In recent years, epidemiological data has demonstrated that alcohol consumption is a risk factor for sunburn, melanoma and nonmelanoma skin cancer. We hypothesized that if the concentration of the antioxidants in the skin has already decreased due to alcohol consumption, then an adequate neutralization of the free radicals induced by ultraviolet light cannot be performed. Based on this hypothesis, we determined the carotenoid concentration in the skin and the minimal erythema dose (MED) of 6 male human volunteers before and after consumption of alcohol or alcohol and orange juice combined. The results showed a significant decrease in the carotenoid concentration in the skin and the MED after alcohol consumption, but no significant decrease after a combined intake of alcohol and orange juice.

OBJECTIVE: To investigate the association of antioxidant intakes from diet and supplements with elevated blood C-reactive protein (CRP) and homocysteine (Hcy) concentrations. DESIGN: A cross-sectional study. The main exposures were vitamins C and E, carotene, flavonoid and Se intakes from diet and supplements. Elevated blood CRP and Hcy concentrations were the outcome measures. SETTING: The US population and its subgroups. SUBJECTS: We included 8335 US adults aged≥19 years from the National Health and Nutrition Examination Survey 1999-2002. RESULTS: In this US population, the mean serum CRP concentration was 4·14 (95 % CI 3·91, 4·37) mg/l. Intakes of vitamins C and E and carotene were inversely associated with the probability of having serum CRP concentrations>3 mg/l in multivariate logistic regression models. Flavonoid and Se intakes were not associated with the odds of elevated serum CRP concentrations. The mean plasma Hcy concentration was 8·61 (95 % CI 8·48, 8·74) μmol/l. Intakes of vitamins C, E, carotenes and Se were inversely associated with the odds of plasma Hcy concentrations>13μmol/l after adjusting for covariates. Flavonoid intake was not associated with the chance of elevated plasma Hcy concentrations. CONCLUSIONS: These results suggest that high antioxidant intake is associated with lower blood concentrations of CRP and Hcy. These inverse associations may be among thepotential mechanisms for the beneficial effect of antioxidant intake on CVD risk mediators in observational studies.

Plants are rich natural sources of antioxidants in addition to other nutrients. Interventions and cross sectional studies on subjects consuming uncooked vegan diet called living food (LF) have been carried out. We have clarified the efficacy of LF in rheumatoid diseases as an example of a health problem where inflammation is one of the main concerns. LF is an uncooked vegan diet and consists of berries, fruits, vegetables and roots, nuts, germinated seeds and sprouts, i.e. rich sources of carotenoids, vitamins C and E. The subjects eating LF showed highly increased levels of beta and alfa carotenes, lycopen and lutein in their sera. Also the increases of vitamin C and vitamin E (adjusted to cholesterol) were statistically significant. As the berry intake was 3-fold compared to controls the intake of polyphenolic compounds like quercetin, myricetin and kaempherol was much higher than in the omnivorous controls. The LF diet is rich in fibre, substrate of lignan production, and the urinary excretion of polyphenols like enterodiol and enterolactone as well as secoisolaricirecinol were much increased in subjects eating LF. The shift of fibromyalgic subjects to LF resulted in a decrease of their joint stiffness and pain as well as an improvement of their self-experienced health. The rheumatoid arthritis patients eating the LF diet also reported similar positive responses and the objective measures supported this finding. The improvement of rheumatoid arthritis was significantly correlated with the day-to-day fluctuation of subjective symptoms. In conclusion the rheumatoid patients subjectively benefited from the vegan diet rich in antioxidants, lactobacilli and fibre, and this was also seen in objective measures.

Astaxanthin and peridinin, two typical carotenoids of marine microalgae, and lycopene were incorporated in phosphatidylcholine multilamellar liposomes and tested as inhibitors of lipid oxidation. Contrarily to peridinin results, astaxanthin strongly reduced lipid damage when the lipoperoxidation promoters-H(2)O(2), tert-butyl hydroperoxide (t-ButOOH) or ascorbate-and Fe(2+):EDTA were added simultaneously to the liposomes. In order to check if the antioxidant activity of carotenoids was also related to their effect on membrane permeability, the peroxidation processes were initiated by adding the promoters to Fe(2+)-loaded liposomes (encapsulated in the inner aqueous solution). Despite that the rigidifying effect of carotenoids in membranes was not directly measured here, peridinin probably has decreased membrane permeability to initiators (t-ButOOH>ascorbate>H(2)O(2)) since its incorporation limited oxidative damage on iron-liposomes. On the other hand, the antioxidant activity of astaxanthin in iron-containing vesicles might be derived from its known rigidifying effect and the inherent scavenging ability.

OBJECTIVE:To evaluate the influence of short-term carotenoid and antioxidant supplementation on retinal function in nonadvanced age-related macular degeneration (AMD).

DESIGN:Randomized controlled trial.

PARTICIPANTS:Twenty-seven patients with nonadvanced AMD and visual acuity>or =0.2 logarithm of the minimum angle of resolution were enrolled and randomly divided into 2 age-similar groups: 15 patients had oral supplementation of vitamin C (180 mg), vitamin E (30 mg), zinc (22.5 mg), copper (1 mg), lutein (10 mg), zeaxanthin (1 mg), and astaxanthin (4 mg) (AZYR SIFI, Catania, Italy) daily for 12 months (treated AMD [T-AMD] group; mean age, 69.4+/-4.31 years; 15 eyes); 12 patients had no dietary supplementation during the same period (nontreated AMD [NT-AMD] group; mean age, 69.7+/-6.23 years; 12 eyes). At baseline, they were compared with 15 age-similar healthy controls.

METHODS:Multifocal electroretinograms in response to 61 M-stimuli presented to the central 20 degrees of the visual field were assessed in pretreatment (baseline) conditions and, in nonadvanced AMD patients, after 6 and 12 months.

MAIN OUTCOME MEASURES:Multifocal electroretinogram response amplitude densities (RAD, nanovolt/deg(2)) of the N1-P1 component of first-order binary kernels measured from 5 retinal eccentricity areas between the fovea and midperiphery: 0 degrees to 2.5 degrees (R1), 2.5 degrees to 5 degrees (R2), 5 degrees to 10 degrees (R3), 10 degrees to 15 degrees (R4), and 15 degrees to 20 degrees (R5).

RESULTS:At baseline, we observed highly significant reductions of N1-P1 RADs of R1 and R2 in T-AMD and NT-AMD patients when compared with healthy controls (1-way analysis of variance P<0.01). N1-P1 RADs of R3-R5 observed in T-AMD and NT-AMD were not significantly different (P>0.05) from controls. No significant differences (P>0.05) were observed in N1-P1 RADs of R1-R5 between T-AMD and NT-AMD at baseline. After 6 and 12 months of treatment, T-AMD eyes showed highly significant increases in N1-P1 RADs of R1 and R2 (P<0.01), whereas no significant (P>0.05) change was observed in N1-P1 RADs of R3-R5. No significant (P>0.05) changes were found in N1-P1 RADs of R1-R5 in NT-AMD eyes.

CONCLUSIONS:In nonadvanced AMD eyes, a selective dysfunction in the central retina (0 degrees -5 degrees ) can be improved by the supplementation with carotenoids and antioxidants. No functional changes are present in the more peripheral (5 degrees -20 degrees ) retinal areas.

OBJECTIVES:To explore the interrelationship and mediating effect of factors that are beneficial (i.e., antioxidants) and harmful (i.e., inflammation and oxidative stress) to the relationship between sleep and cardiometabolic health.

DESIGN:Cross-sectional data from the 2005-2006 National Health and Nutrition Examination Survey.

SETTING:Nationally representative population sample from the US.

PARTICIPANTS:Age≥ 20 y with sleep data; final analytical sample of N = 2,079.

INTERVENTIONS:N/A.

MEASUREMENTS AND RESULTS:Metabolic syndrome was classified according to the Joint Interim Statement, and sleep duration was categorized as very short, short, adequate, and long sleepers (≤4, 5-6, 7-8, and ≥9 h per night, respectively). The indirect mediation effect was quantified as large (≥ 0.25), moderate (≥ 0.09), modest (≥ 0.01), and weak (<0.01). In general, inflammation was above the current clinical reference range across all sleep duration categories, whereas oxidative stress was elevated among short and very short sleepers. Select sleep duration-cardiometabolic health relationships were mediated by C-reactive protein (CRP),γ-glutamyl transferase (GGT), carotenoids, uric acid, and vitamins C and D, and were moderated by sex. Specifically, moderate-to-large indirect mediation by GGT, carotenoids, uric acid, and vitamin D were found for sleep duration-waist circumference and systolic blood pressure relationships, whereas vitamin C was a moderate mediator of the sleep duration-diastolic blood pressure relationship.

CONCLUSIONS:Several factors related to inflammation, oxidative stress, and antioxidant status were found to lie on the casual pathway of the sleep duration-cardiometabolic health relationship. Further longitudinal studies are needed to confirm our results.

OBJECTIVE: To examine in prospective data the relation between dietary intake of carotenoids and vitamins C and E and the risk of cataract in women. DESIGN: Dietary intake was assessed at baseline in 39,876 female health professionals by using a detailed food frequency questionnaire. A total of 35,551 women provided detailed information on antioxidant nutrient intake from food and supplements and were free of a diagnosis of cataract. The main outcome measure was cataract, defined as an incident, age-related lens opacity responsible for a reduction in best-corrected visual acuity in the worse eye to 20/30 or worse based on self-report confirmed by medical record review. RESULTS: A total of 2031 cases of incident cataract were confirmed during a mean of 10 years of follow-up. Comparing women in the extreme quintiles, the multivariate relative risk of cataract was 0.82 (95% confidence interval, 0.71-0.95; test for trend, P = .04) for lutein/zeaxanthin and 0.86 (95% confidence interval, 0.74-1.00; test for trend, P = .03) for vitamin E from food and supplements. CONCLUSION: In these prospective observational data from a large cohort of female health professionals, higher dietary intakes of lutein/zeaxanthin and vitamin E from food and supplements were associated with significantly decreased risks of cataract.

Objective: Several studies have shown an inverse relation between vegetable and fruit intake and pancreatic cancer, but no specific beneficial component of such foods has been consistently identified. We considered the role of 15 selected vitamins and carotenoids and 6 minerals on pancreatic cancer risk in an Italian case-control study. METHODS: Subjects were 326 patients with incident pancreatic cancer and 652 controls, admitted to the same hospitals as cases for acute conditions. Micronutrient computation was based on a validated and reproducible food-frequency questionnaire. We estimated the odds ratios (OR) and confidence intervals (CI) using conditional logistic regression models, adjusted for various confounding factors and for energy intake, according to the residual model. RESULTS: Comparing the highest to the lowest quintile of intake, the OR were 0.60 (95% CI 0.36-0.98) for vitamin E, 0.44 (95% CI 0.27-0.73) for vitamin C, 0.56 (95% CI 0.34-0.93) for folate, and 0.57 (95% CI 0.35-0.92) for potassium. No significant inverse associations were observed for alpha-carotene (OR = 0.69, 95% CI 0.43-1.12), beta-carotene (OR = 0.64, 95% CI 0.39-1.06), and beta-cryptoxanthin (OR = 0.66, 95% CI 0.39-1.09). No relation was found for other micronutrients considered. CONCLUSION: Our findings support a favorable role of vitamins E and C, selected carotenoids, and folate on pancreatic carcinogenesis.

BACKGROUND: Dietary antioxidants may protect against DNA damage induced by endogenous and exogenous sources, including ionizing radiation (IR), but data from IR-exposed human populations are limited. OBJECTIVE: The objective was to examine the association between the frequency of chromosome translocations, as a biomarker of cumulative DNA damage, and intakes of vitamins C and E and carotenoids in 82 male airline pilots. DESIGN: Dietary intakes were estimated by using a self-administered semiquantitative food-frequency questionnaire. Translocations were scored by using fluorescence in situ hybridization with whole chromosome paints. Negative binomial regression was used to estimate rate ratios and 95% CIs, adjusted for potential confounders. RESULTS: Significant and inverse associations were observed between translocation frequency and intakes of vitamin C, beta-carotene, beta-cryptoxanthin, and lutein-zeaxanthin from food (P<0.05). Translocation frequency was not associated with the intake of vitamin E, alpha-carotene, or lycopene from food; total vitamin C or E from food and supplements; or vitamin C or E or multivitamin supplements. The adjusted rate ratios (95% CI) for>or =median compared withor =median compared with

BACKGROUND: Fruits and vegetables rich in antioxidants have been proposed to reduce the risk of renal cell cancer. However, few prospective studies have examined the intakes of fruits, vegetables, and antioxidant vitamins in relation to the risk of renal cell cancer. METHODS: We prospectively examined the associations between the intakes of fruits, vegetables, vitamins A, C, and E, and carotenoids and risk of renal cell cancer in women and men. We followed 88,759 women in the Nurses' Health Study from 1980 to 2000, and 47,828 men in the Health Professionals Follow-up Study from 1986 to 2000. We assessed dietary intake every 2 to 4 years using a validated semiquantitative food frequency questionnaire. The Cox proportional hazards model was used to estimate study-specific multivariate relative risks (RR), which were pooled using a random effects model. RESULTS: A total of 248 (132 women and 116 men) incident renal cell cancer cases were ascertained during 2,316,525 person-years of follow-up. The consumption of fruits and vegetables was associated with a decreased risk of renal cell cancer in men (multivariate RR, 0.45; 95% CI, 0.25-0.81, for>or=6 servings of fruit and vegetable intake/d versus<3 servings/d; P test for trend = 0.02), but not in women (multivariate RR, 1.17; 95% CI, 0.66-2.07, for the same contrast; P test for trend = 0.25; P test for between-studies heterogeneity = 0.02). Intakes of vitamins A and C from food and carotenoids were inversely associated with the risk of renal cell cancer in men only, but we cannot exclude the possibility that this was due to other factors in fruit and vegetables. No clear association was observed for vitamin E in women or men. CONCLUSIONS: Fruit and vegetable consumption may reduce the risk of renal cell cancer in men.

While diets rich in fruit and vegetables appear to reduce lung cancer risk, the evidence for individual carotenoid and vitamin intakes has been judged too limited to reach firm conclusions. Data from a case-control study of lung cancer (Montreal, QC, Canada, 1996-2002) were used to investigate the role of dietary intakes ofβ-carotene, α-carotene, β-cryptoxanthin, lutein/zeaxanthin, lycopene, and vitamin C in lung cancer risk. In-person interviews elicited dietary information from 1,105 incident cases and 1,449 population controls. Usual frequency of consumption of 49 fruits and vegetables 2 years prior to diagnosis/interview was collected. Odds ratios (ORs) and 95% confidence intervals (CIs) between intake variables and lung cancer were estimated using logistic or polytomous regression, adjusting for potential confounding factors including a detailed smoking history. ORs associated with upper versus lower tertiles of intake were 0.66 (95% CI = 0.51-0.84) for β-carotene, 0.70 (95% CI = 0.55-0.90) for α-carotene, 0.65 (95% CI = 0.51-0.84) for β-cryptoxanthin, 0.75 (95% CI = 0.59-0.95) for lycopene, and 0.74 (95% CI = 0.58-0.96) for vitamin C. ORs suggestive of a protective effectwere found for elevated intakes of β-carotene, α-carotene, β-cryptoxanthin, and lycopene in male heavy smokers and of vitamin C in female heavy smokers. Selected antioxidants were also associated with a lower risk of lung cancer in female moderate smokers, and of squamous cell carcinoma, adenocarcinoma, and small cell carcinoma. These results suggest that several dietary antioxidants found in common food sources may protect against lung cancer, even among heavy smokers.

BACKGROUND:Carotenoids and vitamin C are thought to be associated with reduced cancer risk because of their antioxidative capacity.

OBJECTIVE:This study evaluated the associations of plasma carotenoid, retinol, tocopherol, and vitamin C concentrations and risk of breast cancer.

DESIGN:In a nested case-control study within the European Prospective Investigation into Cancer and Nutrition cohort, 1502 female incident breast cancer cases were included, with an oversampling of premenopausal (n = 582) and estrogen receptor-negative (ER-) cases (n = 462). Controls (n = 1502) were individually matched to cases by using incidence density sampling. Prediagnostic samples were analyzed forα-carotene, β-carotene, lycopene, lutein, zeaxanthin, β-cryptoxanthin, retinol, α-tocopherol, γ-tocopherol, and vitamin C. Breast cancer risk was computed according to hormone receptor status and age at diagnosis (proxy for menopausal status) by using conditional logistic regression and was further stratified by smoking status, alcohol consumption, and body mass index (BMI). All statistical tests were 2-sided.

RESULTS:In quintile 5 compared with quintile 1,α-carotene (OR: 0.61; 95% CI: 0.39, 0.98) and β-carotene (OR: 0.41; 95% CI: 0.26, 0.65) were inversely associated with risk of ER- breast tumors. The other analytes were not statistically associated with ER- breast cancer. For estrogen receptor-positive (ER+) tumors, no statistically significant associations were found. The test for heterogeneity between ER- and ER+ tumors was statistically significant only for β-carotene (P-heterogeneity = 0.03). A higher risk of breast cancer was found for retinol in relation to ER-/progesterone receptor-negative tumors (OR: 2.37; 95% CI: 1.20, 4.67; P-heterogeneity with ER+/progesterone receptor positive = 0.06). We observed no statistically significant interaction between smoking, alcohol, or BMI and all investigated plasma analytes (based on tertile distribution).

CONCLUSION:Our results indicate that higher concentrations of plasmaβ-carotene and α-carotene are associated with lower breast cancer risk of ER- tumors.

The chemopreventive action of carotenoids on proteinuria and lymphadenopathy were examined in autoimmune-prone MRL-lpr/lpr (MRL/l) mice. They were fed a synthetic full-fed diet (16-18 kcal/mouse/day) with supplementation of beta-carotene or astaxanthin (0.19 mumoles/mouse, 3 times a week), and the development of lymphadenopathy and proteinuria were examined. MRL/l mice fed a full-fed diet without the supplementation of carotenoids or those fed a calorie-restricted (CR) diet (10-11 kcal/mouse/day, 60% calorie intake of full-fed mice) were employed as controls. CR dramatically delayed the development of proteinuria and lymphadenopathy, as reported previously. Carotenoids also significantly delayed the onset of these symptoms in MRL/l mice fed a full-fed diet. Carotenoids were half as effective as CR and astaxanthin, a carotenoid without provitamin A activity, which appeared to exert more significant preventive actions than beta-carotene in delaying the development of these symptoms. Similar chemopreventive actions of carotenoids were also demonstrated in MRL/l mice fed a regular diet (Lab Chow). CR has been shown to augment IL-2 production and to decrease serum prolactin levels in this strain, which may be related to its dramatic preventive action of autoimmunity. However, carotenoids did not affect IL-2 production nor prolactin levels in full-fed MRL/l mice. The chemopreventive actions of carotenoids observed in autoimmune-prone MRL/l mice may be attributed to yet unknown mechanisms, apart from their provitamin A activity or oxygen-quenching activity.