicators of VAD are commonly used for population surveys:

1 clinically assessed eye signs. Term xerophthalmia encompasses the clinical spectrum of ocular manifestations of VAD, from milder stages of night blindness and Bitots spots, to potentially blinding stages of corneal xerosis, ulceration and necrosis (keratomalacia) 2 biochemically determined concentrations of retinol in plasma or serum

Classification of xerophthalmia

XNN ight blindness X1A Conjunctival xerosis X1BB itots spot X2 Corneal xerosis X3A Corneal ulceration/keratomalacia (< 1/3 corneal surface) X3BCorneal ulceration/keratomalacia ( 1/3 corneal surface) XSCorneal scar XFXerophthalmic fundus

Serum retinol concentrations

serum retinol concentrations in a population

constitutes the second major approach to assessing vitamin A status in a population, with values below a cut-off of 0.70 mol/l representing VAD , and below 0.35 mol/l representing severe VAD. a serum retinol concentration below a cutoff of 1.05 mol/l has been proposed to reflect low vitamin.

Criteria for assessing the public health significance of Clinical (primary) xerophthalmia 1.0% Night blindness (XN)*
Bitots spot (X1B) 0.5% Corneal xerosis and/or ulceration/keratomalacia (X2 + X3A + X3B) 0.01% Xerophthalmia-related corneal scars (XS) 0.05%

Biochemical (supportive) Serum retinol (vitaminA) < 0.35 mol/L (10 g/dL) 5.0%

Universal vitamin A distribution schedule for preschool and lactating mothers

Children 16 years

200,000 IU of vitaminA orally every 36 months. Infants 611 months 100,000 IU of vitaminA orally every 36 months. Lactating mothers 200,000 IU of vitaminA orally once: at delivery or during the first 8 weeks postpartum if breastfeeding or during the first 6 weeks if not breast-feeding

Recommended xerophthalmia treatment schedule

6 -12 months Immediately 100,000 IU Next day 100,000 IU 24 weeks later 100,000 IU > 1 yr 200,000 IU 200,000 lU 200,000 IU

Severe Protein-Energy Malnutrition (PEM)

Monthly until PEM resolves 100,000 IU 200,000 IU

Upper Level for Vitamin A

3000 g retinol Hypervitaminosis A results from long-term

supplement use (2 4 x RDA) Toxicity Fatal dose (12 g)

Hypervitaminosis A
Acute Intoxication:

Results when excessively large single doses >300,000 IU ingested Infants: n/v, drowsiness or irritability w/signs of increased ICP Adults: drowsiness, irritability, headache & vomiting Serum vitamin A values = 200-1000 IU/dl (N: 50-100 IU/dl)

Toxicity of Vitamin A
Acute short-term megadose (100 x

RDA); symptoms disappear when intake stops

GI effects Headaches Blurred vision Poor muscle coordination

Chronic Intoxication

Results when >50,000 IU/day ingested for several wks or more Signs & symptoms in infants: Early are anorexia, pruritus, irritability, tender swollen bones w/motion limitation Alopecia, seborrhea, cheilosis & peeling of palms & soles Hepatomegaly & hypercalcemia observed Craniotabes & hyperostosis of long bones Elevated serum vit A levels confirms diagnosis Reversible manifestations when vitamin A discontinued

Chronic Toxicity of Vitamin A

long-term megadose; possible permanent

damage
Bone and muscle pain Loss of appetite Skin disorders Headache Dry skin Hair loss Increased liver size Vomiting

Toxicity of Vitamin A
Teratogenic (may occur with as little as 3 x

RDA of preformed vitamin A)

Tends to produce physical defect on developing

fetus as a result of excess vitamin A intake Spontaneous abortion Birth defects