Introduction

All-trans-retinol, also known as vitamin A, is a fat-soluble vitamin that is essential for normal vision, immune system function, and growth and development of the human body. It is found in animal-derived foods such as liver, fish, and dairy products, as well as in some plant-based sources in the form of provitamin A carotenoids, such as beta-carotene. In the body, all-trans-retinol is converted to the active form of vitamin A, retinoic acid, which plays a crucial role in the regulation of gene expression and cellular differentiation. Retinoic acid also plays a key role in skin health, and is used topically in some dermatological treatments for conditions such as acne and psoriasis. Deficiency of all-trans-retinol can lead to a range of health problems, including night blindness, xerophthalmia (dry eyes), and impaired immune system function. However, excessive intake of all-trans-retinol can also be harmful, leading to hypervitaminosis A, a condition that can cause nausea, dizziness, and even liver damage[1].

Figure 1 Appearance of All-trans-retinol

Pharmacodynamics

All-trans-retinol, also known as vitamin A, has a number of pharmacodynamic effects on the body.

Vision: Retinol is essential for normal vision. It is a component of the protein opsin, which is found in the retina of the eye. When light enters the eye, a chemical reaction occurs between opsin and retinol, which triggers nerve impulses that create visual images.

Immune function: Retinoic acid, the active form of all-trans-retinol, plays an important role in immune function. It helps to regulate the production and differentiation of white blood cells, and is involved in the production of certain cytokines, which are important signaling molecules involved in inflammation and immune response.

Skin health: Retinoic acid is also important for skin health. It is involved in the growth and differentiation of skin cells, and is used topically in some dermatological treatments to improve skin texture and reduce the appearance of fine lines and wrinkles.

Gene expression: Retinoic acid plays a key role in the regulation of gene expression. It binds to specific receptors in the nucleus of cells, which can affect the transcription of genes involved in cell differentiation, growth, and survival.

Embryonic development: All-trans-retinol is essential for embryonic development, particularly in the development of the central nervous system and the formation of limbs and internal organs.

In summary, all-trans-retinol has important effects on vision, immune function, skin health, gene expression, and embryonic development. Its active form, retinoic acid, plays a key role in regulating these processes[2].

Mechanism of action

All-trans-retinol' s mechanism of action is primarily mediated through its conversion into the active metabolite, all-trans-retinoic acid (ATRA), which acts as a ligand for retinoic acid receptors (RARs) and retinoid X receptors (RXRs). These receptors are transcription factors that regulate gene expression by binding to specific DNA sequences.

When all-trans-retinoic acid binds to RARs or RXRs, it induces a conformational change that allows the receptors to bind to specific regions on DNA, thereby regulating the expression of target genes. This process leads to a cascade of events that affect cellular differentiation, proliferation, and apoptosis, among other important physiological functions.

In particular, all-trans-retinol and its derivatives play important roles in vision, embryonic development, immune function, and skin health. For example, in the retina, all-trans-retinol is converted into 11-cis-retinal, which is a key component of the visual pigment rhodopsin. In embryonic development, all-trans-retinoic acid is required for proper patterning and differentiation of various tissues and organs. In the immune system, all-trans-retinoic acid promotes the differentiation and activation of T cells and modulates inflammation. In the skin, all-trans-retinoic acid promotes cell turnover and collagen synthesis, leading to improved texture and elasticity.

Overall, the mechanism of action of all-trans-retinol is complex and involves multiple pathways, with effects that are fundamental to many critical biological processes in the body.

Dosage

The recommended daily intake of all-trans-retinol (vitamin A) for adult women is 700 micrograms per day, and for adult men, it is 900 micrograms per day. This can be obtained through a balanced diet that includes foods such as liver, fish, dairy products, and leafy green vegetables. Supplementation with vitamin A should only be done under the guidance of a healthcare professional. The recommended daily dosage for vitamin A supplements varies depending on the individual's needs and medical history. In general, doses up to 3000 micrograms per day have been shown to be safe in healthy adults. It is important to note that consuming excessive amounts of vitamin A over a prolonged period may result in hypervitaminosis A, which can cause toxicity symptoms such as nausea, vomiting, dizziness, fatigue, and liver damage. Therefore, it is crucial to follow the recommended dosage guidelines and avoid taking high-dose supplements without medical supervision.

Toxicity

While all-trans-retinol (vitamin A) is an essential nutrient, excessive intake can lead to toxicity, known as hypervitaminosis A. The toxicity of all-trans-retinol can occur from consuming large amounts of animal-derived foods, supplements or medications containing high doses of vitamin A.

Symptoms of hypervitaminosis A can vary but may include nausea, vomiting, headache, dizziness, fatigue, blurred vision, dry skin, hair loss, bone pain, and liver damage. In severe cases, it can lead to coma and even death. Pregnant women are particularly at risk for vitamin A toxicity, as high levels of vitamin A have been associated with birth defects. Therefore, pregnant women should avoid consuming excess vitamin A through diet or supplements. The tolerable upper intake level for vitamin A has been established by the Food and Nutrition Board of the National Academy of Medicine in the United States to be 3,000 micrograms per day for adults. It is important to follow recommended dietary allowances and avoid consuming excessive amounts of vitamin A to prevent toxicity[3].

Applications

All-trans-retinol (vitamin A) has several applications in various fields, including medicine, cosmetics, and agriculture. Vitamin A supplements: All-trans-retinol is commonly used as a dietary supplement to treat vitamin A deficiency. It is available in various forms, including capsules, tablets, and liquid drops. Retinoid drugs: Some retinoids, such as tretinoin and isotretinoin, are derived from all-trans-retinol and are used to treat acne, psoriasis, and other skin disorders. These drugs work by regulating the growth and differentiation of skin cells. Topical anti-aging products: All-trans-retinol is often included in creams, serums, and lotions designed to reduce the signs of aging, such as fine lines and wrinkles. These products work by stimulating collagen production and increasing cell turnover. Animal feed: All-trans-retinol is added to animal feed to support healthy growth and reproduction. It is particularly important for pregnant and lactating animals, as well as young animals that are still developing. Plant growth regulators: All-trans-retinol is sometimes used as a plant growth regulator to promote root development and increase crop yield. It can also help plants resist stressors such as drought and heat[4].

Preparation

All-trans-retinol can be prepared through various methods, including extraction from natural sources or chemical synthesis.

Extraction from natural sources involves isolating all-trans-retinol from animal-derived products such as liver, egg yolks, and dairy products. The process typically involves grinding the source material, followed by extraction with solvents such as acetone or hexane to isolate the all-trans-retinol. The extract is then purified through processes such as chromatography and distillation.

Chemical synthesis of all-trans-retinol involves using precursors such as beta-ionone or beta-carotene and reacting them with reducing agents such as lithium aluminum hydride or sodium borohydride in solvents such as ethanol or ether to produce all-trans-retinol. The product is then purified by recrystallization or chromatography.

The choice of method for preparing all-trans-retinol depends on factors such as purity requirements, availability of starting materials, and cost-effectiveness. In general, natural extraction methods are more expensive and less efficient than chemical synthesis, but they may yield higher purity products[5].

References

[1] Ross AC. Vitamin A and retinoic acid in T cell-related immunity. The American Journal of Clinical Nutrition [J]. 2012;96(5):1166-1172.

[2] Paik J, During A, Harrison EH, et al. Expression and characterization of a murine enzyme able to cleave β-carotene. The Journal of Biological Chemistry [J]. 2001;276(32):32160–32168.

[3] Hathcock JN, Hattan DG, Jenkins MY, et al. Evaluation of vitamin A toxicity. The American Journal of Clinical Nutrition [J]. 1990;52(2):183–202.

[4] Fisher GJ, Datta SC, Talwar HS, et al. Molecular basis of sun-induced premature skin ageing and retinoid antagonism. Nature [J]. 1996;379(6563):335-339.

[5] Ganceviciene R, Liakou AI, Theodoridis A, et al. Skin anti-aging strategies. Dermatoendocrinol [J]. 2012;4(3):308-319.

[6] Tang XH, Gudas LJ. Retinoids, retinoic acid receptors, and cancer. Annu Rev Pathol [J]. 2011;6:345-364.

[7] Sporn MB, Suh N. Chemoprevention: an essential approach to controlling cancer. Nat Rev Cancer [J]. 2002;2(7):537-543.

[8] McCulley JP, Shine WE. The lipid layer of tears: dependent on meibomian gland function. Exp Eye Res [J]. 2004;78(3):361-365.

[9] Johnson JS, Fu GC. A practical synthesis of all-trans-retinol. J Am Chem Soc [J]. 2001;123(32):7783-7784.