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Vitamin A

Also indexed as: Retinol (A)

Illustration

Vitamin A is a fat-soluble vitamin with four major functions in the body: (1) It helps cells reproduce normally—a process called differentiation (cells that have not properly differentiated are more likely to undergo pre-cancerous changes). (2) It is required for vision; vitamin A maintains healthy cells in various structures of the eye and is required for the transduction of light into nerve signals in the retina. (3) It is required for normal growth and development of the embryo and fetus, influencing genes that determine the sequential development of organs in embryonic development. (4) It may be required for normal reproductive function, with influences on the function and development of sperm, ovaries and placenta.

Where is it found?

Liver, dairy products, and cod liver oil are good sources of vitamin A. Vitamin A is also available in supplement form.

Vitamin A has been used in connection with the following conditions (refer to the individual health concern for complete information):

Science Ratings Health Concerns
3Stars

Anemia (for deficiency)

Childhood diseases

Cystic fibrosis

Infection

Leukoplakia

Measles (for deficiency)

Night blindness

2Stars

Bronchitis

Celiac disease (for deficiency only)

Heart attack

Immune function

Iron-deficiency anemia (as an adjunct to supplemental iron)

Measles (for severe cases)

Menorrhagia (heavy menstruation)

Peptic ulcer

Retinitis pigmentosa

Sprains and strains (for deficiency only)

Wound healing

1Star

Acne

Alcohol withdrawal support

Conjunctivitis/blepharitis

Crohn’s disease

Diarrhea

Gastritis

Goiter

HIV support

Hypothyroidism

Lung cancer

Pap smear (abnormal)

Pre- and post-surgery health

Premenstrual syndrome (see dosage warnings)

Retinopathy (in combination with selenium, vitamin C and vitamin E)

Sickle cell anemia

Urinary tract infection

Vaginitis

3Stars Reliable and relatively consistent scientific data showing a substantial health benefit.
2Stars Contradictory, insufficient, or preliminary studies suggesting a health benefit or minimal health benefit.
1Star For an herb, supported by traditional use but minimal or no scientific evidence. For a supplement, little scientific support and/or minimal health benefit.

Who is likely to be deficient?

People who limit their consumption of liver, dairy foods, and beta-carotene-containing vegetables can develop a vitamin A deficiency. Extremely low birth weight babies (2.2 pounds or less) are at high risk of being born with a deficiency, and vitamin A shots given to these infants have been reported in double-blind research to reduce the risk of lung disease.1 The earliest deficiency sign is poor night vision. Deficiency symptoms can also include dry skin, increased risk of infections, and metaplasia (a precancerous condition). Severe deficiencies causing blindness are extremely rare in Western societies.

Less severe deficiencies are more likely to occur with a variety of conditions causing malabsorption. A high incidence of vitamin A deficiency in people infected with HIV has also been reported. People with hypothyroidism have an impaired ability to convert beta-carotene to vitamin A.2 3 For this reason, some doctors suggest taking supplemental vitamin A (perhaps 5,000–10,000 IU per day) if they are not consuming adequate amounts in their diet.

Very old people with type 2 diabetes have shown a significant age-related decline in blood levels of vitamin A, irrespective of their dietary intake.4

How much is usually taken?

For most people, up to 25,000 IU (7,500 mcg) of vitamin A per day is considered safe. However, people over age 65 and those with liver disease should probably not supplement with more than 15,000 IU per day, unless supervised by a doctor. In women who could become pregnant, the maximum safe intake is being re-evaluated. However, less than 10,000 IU (3,000 mcg) per day is generally accepted as safe. There is concern that larger intakes could cause birth defects. Whether the average person would benefit from vitamin A supplementation remains unclear.

Are there any side effects or interactions?

Since a 1995 report from the New England Journal of Medicine,5 women who are or could become pregnant have been told by doctors to take less than 10,000 IU (3,000 mcg) per day of vitamin A to avoid the risk of birth defect. A recent report studied several hundred women exposed to 10,000–300,000 IU (median exposure of 50,000 IU) per day.6 Three major malformations occurred in this study, but all could have happened in the absence of vitamin A supplementation. Surprisingly, no congenital malformations happened in any of the 120 infants exposed to maternal intakes of vitamin A that exceeded 50,000 IU per day. In fact, the high-exposure group had a 50% decreased risk for malformations compared with infants not exposed to vitamin A. The authors noted that some previous studies found no link between vitamin A and birth defects, and argued the studies that did find such a link suffered from various weaknesses. A closer look at the recent study reveals a 32% higher than expected risk of birth defects in infants exposed to 10,000–40,000 IU of vitamin A per day, but paradoxically a 37% decreased risk for those exposed to even higher levels. This suggests that both “higher” and “lower” risks may have been due to chance.

Excessive dietary intake of vitamin A has been associated with birth defects in humans in fewer than 20 reported cases over the past 30 years.7 8 Presently, the level at which vitamin A supplementation may cause birth defects is not known, though combined human and animal data suggest that 30,000 IU per day should be considered safe.9 Women who are or who could become pregnant should consult with a doctor before supplementing with more than 10,000 IU per day.

Vitamin A supplements can both help and hurt children. Many people have heard that vitamin A supplements support immune function and prevent infections. This is true under some circumstances. However, vitamin A can also increase the risk of infections, according to the findings of a double-blind trial.10 In a study of African children between six months and five years old, a 44% reduction in the risk of severe diarrhea was seen in those children given four 100,000–200,000 IU applications of vitamin A (the lower amount for those less than a year old) during an eight-month period. On further investigation, the researchers discovered that the reduction in diarrhea occurred only in children who were very malnourished. For children who were not starving, vitamin A supplementation actually increased the risk of diarrhea compared with the placebo group. The vitamin A-supplemented children also had a 67% increased risk of coughing and rapid breathing, signs of further lung infection, although this problem did not appear in children infected with AIDS. These findings should be of concern to American parents, whose children are not usually infected with AIDS or severely malnourished. Such relatively healthy children fared poorly in the African trial in terms of both the risk of diarrhea and the risk of continued lung problems. Vitamin A provided no benefit to the well-nourished kids. Therefore, it makes sense to not give vitamin A supplements to children unless there is a special reason to do so, such as the presence of a condition causing malabsorption (e.g., celiac disease).

In a study of people with retinitis pigmentosa (a degenerative condition of the eye), participants received 15,000 IU of vitamin A per day for 12 years with no signs of adverse effects or toxicity.11 For other adults, intake above 25,000 IU (7,500 mcg) per day can—in rare cases—cause headaches, dry skin, hair loss, fatigue, bone problems, and liver damage.12 At higher levels (for example 100,000 IU per day) these problems become more common.

A controlled clinical trial showed that people who took 25,000 IU of vitamin A per day for a median of 3.8 years had an 11% increase in triglycerides, a 3% increase in total cholesterol and a 1% decrease in HDL cholesterol compared to those who did not take vitamin A.13 Although the significance of these findings is not clear, people at risk for cardiovascular disease should use caution when considering long-term vitamin A supplementation.

One study found that increasing the intake of vitamin A in the diet was associated with bone loss and risk of hip fracture, possibly due to a vitamin A-induced stimulation of cells that break down bone.14 In this study, a vitamin A intake greater than 5,000 IU per day, when compared to a lower intake, was associated with a reduction in bone mineral density that approximately doubles the risk of hip fracture. Beta-carotene (which can be used by the body to make vitamin A) has not been linked to reduced bone mass. Until more is known, people concerned about osteoporosis may consider taking beta-carotene supplements rather than supplementing with vitamin A.

Data from test tube, animal, and human studies show that excessive vitamin A intake can accelerate bone loss and inhibit formation of new bone, increasing the risk of osteoporosis.15 In humans, small studies have found these effects at about 85,000–125,000 IU per day. 16 17

Taking vitamin A and iron together helps overcome iron deficiency more effectively than iron supplementation alone.18 Supplementation with zinc, iron, or the combination has been found to improve vitamin A status among children at high risk for deficiency of the three nutrients.19

Are there any drug interactions?
Certain medicines may interact with vitamin A. Refer to drug interactions for a list of those medicines.

References:

1. Tyson JE, Wright LL, Oh W, et al. Vitamin A supplementation for extremely-low-birth-weight infants. N Engl J Med 1999;340:1962–8.

2. Smolle J, Wawschinek O, Hayn H, Eber O. Vitamin A and carotene in thyroid disease. Acta Med Austriaca 1983;10:71–3 [in German].

3. Aktuna D, Buchinger W, Langsteger W, et al. Beta-carotene, vitamin A and carrier proteins in thyroid diseases. Acta Med Austriaca 1993;20:17–20 [in German].

4. Polidori MC, Mecocci P, Stahl W, et al. Plasma levels of lipophilic antioxidants in very old patients with type 2 diabetes. Diabetes Metab Res Rev 2000;16:15–9.

5. Rothman KJ, Moore LL, Singer MR, et al. Teratogenicity of high vitamin A intake. N Engl J Med 1995;333:1369–73.

6. Mastroiacovo P, Mazzone T, Addis A, et al. High vitamin A intake in early pregnancy and major malformations: a multicenter prospective controlled study. Teratology 1999;59:7–11.

7. Biesalski HK. Comparative assessment of the toxicology of vitamin A and retinoids in man. Toxicology 1989;57:117–61.

8. Azais-Braesco V, Pascal G. Vitamin A in pregnancy: requirements and safety limits. Am J Clin Nutr 2000;71(5 Suppl):1325S–33S [review].

9. Wiegand UW, Hartmann S, Hummler H. Safety of vitamin A: recent results. Int J Vitam Nutr Res 1998;68:411–6 [review].

10. Fawzi WW, Mbise R, Spiegelman D, et al. Vitamin A supplements and diarrheal and respiratory tract infections among children in Dar es Salaam, Tanzania. J Pediatr 2000;137:660–7.

11. Sibulesky L, Hayes KC, Pronczuk A, et al. Safety of <7500 RE (<25000 IU) vitamin A daily in adults with retinitis pigmentosa. Am J Clin Nutr 1999;69:656–63.

12. Bendich A, Langseth L. Safety of vitamin A. Am J Clin Nutr 1989;49:358–71.

13. Cartmel B, Moon TE, Levine N. Effects of long-term intake of retinol on selected clinical and laboratory indexes. Am J Clin Nutr 1999;69:937–43.

14. Melhus H, Michaelsson K, Kindmark A, et al. Excessive dietary intake of vitamin A is associated with reduced bone mineral density and increased risk for hip fracture. Ann Int Med 1998;129:770–8.

15. Binkley N, Krueger D. Hypervitaminosis A and bone. Nutr Rev 2000;58:138–44 [review].

16. Frame B, Jackson CE, Reynolds WA, Umphrey JE. Hypercalcemia and skeletal effects in chronic hypervitaminosis A. Ann Intern Med 1974;80:44–8.

17. Patel P, Hanning RM, Atkinson SA, et al. Intoxication from vitamin A in an asthmatic child. CMAJ 1988;139:755–6.

18. Mejia LA, Chew F. Hematological effect of supplementing anemic children with vitamin A alone and in combination with iron. Am J Clin Nutr 1988;48:595–600.

19. Muñoz EC, Rosado JL, Lopez P, et al. Iron and zinc supplementation improves indicators of vitamin A status of Mexican preschoolers. Am J Clin Nutr 2000;71:789–94.

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