Reduced absorption capacity in patients with intestinal resections (IR) could result in malabsorption of fat-soluble components like carotenoids, which are of clinical interest in relation to visual health. In this case cohort, we investigated the association between IR and serum lutein, zeaxanthin, β-carotene and macular pigment optical density, when compared with healthy controls. Ten patients with IR and twelve healthy controls were included in the study. Baseline characteristics were comparable between groups, except for higher serum TAG (P < 0·05) and shorter bowel length (P < 0·0001) in the group with IR. Serum lutein, zeaxanthin, β-carotene and macular pigment optical density were >15 % lower in the patient group compared with healthy controls (P < 0·05, adjusted for age) and, in the case of serum lutein and zeaxanthin, also for dietary intake of carotenoids. Results suggest that for a test of macular carotenoid supplementation, subjects with a potentially clinically significant carotenoid deficit could be recruited among patients with IR.

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.

The macular carotenoids lutein (L), zeaxanthin (Z) and meso-zeaxanthin (MZ) accumulate at the macula, where they are collectively referred to as macular pigment (MP). Augmentation of this pigment, typically achieved through diet and supplementation, enhances visual function and protects against progression of age-related macular degeneration. However, it is known that eggs are a rich dietary source of L and Z, in a highly bioavailable matrix. In this single-blind placebo-controlled study, L- and MZ-enriched eggs and control non-enriched eggs were fed to human subjects (mean age 41 and 35 years, respectively) over an 8-week period, and outcome measures included MP, visual function and serum concentrations of carotenoids and cholesterol. Serum carotenoid concentrations increased significantly in control and enriched egg groups, but to a significantly greater extent in the enriched egg group (P<0·001 for L, Z and MZ). There was no significant increase in MP in either study group post intervention, and we saw no significant improvement in visual performance in either group. Total cholesterol increased significantly in each group, but it did not exceed the upper limit of the normative range (6·5 mmol/l). Therefore, carotenoid-enriched eggs may represent an effective dietary source of L, Z and MZ, reflected in significantly raised serum concentrations of these carotenoids, and consequentially improved bioavailability for capture by target tissues. However, benefits in terms of MP augmentation and /or improved visual performance were not realised over the 8-week study period, and a study of greater duration will be required to address these questions.

The xanthophyll carotenoids lutein (L), zeaxanthin (Z) and meso-zeaxanthin (MZ) are found at the macula, the central part of the retina, where they are referred to as macular pigment (MP). MP is studied in human subjects because of its proven role in enhancing visual function and its putative role in protecting against age-related macular degeneration. These benefits are probably due to the antioxidant and short-wavelength filtering properties of MP. It is known that eggs are a dietary source of L and Z. This experiment was designed to measure the egg yolk carotenoid response to hen supplementation with L, Z and MZ. A total of forty hens were used in the trial and were divided into eight groups of five hens. Each group was supplemented (with about 140 mg active xanthophylls/kg feed) with one of the following oil-based carotenoid formulations for 6 weeks: unesterified L (group 1); L diacetate (group 2); unesterified Z (group 3); Z diacetate (group 4); unesterified MZ (group 5); MZ diacetate (group 6); L–MZ (1:1) diacetate mixture (group 7); L–MZ diacetate (1:3) mixture (group 8). Yolk carotenoid content was analysed weekly (in four randomly selected eggs) by HPLC. We found that hens supplemented with Z diacetate and MZ diacetate produced eggs with significantly greater carotenoid concentrations than their free form counterparts. This finding potentially represents the development of a novel food, suitable to increase MP and its constituent carotenoids in serum.

Macular pigment (MP) is composed of lutein (L), zeaxanthin (Z) and meso-zeaxanthin (MZ). The present study reports on serum response to three different MP supplements in normal subjects (n 27) and in subjects with age-related macular degeneration (AMD) (n 27). Subjects were randomly assigned to: Group 1 (20 mg L and 2 mg Z), Group 2 (10 mg L, 2 mg Z and 10 mg MZ) or Group 3 (3 mg L, 2 mg Z and 17 mg MZ). Serum carotenoids were quantified at baseline, and at 4 and 8 weeks using HPLC. Response data for normal and AMD subjects were comparable and therefore combined for analysis. We report response as the average of the 4- and 8-week concentrations (saturation plateau). Serum L increased significantly in Group 1 (0·036 μmol/l per mg (269 %); P< 0·001) and Group 2 (0·079 μmol/l per mg (340 %); P< 0·001), with no significant change in Group 3 (0·006 μmol/l per mg (7 %); P= 0·466). Serum Z increased significantly in Group 1 (0·037 μmol/l per mg (69 %); P= 0·001) and Group 2 (0·015 μmol/l per mg (75 %); P< 0·001), with no significant change in Group 3 ( − 0·0002 μmol/l per mg ( − 6 %); P= 0·384). Serum MZ increased significantly in Group 1 (0·0094 μmol/l (absolute value); P= 0·015), Group 2 (0·005 μmol/l per mg; P< 0·001) and Group 3 (0·004 μmol/l per mg; P< 0·001). The formulation containing all three macular carotenoids (Group 2 supplement) was the most efficacious in terms of achieving the highest combined concentration of the three MP constituent carotenoids in serum, thereby potentially optimising the bioavailability of these compounds for capture by the target tissue (retina).

Zeaxanthin is a predominant xanthophyll in human eyes and may reduce the risk of cataracts and age-related macular degeneration. Spirulina is an algal food that contains a high concentration of zeaxanthin. In order to determine the zeaxanthin bioavailability of spirulina for dietary supplementation in humans, spirulina was grown in nutrient solution with 2H2O for carotenoid labelling. Single servings of 2H-labelled spirulina (4·0–5·0 g) containing 2·6–3·7 mg zeaxanthin were consumed by fourteen healthy male volunteers (four Americans and ten Chinese) with 12 g dietary fat. Blood samples were collected over a 45 d period. The serum concentrations of total zeaxanthin were measured using HPLC, and the enrichment of labelled zeaxanthin was determined using LC-atmospheric pressure chemical ionisation-MS (LC-APCI-MS). The results showed that intrinsically labelled spirulina zeaxanthin in the circulation was detected at levels as low as 10 % of the total zeaxanthin for up to 45 d after intake of the algae. A single dose of spirulina can increase mean serum zeaxanthin concentration in humans from 0·06 to 0·15 μmol/l, as shown in our study involving American and Chinese volunteers. The average 15 d area under the serum zeaxanthin response curve to the single dose of spirulina was 293 nmol × d/μmol (range 254–335) in American subjects, and 197 nmol × d/μmol (range 154–285) in Chinese subjects. It is concluded that the relative bioavailability of spirulina zeaxanthin can be studied with high sensitivity and specificity using 2H labelling and LC-APCI-MS methodology. Spirulina can serve as a rich source of dietary zeaxanthin in humans.

The aim of the present study was to compare the effect of lutein- and zeaxanthin-rich foods and supplements on macular pigment level (MPL) and serological markers of endothelial activation, inflammation and oxidation in healthy volunteers. We conducted two 8-week intervention studies. Study 1 (n 52) subjects were randomised to receive either carrot juice (a carotene-rich food) or spinach powder (a lutein- and zeaxanthin-rich food) for 8 weeks. Study 2 subjects (n 75) received supplements containing lutein and zeaxanthin, β-carotene, or placebo for 8 weeks in a randomised, double-blind, placebo-controlled trial. MPL, serum concentrations of lipid-soluble antioxidants, inter-cellular adhesion molecule 1, vascular cell adhesion molecule 1, C-reactive protein and F2-isoprostane levels were assessed at baseline and post-intervention in both studies. In these intervention studies, no effects on MPL or markers of endothelial activation, inflammation or oxidation were observed. However, the change in serum lutein and zeaxanthin was associated or tended to be associated with the change in MPL in those receiving lutein- and zeaxanthin-rich foods (lutein r 0·40, P = 0·05; zeaxanthin r 0·30, P = 0·14) or the lutein and zeaxanthin supplement (lutein r 0·43, P = 0·03; zeaxanthin r 0·22, P = 0·28). In both studies, the change in MPL was associated with baseline MPL (food study r − 0·54, P < 0·001; supplement study r − 0·40, P < 0·001). We conclude that this 8-week supplementation with lutein and zeaxanthin, whether as foods or as supplements, had no significant effect on MPL or serological markers of endothelial activation, inflammation and oxidation in healthy volunteers, but may improve MPL in the highest serum responders and in those with initially low MPL.

Oxidative stress plays an important role in cataractogenesis. Previous studies have shown that long-term dietary intake of antioxidants (lutein and zeaxanthin) may decrease the risk of age-related cataracts. The aim of the present study was to examine whether plasma concentrations of lutein and zeaxanthin are related to age-related nuclear cataract in the elderly population. Subjects were participants in the Kuopio Ischaemic Heart Disease Risk Factor Study and they were classified into tertiles according to plasma concentrations of lutein and zeaxanthin. The association of plasma lutein and zeaxanthin concentrations with age-related nuclear cataract in 1689 elderly subjects (aged 61–80 years) was investigated in the present cross-sectional study by using the Cox proportional hazards model. A total of 113 cases of incident age-related cataracts were confirmed, of which 108 cases were nuclear cataracts. After adjustment for age, examination year, sex, BMI, smoking, alcohol consumption, serum LDL-cholesterol, serum HDL-cholesterol, years of education, use of oral corticosteroids, history of diabetes and history of hypertension with current use of antihypertensive medication, subjects in the highest tertiles of plasma concentrations of lutein and zeaxanthin had 42 and 41 % lower risks of nuclear cataract, respectively, compared with those in the lowest tertiles (relative risk (RR) = 0·58, 95 % CI 0·35, 0·98; P = 0·041 for lutein and RR = 0·59, 95 % CI 0·35, 0·99; P = 0·046 for zeaxanthin). In conclusion, we suggest that high plasma concentrations of lutein and zeaxanthin were associated with a decreased risk of age-related nuclear cataract in the elderly population.

Lutein and zeaxanthin are thought to decrease the incidence of age-related macular degeneration (AMD); however, findings have been inconsistent. We conducted a systematic literature review and meta-analysis to evaluate the relationship between dietary intake of lutein and zeaxanthin and AMD risk. Relevant studies were identified by searching five databases up to April 2010. Reference lists of articles were retrieved, and experts were contacted. Literature search, data extraction and study quality assessment were performed independently by two reviewers and results were pooled quantitatively using meta-analysis methods. The potential sources of heterogeneity and publication bias were also estimated. The search yielded six longitudinal cohort studies. The pooled relative risk (RR) for early AMD, comparing the highest with the lowest category of lutein and zeaxanthin intake, was 0·96 (95 % CI 0·78, 1·17). Dietary intake of these carotenoids was significantly related with a reduction in risk of late AMD (RR 0·74; 95 % CI 0·57, 0·97); and a statistically significant inverse association was observed between lutein and zeaxanthin intake and neovascular AMD risk (RR 0·68; 95 % CI 0·51, 0·92). The results were essentially consistent among subgroups stratified by participant characteristics. The findings of the present meta-analysis indicate that dietary lutein and zeaxanthin is not significantly associated with a reduced risk of early AMD, whereas an increase in the intake of these carotenoids may be protective against late AMD. However, additional studies are needed to confirm these relationships.

We measured the blood uptake of meso-zeaxanthin (MZ) from a mixture of macular pigments since its bioavailability in man has not been studied. Volunteers (ten men and nine women) were recruited and received one capsule of Lutein Plus®/d. Blood was taken at baseline, day 10 and day 22. One capsule contained 10·8 mg lutein, 1·2 mg (3R,3′R)-zeaxanthin and 8·0 mg MZ. Plasma lutein and total zeaxanthin concentrations were quantified using isocratic liquid chromatography and the eluting xanthophyll fractions were collected and re-chromatographed on a chiral column to assess the proportion of MZ. Plasma concentrations per mg dose at day 22 suggested that (3R,3′R)-zeaxanthin (0·088 μmol/l per mg) was about 50 % more actively retained by the body than lutein (0·056 μmol/l per mg) (although the difference was not significant in women) and 2·5–3·0 times more than MZ (0·026 μmol/l per mg). Concentrations of MZ at day 22 were 2·5 times higher in women than men. The plasma responses from lutein and (3R,3′R)-zeaxanthin in the Lutein Plus® were lower than literature values for the pure substances. That is, their uptake into plasma appeared to be slightly depressed by the presence of MZ. Plasma concentrations of β-carotene were depressed by about 50 % at day 10 and about 35 % at day 22. In conclusion, the lower plasma response to MZ compared with (3R,3′R)-zeaxanthin probably indicates that MZ is less well absorbed than (3R,3′R)-zeaxanthin but work with pure MZ will be needed to confirm that the lower plasma response was not due to the large amount of lutein in the Lutein Plus®.

The retina is unique in the human body in containing three xanthophyll carotenoids; 3R,3′R-zeaxanthin, meso-zeaxanthin (MZ) and lutein. Humans consume 1 to 3 mg lutein per d and the lutein:zeaxanthin ratio in the diet is about 5:1.Xanthophyll pigments occur widely in vegetables and fruits but MZ is found in only a few foods such as the shrimp carapace and fish skin. In spite of the amounts of the different xanthophylls in the diet, zeaxanthin and MZ occur in approximately equal amounts in the eye, and their combined concentration can exceed that of lutein. In the present review the bioavailablity of zeaxanthin and lutein is assessed using the plasma xanthophyll response to dietary intervention. A number of studies have used single and mixed sources of the pure xanthophylls to achieve steady-state plasma responses. Mostly these have been with lutein and zeaxanthin but two using MZ are also described. Responses following the intervention with the pure xanthophylls are compared with those following food intervention. Vegetables are the richest source of dietary lutein and several vegetable-feeding studies are discussed. Intervention studies with eggs, which are a good source of zeaxanthin, suggest that the xanthophyll carotenoids in egg yolk may be more bioavailable than those in other foods and are described separately. MZ has been a component of a xanthophyll supplement added to chicken feed in Mexico in the last 10 years. Egg consumption in Mexico is approximately one egg/person per d and the potential contribution of this food source of MZ to Mexican dietary intakes is described. Very limited information from human feeding studies of MZ-containing supplements suggests that MZ is less well absorbed than zeaxanthin. However, MZ is unusual in the diet and not reported in the plasma. Thus plasma responses may not reflect true absorption if it takes MZ longer to equilibrate with body tissues than the other xanthophylls and competition with zeaxanthin may lower the relative concentrations of MZ in plasma. Lastly, the effects of long-term feeding with both pure and food sources of the xanthophyll pigments on macular pigment optical density is compared and the importance of previous dietary intake on the effects of intervention is discussed.

Approximately 5–7 % of all infants are born prematurely, and birth before 37 weeks is the most common cause of neonatal mortality, morbidity and long-term disability. Premature infants are poorly equipped for life outside the womb, and oxidant stress has been implicated in the aetiology of visual impairment in these infants, who are often exposed to increased O2 concentrations and high light intensity in neonatal units. The carotenoids lutein and zeaxanthin, which give the macular area of the eye its yellow colour, are located in the retinal pigment epithelium of the eye, and are believed to play a role in protecting it against oxidative and light damage. The macular pigments are of dietary origin, and green leafy vegetables are the primary source of lutein and zeaxanthin. Lutein is one of the five most common carotenoids found in the diet. There is current interest in the macular pigment in relation to age-related macular degeneration, but these pigments may also have a protective role in the retinal pigment epithelium of the newborn infant. Little information is available on blood lutein and zeaxanthin levels in neonates. Levels of lutein in human milk are two to three times higher than those of β-carotene, whereas their concentrations in the mothers’ blood are approximately the same. Human milk is the main dietary source of lutein and zeaxanthin for infants until weaning occurs. The biochemical mechanisms which mediate the transport of the macular carotenoids into the eye are not known, but tubulin has been identified as the major carotenoid-binding protein, and may play a role in the physiology of the macula.

The carotenoid zeaxanthin is concentrated within the macula. Increased macular zeaxanthin is suggested to lower the risk of age-related macular degeneration. The small red berry, wolfberry (Fructus barbarum L.; Gou Qi Zi and Kei Tze), is one of the richest natural sources of zeaxanthin. However, carotenoid bioavailability is low, and food-based products with enhanced bioavailability are of interest. The present study investigated zeaxanthin bioavailability from three wolfberry formulations. Berries were homogenised in hot (80°C) water, warm (40°C) skimmed milk and hot (80°C) skimmed milk, with freeze drying of each preparation into a powdered form. A zeaxanthin-standardised dose (15mg) of each was consumed, in randomised order, together with a standardised breakfast by twelve healthy, consenting subjects in a cross-over trial, with a 3–5-week washout period between treatments. Blood samples were taken via a venous cannula immediately before (fasting) and 2, 4, 6, 7, 8 and 10h post-ingestion. Zeaxanthin concentration in the triacylglycerol-rich lipoprotein fraction of plasma was measured by HPLC. Results showed that triacylglycerol-rich lipoprotein zeaxanthin peaked at 6h post-ingestion for all formulations. Zeaxanthin bioavailability from the hot milk formulation was significantly higher (p<0·001) than from the others. Mean area under the curve (n 12) results were 9·73 (sem 2·45), 3·24 (sem 0·72) and 3·14 (sem 1·09) nmol×h/l for the hot milk, warm milk and hot water formulations, respectively. Results showed clearly that homogenisation of wolfberry in hot skimmed milk results in a formulation that has a 3-fold enhanced bioavailability of zeaxanthin compared with both the ‘classical’ hot water and warm skimmed milk treatment of the berries.

Age-related macular degeneration (AMD) is a common disorder that causes irreversible loss of central vision. Increased intake of foods containing zeaxanthin may be effective in preventing AMD because the macula accumulates zeaxanthin and lutein, oxygenated carotenoids with antioxidant and blue light-absorbing properties. Lycium barbarum L. is a small red berry known as Fructus lycii and wolfberry in the West, and Kei Tze and Gou Qi Zi in Asia. Wolfberry is rich in zeaxanthin dipalmitate, and is valued in Chinese culture for being good for vision. The aim of this study, which was a single-blinded, placebo-controlled, human intervention trial of parallel design, was to provide data on how fasting plasma zeaxanthin concentration changes as a result of dietary supplementation with whole wolfberries. Fasting blood was collected from healthy, consenting subjects; fourteen subjects took 15 g/d wolfberry (estimated to contain almost 3 mg zeaxanthin) for 28 d. Repeat fasting blood was collected on day 29. Age- and sex-matched controls (n 13) took no wolfberry. Responses in the two groups were compared using the Mann–Whitney test. After supplementation, plasma zeaxanthin increased 2·5-fold: mean values on day 1 and 29 were 0·038 (sem 0·003) and 0·096 (sem 0·009) μmol/l (P<0·01), respectively, for the supplementation group; and 0·038 (sem 0·003) and 0·043 (sem 0·003) μmol/l (P>0·05), respectively, for the control group. This human supplementation trial shows that zeaxanthin in whole wolfberries is bioavailable and that intake of a modest daily amount markedly increases fasting plasma zeaxanthin levels. These new data will support further study of dietary strategies to maintain macular pigment density.

The combination of nitrogen deprivation and increased cultivation light intensity resulted in the synthesis of secondary carotenoids in flagellates of Haematococcus lacustris. The pigment pattern was characterized by high-pressure liquid chromatography analysis during the accumulation period and in response to inhibitors of carotenoid biosynthesis (diphenylamine, norflurazon and tetcyclacis). Diphenylamine treatment resulted in (i) a decrease in ketocarotenoids and (ii) an accumulation of β-carotene and zeaxanthin due to inhibition of the β-carotene oxygenase. Our results indicate that astaxanthin synthesis in H. lacustris follows the biosynthetic pathway elucidated in the marine bacterium Agrobacterium aurantiacum.