Vitamin A

Vitamin A is one of the first recognized vitamins and is a fat-soluble molecule. The molecules exhibiting vitamin A activity, also known as retinoids, contain isoprene units and are classified as steroids. It is known that carotenoids, the precursors of vitamin A, play a role in preventing cancer by reducing the harmful effects of free radicals through their potent antioxidant properties and thereby limiting the impact of carcinogenic substances.

General Characteristics of Molecules Exhibiting Vitamin A Activity

Vitamin A refers to a group of compounds including the biologically active forms of retinol, which has a polyene alcohol structure composed of four isoprene units. Retinol, in both its natural and synthetic forms, is classified under the term “retinoid.” The vitamin A in natural foods is protected by antioxidants such as vitamin E. β-Carotene supports the antioxidant effects of vitamin E by capturing free peroxyl radicals under low oxygen partial pressure. Molecules exhibiting vitamin A activity are grouped into two main categories: those found in animal tissues and those found in plant tissues. In animals, retinol exists as esters of long-chain fatty acids, while in plants it is present in the form of provitamin β-carotene.

Those found in animal tissues (Retinoids): Retinol, hydroretinol, retinal, and retinoic acid.

Chemical Structure of Retinol (Ayşe Baysal)  

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Chemical Structures of Hydroretinol, Retinal, and Retinoic Acid (Ayşe Baysal)   

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Sulfur-orange pigments in plant foods (Carotenoids): These are converted into retinol in the intestinal mucosa and liver, thereby exhibiting vitamin A activity. Over 500 carotenoids exist in nature, approximately 50 of which possess vitamin A activity. The most well-known is beta-carotene.

Chemical Structures of Beta, Alpha, and Gamma Carotene (Ayşe Baysal)  

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Pure vitamin A (all-trans retinol) and carotenoids are insoluble in water but soluble in fat-soluble solvents such as benzene, ether, and chloroform. They are heat-resistant but degrade under UV light. They are resistant to alkalis. Due to multiple double bonds in their molecules, they are easily oxidized and lose their activity upon oxidation. Ultraviolet radiation induces structural changes in the molecule, leading to loss of activity. Metallic ions, light, and heat accelerate oxidation. Pure vitamin A exists as a pale yellow crystalline substance.

Dietary Sources of Vitamin A

Vitamin A is found in animal sources such as fish liver and body fat, liver, milk and milk fat, and egg yolk. Carotenoids are primarily found in yellow, orange, and green vegetables and fruits. Animals convert carotenoids obtained from plants into vitamin A.

Some Foods Containing Carotenoids (Generated by Artificial Intelligence.)

Utilization in the Body

Vitamin A is absorbed, transported, stored in the liver, and released as needed to exert its various physiological functions through a complex metabolic process.

Absorption and Transport

In foods, retinoids are esterified with fatty acids, while carotenoids are present in free form. In the lumen of the small intestine, retinyl esters are hydrolyzed to retinol with the aid of bile and pancreatic lipase. Retinol is re-esterified within mucosal cells and enters circulation as part of lipid particles in the lymphatic system. A portion also enters the bloodstream via the portal vein. In plasma, retinol is transported bound to a specific protein called retinol-binding protein (RBP). It is believed that RBP is associated with prealbumin. A portion of carotenoids is converted into retinol in the small intestine, while the remainder is absorbed within lipid particles, transported to the liver, and converted into retinol there.

Storage and Release

Retinol transported to the liver is stored as retinyl esters. Approximately 90% of vitamin A is stored in the liver. Beta-carotene is transported by lipoproteins. Stored retinyl esters are hydrolyzed by liver enzymes and then bind to RBP before entering circulation. Blood levels of vitamin A remain constant until liver stores are depleted.

Factors Affecting Absorption

The presence of fat and bile is essential for the absorption of vitamin A and carotenoids. Bile duct insufficiencies and disorders of fat digestion reduce absorption. The absorption of retinoids ranges from 70% to 90%. Carotenoid absorption increases in a fatty environment and decreases in a fat-free environment. The presence of mineral oils in the small intestine inhibits vitamin A absorption. Vitamins E and C help maintain vitamin A in its active form by preventing its oxidation. Carotenoid absorption becomes impossible when dietary fat intake is less than 7% of daily energy. The presence of parasites such as giardiasis and ascariasis also reduces absorption.

Functions

Vitamin A is a vital vitamin involved in regulating many fundamental biological processes, particularly those related to vision, immunity, cellular renewal, and growth.

Visual Function

The retina of the eye contains the pigment rhodopsin, which enables vision in low-light conditions. Rhodopsin dissociates into retinal and opsin upon exposure to light, stimulating the optic nerve and enabling vision. In darkness, retinal is recombined with opsin to regenerate rhodopsin. In vitamin A deficiency, this regeneration is delayed, resulting in night blindness.

Integrity of Epithelial Tissue

Vitamin A is required for maintaining the integrity of protective epithelial tissues lining the skin and organs. Retinoic acid activates retinoid receptors in the nucleus, regulating the expression of various genes (such as alcohol dehydrogenase, matrix proteins, RBP, and receptor proteins).

Immune System

Continuity of immune function depends on cell proliferation and differentiation. It is necessary for maintaining natural killer cell levels, enhancing phagocytic activity in macrophages, and promoting the production of interleukin-1 and other cytokines, as well as T and B lymphocytes. It plays a role in antibody formation and complement activity. For this reason, it is known as an anti-infective vitamin.

Growth and Development

Vitamin A plays a critical role in embryonic development (brain, spinal cord, eyes, heart, ears, and bones). It is essential for the development and health of bones and teeth, as well as for growth and reproductive processes.

Hormonal and Metabolic Functions

Vitamin A is linked to iron metabolism and thyroid hormones; it has been reported to play a role in the conversion of thyroxine (T₄) into the more active triiodothyronine (T₃).

Protection Against Cancer

Vitamin A and carotenoids are believed to have protective effects against cancer. Carotenoids protect cells from oxidative stress by capturing reactive oxygen species.

Deficiency

Vitamin A deficiency leads to various health problems. Among visual disorders is the formation of Bitot’s spots, which can progress to severe blindness. Due to epithelial tissue damage, the skin becomes dry and develops a scaly appearance (follicular hyperkeratosis), increasing susceptibility to infections. Weakening of the gastric and intestinal mucosa leads to ulcers and malabsorption. In protein-energy malnutrition conditions, serum levels of A-RBP and prealbumin decrease. Vitamin A deficiency may develop in liver diseases due to reduced prealbumin. Additionally, zinc deficiency reduces the release and utilization of vitamin A from the liver.

Effects of Vitamin A Deficiency on the Body (Generated by Artificial Intelligence.)

Hypervitaminosis A

Excessive intake of vitamin A leads to a syndrome known as hypervitaminosis A. In this condition, cartilage growth at the epiphyseal ends of bones slows, and the epiphyseal plates close prematurely. Due to strong stimulation of osteoclast activity, the entire skeletal system becomes prone to spontaneous fractures. In the nervous system, increased intracranial pressure may mimic symptoms of a brain tumor. Very high doses of vitamin A are teratogenic; therefore, its use is not recommended during the first trimester of pregnancy unless a deficiency is confirmed.

Requirements

Inadequate nutrition, particularly among pregnant women and children, leads to vitamin and mineral deficiencies, increasing disease incidence and mortality rates. Determination of vitamin A requirements is based on the resolution of deficiency symptoms, blood levels, and dietary intake. The average daily vitamin A requirement for adults is 750 micrograms (mcg) of retinol.

^{Recommended Daily Adequate Vitamin A Intake Values (Retinol Equivalent)} (TÜBER, 2022)^【4】

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