The ALGOVUE Clinical Trial: Effects of the Daily Consumption of Eggs Enriched with Lutein and Docosahexaenoic Acid on Plasma Composition and Macular Pigment Optical Density.

BACKGROUND: Carotenoids and docosahexaenoic acid (DHA) were identified as essential components for eye health and are both naturally present in eggs. OBJECTIVE: We aimed to evaluate the effect of the daily consumption of two eggs enriched with lutein/zeaxanthin and DHA on macular pigment optical density (MPOD) and on circulating xanthophyll and fatty acid concentrations in healthy participants. METHODS: Ninety-nine healthy volunteers consumed either two standard eggs or two enriched eggs per day for 4 months. MPOD was measured at baseline (V0) and at follow-up (V4) using a modified confocal scanning laser ophthalmoscope (primary outcome). Blood samples were collected to determine total plasma and lipoprotein fatty acids and lutein/zeaxanthin compositions at V0 and V4 (secondary outcomes). RESULTS: A slight but significant increase in MPOD was observed for all study participants consuming two eggs per day for 4 months at all eccentricities (0.5°, 1°, 2°, and 4°). Plasma and lipoprotein lutein, zeaxanthin, and DHA concentrations significantly increased in both groups but were greater in the enriched group (for the enriched group (V0 vs. V4): lutein, 167 vs. 369 ng/mL; zeaxanthin, 17.7 vs. 29.2 ng/mL; DHA, 1.89 vs. 2.56% of total fatty acids). Interestingly, lutein from high-density lipoprotein (HDL) was strongly correlated with MPOD at 0.5 and 1° eccentricities (rho = 0.385, p = 0.008, and rho = 0.461, p = 0.001, respectively). CONCLUSIONS: MPOD was slightly increased in both groups. Lutein, zeaxanthin, and DHA plasma concentrations were strongly enhanced in the enriched group compared with the standard group. A significant correlation was found between MPOD level and lutein concentration in HDL.

Clinical Effects of Dietary Supplementation of Lutein with High Bio-Accessibility on Macular Pigment Optical Density and Contrast Sensitivity: A Randomized Double-Blind Placebo-Controlled Parallel-Group Comparison Trial.

Improvements in macular pigment optical density (MPOD) and contrast sensitivity after administration of 12 mg lutein alone and the timing at which efficacy is observed remain unknown. Therefore, lutein (12 mg), a crystalline formulation, was used in this study, considering its bioaccessibility. This study aimed to determine the effects of lutein administration for 16 weeks on MPOD, contrast sensitivity, and glare sensitivity, and changes in serum lutein levels were determined. The study subjects comprised 59 healthy male and female adults aged 20-69 years. The study diet included a placebo (placebo group) or a diet supplemented with 12 mg of lutein (lutein group). Each study diet was continuously administered for 16 weeks. At weeks 8 and 16, MPOD, contrast sensitivity, glare sensitivity, and serum lutein levels were evaluated. Compared with the placebo group, the lutein group showed significantly improved MPOD, contrast sensitivity, and glare sensitivity at week 16 and significantly increased serum lutein levels at weeks 8 and 16. Continuous administration of lutein for 16 weeks, considering its bioaccessibility, increased MPOD; it made the outlines of visible objects clearer and was effective in inhibiting decreases in visual function caused by glare from light.

Efficacy of Commercially Available Nutritional Supplements: Analysis of Serum Uptake, Macular Pigment Optical Density and Visual Functional Response.

Purpose: To compare the change in serum carotenoids, macular pigment optical density (MPOD) and visual function with the intake of two commercially available nutritional supplements. Methods: Participants were given a 24-week supply of a lipid-based micronized liquid medical food, Lumega-Z™ (LM), containing 28 mg of the macular carotenoids lutein (L), zeaxanthin (Z) and meso-zeaxanthin (MZ), or given PreserVision™ AREDS 2 Formula (gel-caps; PV) containing 12 mg of the macular carotenoids L and Z, but no reported MZ. Serum levels of L, Z and MZ were obtained at baseline and after 12 weeks. Macular pigment optical densities (MPOD) and visual function were assessed at baseline and after 24 weeks. Results: Average blood serum concentrations of L, Z and MZ in the two groups at baseline were similar. The increases in L, Z and MZ were 0.434, 0.063 and 0.086 mol/L vs. 0.100, 0.043 and 0.001 mol/L, respectively, in the LM vs. PV group. From baseline to week 24, average MPOD in the LM-group increased by 0.064 from 0.418 to 0.482, whereas in the PV-group, it was essentially unchanged (0.461 to 0.459;). Although log-contrast sensitivity was improved in all groups under three conditions (photopic, mesopic and mesopic with glare), the change in log-contrast sensitivity was not statistically significant. Conclusion: Despite only a 2.3-fold higher carotenoid concentration than PV, LM supplementation provides approximately 3-4-fold higher absorption, which leads to a significant elevation of MPOD levels.

Effects of Lutein Supplementation in Japanese Patients with Unilateral Age-Related Macular Degeneration: The Sakai Lutein Study.

This prospective randomized double-masked study investigated the effects of 20 mg lutein supplementation with two different capsules (beeswax or glycerol fatty acid esters) for 6 months on the fellow eyes of 39 Japanese patients with unilateral age-related macular degeneration, and assessed the factors associated with baseline plasma lutein concentration via lifestyle interviews. Macular pigment optical density (MPOD), determined with the two-wavelength autofluorescence method, increased over time in the beeswax group (ANOVA, p = 0.0451), although the increase from 3 months to 6 months was only marginally significant. No significant increase was observed in the glycerol fatty acid esters group (ANOVA, p = 0.7396). Plasma lutein concentrations significantly increased at 3 and 6 months from baseline in both groups (both p < 0.01). In a multiple regression model, age was negatively associated with higher plasma lutein concentration (p = 0.0305), while consumption of green vegetables was positively associated with baseline plasma lutein concentration (p = 0.0322). In conclusion, a significant increase in MPOD was not fully confirmed with 6 months intake duration despite a significant increase in plasma lutein concentrations. Consumption of green vegetable was confirmed to be associated with plasma lutein concentration after adjusting for other potential factors including age.

Effects of lutein supplementation on inflammatory biomarkers and metabolic risk factors in adults with central obesity: study protocol for a randomised controlled study.

BACKGROUND: The prevalence of central obesity is constantly increasing, and visceral fat is associated with increased production of inflammatory factors and metabolic risk factors. Lutein might retard the development of metabolic disease through its antioxidant and anti-inflammatory properties. Furthermore, epidemiological studies have associated higher dietary intake and serum levels of lutein with decreased adiposity. However, few randomised controlled trials have shown the effects of lutein supplementation on inflammatory biomarkers and metabolic risk factors, especially in adults with central obesity. METHODS: This study will be conducted as a double-blind, parallel placebo-controlled clinical trial in which 120 people who have central obesity, are 18 to 60 years old and are willing to provide informed consent will be randomly assigned to the intervention or placebo group in a 1:1 ratio according to sex, age and waist circumference. The intervention group will receive 10 mg daily lutein supplementation for 12 weeks to explore the effect of lutein supplementation on serum lutein, glycaemic and lipid profiles, inflammatory factors and body composition. Two populations (intention-to-treat population and per-protocol population) will be used in the data analyses. DISCUSSION: Our findings from this trial will contribute to the knowledge of the association between lutein supplementation and inflammatory biomarkers and metabolic risk factors in people with central obesity and will offer a possibility for the prevention of inflammatory diseases. TRIAL REGISTRATION: Chinese Clinical Trial Registry: ChiCTR1800018098. Registered on 30 August 2018.

Randomized controlled trial of a water-soluble formulation of lutein in humans.

Lutein is poorly absorbed owing to their high hydrophobicity and crystallinity. This double-blind crossover trial involved eight healthy males who were administrated capsules containing either a lutein water-soluble formulation or a lutein oil suspension for 8 days. In the formulation group, plasma and erythrocytes lutein concentrations and baseline-corrected AUC were two-fold higher than those in the oil suspension group.

Application of blood concentration biomarkers in nutritional epidemiology: example of carotenoid and tocopherol intake in relation to chronic disease risk.

BACKGROUND: Biomarkers provide potential to objectively measure the intake of nutrients and foods, and thereby to strengthen nutritional epidemiology association studies. However, there are only a few established intake biomarkers, mostly based on recovery of nutrients or their metabolites in urine. Blood concentration measures provide a potential biomarker source for many additional nutritional variables, but their use in disease-association studies requires further development. OBJECTIVE: The aim of this study was to apply recently proposed serum-based carotenoid and tocopherol intake biomarkers and to examine their association with the incidence of major cardiovascular diseases, cancers, and diabetes in a subset of Women's Health Initiative (WHI) cohorts. METHODS: Serum concentrations of α- and ß-carotene, lutein plus zeaxanthin (L + Z), and α-tocopherol were routinely measured at baseline in a subset of 5488 enrollees in WHI cohorts. Intake biomarkers for these 4 micronutrients, obtained by combining serum concentrations with participant characteristics, were recently proposed using a 153-woman feeding study within WHI. These biomarker equations are augmented here to include pertinent disease risk factors and are associated with subsequent chronic disease incidence in this WHI subset. RESULTS: HRs for a doubling of micronutrient intake differed only moderately from the null for the outcomes considered. However, somewhat lower risks of specific cardiovascular outcomes, breast cancer, and diabetes were associated with a higher intake of α- and ß-carotene, lower risk of diabetes was associated with higher L + Z intake, and elevated risks of certain cardiovascular outcomes were associated with a higher intake of α-tocopherol. These patterns remained following the exclusion of baseline users of dietary supplements. CONCLUSIONS: Concentration biomarkers can be calculated from blood specimens obtained in large epidemiologic cohorts and applied directly in disease-association analyses, without relying on self-reported dietary data. Observed associations between carotenoid and tocopherol biomarkers and chronic disease risk could be usefully evaluated further using stored serum specimens on the entire WHI cohort. This study was registered at www.clinicaltrials.gov as NCT00000611.

Effect of Long-Term Xanthophyll and Anthocyanin Supplementation on Lutein and Zeaxanthin Serum Concentrations and Macular Pigment Optical Density in Postmenopausal Women.

Xanthophylls (lutein, L; zeaxanthin, Z) and anthocyanins are often included in food supplements to improve ocular health. There are no dietary reference intakes for them. The aim was to assess the effects of L, Z and anthocyanin supplementation on short and long-term lutein status markers (serum concentration and macular pigment optical density (MPOD)). Seventy-two postmenopausal women were randomized into a parallel study of 8 months: Group A-anthocyanines (60 mg/day); Group X-xanthophylls (6 mg L + 2 mg Z/day); Group X+A-anthocyanines (60 mg/day) + xanthophylls (6 mg L + 2 mg Z/day). At the beginning of the study, 4 and 8 month serum L and Z concentrations were determined (HPLC), as well as L, Z and anthocyanine dietary intake and MPOD (heterochromic flicker photometry). Baseline concentrations of L (0.35 ± 0.19 µmol/L), Z (0.11 ± 0.05 µmol/L), L+Z/cholesterol/triglycerides (0.07 ± 0.04 µmol/mmol) increased in Group X (2.8- and 1.6-fold in L and Z concentrations) and in group XA (2- and 1.4-fold in L and Z concentrations). MPOD (baseline: 0.32 ± 0.13 du) was not modified in any of the groups at the end of the study. There were no differences in the dietary intake of L+Z and anthocyanin at any point in time in any group. Supplementation of L and Z at a dietary level provoked an increase in their serum concentration that was not modified by simultaneous supplementation with anthocyanins.

Impact of biofortified maize consumption on serum carotenoid concentrations in Zambian children.

Biofortified maize, designed as an intervention strategy to prevent vitamin A deficiency, can provide upwards of 15 µg ß-carotene per g dry weight. Some varieties also have elevated concentrations of other carotenoids. We conducted a cluster randomized, controlled feeding trial in rural Zambia to test the impact of daily consumption of biofortified maize over a 6-month period on vitamin A status. Serum concentrations of retinol and carotenoids were assessed by high-performance liquid chromatography. Data on circulating carotenoids by intervention group in 679 children are reported here. As previously shown, consumption of this ß-carotene-rich maize significantly improved serum ß-carotene concentrations (0.273 vs. 0.147 µmol/L, p < 0.001, in this subset of children). Here we show significant increases in α-carotene, ß-cryptoxanthin, and zeaxanthin (p < 0.001). There was no impact on lutein or lycopene concentrations. Consumption of biofortified maize can have broader implications beyond the control of vitamin A deficiency (Trial registration: NCT01695148).

The Relationship Between Plasma Concentrations of Lutein and Zeaxanthin with Self-Reported and Actual Prevalence of AMD in an Irish Population-Based Sample.

PURPOSE: To investigate plasma lutein (L) and zeaxanthin (Z) concentrations with grading-confirmed and self-reported prevalence of age-related macular degeneration (AMD). MATERIAL AND METHODS: Data collected from a nationally representative prospective cohort study of community-dwelling adults aged 50 years and over in the Republic of Ireland. Participants underwent a computer-assisted personal interview and a center-based health assessment. Plasma concentrations of L and total Z (Z and meso-zeaxanthin [MZ]) were measured by high performance liquid chromatography, and retinal photographs were graded using a version of the AMD International Classification and Grading System. Consumption of supplements containing L and/or Z and/or MZ was recorded as supplement use. Four groups were identified: Group 1 (n = 24): AMD-afflicted and correctly aware; Group 2 (n = 264): AMD-afflicted but unaware; Group 3 (n = 41): AMD-free and incorrectly believed that they were afflicted with the condition; Group 4 (n = 4094): AMD-free and correctly self-reported absence of AMD. RESULTS: Of 4,423 participants with plasma concentrations of L and Z and gradable retinal photographs, 288 (6.5%) were afflicted with AMD, and 65 (1.5%) self-reported AMD. Controlling for family history and age, the relationship between grading-confirmed AMD and plasma L was positive and significant (p < 0.001). Mean plasma concentrations of L in Group 2 (mean = 0.2162 ± 0.132 µmol) and Group 4 (mean = 0.2040 ± 0.121 µmol/L) were significantly lower than Group 1 (mean = 0.4691 ± 0.0.372 µmol/L) and Group 3 (mean = 0.3176 ± 0.0.235 µmol/L). Supplement use was reported by 41.7% and 17.1% of participants in Groups 1 and 3, respectively, but only 2.7% and 1.9% of participants in Groups 2 and 4, respectively. CONCLUSION: A belief that one suffers from AMD, whether justified or not, is associated with supplement use and with higher plasma concentrations of L.

Supplementation with macular carotenoids reduces psychological stress, serum cortisol, and sub-optimal symptoms of physical and emotional health in young adults.

PURPOSE: Oxidative stress and systemic inflammation are the root cause of several deleterious effects of chronic psychological stress. We hypothesize that the antioxidant and anti-inflammatory capabilities of the macular carotenoids (MCs) lutein, zeaxanthin, and meso-zeaxanthin could, via daily supplementation, provide a dietary means of benefit. METHODS: A total of 59 young healthy subjects participated in a 12-month, double-blind, placebo-controlled trial to evaluate the effects of MC supplementation on blood cortisol, psychological stress ratings, behavioural measures of mood, and symptoms of sub-optimal health. Subjects were randomly assigned to one of three groups: placebo, 13 mg, or 27 mg / day total MCs. All parameters were assessed at baseline, 6 months, and 12 months. Serum MCs were determined via HPLC, serum cortisol via ELISA, and macular pigment optical density (MPOD) via customized heterochromatic flicker photometry. Behavioural data were obtained via questionnaire. RESULTS: Significant baseline correlations were found between MPOD and Beck anxiety scores (r = -0.28; P = 0.032), MPOD and Brief Symptom Inventory scores (r = 0.27; P = 0.037), and serum cortisol and psychological stress scores (r = 0.46; P < 0.001). Supplementation for 6 months improved psychological stress, serum cortisol, and measures of emotional and physical health (P < 0.05 for all), versus placebo. These outcomes were either maintained or improved further at 12 months. CONCLUSIONS: Supplementation with the MCs significantly reduces stress, cortisol, and symptoms of sub-optimal emotional and physical health. Determining the basis for these effects, whether systemic or a more central (i.e. brain) is a question that warrants further study.

Dietary guidance for lutein: consideration for intake recommendations is scientifically supported.

Lutein, a yellow xanthophyll carotenoid found in egg yolks and many colorful fruits and vegetables, has gained public health interest for its putative role in visual performance and reducing the risk of age-related macular degeneration. The National Academies of Sciences, Engineering and Medicine's recommended Dietary Reference Intakes (DRIs) focus on preventing deficiency and toxicity, but there is a budding interest in establishing DRI-like guidelines for non-essential bioactives, like lutein, that promote optimal health and/or prevent chronic diseases. Lupton et al. developed a set of nine criteria to determine whether a bioactive is ready to be considered for DRI-like recommendations. These criteria include: (1) an accepted definition; (2) a reliable analysis method; (3) a food database with known amounts of the bioactive; (4) cohort studies; (5) clinical trials on metabolic processes; (6) clinical trials for dose-response and efficacy; (7) safety data; (8) systematic reviews and/or meta-analyses; (9) a plausible biological rationale. Based on a review of the literature supporting these criteria, lutein is ready to be considered for intake recommendations. Establishing dietary guidance for lutein would encourage the consumption of lutein-containing foods and raise public awareness about its potential health benefits.

Mono- and diglycerides improve lutein absorption in healthy adults: a randomised, double-blind, cross-over, single-dose study.

With the association between increased carotenoid intake and lower risk of chronic diseases, the absorption of lutein from the diet becomes an important factor in its delivery and physiological action. The primary objective of this study was to gain an understanding of how a new formulation technology (mixture of mono- and diglycerides (MDG)), affected lutein absorption. Subjects (n 24) were randomised in a cross-over, double-blind study to receive a single dose of 6 mg lutein (FloraGLO 20 %) provided as capsules containing either high-oleic safflower (SAF) oil or a MDG oil. Subjects receiving a single dose of lutein in MDG showed a significantly greater change from baseline (0 h) to 4, 6, 8, 12, 24, 48 and 336 h (P<0·05) and baseline adjusted AUC for plasma lutein at 48 and 336 h (P<0·001) as compared with subjects given lutein in SAF. Analysis of the 48 h absorption kinetics of lutein showed that the time to peak level of lutein (12 h) was the same for SAF and MDG groups, but the change in plasma lutein at 12 and 48 h were 129 and 320 % higher, respectively, for MDG compared with SAF. This difference continued as the adjusted AUC 0-48 and 0-336 h for the MDG group was 232 and 900 % higher, respectively, v. SAF. The study data show that by changing the lipid that is combined with a lutein supplement results in significant increases in lutein absorption in healthy adults.

Status of Vitamin A and Related Compounds and Clinical Outcomes in Maternal-Infant Pairs in the Midwestern United States.

BACKGROUND: Vitamin A is an essential nutrient for pregnant women, and other vitamin A-related compounds, including lutein and lycopene, have been associated with maternal-infant outcomes. The objective of this study was to quantify the status of vitamin A and related compounds in maternal-infant pairs at the time of delivery, and to determine its impact on clinical outcomes. METHODS: Maternal and cord blood samples were collected in 189 mother-infant pairs. Concentrations of lutein + zeaxanthin, ß-cryptoxanthin, lycopene, carotenes, and retinol were measured using high-performance liquid chromatography. Descriptive statistics was calculated and Spearman coefficients were used to assess correlations between maternal and cord measurements. Kruskal-Wallis and independent samples t test were used to compare measures between retinol groups. Linear and logistic regression models were used to adjust for relevant confounders. p < 0.05 was considered statistically significant. RESULTS: Ten percent of mothers had serum retinol concentrations ≤0.70 µmol/L; 80% of infants had serum retinol concentrations ≤0.70 µmol/L. Low maternal retinol concentrations were associated with maternal anemia (p = 0.04) and a trend toward low birth weight (p = 0.06). Maternal and infant concentrations of vitamin A compounds were highly correlated. After adjustment for confounders, maternal lutein was associated with a C-section (p = 0.03) and a diagnosis of respiratory distress syndrome in the infant (p = 0.02). Maternal lycopene was associated with growth parameters in the infant. CONCLUSIONS: As vitamin A-related compounds are modifiable by diet, future research determining the clinical impact of these compounds is warranted.

Modeling the dose effects of soybean oil in salad dressing on carotenoid and fat-soluble vitamin bioavailability in salad vegetables.

Background: Previously, we showed that vegetable oil is necessary for carotenoid absorption from salad vegetables. Research is needed to better define the dose effect and its interindividual variation for carotenoids and fat-soluble vitamins.Objective: The objective was to model the dose-response relation between the amount of soybean oil in salad dressing and the absorption of 1) carotenoids, phylloquinone, and tocopherols in salad vegetables and 2) retinyl palmitate formed from the provitamin A carotenoids.Design: Women (n = 12) each consumed 5 vegetable salads with salad dressings containing 0, 2, 4, 8, or 32 g soybean oil. Blood was collected at selected time points. The outcome variables were the chylomicron carotenoid and fat-soluble vitamin area under the curve (AUC) and maximum content in the plasma chylomicron fraction (Cmax). The individual-specific and group-average dose-response relations were investigated by fitting linear mixed-effects random coefficient models.Results: Across the entire 0-32-g range, soybean oil was linearly related to the chylomicron AUC and Cmax values for α-carotene, lycopene, phylloquinone, and retinyl palmitate. Across 0-8 g of soybean oil, there was a linear increase in the chylomicron AUC and Cmax values for ß-carotene. Across a more limited 0-4-g range of soybean oil, there were minor linear increases in the chylomicron AUC for lutein and α- and total tocopherol. Absorption of all carotenoids and fat-soluble vitamins was highest with 32 g oil (P < 0.002). For 32 g oil, the interindividual rank order of the chylomicron AUCs was consistent across the carotenoids and fat-soluble vitamins (P < 0.0001).Conclusions: Within the linear range, the average absorption of carotenoids and fat-soluble vitamins could be largely predicted by the soybean oil effect. However, the effect varied widely, and some individuals showed a negligible response. There was a global soybean oil effect such that those who absorbed more of one carotenoid and fat-soluble vitamin also tended to absorb more of the others. This trial was registered at clinicaltrials.gov as NCT02867488.

Correlations Between Macular, Skin, and Serum Carotenoids.

Purpose: Ocular and systemic measurement and imaging of the macular carotenoids lutein and zeaxanthin have been employed extensively as potential biomarkers of AMD risk. In this study, we systematically compare dual wavelength retinal autofluorescence imaging (AFI) of macular pigment with skin resonance Raman spectroscopy (RRS) and serum carotenoid levels in a clinic-based population. Methods: Eighty-eight patients were recruited from retina and general ophthalmology practices from a tertiary referral center and excluded only if they did not have all three modalities tested, had a diagnosis of macular telangiectasia (MacTel) or Stargardt disease, or had poor AFI image quality. Skin, macular, and serum carotenoid levels were measured by RRS, AFI, and HPLC, respectively. Results: Skin RRS measurements and serum zeaxanthin concentrations correlated most strongly with AFI macular pigment volume under the curve (MPVUC) measurements up to 9° eccentricity relative to MPVUC or rotationally averaged macular pigment optical density (MPOD) measurements at smaller eccentricities. These measurements were reproducible and not significantly affected by cataracts. We also found that these techniques could readily identify subjects taking oral carotenoid-containing supplements. Conclusions: Larger macular pigment volume AFI and skin RRS measurements are noninvasive, objective, and reliable methods to assess ocular and systemic carotenoid levels. They are an attractive alternative to psychophysical and optical methods that measure MPOD at a limited number of eccentricities. Consequently, skin RRS and MPVUC at 9° are both reasonable biomarkers of macular carotenoid status that could be readily adapted to research and clinical settings.

Effect of Carotenoid Supplemented Formula on Carotenoid Bioaccumulation in Tissues of Infant Rhesus Macaques: A Pilot Study Focused on Lutein.

Lutein is the predominant carotenoid in the developing primate brain and retina, and may have important functional roles. However, its bioaccumulation pattern during early development is not understood. In this pilot study, we investigated whether carotenoid supplementation of infant formula enhanced lutein tissue deposition in infant rhesus macaques. Monkeys were initially breastfed; from 1 to 3 months of age they were fed either a formula supplemented with lutein, zeaxanthin, ß-carotene and lycopene, or a control formula with low levels of these carotenoids, for 4 months (n = 2/group). All samples were analyzed by high pressure liquid chromatography (HPLC). Final serum lutein in the supplemented group was 5 times higher than in the unsupplemented group. All brain regions examined showed a selective increase in lutein deposition in the supplemented infants. Lutein differentially accumulated across brain regions, with highest amounts in occipital cortex in both groups. ß-carotene accumulated, but zeaxanthin and lycopene were undetectable in any brain region. Supplemented infants had higher lutein concentrations in peripheral retina but not in macular retina. Among adipose sites, abdominal subcutaneous adipose tissue exhibited the highest lutein level and was 3-fold higher in the supplemented infants. The supplemented formula enhanced carotenoid deposition in several other tissues. In rhesus infants, increased intake of carotenoids from formula enhanced their deposition in serum and numerous tissues and selectively increased lutein in multiple brain regions.

Lutein and atherosclerosis: Belfast versus Toulouse revisited.

In 1995 we reported that mean plasma lutein concentrations in salaried men and women from Toulouse in Southern France were double those in subjects recruited from general practitioner lists in Belfast, Northern Ireland. At the time incidence of coronary heart disease (CHD) in Southern France was among the lowest in Europe and was much higher in Northern Ireland. Plasma lutein is a biomarker of vegetable and fruit intake and evidence suggests that high concentrations are generally associated with better cardiometabolic health. At the time we speculated like others that role of the carotenoids may well have been to prevent oxidation of lipid in the lipoproteins and so reduce the uptake of oxidised lipid by macrophages and its deposition within the intimal layers of the major arteries as plaque. It is now widely accepted that CHD is an inflammatory disease and that macrophages within plaque together with tissue damage contribute to this inflammation. Stimulated macrophages release cytokines to activate the immune system both locally and systemically. Precursor complement proteins in the blood are activated to assist immune cells in phagocytosis and cell repair. Individuals with a history of arteriosclerosis display significantly higher concentrations of complement factors C3 and C3a than subjects without such a history. Metabolism of C3 via the alternate complement pathway can give rise to the membrane attack complex (MAC) which creates a hole or pore in pathogens or host cells, killing the cell. Recent studies in patients with early age related macular disease (AMD) who also exhibit similar elevated concentrations of complement proteins in their blood, showed supplementation with lutein progressively decreased the amount of the MAC and other complement factors in the blood. Lutein was used in the supplementation experiments because it is an important constituent of macular pigment. Thus the healthier cardiometabolic features displayed by the people in Toulouse may have been due to the effects of concurrent high concentrations of plasma lutein on the immune system and complement in particular. Other carotenoids may exert similar antioxidant effects but we and others found no differences in antioxidant nutrients between subjects in Toulouse and Belfast or between subjects with asymptomatic markers of atherosclerosis and controls.

Plasma Carotenoids, Tocopherols, and Retinol in the Age-Stratified (35-74 Years) General Population: A Cross-Sectional Study in Six European Countries.

Blood micronutrient status may change with age. We analyzed plasma carotenoids, α-/γ-tocopherol, and retinol and their associations with age, demographic characteristics, and dietary habits (assessed by a short food frequency questionnaire) in a cross-sectional study of 2118 women and men (age-stratified from 35 to 74 years) of the general population from six European countries. Higher age was associated with lower lycopene and α-/ß-carotene and higher ß-cryptoxanthin, lutein, zeaxanthin, α-/γ-tocopherol, and retinol levels. Significant correlations with age were observed for lycopene (r = -0.248), α-tocopherol (r = 0.208), α-carotene (r = -0.112), and ß-cryptoxanthin (r = 0.125; all p < 0.001). Age was inversely associated with lycopene (-6.5% per five-year age increase) and this association remained in the multiple regression model with the significant predictors (covariables) being country, season, cholesterol, gender, smoking status, body mass index (BMI (kg/m²)), and dietary habits. The positive association of α-tocopherol with age remained when all covariates including cholesterol and use of vitamin supplements were included (1.7% vs. 2.4% per five-year age increase). The association of higher ß-cryptoxanthin with higher age was no longer statistically significant after adjustment for fruit consumption, whereas the inverse association of α-carotene with age remained in the fully adjusted multivariable model (-4.8% vs. -3.8% per five-year age increase). We conclude from our study that age is an independent predictor of plasma lycopene, α-tocopherol, and α-carotene.