The Effect of Lutein/Zeaxanthin Intake on Human Macular Pigment Optical Density: A Systematic Review and Meta-Analysis.
ABSTRACT: Lutein, zeaxanthin, and meso-zeaxanthin are the only carotenoids found in the human macula and may have a role in visual function. These carotenoids are reported to protect the retina, and thus vision, as antioxidants and by acting as a blue light filter. Our objective was to determine a minimum concentration of lutein/zeaxanthin intake that is associated with a statistically significant and/or clinically important change in macular pigment optical density (MPOD) among adults with healthy eyes. We searched Ovid MEDLINE, CENTRAL, and the Commonwealth of Agriculture Bureau for English-language studies through to July 2020. Two reviewers screened results to identify studies that evaluated supplements or dietary sources of lutein/zeaxanthin on MPOD among adults with healthy eyes. One reviewer extracted data and assessed strength of evidence, which was confirmed by a second reviewer. Two independent reviewers assessed the risk of bias. Meta-analyses were stratified by total lutein/zeaxanthin dose. We included 46 studies (N = 3189 participants; mean age = 43 y; 42% male). There was no statistically significant change in MPOD among studies evaluating <5 mg/d of total lutein/zeaxanthin intake which primarily assessed dietary interventions for 3-6 mo (pooled mean difference, 0.02; 95% CI: -0.01 to 0.05). The pooled mean increase in MPOD was 0.04 units (95% CI: 0.02 to 0.07) among studies evaluating 5 to <20 mg/d of lutein/zeaxanthin and was 0.11 units (95% CI: 0.06 to 0.16) among studies evaluating ≥20 mg/d of lutein/zeaxanthin for 3-12 mo. MPOD increased with lutein/zeaxanthin intake, particularly at higher doses, among adults with healthy eyes. The effects of lutein/zeaxanthin intake at doses <5 mg/d or from dietary sources is less clear. Increased lutein/zeaxanthin intake can help with maintaining ocular health. Future research is needed to determine the minimum dose and duration of lutein/zeaxanthin intake that is associated with a clinically important change in MPOD or visual function.
Project description:<h4>Introduction</h4>The dietary carotenoids lutein (L) and zeaxanthin (Z) are transported in the bloodstream by lipoproteins, sequestered by adipose tissue, and eventually captured in the retina where they constitute macular pigment. There are no L&Z dietary intake recommendations nor desired blood/tissue concentrations for the Spanish general population. Our aim was to assess the correlation of L&Z habitual dietary intake (excluding food supplements), resulting serum concentrations and lipid profile with macular pigment optical density (MPOD) as well as the contrast sensitivity (CT), as visual outcome in normolipemic subjects (n = 101) aged 45-65.<h4>Methods</h4>MPOD was measured by heterochromatic flicker photometry, serum L&Z by HPLC, the dietary intake by a 3-day food records and CT using the CGT-1000-Contrast-Glaretester at six stimulus sizes, with and without glare.<h4>Results</h4>Lutein and zeaxanthin concentrations (median) in serum: 0.361 and 0.078 μmol/L, in dietary intake: 1.1 mg L+Z/day. MPOD: 0.34du. L+Z intake correlates with their serum concentrations (rho = 0.333, p = 0.001), which in turn correlates with MPOD (rho = 0.229, p = 0.000) and with fruit and vegetable consumption (rho = 0.202, p = 0.001), but not with lutein+zeaxanthin dietary intake. MPOD correlated with CT, with and without glare (rho ranges: -0.135, 0.160 and -0.121, -0.205, respectively). MPOD predictors: serum L+Z, L+Z/HDL-cholesterol (β-coeficient: -0.91±0.2, 95%CI: -1.3,-0.5) and HDL-cholesterol (R2 = 15.9%). CT predictors: MPOD, mainly at medium and smaller visual angles (corresponding to spatial frequencies for which sensitivity declines with age) and gender (β-coefficients ranges: -0.95,-0.39 and -0.13,-0.39, respectively).<h4>Conclusion</h4>A higher MPOD is associated with a lower ratio of L+Z/HDL-cholesterol and with a lower CT (higher contrast sensitivity). The HDL-cholesterol would also act indirectly on the CT improving the visual function.
Project description:<h4>Purpose</h4>While the role of the macular pigment carotenoids in the prevention of age-related macular degeneration has been extensively studied in adults, comparatively little is known about the physiology and function of lutein and zeaxanthin in the developing eye. We therefore developed a protocol using a digital video fundus camera (RetCam) to measure macular pigment optical density (MPOD) and distributions in premature infants and in children.<h4>Methods</h4>We used blue light reflectance to image the macular pigment in premature babies at the time of retinopathy of prematurity (ROP) screening and in children aged under 7 years who were undergoing examinations under anesthesia for other reasons. We correlated the MPOD with skin carotenoid levels measured by resonance Raman spectroscopy, serum carotenoids measured by HPLC, and dietary carotenoid intake.<h4>Results</h4>We enrolled 51 infants and children ranging from preterm to age 7 years. MPOD correlated significantly with age (r = 0.36; P = 0.0142), with serum lutein + zeaxanthin (r = 0.44; P = 0.0049) and with skin carotenoid levels (r = 0.42; P = 0.0106), but not with dietary lutein + zeaxanthin intake (r = 0.13; P = 0.50). All premature infants had undetectable macular pigment, and most had unusually low serum and skin carotenoid concentrations.<h4>Conclusions</h4>Our most remarkable finding is the undetectable MPOD in premature infants. This may be due in part to foveal immaturity, but the very low levels of serum and skin carotenoids suggest that these infants are carotenoid insufficient as a consequence of low dietary intake and/or severe oxidative stress. The potential value of carotenoid supplementation in the prevention of ROP and other disorders of prematurity should be a fruitful direction for further investigation.
Project description:Pregnancy and lactation can change the maternal nutrient reserve. Non-invasive, quantitative markers of maternal nutrient intake could enable personalized dietary recommendations that improve health outcomes in mothers and infants. Macular pigment optical density (MPOD) is a candidate marker, as MPOD values generally reflect carotenoid intake. We evaluated the association of MPOD with dietary and breastmilk carotenoids in postpartum women. MPOD measurements and dietary intake of five carotenoids were obtained from 80 mothers in the first three months postpartum. Breastmilk samples from a subset of mothers were analyzed to determine their nutrient composition. The association between MPOD and dietary or breastmilk carotenoids was quantitatively assessed to better understand the availability and mobilization of carotenoids. Our results showed that dietary α-carotene was positively correlated with MPOD. Of the breastmilk carotenoids, 13-cis-lutein and trans-lutein were correlated with MPOD when controlled for the total lutein in breastmilk. Other carotenoids in breastmilk were not associated with MPOD. Maternal MPOD is positively correlated with dietary intake of α-carotene in the early postpartum period, as well as with the breastmilk content of lutein. MPOD may serve as a potential marker for the intake of carotenoids, especially α-carotene, in mothers in the early postpartum period.
Project description:To investigate genetic determinants of macular pigment optical density in women from the Carotenoids in Age-Related Eye Disease Study (CAREDS), an ancillary study of the Women's Health Initiative Observational Study.1585 of 2005 CAREDS participants had macular pigment optical density (MPOD) measured noninvasively using customized heterochromatic flicker photometry and blood samples genotyped for 440 single nucleotide polymorphisms (SNPs) in 26 candidate genes related to absorption, transport, binding, and cleavage of carotenoids directly, or via lipid transport. SNPs were individually tested for associations with MPOD using least-squares linear regression.Twenty-one SNPs from 11 genes were associated with MPOD (P ? 0.05) after adjusting for dietary intake of lutein and zeaxanthin. This includes variants in or near genes related to zeaxanthin binding in the macula (GSTP1), carotenoid cleavage (BCMO1), cholesterol transport or uptake (SCARB1, ABCA1, ABCG5, and LIPC), long-chain omega-3 fatty acid status (ELOVL2, FADS1, and FADS2), and various maculopathies (ALDH3A2 and RPE65). The strongest association was for rs11645428 near BCMO1 (?A = 0.029, P = 2.2 × 10(-4)). Conditional modeling within genes and further adjustment for other predictors of MPOD, including waist circumference, diabetes, and dietary intake of fiber, resulted in 13 SNPs from 10 genes maintaining independent association with MPOD. Variation in these single gene polymorphisms accounted for 5% of the variability in MPOD (P = 3.5 × 10(-11)).Our results support that MPOD is a multi-factorial phenotype associated with variation in genes related to carotenoid transport, uptake, and metabolism, independent of known dietary and health influences on MPOD.
Project description:Age-related macular degeneration (AMD) is the third leading cause of blindness worldwide. Macular pigment optical density (MPOD), a biomarker for AMD, is a non-invasive measure to assess risk. The macula xanthophyll pigments lutein (L) and zeaxanthin (Z) protect against blue light and provide oxidant defense, which can be indexed by MPOD. This study examined the effects of Z-rich goji berry intake on MPOD and skin carotenoids in healthy individuals. A randomized, unmasked, parallel-arm study was conducted with 27 participants, aged 45-65, who consumed either 28 g of goji berries or a supplement containing 6 mg L and 4 mg Z (LZ), five times weekly for 90 days. After 90 days, MPOD was significantly increased in the goji berry group at 0.25 and 1.75 retinal eccentricities (<i>p</i> = 0.029 and <i>p</i> = 0.044, respectively), while no changes were noted in the LZ group. Skin carotenoids were significantly increased in the goji berry group at day 45 (<i>p</i> = 0.025) and day 90 (<i>p</i> = 0.006), but not in the LZ group. Regular intake of goji berries in a healthy middle-aged population increases MPOD may help prevent or delay the development of AMD.
Project description:<h4>Importance</h4>Nutritional uptake of lutein, zeaxanthin, and ω-3 polyunsaturated fatty acids may increase macular pigment optical density (MPOD) and thereby protect against the development of age-related macular degeneration (AMD).<h4>Objectives</h4>To estimate the efficiency of dietary supplementation containing lutein, zeaxanthin, ω-3 polyunsaturated fatty acids, and vitamins to increase the density of macular pigment in first-generation offspring of parents with neovascular AMD.<h4>Design, setting, and participants</h4>This study was a randomized clinical trial (Lutein Influence on Macula of Persons Issued From AMD Parents [LIMPIA]) with a 6-month treatment period, followed by a 6-month follow-up period. Analyses were based on the intent-to-treat principle. The setting was 2 university hospitals in France (at Bordeaux and Dijon) from January 2011 (first participant first visit) to February 2013 (last participant last visit). The analysis was conducted from January to November 2016. Participants were 120 individuals free of any retinal ocular disease. They were first-generation offspring of parents with neovascular AMD.<h4>Interventions</h4>Participants were randomized in a 1:1 ratio to receive either 2 daily dietary supplementation capsules or placebo for 6 months.<h4>Main outcomes and measures</h4>The primary assessment criterion was the evolution of MPOD after 6 months of supplementation (value of both eligible eyes) measured using the modified MPD-Visucam 200 (Carl Zeiss Meditec) and the modified Heidelberg Retina Angiograph (Heidelberg Engineering) (HRA) at 0.98° eccentricity. The statistical analysis was adjusted for hospital and for risk factors.<h4>Results</h4>Overall, 120 participants (60 in each group) were included, and 239 eyes were analyzed (119 in the lutein plus zeaxanthin [L + Z] group and 120 in the placebo group). Their mean (SD) age was 56.7 (6.6) years, and 71.7% (n = 86) were female. A statistically significant increase in plasma lutein and zeaxanthin was shown in the L + Z group after 3 months and 6 months of treatment compared with the placebo group. However, the difference between groups in the evolution of MPOD measured by HRA 0.98° eccentricity between 6 months and baseline was 0.036 (95% CI, -0.037 to 0.110) (P = .33).<h4>Conclusions and relevance</h4>Among first-generation offspring of parents with neovascular AMD in the LIMPIA trial, MPOD as measured with the modified HRA and the MPD-Visucam was not modified after 6 months of lutein and zeaxanthin dietary supplementation despite plasma levels showing continuous exposure to lutein and zeaxanthin. Further research is necessary to understand the mechanism of absorption and metabolism of these nutrients in the macula, the best way to measure MPOD, and the clinical benefit for the patients.<h4>Trial registration</h4>clinicaltrials.gov Identifier: NCT01269697.
Project description:Carotenoids are diet-dependent milk components that are important for the visual and cognitive development of an infant. This study determined ?-carotene, lycopene and lutein + zeaxanthin in breastmilk and its associations with dietary intake from healthy Polish mothers in the first six months of lactation. Concentrations of carotenoids in breastmilk were measured by HPLC (high-performance liquid chromatography) (first, third, sixth month of lactation) and dietary intake was assessed based on a three-day dietary record (third and sixth month of lactation). The average age of participants (n = 53) was 31.4 ± 3.8 years. The breastmilk concentrations of carotenoids were not changed over the progress of lactation. Lycopene was a carotenoid with the highest content in breastmilk (first month 112.2 (95% CI 106.1?118.3)-sixth month 110.1 (103.9?116.3) nmol/L) and maternal diet (third month 7897.3 (5465.2?10329.5) and sixth month 7255.8 (5037.5?9474.1) µg/day). There was a positive correlation between carotenoids in breastmilk and dietary intake (lycopene r = 0.374, r = 0.338; lutein + zeaxanthin r = 0.711, r = 0.726, 3rd and 6th month, respectively) and an inverse correlation with maternal BMI in the third month of lactation (?-carotene: r = -0.248, lycopene: r = -0.286, lutein + zeaxanthin: r = -0.355). Adjusted multivariate regression models confirmed an association between lutein + zeaxanthin intake and its concentration in breastmilk (third month: ? = 0.730 (0.516?0.943); 6th: ? = 0.644 (0.448?0.840)). Due to the positive associations between dietary intake and breastmilk concentrations, breastfeeding mothers should have a diet that is abundant in carotenoids.
Project description:Age-Related Eye Disease Study 2 (AREDS2) is a randomized, placebo-controlled study designed to determine whether supplementation with 10 mg of lutein and 2 mg of zeaxanthin per day can slow the rate of progression of age-related macular degeneration (AMD). Although some biomarkers of response to carotenoid supplementation such as serum concentrations are part of the AREDS2 protocol, measurement of carotenoid concentrations in the eye and other tissues is not. In this approved ancillary study, macular pigment optical density (MPOD), macular pigment distributions, and skin carotenoid levels at enrollment and at each annual visit were measured to assess baseline carotenoid status and to monitor response to assigned interventions.All subjects enrolled at the Moran Eye Center had MPOD and macular pigment spatial distributions measured by dual-wavelength autofluorescence imaging and total skin carotenoids measured by resonance Raman spectroscopy. Results. Baseline MPOD in enrolled subjects was unusually high relative to an age-matched control group that did not consume carotenoid supplements regularly, consistent with the high rate of habitual lutein and zeaxanthin consumption in Utah AREDS2 subjects prior to enrollment. MPOD did not correlate with serum or skin carotenoid measurements.Useful information is provided through this ancillary study on the ocular carotenoid status of AREDS2 participants in the target tissue of lutein and zeaxanthin supplementation: The macula. When treatment assignments are unmasked at the conclusion of the study, unique tissue-based insights will be provided on the progression of AMD in response to long-term, high-dose carotenoid supplementation versus diet alone. (ClinicalTrials.gov number, NCT00345176.).
Project description:<h4>Background</h4>Studies have reported a protective relation to cognitive decline with long-term intake of total and individual dietary carotenoids. However, the underlying mechanisms have not yet been clearly established in humans.<h4>Objectives</h4>To evaluate the prospective association between intakes of total and individual carotenoids and risk of incident Alzheimer dementia (AD) and explore the underlying neuropathological basis.<h4>Methods</h4>Among 927 participants from the Rush Memory and Aging Project who were free from AD at baseline and were followed up for a mean of 7 y, we estimated HRs for AD using Cox proportional hazards models by intakes of energy-adjusted carotenoids. Brain AD neuropathology was assessed in postmortem brain autopsies among 508 deceased participants. We used linear regression to assess the association of carotenoid intake with AD-related neuropathology.<h4>Results</h4>Higher intake of total carotenoids was associated with substantially lower hazard of AD after controlling for age, sex, education, ApoE-ε4, participation in cognitively stimulating activities, and physical activity level. Comparing the top and bottom quintiles (median intake: 24.8 compared with 6.7 mg/d) of total carotenoids, the multivariate HR (95% CI) was 0.52 (0.33, 0.81), P-trend < 0.01. A similar association was observed for lutein-zeaxanthin, a weaker linear inverse association was observed for β-carotene, and a marginally significant linear inverse association was found for β-cryptoxanthin. Among the deceased participants, consumers of higher total carotenoids (top compared with bottom tertile, 18.2 compared with 8.2 mg/d) had less global AD pathology (b: -0.10; SE = 0.04; P-trend = 0.01). For individual carotenoids, lutein-zeaxanthin and lycopene were inversely associated with brain global pathology, whereas lutein-zeaxanthin showed additional inverse associations with AD diagnostic score, neuritic plaque severity, and neurofibrillary tangle density and severity.<h4>Conclusions</h4>Our findings support a beneficial role of total carotenoid consumption, in particular lutein/zeaxanthin, on AD incidence that may be related to the inhibition of brain β-amyloid deposition and fibril formation.
Project description:Lutein is a carotenoid that varies in breast milk depending on maternal intake. Data are lacking with regard to the effect of dietary lutein supplementation on breast milk lutein concentration during lactation and subsequent plasma lutein concentration in breast-fed infants. This study was conducted to determine the impact of lutein supplementation in the breast milk and plasma of lactating women and in the plasma of breast-fed infants 2-3 mo postpartum. Lutein is the dominant carotenoid in the infant brain and the major carotenoid found in the retina of the eye. Eighty-nine lactating women 4-6 wk postpartum were randomly assigned to be administered either 0 mg/d of lutein (placebo), 6 mg/d of lutein (low-dose), or 12 mg/d of lutein (high-dose). The supplements were consumed for 6 wk while mothers followed their usual diets. Breast milk carotenoids were measured weekly by HPLC, and maternal plasma carotenoid concentrations were measured at the beginning and end of the study. Infant plasma carotenoid concentrations were assessed at the end of the study. No significant differences were found between dietary lutein + zeaxanthin intake and carotenoid concentrations in breast milk and plasma or body mass index at baseline. Total lutein + zeaxanthin concentrations were greater in the low- and high-dose-supplemented groups than in the placebo group in breast milk (140% and 250%, respectively; P < 0.0001), maternal plasma (170% and 250%, respectively; P < 0.0001), and infant plasma (180% and 330%, respectively; P < 0.05). Lutein supplementation did not affect other carotenoids in lactating women or their infants. Lactating women are highly responsive to lutein supplementation, which affects plasma lutein concentrations in the infant. This trial was registered at clinicaltrials.gov as NCT01747668.