Vitamin A is a micronutrient which is present in some food and is necessary for normal human function. It is present at relatively high levels in most Western diets and can be stored in the liver and intestines for long periods, making vitamin A deficiency rare.

Several studies have shown that vitamin A plays an important role in the immune system. Animal studies have shown that a shortage of vitamin A can cause immune problems and disease, and in areas where vitamin A deficiency is more common, such as parts of India, providing supplements of vitamin A has been shown to decrease childhood mortality from infectious disease.

Studies have suggested that some people with HIV have vitamin A deficiency and that this may be associated with lower CD4 cell counts and an increased risk of mortality. Vitamin A deficiency may be a secondary consequence of malnutrition in people with HIV or could be a consequence of HIV infection itself, since infection and fever are known to cause depletion of the vitamin. In test tube studies, vitamin A increases HIV replication in some cell types and decreases replication in others.

Vitamin A is sometimes referred to as retinoic acid, a substance into which it is converted in the body.

Taking it

Vitamin A is naturally present at high levels in meat and liver, tomatoes, apricots, sweet potatoes, broccoli, kale, spinach, red peppers, carrots and lettuce. It can also be purchased as a supplement from health food shops. This supplement is toxic in doses above 25,000IU per day if taken for more than a few weeks. Signs of toxicity include headaches, nausea, blurred vision, sores on the skin and in more serious cases, internal bleeding, spontaneous fractures and bone malformations.

The safest way to supplement vitamin A intake is by taking beta-carotene. This is a substance which is converted into an active form of vitamin A in the body when it is needed, thus preventing overdosing. A study in HIV-negative people suggested that beta-carotene is best absorbed when split into three doses during the day and taken with fatty food. In individuals who have problems absorbing fat, it is possible to take vitamin A in a water soluble form. Individuals with hypothyroidism, liver dysfunction or diabetes cannot convert beta-carotene into vitamin A.

Beta-carotene is usually taken with 'rest periods', such as taking it for 20 days out of every 30. The rest period is assumed to be necessary to avoid the gradual lessening of the immunomodulatory effects of the vitamin.

Doses of vitamin E is excess of 600IU per day have been observed to interfere with beta-carotene absorption and utilisation.

Current use

It is unclear whether taking supplements of vitamin A can reverse deficiency or improve the clinical outcome of people with HIV.

Vitamin A, taken in the form of beta-carotene, was shown to improve symptoms and stabilise CD4 cell counts in a small two-year study conducted amongst HIV-positive people in Italy. However, two other trials comparing high dose beta-carotene supplements to placebo found no evidence of any beneficial effects on immunologic or virologic measurements. For example, in one study 21 people took a high dose of 180mg beta-carotene per day, with no immunological or virological changes after 4 weeks. Furthermore, people with low baseline vitamin A blood levels were no more likely to have significant changes than people with normal baseline vitamin A levels.

Several studies have explored whether vitamin A supplementation in pregnant HIV-infected women reduces the risk of mother-to-infant HIV transmission. One study has suggested that HIV-positive pregnant women in Africa who have vitamin A deficiency may be more likely to transmit HIV to their children. However, low vitamin A levels did not predict HIV mother-to-infant transmission in American women, suggesting that vitamin A may not be a significant factor in industrialised countries. Moreover, taking too much vitamin A during pregnancy increases the risk that the child will have birth defects. More recently, a large randomised study of pregnant women in Tanzania found that vitamin A supplementation was associated with an increased risk of HIV transmission. In contrast, multivitamin supplements did improve the health of the babies, reducing rates of diarrhoea and boosting CD4 and CD8 cell counts (Fawzi 2003; Villamor 2003).

Furthermore, two randomised studies of HIV-infected women in Kenya and Tanzania found that vitamin A supplementation had no impact on viral load in vaginal secretions, or on viral load and CD4 cell counts in the blood, HIV progression or the risk of sexual transmission (Baeten 2003; Fawzi 2004). A similar study also showed no decrease in herpes simplex virus-2 (HSV2) shedding with vitamin A supplementation (Baeten 2004).

In HIV-negative people at risk of developing oral cancer, beta-carotene supplementation has been shown to reduce the size of pre-cancerous leucoplakia lesions.

The only side-effect of high doses of beta-carotene is the acquisition of orange skin tone. When this happens it means that fatty tissues are saturated with the vitamin.

Drug interactions and side-effects

Overlapping metabolic pathways mean that heavy use of alcohol and other drugs may interfere with vitamin A absorption. Furthermore, taking vitamin A supplement in the presence of alcohol and smoking increases a person's chances of liver damage, liver cancer and pulmonary cancer (Leo 1999).

Key research

Baeten (2004) recruited 376 HIV-positive women to a randomised, double blind, placebo-controlled study of vitamin A supplementation (10,000IU per day) on HSV2 shedding. After 6 weeks, there was no difference in genital shedding of HSV2 (40% supplementation vs. 44% placebo; p = 0.5), nor in the number of women with genital ulceration (20 vs. 19; p = 1.0). The same effect was found in women with CD4 cell counts >200 cells/mm³.

Baeten (2003) enrolled 400 HIV-infected into a study of vitamin a supplementation. There was no significant difference in the prevalence of HIV DNA (18% vs 21%, p = 0.4) or the amount of HIV RNA (3.12 vs 3.00 log copies/swab, p = 1.0) in vaginal secretions of women receiving vitamin A compared to women receiving placebo. Supplementation had no effect on plasma HIV viral load or CD4 counts. Low vitamin A levels were associated with more active HIV infection rather than true deficiency.

Villamor (2003) randomised 1075 pregnant, HIV-positive women from Dar es Salaam, Tanzania, to 1 of 4 regimens: multivitamins (thiamine, riboflavin, niacin, folic acid, and vitamins B-6, B-12, C, and E), vitamin A, multivitamins including vitamin A, or placebo. Women who received multivitamins were less likely to experience low weight gain during the third trimester compared with women on placebo. A multivitamin plus vitamin A provided further protection.

Fawzi (2003) presented further data from the Tanzanian study (Villamor above). Higher rates of HIV infection occurred in babies whose mothers were given vitamin A, so the vitamin A supplementation was discontinued. Infants were subsequently directly given vitamin A supplements. Multivitamin supplementation continued during lactation and was associated with lower rates of diarrhoea and higher CD4 levels in the infants. Maternal vitamin A supplementation was associated with a lower risk of pneumonia in the infant.

Semba (1995) reported that in a cohort of HIV-positive intravenous drug users, 50 who died were matched with 235 controls who survived. Vitamin A deficiency occurred in 50% at the last visit before they died. CD4 cell count below 200, wasting and vitamin A deficiency were associated with mortality. Karter, Ward and Beach independently reported similar evidence of vitamin A deficiency among HIV-infected people.

Semba (1994) reported that mean vitamin A concentration in 74 women in Malawi who transmitted HIV to their children was significantly lower than that in 264 women who did not transmit HIV to their children. However, Burger reported no association between vitamin A levels and mother-to-child HIV transmission in the USA.

Semba (1998) randomized 120 HIV-infected injecting drug users to receive high-dose vitamin A (60mg retinol equivalent; 200,000 IU) or placebo. Supplementation had no significant impact on HIV viral load or CD4 lymphocyte count at 2 and 4 weeks after treatment.

Bianchi-Santamaria enrolled 64 HIV-positive ex-drug users with ARC or lymphadenopathy who were resident in a drug rehabilitation unit in a study of beta-carotene (60 mg day for 20 out of every 30 days). 11 completed 24-36 months of treatment. A reduction in symptoms such as night sweats, fever, weight loss and diarrhoea was observed soon after the first 20 days of supplementation. During extended follow-up there was an average CD4 count increase of 11.5% in 9/11, none of whom developed further symptoms.

Coodley conducted a placebo-controlled study of beta-carotene (180 mg/day) in 72 people with HIV, half of whom had a CD4 count below 200 and some of whom were also receiving AZT. Participants also received a multivitamin supplement over the 3-month study period. No effects on T-cell subsets, natural killer cells, HIV p24 antigen or other factors were seen at baseline or after 1 or 3 months of treatment.

Garewal treated 11 HIV-positive men with CD4 counts above 200 with beta-carotene (60 mg/day) for 4 months. Natural killer cell levels rose, peaking at 3 months. No changes in CD4 or CD8 counts were observed.

Fawzi studied 1075 HIV-positive, pregnant women who were allocated to one of the following treatment arms: placebo (267); vitamin A (269); multivitamins without vitamin A (269); multivitamins including vitamin A (270). Intention to treat analysis found 30 fetal deaths in the multivitamin groups and 49 fetal deaths among the women not on multivitamins. Multivitamin supplements reduced the risk of low birth weight and delivery before 34 weeks. Multivitamins, but not vitamin A, were associated with significant increases in CD4 and CD8 counts.

References

Baeten JM et al. The influence of vitamin A and hormonal contraception on HIV transmission and disease progression in women. Tenth Conference on Retroviruses and Opportunistic Infections, abstract 116, 2003.

Baeten JM et al. Vitamin A supplementation and genital shedding of herpes simplex virus among HIV-infected women: a randomized controlled trial. J Infect Dis 189: 1466-1471, 2004.

Beach RS et al. Specific nutrient abnormalities in asymptomatic HIV-1 infection. AIDS 6: 701-708, 1992.

Bianchi-Santamaria A et al. Possible activity of beta-carotene in patients with the AIDS related complex: a pilot study. Med Oncol & Tumor Pharmacother 9(3): 151-153, 1992.

Burger H et al. Maternal serum vitamin A levels are not associated with mother-to-child transmission of HIV-1 in the United States. Journal of Acquired Immune Deficiency Syndromes and Human Retrovirology 14(4): 321-326, 1997.

Coodley GO et al. Beta-carotene in HIV infection: an extended evaluation. AIDS 10: 967-973, 1996.

Fawzi WW et al. Randomised trial of effects of vitamin supplements on pregnancy outcomes and T cell counts in HIV-1 infected women in Tanzania. Lancet 351(9114): 1477-1482, 1998.

Fawzi WW et al. Effect of providing vitamin supplements to human immunodeficiency virus-infected, lactating mothers on the childs morbidity and CD4+ cell counts. Clinical Infectious Diseases 36(8): 1053-1062, 2003.

Fawzi WW et al. A randomized trial of multivitamin supplements and HIV disease progression and mortality. New Engl J Med 351: 23-32, 2004.

Garewal HS et al. A preliminary trial of beta-carotene in subjects infected with the human immunodeficiency virus. Journal of Nutrition 122: 728-732, 1991.

Karter DL et al. Vitamin A deficiency in patients with AIDS: a cross-sectional study. Eighth International Conference on AIDS, Amsterdam, abstract PoB 3698, 1992.

Leo MA et al. Alcohol, vitamin A, and beta-carotene: adverse interactions, including hepatotoxicity and carinogenicity. American Journal of Clinical Nutrition 69(6): 1071-1085, 1999.

Nimmagadda AP et al. Effect of oral beta carotene supplementation on plasma human immunodeficiency virus RNA levels and CD4+ cell counts in HIV-infected patients. Clinical Infectious Disease 27 5: 1311-1313, 1998.

Semba RD et al. Maternal vitamin A deficiency and mother-to-child transmission of HIV-1. Lancet 343: 1593-1597, 1994.

Semba RD et al. Vitamin A deficiency and wasting as predictors of mortality in human immunodeficiency virus-infected drug users. Journal of Infectious Diseases 171(5): 1196-1202, 1995.

Semba RD et al. Vitamin A supplementation and human immunodeficiency virus load in injection drug users. Journal of Infectious Diseases 177(3): 611-616, 1998.

Villamor E et al. Effect of multivitamin and vitamin A supplements on weight gain during pregnancy among HIV-1-infected women. American Journal of Clinical Nutrition 76(5): 1082-1090.

Ward BJ et al. Vitamin A status in HIV infection. Nutrition Research 13: 157-166, 1993.