Plasma carotenoids, retinol, and tocopherols and risk of breast cancer

The roles of carotenoids, retinol, and tocopherols in breast cancer etiology have been inconclusive. The authors prospectively assessed the relations between plasma alpha-carotene, beta-carotene, beta-cryptoxanthin, lycopene, lutein/zeaxanthin, retinol, alpha-tocopherol, and gamma-tocopherol and breast cancer risk by conducting a nested case-control study using plasma collected from women enrolled in the Nurses' Health Study. A total of 969 cases of breast cancer diagnosed after blood draw and prior to June 1, 1998, were individually matched to controls. The multivariate risk of breast cancer was 25-35% less for women with the highest quintile compared with that for women with the lowest quintile of alpha-carotene (odds ratio (OR) = 0.64, 95% confidence interval (CI): 0.47, 0.88; p(trend) = 0.01), beta-carotene (OR = 0.73, 95% CI: 0.53, 1.02; p(trend) = 0.01), lutein/zeaxanthin (OR = 0.74, 95% CI: 0.55, 1.01; p(trend) = 0.04), and total carotenoids (OR = 0.76, 95% CI: 0.55, 1.05; p(trend) = 0.05). The inverse association observed with alpha-carotene and breast cancer was greater for invasive cancers with nodal metastasis. The authors conclude that some carotenoids are inversely associated with breast cancer. Although the association was strongest for alpha-carotene, the high degree of collinearity among plasma carotenoids limits our ability to conclude that this association is specific to any individual carotenoid.     

Plasma antioxidant vitamins and carotenoids in five Japanese populations with varied mortality from gastric cancer.

To examine the geographic associations between plasma antioxidant levels and gastric cancer risk, we conducted an ecological study in five regions of Japan representing the threefold variation in the disease mortality within the country. Subjects were 634 men aged 40-49 years sampled randomly from the five regions with 72% response rates. Plasma concentrations of five carotenoids (beta-carotene, alpha-carotene, lycopene, lutein, and zeaxanthin), alpha-tocopherol, and ascorbic acid were measured, and the mean levels were correlated with age-adjusted mortality rates from gastric cancer. beta-Carotene and alpha-tocopherol were inversely correlated with gastric cancer rates (r = -0.31 and -0.89, respectively). alpha-Carotene and lycopene showed stronger inverse correlation than did beta-carotene (r = -0.67 and -0.56, respectively), but these relations disappeared after the exclusion of one outlying region in Okinawa with the lowest mortality. In contrast, ascorbic acid revealed a negative correlation with the exclusion of this outlier (r = -0.61). Lutein and zeaxanthin were not inversely associated with risk. The results suggest that plasma levels of beta-carotene and alpha-tocopherol, and possibly alpha-carotene, lycopene, and ascorbic acid, may partly account for the regional difference in gastric cancer mortality in Japan.     

Retinol, carotenoids, and tocopherols in the milk of lactating adolescents and relationships with plasma concentrations

OBJECTIVE: We determined the concentrations of retinol, carotenoids, and tocopherols in breast milk of adolescents and evaluated their associations with plasma levels and with maternal characteristics (period of lactation, body mass index, age of menarche, and years postmenarche). METHODS: This was a single cross-sectional survey of retinol, carotenoid, and tocopherol composition of milk and plasma of lactating adolescent mothers (n = 72; 30-120 d postpartum) attending public daycare clinics in Rio de Janeiro, Brazil. Milk and plasma components were analyzed by high-performance liquid chromatography. RESULTS: Nutrient concentrations (micromoles per liter, mean +/- SE) in plasma and milk were, respectively, retinol 2.1 +/- 0.5 and 0.62 +/- 0.44, beta-carotene 0.18 +/- 0.19 and 0.016 +/- 0.017, alpha-carotene 0.05 +/- 0.04 and 0.0035 +/- 0.002, lutein plus zeaxanthin 0.15 +/- 0.11 and 0.025 +/- 0.024, lycopene 0.1 +/- 0.11 and 0.016 +/- 0.025, alpha-tocopherol 10.8 +/- 5.3 and 2.7 +/- 1.8, gamma-tocopherol 2.6 +/- 2.3 and 0.37 +/- 0.15. The milk/plasma molar ratios of retinol and tocopherols were two times higher than those of carotenoids. Significant correlations (P < 0.001) between milk and plasma nutrient levels were observed for beta-carotene (r = 0.41), alpha-carotene (r = 0.60), and lutein plus zeaxanthin (r = 0.57), but not for lycopene, retinol, and tocopherols. Nutrient concentrations in plasma and in milk were not associated with the maternal characteristics investigated. CONCLUSION: Concentrations of the nutrients studied, especially retinol and alpha-tocopherol, in mature milk of lactating adolescents were, in general, lower than in milk of adult lactating women. Milk concentrations were associated with plasma concentrations only for beta-carotene, alpha-carotene, and lutein plus zeaxanthin.     

Diet, plasma levels of beta-carotene and alpha-tocopherol, and risk of malignant melanoma

Dietary intake and the plasma levels of retinol, alpha-tocopherol, lycopene, alpha-carotene, and beta-carotene for 204 cases with malignant melanoma were compared with those of 248 controls. Cases and controls were patients 18 years of age or older making their first visit to a dermatology subspecialty clinic for pigmented lesions from July 1, 1982 to September 1, 1985. Intakes of nutrients were estimated using a semiquantitative food frequency questionnaire. No significant associations with malignant melanoma were observed for higher plasma levels of lycopene, retinol, or alpha-carotene in logistic regression analyses after controlling for age, sex, plasma lipids, and known constitutional risk factors (hair color and ability to tan). In similar models, the odds ratio comparing the highest with the lowest quintile was 0.9 (95% confidence interval (CI) 0.5-1.5) for plasma beta-carotene, 0.7 (95% CI 0.5-1.3) for plasma alpha-tocopherol, 0.7 (95% CI 0.4-1.2) for carotene intake, and 0.7 (95% CI 0.4-1.3) for total vitamin E intake. A trend toward reduced risk of melanoma was observed for increasing intake of iron (not including supplements); this was related to the more frequent consumption of baked goods, such as cake, among controls. Alcohol consumption was positively associated with risk of melanoma (chi for trend = 2.1, p = 0.03); the odds ratio for consumption of over 10 g/day compared with persons with no alcohol intake was 1.8 (95% CI 1.0-3.3).     

Status of carotenoids, vitamin A, and vitamin E in the mother-infant dyad and anthropometric status of infants in Malawi

This prospective study was carried out during February 2000-April 2003 to characterize the relationship between the status of carotenoids, vitamin E, and retinol and anthropometric status in apparently healthy infants and their mothers in Blantyre, Malawi. Anthropometric status of infants and concentrations of carotenoids (alpha-carotene, beta-carotene, beta-cryptoxanthin, lutein, zeaxanthin, and lycopene), retinol, and alpha-tocopherol in plasma were measured in 173 infants at 12 months of age, and concentrations of carotenoids, retinol, and a-tocopherol in plasma were measured in their mothers two weeks postpartum. In multivariate analyses, concentrations of retinol, total carotenoids, non-provitamin A carotenoids, and alpha-tocopherol in infants were associated with under-weight (p = 0.05). Concentrations of a-tocopherol were associated with wasting (p = 0.04). Concentrations in mothers and infants were all correlated (correlation coefficients from 0.230 to 0.502, p < 0.003). The findings suggest that poor status of carotenoids, retinol, and alpha-tocopherol in infants is associated with their poor anthropometric status, and status of carotenoids, retinol, and alpha-tocopherol in mothers and infants has a low-to-moderate association in the mother-infant dyad.     

The relationship between total plasma carotenoids and risk factors for chronic disease among middle-aged and older men

Individual plasma carotenoids have been associated with various chronic diseases but little is known about the relationship between total plasma carotenoids and risk factors for chronic diseases. In the Physicians' Health Study, we examined 492 men free of CVD and cancer for the relationship between total plasma carotenoids (the sum of alpha-carotene, beta-carotene, lycopene, zeaxanthin, lutein and beta-cryptoxanthin) and a wide variety of factors that predict chronic disease. Multivariate linear and logistic regression was performed to calculate parameter estimates (95% CI) and OR (95% CI) for total plasma carotenoids. In linear regression models, BMI, hypertension, alcohol intake and plasma levels of each lipid parameter and a-tocopherol significantly predicted levels of total plasma carotenoids. Upon adjustment for multiple chronic disease risk factors, the OR for levels of total plasma carotenoids greater than or equal to the median (> or=1.301 micromol/l) was statistically significant for current smoking (OR 0.21; 95% CI 0.06, 0.77), weekly alcohol ingestion (OR 2.30; 95% CI 1.06, 4.99), daily alcohol ingestion (OR 2.46; 95% CI 1.29, 4.67), each 100 mg/l increase in total cholesterol (OR 0.73; 95% CI 0.58, 0.91), LDL-cholesterol (OR 1.48; 95% CI 1.17, 1.89) and HDL-cholesterol (OR 1.58; 95% CI 1.26, 1.99), each 100 mg/ml increase in intercellular adhesion molecule-1 (OR 0.70; 95% CI 0.53, 0.93) and each 10 micromol/l increase in alpha-tocopherol (OR 1.33; 95% CI 1.12, 1.57), using logistic regression. Few lifestyle and clinical risk factors appear to be related to levels of total plasma carotenoids; however, levels of biomarkers such as plasma lipids and alpha-tocopherol may be strongly related.     

Serum concentrations of retinol, alpha-tocopherol and the carotenoids are influenced by diet, race and obesity in a sample of healthy adolescents

An important part of understanding the functions of vitamin A, vitamin E and the carotenoids in nutritional status assessment, health promotion and disease prevention is knowledge of factors that influence their distribution in human tissues. Our objective was to examine serum concentrations of these nutrients and compounds in a sample of 285 healthy participants, 12-17 y old, from three U. S. cities. Pearson correlations between diet measured with a food frequency questionnaire and serum nutrient concentrations among these adolescents (adjusted for total serum cholesterol, age, sex, race and body mass index) were as follows: retinol, 0.23; alpha-tocopherol, 0.16; alpha-carotene, 0.31; beta-carotene, 0.15; beta-cryptoxanthin, 0.38; lycopene, 0.08; and lutein + zeaxanthin, 0.25. Multivariate linear regression modeled associations of demographic, dietary and physiologic variables with serum concentrations of these nutrients. African-American participants had significantly lower concentrations of serum retinol (P < 0.001), alpha-tocopherol (P < 0.01) and alpha-carotene (P < 0.02), but higher concentrations of lutein + zeaxanthin (P = 0.001) compared with Caucasians. Obese participants had serum nutrient concentrations that were 2-10% (P < 0.05) lower than normal weight participants. Dietary intake was a significant predictor of all serum analytes (P < 0.01) except lycopene. These models explained 20% of the variability in serum retinol, 28% of the variability in serum alpha-tocopherol, and 14-24% of the variability in serum carotenoids.     

Plasma lycopene, other carotenoids, and the risk of type 2 diabetes in women

The authors conducted a nested case-control study from 1992 to 2003 among US women aged 45 years or older and free from cardiovascular disease and cancer to examine the prospective association among plasma lycopene, other carotenoids, and the risk of developing type 2 diabetes. During 10 years of follow-up, 470 cases of incident type 2 diabetes were selected and individually matched on age (+/- 1 year) and follow-up time to 470 nondiabetic controls. Baseline plasma levels of lycopene, alpha-carotene, beta-carotene, beta-cryptoxanthin, and lutein/zeaxanthin were similar in cases and controls (all p > 0.05). A possible crude inverse association between plasma lycopene and risk of type 2 diabetes was attenuated upon multivariate adjustment. After control for plasma total cholesterol and known diabetes risk factors, the multivariate odds ratios of type 2 diabetes in the highest versus the lowest quartile of plasma carotenoids were 1.13 (95% confidence interval (CI): 0.60, 2.13) for lycopene, 1.27 (95% CI: 0.63, 2.57) for alpha-carotene, 1.10 (95% CI: 0.57, 2.13) for beta-carotene, 0.91 (95% CI: 0.46, 1.81) for beta-cryptoxanthin, and 1.35 (95% CI: 0.68, 2.69) for lutein/zeaxanthin. There was no prospective association between baseline plasma carotenoids and the risk of type 2 diabetes in middle-aged and older women.     

Vitamin A, retinol, and carotenoids and the risk of gastric cancer: a prospective cohort study

BACKGROUND: Vitamin A may influence gastric carcinogenesis through its essential role in controlling cell proliferation and differentiation. However, epidemiologic studies of vitamin A, retinol (preformed vitamin A), and provitamin A carotenoids in relation to the risk of gastric cancer have documented inconsistent results. OBJECTIVE: The objective of the study was to examine the associations between intakes of vitamin A, retinol, and specific carotenoids and the risk of gastric cancer in a prospective population-based cohort study of Swedish adults. DESIGN: The study cohort consisted of 82 002 Swedish adults aged 45-83 y who had completed a food-frequency questionnaire in 1997. The participants were followed through June 2005. RESULTS: During a mean 7.2-y follow-up, 139 incident cases of gastric cancer were diagnosed. High intakes of vitamin A and retinol from foods only (dietary intake) and from foods and supplements combined (total intake) and of dietary alpha-carotene and beta-carotene were associated with a lower risk of gastric cancer. The multivariate relative risks for the highest versus lowest quartiles of intake were 0.53 (95% CI: 0.32, 0.89; P for trend = 0.02) for total vitamin A, 0.56 (95% CI: 0.33, 0.95; P for trend = 0.05) for total retinol, 0.50 (95% CI: 0.30, 0.83; P for trend = 0.03) for alpha-carotene, and 0.55 (95% CI: 0.32, 0.94; P for trend = 0.07) for beta-carotene. No significant associations were found for beta-cryptoxanthin, lutein and zeaxanthin, or lycopene intake. CONCLUSION: High intakes of vitamin A, retinol, and provitamin A carotenoids may reduce the risk of gastric cancer.     

Dietary carotenoids and risk of breast cancer in Chinese women

There has been considerable interest in the role of carotenoids in the chemoprevention of cancer. However, the protective effect of carotenoids on breast cancer has been inconclusive. To investigate whether intake of lycopene, alpha-carotene, beta-carotene, beta-cryptoxanthin, and lutein/zeaxanthin is inversely associated with breast cancer risk, a case-control study was conducted in China during 2004-2005. The cases were 122 female patients aged 24-87 years with histopathologically confirmed breast cancer. 632 healthy women age-matched were randomly recruited from outpatient clinics. Habitual dietary intake and lifestyle were collected by face-to-face interview using a validated and reliable food frequency questionnaire. The USDA nutrient composition database was used to calculate intake of the specific carotenoids. Unconditional logistic regression analyses were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs), accounting for age, locality, education, body mass index, smoking, passive smoking, physical activity, number of children breastfed, menopausal status, oral contraceptive use, biopsy-confirmed benign breast diseases, family history of breast cancer, and total energy intake. Compared with the highest versus lowest quartile of intake, the adjusted ORs were 0.26 (95% CI 0.14-0.46) for lycopene, 0.38 (95% CI 0.21-0.71) for beta-carotene, 0.43 (95% CI 0.23-0.82) for beta-cryptoxanthin, and 0.37 (95% CI 0.20-0.68) for total carotenoids, with statistically significant tests for trend. There was no association with breast cancer for alpha-carotene and lutein/zeaxanthin. It is concluded that higher intake of lycopene, beta-carotene and beta-cryptoxanthin is associated to a lower risk of breast cancer among Chinese women. More research to examine the relationship between carotenoids and breast cancer risk is warranted.     

Plasma concentrations of carotenoids, retinol, and tocopherols in preeclamptic and normotensive pregnant women

This case-control study was conducted in Lima, Peru, from June 1997 through January 1998 to assess whether plasma concentrations of carotenoids (alpha-carotene, beta-carotene, lycopene, lutein, zeaxanthin, beta-cryptoxanthin), retinol, and tocopherols (alpha-tocopherol and gamma-tocopherol) are decreased in women with preeclampsia. A total of 125 pregnant women with preeclampsia and 179 normotensive pregnant women were included. Plasma concentrations of antioxidants were determined using high performance liquid chromatography. After adjusting for maternal demographic, behavioral, and reproductive characteristics and total plasma lipid concentrations, the authors found a linear increase in risk of preeclampsia with increasing concentrations of alpha-tocopherol (odds ratio of the highest quartile = 3.13; 95% confidence interval: 1.06, 9.23, with the lowest quartile as the reference group; p value of the test of linear trend = 0.040). The risk of preeclampsia decreased across increasing quartiles of concentrations for retinol (odds ratio of the highest quartile = 0.32; 95% confidence interval: 0.15, 0.69, with the lowest quartile as the reference group; p value of the test of linear trend = 0.001). Some of these results are inconsistent with the prevailing hypothesis that preeclampsia is an antioxidant-deficient state. Preliminary findings confirm an earlier observation of increased plasma concentrations of alpha-tocopherol among women with preeclampsia as compared with normotensive pregnant women.     

The homeostasis model assessment-insulin resistance index is inversely associated with serum carotenoids in non-diabetic subjects

BACKGROUND: Carotenoids may reduce the risk for diabetes mellitus, but little is known about the association of insulin resistance with serum carotenoids in non-diabetic subjects. This study aimed to investigate whether the homeostasis model assessment-insulin resistance (HOMA-IR) index would be lower in the presence of high serum carotenoid concentrations in non-diabetic subjects. METHODS: A total of 812 subjects (256 males and 556 females) who had received health examinations in 2003 participated in the study. The associations of the serum-carotenoid concentrations and HOMA-IR were evaluated cross-sectionally. The multivariate-adjusted geometric means of HOMA-IR by the tertiles of the serum carotenoid concentration were calculated after adjusting for age, body mass index, systolic blood pressure, total cholesterol, triacylglycerols, current tobacco use, regular alcohol intake, exercise habits and total energy intake. Associations among high HOMA-IR (3.0+mUxmmol/L2) across tertiles of serum carotenoid concentration were assessed by tests for logistic regression analysis. RESULTS: In male subjects, the multivariate adjusted geometric mean of HOMA-IR was inversely associated with the serum beta-cryptoxanthin concentrations. In female subjects, an inverse association of the serum carotenoid concentration and HOMA-IR was observed in lycopene, beta-cryptoxanthin, and zeaxanthin. The confounding factor-adjusted odds ratios (OR) for high HOMA-IR on the highest tertiles of serum alpha-carotene, beta-carotene, beta-cryptoxanthin, and zeaxanthin were 0.18 [95% confidence interval (CI): 0.06-0.52], 0.22 (95% CI: 0.07-0.67), 0.34 (95% CI: 0.12-0.96), and 0.30 (95% CI: 0.11-0.79), respectively, in male subjects. On the other hand, in female subjects, the adjusted OR for high HOMA-IR on the highest tertiles of serum lycopene and beta-cryptoxanthin were 0.39 (95% CI: 0.21-0.73) and 0.51 (95% CI: 0.28-0.95), respectively. CONCLUSIONS: The serum antioxidant carotenoids were inversely associated with HOMA-estimated insulin resistance in non-diabetic subjects.     

Serum antioxidants and subsequent mortality rates of all causes or cancer among rural Japanese inhabitants

The purpose of this study was to investigate whether a relationship exists between mortality rates and serum antioxidant levels among Japanese inhabitants. The follow-up subjects, who participated in comprehensive health examinations, consisted of 2444 inhabitants (949 males and 1495 females) of a rural area in Hokkaido, Japan. Between 1991 and December 2000, 146 subjects (94 males and 52 females) died, with cancer accounting for 76 of these deaths (48 males and 28 females). Serum samples at fasting were collected at entry into the study, and serum levels of beta- and alpha-carotenes, lycopene, beta-cryptoxanthin, canthaxanthin, zeaxanthin/lutein, tocopherols, and retinol were measured separately by high-performance liquid chromatography (HPLC). The statistical analyses were conducted using the Cox proportional hazard model. Age- and gender-adjusted hazard ratios of the groups with high serum levels of lycopene, beta-carotene, zeaxanthin/lutein, and total carotenoids compared to those with low serum levels were 0.36 (95% C.I: 0.19-0.69), 0.53 (0.29-0.95), 0.73 (0.43-1.25), and 0.52 (0.30-0.92) for cancers of all sites, and 0.44 (95% C.I: 0.28-0.69), 0.59 (0.39-0.90), 0.61 (0.40-0.93), and 0.50 (0.33-0.76) for all causes, respectively. Similar results were found after adjusting for gender, age, smoking habits, alcohol consumption, and serum levels of total cholesterol and glutamic pyruvic transaminase (GPT) activity. Moreover, after excluding mortality within the first three years of follow-up, the hazard ratios of subjects with high serum levels of lycopene, total carotenes, and total carotenoids were significantly and inversely associated with subsequent mortality from all causes and cancers of all sites after adjusting for gender, age, and serum levels of total cholesterol, alpha-tocopherol, and retinol. These results suggest that high serum levels of antioxidants, such as lycopene, beta-carotene and zeaxanthin/lutein, play roles in preventing death from cancer and from all causes. However, high serum levels of tocopherols and retinol did not demonstrate clear associations with either low mortality rates from all causes or cancer of all sites.     

Both alpha- and beta-carotene, but not tocopherols and vitamin C, are inversely related to 15-year cardiovascular mortality in Dutch elderly men

The role of beta-carotene, alpha-tocopherol, and vitamin C in the prevention of cardiovascular diseases (CVD) is controversial. Prospective studies on gamma-tocopherol and carotenoids other than beta-carotene are sparse. We assessed relations between the intake of different carotenoids, alpha- and gamma-tocopherol, and vitamin C with 15-y CVD mortality in elderly men who participated in the Zutphen Elderly Study. Information on diet and potential confounding factors was collected in 1985, 1990, and 1995. In 1985, 559 men (mean age approximately 72 y) free of chronic diseases were included in the current analysis. After 15 y of follow-up, comprising 5744 person-years, 197 men had died from CVD. After adjustment for age, smoking, and other potential lifestyle and dietary confounders, relative risks (RR) (95% CI) of CVD death for a 1-SD increase in intake were 0.81 (0.66-0.99) for alpha-carotene and 0.80 (0.66-0.97) for beta-carotene. Carrots were the primary source of alpha- and beta-carotene and their consumption was related to a lower risk of death from CVD (adjusted RR, 0.83; 95% CI = 0.68-1.00). Intakes of carotenoids other than alpha- and beta-carotene were not associated with CVD mortality, nor were vitamin C and alpha- and gamma tocopherol. In conclusion, dietary intakes of alpha-carotene and beta-carotene are inversely associated with CVD mortality in elderly men. This study does not indicate an important role for other carotenoids, tocopherols, or vitamin C in lowering the risk of CVD death.     

Intake of specific carotenoids and the risk of epithelial ovarian cancer

There has been considerable interest in the role of carotenoids in the chemoprevention of cancer. However, few studies have examined the association between intake of specific carotenoids and the risk of epithelial ovarian cancer and the results for carotenoids have been inconclusive. To investigate whether the intake of alpha-carotene, beta-carotene, beta-cryptoxanthin, lutein and zeaxanthin, and lycopene is inversely associated with ovarian cancer risk, a case-control study was conducted in China during 1999-2000. The cases were 254 patients with histologically confirmed epithelial ovarian cancer and 652 age-matched controls were randomly recruited during the same period. Habitual dietary intake and lifestyle were collected by face-to-face interview using a validated and reliable FFQ. The US Department of Agriculture nutrient composition database was used to calculate the intake of specific carotenoids. Unconditional logistic regression analyses were used to estimate OR and 95 % CI, accounting for age, locality, education, BMI, smoking, tea drinking, parity, oral contraceptive use, hormone replacement therapy, menopausal status, family history of ovarian cancer, physical activity and energy intake. Compared with the highest v. the lowest quartile of intake, the adjusted OR were 0.39 (95 % CI 0.23, 0.66) for alpha-carotene, 0.51 (95 % CI 0.31, 0.84) for beta-carotene, 0.51 (95 % CI 0.31, 0.83) for beta-cryptoxanthin, 0.45 (0.27, 0.76) for lutein and zeaxanthin, and 0.33 (95 % CI 0.20, 0.56) for total carotenoids, with statistically significant tests for trend. It is concluded that a higher intake of carotenoids can reduce the risk of epithelial ovarian cancer.     

Plasma Carotenoids and Retinol and Overall and Breast Cancer Risk: A Nested Case-Control Study

Experimental studies suggest that carotenoids and retinol may play a role in carcinogenesis, but epidemiological evidence is lacking. We investigated the prospective associations between plasma concentrations of major carotenoids and retinol, and overall and breast cancer risk. A nested case-control study included all first incident cancer cases diagnosed in the SU.VI.MAX cohort between 1994 and 2002 (n = 159 cases, 1 matched control/case). Baseline plasma concentrations of carotenoids and retinol were measured by high-performance liquid chromatography. Conditional logistic regression was used to assess odds ratios for an increase of 0.1 μmol/L [odds ratio (OR)] and 95% confidence intervals (CI). Plasma β-carotene (OR = 0.95, 95% CI = 0.90–0.99, P_trend = 0.04) and β-cryptoxanthin concentrations (OR = 0.89, 95% CI = 0.81–0.99, P_trend = 0.03) were inversely associated with overall cancer risk. Plasma β-cryptoxanthin concentration was inversely associated with breast cancer risk (OR = 0.83, 95% CI = 0.71–0.96, P_trend = 0.02). The OR between plasma lycopene concentration and overall cancer risk was 1.07 (0.99–1.15), P_trend = 0.06. This association turned significant (P_trend = 0.01) when excluding cancer cases diagnosed during the first year of follow-up. This prospective study suggests an inverse association between plasma concentrations of β-cryptoxanthin and both overall and breast cancer risk, and an inverse association between β-carotene and overall cancer risk. The direct association between lycopene concentration and cancer risk deserves further investigation.     

Correlations of vitamin A and E intakes with the plasma concentrations of carotenoids and tocopherols among American men and women.

The authors investigated the association of diet and other factors with the plasma concentrations of carotenoids, retinol and tocopherols in a sample of 121 men and 186 women participating in two prospective investigations of dietary etiologies of chronic diseases. Lycopene (mean concentration, 0.82 mumol/L in men, 0.76 mumol/L in women), beta-carotene (mean 0.46 mumol/L in men, 0.58 mumol/L in women) and lutein (mean 0.28 mumol/L in men, 0.27 mumol/L in women) were the major circulating carotenoids. Among nonsmokers, dietary carotenoid, as typically calculated in epidemiologic studies, was significantly correlated with plasma beta-carotene (r = 0.34 in men, r = 0.30 in women), alpha-carotene (r = 0.52 in men, r = 0.37 in women) and lutein (r = 0.36 in men, r = 0.19 in women), but not with plasma zeaxanthin (r = 0.11 and r = 0.02) or lycopene (r = 0.13 and r = 0.01) after adjusting for plasma cholesterol and triglycerides, body mass index and energy intake. Total vitamin E intake was positively associated with plasma concentrations of alpha-tocopherol (r = 0.51 in men, r = 0.41 in women) and inversely associated with plasma concentrations of gamma-tocopherol (r = -0.51 in men r = -0.42 in women), but this was primarily due to use of vitamin E supplements. Measurements of specific carotenoids can provide independent information beyond the usual calculation of carotene intake in epidemiologic studies.     

Serum antioxidants, inflammation, and total mortality in older women

The inflammatory cytokine interleukin-6 (IL-6) has been linked to poor health outcomes in older adults. Oxidative stress triggers the production of IL-6, and antioxidant micronutrients play a critical role in decreasing this inflammatory response. The authors sought to identify the relations between serum levels of antioxidant nutrients and IL-6 and mortality in older women. Levels of alpha- and beta-carotene, lycopene, lutein/zeaxanthin, alpha-cryptoxanthin, total carotenoids, retinol, alpha-tocopherol, zinc, and selenium were measured at baseline in 619 participants in Women's Health and Aging Study I (Baltimore, Maryland, 1992-1998). IL-6 was measured at baseline and at follow-up 1 and 2 years later, and all-cause mortality was determined over a 5-year period. Participants with the highest serum levels of alpha-carotene, total carotenoids, and selenium were significantly less likely to be in the highest tertile of serum IL-6 at baseline (p < 0.0001). Those with the lowest levels of alpha- and beta-carotene, lutein/zeaxanthin, and total carotenoids were significantly more likely to have increasing IL-6 levels over a period of 2 years. Those with the lowest selenium levels had a significantly higher risk of total mortality over a period of 5 years (hazard ratio = 1.54, 95% confidence interval: 1.03, 2.32). These findings suggest that specific antioxidant nutrients may play an important role in suppressing IL-6 levels in disabled older women.     

Associations of plasma carotenoids with risk factors and biomarkers related to cardiovascular disease in middle-aged and older women

BACKGROUND: Cardiovascular disease (CVD) risk factors may potentially influence plasma concentrations of carotenoids. However, data on the association of plasma carotenoids with CVD related biomarkers are only limited. OBJECTIVE: We examined the cross-sectional association of plasma carotenoids with blood lipids, glycated hemoglobin (Hb A(1c)), and C-reactive protein (CRP) in middle-aged and older women initially free of CVD and cancer. DESIGN: Participants from 3 nested case-control studies in the Women's Health Study were pooled. Baseline plasma carotenoids, including alpha-carotene, beta-carotene, beta-cryptoxanthin, lycopene, and lutein-zeaxanthin, blood lipids, Hb A(1c), and CRP were available for 2895 women. RESULTS: Women who were current smokers or obese had lower plasma concentrations of most carotenoids expect for lycopene. After adjusting for age, race, lifestyle factors, clinical factors, plasma total cholesterol, and dietary carotenoids, an increase of 30 mg/dL in LDL cholesterol was associated with a 17% increase in alpha-carotene, a 16% increase in beta-carotene, and an 8.5% increase in lycopene; an increase of 10 mg/dL in HDL cholesterol was associated with a 5.3% decrease in lycopene; an increase of 0.3% in Hb A(1c) was associated with a 1.4% increase in lycopene; and an increase of 2 mg/L in CRP was associated with a 1.3% decrease in beta-carotene (all P < 0.01). CONCLUSIONS: In middle-aged and older women free of CVD and cancer, plasma carotenoids were associated with smoking, obesity, LDL cholesterol, HDL cholesterol, Hb A(1c), and CRP. The associations differ among individual carotenoids, possibly reflecting metabolic effects of lifestyle and physiologic factors on plasma carotenoids, and may partially explain the inverse association of plasma carotenoids with CVD outcomes observed in epidemiologic studies.     

Serum carotenoids and breast cancer.

The consumption of vegetables and fruit may protect against many types of cancer, but research evidence is not compelling for breast cancer. Carotenoids are pigments that are present in most plants and have known antioxidant properties. Blood concentrations of carotenoids have been proposed as integrated biochemical markers of vegetable, fruit, and synthetic supplements consumed. In a case-control study (270 cases, 270 controls) nested within a cohort in New York during 1985-1994, the carotenoids lutein, zeaxanthin, beta-cryptoxanthin, lycopene, alpha-carotene, and beta-carotene were measured in archived serum samples using liquid chromatography. There was an evident increase in the risk of breast cancer for decreasing beta-carotene, lutein, alpha-carotene, and beta-cryptoxanthin. The risk of breast cancer approximately doubled among subjects with blood levels of beta-carotene at the lowest quartile, as compared with those at the highest quartile (odds ratio = 2.21; 95% confidence interval (CI): 1.29, 3.79). The risk associated with the other carotenoids was similar, varying between 2.08 (95% CI: 1.11, 3.90) for lutein and 1.68 (95% CI: 0.99, 2.86) for beta-cryptoxanthin. The odds ratio for the lower quartile of total carotenoids was 2.31 (95% CI: 1.35, 3.96). These observations offer evidence that a low intake of carotenoids, through poor diet and/or lack of vitamin supplementation, may be associated with increased risk of breast cancer and may have public health relevance for people with markedly low intakes.