Plasma Lutein, a Nutritional Biomarker for Development of Advanced Age-Related Macular Degeneration: The Alienor Study.

Lutein and zeaxanthin may lower the risk of age-related macular degeneration (AMD). We evaluated the associations of plasma lutein and zeaxanthin with the incidence of advanced AMD in the Alienor study (Antioxydants Lipides Essentiels Nutrition et Maladies Oculaires). Alienor study is a prospective population-based cohort of 963 residents of Bordeaux, France, who were 73 years or older at baseline (2006-2008). The present study included 609 participants with complete ophthalmologic and plasma carotenoids data. Examinations were performed every two years over an eight-year period (2006 to 2017). Plasma lutein and zeaxanthin were determined at baseline from fasting blood samples using high-performance liquid chromatography. Cox proportional hazard models were used to assess associations between plasma lutein, zeaxanthin, and their (total cholesterol (TC) + triglycerides (TG)) ratios with AMD. Among the 609 included participants, 54 developed advanced incident AMD during a median follow-up time of 7.6 years (range 0.7 to 10.4). Participants with higher plasma lutein had a reduced risk for incident advanced AMD in the fully adjusted model (HR = 0.63 per 1-SD increase (95% CI, 0.41-0.97), p = 0.03). A similar association was observed using the lutein/(TC + TG) ratio (HR = 0.59 (95% CI, 0.39-0.90), p = 0.01). No associations were evidenced for other carotenoids. Higher plasma lutein was associated with a 37% reduced risk of incident advanced AMD.

Plasma Carotenoids Are Inversely Associated With Dementia Risk in an Elderly French Cohort.

BACKGROUND: Although intake of fruits and vegetables has been associated with a decreased risk of dementia, studies focusing on nutrients underlying this association are lacking. Our objective was to analyze the relation between plasma carotenoids and the risk of dementia and Alzheimer's disease (AD) in French elderly community dwellers. METHODS: The study population consisted of 1,092 nondemented older participants, from the Three-City-Bordeaux cohort followed for up to 10 years (range: 1.8-10.8 years, median: 9.5 years). Dementia and AD were diagnosed by a committee of neurologists. The concentration of plasma carotenoids (beta-carotene, alpha-carotene, lycopene, lutein, zeaxanthin, and beta-cryptoxanthin) was determined at baseline. Longitudinal analyses of the association between each plasma carotenoid, either crude or expressed as a ratio to plasma lipids (total cholesterol + triglycerides), and the risk of dementia or AD were performed by multivariate Cox models. RESULTS: During follow-up, 199 dementia cases, including 132 AD, occurred. After adjustment for sociodemographic data, diet quality, and clinical variables, including baseline cognitive performances, only higher lutein concentration, considered as a function of plasma lipids, was consistently significantly associated with a decreased risk of all-cause dementia and AD (hazard ratio = 0.808, 95% confidence interval = 0.671-0.973, p = .024 and hazard ratio = 0.759, 95% confidence interval = 0.600-0.960, p = .021, respectively for +1 SD). CONCLUSION: This large cohort of older participants suggests that maintaining higher concentrations of lutein in respect to plasma lipids may moderately decrease the risk of dementia and AD.

Macular pigment carotenoids in the retina and occipital cortex are related in humans.

OBJECTIVES: Lutein and zeaxanthin are dietary carotenoids that preferentially accumulate in the macular region of the retina. Together with meso-zeaxanthin, a conversion product of lutein in the macula, they form the macular pigment. Lutein is also the predominant carotenoid in human brain tissue and lutein status is associated with cognitive function in adults. The study objective was to evaluate the relationship between retinal and brain lutein and zeaxanthin in humans. METHODS: Donated brain tissue (occipital cortex and hippocampus) and matched retina were obtained from the National Disease Research Interchange, a national human tissue resource center which adheres to strict consent and confidentiality procedures. Decedents were men and women aged >50 years who either had normal cognitive function or Alzheimer's disease. Tissues were analyzed using standard lipid extractions followed by analysis on reverse-phase high performance liquid chromatography (HPLC) and normal-phase HPLC (for meso-zeaxanthin). RESULTS: Macular pigment carotenoids (lutein, meso-zeaxanthin, and zeaxanthin combined) in the retina were significantly related to the combined concentrations of lutein and zeaxanthin in the occipital cortex. When analyzed separately, only retinal lutein (plus meso-zeaxanthin), not zeaxanthin, was significantly related to lutein in the occipital cortex. No correlations were observed with lutein and zeaxanthin in the hippocampus. DISCUSSION: Total macular pigment density measured via non-invasive, psychophysical techniques can be used as a biomarker to ascertain brain lutein and zeaxanthin status in clinical studies.

A double-blind, placebo-controlled study on the effects of lutein and zeaxanthin on photostress recovery, glare disability, and chromatic contrast.

PURPOSE: Past studies have shown that higher macular pigment optical density (MPOD) and lutein (L) and zeaxanthin (Z) supplementation are related to improvements in glare disability, photostress recovery, and chromatic contrast. This study assessed those links using a randomized, double-blind, placebo-controlled design. METHODS: The visual effects of 1 year of supplementing L (10 mg/d) and Z (2 mg/d) were investigated. One hundred fifteen young, healthy subjects were recruited and randomized into the study (58 received placebo, 57 L+Z). Several dependent measures were collected at baseline and then once every 3 months: serum L and Z measured by HPLC chromatography; MPOD measured using customized heterochromatic flicker photometry; photostress recovery assessed by measuring the time needed to recover visual acquisition of a grating target after 30 seconds of an intense xenon white flash exposure; glare disability evaluated as the energy in a surrounding annulus necessary to veil a central grating target; and chromatic contrast assessed by measuring thresholds for a yellow grating target superposed on a 460-nm background. RESULTS: Macular pigment optical density increased significantly versus placebo at all eccentricities (10, 30, 60, and 105 minutes from the center of the macula). Serum L and Z also increased significantly by the first follow-up visit (at 3 months), and remained elevated throughout the intervention period of 1 year. Chromatic contrast and photostress recovery time improved significantly versus placebo. Glare disability was correlated with macular pigment density throughout the study period but did not increase significantly in the treated group. CONCLUSIONS: Daily supplementation with L+Z resulted in significant increase in serum levels and MPOD and improvements in chromatic contrast and recovery from photostress. These results are consistent with past studies showing that increasing MPOD leads to improved visual performance. (ClinicalTrials.gov number, NCT00909090.).

Macular pigment optical density is related to cognitive function in older people.

BACKGROUND: the xanthophylls lutein (L) and zeaxanthin (Z) exist in relatively high concentration in multiple central nervous tissues (e.g. cortex and neural retina). L + Z in macula (i.e. macular pigment, MP) are thought to serve multiple functions, including protection and improvement of visual performance. Also, L + Z in the macula are related to L + Z in the cortex. OBJECTIVE: to determine whether macular pigment optical density (MPOD, L + Z in the macula) is related to cognitive function in older adults. METHODS: participants were older adults (n = 108, 77.6 ± 2.7 years) sampled from the age-related maculopathy ancillary study of the Health Aging and Body Composition Study (Memphis, TN, USA). Serum carotenoids were measured using high performance liquid chromatography. MPOD was assessed using heterochromatic flicker photometry. Eight cognitive tests designed to evaluate several cognitive domains including memory and processing speed were administered. Partial correlation coefficients were computed to determine whether cognitive measures were related to serum L + Z and MPOD. RESULTS: MPOD levels were significantly associated with better global cognition, verbal learning and fluency, recall, processing speed and perceptual speed, whereas serum L + Z was significantly related to only verbal fluency. CONCLUSION: MPOD is related to cognitive function in older people. Its role as a potential biomarker of cognitive function deserves further study.

Relationship between Serum and Brain Carotenoids, α-Tocopherol, and Retinol Concentrations and Cognitive Performance in the Oldest Old from the Georgia Centenarian Study.

Oxidative stress is involved in age-related cognitive decline. The dietary antioxidants, carotenoids, tocopherols, and vitamin A may play a role in the prevention or delay in cognitive decline. In this study, sera were obtained from 78 octogenarians and 220 centenarians from the Georgia Centenarian Study. Brain tissues were obtained from 47 centenarian decedents. Samples were analyzed for carotenoids, α-tocopherol, and retinol using HPLC. Analyte concentrations were compared with cognitive tests designed to evaluate global cognition, dementia, depression and cognitive domains (memory, processing speed, attention, and executive functioning). Serum lutein, zeaxanthin, and ß-carotene concentrations were most consistently related to better cognition (P < 0.05) in the whole population and in the centenarians. Only serum lutein was significantly related to better cognition in the octogenarians. In brain, lutein and ß-carotene were related to cognition with lutein being consistently associated with a range of measures. There were fewer significant relationships for α-tocopherol and a negative relationship between brain retinol concentrations and delayed recognition. These findings suggest that the status of certain carotenoids in the old may reflect their cognitive function. The protective effect may not be related to an antioxidant effect given that α-tocopherol was less related to cognition than these carotenoids.

Effects of formulation on the bioavailability of lutein and zeaxanthin: a randomized, double-blind, cross-over, comparative, single-dose study in healthy subjects.

PURPOSE: Lutein and zeaxanthin are macular pigments with a protective function in the retina. These xanthophylls must be obtained from the diet or added to foods or supplements via easy-to-use, stable formulations. The technique employed to produce these formulations may affect the bioavailability of the xanthophylls. METHODS: Forty-eight healthy volunteers were randomized into this double-blind, cross-over study investigating the plasma kinetics of lutein provided as two different beadlet formulations. Subjects (n = 48) received a single dose of 20 mg of lutein as either a starch-matrix ("SMB", FloraGLO® Lutein 5 %) or as a cross-linked alginate-matrix beadlet ("AMB", Lyc-O-Lutein 20 %) formulation. Plasma concentrations of lutein and zeaxanthin were measured at 0, 1, 3, 6, 9, 12, 14, 24, 26, 28, 32, 36, 48, 72, 168, and 672 h. RESULTS: The mean plasma AUC(0-72h), AUC(0-672h), and C(max) for total lutein and zeaxanthin and their all-E-isomers were significantly increased (p < 0.001) from pre-dose concentrations in response to SMB and AMB. There was no difference in lutein T max between the two test articles. However, by 14 h post-dose, total plasma lutein increased by 7 % with AMB and by 126 % with SMB. Total lutein AUC(0-72h) and AUC(0-672h) were 1.8-fold and 1.3-fold higher, respectively, for SMB compared to AMB. Both formulations were well tolerated by subjects in this study. CONCLUSION: These findings confirm that the bioavailability of lutein and zeaxanthin critically depends on the formulation used and document a superiority of the starch-based over the alginate-based product in this study.

Macular lutein and zeaxanthin are related to brain lutein and zeaxanthin in primates.

OBJECTIVES: Xanthophyll pigments lutein and zeaxanthin cross the blood-retina barrier to preferentially accumulate in the macular region of the neural retina. There they form macular pigment, protecting the retina from blue light damage and oxidative stress. Lutein and zeaxanthin also accumulate in brain tissue. The objective of the study was to evaluate the relationship between retinal and brain levels of these xanthophylls in non-human primates. METHODS: Study animals included rhesus monkeys reared on diets devoid of xanthophylls that were subsequently fed pure lutein or pure zeaxanthin (both at 3.9 µmol/kg per day, n = 6/group) and normal rhesus monkeys fed a stock diet (0.26 µmol/kg per day lutein and 0.24 µmol/kg per day zeaxanthin, n = 5). Retina (4 mm macular punch, 4-8 mm annulus, and periphery) and brain tissue (cerebellum, frontal cortex, occipital cortex, and pons) from the same animals were analyzed by reverse-phase high-performance liquid chromatography. RESULTS: Lutein in the macula and annulus was significantly related to lutein levels in the cerebellum, occipital cortex, and pons, both in bivariate analysis and after adjusting for age, sex and n-3 fatty acid status. In the frontal cortex the relationship was marginally significant. Macular zeaxanthin was significantly related to zeaxanthin in the cerebellum and frontal cortex, while the relationship was marginally significant in the occipital cortex and pons in a bivariate model. DISCUSSION: An integrated measure of total macular pigment optical density, which can be measured non-invasively, has the potential to be used as a biomarker to assess brain lutein and zeaxanthin status.

Association of macular pigment density with plasma ω-3 fatty acids: the PIMAVOSA study.

PURPOSE: To assess the correlation between macular pigment optical density and plasma levels of lutein, zeaxanthin, and fatty acids, especially omega-3 polyunsaturated fatty acids (PUFAs). METHODS: The PIMAVOSA study is an observational study of 107 healthy volunteers, aged 20 to 60 years and born in southwest France, without histories of ocular disease. Macular pigment optical density (MPOD) was measured using the two-wavelength autofluorescence method with a modified scanning laser ophthalmoscope. Plasma measurements (lutein, zeaxanthin, and fatty acids) were performed from fasting blood samples collected on the day of the eye examination. RESULTS: MPOD within 6° correlated with plasma levels of lutein and zeaxanthin (r = 0.35, P < 0.001, and r = 0.30, P < 0.005, respectively). MPOD also significantly correlated with total plasma omega-3 PUFAs (r = 0.22, P < 0.05). Among the different omega-3 PUFAs, docosapentaenoic acid (DPA) had the highest correlation with MPOD (r = 0.31, P < 0.001), whereas correlation with eicosapentaenoic acid (EPA) was moderate (r = 0.21, P < 0.05) and did not reach statistical significance for docosahexaenoic acid (r = 0.14, P = 0.14). CONCLUSIONS: In the present study, macular pigment density was associated not only with plasma lutein and zeaxanthin but also with omega-3 long-chain PUFAs, particularly with EPA and DPA. Further studies will be needed to confirm these findings and to identify the underlying mechanisms.

Nutritional manipulation of primate retinas, V: effects of lutein, zeaxanthin, and n-3 fatty acids on retinal sensitivity to blue-light-induced damage.

PURPOSE: Blue-light photooxidative damage has been implicated in the etiology of age-related macular degeneration (AMD). The macular pigment xanthophylls lutein (L) and zeaxanthin (Z) and n-3 fatty acids may reduce this damage and lower the risk of AMD. This study investigated the effects of the lifelong absence of xanthophylls followed by L or Z supplementation, combined with the effects of n-3 fatty acid deficiency, on acute blue-light photochemical damage. METHODS: Subjects included eight rhesus monkeys with no lifelong intake of xanthophylls and no detectable macular pigment. Of these, four had low n-3 fatty acid intake and four had adequate intakes. Control subjects had typical L, Z, and n-3 fatty acid intake. Retinas received 150-µm-diameter exposures of low-power 476-nm laser light at 0.5 mm (∼2°) eccentricity, which is adjacent to the macular pigment peak, and parafoveally at 1.5 mm (∼6°). Exposures of xanthophyll-free animals were repeated after supplementation with pure L or Z for 22 to 28 weeks. Ophthalmoscopically visible lesion areas were plotted as a function of exposure energy, with greater slopes of the regression lines indicating greater sensitivity to damage. RESULTS: In control animals, the fovea was less sensitive to blue-light-induced damage than the parafovea. Foveal protection was absent in xanthophyll-free animals but was evident after supplementation. In the parafovea, animals low in n-3 fatty acids showed greater sensitivity to damage than animals with adequate levels. CONCLUSIONS: After long-term xanthophyll deficiency, L or Z supplementation protected the fovea from blue light-induced damage, whereas adequate n-3 fatty acid levels reduced the damage in the parafovea.

Serum lutein response is greater from free lutein than from esterified lutein during 4 weeks of supplementation in healthy adults.

BACKGROUND: Current data suggest great variability in serum response following lutein ingestion from various sources. OBJECTIVE: To compare the relative serum response during supplementation with free lutein (fL) and lutein esters (Le). METHODS: 72 volunteers (23-52 years; body mass index [BMI] >20 and <30 kg/m2; baseline serum lutein <20 µg/dL [<352 nmol/L]) were identified. Subjects, matched for gender, age, and BMI, were randomly assigned to the fL or Le group. fL and Le capsules contained 12.2 mg of free lutein or 27 mg of lutein ester (equivalent to 13.5 mg free lutein), respectively. Fasting blood was obtained at baseline and after 7, 14, 21, and 28 days of supplementation. Supplements were consumed with standard portions of dry, ready-to-eat cereal and 2% cow's milk. RESULTS: Absolute changes in serum lutein, per mg daily dose, were significantly greater in fL vs. Le after 21 days (p  =  0.0012) and remained so after 28 days (p  =  0.0011) of supplementation. Serum lutein Area Under the Curve [AUC((day 0-28))] response was 17% greater for fL vs. Le (p  =  0.0187). Regression models were used and determined that (1) baseline serum lutein levels and (2) the form of lutein ingested (fL > Le) influence the serum lutein response during supplementation, while subject age, gender, BMI, and serum lipids do not affect serum response. CONCLUSIONS: These results suggest that the relative serum lutein response will be significantly greater from supplements containing free lutein than from supplements containing lutein esters. These findings should be useful for future clinical trials exploring the effectiveness of lutein supplementation in the prevention of or protection against age-related macular degeneration and/or cataracts.

Metabolism of lutein and zeaxanthin in rhesus monkeys: identification of (3R,6'R)- and (3R,6'S)-3'-dehydro-lutein as common metabolites and comparison to humans.

Lutein and zeaxanthin are xanthophylls that can be found highly concentrated in the macula of the retina. They are thought to protect the macula through their role as blue-light filters and because of their antioxidant and singlet oxygen quenching properties. Examination of metabolites unique to lutein and zeaxanthin such as 3'-dehydro-lutein, and of their stereochemistry may provide insight to the mechanism by which they are formed and by which they exert protection. To evaluate the formation of such metabolites, eleven monkeys were raised on a xanthophyll-free diet, and supplemented with pure lutein or pure zeaxanthin (2.2 mg/kg body weight/d). The period of supplementation ranged between 12 and 92 weeks. At study start and throughout the study, serum samples were taken and analyzed for xanthophylls using different HPLC systems. Xanthophyll metabolites were identified using UV/VIS and HR-MS detection. Lutein and zeaxanthin metabolites were found in detectable amounts with 3'-dehydro-lutein being a common metabolite of both. Using chiral-phase HPLC, two diastereomers, (3R,6'R)-3'-dehydro-lutein and (3R,6'S)-3'-dehydro-lutein, were identified and shown to be present in nearly equimolar amounts. A pathway for their formation from either lutein or zeaxanthin is proposed. These findings were comparable to results obtained with human plasma.

Xanthophyll accumulation in the human retina during supplementation with lutein or zeaxanthin - the LUXEA (LUtein Xanthophyll Eye Accumulation) study.

The xanthophylls lutein (L) and zeaxanthin (Z) form the macular pigment with the highest density in the macula lutea. We investigated Macular Pigment Optical Density (MPOD) responses to supplementation with identically formulated (Actilease) L or Z (OPTISHARP) or L+Z over 6-12 months using doses of 10 or 20mg/day. MPOD as well as blue light sensitivity in fovea and parafovea were measured monthly by heterochromatic flicker photometry. Average xanthophyll plasma concentrations, analysed monthly by HPLC, increased up to 27-fold. MPOD increased by 15% upon L or L+Z supplementation. Supplementation of Z alone produced similar pigment accumulation in fovea and parafovea, which confounded MPOD measurements. After correction for this, a 14% MPOD increase resulted for Z. Thus, during supplementation with xanthophylls, L is predominantly deposited in the fovea while Z deposition appears to cover a wider retinal area. This may be relevant to health and disease of the retina.

Supplementation with the carotenoids lutein or zeaxanthin improves human visual performance.

BACKGROUND: Macular pigment (MP) is found in diurnal primate species when vision spans a range of ambient illumination and is mediated by cone and rod photoreceptors. The exact role of MP remains to be determined. In this study we investigate two new hypotheses for possible MP functions. OBJECTIVE: As MP absorption coincides partly with that of rhodopsin, MP may reduce rod signal effectiveness in the mesopic range, thus extend the usefulness of cone-mediated vision into the mesopic range. Forward light scatter in the eye can reduce retinal image contrast. If blue light contributes significantly to intraocular scatter, selective blue light absorption by MP could reduce the effects of scatter. DESIGN: We investigated 34 subjects from a carotenoid supplementation trial. The measurements included high mesopic contrast acuity thresholds (CATs), macular pigment optical density (MPOD), wavefront aberrations, and scattered light. The measurements were made after 6 months of daily supplementation with zeaxanthin (Z, OPTISHARP), lutein (L), a combination of the two (C), or placebo (P), and again after a further 6 months of doubled supplementation. RESULTS: The data reveal a trend toward lower CATs in all groups supplemented, with a statistically significant improvement in the lutein group (p = 0.001), although there was no correlation with MPOD. Light scattering in the eye and the root-mean-square wavefront aberrations show decreasing trends as a result of supplementation, but no correlation with MPOD. CONCLUSIONS: The results suggest that supplementation with L or Z increases MPOD at the fovea and at 2.5 degrees , and that supplementation can improve CATs at high mesopic levels and hence visual performance at low illumination.

Plasma lutein and zeaxanthin and other carotenoids as modifiable risk factors for age-related maculopathy and cataract: the POLA Study.

PURPOSE: To assess the associations of plasma lutein and zeaxanthin and other carotenoids with the risk of age-related maculopathy (ARM) and cataract in the population-based Pathologies Oculaires Liées à l'Age (POLA) Study. METHODS: Retinal photographs were graded according to the international classification. ARM was defined by the presence of late ARM (neovascular ARM, geographic atrophy) and/or soft indistinct drusen (>125 microm) and/or soft distinct drusen (>125 microm) associated with pigmentary abnormalities. Cataract classification was based on a direct standardized lens examination at the slit lamp, according to Lens Opacities Classification System III. Plasma carotenoids were measured by high-performance liquid chromatography (HPLC), in 899 subjects of the cohort. RESULTS: After multivariate adjustment, the highest quintile of plasma zeaxanthin was significantly associated with reduced risk of ARM (OR=0.07; 95% CI: 0.01-0.58; P for trend=0.005), nuclear cataract (OR=0.23; 95% CI: 0.08-0.68; P for trend=0.003) and any cataract (OR=0.53; 95% CI: 0.31-0.89; P for trend=0.01). ARM was significantly associated with combined plasma lutein and zeaxanthin (OR=0.21; 95% CI: 0.05-0.79; P for trend=0.01), and tended to be associated with plasma lutein (OR=0.31; 95% CI: 0.09-1.07; P for trend=0.04), whereas cataract showed no such associations. Among other carotenoids, only beta-carotene showed a significant negative association with nuclear cataract, but not ARM. CONCLUSIONS: These results are strongly suggestive of a protective role of the xanthophylls, in particular zeaxanthin, for the protection against ARM and cataract.

The effects of supplementation with lutein and/or zeaxanthin on human macular pigment density and colour vision.

BACKGROUND: Both yellow-blue (YB) discrimination thresholds and macular pigment optical density (MPOD) measurements in the eye exhibit large variability in the normal population. Although it is well established that selective absorption of blue light by the macular pigment (MP) can significantly affect trichromatic colour matches, the extent to which the MP affects colour discrimination (CD) sensitivity remains controversial. OBJECTIVE: In this study, we assess whether the variability in YB thresholds is attributable to differences in MPOD, both at the fovea and in the paracentral visual field. We also investigated whether higher levels of MP offer any advantage in other visual functions such as red-green (RG) CD sensitivity. DESIGN: CD thresholds and spatial MPOD profiles were measured in 24 normal trichromats supplemented with zeaxanthin (OPTISHARP) and/or lutein. Novel stimulus conditions that isolate YB and RG chromatic mechanisms were employed and MPOD profiles were measured up to an eccentricity of 8 degrees. RESULTS: The data reveal an increase in MPOD in the supplemented subjects that was almost uniform within a centre region around the fovea subtending +/-4 degrees. RG sensitivity was high in all subjects with thresholds well within the normal range. Unexpectedly, YB thresholds were also normal and showed no correlation with MPOD. A model for threshold CD based on appropriate combinations of cone contrast signals was developed to explain the experimental findings. CONCLUSIONS: YB thresholds remain unaffected by supplementation with lutein and/or zeaxanthin rather, at increased MPOD levels, RG vision tends to be improved. The model accounts for the absence of correlation between MPOD and YB thresholds and predicts a marginal improvement in RG discrimination when MPOD is high.

Plasma kinetics of lutein, zeaxanthin, and 3-dehydro-lutein after multiple oral doses of a lutein supplement.

BACKGROUND: Adequate intake of lutein is postulated to reduce the risk of age-related macular degeneration, but kinetic information for developing a dosing regimen is sparse. OBJECTIVE: The objective was to characterize lutein plasma kinetics in a multiple dosing design and to assess the effects of lutein intake on concentrations of other plasma carotenoids. DESIGN: After a run-in period of 7 d, 19 healthy volunteers were assigned to receive daily oral doses of 4.1 mg lutein (n = 8; group 1) or 20.5 mg lutein (n = 8; group 2) for 42 d or no lutein (n = 3; control group). The supplement contained 8.3% zeaxanthin relative to lutein (100%). The time profiles of plasma xanthophyll concentrations were monitored over the dosing phase, and samples were collected frequently on day 42 and for 24 d after dosing. RESULTS: Average plasma all-E-lutein concentrations increased from 0.14 to 0.52 +/- 0.13 and 1.45 +/- 0.69 micromol/L in groups 1 and 2, respectively. Dose-normalized lutein bioavailability in group 2 was approximately 60% of that in group 1. Kinetic disposition half-life did not differ significantly between groups. On average, dosing for 18 d was required to reach a >90% fraction of the steady state concentration, which is consistent with an effective half-life for accumulation of approximately 5.6 d. Plasma kinetics of all-E-lutein were paralleled by those of all-E-3-dehydro-lutein. Kinetic analysis indicated formation of all-E-3-dehydro-lutein from lutein. Lutein was well tolerated and did not affect the concentrations of other carotenoids. CONCLUSION: Long-term supplementation with 4.1 and 20.5 mg lutein as beadlets increased plasma lutein concentrations approximately 3.5- and 10-fold, respectively.

Nutritional manipulation of primate retinas, III: Effects of lutein or zeaxanthin supplementation on adipose tissue and retina of xanthophyll-free monkeys.

PURPOSE: Macular pigment (MP) is composed of the xanthophylls lutein (L) and zeaxanthin (Z) and may help to prevent age-related macular degeneration or retard its progression. In this study the effects of L or Z supplementation on carotenoid levels was examined in serum, adipose tissue, and retina in rhesus monkeys with no previous intake of xanthophylls. METHODS: From birth to 7 to 16 years of age, 18 rhesus monkeys were fed semipurified diets containing all essential nutrients but no xanthophylls. Six were supplemented with pure L and 6 with pure Z at 3.9 micromol/kg per day for 24 to 101 weeks. At baseline and at 4- to 12-week intervals, carotenoids in adipose tissue were measured by HPLC. At study completion, carotenoids in serum and retina (central 4 mm, 8-mm annulus, and the periphery) were determined. Results were compared with data from control monkeys fed a standard laboratory diet. RESULTS: Monkeys fed xanthophyll-free diets had no L or Z in serum or tissues. After L or Z supplementation, serum and adipose tissue concentrations significantly increased in the supplemented groups. Both L and 3R,3'S-Z (RSZ or meso-Z, not present in the diet) were incorporated into retinas of monkeys supplemented with L, with RSZ present only in the macula (central 4 mm). All-trans Z, but no RSZ, accumulated in retinas of monkeys supplemented with Z. CONCLUSIONS: L is the precursor of RSZ, a major component of macular pigment. Xanthophyll-free monkeys can accumulate retinal xanthophylls and provide a valuable model for examining their uptake and conversion.

Comparative multiple dose plasma kinetics of lycopene administered in tomato juice, tomato soup or lycopene tablets.

BACKGROUND: Lycopene is mainly provided in tomato and tomato products in Western diet. Among other factors the systemic availability of lycopene from natural sources is dependent on release from the cell matrix as achieved by food processing. AIMS OF THE STUDY: The purpose of this study was to compare plasma concentration responses of total lycopene and its major isomers to dosing of the carotenoid as tomato juice, tomato soup or tablets containing synthetic lycopene. METHODS: Intake of lycopene rich food products was restricted throughout this randomized, parallel group study, including 6 volunteers per group. Following a 14 day lycopene depletion phase subjects ingested 20 mg of lycopene daily for 8 days as tomato juice, soup prepared from tomato paste or lycopene tablets. Lycopene plasma concentrations were monitored throughout the depletion and dosing phases and for 22 days post-dosing and kinetics were evaluated using both empirical and compartmental modelling. RESULTS: Irrespective of the lycopene treatment all-E lycopene was the predominant lycopene isomer, whereas 5-Z lycopene was the most abundant Z isomer. Plasma concentration response of total and all-E lycopene to dosing of the carotenoid in tablets and tomato soup was comparable but exceeded that of intake in tomato juice. No differences were noted in dose normalized 5-Z lycopene concentrations between groups. The estimates of efficient half-life were approximately 5 and 9 days for all-E and 5-Z lycopene, respectively. CONCLUSIONS: The systemic availability of synthetic lycopene from a tablet formulation is comparable to that observed from processed tomatoes (soup from tomato paste) and superior to that from tomato juice. No differences were observed in disposition kinetics of natural and synthetic lycopene. The synthetic lycopene tablet formulation used in this investigation may be of value for future clinical investigations.

Plasma kinetics of zeaxanthin and 3'-dehydro-lutein after multiple oral doses of synthetic zeaxanthin.

BACKGROUND: Zeaxanthin is hypothesized to reduce the risk of age-related macular degeneration; however, kinetic information is limited. OBJECTIVES: The objective was to investigate the plasma kinetics of synthetic zeaxanthin after repeated oral doses and to assess the possible influence of other carotenoids on plasma zeaxanthin concentrations. DESIGN: After a run-in of 3 d, 20 healthy volunteers assigned to 2 parallel dose groups received once daily oral doses of either 1 mg (1.76 micro mol) or 10 mg (17.6 micro mol) zeaxanthin for 42 d. Plasma concentration-time profiles on days 1 and 42, concentrations immediately before zeaxanthin intake during the dosing period, and concentrations after the last dose until day 76 were monitored. RESULTS: all-E-Zeaxanthin concentrations increased from 0.048 +/- 0.026 micro mol/L at baseline to 0.20 +/- 0.07 and 0.92 +/- 0.28 micro mol/L with 1 and 10 mg zeaxanthin, respectively. The dose-normalized bioavailability of all-E-zeaxanthin after the10-mg dose was 40% lower (P < 0.001) than after the 1-mg dose. Other kinetic parameters did not differ significantly between groups. After 17 d of dosing, >90% of steady state concentrations were reached, which was compatible with an effective half-life for accumulation of 5 d. The terminal elimination half-life was 12 +/- 7 d (n = 20). The time course of plasma all-E-3-'dehydro-lutein concentrations resembled that of all-E-zeaxanthin. The data provided evidence that all-E-3-'dehydro-lutein was derived from all-E-zeaxanthin. Concentrations of other carotenoids were not affected. Zeaxanthin was well tolerated. CONCLUSION: Long-term oral intake of 1 and 10 mg zeaxanthin as beadlets increases plasma zeaxanthin concentrations approximately 4- and 20-fold, respectively. Evidence that all-E-3-dehydro-lutein is formed from zeaxanthin was strong.