BACKGROUND: Experimental research indicates that oxidative stress is implicated in aging and in the pathogenesis of diabetes and its complications. This evidence is limited in elderly patients with non-insulin dependent diabetes, in which age- and disease-related production of reactive oxygen species might exert synergistic damaging effects on tissues and organs. METHODS: Plasma levels of lipid-soluble compounds with antioxidant properties including vitamin A, vitamin E and carotenoids (lutein, zeaxanthin, beta-cryptoxanthin, lycopene, alpha- and beta-carotene) were measured by HPLC in 72 elderly patients with non-insulin dependent diabetes (75.70.8 years, 40 F, 32 M) and in 75 age-matched controls (77.21.2 years, 48 F, 27 M). RESULTS: All compounds measured were significantly lower in plasma from diabetic patients as compared to controls (p<0.0001). Plasma levels of vitamins A and E and of carotenoids did not significantly correlate with dietary intake and lipid profile in both groups. In
patients, significant inverse correlations were found between age and levels of
vitamin E, beta-cryptoxanthin, lycopene and beta-carotene. CONCLUSIONS: We conclude that patients of very old age with Type 2 diabetes show a poor plasma status of vitamins A and E and carotenoids, which negatively correlates with age. Further studies are needed to explore the possible therapeutic role of
lipid-soluble vitamin supplements in elderly diabetic subjects. Copyright 2000
John Wiley & Sons, Ltd.

The possible immuno-modulatory action of dietary lutein in dogs is not known.
Female Beagle dogs (17-18-month old; 11.40.4kg body weight) were supplemented daily with 0, 5, 10 or 20mg lutein for 12 weeks. Delayed-type hypersensitivity (DTH) response to saline, phytohemagglutinin (PHA) and a polyvalent vaccine was assessed on Weeks 0, 6 and 12. Blood was sampled on Weeks 0, 2, 4, 8 and 12 to assess (1) lymphocyte proliferative response to PHA, concanavalin A (Con A), and pokeweed mitogen (PWM), (2) changes in peripheral blood mononuclear cell (PBMC) populations, (3) interleukin-2 (IL-2) production and (4) IgG and IgM production. After the completion of 12-week study, we continued to collect the blood weekly up to 17 weeks to evaluate the changes in immunoglobulin production upon first and second antigenic challenges on Weeks 13 and 15. Plasma lutein was undetectable in unsupplemented dogs but concentrations increased (P<0.05)
rapidly on Week 2 in lutein-supplemented dogs. Thereafter, concentrations
generally continued to increase in dose-dependent manner, albeit at a much
slower rate. Dogs fed lutein had heightened DTH response to PHA and vaccine by Week 6. Dietary lutein increased (P<0.05) lymphocyte proliferative response to all three mitogens and increased the percentages of cells expressing CD5, CD4, CD8 and major histocompatibility complex class II (MHC II) molecules. The production of IgG increased (P<0.05) in lutein-fed dogs after the second
antigenic challenge. Lutein did not influence the expression of CD21 lymphocyte
marker, plasma IgM or IL-2 production. Therefore, dietary lutein stimulated both
cell-mediated and humoral immune responses in the domestic canine.

Post hoc analysis of data obtained from a study designed to modulate oxidative
damage by dietary intervention revealed consistently strong inverse correlations
between plasma xanthophyll carotenoids and oxidative damage indices.
Thirty-seven women participated in a 14-day dietary intervention that increased
mean vegetable and fruit (VF) consumption to approximately 12 servings/day. An additional 10 subjects participated in an intervention that limited VF
consumption to less than four servings per day. 8-Hydroxy-2'-deoxyguanosine
(8-OHdG) in DNA isolated from peripheral lymphocytes and 8-OHdG excreted in
urine were measured as indices of oxidative DNA damage. Lipid peroxidation was assessed by measuring 8-epiprostaglandin F2alpha (8-EPG) in urine. Plasma levels of selected carotenoids were also determined, with the intention of using a-carotene as a biochemical index of VF consumption. Urinary 8-OHdG and 8-EPG were measured by ELISA, and plasma carotenoids were measured by high performance liquid chromatography. Lymphocyte 8-OHdG was measured by reverse phase high performance liquid chromatography with electrochemical detection. We observed that the structurally related xanthophyll carotenoids, lutein and beta-cryptoxanthin, which occur in dissimilar botanical families, were consistently inversely associated with these oxidative indices. Statistically significant inverse correlations were observed between plasma lutein and/or beta-cryptoxanthin levels and lymphocyte 8-OHdG and urinary 8-EPG. Moreover, an inverse correlation was observed between change in plasma xanthophylls and change in lymphocyte 8-OHdG concentration that occurred during the course of the study. These data lead us to hypothesize that lutein and beta-cryptoxanthin serve as markers for the antioxidant milieu provided by plants from which they are derived. Whether these carotenoids are directly responsible for the observed antioxidant phenomena merits further investigation.

Many studies have reported inverse associations between vegetable and fruit
consumption and lung cancer risk. The aim of the present study was to elucidate
the role of several antioxidants and folate in this relationship. In the
Netherlands Cohort Study on Diet and Cancer, 58,279 men of ages 55-69 years at baseline in 1986 returned a questionnaire including a 150-item food frequency questionnaire. After 6.3 years of follow-up, 939 male lung cancer cases were registered. A new Dutch carotenoid database was used to estimate intake of alpha-carotene, beta-carotene, lutein + zeaxanthin, beta-cryptoxanthin, and lycopene, completed with the antioxidant vitamins C and E and folate. Using
case-cohort analysis, rate ratios were calculated, adjusted for age, smoking,
educational level, and family history of lung cancer. Protective effects on lung
cancer incidence were found for lutein + zeaxanthin, beta-cryptoxanthin, folate,
and vitamin C. Other carotenoids (alpha-carotene, beta-carotene, and lycopene)
and vitamin E did not show significant associations. After adjustment for
vitamin C, only folate remained inversely associated, and after adjustment for
folate, only beta-cryptoxanthin and vitamin C remained significantly associated.
Inverse associations were strongest among current smokers and weaker for former smokers at baseline. Inverse associations with carotenes, lutein + zeaxanthin, and beta-cryptoxanthin seemed to be limited to small cell and squamous cell carcinomas. Only folate and vitamin C intake appeared to be inversely related to small cell and squamous cell carcinomas and adenocarcinomas. Folate, vitamin C, and beta-cryptoxanthin might be better protective agents against lung cancer in smokers than alpha-carotene, beta-carotene, lutein + zeaxanthin, and lycopene.

The effects of carotenoids--alpha-carotene, beta-carotene, lycopene,
beta-cryptoxanthin, zeaxanthin, lutein, canthaxanthin, astaxanthin--on the
invasion of rat ascites hepatoma AH109A cells were investigated by co-culturing
the hepatoma cells with rat mesentery-derived mesothelial cells (M-cells). All
the carotenoids examined inhibited AH109A invasion in a dose-dependent manner up to 5 microM. Cancer cells previously cultured with hypoxanthine (HX) and xanthine oxidase (XO) showed a highly invasive activity. Carotenoids, 5 microM of beta-carotene and astaxanthin, suppressed this reactive oxygen
species-potentiated invasive capacity by simultaneously treating AH109A cells
with the carotenoids, HX and XO. These results suggest that the antioxidative
property of these carotenoids may be involved in their anti-invasive action.

PURPOSE: In addition to acting as an optical filter, macular (carotenoid)
pigment has been hypothesized to function as an antioxidant in the human retina by inhibiting the peroxidation of long-chain polyunsaturated fatty acids.
However, at its location of highest density in the inner (prereceptoral) layers
of the foveal retina, a specific requirement for antioxidant protection would
not be predicted. The purpose of this study was to determine whether lutein and
zeaxanthin, the major carotenoids comprising the macular pigment, are present in rod outer segment (ROS) membranes where the concentration of long-chain
polyunsaturated fatty acids, and susceptibility to oxidation, is highest.
METHODS: Retinas from human donor eyes were dissected to obtain two regions: an annular ring of 1.5- to 4-mm eccentricity representing the area centralis excluding the fovea (perifoveal retina) and the remaining retina outside this region (peripheral retina). ROS and residual (ROS-depleted) retinal membranes were isolated from these regions by differential centrifugation and their purity checked by polyacrylamide gel electrophoresis and fatty acid analysis. Lutein and zeaxanthin were analyzed by high-performance liquid chromatography and their concentrations expressed relative to membrane protein. Preparation of membranes and analysis of carotenoids were performed in parallel on bovine retinas for comparison to a nonprimate species. Carotenoid concentrations were also determined for retinal pigment epithelium harvested from human eyes. RESULTS: ROS membranes prepared from perifoveal and peripheral regions of human retina were found to be of high purity as indicated by the presence of a dense opsin band on protein gels. Fatty acid analysis of human ROS membranes showed a characteristic enrichment of docosahexaenoic acid relative to residual membranes. Membranes prepared from bovine retinas had protein profiles and fatty acid composition similar to those from human retinas. Carotenoid analysis showed that lutein and zeaxanthin were present in ROS and residual human retinal membranes. The combined concentration of lutein plus zeaxanthin was 70% higher in human ROS than in residual membranes. Lutein plus zeaxanthin in human ROS
membranes was 2.7 times more concentrated in the perifoveal than the peripheral retinal region. Lutein and zeaxanthin were consistently detected in human retinal pigment epithelium at relatively low concentrations. CONCLUSIONS: The presence of lutein and zeaxanthin in human ROS membranes raises the possibility that they function as antioxidants in this cell compartment. The finding of a higher concentration of these carotenoids in ROS of the perifoveal retina lends support to their proposed protective role in age-related macular degeneration.

We examined the effects of all-trans retinoic acid (ATRA) and lutein (a
nonprovitamin A carotenoid), on apoptosis and chemosensitivity in primary normal human mammary epithelial cells, SV40 transformed mammary cells, and MCF-7 human mammary carcinoma cells. ATRA and lutein selectively induced apoptosis in transformed but not normal human mammary cells. In addition, both compounds protected normal cells, but not transformed cells, from apoptosis induced by the chemotherapy agents etoposide and cisplatin. Furthermore, lutein and ATRA selectively increased the ratio of Bcl-xL:Bax protein expression in normal cells but not transformed mammary cells, suggesting a possible mechanism for selective
modulation of apoptosis. The differential effects of lutein and ATRA on
apoptotic pathways in normal versus transformed mammary epithelial cells may
have important implications for chemoprevention and therapy.

The immuno-modulatory role of dietary lutein in domestic cats is unknown. Female Tabby cats (10-month old; n=56) were supplemented daily for 12 weeks with 0, 1, 5 or 10mg lutein. Blood was collected on Weeks 0, 2, 4, 8 and 12 to assess the following: (1) mitogen-induced peripheral blood mononuclear cells (PBMCs) proliferation, (2) changes in PBMC subpopulations, (3) interleukin-2 (IL-2) production and (4) plasma immunoglobulin (Ig)G production. In addition,
delayed-type hypersensitivity (DTH) response to concanavalin A (Con A) or a
polyvalent vaccine was performed on Weeks 0, 6 and 12. Dietary lutein increased plasma lutein concentrations in a dose-dependent manner (p<0.001) and concentrations had not reached steady state after 12 weeks of feeding in cats given 5 or 10mg lutein. Concentrations of plasma retinol and alpha-tocopherol were not influenced by diet. The DTH response to vaccine but not to Con A increased (p<0.05) in a dose-dependent manner on Week 6. Compared to control, cats fed lutein also showed enhanced Con A- and pokeweed mitogen-stimulated PBMCs proliferation. Dietary lutein also increased the percentages of CD4+ and CD21+ lymphocytes on Week 12 but had no significant effect on pan T, CD8 and MHC class II markers. Plasma IgG was higher (p<0.05) in cats fed 10mg lutein on Weeks 8 and 12. These results support the immuno-modulatory action of lutein in domestic cats.

Antioxidant vitamins (provitamins) may protect against loss of lung function
over time. We studied the association between serum carotenoids (alpha-carotene, beta-carotene, lycopene, beta-cryptoxanthin, zeaxanthin, and lutein),
alpha-tocopherol, and lung function among noninstitutionalized Dutch elderly age 65 to 85 yr (n = 528). Multiple linear regression analysis was performed with
FEV(1) or FVC as dependent variables and serum levels of antioxidants in
quintiles as independent variables. We adjusted for age, gender, height, and
pack-years of smoking. Subjects in the fifth quintile of serum beta-carotene had
a 195 ml (95% confidence interval [95% CI]: 40 to 351 ml) higher and those in
the fifth quintile of alpha-carotene had a 257 ml (95% CI: 99 to 414 ml) higher
FEV(1) compared with subjects in the first quintile of these carotenoids.
Significant (p < 0.05) positive trends were observed between alpha-carotene,
beta-carotene, lycopene, and FEV(1) and between alpha-carotene, beta-carotene, and FVC. Subjects in the highest quintile of the other carotenoids or
alpha-tocopherol did not have significantly higher FEV(1) or FVC compared with
subjects in the first quintile of these antioxidants. In conclusion, this study
shows that from the six major serum carotenoids and alpha-tocopherol studied,
particularly alpha-carotene, beta-carotene, and lycopene were positively
associated with lung function in the elderly and may be considered as candidates for further investigations.

We conducted a population-based study of diet and lung cancer among the
multiethnic population of Hawaii in 1983-1985. We completed interviews for 230
men and 102 women with lung cancer and 597 men and 268 women controls,
frequency-matched to the patients by age and sex. A quantitative dietary history
assessed the usual intake of foods rich in vitamins A and C and carotenoids. A
clear dose-dependent negative association was demonstrated between dietary
beta-carotene and lung cancer risk in both sexes. After adjusting for smoking
and other covariates, the men in the lowest quartile of beta-carotene intake had
an odds ratio of 1.9 (95% confidence interval, 1.1-3.2) compared to those in the
highest quartile of intake. The corresponding odds ratio for women was 2.7 (95% confidence interval, 1.2-6.1). No clear association was found for retinol,
vitamin C, folic acid, iron, dietary fiber, or fruits. All vegetables, dark
green vegetables, cruciferous vegetables, and tomatoes showed stronger inverse associations with risk than beta-carotene. This observation suggests that other constituents of vegetables, such as lutein, lycopene, and indoles, and others, may also protect against lung cancer in humans.