Vitamin A

Vitamin A is a natural supplement belonging to the supplement category of the fat-soluble vitamins class.

Vitamin A is also called xerophythol or retinol.

Vitamin A deficiency may lead to Xerophthalmia. Xerophthalmia is a severe eye disorder in which the eye fails to produce tears, and it includes conjunctival and corneal xerosis, bitot's spots, keratomalacia, nyctalopia, and retinopathy.

Vitamin A is vital for normal growth and development, the immune system, reproduction, and vision. The cardiovascular system, lung function, and other organs perform generally with the help of vitamin A.

The human body is not able to produce vitamin A. Therefore, it is necessary to obtain it from the diet as provitamin A carotenoids or as preformed vitamin A. Provitamin A carotenoids can be found mostly in fruits, vegetables, and other plant-based foods. Retinyl esters, or preformed vitamin A, on the other hand, are present in foods that come from animals, including fish, milk, butter, cream, liver, red meat, and eggs.

Vitamin A is absorbed from the intestinal lumen as retinyl esters and depends on bile and fat for optimal absorption. It is primarily stored in the liver, which is released as retinol, a free alcoholic substance, facilitating circulation throughout the body via the lymphatic and thoracic systems. In the liver, the retinol is metabolised to various products, some of which are conjugated with glucuronic acid or taurine for excretion in urine and faeces via bile.

Peak plasma time: 4-5 hr for oil solution; 304 hr for water-miscible.

The common side effects of using Vitamin A include blurry vision, diarrhoea, dizziness, headache, loss of appetite, nausea, dry mucus, pink eye, bone or joint pain, unusual tiredness, skin irritation and liver damage(long-term use).

Vitamin A is available in various forms like tablets, capsules and injectable solutions.

Biochemical Action of Vitamin A

 Vitamin A, belonging to the fat-soluble vitamins, acts as a cofactor in several enzymatic processes. Retinol is converted to retinyl esters in the liver and stored in stellate cells. The tissues oxidise retinol and beta-carotene to retinal and retinoic acid, which are necessary for vision and gene control, respectively. To regulate gene expression, these active metabolites bind to nuclear receptors of the RAR family.

• Antioxidant & Pro-oxidant Effects: Vitamin A possess a dual role in scavenging radicals & triggering oxidative stress in high doses.
• Growth & development: Crucial for embryonic growth, healthy bones, and T-cell function maintenance.
• Vision: Preserving eyesight and promoting normal cell differentiation in the eyes.
• Brain Booster & Chemopreventive: Impact on cognitive development and potential cancer-fighting abilities.
• Immunity: Vitamin A maintains the health of epithelial cells in the body, which form an essential barrier to infection.

Vitamin A is available in various forms like tablets, capsules, and injectable solutions.

• Tablets/ capsules are to be swallowed whole with water/liquid, as applicable.
• Topical vitamin A is to be applied in a little quantity generally about the size of a pea in a thin layer as prescribed by your doctor, as applicable.
• Injectable solutions are to be administered parenterally, as applicable.

Vitamin A can be used as a supplement for maintaining vision, cell growth, immune function, and fetal development. As an antioxidant, vitamin A supplements are recommended to reduce the risk of lung, prostate, cervical and other types of cancer.

Vitamins and natural supplements should not replace a balanced diet

This product is not intended to diagnose, treat or prevent any disease(s)

Vitamin A may be useful as a supplement that benefits health in numerous ways.

• Xerophthalmia: Vitamin A is a critical component of rhodopsin, a photopigment crucial for vision in low-light conditions. If a vitamin A deficit is severe enough, it may also result in blindness through photoreceptor degradation and night blindness. The nutrient's role extends to ocular health, as it helps maintain the differentiation of cells in the eyes, preventing dry eye and corneal ulceration.
• Cancer: Vitamin A is a potential strategy for decreasing cancer incidence; DNA damage and other deleterious cellular changes may be attenuated by reducing oxidative stress.
• Measles: Vitamin A can be used to treat measles and may be beneficial either by reducing the effects of measles infection (therapeutic effect) or preventing the subsequent development of secondary infection (protective effect), or both.
• Cardiovascular disease: The risk of developing cardiac disease from raised BP, atherosclerosis, myocardial ischemia, arrhythmias, and heart failure can be lowered by intake of vitamin A as it possesses a potent antioxidant.
• Dermatology: The Food and Drug Administration (FDA) had originally identified vitamin A as a potential anti-wrinkle agent that alters the appearance of the skin's surface and has anti-ageing effects, which are regulated by retinoids.
• Fertility and fetal development: Vitamin A is vital for both male and female reproduction organs because it has a vital role in sperm and egg development. It is also critical for placental health, fetal tissue development and maintenance, and fetal growth.

Night blindness is also referred to as nyctalopia. A person with night blindness has difficulty seeing in low-light situations, such as at night or in places with dim lighting.

The dosage of vitamin A that should be administered to treat night blindness depends on age, health, and how severe the problem is. Before beginning any vitamin A supplementation, it is essential to consult with a medical expert.

Vitamin A Deficiency

Deficiency prophylaxis: 10,000-50,000 U oral qDay

In case of malabsorption or when oral administration is not feasible, Take 100,000 U/day IM for three days, then 50,000 U/day for two weeks, which should be followed by oral therapy given to the patient.

Oral therapy: Take oral multivitamin containing vitamin A of 10,000-20,000 U/day for 2 months

Vitamin A supplementation may be administered orally, topically or intramuscularly.

• Use the IM route when oral administration is impossible or in malabsorption syndrome.
• When Vitamin A supplements are taken orally, it is best to take them along with a fat-containing meal to promote optimal absorption due to their lipophilic nature.
• Vitamin A supplements are applied topically to improve the health of your skin.

Vitamins and natural supplements should not replace a balanced diet

This product is not intended to diagnose, treat or prevent any disease(s).

• Tablet:10,000 U, 15,000 U
• Capsule: 7500 U, 8000 U, 10000 U, 25000 U
• Injectable solution: 50,000 U/mL

Dosage Adjustment for Adult Patients

• Xerophthalmia (Off-label)

Recommended recommended dosage, excluding women who are fertile: 200,000units PO qDay for 2 days; repeat dose again after 2 weeks

Females night blindness or Bitot's spots of reproductive age with 5000-10,000 units/day and a maximum of 10,000 units/day or ≤25,000 units once weekly for ≥4 weeks.

Vitamin A is available in various forms like tablets, capsules and injectable solutions.

• The advantages of vitamin A are countered by any meal or drink that contains caffeine, including coffee, tea, chocolate, and soda.
• Limit alcoholic beverages.
• Stay within your daily calorie needs.

The dietary restriction should be individualized as per patient requirements.

Recommended Daily Allowance (RDA)

900 and 700 g of retinol activity equivalents (RAE) per day, respectively, are recommended for men and women.

Upper Tolerable Intake (UTL):

For adults, it is set at 3,000 μg/day

• Doses greater than 10,000 IU/day long-term should be cautiously used.
• People with liver or renal disease, alcoholism or severe osteoporosis should use vitamin A supplements cautiously.
• In women who are pregnant, nursing, or who have a history of medication hypersensitivity, vitamin A is not recommended.
• Patients with hepatic disease and acne vulgaris should only be given it under strict supervision.

Taking too much vitamin A while pregnant can cause congenital disabilities in your baby, including abnormal eyes, skull, lungs, and heart.

High-dose supplements of vitamin A should not be taken during pregnancy or breastfeeding.

Due to its fat-soluble nature, vitamin A is not easily eliminated from the body; thus, it is essential to follow the recommended dosage since exceeding it may result in difficulties.

Caution is advised when consuming alcohol with Vitamin A. 

Daily doses above 3,000 mcg should be avoided in the mother. Excessive use of vitamin A during pregnancy has been associated with heart defects in vivo.

Vitamin A is safe to use during pregnancy. Higher doses above 10,000 IU per day of preformed vitamin A may be a potential risk of teratogenicity.

Vitamin A is generally well-tolerated.

The adverse reactions related to vitamin A can be categorized as-

• Common: Vomiting, diarrhoea, loss of appetite, unusual tiredness and hair loss.
• Less Common: Double vision, bleeding gums, mouth pain and bone or joint pain.
• Rare: Anaphylaxis & death after parenteral use, teratogenicity, hepatotoxicity.

The clinically relevant drug interactions of vitamin A are briefly summarized here:

• Cholestyramine: Reduces vitamin A absorption — increase dietary intake of vitamin A-rich foods or consider supplementation with long-term use.
• Chemotherapeutic agents: Adjunctive treatment may improve drug response- consider individual patient characteristics, form and presentation of cancer, drugs used before administration — use only under professional supervision.
• Colchicine: Colchicine may interfere with vitamin A absorption and homeostasis — co-administer for beneficial interaction.
• HMG-CoA reductase inhibitor drugs (statins): These drugs increase the serum levels of vitamin A, the clinical significance of which is unclear — observe patients taking this combination.
• Isotretinoin: Toxicity may be increased — avoid this combination.
• Minocycline: Long-term vitamin A use with this drug increases the risk of pseudo-tumour cerebri — use cautiously.
• Oral contraceptives: Increased vitamin A levels occur in oral contraceptive pill users due to more extended storage in the liver; use caution with large doses of retinol.
• Orlistat: Reduces vitamin A levels — increase dietary intake of vitamin A-rich foods or consider supplementation with long-term use.
• Tetracyclines: Adjunctive use may increase side effects such as headaches, pseudotumour cerebri — avoid.

The common side effects of Vitamin A include the following:

• fever, sweating, unusual tiredness
• mood changes
• dry mucus
• conjunctivitis(pink eye)
• bone or joint pain
• diarrhoea, vomiting, and appetite loss
• alterations to the menstrual cycle
• disorientation or feeling agitated, double vision, bleeding gums, mouth discomfort,
• seizure
• hair loss, peeling skin, damaged tissue around the mouth, or other symptoms of discolouration.

• Pregnancy: For the maintenance of maternal night vision and foetal ocular health as well as the development of other organs, the foetal skeleton, and the healthy functioning of the foetus' immune system, vitamin A is crucial for both the pregnant mother and the foetusIt is recommended not to exceed the therapeutic dose nor abruptly cease supplementation.

Higher doses above 10,000 IU per day of preformed vitamin A may be a potential risk of teratogenicity.

• Paediatrics: Vitamin A helps boost immunity and protects children under five from preventable diseases and blindness. When Vitamin A deficiency occurs, vitamin A recommended for infants and children 6–59 months as it reduces child morbidity and mortality.

Dosage Adjustment for Paediatric Patients

Vitamin A deficiency

Use IM route when oral administration is not feasible or in malabsorption syndrome.

Infants: 7500-15000 units/day for 10 days

1-8 years: 17,500-35,000 units/day for 10 days

>8 years

Infeasible for oral administration or malabsorption: After oral therapy, administer 100,000 U/day IM for three days, followed by 50,000 U/day for two weeks.

Oral treatment: For two months, take an oral therapeutic multivitamin with 10,000–20,000 U/day of vitamin A.

Deficiency prophylaxis: 10,000-50,000 U PO qDay

Xerophthalmia

<6 months: 50,000 units qDay for 2 days; repeat once with single dose after 2 weeks

6-12 months: 100,000 units qDay for 2 days; repeat with single dose after 2 weeks

>1 year except for females of reproductive age: 200,000 units qDay for 2 days; repeat with a single dose after 2 weeks.

Females who have Bitot's spots or night blindness should take a recommended dose of between 5,000 - 10,000 units per day, with a daily maximum of 10,000 units or 25,000 units once every week for four weeks.

• Geriatrics: Vitamin A may have anticancer effects and protect against age-associated conditions such as macular degeneration. However, retinol (vitamin A) can be toxic when taken in excess, and the elderly may be at particular risk for hypervitaminosis A.
• Lactating mothers: Daily doses above 3,000 mcg should be avoided in the mother. Vitamin A is a normal component of human milk and is a key milk antioxidant.

Dosage Adjustment in Kidney Impairment

There are no specific dosage adjustments provided.

Dosage Adjustment in Hepatic Impairment

There are no specific dosage adjustments provided.

Overdose of can lead to hypervitaminosis A causing headaches, dizziness, and even liver damage. In extreme cases, getting too much-preformed vitamin A can lead to coma and death.

There is no specific treatment in the event of an overdose. In the event of an overdose, the mainstay treatment is stopping the exogenous vitamin A supplementation by focusing on lowering calcium levels and treating the patient symptomatically, and supportive measures are instituted as required.

Biochemistry profile of Vitamin A

All-trans retinoic acid, a nuclear hormone that forms a heterodimer with retinoic acid receptors (RAR) in the nucleus, is a precursor of vitamin A. RAR-retinoid X receptor heterodimers act as transcription factors by binding to specific sites of gene promoters. These genes produce enzymes, extracellular matrix proteins, and crucial structural proteins that are found throughout the body. The ability of the retinal, a component of vitamin A, to make rhodopsin in the retina gives it the term "retina," which helps with vision, especially in low light conditions. The differentiation of T lymphocytes and the activation of B lymphocytes in response to immunological stimuli are both stimulated by vitamin A.

Kinetic profile:

• Absorption: Vitamin A is mainly obtained orally from the diet. However, when used as a drug, additional administration routes, including intramuscular and topical ways, are possible. Absorption in the intestinal lumen can happen through passive diffusion or mediated by the membrane proteins SCARB1 and CD36.
• Distribution: Chylomicrons (ChM), retinyl esters (RE) and β-carotene are secreted into the lymphatic system. Later, they reach the blood (systemic circulation) and are subsequently delivered to the liver, which functions as the main retinoid storage organ in the body or target tissues/cells.
• Metabolism: In the liver, retinol is mobilized as the free alcohol retinol. Retinol is first metabolized into retinal by alcohol dehydrogenases, and it later binds to a cellular retinoic acid-binding protein (CRBP). In the second step, retinal dehydrogenases oxidize retinal into ATRA, which then binds to the cellular retinoic acid-binding protein (CRABP). All-trans-retinoic acid (ATRA), the acidic form of vitamin A, is the final product of vitamin A oxidation and cannot be further reduced back into retinal or retinol and cannot be stored.
• Elimination: The elimination of retinoids happens through the kidneys or via the liver into bile. The evacuation of stored retinoids formed in the body is slower than water-soluble vitamins because Vitamin A is stored in different organs.

• https://ods.od.nih.gov/factsheets/VitaminA-HealthProfessional/#h9
• https://www.ncbi.nlm.nih.gov/books/NBK482362/#article-31210.r1
• https://www.ncbi.nlm.nih.gov/books/NBK532916/
• https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8157347/
• Braun L, Cohen M. October 1, 2014.Herbs and Natural Supplements; 4^th Edition Vol-2. Australia. Elsevier.