Distribution and Impact on Health

In general, carotenoid concentrations in serum reflect concentrations contained in the food that is ingested. Carotenoids have been found in various human organs and tissues. These include human liver, lung, breast, cervix, skin, and adipose and ocular tissues. The major storage organs are adipose tissue (probably because of its volume) and the liver. Tissues containing large amounts of LDL receptors seem to accumulate high levels of carotenoids, probably as a result of nonspecific uptake by lipoprotein carriers. Preferential uptake, however, is indicated in some cases. For example, unusually high concentrations of phytoene in the lung, ^-carotene and phytofluene in breast tissue, lycopene in the prostate and colon, lycopene, ^-carotene, and phytofluene in cervical tissue, and lutein and zeaxanthin in ocular tissues have been found.

The epidemiological findings that the ingestion of tomato and tomato products is strongly correlated with a reduced risk of several types of cancer, particularly prostate cancer, has stimulated a great deal of research on the protective effects of lycopene. Lyco-pene is the most efficient biological antioxidant. Hence, it has been assumed that it is this anti-oxidant activity that is responsible for the protection against prostate cancer. However, a recent study in which carcinogenesis was induced in rats using

N-methyl-N-nitrosourea showed that a diet containing whole tomato powder inhibited development of prostate cancer, but the same diet to which pure synthetic lycopene was added instead did not. These results indicate that lycopene alone was ineffective in reducing the incidence of prostate cancer. Therefore, either some other element in the tomato powder was the effective agent or the effect was obtained by lycopene working in concert with other tomato constituents. Obviously, more studies are required to determine which elements contained in tomato are responsible for the protective effect.

The finding that lutein and zeaxanthin are accumulated in the macula lutea of the eye has led to the hope that dietary supplementation might reduce the risk of age-related macular degeneration (AMD), which affects the central portion of the retina and is the most common cause of irreversible blindness in the Western world. Some studies have indicated benefits of diets supplemented with lutein and zeaxanthin from spinach in preventing AMD; others found no significant correlation between plasma levels of these carotenoids and reduced risk of AMD. Lutein, zeaxanthin, and a zeaxanthin stereoisomer 3R, 3'S(=meso)-zeaxanthin form the yellow pigment of the macula lutea. 3R, 3'S(=meso)-zeaxanthin is not found in either food or plasma in significant amounts. Also notable is that, in most food consumed in large quantities, the concentration of lutein is much greater than that of zeaxanthin (e.g., see Table 1, spinach, kale, broccoli, tomato). The yellow pigment of the macula is located in the center of the macula, covering the central fovea and overlapping the avascular zone. This location would allow the pigment to shield the photoreceptors from blue light. An environmental factor that seems to play a role in the development of age-related macular degeneration is ocular exposure to sunlight, in particular a history of exposure to blue light in the preceding 20 years. Light has been shown to induce oxidative damage in the presence of photosensitizers. Macular carotenoids are distributed in a pattern that is particularly advantageous. The two stereoisomers of zeaxanthin are concentrated in the central area and lutein in higher concentrations in the more peripheral regions. The lutein: zeaxanthin ratio in the center of the macula is about 0.8, in the peripheral regions about 2.4, but in plasma between 4 and 7. Therefore, the macula is able to concentrate lutein and zeaxanthin, change concentration ratios that are normally found in plasma, and invert the ratio to achieve higher zeax-anthin concentrations in the center of the macula lutea. The exact mechanism for this accumulation is not known; however, a specific membrane-

associated, xanthophyll-binding protein was recently isolated from the human retina.

Carotenoids are believed to play a significant role in protecting skin from oxidative damage. In vivo measurements in humans of lycopene, ß-, (-, 7-, and a-carotenes, lutein and zeaxanthin, phytoene, and phytofluene have shown that carotenoid concentrations are correlated with the presence or absence of skin cancer and precancerous lesions. Carotenoids are also believed to protect against several other types of cancer, cardiovascular diseases, and cataract formation and aid in immune function and gap-junction communication between cells, which is believed to be a protective mechanism related to their cancer-preventative activities.

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