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Home > Vision Resources > Literature Review > Carotenoid Literature Review - February 2014

Carotenoid Literature Review - February 2014

Lutein and Zeaxanthin

The association of retinal structure and macular pigment distribution

Verena Kirsten Meyer zu Westrup, Martha Dietzel, Daniel Pauleikhoff and Hans Werner

Hense. Invest. Ophthalmol. Vis. Sci. January 28, 2014 IOVS-13-12903.

Introduction: Macular pigment optical density (MPOD) and age-related macular degeneration (AMD) are thought to be associated; however, the details are not yet clearly understood. This study aimed at investigating how retinal anatomical structures relate with the spatial MPOD distribution in single eyes. Study setting and methods: In a subgroup of the third follow-up examination of the Münster Aging and Retina Study (MARS) cohort (mean age 78.4 years), 124 single eyes of 79 participants were examined. MPOD was assessed using 2-wavelength autofluorescence (AF). Retinal thickness (RT) and fovea pit profile slopes were measured using optical coherence tomography (OCT). The results were analyzed for interocular correlation in 58 pairs of eyes, and for the association of MPOD distribution patterns with RT using uni- and multivariate statistical methods. Results: The interocular correlations for several measures of RT and RT layers were high (p < 0.001). RT was inversely and significantly related to MPOD at 1.0° and at 2.0° from the foveal center but not to central MPOD. After controlling for sex, age,

smoking and spherical equivalent, RT was significantly thinner (-39.7 micrometers, p < 0.001) in eyes with ring-like as compared to normal MPOD distribution. In particular, a thinner layer between internal and external limiting membrane showed strong associations with ring-like structures. Conclusion: Higher values of MPOD at 1° and 2° as well as a ring-like distribution of MPOD were significantly associated with thinner maculae, due to thinner inner retinal layers. The MPOD distribution was unrelated to the slope of the foveal pit or the choroidal thickness. Our results suggest that the retinal section between the internal and external limiting membrane is involved in the spatial distribution of MPOD.

Genetic Evidence for Role of Carotenoids in Age-Related Macular Degeneration in the Carotenoids in Age-Related Eye Disease Study (CAREDS)

Kristin J. Meyers, Julie A. Mares, Robert P. Igo Jr, Barbara Truitt, Zhe Liu, Amy E. Millen, Michael Klein, Elizabeth J. Johnson, Corinne D. Engelman, Chitra K. Karki, Barbara Blodi, Karen Gehrs, Lesley Tinker, Robert Wallace, Jennifer Robinson, Erin S. LeBlanc, Gloria Sarto, Paul S. Bernstein, John Paul SanGiovanni and Sudha K. Iyengar. Invest. Ophthalmol. Vis. Sci. January 29, 2014 vol. 55 no. 1 587-599.

Purpose. We tested variants in genes related to lutein and zeaxanthin status for association with age-related macular degeneration (AMD) in the Carotenoids in Age-Related Eye Disease Study (CAREDS). Methods. Of 2005 CAREDS participants, 1663 were graded for AMD from fundus photography and genotyped for 424 single nucleotide polymorphisms (SNPs) from 24 candidate genes for carotenoid status. Of 337 AMD cases 91% had early or intermediate AMD. The SNPs were tested individually for association with AMD using logistic regression. A carotenoid-related genetic risk model was built using backward selection and compared to existing AMD risk

factors using the area under the receiver operating characteristic curve (AUC). Results. A total of 24 variants from five genes (BCMO1, BCO2, NPCL1L1, ABCG8, and FADS2) not previously

related to AMD and four genes related to AMD in previous studies (SCARB1, ABCA1, APOE,

1 February 2014 - Carotenoid Literature Review

and ALDH3A2) were associated independently with AMD, after adjusting for age and ancestry. Variants in all genes (not always the identical SNPs) were associated with lutein and zeaxanthin in serum and/or macula, in this or other samples, except for BCO2 and FADS2. A genetic risk score including nine variants significantly (P = 0.002) discriminated between AMD cases and controls beyond age, smoking, CFH Y402H, and ARMS2 A69S. The odds ratio (95%

confidence interval) for AMD among women in the highest versus lowest quintile for the risk score was 3.1 (2.0–4.9). Conclusions. Variants in genes related to lutein and zeaxanthin status

were associated with AMD in CAREDS, adding to the body of evidence supporting a protective role of lutein and zeaxanthin in risk of AMD.

Association Between Aspirin Use and Age-Related Macular DegenerationA Meta-Analysis

Juan Ye1, Yufeng Xu, Jinjing He and Lixia Lou. Invest. Ophthalmol. Vis. Sci. February 7,

2014 IOVS-13-13206

Purpose: We conducted a meta-analysis of randomized controlled trials (RCTs) and observational studies to evaluate the association between aspirin use and age-related macular degeneration (AMD). Methods: The pertinent studies were identified via literature search through four databases (Medline, Web of Science, Cochrane Library, Embase) and reference lists of retrieved studies. RCTs and cohort and case-control studies meeting the predefined criteria were included. We extracted relative risk (RR) or odds ratio (OR) or hazard ratio (HR) and 95% confidence interval (CI) from each study. Overall and study-specific risk estimates were pooled using fixed-effects and random-effects models, respectively. Subgroup analyses based on several stratified factors were also performed. Results: In total, two RCTs, three cohort studies, and four case-control studies involving 177,683 subjects were included. The pooled effect of all nine studies showed no significant association between aspirin use and occurrence of AMD (RR, 1.00; 95% CI 0.96-1.04), and no significant association was observed in any specific study design (RR, 0.93; 95% CI 0.71-1.22 for RCT; RR, 1.02; 95% CI 0.87-1.20 for cohort study; RR, 1.00; 95% CI 0.96-1.04 for case-control study). However, subgroup analysis showed aspirin use to be significantly associated with an increased risk of neovascular AMD (RR, 1.59; 95% CI 1.09-2.31). Conclusions: The pooled effects from current literatures suggest that aspirin use is not associated with AMD, but it increased the risk of the neovascular form of AMD.

Beneficial effects of the nutritional supplements on the development of diabetic retinopathy.

Kowluru RA, Zhong Q, Santos JM, Thandampallayam M, Putt D, Gierhart DL. Nutr Metab

(Lond). 2014 Jan 30;11(1):8. [Epub ahead of print]

PURPOSE: Increased oxidative stress and inflammatory mediators are implicated in the development of diabetic retinopathy, and in rats, its development can be prevented by antioxidants. Carotenoids are some of the powerful antioxidants, and diabetes decreases lutein and zeaxanthin levels in the serum and retina. The aim of this study is to investigate the effect of carotenoid containing nutritional supplements (Nutr), which is in clinical trials for 'Diabetes Vision Function', on diabetic retinopathy.

2 February 2014 - Carotenoid Literature Review

METHODS: Streptozotocin-induced diabetic rats (Wistar, male) were fed Purina 5001 supplemented with nutritional supplements containing zeaxanthin, lutein, lipoic acid, omega-3 fatty acids and other nutrients, or without any supplementation. Retinal function was analyzed at

~4 months of diabetes by electroretinography. After 11 months of diabetes, capillary cell apoptosis (TUNEL-staining) and histopathology (degenerative capillaries) were quantified in

trypsin-digested retinal vasculature. Retina was also analyzed for mitochondrial damage (by
quantifying gene expressions of mtDNA-encoded proteins of the electron transport chain),
VEGF and inflammatory mediators, interleukin-1beta and NF-kB. RESULTS: Diabetes impaired retinal function decreasing the amplitudes of both a- and b-waves. In the same animals, retinal capillary cell apoptosis and degenerative capillaries were increased by 3-4 fold. Gene expressions of mtDNA encoded proteins were decreased, and VEGF, interleukin-1beta and NF- kB levels were elevated. Supplementation with the nutrients prevented increased capillary cell apoptosis and vascular pathology, and ameliorated these diabetes-induced retinal
abnormalities. CONCLUSIONS: Nutritional supplementation prevents diabetic retinopathy, and also maintains normal retinal function, mitochondrial homeostasis and inflammatory mediators.
Thus, this supplementation could represent an achievable and inexpensive adjunct therapy to
also inhibit retinopathy, a slow progressing disease feared most by diabetic patients.

Carotenoids inhibit lipid peroxidation and hemoglobin oxidation, but not the depletion of glutathione induced by ROS in human erythrocytes.

Chisté RC, Freitas M, Mercadante AZ, Fernandes E. Life Sci. 2014 Jan 28. pii: S0024-

3205(14)00161-1. doi: 10.1016/j.lfs.2014.01.059. [Epub ahead of print]

AIMS: Despite the presence of endogenous antioxidants in erythrocytes, these cells are highly susceptible to oxidative damage and some exogenous antioxidants, such as carotenoids, are able to inhibit the pro-oxidant effect provided by reactive oxygen species. In this study, we evaluated the potential of carotenoids usually detected in human blood plasma (β-carotene, zeaxanthin, lutein, β-cryptoxanthin and lycopene) to prevent the oxidative damage in erythrocytes. MAIN METHODS: Human erythrocytes were subjected to induced oxidative damage and the following biomarkers of oxidative stress were monitored: lipid peroxidation [induced by tert-butyl hydroperoxide (tBHP) or by 2,2´-azobis (2-methylpropionamidine) dihydrochloride (AAPH)] and AAPH-induced oxidation of hemoglobin and depletion of glutathione. KEY FINDINGS: When tBHP was used to induce lipid peroxidation, lycopene was the most efficient carotenoid (IC50=2.2±0.4µM), whilst lutein was the most efficient
(IC50=2.5±0.7µM) when peroxyl radicals (ROO) were generated by AAPH. In relation to the
hemoglobin oxidation induced by AAPH, β-carotene and zeaxanthin were the most efficient antioxidants (IC50=2.9±0.3µM and 2.9±0.1µM, respectively). Surprisingly β-cryptoxanthin and lycopene did not inhibit hemoglobin oxidation or lipid peroxidation when induced by AAPH, even at the highest tested concentration (3µM). Additionally, the tested carotenoids did not prevent ROO- mediated GSH depletion and GSSG formation probably due to the lack of interaction between carotenoids (apolar) and glutathione (polar). SIGNIFICANCE: Our study contributes with important insights that carotenoids may exert therapeutical potential to act as natural antioxidant to prevent ROO-induced toxicity in human erythrocytes.

3 February 2014 - Carotenoid Literature Review

Dietary Intake of Carotenoids and Their Antioxidant and Anti-Inflammatory Effects in Cardiovascular Care.

Ciccone MM, Cortese F, Gesualdo M, Carbonara S, Zito A, Ricci G, De Pascalis F, Scicchitano P, Riccioni G. Mediators Inflamm. 2013;2013:782137. Epub 2013 Dec 31. Abstract: Cardiovascular disease related to atherosclerosis represents nowadays the largest cause of morbidity and mortality in developed countries. Due to inflammatory nature of atherosclerosis, several studies had been conducted in order to search for substances with anti- inflammatory activity on arterial walls, able to exert beneficial roles on health. Researches investigated the role of dietary carotenoids supplementation on cardiovascular disease, due to their free radicals scavenger properties and their skills in improving low-density lipoprotein cholesterol resistance to oxidation. Nevertheless, literature data are conflicting: although some studies found a positive relationship between carotenoids supplementation and cardiovascular risk reduction, others did not find any positive effects or even prooxidant actions. This paper aimed at defining the role of carotenoids supplementation on cardiovascular risk profile by reviewing literature data, paying attention to those carotenoids more present in our diet ( β - carotene, α -carotene, β -cryptoxanthin, lycopene, lutein, zeaxanthin, and astaxanthin).

Higher dose lutein and a longer supplementation period would be good for visual performance.

Qiu Q, Yao Y, Wu X, Han D. Nutrition. 2013 Jul-Aug;29(7-8):1072-3. doi:

10.1016/j.nut.2013.03.001.

Comment on

Lutein supplementation improves visual performance in Chinese drivers: 1-year randomized, double-blind, placebo-controlled study. [Nutrition. 2013]

Re: lutein supplementation improves visual performance in Chinese drivers: 1-year randomized, double-blind, placebo-controlled study: the importance of supplementing

with all three macular carotenoids. [Nutrition. 2013]

Lutein supplementation improves visual performance in Chinese drivers: 1-year randomized, double-blind, placebo-controlled study.

Yao Y, Qiu QH, Wu XW, Cai ZY, Xu S, Liang XQ. Nutrition. 2013 Jul-Aug;29(7-8):958-64. doi: 10.1016/j.nut.2012.10.017. Epub 2013 Jan 27.

OBJECTIVES: Although it is known that the carotenoid lutein can affect visual performance, we still have much to learn about its effect in occupational populations, like drivers. The aim of this study was to examine the effect of lutein supplementation on visual function in healthy drivers with long-term light exposure. METHODS: The study was a randomized, double-blind, placebo-controlled, 1-y intervention study. It included 120 normal participants (drivers). The active (A) group consumed 20 mg of lutein daily. Participants were assessed at baseline, 1, 3,

6, and 12 mo (V0, V1, V2, V3, and V4, respectively). Assessment included visual acuity, serum lutein concentrations, macular pigment optical density (MPOD), and visual performance. At the onset and at the end of the intervention, dietary intakes of lutein and visual-related quality of life

4 February 2014 - Carotenoid Literature Review

were measured. RESULTS: There was a trend (in the active group) toward an increase in best spectacle-corrected visual acuity measured, but there were no significant differences. Serum lutein and central MPOD in the active group increased significantly, whereas no change was observed in the placebo group. We observed significant increases in contrast and glare sensitivity, especially in the mesopic condition. There were significant improvements in the
score of the National Eye Institute 25-Item Visual Functioning Questionnaire driving subscale in the active group. CONCLUSIONS: Daily supplementation with 20 mg of lutein increases MPOD levels. Lutein may benefit driving at night and other spatial discrimination tasks carried out
under low illumination.

Macular pigment spatial profiles in South Asian and White subjects.

Huntjens B, Asaria TS, Dhanani SD, Konstantakopoulou E, Ctori I. Invest Ophthalmol Vis Sci. 2014 Jan 30. pii: iovs.13-13204v1. doi: 10.1167/iovs.13-13204. [Epub ahead of print] Purpose: Variability in central macular pigment optical density (MPOD) has been reported amongst healthy individuals. These variations seem to be related to risk factors of age-related macular degeneration, such as female gender, smoking, and ethnicity. This study investigates the variations in MPOD spatial profiles amongst ethnicities. Methods: Using heterochromatic flicker photometry (HFP), MPOD was measured at 7 retinal locations in 54 healthy young South Asian and 19 White subjects of similar age. Macular pigment spatial profiles were classified as either typical 'exponential', atypical 'ring-like' or atypical 'central dip'. Results: Central MPOD

was significantly greater in South Asian (0.56 ± 0.17) compared to White subjects (0.45 ± 0.18; P = 0.015). Integrated MPOD up to 1.8° i.e. MPODav(0-1.8) was also significantly increased in Asian (0.34 ± 0.09) versus White subjects (0.27 ± 0.10; P = 0.003). MPODav(0-1.8) was significantly increased in all subjects presenting a ring-like profile (0.35 ± 0.08) or central dip profile (0.39 ± 0.09), compared to typical exponential profiles (0.28 ± 0.09; P < 0.0005). We found a statistically significant association between ethnicity and spatial profile type (P = 0.008), whereby an exponential profile was present in 79% of White compared to 41% of the South Asian subjects. Conclusion: Central MPOD, MPODav(0-1.8), and the prevalence of atypical spatial profiles were significantly increased in South Asian compared to White subjects. Atypical profiles resulted in increased integrated MPOD up to 1.8° and may therefore offer enhanced macular protection from harmful blue light.

Carotenoids inhibit lipid peroxidation and hemoglobin oxidation, but not the depletion of glutathione induced by ROS in human erythrocytes.

Chisté RC, Freitas M, Mercadante AZ, Fernandes E. Life Sci. 2014 Jan 28. pii: S0024-

3205(14)00161-1. doi: 10.1016/j.lfs.2014.01.059. [Epub ahead of print]

AIMS: Despite the presence of endogenous antioxidants in erythrocytes, these cells are highly susceptible to oxidative damage and some exogenous antioxidants, such as carotenoids, are able to inhibit the pro-oxidant effect provided by reactive oxygen species. In this study, we evaluated the potential of carotenoids usually detected in human blood plasma (β-carotene, zeaxanthin, lutein, β-cryptoxanthin and lycopene) to prevent the oxidative damage in
erythrocytes. MAIN METHODS: Human erythrocytes were subjected to induced oxidative

5 February 2014 - Carotenoid Literature Review

damage and the following biomarkers of oxidative stress were monitored: lipid peroxidation [induced by tert-butyl hydroperoxide (tBHP) or by 2,2´-azobis (2-methylpropionamidine) dihydrochloride (AAPH)] and AAPH-induced oxidation of hemoglobin and depletion of glutathione. KEY FINDINGS: When tBHP was used to induce lipid peroxidation, lycopene was the most efficient carotenoid (IC50=2.2±0.4µM), whilst lutein was the most efficient
(IC50=2.5±0.7µM) when peroxyl radicals (ROO) were generated by AAPH. In relation to the
hemoglobin oxidation induced by AAPH, β-carotene and zeaxanthin were the most efficient antioxidants (IC50=2.9±0.3µM and 2.9±0.1µM, respectively). Surprisingly β-cryptoxanthin and lycopene did not inhibit hemoglobin oxidation or lipid peroxidation when induced by AAPH, even at the highest tested concentration (3µM). Additionally, the tested carotenoids did not prevent ROO- mediated GSH depletion and GSSG formation probably due to the lack of interaction between carotenoids (apolar) and glutathione (polar). SIGNIFICANCE: Our study contributes with important insights that carotenoids may exert therapeutical potential to act as natural antioxidant to prevent ROO-induced toxicity in human erythrocytes.

Relationships between macular pigment optical density and cognitive function in unimpaired and mildly cognitively impaired older adults.

Renzi LM, Dengler MJ, Puente A, Miller LS, Hammond BR Jr. Neurobiol Aging. 2013 Dec

27. pii: S0197-4580(13)00666-0. doi: 10.1016/j.neurobiolaging.2013.12.024. [Epub ahead of print]

Abstract: Low carotenoid status (especially of the xanthophylls, lutein [L], and zeaxanthin [Z]) is common in older adults and has been associated with a number of degenerative diseases of the central nervous system ranging from retina (e.g., macular degeneration) to brain (e.g., Alzheimer's disease). In this study, we tested whether retinal measures of L + Z (macular pigment optical density [MPOD]), used as a surrogate for brain L + Z levels, were related to cognitive function when comparing healthy older adults with mildly cognitively impaired older adults. Twenty-four subjects with mild cognitive impairment were compared with 24 matched controls. Subjects were matched with respect to age, body mass index, ethnicity, sex, and smoking status. Degree of cognitive impairment and cognitive ability was determined via structured clinical interview. MPOD was measured psychophysically. In healthy older adults, MPOD was only related to visual-spatial and constructional abilities (p = 0.04). For subjects with mild cognitive impairment (MCI), however, MPOD was broadly related to cognition including the composite score on the mini-mental state examination (p = 0.02), visual-spatial and constructional abilities (p = 0.04), language ability (p = 0.05), attention (p = 0.03), and the total scale on the Repeatable Battery for the Assessment of Neuropsychological Status (p = 0.03). It is possible that L/Z status may be more strongly related to cognition when individuals are considered with established onset of cognitive decline.

6 February 2014 - Carotenoid Literature Review

Specific carotenoid intake is inversely associated with the risk of breast cancer among Chinese women.

Wang L, Li B, Pan MX, Mo XF, Chen YM, Zhang CX. Br J Nutr. 2014 Feb 6:1-10. [Epub ahead of print]

Abstract: The protective effect of dietary carotenoid intake on the risk of breast cancer is inconclusive. Moreover, data on dietary carotenoids in relation to breast cancer in non-Western populations are scarce. The aim of the present study was to examine the association between dietary carotenoid intake and the risk of breast cancer among Chinese women. A total of 561 cases and 561 controls who were frequency matched by age (5-year interval) and residence were recruited in the present case-control study. Dietary intake information was collected by a face-to-face interview using a validated FFQ. The OR and 95 % CI were assessed by multivariate logistic regression after adjusting for various potential confounders. An inverse association was observed between the consumption of α-carotene, β-carotene, β-cryptoxanthin and lutein/zeaxanthin and the risk of breast cancer. The multivariate-adjusted OR for the highest quartile of intake compared with the lowest quartile of intake were 0·61 (95 % CI 0·43, 0·88) for

α-carotene, 0·54 (95 % CI 0·38, 0·78) for β-carotene, 0·38 (95 % CI 0·26, 0·52) for β- cryptoxanthin and 0·49 (95 % CI 0·34, 0·71) for lutein/zeaxanthin. Lycopene intake was not

found to be associated with the risk of breast cancer, with the adjusted OR of 0·89 (95 % CI
0·61, 1·30). These inverse associations were more evident among pre-menopausal women and women who were exposed to second-hand smoke. The protective effect of specific carotenoid
intake was observed for all subtypes of hormone receptor status of breast cancer. The present
study indicated that a greater intake of specific carotenoids was associated with a decreased risk of breast cancer among Chinese women residing in Guangdong.

Understanding RPE lipofuscin.

Sparrow JR, Dowling JE, Bok D. Invest Ophthalmol Vis Sci. 2013 Dec 19;54(13):8325-6. doi: 10.1167/iovs.13-13214.

Comment on

Rethinking A2E. [Invest Ophthalmol Vis Sci. 2013]

Identification of a novel lipofuscin pigment (iisoA2E) in retina and its effects in the retinal pigment epithelial cells.

Li J, Yao K, Yu X, Dong X, Gan L, Luo C, Wu Y. J Biol Chem. 2013 Dec 13;288(50):35671-

82. doi: 10.1074/jbc.M113.511386. Epub 2013 Oct 29.

Abstract: Lipofuscin accumulation in retinal pigment epithelial (RPE) cells of the eye implicates the etiologies of Stargardt disease and age-related macular degeneration, a leading cause of blindness in the elderly. Here, we have identified a previously unknown RPE lipofuscin component. By one- and two-dimensional NMR techniques and mass spectrometry, we confirmed that this compound is a new type of pyridinium bisretinoid presenting an unusual structure, in which two polyenic side chains are attached to adjacent carbons of a pyridinium ring. This pigment is a light-induced isomer of isoA2E, rather than A2E, referred to as iisoA2E.
This pigment is a fluorescent lipofuscin compound with absorbance maxima at 430 and 352
nm detected in human, pig, mouse, and bovine eyes. Formation of iisoA2E was found in reaction mixtures of all-trans-retinal and ethanolamine. Excess intracellular accumulation of this

7 February 2014 - Carotenoid Literature Review

adduct in RPE cells in vitro leads to a significant loss of cell viability and caused membrane damage. Phospholipase D-mediated phosphodiester cleavage of the A2PE series generated isoA2E and iisoA2E, in addition to A2E, thus corroborating the presence of isoA2PE and iisoA2PE that may serve as biosynthetic precursors of isoA2E and iisoA2E.

Concordance of macular pigment measurements obtained using customized heterochromatic flicker photometry, dual-wavelength autofluorescence, and single-wavelength reflectance.

Dennison JL, Stack J, Beatty S, Nolan JM. Exp Eye Res. 2013 Nov;116:190-8. doi:

10.1016/j.exer.2013.08.014. Epub 2013 Sep 3.

Abstract: This study compares in vivo measurements of macular pigment (MP) obtained using customized heterochromatic flicker photometry (cHFP; Macular Metrics Densitometer(™)), dual- wavelength fundus autofluorescence (Heidelberg Spectralis(®) HRA + OCT MultiColor) and single-wavelength fundus reflectance (Zeiss Visucam(®) 200). MP was measured in one eye of
62 subjects on each device. Data from 49 subjects (79%) was suitable for analysis. Agreement between the Densitometer and Spectralis was investigated at various eccentricities using a
variety of quantitative and graphical methods, including: Pearson correlation coefficient to measure degree of scatter (precision), accuracy coefficient, concordance correlation coefficient
(ccc), paired t-test, scatter and Bland-Altman plots. The relationship between max MP from the Visucam and central MP from the Spectralis and Densitometer was investigated using regression methods. Agreement was strong between the Densitometer and Spectralis at all
central eccentricities (e.g. at 0.25° eccentricity: accuracy = 0.97, precision = 0.90, ccc = 0.87). Regression analysis showed a very weak relationship between the Visucam and Densitometer
(e.g. Visucam max on Densitometer central MP: R(2) = 0.008, p = 0.843). Regression analysis also demonstrated a weak relationship between MP measured by the Spectralis and Visucam
(e.g. Visucam max on Spectralis central MP: R(2) = 0.047, p = 0.348). MP values obtained using the Heidelberg Spectralis are comparable to MP values obtained using the Densitometer. In contrast, MP values obtained using the Zeiss Visucam are not comparable with either the
Densitometer or the Spectralis MP measuring devices. Taking cHFP as the current standard to which other MP measuring devices should be compared, the Spectralis is suitable for use in a
clinical and research setting, whereas the Visucam is not.

Dietary influence on MAPK-signaling pathways and risk of colon and rectal cancer.

Slattery ML, Lundgreen A, Wolff RK. Nutr Cancer. 2013;65(5):729-38. doi:

10.1080/01635581.2013.795599.

Abstract: Mitogen-activated protein kinase (MAPK) pathways regulate cellular functions including cell proliferation, differentiation, migration, and apoptosis. Associations between genes in the DUSP, ERK1/2, JNK, and p38 MAPK-signaling pathways and dietary factors associated with growth factors, inflammation, and oxidative stress and risk of colon and rectal cancer were evaluated. Data include colon cases (n = 1555) and controls (n = 1956) and rectal cases (n =
754) and controls (n = 959). Statistically significant interactions were observed for the MAPK- signaling pathways after adjustment for multiple comparisons. DUSP genes interacted with
carbohydrates, mutagen index, calories, calcium, vitamin D, lycopene, dietary fats, folic acid,
and selenium. MAPK1, MAPK3, MAPK1, and RAF1 within the ERK1/2 MAPK-signaling pathway interacted with dietary fats and cruciferous vegetables. Within the JNK MAPK-signaling

8 February 2014 - Carotenoid Literature Review

pathway, interactions between MAP3K7 and protein, vitamin C, iron, folic acid, carbohydrates, and cruciferous vegetables; MAP3K10 and folic acid; MAP3K9 and lutein/zeaxanthin; MAPK8 and calcium; MAP3K3 and calcium and lutein; MAP3K1 and cruciferous vegetables. Interaction within the p38-signaling pathway included MAPK14 with calories, carbohydrates saturated fat, selenium, vitamin C; MAP3K2 and carbohydrates, and folic acid. These data suggest that
dietary factors involved in inflammation and oxidative stress interact with MAPK-signaling genes to alter risk of colorectal cancer.

Relationship of serum carotenoid concentrations with allostatic load as a measure of chronic stress among middle-aged adults in the USA.

Rosenberg N, Park CG, Eldeirawi K. Public Health Nutr. 2014 Feb 11:1-9. [Epub ahead of print]

OBJECTIVE: Chronic stress and repeated physiological attempts at stress adaptation may result in 'fatigue' and suboptimal performance of multiple physiological systems, i.e. allostatic load (AL). Although carotenoids have been linked with individual cardiovascular, metabolic and inflammatory biomarkers, little is known about the relationship of carotenoids with the multi- system biomarker measure of stress, AL. The present study examined the association of serum concentrations of carotenoids with AL among middle-aged adults.

Total antioxidant capacity of diet and serum, dietary antioxidant vitamins intake, and serum hs-CRP levels in relation to depression scales in university male students.

Prohan M, Amani R, Nematpour S, Jomehzadeh N, Haghighizadeh MH. Redox Rep. 2014

Feb 14. [Epub ahead of print]

Objectives Oxidative stress and inflammation have been reported to be higher in subjects with depression, but it is unclear whether this is due to inadequate dietary antioxidant intake or the pathophysiology of depression. The aim of this study was to assess the association between dietary and serum antioxidant status with depression scales in young male university students. Methods This research was a case-control study carried out on 60 male university students (30 students diagnosed with depression and 30 matched healthy controls). Beck Depression Inventory-II was used to assess the major depressive disorder (MDD) scales. A semi- quantitative food frequency questionnaire and 2-day 24-h recalls were used for dietary assessment. Dietary and serum total antioxidant capacity (TAC) and high-sensitive C-reactive protein (hs-CRP) concentrations were also measured. Results MDD subjects consumed less fruits (P < 0.05), legumes (P < 0.001), nuts and seeds (P = 0.003), vitamin C (P = 0.005), beta carotene (P < 0.001), lutein, and zeaxanthin (P = 0.006) than the controls. Moreover, the depressed group had lower serum TAC levels than their controls (P < 0.05). There were no significant differences in serum hs-CRP concentrations and dietary TAC levels between the study groups. Discussion Students with depression had significantly lower intake of dietary antioxidants. However, dietary TAC and serum hs-CRP levels were not significantly different between depressed and normal university male students. Intake of foods rich in antioxidants is

encouraged in male students.

9 February 2014 - Carotenoid Literature Review

Oxidative stress in rats with hyperhomo-cysteinemia and intervention effect of lutein.

Wang S, Wang M, Zhang S, Zhao L. Eur Rev Med Pharmacol Sci. 2014 Feb;18(3):359-64. AIM: The current study aims to explore the possible molecular mechanism of hyperhomocysteinemia (HHcy) mediated atherosclerosis (AS) and to find an effective intervention method for AS. MATERIALS AND METHODS: A total of 40 Wistar rats were equalized into four groups: blank control, HHcy, folacin intervention, and lutein intervention groups. HHcy rat models were established. The intervention groups were respectively lavaged with folacin and lutein. Oxidative stress states, the levels of nitric oxide (NO) and endothelin-1 (ET-1), as well as the expression of nuclear factor (NF)-κB p65 and intercellular adhesion molecule (ICAM)-1 were compared. RESULTS: In the HHcy rats, the activity of serum superoxide dismutase (SOD) and glutathione peroxidase (GPx) significantly decreased,
whereas the malondialdehyde content and hydroxyl radical level noticeably increased, indicating that the rats stayed in aggravated oxidative stress states. Lutein intervention inhibited HHcy-
induced oxidative stress excitement. In the HHcy rats, the NO level significantly decreased, whereas the ET-1 level significantly increased, indicating that HHcy mediated vascular
endothelial dysfunction. Lutein reversed such dysfunction. In the HHcy rats, the mRNA and protein expression of SOD2 and GPX1 in the aortic wall tissue decreased, whereas that of NF-

κB p65 and ICAM-1 increased. Lutein significantly upregulated the mRNA and protein

expression of SOD2 and GPx1 and downregulated the expression of NF-κB p65 and ICAM-1. CONCLUSIONS: Oxidative stress and inflammation are the important mechanisms of HHcy- mediated AS. In particular, HHcy-induced aggravated oxidative stress may function as the initial AS-mediating mechanism, upregulating the expression of NF-κB p65 and ICAM-1 and thereby becoming associated with AS. Lutein noticeably intervenes in and inhibits Hcy-mediated oxidative stress excitement and downregulates the expression of inflammation-associated informational molecules.

The Relationship between BCMO1 Gene Variants and Macular Pigment Optical

Density in Persons with and without Age-Related Macular Degeneration.

Feigl B1, Morris CP2, Voisey J2, Kwan A3, Zele AJ4. PLoS One. 2014 Feb 19;9(2):e89069. doi: 10.1371/journal.pone.0089069. eCollection 2014.

BACKGROUND: Recent evidence indicates that gene variants related to carotenoid metabolism play a role in the uptake of macular pigments lutein (L) and zeaxanthin (Z). Moreover, these pigments are proposed to reduce the risk for advanced age-related macular degeneration (AMD). This study provides the initial examination of the relationship between the gene variants related to carotenoid metabolism, macular pigment optical density (MPOD) and their combined expression in healthy humans and patients with AMD. PARTICIPANTS AND METHODS: Forty-four participants were enrolled from a general population and a private practice including 20 healthy participants and 24 patients with advanced (neovascular) AMD. Participants were genotyped for the three single nucleotide polymorphisms (SNPs) upstream from BCMO1, rs11645428, rs6420424 and rs6564851 that have been shown to either up or down regulate beta-carotene conversion efficiency in the plasma. MPOD was determined by heterochromatic flicker photometry.

10 February 2014 - Carotenoid Literature Review

RESULTS: Healthy participants with the rs11645428 GG genotype, rs6420424 AA genotype and rs6564851 GG genotype all had on average significantly lower MPOD compared to those with the other genotypes (p<0.01 for all three comparisons). When combining BCMO1 genotypes reported to have "high" (rs11645428 AA/rs6420424 GG/rs6564851 TT) and "low" (rs11645428 GG/rs6420424 AA/rs6564851 GG) beta-carotene conversion efficiency, we demonstrate clear differences in MPOD values (p<0.01). In patients with AMD there were no significant differences in MPOD for any of the three BCMO1 gene variants. CONCLUSION: In healthy participants MPOD levels can be related to high and low beta-carotene conversion BCMO1 genotypes. Such relationships were not found in patients with advanced neovascular AMD, indicative of additional processes influencing carotenoid uptake, possibly related to other AMD susceptibility genes. Our findings indicate that specific BCMO1 SNPs should be determined when assessing the effects of carotenoid supplementation on macular pigment and that their expression may be influenced by retinal disease.

11 February 2014 - Carotenoid Literature Review



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