Hydrocarbon Carotenoid bCarotene

^-Carotene is one of the most widely studied carot-enoids - for both its vitamin A activity and its abundance in fruits and vegetables. Epidemiological studies have often pointed to an abundance of carot-enoids in the diet being protective against many diseases. Diets rich in fruits and vegetables are recommended to reduce the risk of cardiovascular disease and some forms of cancer. However, when /3-carotene is removed from the plant matrix and administered as a supplement, these benefits sometimes disappear. For example, because lung cancer is

Table 2 A summary of epidemiologic and/or clinical studies where carotenoids and a significant association to a specific disease risk has been shown in at least one studya

Carotenoid Cardiovascular disease Cataract Macular degeneration Lung cancer Prostate cancer

Table 2 A summary of epidemiologic and/or clinical studies where carotenoids and a significant association to a specific disease risk has been shown in at least one studya

Carotenoid Cardiovascular disease Cataract Macular degeneration Lung cancer Prostate cancer

ß-Carotene

Yes

-

Yesb

-

a-Carotene

Yes

-

-

Yes

-

ß-Cryptoxanthin

-

-

-

Yes

-

Lycopene

Yes

-

-

Yes

Yes

Lutein/zeaxanthin

Yes

Yes

Yes

Yes

-

aFor a more complete discussion of the association of specific carotenoids to disease please refer to: Krinsky NI, Mayne SI, and Sies H, (eds.) (2004) Carotenoids in Health and Disease. New York: Marcel Dekker. ^The opposite finding has been observed in clinical trials.

aFor a more complete discussion of the association of specific carotenoids to disease please refer to: Krinsky NI, Mayne SI, and Sies H, (eds.) (2004) Carotenoids in Health and Disease. New York: Marcel Dekker. ^The opposite finding has been observed in clinical trials.

the leading cause of cancer death in many developed countries, the fi-Carotene and Retinol Efficacy Trial (CARET) in the 1990s set out to test whether fi-carotene conferred protection against cancer. CARET was based on a number of observational studies that showed high levels of fi-carotene from food sources were protective against lung cancer. However, the CARET trial was halted for showing an increased risk for lung cancer in the treatment group over the control. Subsequent studies in ferrets showed that the amounts of fi-carotene commonly consumed from fruit and vegetables were protective against lung damage but higher amounts, equivalent to those in CARET, increased the formation of abnormal tissue in the lung.

A similar outcome was observed among smokers in the a-Tocopherol fi-Carotene (ATBC) Study Group. Although evidence clearly exists showing an association between fi-carotene and enhanced lung function, as in the CARET study, the ATBC trial also found an increase in lung cancer rates among smokers. It is plausible that the lung cancer had already been initiated in the smokers and supplementation with fi-carotene could not prevent the development of cancer. The ATBC study also showed an increased incidence of angina pectoris, a mild warning sign of heart disease characterized by chest pain, among heavy smokers. This may have been due to low blood levels of vitamin C in the study group leading to the inability of the individuals to quench fi-carotene radicals, but this relationship requires more research.

In both the CARET and ATBC intervention trials, much higher doses of fi-carotene were used than could be obtained from the diet, and the blood levels attained were two to six times higher than the 95th percentile level of fi-carotene in a survey of a representative sample of the US population. Thus, it remains unclear whether fi-carotene is a procarcino-gen or an anticarcinogen. The associations for lower disease risk observed in epidemiologic studies may reflect other protective dietary agents or an interaction between dietary components. Furthermore, people with higher intake of fruits and vegetables may have healthier lifestyles that contribute to their lower risk of chronic diseases. The higher disease risk observed in the clinical trials may be correlated with the use of high doses of fi-carotene where the mechanisms have not yet been identified, the limited duration of treatment, and/or the timing of the interventions was too late for cancers that were already present due to a history of heavy smoking. More research on fi-carotene's biological actions is needed to explore the mechanisms involved. Current consensus is that the beneficial effects of fi-carotene are associated with dietary consumption, whereas the harmful effects in some subpopulations are with pharmacological supplements.

Another explanation for a lack of a beneficial outcome with fi-carotene supplementation may be that not all people respond to the same degree to fi-carotene treatment, some being low- or non-responders. Some researchers believe that individuals who do not respond to fi-carotene supplementation may be better at converting it to vitamin A. Blood response to fi-carotene supplementation is also inversely related to body mass index (BMI), which may be due to increased sequestration of lipophilic fi-carotene by the larger amount of fat stores present in people with larger BMI. This theory may not hold true as individuals with larger BMIs do not necessarily have a high body fat percentage, but rather increased lean muscle mass.

Excellent food sources of fi-carotene include carrots, winter squash, red-orange sweet potato, and various types of dark green leafy vegetables. No deficiency or toxicity has been observed from dietary fi-carotene intake, although very rarely high intakes can be associated with yellow pigmentation of the skin as carotenoids are stored in adipose tissue. Supplements containing fi-carotene are common. In the Women's Health Initiative, the largest observational/intervention study in postmenopausal women to date, approximately 50% reported using a supplement containing fi-carotene. This trial included both a clinical trial and observational study involving more than 160 000 women. The Physicians' Health Study II also included fi-carotene as one of its interventions to determine the balance of risks and benefits of this carotenoid with cancer, cardiovascular disease, and eye disease.

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