Natural Carotenoids

E. Immune Function

• 1. Dietary carotenoids and human immune function.

  Hughes et al. Nutrition. 2001 Oct;17(10):823-7.

  The colorful group of compounds known as carotenoids are present in many plants, where they provide photoprotection and act as accessory pigments in photosynthesis. Many epidemiologic studies have shown strong associations between diets rich in carotenoids and a reduced incidence of many forms of cancer, and that finding led to the suggestion that the antioxidant properties of those compounds might help protect immune cells from oxidative damage, thus enhancing their ability to detect and eliminate tumor cells. Since the early 1980s, there have been reports supporting that hypothesis. However, more recently, after large prospective studies did not show protective effects of beta-carotene supplementation, more attention has been given to studies defining optimal levels of intake that can be achieved within a well-balanced diet. The latest intervention studies have suggested that, in well-nourished, healthy individuals, a moderate level of carotenoid supplementation is neither beneficial nor harmful. However, supplementation might be appropriate in undernourished or less healthy individuals, particularly if they are elderly. Future studies comparing supplements with real foodstuffs, combined with postgenomic technologies, will help define optimal intakes for different sectors of the population.

• 2. Impact of nutritional status and nutrient supplements on immune responses and incidence of infection in older individuals.

  Chandra et al. Ageing Res Rev. 2004 Jan;3(1):91-104.

  With advancing age there is a progressive decline in immune responses although this is not inevitable. The impairment in immunocompetence is noticeable as early as 35-40 years in many individuals. At the same time, some persons even in the 80s may show a vigorous immune system comparable with that of the young adult. Nutrient deficiencies are frequent in older populations. A variety of nutrients are affected: zinc, iron, beta-carotene, Vitamins B6, B12, C, D and E, ad folic acid. The causal interaction between nutritional deficiencies and impaired immunity has been known in children; a similar relationship has been postulated in the elderly. In the last 25 years, many studies employing different designs have examined the role of diet, nutritional status, and nutrient supplements in the immune responses of older individuals. Some nutrients, for example zinc and Vitamin E, have been shown to increase selected immune responses but have not been beneficial in terms of reduction in infectious morbidity. A growing consensus indicates that the use of a multinutrient containing optimum amounts of essential trace elements and vitamins is likely to result in enhanced immune responses and reduction in the occurrence of common infections. These findings have considerable fundamental, clinical and public health significance.

• 3. The effects of 13-cis-retinoic acid and beta-carotene on cellular immunity in humans.

  Prabhala et al. Cancer. 1991 Mar 15;67(6):1556-60.

  Deficiency of vitamin A and/or its precursors has been associated with increased cancer risk in animals and humans. Therapeutic trials of vitamin A and related compounds have demonstrated activity in several cancerous and precancerous conditions. The authors measured the effects of a retinoid, 13-cis-retinoic acid, and a carotenoid, beta-carotene, on the human immune system in vivo in conjunction with their use in ongoing clinical trials. Immune cell subpopulations were analyzed by quantifying the expression of markers using flow cytometric study. Both compounds produced significant effects on immune cell populations. 13-cis-Retinoic acid resulted in an increase in the percentage of peripheral blood lymphoid cells expressing surface markers for T-helper cells with only minimal effect on natural killer cell marker expression. In contrast, beta-carotene produced an increase in the percentage of cells expressing natural killer cell markers with smaller effect on T-helper markers. Modest increases in the percentage of cells expressing Ia antigen, transferrin, and interleukin-2 receptors were produced by both drugs. These results suggest that retinoids and carotenoids can produce major changes in immune cellular marker expression in vivo in humans at doses relevant to their potential clinical use.

• 4. Natural killer cell activity in elderly men is enhanced by beta-carotene supplementation.

  Santos et al. Am J Clin Nutr. 1996 Nov;64(5):772-7.

  Natural killer (NK) cell activity has been postulated to be an immunologic link between beta-carotene and cancer prevention. In a cross-sectional, placebo-controlled, double-blind study we examined the effect of 10-12 y of beta-carotene supplementation (50 mg on alternate days) on NK cell activity in 59 (38 middle-aged men, 51-64 y; 21 elderly men, 65-86 y) Boston area participants in the Physicians' Health Study. No significant difference was seen in NK cell activity due to beta-carotene supplementation in the middle-aged group. The elderly men had significantly lower NK cell activity than the middle-aged men; however, there was no age-associated difference in NK cell activity in men supplemented with beta-carotene. beta-carotene-supplemented elderly men had significantly greater NK cell activity than elderly men receiving placebo. The reason for this is unknown; however, it was not due to an increase in the percentage of NK cells, nor to an increase in interleukin 2 (IL-2) receptor expression, nor to IL-2 production. beta-carotene may be acting directly on one or more of the lytic stages of NK cell cytotoxicity, or on NK cell activity-enhancing cytokines other than IL-2, such as IL-12. Our results show that long-term beta-carotene supplementation enhances NK cell activity in elderly men, which may be beneficial for viral and tumoral surveillance.

• 5. Effects of carotenoids on human immune function.

  Hughes et al. Proc Nutr Soc. 1999 Aug;58(3):713-8.

  Many epidemiological studies have shown an association between diets rich in carotenoids and a reduced incidence of many forms of cancer, and it has been suggested that the antioxidant properties of these compounds are a causative factor. Attention has focused on the potential role of one specific carotenoid, beta-carotene, in preventing cancer, and numerous publications have described in vitro experiments and animal studies which suggest that not only can this carotenoid protect against the development of cancer, but also several other chronic diseases. Since the immune system plays a major role in cancer prevention, it has been suggested that beta-carotene may enhance immune cell function. Several human trials, using dietary beta-carotene supplementation with a wide range of intakes, have been undertaken to address this hypothesis. The general conclusion of these studies is that this compound can enhance cell-mediated immune responses, particularly in the elderly. The present article will review some of these human studies and, hopefully, complement the reviews of other authors associated with the present symposium, some of whom will also describe work in this area. Potential mechanisms for the effects of carotenoids on immune function will also be reviewed. Finally, possible reasons for the failure of three major prospective studies to demonstrate a beneficial effect of beta-carotene supplementation on lung cancer risk will be discussed.