Previous studies have been conducted using multiple dosing regimens and variable doses to determine the plateau concentration of lutein in the bloodstream. The current study was designed to assess the effect of different formulation technologies on the bioavailability profile of lutein and zeaxanthin after single oral doses of two comparative test articles both of which contained lutein and zeaxanthin, specifically in a starch-based or in an alginate-based matrix.
SMB demonstrated greater bioavailability than AMB exhibiting a 126.0 % increase at 14 h in total lutein and a 144.1 % increase from pre-dose in its principle isomer all-E-lutein while AMB showed an 7.1 % increase in total lutein and a 7.1 % increase from pre-dose in all-E-lutein. Seventy-two hours post-administration, the plasma concentrations of total lutein and all-E-lutein remained approximately 65 % higher than pre-dose values for SMB, whereas plasma values were at or below pre-dose concentrations for AMB by 72 h.
Although to a much lower degree due to the lower dose, zeaxanthin plasma profiles were similar to those of lutein, SMB performed better than AMB with a 12.9 % increase at 14 h from pre-dose in total zeaxanthin and a 16.3 % increase in its principle isomer all-E-zeaxanthin, while AMB showed an 5.1 % increase at 14 h from pre-dose in total zeaxanthin and a 6.4 % increase in all-E-zeaxanthin. Bioavailability of total and all-E-zeaxanthin in response to AMB exhibited an absorption pattern limited to the first 24 h post-test article administration followed by a decrease in blood concentrations below pre-dose levels. There was an increase in plasma concentrations after 72 h continuing through 672 h, perhaps suggesting a dietary influence. However, SMB demonstrated a plasma zeaxanthin profile that was maintained for greater than 72 h post-supplementation and, similar to AMB, the profile showed an increase in plasma values from 168 to 672 h. The serum profiles of all-E-lutein and all-E-zeaxanthin were similar to and closely followed the profiles of total lutein and total zeaxanthin suggesting that all-E-lutein and all-E-zeaxanthin are the predominant isomers in the plasma. The profile for the 72 h total lutein mimicked that of total zeaxanthin during the initial 72 h in response to SMB with an initial peak seen after 14 h and a second peak of lesser magnitude around 32 h.
It is interesting that this second peak appears in the profiles of both zeaxanthin (Fig. 4) as well as lutein (Fig. 2) and reaches maximum values after approximately 32 h in each case. The appearance of this second peak was not observed by Yao et al.  who measured lutein in the bloodstream of humans using a 13C tracer technique. However, the latter study included only one measurement of plasma lutein in the interval between 16 and 48 h, namely at 24 h. The lack of additional measurements within this timeframe when the second peak was observed in the present study, probably accounts for the differences observed. This second peak, visible for SMB only, could be explained by the general characteristics of carotenoid absorption. After ingestion of a single dose of β-carotene, a similar second plasma concentration peak has been reported . The authors have concluded that the early rise in circulating β-carotene concentrations is caused by the intestinal input, whereas hepatic secretion is the source of later increases. It is likely that the xanthophylls behave similar to beta-carotene. Additionally, the second peak may arise from further release of xanthophylls into the circulation via newly synthesized chylomicrons from the intestine induced by a subsequent meal (fat). Such distinctive profiles in plasma response were not seen with AMB.
Statistical analysis of pharmacokinetic parameters demonstrated that total and all-E-lutein were significantly increased in the plasma in response to SMB. Mean total lutein and all-E-lutein AUC(0–72h) were significantly increased (p < 0.001) in response to SMB as compared to AMB. Mean maximum plasma total lutein and all-E-lutein concentrations (C
max) were significantly (p < 0.001) higher in subjects after administration of SMB. Though the time to reach maximum concentration (T
max) was not significantly different between test products as measured by total or all-E-lutein, there was a faster response to SMB for total lutein and all-E-lutein as compared to AMB.
Numerous studies in the literature attest to the importance of the role of lutein and zeaxanthin in the prevention of age-related eye diseases in high-risk populations. In the course of the Lutein Antioxidant Supplementation Trial (LAST), a double-blind, placebo-controlled trial in 90 patients with atrophic AMD, 10 mg of lutein was supplemented for 1 year. Along with increases in macular pigment optical density, there was net improvement in several visual function parameters (glare and contrast sensitivity, visual acuity) in addition to a reversal of the symptoms of AMD indicating a potentially preventative activity against the development of AMD . Nutritional studies correlating the effects of high dietary intake of antioxidants with protection against AMD reported that higher intakes of carotenoids were associated with a reduced risk of exudative neovascular macular degeneration . The carotenoids lutein and zeaxanthin obtained principally from dark green, leafy vegetables such as spinach, kale, collard greens, mustard greens, and turnip greens were most strongly associated with reduced risk of AMD. Additionally, several prospective studies have reported that higher intakes of lutein and zeaxanthin were associated with decreased risk of cataracts . After a 10-year follow-up, women consuming the most lutein and zeaxanthin had an 18 % lower risk of developing cataracts than those who consumed the least. More recently, older women with high dietary concentrations of lutein and zeaxanthin have been associated with decreased prevalence of nuclear cataracts .
Knowledge relating to the formulation of supplements and the pharmacokinetics of lutein absorption is critical to a better understanding of plasma bioavailability of these carotenoids. A variation of lutein from different food sources [25, 26] and the vast individual variation in macular accumulation and its variance in target populations  make it important that bioavailability studies research the pharmacokinetics of supplements prior to the implementation of long-term clinical trials. Furthermore, due to the fact that the polarities of lutein and zeaxanthin are similar, most researchers report combined values for lutein and zeaxanthin when reporting results. In the current study, plasma samples were analyzed for the xanthophylls lutein and zeaxanthin and their all-E-isomers thereby providing a more comprehensive assessment of the availability of the prevalent isomer in the plasma. Thus, the data generated from this study provide clear kinetics of the two materials evaluated after a single dose and allowed for the assessment of the bioavailability of the materials. In light of the high prevalence of eye disease in aging populations and the impact of lutein and zeaxanthin in its prevention, the results of the current study are significant.
Of the subjects enrolled into the current study, 87.5 % were White, while 4.2 % were Asian–Oriental, 4.2 % Black, and 4.2 % East Indian; 14.6 % of enrolled subjects were current smokers. Pooled data from several studies have identified that there is a strong age-related increase in AMD in people of European descent with significant increases in rates in both men and women older than 80 years of age .
In this population of subjects, a single dose of SMB resulted in a 126.0 % increase in total plasma lutein and a 144.1 % increase from pre-dose in its principle isomer all-E-lutein within the first 14 h as well as a significant increase in AUC(0–72h) for total plasma lutein, all-E-lutein, total zeaxanthin and all-E-zeaxanthin and AUC(0–672h) for total plasma lutein and all-E-lutein. AUC values were significantly higher than those reached after AMB administration, demonstrating the superiority of SMB over AMB. Additionally, the data gathered should be helpful to future research and clinical studies in relation to determining optimal dosing regimens and anticipated blood concentrations of lutein and zeaxanthin from the dosages chosen.
Although case–control studies suggest a combined dose of 6 mg of lutein and zeaxanthin per day for reducing the risk of AMD, the average North American ingests only 1–2 mg of lutein daily from their diet [22, 28]. This may lead to a deficit of these important carotenoids. With the dramatic increase in age-related eye diseases, it becomes very important to more thoroughly understand the issues associated with the bioavailability of lutein and zeaxanthin supplement formulations and their potential impact upon target populations.