Background: Reports from several studies have suggested that carotenoids, and in particular lycopene, could be prostate cancer–preventive agents. This has stimulated extensive laboratory and clinical research, as well as much commercial and public enthusiasm. However, the epidemiologic evidence remains inconclusive.

Materials and Methods: We investigated the association between prediagnostic serum carotenoids (lycopene, {alpha}-carotene, ß-carotene, ß-cryptoxanthin, lutein, and zeaxanthin) and risk of prostate cancer in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, a multicenter study designed to examine methods of early detection and risk factors for cancer. The study included 692 incident prostate cancer cases, diagnosed 1 to 8 years after study entry, including 270 aggressive cases, with regional or distant stage (n = 90) or Gleason score ≥7 (n = 235), and 844 randomly selected, matched controls. As study participants were selected from those who were assigned to annual standardized screening for prostate cancer, results are unlikely to be biased by differential screening, a circumstance that is difficult to attain under non–trial conditions.

Results: No association was observed between serum lycopene and total prostate cancer [odds ratios (OR), 1.14; 95% confidence intervals (95% CI), 0.82-1.58 for highest versus lowest quintile; P for trend, 0.28] or aggressive prostate cancer (OR, 0.99; 95% CI, 0.62-1.57 for highest versus lowest quintile; P for trend, 0.433). ß-Carotene was associated with an increased risk of aggressive prostate cancer (OR, 1.67; 95% CI, 1.03-2.72 for highest versus lowest quintile; P for trend, 0.13); in particular, regional or distant stage disease (OR, 3.16; 95% CI, 1.37-7.31 for highest versus lowest quintile; P for trend, 0.02); other carotenoids were not associated with risk.

Conclusion: In this large prospective study, high serum ß-carotene concentrations were associated with increased risk for aggressive, clinically relevant prostate cancer. Lycopene and other carotenoids were unrelated to prostate cancer. Consistent with other recent publications, these results suggest that lycopene or tomato-based regimens will not be effective for prostate cancer prevention.

(Cancer Epidemiol Biomarkers Prev 2007;16(5):962–8)

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Ulrike Peters1,2,3, Michael F. Leitzmann3, Nilanjan Chatterjee3, Yinghui Wang1, Demetrius Albanes3, Edward P. Gelmann4, Marlin D. Friesen5, Elio Riboli6 and Richard B. Hayes3

1 Fred Hutchinson Cancer Research Center; 2 University of Washington, Seattle, Washington; 3 Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Department of Health and Human Services, Rockville, Maryland; 4 Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, District of Columbia; 5 Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland; and 6 Nutrition and Cancer Unit, International Agency for Research on Cancer, Lyon, France

Requests for reprints: Ulrike Peters, Cancer Prevention Program, Fred Hutchinson Cancer Research Center, P.O. Box 19024, 1100 Fairview Avenue North M4-B402, Seattle, WA 98109-1024. Phone: 206-667-2450; Fax: 206-667-7850. E-mail: upeters@fhcrc.org

Lutein (from Latin lutea meaning “yellow”) is one of over 600 known naturally occurring carotenoids. Found in green leafy vegetables such as spinach and kale, lutein is employed by organisms as an antioxidant and for blue light absorption. Lutein is covalently bound to one or more fatty acids present in some fruits and flowers, notably marigolds.

Lutein was found to be present in a concentrated area of the macula, a small area of the retina responsible for central vision. The hypothesis for the natural concentration is that lutein helps protect from oxidative stress and high-energy light. Various research studies have shown that a direct relationship exists between lutein intake and pigmentation in the eye. Several studies also show that an increase in macula pigmentation decreases the risk for eye diseases such as Age-related Macular Degeneration (AMD).

Lutein is a natural part of human diet when fruits and vegetables are consumed. For individuals lacking sufficient lutein intake, lutein-fortified foods are available, or in the case of elderly people with a poorly absorbing digestive system, fortification via a sublingual spray ensures maximum benefit to the eyes. As early as 1996, lutein has been incorporated into dietary supplements. While no recommended daily allowance currently exists for lutein as for other nutrients, positive effects have been seen at levels of 6 mg/day. The only definitive side effect of excess lutein consumption is the same observed for β-carotene overdose, namely bronzing of the skin (carotenodermia). The normal levels of Lutein found in a daily vitamin tablet can be as low as 0.25 mg.

Retinol, the animal form of vitamin A, is a yellow fat-soluble, antioxidant vitamin important in vision and bone growth. It belongs to the family of chemical compounds known as retinoids. Retinol is ingested in a precursor form; animal sources (milk and eggs) contain retinyl esters, whereas plants (carrots, spinach) contain pro-vitamin A carotenoids. Hydrolysis of retinyl esters results in retinol while pro-vitamin A carotenoids can be cleaved to produce retinal. Retinal, also known as retinaldehyde, can be reversibly reduced to produce retinol or it can be irreversibly oxidized to produce retinoic acid. The best described active retinoid metabolites are 11-cis-retinal and the all-trans and 9-cis-isomers of retinoic acid.