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

• Retinoic acid is necessary for cellular 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 beta-

carotene), 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 0–4

Vitamin A requirement

Units of measuring vitamin A

Each μg RAE corresponds to 1 μg retinol, 2 μg of β-carotene in oil, 12 μg 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 sub clinical clinical

VAD (%) VAD (%) Afghanistan 53 - Bangladesh 28 0.7 Bhutan 32 0.7 INDIA 57 0.7 Nepal 33 1 Pakistan 35

7.11.2.1 India’s Undernourished Children: A Call For Reform and Action, World Bank Report:http://siteresources.worldbank.org/HEALTHNUTRITIONANDPOPULATION/Resources/281627-

1095698140167/IndiaUndernourishedChildrenFinal.pdf; last accessed on 24/09/07

High risk group 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

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 Bitot’s 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 itot’s 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 μmol/l representing VAD , and below 0.35 μmol/l representing severe VAD.

a serum retinol concentration below a cutoff of 1.05 μmol/l has been proposed to reflect low vitamin.

Criteria for assessing the publichealth significance of xerophthalmia

Clinical (primary) Night blindness (XN)* 1.0% Bitot’s 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 μmol/L (10

μg/dL) 5.0%

Universal vitamin A distribution schedule for preschool and lactating mothers

Children 1–6 years 200,000 IU of vitaminA orally every 3–6

months. Infants 6–11 months 100,000 IU of vitaminA orally every 3–6

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 > 1 yr Immediately 100,000 IU 200,000 IU Next day 100,000 IU 200,000 lU 2–4 weeks later 100,000 IU 200,000 IU

Severe Protein-Energy Malnutrition (PEM) Monthly until PEM resolves 100,000 IU 200,000 IU

Upper Level for Vitamin A

3000 μg 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