Beta-carotene supplementation for patients with low baseline levels and decreased risks of total and prostate cancer

Harvard University, Cambridge, Massachusetts, United States
Cancer (Impact Factor: 4.89). 11/1999; 86(9):1783-1792. DOI: 10.1002/(SICI)1097-0142(19991101)86:93.0.CO;2-N


The Physicians' Health Study was a randomized, double-blind, placebo-controlled trial using a 2x2 factorial design including supplementation with beta-carotene (50 mg every other day) in the primary prevention of cancer among 22,071 U.S. male physicians ages 40-84 years at randomization. Before randomization, the authors collected baseline blood specimens to determine whether any benefit was greater among or confined to those with low baseline levels of beta-carotene.
Baseline blood samples were collected from 14,916 participants. These samples were assayed, according to a nested case-control design, from 1439 men subsequently diagnosed with cancer over 12 years of follow-up (631 with prostate carcinoma) and 2204 controls matched by age and smoking habits.
Men in the lowest quartile for plasma beta-carotene at baseline had a marginally significant (P = 0.07) increased risk of cancer compared with those in the highest quartile (relative risk [RR] = 1.30, 95% confidence interval [CI], 0.98-1.74). Men in the lowest quartile assigned at random to beta-carotene supplementation had a possible but nonsignificant decrease in overall cancer risk (RR = 0.83, 95% CI, 0.63-1.09) compared with those assigned to placebo. This was primarily due to a significant reduction in the risk of prostate carcinoma (RR = 0.68, 95% CI, 0. 46-0.99) in this group. After the first 2 years of follow-up were excluded, the results were virtually unchanged.
These prespecified subgroup analyses appeared to support the idea that beta-carotene supplementation may reduce risk of prostate carcinoma among those with low baseline levels. Further follow-up of this population will help determine whether these findings are valid.

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    ABSTRACT: Purpose: Clinical-based hypotheses concerning the consequences of antioxidant uses concurrent with cancer therapeutic interventions range from beneficial to indetermi- nate to harmful outcomes. Available scientific validity in support of these speculations needs to be examined to clari- fy the role of antioxidant agents in cancer therapeutic man- agement. Methods: We reviewed scientific and clinical findings addressing the basis for the primary hypotheses in this area, and identified recent results on antioxidant uses in cancer therapy that help define clinical management issues. Results: Many hypotheses of speculated harm suffer from absent formal clinical trials evaluation. Other hypotheses are dependent on models of free-radical reduc- tion which are no longer informed models. Available but limited published data are generally not supportive of harm- ful outcomes, while other data indicate possibly positive adjunctive therapeutic support. Conclusion: Hypotheses that antioxidants' inhibition of free-radical activity may negate cytotoxic properties of some cancer therapies have been dependent on naive and inaccu- rate assumptions. The available data suggest a rational basis for the continued use of selected antioxidant agents as thera- peutic adjuncts in cancer therapy, with such use also offering a potential to abrogate the carcinogenic process and muta- tion-driven drug resistance, but convincing data and wide- spread acceptance of such a role is dependent on additional, appropriately relevant trials.
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    ABSTRACT: In dieser Arbeit wurde der Gehalt der 6 Hauptcarotinoide (Lutein, Zeaxanthin,ß-Cryptoxanthin, Lycopin, a- und ß-Carotin) im Blutserum von 115 Frauen und 45 Männern verschiedener Altersgruppen in Deutschland bestimmt. Das gefundene Serumcarotinoidprofil korreliert gut mit den Ergebnissen in Studien anderer Staaten mit westlichem Lebensstil (Spanien, Italien, England und USA). Signifikante geschlechtsspezifische Unterschiede werden im Serumgehalt der provitamin-A-aktiven Carotinoide ß-Carotin und ß-Cryptoxanthin gefunden. Ein möglicher Erklärungsansatz ist, daß Männer ß-Carotin bzw. ß-Cryptoxanthin schneller zu Retinol metabolisieren, da bei Männern signifikant höhere Retinolserumwerte gefunden wurden. Der Carotinoidserumgehalt der übrigen Carotinoide, einschließlich der Unterschiede in den Altersgruppen, spiegelt vermutlich im wesentlichen Ernährungsgewohnheiten wider. Die im Hautfibroblastenmodell getesteten Carotinoide, Lutein, Lycopin und ß-Carotin,zeigen eine ähnliche Konzentrationsabhängigkeit der UV-induzierten TBARS-Bildung.Charakterisiert werden diese Kurven durch eine optimale Schutzkonzentration, einen Konzentrationsbereich, in dem eine Schutzwirkung erreicht wird, und eine maximale Schutzwirkung. Unterschiede in der Konzentrationsabhängigkeit der verschiedenen Carotinoide zeigen sich vor allem in optimalen Schutzkonzentration und der Größe des Konzentrationsbereichs, in dem eine Schutzwirkung erreicht wird. Lycopin zeigt seine maximale Schutzwirkung bei einer Konzentration, die 6 bzw. 8 fach niedriger ist als bei Lutein bzw. ß-Carotin. ß-Carotin zeigt von den getesteten Carotinoiden den größten Konzentrationsbereich, in dem eine Schutzwirkung erreicht wird. Alle drei getesteten Carotinoide, sowie zwei der vier untersuchten Carotinoidmischungen, zeigten eine maximale Schutzwirkung von etwa 40-50% bei optimaler Schutzkonzentration. In der vorliegenden Arbeit wurde in einer Interventionsstudie 10 Wochen mit Tomatenmark supplementiert. Dabei wurde eine signifikante Verminderung der Erythemintensität (Hautrötung) um 40%, 24 h nach UV-Bestrahlung mit der 1,25 fachen individuellen Minimalen Erythemdosis (MED), beobachtet. Von besonderer Bedeutung ist, daß ein systemischer Schutz vor UV-induzierten Hautschäden (Erythem) durch ein frei verfügbares Lebensmittel (Tomatenmark) nachgewiesen wurde. In einer weiteren Interventionsstudie zeigte sich nach 12 Wochen Supplementierung mit ß-Carotin ebenfalls eine Verminderung des Erythems der Probanden um ca. 40% 24 h nach UV-Bestrahlung mit der 1,6 fachen individuellen MED. Bei Probanden, die mit einer Carotinoidkombination aus Lutein, Lycopin und ß-Carotin supplementiert wurden, konnte aufgrund von Veränderungen des Farbtons der Haut bei 5 der 12 Probanden keine endgültige Aussage über eine mögliche Schutzwirkung getroffen werden. UV light is damaging to tissues due to interactions with important biomolecules or related to the induction of reactions resulting in the formation of reactive oxygen and/or nitrogen species. Those reactive intermediates may chemically modify DNA, proteins, lipids or carbohydrates, thus initiating or triggering pathological processes. Diseases related to light-exposure include for example skin cancer, skin erythema formation as well as ophthalmological disorders like cataract and age-related macular degeneration. There is increasing evidence that dietary antioxidants such as carotenoids, may protect against photooxidative reactions and thus play a role in the prevention of diseases related to photooxidative stress. Carotenoids are lipophilic micronutrients which are ingested with fruit and vegetables and are found in human blood and tissues including the skin. Three studies which investigate the influence of carotenoids on harmful effects of UV-light on skin are reported here. The first study was to investigate whether intervention with a natural dietary source rich in lycopene (tomato paste) protects against UV-induced erythema in humans. Erythema was induced by illumination of dorsal skin with a solar simulator at the beginning of the study, after 4 weeks and after 10 weeks. Intensity of erythema was measured by chromatometry 24 h after irradiation. Carotenoid serum levels were followed by HPLC at the time points of erythema induction. At week 10, dorsal erythema formation was significantly lower by 40% in the group that consumed tomato paste as compared to controls (p = 0.02; Wilcoxon-Mann-Whitney-test). The data demonstrate that it is feasible to achieve protection against UV-light-induced erythema by ingestion of carotenoids with diet. The influence of the lutein, lycopene and b-carotene on UV-induced lipid peroxidation was examined in the second study. Fibroblasts were loaded with carotenoids via liposomes and were exposed to UV light (0.8 mW; l = 295 to 325 nm) for 20 min. After 1 hr of incubation at 37 °C, cellular protein and TBARS (thiobarbituric acid reactive substances) content was determined. b-Carotene, lycopene and lutein lowered UV-induced TBARS formation to a level of about 45% of control. The amount of carotenoid needed for optimal protection was 0.4, 0.05 and 0.29 nmol/mg protein for b-carotene, lycopene and lutein, respectively. At high levels all tested carotenoids exhibited prooxidant effects. The differences of antioxidant properties related to the concentration of the carotenoids tested here might be due to different orientations in cellular membranes and related to their polarity of the different compounds. The last study was to measure the status of the six major carotenoids (b-carotene, a-carotene, lycopene, b-cryptoxanthin, lutein, zeaxanthin) in blood serum of healthy German volunteers (115 w/ 45 m) of different age by means of HPLC. The profiles of carotenoids in our subjects were consistent with profiles determined in studies in other western countries. Significant sex-related differences were found for concentrations of the provitamin A active carotenoids b-carotene and b-cryptoxanthin. Age-related differences in carotenoid serum profile of our subjects are likely to reflect differences in dietary habits between older and younger subjects. Significant correlations between carotenoid concentrations of lutein and zeaxanthin, lutein and a-carotene as well as between b-carotene and b-cryptoxanthin were found.
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