Provitamin A

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

Provitamin A is also known as carotenoids and beta-carotene.

A deficiency of provitamin A leads to impaired vision, a weakened immune system, skin problems, and reduced antioxidant protection.

Provitamin A can be used as antioxidant support, eye health, immune system boost, and skin protection by converting to active vitamin A (retinol) through enzymatic reactions in the body.

Beta-carotene is primarily found in carrots but also in rockmelon, broccoli, and spinach. The richest natural source of beta-carotene, Dunaliella salina (also known as D. bradawl), is a micro marine alga (phytoplankton) that is typically derived from palm oil or other vegetable sources.

The common side effects of provitamin A include high doses of nausea, vomiting, dizziness, headache, and skin irritation.

Provitamin A is available in the form of capsules.

Biochemical action of provitamin A

Provitamin A belonging to the supplement class of fat soluble vitamins, acts as an antioxidant agent. Provitamin A acts via the beta-carotene conversion pathway.

The body converts provitamin A into active vitamin A (retinol), which has biochemical effects. Provitamin A carotenoids are digested and transformed into retinol by intestinal mucosal enzymes, which are subsequently distributed to numerous organs. Retinol is necessary for the retina's synthesis of pigments that are sensitive to light, which improves vision in dim light. Additionally essential for good immunological function, cell differentiation, and growth, vitamin A is also necessary for the preservation of healthy skin, mucous membranes, and other tissues.

Provitamin A functions as an antioxidant, aiding the body in scavenging dangerous free radicals, which may result in several health advantages and protection against oxidative stress.

Beta-carotene and other carotenoids play a crucial photoprotective role in photosynthetic organisms by dissipating excess energy as heat and scavenging reactive oxygen species to prevent lipid peroxidation.

Onset: Photoprotection occurs after 4-6 weeks when plasma concentrations reach a maximum.

Peak plasma time: ~4-6 weeks

Therapeutic plasma concentration: 4-6 mcg/mL.

Supplements of provitamin A are available in capsules.

Capsules: To be swallowed whole with water/liquid, as applicable.

Provitamin A is a precursor to vitamins, and supplementation of this vitamin supports vision, immune function, and skin health.

Taking Carotenoids as a supplement helps lower the risk of certain types of cancer like lung, breast, and prostate cancer.

Provitamin A supplement improves heart health by reducing the risk of cardiovascular diseases.

Provitamin A supplement enhances bone health and density, especially with other nutrients like vitamin D and calcium.

Vitamins and natural supplements should not replace a balanced diet.

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

Supplemental provitamin A may be useful as a supplement for the following health benefits:

• Vitamin A deficiency: supplementing with beta-carotene lowers the risk of infection-related death in night-blind women due to vitamin A deficiency. The safer alternative should be dietary beta-carotene. Women's night vision has been associated with increased carrot consumption.
• Cancer prevention: Vitamin A is a potential strategy for decreasing cancer incidence. Oxidative stress can be reduced by damaging the DNA and changing other deleterious cellular functions.
• Cardiovascular disease: Some clinical research supports the assumption that a diet high in carotenoids is associated with a lower risk of developing heart disease.
• Cystic fibrosis: Exocrine pancreatic insufficiency, impaired fat-soluble vitamin absorption, chronic lung inflammation, and increased oxygen-free radical production are all effects of cystic fibrosis (CF). Low beta-carotene levels in CF patients may benefit from supplementation with beta-carotene.
• Age-related macula degeneration: Beta-carotene and other nutrients may prevent age-related macula degeneration (ARMD). However, the carotenoids lutein and zeaxanthin provide greater protection. Foods and supplements high in beta-carotene may slow the progression of ARMD and vision loss.
• Erythropoietic protoporphyria and Photosensitivity: Patients with erythropoietic protoporphyria and patients with other photosensitivity diseases like solar urticaria, porphyria cutanea tarda, and actinic reticulosis, high doses of beta-carotene (between 180 and 300 mg/day) have been used to prevent or lessen photosensitivity effectively.
• Cognitive function: Long-term usage of beta-carotene supplements has been linked to potential mental benefits, suggesting that it may eventually help to improve overall brain health and cognitive function.

• Orally: All oral solid forms of provitamin A are often taken before or after meals with water. For individuals with difficulty swallowing capsules, their contents can be combined with orange or tomato juice.

The dosage and duration of treatment should be as per the clinical judgment of the treating healthcare professional.

Vitamins and natural supplements should not replace a balanced diet

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

• Orally: All oral solid forms of Provitamin A are often taken before or after meals with water. For individuals with difficulty swallowing capsules, their contents can be combined with orange or tomato juice.

The dosage and duration of treatment should be as per the clinical judgment of the treating healthcare professional.

Vitamins and natural supplements should not replace a balanced diet

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

Provitamin A is available in the form of capsules.

• 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.
• Liver and liver products( due to their high vitamin A content).

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

Provitamin A may be contraindicated in the following conditions:

• Avoid supplementation in case of hypersensitivity to provitamin A or carotenoids.

• The healing process after angioplasty may be delayed when antioxidant vitamins, such as beta-carotene, are taken concurrently.

• Heavy smokers should be advised not to take synthetic beta-carotene supplements for long periods.

• Avoid retinoid medications as they may increase the risk of vitamin A toxicity.

Allergic reactions or gastrointestinal issues should be cautiously monitored.

• Patients with underlying medical issues should be managed cautiously; dosage recommendations might vary.

• Women who are pregnant or nursing should adhere to dosage recommendations.

• After initiating large doses, carotenoderma (skin yellowing) has been reported 4-6 weeks later.

• Provitamin A supplements should not be used in place of a healthy diet.

Caution is advised when consuming alcohol with provitamin A.

Provitamin A is safe to use during breastfeeding.

Provitamin A is safe to use during pregnancy.

Limit the consumption of foods and beverages that include caffeine, such as coffee, tea, chocolate, and alcoholic beverages, as this substance could hinder the absorption of provitamin A.

Provitamin A supplements are generally safe and well-tolerated.

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

• Common: Orange-yellow colouration of the skin (carotenodermia), diarrhoea, nausea and stomach cramps
• Less common: Dizziness, headache, fatigue, itching or rash
• Rare: Allergic reactions, severe skin discolouration, photosensitivity (increased sensitivity to sunlight).

• Drugs reducing fat absorption: Beta-carotene absorption may be affected by medications like cholestyramine, colestipol, and orlistat that decrease fat absorption.-Separating the administration of these medications by at least two hours can prevent this.
• Fibrates: Natural beta-carotene has been shown to raise HDL cholesterol levels in fibrate-treated humans and animals considerably, and fibrate may interact synergistically.
• Valproate: Reduced plasma concentrations of beta-carotene and other fat-soluble antioxidant vitamins have been seen in epileptic patients who gain weight while receiving valproate medication; this is reversible after valproate withdrawal.

Common side effects of provitamin A supplementation include:

• Nausea

• Vomiting

• Dizziness

• Headache

• Skin irritation in high doses

• Mild skin discolouration (yellowing)

• Gastrointestinal disturbances

• Pregnancy: Provitamin A is considered safe in pregnancy. As provitamin A is vital for the development of the fetus, it has been recommended that pregnant women increase their vitamin A intake by 40%. Increasing dietary beta-carotene is an effective way for women to maintain their vitamin A levels.

Pregnancy Category: A/C-when exceeding RDA recommendations.

Safe during pregnancy, but when taken in high doses, use with caution if the benefits outweigh the risks.

• Paediatrics: Provitamin A is necessary for a strong immune system, helps improve vision in low light, and maintains healthy skin.

Dosage Adjustment for Paediatric Patients

Erythropoietic Protoporphyria

Indicated to lower sun sensitivity in erythropoietic protoporphyria

180 mg/day oral as a once-daily dose or divided several times per day

If sun sensitivity still exists, it may increase by 30-60 mg/day; however, not to exceed 300 mg/day

• Geriatrics: Provitamin 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: Provitamin A is naturally present in human milk, and administration of the approved recommended dose is not expected to cause any harm to a breastfed child.

Dosage Adjustment in Kidney Impairment

There are no specific dosage adjustments provided.

Dosage Adjustment in Hepatic Impairment

There are no specific dosage adjustments provided.

Dosage Adjustment in Adult Patients

Erythropoietic Protoporphyria

Indicated to lower the sensitivity of sun in erythropoietic protoporphyria

180 mg/day oral once-daily dose or divided several times per day.

If sun sensitivity still exists, the dose may increase by 30-60 mg/day, however not to exceed 300 mg/day

Beta carotene equivalents

1 IU beta carotene = 0.6 mcg beta carotene

1 retinol equivalent (RE expressed as vitamin A equivalent) = 6 mcg beta carotene.

Overdosage of provitamin A supplements can cause hypervitaminosis A. On extremely high doses may show symptoms like headache, blurred vision, nausea, dizziness, and skin rashes, which are usually self-limiting.

There is no specific treatment that is recommended in the event of an overdose. When an overdose is suspected, provitamin A should be terminated immediately. Supportive therapy should also be given, along with addressing any symptoms that persist or worsen. In severe cases, liver function tests may be conducted to assess potential liver damage.

Biochemistry profile of provitamin A

Both natural and artificial versions of beta-carotene exist. The 9-cis and all-trans isomers of naturally occurring beta-carotene, which is derived from algae, are present in approximately equal proportions, along with traces of the 13-cis isomer. The all-trans isomer accounts for most synthetic beta-carotene, while the 13-cis isomer only makes up a small portion of it. The 9-cis isomer of beta-carotene functions as an effective antioxidant and is not transformed into vitamin A, whereas all-trans beta-carotene is. Vitamin A is essential for eyesight, growth, reproduction, immunity, and skin health.

Kinetic profile:

• Absorption: Provitamin A is absorbed in the small intestine, where it binds with chylomicrons, which are distinct particles that transport lipids through the lymphatic system and finally into the bloodstream.
• Distribution: Provitamin A is transported by chylomicrons and lipoproteins throughout the body once it reaches the bloodstream. Wherever it is required, it is given to various tissues and organs.
• Metabolism: In the body, provitamin A is converted by enzymes to active vitamin A (retinol). Beta-carotene is broken down into two molecules of retinaldehyde, which is then converted to retinol in the intestinal mucosa, liver, and other organs. To avoid a toxicity-causing accumulation of vitamin A, this conversion process is strictly monitored.
• Excretion: The body excretes excess vitamin A, including any provitamin A that has not been transformed, through the urine and bile. Since excessive amounts of vitamin A can have adverse effects, the body maintains a delicate equilibrium to prevent vitamin A toxicity.

1. Braun L, Cohen M. October 1, 2014.Herbs and Natural Supplements; 4^th Edition Vol-2. Australia. Elsevier.
2. https://ods.od.nih.gov/factsheets/VitaminA-HealthProfessional/
3. https://reference.medscape.com/drug/lumitene-provitamin-a-beta-carotene-999912
4. https://ods.od.nih.gov/factsheets/VitaminA-Consumer/
5. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3525326/
6. https://www.ncbi.nlm.nih.gov/books/NBK554545/