Vitamin A

 

Vitamin A

Vitamin A is the name given to a group of compounds which have certain actions in the body. One of these compounds is called retinol and it is used as a standard against which the activity of other compounds can be measured. While the vitamin A we obtain from food comes in many different forms, these can be divided into two main types - pre-formed vitamin A and provitamin A. Pre-formed vitamin A which is often in the form of retinol or retinal, is found in foods of animal origin such as liver and butter. Provitamin A is the name given to around 50 compounds in a group of plant pigments known as carotenes (or carotenoids), with beta carotene being the best known of these. This is because these compounds can be turned into vitamin A in the body. Both pre-formed vitamin A and provitamin A are fat soluble.

What it does in the body

Vitamin A is essential, either directly or indirectly, for the function of all the organs in your body and is particularly important for growth and development. Despite the fact that vitamin A was the first vitamin to be discovered, its actions in the cells of our bodies are not well understood at a chemical level.

Maintenance of normal vision

Our eyes need vitamin A to function effectively as vitamin A is involved in the production of a chemical called visual purple, which helps us to see in dim light.

Growth, repair and cell differentiation

Vitamin A is necessary for the growth and repair of many body cells including those of bones, teeth, collagen and cartilage. It is also essential for a process known as cell differentiation in which unspecialized cells are modified so that they can perform specific functions. Thus vitamin A plays a central role in tissue development and maintenance.

Health of epithelial cells

Vitamin A is vital for the formation of healthy epithelial cells. These cells cover the internal and external surfaces of the body and are found in the skin, lungs, developing teeth, inner ear, cornea of the eye, sex organs, glands and their ducts, gums, nose, cervix and other areas. Many epithelial cells produce mucus which is necessary to lubricate body surfaces and protect against invading micro-organisms. For example, the good health of the digestive tract lining is important in protecting against ulcers, and maintenance of the lining of the vagina and uterus is important in fertility.

Pregnancy and fetal development

Because of its vital role in cell development and differentiation, adequate vitamin A helps to ensure that the changes which occur in the cells and tissues during fetal development take place normally. It may be involved in cell to cell communication.

Protection against infection

Known as 'the anti-infective vitamin', vitamin A plays an essential role in protecting your body from infection. It keeps body surfaces healthy so they can act as barriers to invading micro-organisms. Vitamin A stimulates and enhances many immune functions including antibody response and the activity of various white blood cells such as T helper cells and phagocytes. This immune-enhancing function promotes healing of infected tissues and increases resistance to infection.

Other actions

Laboratory experiments have shown vitamin A to have antiviral activity. Vitamin A also has antioxidant activity and has a role in protecting against free radical damage which contributes to many common diseases.  Vitamin A is involved in iron metabolism and storage.

Absorption and metabolism

The presence of fat and bile in the intestines is necessary for vitamin A absorption. Around 80 to 90 per cent of vitamin A in the diet is absorbed, although this is reduced in older people and those who have trouble absorbing fat, such as pancreatitis, celiac disease and cystic fibrosis sufferers, who may run the risk of vitamin A deficiency.

Vitamin A is joined to fatty acids in the intestinal lining, combined with other substances and transported to the liver, which stores 90 per cent of the body's vitamin A.

Deficiency

The World Health Organization estimates that as many as 250 million children worldwide are threatened by vitamin A deficiency. However, it is relatively rare in developed countries and is usually limited to those who have absorption difficulties, liver disease or who drink a lot of alcohol. Vitamin A deficiency is common in alcoholics and contributes to some of the disorders of alcoholism such as night blindness, skin problems, cirrhosis of the liver and susceptibility to infections.

Eyes

One of the first symptoms of deficiency is night blindness due to lack of visual purple. Prolonged deficiency leads to xerophthalmia, a condition in which eyes become dry, ulcers appear on the cornea, the eyelids become swollen and sticky, and which eventually leads to blindness. Vitamin A deficiency is the leading preventable cause of blindness in developing countries.

Skin

Prolonged deficiency leads to thickened dry skin which is prone to infections. Small hardened bumps of a protein known as keratin may develop around the hair follicles.

Growth

Deficiency causes growth retardation; weight loss; diarrhea, thickening of bone shafts; congenital malformations; impaired hearing, taste and smell; wasting of testicles; and reduced sperm count. Inadequate vitamin A intake can lead to improper tooth formation in children and to gum disease.

Immune system

Epithelial surfaces are adversely affected by vitamin A deficiency, causing increased susceptibility to skin and respiratory infections. Immune cells and antibody functions are also affected which may lead to an increase in pre-cancerous cells in the epithelial tissues of the mouth, throat and lungs.

Many studies have shown that vitamin A deficiency is associated with increased risk of infection in developing countries. This may also be the case in developed countries. A 1992 study involving 20 children with measles in Long Beach, California found that half of them were vitamin A deficient.1

Vitamin A deficiency is often seen in HIV-positive people and this may be due to metabolic changes associated with HIV infection. A 1995 study done on HIV-infected drug users in the US found that there was a higher risk of death in those with vitamin A deficiency. Vitamin A deficiency is often seen in HIV-positive pregnant women and severe deficiency increases infant mortality and the risk of mother-to-child transmission of HIV.

Thyroid gland

A deficiency of vitamin A can contribute to lower levels of active thyroid hormone with symptoms of low body temperature, depression, difficulty with weight loss, headaches and lethargy.

Cancer

Several population studies suggest links between low vitamin A intakes and various types of cancer, particularly those of the lungs, head and neck. Vitamin A deficiency may also increase the risk of breast cancer. In a study published in 1997, researchers at Harvard School of Public Health compared the concentrations of various forms of vitamin A in the breast fat tissue from 46 cancer patients and 63 women with benign breast lumps. They found an increased risk of disease in those with low levels of vitamin A.2

Other disorders

Low blood levels of vitamin A may be associated with the development of heart disease. Researchers involved in a 1997 study done in Madrid, Spain looked at vitamin A levels in 62 heart attack patients and compared these with levels in 62 people free of heart disease. The results showed that vitamin A levels in heart attack patients were almost 25 per cent lower.3 Vitamin A levels have also been found to be low in rheumatoid arthritis and systemic lupus erythematosus sufferers. Vitamin A metabolism may be altered in diabetics.

Sources

Pre-formed vitamin A occurs in foods of animal origin such as cod liver oil, beef liver, some seafood, butter, whole milk and egg yolks. It is sometimes added to milk.

Liver, fried 100g 10729 mcg RE

Cod liver oil 1 tbsp 4080 mcg RE

Liverwurst 28g 2353 mcg RE

Carrot, raw, peeled ½ cup, slices 1715 mcg RE

Squash 1 cup 1435 mcg RE

Kale, boiled 1 cup 962 mcg RE

Mangoes, raw, peeled 1 fruit 805 mcg RE

Vegetable soup, canned 1 cup 588 mcg RE

Cantaloupe melon, raw, peeled 1 cup, diced 502 mcg RE

Apricots, canned in syrup 1 cup 412 mcg RE

Mixed vegetables, frozen, boiled ½ cup 389 mcg RE

 

Recommended dietary allowances

Vitamin A is the name for a group of compounds which have the biological activity of retinol. Vitamin A is measured in retinol equivalents (RE) which allows the different forms of vitamin A to be compared. One retinol equivalent equals 1 mcg of retinol or 6 mcg of beta carotene. Vitamin A is also measured in international units (IU) with 1 mcg RE equivalent to 3.33 IU.

 

Supplements

Cod liver oil is a rich source of vitamin A and is sometimes used to make supplements. Vitamin A palmitate and vitamin A acetate are synthetic forms of vitamin A found in supplements and fortified foods. Vitamin A palmitate can be absorbed in the absence of dietary fat.

Low dose supplementary vitamin A may be beneficial in the elderly and in those who cannot absorb fats. Vitamin A needs may be increased in cases of trauma, anxiety, stress, alcohol use and smoking.

Toxic effects of excess intake

As vitamin A is fat soluble and can be stored in the liver for long periods of time, it has a high potential for toxicity. The first sign of vitamin A overdose is usually headache, followed by chapped lips, dry skin, fatigue, emotional instability and bone and joint pain. There may also be hair loss, vertigo, vision problems, poor appetite, loss of weight, vomiting, liver damage and amenorrhea (cessation of menstrual periods). Individual tolerance to vitamin A varies widely and these effects can occur at doses over 7500 mcg RE (25 000 IU) although in most adults signs of toxicity occur with single doses over 75 000 mcg RE (250 000 IU) or smaller doses of 15 000 mcg RE (50 000 IU) taken for long periods. It is recommended that regular daily intake of vitamin A does not exceed 7500 mcg RE (25 000 IU) for adults and 3000 mcg RE (10 000 IU) in children.

Pregnant women who take above 3000 mcg RE (10 000 IU) per day have a greater chance of giving birth to malformed babies. Vitamin A acne cream has been known to cause birth deformities and is now available only on prescription.

In a study published in 1995, researchers at Boston University School of Medicine assessed the links between vitamin A from food and supplements in 22,748 women who were pregnant between October 1984 and June 1987. Women who consumed more than 4500 mcg RE (15,000 IU) of pre-formed vitamin A per day from food and supplements were over three times more likely to have a baby with a birth defect than women who consumed 1500 mcg RE (5000 IU) or less per day. For vitamin A from supplements alone, women who consumed more than 3000 mcg RE (10 000 IU) per day had almost five times the risk of birth defects than women who consumed less than 1500 mcg RE (5000 IU) per day. The increased frequency of defects was concentrated among the babies born to women who had consumed high levels of vitamin A before the seventh week of pregnancy. The researchers estimated that among the babies born to women who took more than 3000 mcg RE (10,000 IU) of pre-formed vitamin A per day in the form of supplements, about one infant in 57 had a malformation attributable to the supplement.4

However, a 1997 study conducted by researchers at the National Institute of Child Health and Human Development did not find a link between vitamin A consumption and birth defects. Their results showed that the proportion of women consuming doses of vitamin A between 2400 mcg RE (8000 IU) and 7500 mcg RE (25,000 IU) was no higher in those with birth defects than in the normal control group.5

Overdose is reasonably common with as many as 5 per cent of people taking vitamin A suffering from the toxicity symptoms. Stopping the large doses usually reverses the symptoms with no lasting damage, although in children damage can be permanent.

Therapeutic uses of supplements

The main use of vitamin A supplements the prevention and treatment of deficiency. They are often used in developing countries to protect against or treat measles and other viral infections.

Immunity

Adequate vitamin A intake, either from diet or supplements, is very important in boosting immunity and preventing sickness and death in children. Many studies have found that vitamin A supplementation reduces the risk of infectious diseases in areas where vitamin A deficiency is widespread. A recent research review analyzing the results of several studies found that adequate vitamin A intake in children resulted in a 30 per cent decrease in deaths from all causes. Children in developing countries are often at high risk of vitamin A deficiency. In developed countries, ensuring adequate vitamin A intake is particularly important in those with life threatening infections such as measles and in those at risk of relative deficiency, such as premature infants.6

In a 1995 double-blind, randomized trial done in South Africa, vitamin A supplements were shown to reduce sickness rates in children born to HIV-infected women. The patients in this study were not in a population at high risk for vitamin A deficiency and the effect was particularly noticeable in those children who were HIV-positive.7

Cancer

Many studies suggest that high blood levels of vitamin A can help prevent certain forms of cancer, particularly cancers of epithelial tissue. This may be due to the importance of vitamin A in maintaining healthy epithelial cells, strengthening the immune system and stimulating the response to abnormal cells.

A 1993 Italian study tested the effects of vitamin A on cancer recurrence in smokers who had undergone surgery for lung cancer. The 307 patients took daily doses of 90 000 mcg RE (300 000 IU) for one year. After a follow-up period of 46 months, the number of patients with either recurrence or new tumors was 56 (37 per cent) in the vitamin A group and 75 (48 per cent) in the control group. Eighteen patients in the treated group developed a second primary tumor, and 29 patients in the control group developed 33 second primary tumors.8

Results from the recent large scale Beta Carotene and Retinol Efficacy Trial (CARET) involving a total of 18 314 smokers, former smokers, and workers exposed to asbestos failed to show any benefit of vitamin A supplementation on lung cancer. This may be due to the adverse effects of cigarette smoke on beta carotene. 

In a 1998 study done in Western Australia, 1024 blue asbestos workers known to be at high risk of diseases such as mesothelioma and lung cancer, were enrolled in a cancer prevention program using vitamin A. Half the subjects were given 30 mg per day of beta carotene and the other half 7500 mcg (25,000 IU) of retinol. The workers were followed up from the start of the study in June 1990 until May 1995. Four cases of lung cancer and three cases of mesothelioma were observed in those in the vitamin A group, and six cases of lung cancer and 12 cases of mesothelioma in the beta carotene group. In the retinol group, there was also a significantly lower rate of death from all causes.9 When the researchers compared these results with those workers who had not taken part in the study they found that those taking part in the study had significantly lower death rates than non-participants.10

Vitamin A has also been shown to exert protective effects against leukoplakia, a pre-cancerous change in mucous membranes. It often occurs in the mouth and throat and is related to smoking. In a study done in 1997 researchers tested the effects of the retinyl palmitate form of vitamin A on leukoplakia of the larynx. The treatment period was five weeks and the doses used ranged from 90 000 mcg RE per day (300 000 IU) to 270 000 mcg (1 500 000 IU) per day. Complete remission was observed in 15 out of 20 patients and partial response was seen in the remaining five patients.11

Results of a US study reported in the Journal of the National Cancer Institute in 1997 suggest that the development of lung cancer may be due to a decreased ability of cells to respond to vitamin A-related compounds known as retinoids. When researchers at the University of Texas looked at the lung tissue from 79 patients with lung cancer and 17 without lung cancer they found that all the healthy cells carried receptors that bound retinoids. However, only 42 to 76 per cent of the cancerous cells had this ability. Of the six different types of retinoid receptors, three were found at lower levels in cancer cells.12 Retinoids play an important role in the growth and differentiation of cells. This study raises the possibility that increasing dietary intake of vitamin A or taking supplements can be used to reduce the risk of lung cancer.

Lung function

Vitamin A supplements may be useful in treating chronic obstructive pulmonary disease. Researchers involved in a Brazilian study published in 1996 examined vitamin A levels in healthy non-smokers, healthy smokers, those with mild chronic obstructive pulmonary disease, and those with more severe symptoms. Patients in the last group had low vitamin A levels. Supplements of 1000 mcg RE (3330 IU) per day improved lung function.13

In a study reported in Nature Medicine in 1997, researchers at Georgetown University in Washington investigating the treatment of emphysema in rats found that the retinoic acid form of vitamin A reversed the lung abnormalities seen in the disease. The researchers induced emphysema in the rats and then gave them injections of retinoic acid for 12 days. The condition of the lungs improved almost to pre-disease levels.14

Skin disorders

Because of its important role in the formation of healthy skin, vitamin A is used to treat skin disorders including rashes, ulcers and wounds.

Acne

Vitamin A may have some benefit in the treatment of acne although most of the studies that support the effectiveness of vitamin A have involved the use of very large doses. Synthetic vitamin A derivative drugs known as retinoids are used to treat cases of severe acne which have not responded to other treatment or which have only shown partial response to antibiotic therapy. These drugs, including tretinoin, isotretinoin and etretinate are prescription medications which are used under the supervision of a doctor. Side effects are relatively common and are similar to the symptoms of vitamin A toxicity. These drugs can cause birth defects if taken during pregnancy and should also be avoided by breastfeeding women. A 1995 study by National Cancer Institute researchers suggests that long-term therapy with etretinate may increase the risk of osteoporosis.15

Psoriasis

Vitamin A derivative drugs are also used to treat psoriasis, particularly pustular psoriasis. These drugs help to normalize skin development by reducing the increased growth, turnover and keratinization of skin which occurs in the disorder. Similar cautions apply to the use of these drugs in the treatment of psoriasis.

Skin aging

According to a 1997 report in the New England Journal of Medicine, creams that contain the vitamin A derivative tretinoin, may help to combat premature skin aging. Researchers studied the activity of enzymes known as metalloproteinases which break down collagen and found that exposure to ultraviolet light increased the activity of these enzymes. Even a small amount of ultraviolet light, although not sufficient to cause redness, was enough to increase enzyme activity. This suggests that exposure to a few minutes of sunlight periodically over several years may lead to premature skin aging.

This increase in enzyme activity was blocked by treatment with tretinoin before radiation. The researchers conclude that tretinoin may be useful in treating patients with signs of premature skin aging but note that careful monitoring of tretinoin use is essential as over-treatment can cause irritation and reddening of skin. The results of this study may lead to the development of new sunscreens and anti-aging creams containing vitamin A derivatives.16

Other uses

Vitamin A eye drops have been used to treat eye problems including blurred vision, cataracts, glaucoma, conjunctivitis and dry eyes. Other disorders for which vitamin A has been tried include asthma, sebaceous cysts, fibrocystic breast disease and premenstrual syndrome.

Vitamin A may also be useful in the prevention of ulcers. In a study involving almost 48 000 men reported in 1997 in the American Journal of Epidemiology researchers found a lower risk of ulcer in those with high intakes of vitamin A, either from food or supplements.17

Interactions with other nutrients

Vitamin E plays a role in the absorption, storage and utilization of vitamin A and protects it from oxidation. Vitamin E may protect against some of the effects of excess vitamin A.

Vitamin A is necessary for calcium metabolism and is also necessary for the absorption, metabolism and storage of iron. Vitamin A deficiency lowers blood levels of hemoglobin. When iron supplements are given it is important to ensure that vitamin A levels are high enough to protect against the exacerbation of bacterial activity that iron may cause.18 With zinc deficiency, levels of vitamin A in the liver rise and blood levels fall.

Interactions with drugs

Vitamin A absorption is reduced by mineral oil laxatives. Antacids; the anti-gout drug, colchicine; and the cholesterol-reducing drug, cholestyramine also inhibit vitamin A absorption. Broad spectrum antibiotics should not be taken with high doses of vitamin A.

Alcohol irritates the digestive tract and inhibits the absorption of vitamin A. It also depletes the body's tissue stores.

Cautions

Vitamin A supplements in doses of more than 3000 mcg RE (10 000 IU) should not be taken by women who may become pregnant.

Vitamin A supplements should not be taken with vitamin A derivative drugs or by anyone with impaired liver or kidney function. If vitamin A supplements are taken with large amounts of alcohol, liver damage may occur.

1 Arrieta AC; Zaleska M; Stutman HR; Marks MI. Vitamin A levels in children with measles in Long Beach, California. J Pediatr, 1992 Jul, 121:1, 75-8

2 Zhang S; Tang G; Russell RM; Mayzel KA; Stampfer MJ; Willett WC; Hunter DJ. Measurement of retinoids and carotenoids in breast adipose tissue and a comparison of concentrations in breast cancer cases and control subjects. Am J Clin Nutr, 1997 Sep, 66:3, 626-32

3 Ruiz Rejón F; Martín Pena G; López Manglano C; Seijas Martínez V; Ruiz Galiana J. Plasma levels of vitamins A and E and the risk of acute myocardial infarct. Rev Clin Esp, 1997 Jun, 197:6, 411-6

4 Rothman KJ; Moore LL; Singer MR; Nguyen US; Mannino S; Milunsky A Teratogenicity of high vitamin A intake. N Engl J Med, 1995 Nov, 333:21, 1369-73

5 Mills JL; Simpson JL; Cunningham GC; Conley MR; Rhoads GG. Vitamin A and birth defects. Am J Obstet Gynecol, 1997 Jul, 177:1, 31-6

6 Glasziou P, Mackerras D. Vitamin A supplementation in infectious diseases. Br Med J. 1993;306: 366-370

7 Coutsoudis A et al. The effects of vitamin A supplementation on the morbidity of children born to HIV-infected women. Am J Public Health, 85: 8 Pt 1, 1995 Aug, 1076-81

8 Pastorino U; Infante M; Maioli M; Chiesa G; Buyse M; Firket P; Rosmentz N; Clerici M; Soresi E; Valente M; et al Adjuvant treatment of stage I lung cancer with high-dose vitamin A. J Clin Oncol, 1993 Jul, 11:7, 1216-22

9 de Klerk NH; Musk AW; Ambrosini GL; Eccles JL; Hansen J; Olsen N; Watts VL; Lund HG; Pang SC; Beilby J; Hobbs MS. Vitamin A and cancer prevention II: comparison of the effects of retinol and beta-carotene. Int J Cancer, 1998 Jan, 75:3, 362-7

10 Musk AW; de Klerk NH; Ambrosini GL; Eccles JL; Hansen J; Olsen NJ; Watts VL; Lund HG; Pang SC; Beilby J; Hobbs MS. Vitamin A and cancer prevention I: observations in workers previously exposed to asbestos at Wittenoom, Western Australia. Int J Cancer, 1998 Jan, 75:3, 355-61

11 Issing WJ; Struck R; Naumann A. Positive impact of retinyl palmitate in leukoplakia of the larynx. Eur Arch Otorhinolaryngol Suppl, 1997, 1:, S105-9

12 Xu XC; Sozzi G; Lee JS; Lee JJ; Pastorino U; Pilotti S; Kurie JM; Hong WK; Lotan R. Suppression of retinoic acid receptor beta in non-small-cell lung cancer in vivo: implications for lung cancer development. J Natl Cancer Inst, 1997 May, 89:9, 624-9

13 Paiva SA; Godoy I; Vannucchi H; Fávaro RM; Geraldo RR; Campana AO Assessment of vitamin A status in chronic obstructive pulmonary disease patients and healthy smokers. Am J Clin Nutr, 1996 Dec, 64:6, 928-34

14 Massaro GD; Massaro D. Retinoic acid treatment abrogates elastase-induced pulmonary emphysema in rats. Nat Med, 1997 Jun, 3:6, 675-7

15 DiGiovanna JJ; Sollitto RB; Abangan DL; Steinberg SM; Reynolds JC. Osteoporosis is a toxic effect of long-term etretinate therapy. Arch Dermatol, 1995 Nov, 131:11, 1263-7

16 Fisher GJ; Wang ZQ; Datta SC; Varani J; Kang S; Voorhees JJ. Pathophysiology of premature skin aging induced by ultraviolet light. N Engl J Med, 1997 Nov, 337:20, 1419-28

17 Aldoori WH; Giovannucci EL; Stampfer MJ; Rimm EB; Wing AL; Willett WC. Prospective study of diet and the risk of duodenal ulcer in men. Am J Epidemiol, 1997 Jan, 145:1, 42-50

18 Ribaya-Mercado JD Importance of adequate vitamin A status during iron supplementation. Nutr Rev, 1997 Aug, 55:8, 306-7