Vitamin Supplements

Vitamin A and the Immune System

Numerous studies have documented that Vitamin A has a critical role in the function and differentiation of many cell types, including immune cells, although its mechanism of action is undefined. Animal studies indicate that vitamin A deficiency causes immune system dysfunction and pathology. Chickens that are experimentally infected with Newcastle disease virus (a serious respiratory and nervous disease in fowl that can cause transient conjunctivitis in humans), when fed a diet deficient in Vitamin A, show increased pathology and an altered disease pathogenesis.²

Another study of chicks infected with Newcastle disease virus demonstrated that immunoglobulin levels were decreased during vitamin a deficiency.³ Rats infected with Angiostrongylus cantonesis (a parasitic disease, transmitted by shellfish, that causes a lung infection in rodents and may infect humans) show increased susceptibility and more disease when deprived of Vitamin A.⁴ Chicks infected with Escherichia coli have decreased resistance to infection and an altered immune response when fed diets either high or low in Vitamin A.⁵ Vitamin A-deficient rats have impaired phagocyte activity during bacterial infection.⁶ Antibody synthesis and T cell proliferation are increased in chickens supplemented with Vitamin A.⁷ Finally, lymphoid organs appear atrophied and underdeveloped in Vitamin A-deficient rats.⁸

Several clinical studies of Vitamin A deficiency and supplementation confirm that also has a role in human immune function. The most convincing study of the benefits of Vitamin A supplementation on reduced infections and mortality was conducted in India, where deficiencies of the vitamin are common.⁹ The well-designed, blinded study enrolled 15,419 preschool children in an area of Southern India where Vitamin A deficiency is common. They were randomized to receive weekly Vitamin A supplements (8333 IU) or Vitamin E (20mg) for over one year. The study reports a startling 54 percent reduction in childhood mortality, primarily through reductions in diarrhea and infections. An editorial in The New England Journal of Medicine that accompanied the article said that "the available evidence now supports the immediate implementation of Vitamin A programs in specific cases -- wherever there is evidence that a population has a vitamin a deficiency, wherever protein-energy malnutrition is common, and wherever there is an excess of measles deaths."¹⁰

Other clinical trials have pointed to the same conclusions about Vitamin A supplementation in high-risk populations, although they were not as large nor as well-designed as the Indian study. An Australian study of 147 young children found that daily vitamin A supplements reduced the incidence of respiratory infection compared with placebo.¹¹ A randomized study of 450 villages in Sumatra (an Indonesian Island) found that children in villages randomized to receive one or two vitamin a supplements (200,000 IU) over several months had a 50 percent reduction in mortality compared with children in villages which received placebo.¹² A South African study of 189 young children hospitalized with measles found that vitamin a given in a total dose 400,000 IU reduced the length of recovery from pneumonia and diarrhea, shortened hospitalization, and improved survival compared with placebo.¹³

Vitamin A and AIDS

Vitamin A deficiency may occur in people with HIV through an unknown mechanism, according to several preliminary reports. Vitamin A deficiency may be secondary to an overall state of protein-energy malnutrition in people with HIV or could be related to the host response to infection. Infection and fever increase the metabolism of Vitamin A, increase its urinary excretion, impair its intestinal absorption, and can diminish hepatic stores of the vitamin, all leading to systemic deficiency. Vitamin A deficiency may lead to increased risk of infection and further vitamin deficiency, leading several investigators to describe this relationship as a "vicious cycle."^{[14,15, 16, 17, 18]}

However, serum vitamin A levels may be affected by the APR, so serum diagnosis is difficult and can not be considered definitive. A study from Baltimore examined serum Vitamin A levels in 179 intravenous drug users (126 HIV-infected, 59 uninfected). Fifteen percent of the HIV-infected people had serum levels consistent with Vitamin A deficiency. Overall, the infected group had lower mean plasma levels of the vitamin compared with the uninfected controls. Vitamin A deficiency was associated with lower CD4 counts and an increased risk of mortality. An abstract presented at the 1992 International AIDS Conference found that people with HIV were more likely than historical, uninfected controls to have lower serum vitamin A levels and deficiencies. Vitamin A levels were only partially associated with decreased dietary intake in this study. Serum vitamin A levels were also reduced in 18 percent of asymptomatic HIV-infected people, according to a 100-person study from the University of Miami. Despite growing evidence that vitamin A deficiency can occur in some people with HIV, the mechanism(s) of the deficiency and the clinical significance of this finding are unknown. Furthermore, it remains unclear if vitamin A supplementation can reverse the deficiency and, more importantly, improve the clinical outcome of patients. This uncertainty is increased by evidence that Vitamin A can both increase and decrease HIV replication, depending on cell type, in vitro.