Vitamin A

Overview

Vitamin A was the first fat-soluble vitamin to be isolated. It was discovered in 1913 as a result of its ability to prevent night blindness and xerophthalmia (a drying and hardening of the mucous membrane that lines the eyelids). In 1932, beta-carotene (pro-vitamin A) was discovered to be the precursor to vitamin A and it is sometimes referred to as provitamin A. Vitamin A belongs to a class of compounds called retinoids, which only occur in animal products. Retinoids with vitamin A activity occur in nature in three different forms: a) the alcohol, retinol, b) the aldehyde, retinal or retinaldehyde, and c) the acid, retinoic acid. Vitamin A requires fats as well as minerals in order to be properly absorbed from the digestive tract. Substantial amounts of vitamin A are stored in the liver, and therefore, it does not need to be supplied in the diet on a daily basis.

Beta-carotene, which is also called pro-vitamin A, is found exclusively in plant (fruit and vegetable) sources. Beta-carotene consists of two molecules of vitamin A linked head to head (A-A). Enzymes in the intestinal tract split beta-carotene into two molecules of vitamin A whenever the body needs it. (1)

The Nurses' Health Study has evaluated the health over 72,000 postmenopausal women 34 to 77 years old for a variety of reasons. One group of investigators evaluated the relationship between high vitamin A intake from foods and supplements and the risk of hip fracture among 72,337 postmenopausal women. Women in the highest group of vitamin A intake (3000 mcg/day of retinol equivalents [RE]) had a significantly elevated relative risk of a hip fracture compared to women in the group with the lowest intake of vitamin A (

Dosage Info

Dosage Range

2,000-35,000 IU daily. For some conditions, doses greater than 100,000IU daily are used for short periods of time, but high doses such as these should be supervised by a physician.

Most Common Dosage

5,000IU daily.

1mcg vitamin A = 3.33IU vitamin A

1mcg all-trans retinol (dietary)=
1RE (retinol equivalent) =
6mcg of all-trans beta-carotene (dietary)

1mcg retinol =
1RAE (retinol activity equivalents) =
2mcg beta-carotene (supplement) =
12mcg beta-carotene (dietary)

Dosage Forms

Tablets, gel capsules, emulsified liquid drops, micellized liquid drops, and injectable (Rx only).

Adult RDI

5,000 IU

Adult ODA

10,000-35,000 IU

RDA

  • Infants <6 months: 400mcg (Adequate Intake, AI)
  • Infants 7-12 months: 500mcg (AI)
  • Children 1-3 years: 300mcg
  • Children 4-8 years: 400mcg
  • Children 9-13 years: 600mcg
  • Males >14 years: 900mcg
  • Females >14 years: 700mcg
  • Pregnancy 14-18 years: 750mcg
  • Pregnancy >19 years: 770mcg
  • Lactation 14-18 years: 1,200mcg
  • Lactation >19 years: 1,300mcg

Interactions and Depletions

Interactions

Depletions

Active Forms

Retinol acetate, retinol palmitate.

Absorption

Vitamin A and beta-carotene are both hydrophobic, or fat-soluble substances that must be broken down by pancreatic digestive enzymes in the intestine in order to be absorbed. This breaks them down to micelle size, which allows them to be dispersed in the aqueous environment of the small intestine. After being micellized, both vitamin A and beta-carotene diffuse passively into the intestinal mucosal epithelial cells.

Toxicities & Precautions

General

Since vitamin A is fat soluble, excesses can accumulate in fatty tissues to toxic levels. (2)

Signs of vitamin A toxicity include dry itchy skin, brittle nails, hair loss, bone pain, gingivitis, headaches, muscle and joint pains, anorexia, fatigue, diarrhea, increased infections, enlarged liver and abnormal liver function. Symptoms are reversible when vitamin A is discontinued.

Hypervitaminosis A has been reported in adults taking in excess of 50,000 IU daily for several years, and in a case of taking a water soluble synthetic vitamin A at 18,500 to 60,000 IU for several months.

Functions in the Body

Eyes and Vision

Required for night vision. It combines with the protein opsin to form the photosensitive pigments rhodopsin and iodopsin in the rods and cones of the eyes, which are necessary for night vision. It is also essential for the lubricant from tear glands that prevents drying of the cornea.

Epithelial Tissue

Plays an important role in maintaining the integrity of epithelial tissue which are the mucous membrane-secreting cells that line all the glands and organs of the body. Many studies show that adequate intake of vitamin A is associated with reduced risk to various epithelial-cell cancers (mouth, skin, lungs, bladder, breast, stomach, cervix, etc.) (3)

Immune System

Helps maintain healthy epithelial cells (surface cells of many glands, organs, and skin); helps to facilitate effective barriers to infections. (4)

Growth and Bone Development

Essential for the growth of bone and soft tissue. It is also necessary for the formation of tooth enamel in the development of teeth. A deficiency of Vitamin A can contribute to bone loss associated with osteoporosis. (5)

Clinical Applications

Night Blindness

Has been reported to be corrected with supplements or vitamin A-rich foods. (6)

Cervical Dysplasia

Low levels of vitamin A are associated with increased risk. (7)

Measles

Directly associated with the level of vitamin A deficiency. (8) In one study, children with severe measles treated with vitamin A 400,000 IU daily had 80 percent fewer deaths and 50 percent reduction in major complications during hospitalization. (9) Dose should be supervised by a physician.

Menorrhagia

Heavy menstruation improved in 92 percent of women treated with vitamin A 25,000 IU daily for 15 days. (10)

Acne

Doses from 300,000-500,000 IU daily for 3-4 months is effective but side effects occur in some patients and physician monitoring is required. (11)

Aids

Vitamin A deficiency, which is common in HIV-infected patients, results in decreased circulating CD4 cells and increased mortality. (12)

Cancer Prevention

Low levels of vitamin A and beta-carotene are associated with an increased risk of many types of cancer. (13)

Crohn's Disease

Levels are low and patients respond well to vitamin A therapy. (14)

PMS

89 percent of women receiving up to 300,000 IU daily experienced partial to complete relief of symptoms; it is critical to avoid pregnancy on these high doses. (15)

Symptoms and Causes of Deficiency

Vitamin A deficiency can be caused by inadequate dietary intake or metabolic dysfunction that interferes with absorption, storage or transport of the vitamin.

    Deficiency of vitamin A is associated with the development and promotion of epithelial cell cancers in various glands and organs in the body. Vision problems: Night blindness (nyctalopia) is the classic vision problem resulting from vitamin A deficiency. Xerophthalmia (a drying and hardening of the epithelial cell membranes in the eye) can also develop. This condition causes blindness in hundreds of thousands of infants and children yearly world wide, but seldom occurs in the United States. Long term vitamin A deficiency causes a condition known as follicular hyperkeratosis in which the skin becomes dry, scaly, and rough. Small hard bumps develop on the skin because hair follicles plug up with a hard protein called keratin. Vitamin A deficiency in infants and children hinders growth and development. Bone deformities and dental problems often occur.

Dietary Sources

Good food sources of vitamin A include liver, kidney, butter, egg yolk, whole milk and cream, and fortified skim milk. Good food sources of beta-carotene (pro-vitamin A) include yellow and dark leafy green vegetables (carrots, collards, spinach, sweet potatoes, squash) and yellow fruit (apricots, peaches, cantaloupe). Cod liver oil and halibut fish oil contain high levels of vitamin A.

References

  1. View Abstract: Nagao A, et al. Stoichiometric Conversion of All Trans-beta-carotene to Retinal by Pig Intestinal Extract. Arch Biochem Biophys. Apr1996;328(1):57-63.
  2. View Abstract: Russell RM. The vitamin A spectrum: from deficiency to toxicity. Am J Clin Nutr. Apr2000;71(4):878-84.
  3. View Abstract: Basu TK. Vitamin A and Cancer of Epithelial Origin. J Hum Nutr. Feb1979;33(1):24-31.
  4. View Abstract: Hof H. Vitamin A: The ‘Anti-infective’ Vitamin? MMW Munch Med Wochenschr. Nov1976;118(46):1485-88.
  5. View Abstract: Advani S, Wimalawansa SJ. Bones and nutrition: common sense supplementation for osteoporosis. Curr Womens Health Rep. 2003 Jun;3(3):187-92.
  6. View Abstract: Lindeboom GA. Historical Milestones in the Treatment of Night Blindness. Clio Med. 1984;19(1-2):40-49.
  7. View Abstract: Wylie-Rosett JA, et al. Influence of Vitamin A on Cervical Dysplasia and Carcinoma in Situ. Nutr Cancer. 1984;6(1):49-57.
  8. View Abstract: Butler JC, et al. Measles Severity and Serum Retinol (Vitamin A) Concentration among Children in the United States. Pediatrics. Jun1993;91(6):1176-81.
  9. View Abstract: Hussey GD, et al. A Randomized, Controlled Trial of Vitamin A in Children with Severe Measles. N Engl J Med. Jul1990;323(3):160-64.
  10. View Abstract: Lithgow DM, et al. Vitamin A in the Treatment of Menorrhagia. S Afr Med J. Feb1977;51(7):191-93.
  11. View Abstract: Kligman AM, et al. Oral Vitamin A in Acne Vulgaris. Preliminary Report. Int J Dermatol. May1981;20(4):278-85.
  12. View Abstract: Semba RD, et al. Increased Mortality Associated with Vitamin A Deficiency during Human Immunodeficiency Virus Type 1 Infection. Arch Intern Med. Sep1993;153(18):2149-54.
  13. Werbach MR. Nutritional Influences on Illness. Second edition. Tarzana, CA: Third Line Press; 1993:138-40.
  14. Dvorak AM. Vitamin A in Crohn's Disease. Lancet. Jun1980;1(8181):1303-04.
  15. Block E. The Use of Vitamin A in Premenstrual Tension. Acta Obstet Bynecol Scand. 1960;39:586-92.