The term “Vitamin A” actually refers to a number of different but related compounds. The two categories of vitamin A are related to the food source being animal or plant. When from animal foods, we refer to this nutrient as preformed vitamin A. Preformed vitamin A is absorbed as retinol; an active and usable form of vitamin A. In turn, the body can convert retinol into other active forms of vitamin A, including retinal and retinoic acid.1 Food sources include liver, whole milk, and some fortified food products.
When from plant foods such as colorful fruits and vegetables, vitamin A is considered to be a provitamin A carotenoid. In the body these carotenoids can be converted into retinol in the body. Men consume about 26 percent of vitamin A, and 34 percent of vitamin A is consumed by women as provitamin A carotenoids in the United States.2 Beta-carotene, alpha-carotene, and beta-cryptoxanthin are the common provitamin A carotenoids found in plant foods.3 Beta-carotene is the most efficient among these in being converted into retinol.4,5,6,7 Alpha-carotene and beta-cryptoxanthin are only half as efficient as beta-carotene in being converted into retinol.8 It is these provitamin A carotenoids, especially beta-carotene, that serve as powerful and effective antioxidants, protecting us against the damaging effects of free radicals and oxidative damage.
What are the antioxidant effects of beta-carotene?
Research has shown that beta-carotene has antioxidant activities and prevents lipid peroxidation.9 These antioxidant properties have broad-reaching benefits. For example, with higher blood levels of beta-carotene come lower blood levels of C-reactive protein, a marker of inflammation associated with tumor recurrence and arteriosclerotic cardiovascular disease events.10 In fact, its antioxidant effects may help prevent cancer by reducing free radical-induced DNA damage.11,12 Research has also reported a relationship between higher beta-carotene levels and a lower incidence of various cancers. In-vitro studies show that beta-carotene inhibits tumor cell growth,13,14,15 and there is also evidence that beta-carotene and other carotenoids can inhibit breast cancer cell growth. Of course once beta-carotene is converted to vitamin A, many functions are served beyond that of antioxidant.
What does vitamin A do?
Vitamin A plays an important role in vision, bone growth, reproduction, gene expression (i.e., the process by which the information coded in genes (DNA) is converted to proteins and other cellular structures), cell division, and cell differentiation (i.e., the process during which a cell becomes part of the brain, muscle, lungs, blood, or other specialized tissue).16,17,18,20 Vitamin A helps regulate the immune system, which helps prevent or fight off infections by making white blood cells that destroy harmful bacteria and viruses.21,22,23,24,25,26 Vitamin A’s three major functions are worth examining in greater detail: visual system, gene expression and immunity.
Visual system
The retina of the eye contains light-sensitive, rod and cone photoreceptor cells. These cells convert light that enters the eye into nerve impulses to be interpreted by the brain. A form of vitamin A accumulates in the retina,27 and is transported to rod cells to form the visual pigment rhodopsin (aka, visual purple) leading to the generation of a nerve impulse that travels via the optic nerve to the brain’s visual cortex. Consequently, adequate vitamin A is required for the normal functioning of the retina, dim-light vision, and color vision, while inadequate vitamin A may result in impaired dark adaptation (i.e. night blindness) and, in the most severe cases, blindness.28
Gene expression
Various forms of retinoic acid known as isomers (aka, RA isomers) act as hormones to affect gene expression and thereby influence numerous physiological processes. RA isomers and RA are transported to the nucleus of the cell where they bind RA-receptor proteins. This binding of RA isomers and RA allows the complex to regulate the rate of gene transcription, thereby influencing the synthesis of certain proteins, including hormones and other body proteins.
In addition, RA isomers are involved in binding with thyroid hormone receptors or vitamin D receptors. In this way, vitamin A, thyroid hormone, and vitamin D may interact to influence gene transcription.29 Through the stimulation and inhibition of transcription of specific genes, RA plays a major role in cellular differentiation, the specialization of cells for highly specific physiological roles. Many of the physiological effects attributed to vitamin A appear to result from its role in cellular differentiation.
Immunity
Since vitamin A contributes to the process of maintaining normal functioning of the immune system, it is commonly known as the anti-infective vitamin.30 Here’s how it works. The skin and mucosal cells (cells that line the eyes and the respiratory, urinary, and intestinal tract) function as a barrier and form the body’s first line of defense against infection. When those linings break down, it becomes easier for bacteria to enter the body and cause infection. Vitamin A promotes healthy surface linings of the eyes and the respiratory, urinary, and intestinal tracts,31 helping the skin and mucous membranes function as a barrier to bacteria and viruses.32,33,34 In addition vitamin A and RA play a central role in the development and differentiation of white blood cells, such as lymphocytes, which play critical roles in the immune response by fighting infections.35
Who should use it?
Everyone needs vitamin A. In fact, the onset of infection reduces blood retinol levels rapidly. This stimulates a vicious cycle, because inadequate vitamin A nutritional status is related to increased likelihood of infectious disease.
Dosage/Timing
The Daily Value for vitamin A is 5,000 IU. Most multivitamins provide between 5,000 and 10,000 IU of vitamin A, while most vitamin A stand-alone supplements provide 10,000 IU (though some provide as much as 25,000 IU). A reasonable dose is between 5,000 and 10,000 IU. Beta-carotene is a common source of vitamin A in supplements, and many supplements provide a combination of retinol and beta-carotene.37 Particularly in the case of doses exceeding 5,000 IU, having beta-carotene as one of the sources of vitamin A (or the exclusive source) makes sense since beta-carotene will only be converted into vitamin A as the body needs it, so the beta-carotene will not contribute toward potential vitamin A toxicity (more about toxicity below). The best time to take vitamin A is with a meal.
Adverse reactions/interactions
Vitamin A toxicity is caused by over-consumption of preformed vitamin A (i.e., retinol), not provitamin A (i.e., carotenoids). Since preformed vitamin A is rapidly absorbed and slowly cleared from the body, toxicity may result acutely from high-dose exposure over a short period of time or chronically from a much lower intake.38 Although relatively rare, acute vitamin A toxicity is possible and symptoms include nausea, headache, fatigue, loss of appetite, dizziness, dry skin, desquamation (skin peeling), and cerebral edema. In addition, signs of chronic toxicity include dry itchy skin, desquamation, loss of appetite, headache, cerebral edema, and bone and joint pain. Toxicity is most likely to occur with long-term consumption of preformed vitamin A in doses exceeding 25,000 to 33,000 IU/ day. In January 2001, the Food and Nutrition Board (FNB) of the Institute of Medicine set the tolerable upper intake level (UL) of vitamin A intake for adults 10,000 IU/day of preformed vitamin A.39 Retinoids or retinoid analogs, including acitretin, all-trans-retinoic acid, bexarotene, etretinate and isotretinoin (Accutane), should not be used in combination with vitamin A supplements, because they may increase the risk of vitamin A toxicity.40
Pregnancy
Although normal fetal development requires sufficient vitamin A intake, consumption of excess preformed vitamin A (retinol) during pregnancy may cause birth defects. However, there is no known increased risk of vitamin A-associated birth defects with preformed vitamin A from supplements below 10,000 IU/day.41 Since a number of foods in the U.S. are fortified with preformed vitamin A, pregnant women should avoid multivitamin or prenatal supplements that contain more than 1,500 mcg (5,000 IU) of preformed vitamin A. Vitamin A from beta-carotene is not known to increase the risk of birth defects.
References:
- Institute of Medicine. Food and Nutrition Board. Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc. National Academy Press, Washington, DC, 2001.
- Institute of Medicine. Food and Nutrition Board. Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc. National Academy Press, Washington, DC, 2001.
- de Pee S, West CE. Dietary carotenoids and their role in combating vitamin A deficiency: A review of the literature. Eur J Clin Nutr 1996;50 Suppl 3:S38–53.
- Institute of Medicine. Food and Nutrition Board. Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc. National Academy Press, Washington, DC, 2001.
- Olson JA, Kobayashi S. Antioxidants in health and disease: Overview. Proc Soc Exp Biol Med 1992;200:245–7.
- Olson JA. Benefits and liabilities of vitamin A and carotenoids. J Nutr 1996;126:1208S–12S.
- Pavia SA, Russell RM. Beta-carotene and other carotenoids as antioxidants. J Am Coll Nutr 1999;18:426–33.
- Institute of Medicine. Food and Nutrition Board. Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc. National Academy Press, Washington, DC, 2001.
- Omenn GS. Chemoprevention of lung cancer: the rise and demise of beta-carotene. Annu Rev Public Health 1998;19:73–99.
- Erlinger TP, Guallar E, Miller ER, et al. Relationship between systemic markers of inflammation and serum beta-carotene levels. Arch Intern Med 2001;161:1903–8.
- van der Vliet A. Cigarettes, cancer and the carotenoids: a continuing, unresolved antioxidant paradox. Am J Clin Nutr 2000;72:1421–3.
- Green A, Williams G, Neale R, et al. Daily sunscreen applications and beta-carotene supplementation in prevention of basal-cell and squamous-cell carcinomas of the skin: a randomized controlled trial. Lancet 1999;354:723–9.
- van der Vliet A. Cigarettes, cancer and the carotenoids: a continuing, unresolved antioxidant paradox. Am J Clin Nutr 2000;72:1421–3.
- Patrick L. Beta-carotene: the controversy continues. Alt Med Rev 2000;5:530–45.
- Nesaretnam K, Radhakrishnan A, Selvaduray KR, et al. Effect of palm oil carotene on breast cancer tumorigenicity in nude mice. Lipids 2002;37:557–60.
- Institute of Medicine. Food and Nutrition Board. Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc. National Academy Press, Washington, DC, 2001.
- Gerster H. Vitamin A-functions, dietary requirements and safety in humans. Int J Vitam Nutr Res 1997;67:71–90.
- Futoryan T, Gilchrest BE. Retinoids and the skin. Nutr Rev 1994;52:299–310.
- Hinds TS, West WL, Knight EM. Carotenoids and retinoids: A review of research, clinical, and public health applications. J Clin Pharmacol 1997;37:551–8.
- Ross AC, Gardner EM. The function of vitamin A in cellular growth and differentiation, and its roles during pregnancy and lactation. Adv Exp Med Biol 1994;352:187–200.
- Institute of Medicine. Food and Nutrition Board. Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc. National Academy Press, Washington, DC, 2001.
- Ross AC. Vitamin A and retinoids. In: “Modern Nutrition in Health and Disease.” 9th Edition (edited by Shils ME, Olson J, Shike M, Ross AC). Lippincott Williams and Wilkins, New York, 1999, pp. 305–27.
- Ross AC, Stephensen CB. Vitamin A and retinoids in antiviral responses. FASEB J 1996;10:979–85.
- Semba RD. The role of vitamin A and related retinoids in immune function. Nutr Rev 1998;56:S38–48.
- Ross DA. Vitamin A and public health: Challenges for the next decade. Proc Nutr Soc 1998;57:159–65.
- Harbige LS. Nutrition and immunity with emphasis on infection and autoimmune disease. Nutr Health 1996;10:285–312.
- Zhong M, Kawaguchi R, Ter-Stepanian M, Kassai M, Sun H. Vitamin A transport and the transmembrane pore in the cell-surface receptor for plasma retinol binding protein. PLoS One. 2013;8(11):e73838.
- Food and Nutrition Board, Institute of Medicine. Vitamin A. Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc. Washington, D.C.: National Academy Press; 2001:65–126.
- Semba RD. The role of vitamin A and related retinoids in immune function. Nutr Rev. 1998;56(1 Pt 2):S38–48.
- Semba RD. Impact of vitamin A on immunity and infection in developing countries. In: Bendich A, Decklebaum RJ, eds. Preventive Nutrition: The Comprehensive Guide for Health Professionals. 2nd ed. Totowa: Humana Press Inc; 2001:329-346.
- Semba RD. The role of vitamin A and related retinoids in immune function. Nutr Rev. 1998;56(1 Pt 2):S38-48.
- Ross DA. Vitamin A and public health: Challenges for the next decade. Proc Nutr Soc 1998;57:159–65.
- Harbige LS. Nutrition and immunity with emphasis on infection and autoimmune disease. Nutr Health 1996;10:285–312.
- de Pee S, West CE. Dietary carotenoids and their role in combating vitamin A deficiency: A review of the literature. Eur J Clin Nutr 1996;50 Suppl 3:S38–53.
- Semba RD. The role of vitamin A and related retinoids in immune function. Nutr Rev. 1998;56(1 Pt 2):S38–48.
- Thurnham DI, Northrop-Clewes CA. Optimal nutrition: vitamin A and the carotenoids. Nutr Soc. 1999;58(2):449–57.
- Hendler SS, Rorvik DR, eds. PDR for Nutritional Supplements. Montvale: Medical Economics Company, Inc; 2001.
- Ross AC. Vitamin A and retinoids. In: Shils M, Olson JA, Shike M, Ross AC. ed. Modern Nutrition in Health and Disease. 9th ed. Baltimore: Lippincott Williams & Wilkins; 1999:305–27.
- Food and Nutrition Board, Institute of Medicine. Vitamin A. Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc. Washington, D.C.: National Academy Press; 2001:65–126.
- Hendler SS, Rorvik DR, eds. PDR for Nutritional Supplements. Montvale: Medical Economics Company, Inc; 2001.
- Food and Nutrition Board, Institute of Medicine. Vitamin A. Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc. Washington, D.C.: National Academy Press; 2001:65–126.