Determine Whether Vitamin a Enhances Immune Response

Several approaches have been taken in an attempt to determine whether Vitamin A supplementation enhances immune response and resistance or recovery from infection. In some investigations, researchers have attempted to correlate plasma concentrations of beta-carotene or retinol with immune response or susceptibility to infection. One limitation of this approach is related to the fact that plasma concentrations may have depressed plasma retinol levels as a result of disease. Therefore, it is not possible to establish whether low plasma retinol levels resulted in suppressed immune response or if plasma retinol levels decreased in response to disease or infection. Another approach used is to supplement the diet with retinol precursors and examine immune response at a later time point. This approach may be useful in examining the particular aspects of immunity that may be altered by supplementation, but additional studies are necessary to determine whether these effects have clinical significance in terms of disease outcome. Vitamin A has been fairly well studied in terms of its immunomodulatory effects, and we will review the evidence from randomized controlled trials as well as potential mechanisms of action.

Vitamin A supplementation may afford some protection from infection in malnourished individuals, but the potential benefits of supplementation in normal well­nourished individuals remain to be established. There is evidence from several studies that suggests that vitamin A deficiency is associated with depressed immune function and an impaired response to influenza infection. Supplementation of vitamin A is associated with a reduction of mortality and morbidity among certain populations. It appears that populations suffering from mal­nutrition may benefit from adequate or additional vitamin A supplementation. However, it is less clear if normal, healthy, well-nourished individuals will benefit from additional supplementation with respect to enhanced immunity. The results from several studies involving beta-carotene supplementation in the diet of healthy individuals suggest that certain aspects of innate immunity, such as NK cytotoxicity and monocyte production of the cytokine TNFcx, are enhanced. It appears that lymphocyte subsets or the lymphocyte response to mitogens are not altered. In addition, one study of healthy older individuals found that vitamin A supplementation was associated with a reduction in the number of T lymphocytes. Whether these observed changes of immune function in response to supplementation actually result in reduced susceptibility to infection in healthy individuals is not well established. The results from one study demonstrated no association between vitamin A supplementation and incidence of bacterial infection. we are not aware of any long-term, randomized clinical trials that have evaluated the incidence of viral infection in response to supplementation with vitamin A alone. However, several studies have examined the possibility that supplementation with several multivitamins and or trace elements such as zinc, may alter susceptibility to infection. In general, the findings from these studies show no protection from infection in association with vitamin intake, but a slight decrease in the incidence of infection in those individuals consuming supplemental trace elements such as zinc and selenium. At this time, the potential benefits of vitamin A supplementation for healthy well-nourished individuals regarding susceptibility to infection remain to be established.

A high beta-carotene intake has also been associated with a reduced risk of cancer. Earlier epidemiological studies suggested a high natural (fruits and vegetables) intake of beta-carotene was associated with reduced risk of cancer. However, more recent studies have not observed any benefit of beta-carotene intake on incidence of cancer and two studies actually observed an increased incidence of lung cancer in those participants consuming beta-carotene supplements. The presence of other carotenoids in fruits and vegetables has been suggested to be the protective factor in regards to cancer incidence in the early epidemiological studies based on the findings from these recent studies, dietary supplementation with high doses of synthetic beta-carotene may be contraindicated for smokers. As a reminder, it has been known for some time that a high intake of vitamin A results in adverse effects (neurologic, dermatologic, musculoskeletal, gastrointestinal, birth defects) and the results from the most recent studies suggest a potential risk of high doses of synthetic beta-carotene in certain populations. At this time it is probably safest to follow the National Cancer Institute recommendations that suggest five or more servings of fruits and vegetables per day.

Immune Effects and Exercise

We are currently aware of only one study that has examined whether vitamin A supplementation is associated with a reduced incidence of infection in athletes. Several studies have shown that the risk of upper respiratory infection is increased following competition in marathons or ultramarathons However, vitamin A supplementation before marathon competition did not reduce the incidence of infection in the postrace period. Therefore, to our knowledge, vitamin A supplementation has not been associated with enhanced resistance to infection in healthy athletes.