Vitamin A, The Good and The Bad

VITAMIN A, THE GOOD & THE BAD.
Humans require vitamin A for proper Immune function, Good vision, Reproduction and Tissue growth. However, taking vitamin A supplements in excess may lead to headache symptoms, as well as, Birth defects.

Humans get vitamin A from Plants and Animal produce.

While Animals produce, provide humans with already formed sources of vitamin A, mainly retinol, and retinyl esters, Plants produce, provide humans with vitamin A precursors only, known as the Carotenoids.

Biochemistry:

1. Plant precursors (carotenoids).

The red-yellow pigments, found in vegetables and fruits, are vitamin A precursors. The most important precursor is Beta-carotene.

Intestinal digestion, releases free beta-carotene, which then needs to mix with bile, and other products of fat digestion to form liquid micelles, that allow the beta-carotene to cross into the intestinal mucosa.

In the intestinal mucosa, the beta-carotene is cleaved into 2 vitamin A aldehydes: retinal, (by an enzyme Beta-carotene dioxygenase)

The enzyme, retinaldehyde dehydrogenase add Hydrogen atoms to the aldehyde, retinal, converting it to the alcohol form, Retinol.

The Retinol, and remaining beta-carotenes are packaged into Chylomicrons and transported into the liver. The liver has the capability to convert the remaining beta-carotene into retinol, too.

In the liver, retinol is stored as Retinyl esters. Retinyl esters are de-esterified into retinol, when needed

Not all the beta-carotene in the diet is converted to retinol (vitamin A).

The conversion of beta-carotene to vitamin A decrease as the dietary dose of beta-carotene increases.

On the average, 12mcg of beta-carotene, generates 1mcg of retinol.

PLANT VITAMIN A PRECURSORS:
. Green leafy vegetables, Spinach, Broccoli
. Orange and yellow vegetables, Squash, Carrots, Pumpkin

. Tomato products
. Fruits, Pink Grapefruits, Pawpaw, Mango, Oranges

2. ANIMAL PRODUCE

Retinol and Retinyl ester are the already formed vitamin A in animal products: Fish, Dairy, and Meat (especially the liver) .

On the average, there is 1:1 conversion of ingested food Retinol to body Retinol.

1mcg of food retinol generates 1mcg of retinol.
FUNCTIONS OF VITAMIN A
Vitamin A exists in three forms:
Storage form: Retinyl-esters, in the liver (mainly), but also in the lungs and bones

Transportable form: Retinol, which circulates, attached to retinol binding proteins.

Metabolically active form: Retinoic acid. Inside the cells, retinol is converted to retinal which is then reduced to retinoic acid. Retinoic acid binds to receptors to either activate or repress genes transcriptions.

Cytochrome P450 family oxidize retinoic acid to degradable forms.

VITAMIN A AND VISION
Retinol is carried to the retina where it is oxidized to retinal in rod cells. Retinal then combines with the pigment, Opsin, to form rhodopsin in the eye rods.

When a photon of light hit Rhodopsin, it catalyzes the switch of retinal, from –cis to –trans form, and this, initiates signal transmission to the optic nerve and the brain, for us to see objects in dim light.

Night blindness, is due to inadequate supply of retinol to the eye rods, but could also be due to zinc deficiency.

VITAMIN A AND EPITHELIAL CELLS
Vitamin A modulates the transcription of several hundreds of genes.

Vitamin A support cell growth and differentiation. It plays a critical role in the normal functioning of Heart, Kidneys and Lungs.

Vitamin A maintains the integrity and barrier-function of the skin and mucosal lining of the airways, digestive and urinary tracts, against infections. Cell linings protective of tissue surfaces fail to regenerate and differentiate, become flat and pile up keratin. They fail to generate protective secretions and cells required for immunity.

Epithelial tissues become Dry (Xerosis). Dry eyes are common.

Absence of vitamin A from diets has been associated with general susceptibility to infection.

Vitamin A deficiency increases the severity and mortality of infections like Diarrhea and measles.

Vitamin A is required for Sperm development in adult males and in the absence of vitamin A, sperm development is arrested.

VITAMIN A AND HUMAN EMBRYO.
The human embryo, needs a steady and adequate supply of maternal vitamin A, for normal development.

Retinoic acid, via retinoid receptors is involved in pathways that regulate development.

Both the lack and excess of vitamin A during embryonic development results in birth defects.

Vitamin A plays a major role in migration and differentiation of Neurons, during neurodevelopment.

Also, during the 2nd Trimester, low maternal Vitamin A is associated with x3 fold increase in risk if schizophrenia in adult offspring.

Lung development and maturation requires adequate vitamin A maternal diet

VITAMIN A AND MEASLES
Vitamin A deficiency is a risk factor for severe forms of measles infection.

The World Health Organization recommends children aged 1 year and over to take 200000 IU of Vitamin A daily for 2 days, when they develop measles infection. This practice helps prevent pneumonia deaths in children aged less than 2 years who develop measles.

Children deficient in vitamin A, account for half the percentage of kids who develop corneal ulcers with measles.

Half of the children who develop bilateral blindness, after measles infections, have vitamin A deficiency.

Vitamin A deficiency is one of the top causes of preventable blindness in children.

GROUPS AT RISK OF VITAMIN A DEFICIENCY
Serum Retinol level above 1.051micromol/L, marks adequacy.

Serum Retinol level 0.35-1.05micromol/L denotes subclinical deficiency.

Serum Retinol level below 0.35micromol/L is associated with Corneal diseases.

Preterm Infants.
Prematurely born children do not have adequate liver stores of vitamin A.

Vitamin A is required for lung development and maturation.

Vitamin A-deficient preterm infants have increased risk of Eye, Chronic Lung and Bowel diseases.

Infants and Toddlers
Exclusively breastfed infants, of mothers with vitamin A deficiency do not have adequate liver stores for vitamin A. Most kids develop Xerophthalmia after breast feeding.

Pregnant & Lactating Women.
Vitamin A Requirement during pregnancy increases, to support maternal metabolism and fetal growth.

Vitamin A deficiency in pregnant and breast-feeding women, lead to increase morbidity and mortality, for the mother and child. The children born to these women are at risk for Anemia and slower growth and development.

Intestinal Malabsorption
People with cystic fibrosis and other diseases associated with poor bowel absorption, are also at risk of Vitamin A deficiency. The good news is that Vitamin A supplements help to alleviate this problem.

Orlistat, the weight loss medication, decreases absorption of beta carotenes

VITMIN A TOXICITY.
Vitamin A is stored in the liver when not required, and the levels could pile up readily.

CONVERSION FACTOR:
Plant sources of Beta-carotene, do not lead to vitamin A toxicity. This is because, Nature has a way to reduce the conversion of beta-carotene to retinol, when ingested.

The more beta-carotene you eat, the less is converted to retinol.

The rest of ingested beta-carotene is stored in fat reserves in the body. Even though too much consumption of beta-carotene shall make your palm and skin yellow, you do not develop vitamin A toxicity.

On the average it requires 12mcg of beta-carotene to generate 1mcg of retinol. (12:1conversion factor)

The situation is different when one consumes preformed vitamin A from diet and nutritional supplements.

1mcg of preformed dietary Retinol, (from animal produce) generates 1mcg of retinol in the body. (1:1 conversion).

Unless one has vitamin A deficiency, Vitamin A dietary supplements could be unnecessarily dangerous.

Studies indicate that, taking nutritional supplements like Beta carotene 30mg daily, or Retinyl palmitate 25000IUdaily for 5-8 years increases risk of death from Lung cancer and Heart diseases

Eating fruits and vegetables is more beneficial and superior to dietary vitamin A supplements.

Daily Vitamin A requirements in microgram of Retinol Activity Equivalents (RAE)

. Male Adults & Teenagers: 900 mcg RAE
. Female, Adults & Teenagers:700mcg RAE
. Lactating Females: 1300mcgRAE
. 0-6month: 400mcgRAE/7-12 months:500mcgRAE/1-3 years: 300mcgRAE/4-8years:400mcgRAE/

. 9-13 years: 600 mcg RAE
SYMPTOMS OF HEPERVITAMINOSIS A include: Dizziness/Headaches/Bone and Joints pain/Skin irritation

Increased intracranial pressure/Coma/Death.