Plasma lipophilic antioxidants and malondialdehyde in congestive heart failure patients: relationship to disease severity.

Plasma levels of malondialdehyde (MDA), vitamin A, and of antioxidant micronutrients including vitamin E, lutein, zeaxanthin, beta-cryptoxanthin, lycopene, and alpha- and beta-carotene were measured in 30 patients with class II and III congestive heart failure (CHF) according to the New York Heart Association (NYHA) classification and in 55 controls. Ejection fraction was evaluated by echocardiography in all patients as a measure of the emptying capacity of the heart. Plasma levels of all measured compounds were significantly lower and MDA significantly higher in patients compared to controls (p <.001). Class II NYHA patients showed significantly lower MDA levels and significantly higher levels of vitamin A, vitamin E, lutein, and lycopene than class III patients. Ejection fraction was inversely correlated with MDA levels and directly correlated with vitamin A, vitamin E, lutein, and lycopene levels in patients. The present study supports the concept that an increased consumption of vitamin-rich fruits and vegetables might help in achieving cardiovascular health.     

Oxidation of carotenoids by heat and tobacco smoke

The stability to autoxidation of the polar carotenoids, lutein and zeaxanthin, was compared to that of the less polar carotenoids, beta-carotene and lycopene at physiologically or pathophysiologically relevant concentrations of 2 and 6 microM, after exposure to heat or cigarette smoke. Three methodological approaches were used: 1) Carotenoids dissolved in solvents with different polarities were incubated at 37 and 80 degrees C for different times. 2) Human plasma samples were subjected to the same temperature conditions. 3) Methanolic carotenoid solutions and plasma were also exposed to whole tobacco smoke from 1-5 unfiltered cigarettes. The concentrations of individual carotenoids in different solvents were determined spectrophotometrically. Carotenoids from plasma were extracted and analyzed using high performance liquid chromatography. Carotenoids were generally more stable at 37 than at 80 degrees C. In methanol and dichloromethane the thermal degradation of beta-carotene and lycopene was faster than that of lutein and zeaxanthin. However, in tetrahydrofuran beta-carotene and zeaxanthin degraded faster than lycopene and lutein. Plasma carotenoid levels at 37 degrees C did not change, but decreased at 80 degrees C. The decrease of beta-carotene and lycopene levels was higher than those for lutein and zeaxanthin. Also in the tobacco smoke experiments the highest autoxidation rates were found for beta-carotene and lycopene at 2 microM, but at 6 microM lutein and zeaxanthin depleted to the same extent as beta-carotene. These data support our previous studies suggesting that oxidative stress degrade beta-carotene and lycopene faster than lutein and zeaxanthin. The only exception was the thermal degradation of carotenoids solubilized in tetrahydrofuran, which favors faster breakdown of beta-carotene and zeaxanthin.     

Carotenoid-containing unilamellar liposomes loaded with glutathione: a model to study hydrophobic-hydrophilic antioxidant interaction

Unilamellar liposomes are used as a simple two-compartment model to study the interaction of antioxidants. The vesicle membrane can be loaded with lipophilic compounds such as carotenoids or tocopherols, and the aqueous core space with hydrophilic substances like glutathione (GSH) or ascorbate, mimicking the interphase between an aqueous compartment of a cell and its surrounding membrane.

Unilamellar liposomes were used to investigate the interaction of GSH with the carotenoids lutein, β-carotene and lycopene in preventing lipid peroxidation. Lipid peroxidation was initiated with 2,2′-azo-bis-[2,4-dimethylvaleronitrile] (AMVN). Malondialdehyde (MDA) formation was measured as an indicator of oxidation; additionally, the loss of GSH was followed. In liposomes without added antioxidant, MDA levels of 119 ± 6 nmol/mg phospholipid were detected after incubation with AMVN for 2 h at 37°C. Considerably lower levels of 57 ± 8 nmol MDA/mg phospholipid were found when the liposomal vesicles had been loaded with GSH. Upon incorporation of β-carotene, lycopene or lutein, the resistance of unilamellar liposomes towards lipid peroxidation was further modified. An optimal further protection was observed with 0.02 nmol β-carotene/mg phospholipid or 0.06 nmol lycopene/mg phospholipid. At higher levels both these carotenoids exhibited prooxidant effects. Lutein inhibited lipid peroxidation in a dose-dependent manner between 0.02 and 2.6 nmol/mg phospholipid. With increasing levels of lycopene and lutein the consumption of encapsulated GSH decreased moderately, and high levels of β-carotene led to a more pronounced loss of GSH.

The data demonstrate that interactions between GSH and carotenoids may improve resistance of biological membranes towards lipid peroxidation. Different carotenoids exhibit specific properties, and the level for optimal protection varies between the carotenoids.     

Carotenoid-containing unilamellar liposomes loaded with glutathione: a model to study hydrophobic-hydrophilic antioxidant interaction

Unilamellar liposomes are used as a simple two-compartment model to study the interaction of antioxidants. The vesicle membrane can be loaded with lipophilic compounds such as carotenoids or tocopherols, and the aqueous core space with hydrophilic substances like glutathione (GSH) or ascorbate, mimicking the interphase between an aqueous compartment of a cell and its surrounding membrane.

Unilamellar liposomes were used to investigate the interaction of GSH with the carotenoids lutein, β-carotene and lycopene in preventing lipid peroxidation. Lipid peroxidation was initiated with 2,2'-azo-bis-[2,4-dimethylvaleronitrile] (AMVN). Malondialdehyde (MDA) formation was measured as an indicator of oxidation; additionally, the loss of GSH was followed. In liposomes without added antioxidant, MDA levels of 119 ± 6 nmol/mg phospholipid were detected after incubation with AMVN for 2 h at 37°C. Considerably lower levels of 57 ± 8 nmol MDA/mg phospholipid were found when the liposomal vesicles had been loaded with GSH. Upon incorporation of β-carotene, lycopene or lutein, the resistance of unilamellar liposomes towards lipid peroxidation was further modified. An optimal further protection was observed with 0.02 nmol β-carotene/mg phospholipid or 0.06 nmol lycopene/mg phospholipid. At higher levels both these carotenoids exhibited prooxidant effects. Lutein inhibited lipid peroxidation in a dose-dependent manner between 0.02 and 2.6 nmol/mg phospholipid. With increasing levels of lycopene and lutein the consumption of encapsulated GSH decreased moderately, and high levels of β-carotene led to a more pronounced loss of GSH.

The data demonstrate that interactions between GSH and carotenoids may improve resistance of biological membranes towards lipid peroxidation. Different carotenoids exhibit specific properties, and the level for optimal protection varies between the carotenoids.     

High dietary intake of phytosterol esters decreases carotenoids and increases plasma plant sterol levels with no additional cholesterol lowering

The objective of this study was to measure the effects on serum lipids and plasma phytosterols of 6.6 g/day phytosterols from three foods (bread, breakfast cereal, and spread) consumed for 12 weeks compared with a diet that was not enriched with phytosterols. Thirty-five subjects undertook a nonrandomized, single-blind study consisting of a 2 week baseline period, 6 weeks on high-phytosterol intake, 6 weeks on high-phytosterol intake plus increased fruit and vegetable intake, and a final 2 week washout period. Serum total cholesterol decreased by 8.3% from 6.59 to 6.04 mmol/l, and LDL cholesterol decreased by 12.6% from 4.44 to 3.88 mmol/l. Plasma phytosterol levels increased by 45% (sitosterol) and 105% (campesterol). Cholesterol-adjusted plasma alpha- and beta-carotene levels decreased by 19-23%, lutein by 14%, and lycopene by 11%. Levels of alpha-carotene and lutein increased with extra fruit and vegetables. Only lycopene failed to increase during the washout phase. There were no significant changes in biochemical parameters. Serum LDL cholesterol lowering with 6.6 g/day ingested phytosterols was in the range seen with 1.6-3.2 g/day phytosterols. Lowering of plasma carotenoids was greater than that seen with lower phytosterol intake and was partially reversed by increased fruit and vegetable intake.     

Addition of lutein, lycopene, or β-carotene to LDL or serum in vitro: Effects on carotenoid distribution, LDL composition, and LDL oxidation

Carotenoids are dietary antioxidants transported with plasma lipoproteins, primarily low-density lipoprotein (LDL). In this study in vitro methods were used to increase the amounts of specific, individual carotenoids in LDL. By addition of carotenoid to isolated LDL or to serum, followed by (re)isolation of the lipoproteins, samples of LDL were enriched 4- to 150-fold with lutein, 2- to 15-fold with lycopene, or 3- to 25-fold with β-carotene. Enrichment with specific carotenoids was achieved without affecting the electrophoretic mobility of the lipoprotein, its cholesterol to protein ratio, or the levels of other cartenoids or -tocopherol. The distributions among lipoproteins of carotenoid added to serum were similar, but not identical, to the distributions of the endogenous carotenoids. In particular, for added lutein, a greater proportion was found in HDL, and for added β-carotene, more was found in very low-density lipoprotein (VLDL). We then studied the effect of enriching LDL with specific carotenoids on its susceptibility to oxidation by copper ions. Lutein, β-cryptoxanthin, lycopene, and β-carotene, the four major plasma carotenoids, and -tocopherol were destroyed before the formation of lipid peroxidation products. The rates of destruction of the individual carotenoids differed; lycopene was destroyed most rapidly and lutein most slowly. Upon oxidation of β-carotene-enriched LDL, the rates of destruction of β-carotene, lycopene, and lutein were slowed and the lag times before the initiation of lipid peroxidation increased from 19 to 65 min. Neither effect was observed in LDL enriched with lutein or lycopene. Thus, β-carotene was unique among the carotenoids studied in having a small, but significant effect on LDL oxidation in vitro.     

急性缺血性脑卒中患者入院时血浆BNP水平与梗死部位关系

目的：分析急性缺血性脑卒中患者入院时血浆脑钠肽（BNP）水平与缺血性脑卒中梗死部位的关系。方法：随机入选88例急性缺血性脑卒中患者,按梗死部位,将其分为前循环病灶组（66名）和后循环病灶组（22名）两组进行比较。测定入院时血浆脑钠肽（BNP）水平进行比较。两组脑卒中病人的危险因素血糖、糖化血红蛋白、血脂全套,肝肾功能分析对比,并将急性缺血性脑卒中患者梗死部位相关的多个变量采用单因素logistic回归分析。结果：前循环病灶组血浆脑利钠肽水平的中位数是225.90 pg/mL,四分位数间距为596.00 pg/mL;后循环病灶组的中位数是750.95 pg/mL,四分位数间距为907.00 pg/mL。后循环病灶组血浆脑利钠肽水平要显著高于前循环病灶组血浆脑利钠肽水平,两个部位间入院时的脑利钠肽水平有统计学差异（P=0.004）。通过入院时脑利钠肽水平与缺血性脑卒中梗死部位的关系的ROC曲线,得出截点299.50 pg/mL。入院时血浆脑利钠肽水平≥299.50 pg/mL可以作为后循环病灶组的预测指标,其敏感性72.72%,特异性62.12%。结论：急性缺血性脑卒中患者入院时血浆BNP水平可作为急性期区别前后循环脑梗死的预测因子。     

Lycopene and beta-carotene decompose more rapidly than lutein and zeaxanthin upon exposure to various pro-oxidants in vitro

Major carotenoids of human plasma and tissues were exposed to radical-initiated autoxidation conditions. The consumption of lutein and zeaxanthin, the only carotenoids in the retina, and lycopene and beta-carotene, the most effective quenchers of singlet oxygen in plasma, were compared. Under all conditions of free radical-initiated autoxidation of carotenoids which were investigated, the breakdown of lycopene and beta-carotene was much faster than that of lutein and zeaxanthin. Under the influence of UV light in presence of Rose Bengal, by far the highest breakdown rate was found for beta-carotene, followed by lycopene. Bleaching of carotenoid mixtures mediated by NaOCl, addition of azo-bis-isobutyronitril (AIBN), and the photoirradiation of carotenoid mixtures by natural sunlight lead to the following sequence of breakdown rates: lycopene > beta-carotene > zeaxanthin > lutein. The slow degradation of the xanthophylls zeaxanthin and lutein may be suggested to explain the majority of zeaxanthin and lutein in the retina of man and other species. In correspondence to that, the rapid degradation of beta-carotene and lycopene under the influence of natural sunlight and UV light is postulated to be the reason for the almost lack of those two carotenoids in the human retina. Nevertheless, a final proof of that theory is lacking.     

Enhancing the carotenoid content of <Emphasis Type="Italic">Brassica napus</Emphasis> seeds by downregulating lycopene epsilon cyclase

The accumulation of carotenoids in higher plants is regulated by the environment, tissue type and developmental stage. In Brassica napus leaves, beta-carotene and lutein were the main carotenoids present while petals primarily accumulated lutein and violaxanthin. Carotenoid accumulation in seeds was developmentally regulated with the highest levels detected at 35-40 days post anthesis. The carotenoid biosynthesis pathway branches after the formation of lycopene. One branch forms carotenoids with two beta rings such as beta-carotene, zeaxanthin and violaxanthin, while the other introduces both beta- and epsilon-rings in lycopene to form alpha-carotene and lutein. By reducing the expression of lycopene epsilon-cyclase (epsilon-CYC) using RNAi, we investigated altering carotenoid accumulation in seeds of B. napus. Transgenic seeds expressing this construct had increased levels of beta-carotene, zeaxanthin, violaxanthin and, unexpectedly, lutein. The higher total carotenoid content resulting from reduction of epsilon-CYC expression in seeds suggests that this gene is a rate-limiting step in the carotenoid biosynthesis pathway. epsilon-CYC activity and carotenoid production may also be related to fatty acid biosynthesis in seeds as transgenic seeds showed an overall decrease in total fatty acid content and minor changes in the proportions of various fatty acids.     

Significant correlations of dermal total carotenoids and dermal lycopene with their respective plasma levels in healthy adults

Carotenoids in skin have been known to play a role in photoprotection against UV radiation. We performed dermal biopsies of healthy humans (N = 27) and collected blood samples for pair-wise correlation analyses of total and individual carotenoid content by high performance liquid chromatography (HPLC). The hydrocarbon carotenoids (lycopene and beta-carotene) made up the majority of carotenoids in both skin and plasma, and skin was somewhat enriched in these carotenoids relative to plasma. Beta-cryptoxanthin, a monohydroxycarotenoid, was found in similar proportions in skin as in plasma. In contrast, the dihydroxycarotenoids, lutein and zeaxanthin, were relatively lacking in human skin in absolute and relative levels as compared to plasma. Total carotenoids were significantly correlated in skin and plasma (r = 0.53, p < 0.01). Our findings suggest that human skin is relatively enriched in lycopene and beta-carotene, compared to lutein and zeaxanthin, possibly reflecting a specific function of hydrocarbon carotenoids in human skin photoprotection.     

Processing of vegetable-borne carotenoids in the human stomach and duodenum

Carotenoids are thought to diminish the incidence of certain degenerative diseases, but the mechanisms involved in their intestinal absorption are poorly understood. Our aim was to obtain basic data on the fate of carotenoids in the human stomach and duodenum. Ten healthy men were intragastrically fed three liquid test meals differing only in the vegetable added 3 wk apart and in a random order. They contained 40 g sunflower oil and mashed vegetables as the sole source of carotenoids. Tomato purée provided 10 mg lycopene as the main carotenoid, chopped spinach (10 mg lutein), and carrot purée (10 mg beta-carotene). Samples of stomach and duodenal contents and blood samples were collected at regular time intervals after meal intake. all-trans and cis carotenoids were assayed in stomach and duodenal contents, in the fat and aqueous phases of those contents, and in chylomicrons. The cis-trans beta-carotene and lycopene ratios did not significantly vary in the stomach during digestion. Carotenoids were recovered in the fat phase present in the stomach during digestion. The proportion of all-trans carotenoids found in the micellar phase of the duodenum was as follows (means +/- SE): lutein (5.6 +/- 0.4%), beta-carotene (4.7 +/- 0.3%), lycopene (2.0 +/- 0.2%). The proportion of 13-cis beta-carotene in the micellar phase was significantly higher (14.8 +/- 1.6%) than that of the all-trans isomer (4.7 +/- 0.3%). There was no significant variation in chylomicron lycopene after the tomato meal, whereas there was significant increase in chylomicron beta-carotene and lutein after the carrot and the spinach meals, respectively. There is no significant cis-trans isomerization of beta-carotene and lycopene in the human stomach. The stomach initiates the transfer of carotenoids from the vegetable matrix to the fat phase of the meal. Lycopene is less efficiently transferred to micelles than beta-carotene and lutein. The very small transfer of carotenoids from their vegetable matrices to micelles explains the poor bioavailability of these phytomicroconstituents.     

A Mediterranean-style low-glycemic-load diet increases plasma carotenoids and decreases LDL oxidation in women with metabolic syndrome

Thirty-five women with metabolic syndrome and high plasma low-density lipoprotein (LDL) cholesterol (≥100 mg/dl) participated in a dietary intervention consisting of a Mediterranean-style low-glycemic-load diet for 12 weeks. Participants were randomly allocated to consume diet only (n=15) or diet plus a medical food containing soy protein and plant sterols (n=20). Plasma concentrations of carotenoids, lipoprotein subfractions and oxidized LDL (OxLDL) were measured. Independent of treatment, women had a significant increase in plasma lutein (P<.0001) and β-carotene (P<.0001), while plasma lycopene was reduced (P<.05) after 12 weeks. Low-density lipoprotein cholesterol was reduced from 138±35 to 114±33 mg/dl (P<.0001). In addition, decreases were observed in the atherogenic subfractions: large very low-density lipoprotein (P<.05), small LDL (P<.00001) and medium high-density lipoprotein (P<.05). Oxidized LDL was significantly reduced by 12% in both groups (P<.01). Changes in OxLDL were inversely correlated with plasma lutein (r=-.478, P<.0001). The data indicate that women complied with the dietary regimen by increasing fruits and vegetable intake. Decreased consumption of high-glycemic foods frequently co-consumed with lycopene-rich tomato sauce such as pasta and pizza may be responsible for the lowering of this carotenoid in plasma after 12 weeks. These results also suggest that plasma lutein concentrations may protect against oxidative stress by reducing the concentrations of OxLDL.     

Lycopene,atherosclerosis, and coronary heart disease

Diets rich in fruits and vegetables containing carotenoids have been of interest because of their potential health benefit against chronic diseases such as cardiovascular diseases (CVD) and cancer. Interest particularly in lycopene is growing rapidly following the recent publication of epidemiological studies that have associated high lycopene levels with reductions in CVD incidence. Two studies were conducted. In the first one, we examined the role of lycopene as a risk-lowering factor with regard to acute coronary events and stroke in the prospective Kuopio Ischemic Heart Disease Risk Factor (KIHD) Study. The subjects were 725 middle-aged men free of coronary heart disease and stroke at the study baseline. In a Cox's proportional hazards' model adjusting for covariates, men in the lowest quartile of serum levels of lycopene had a 3.3-fold (P < 0.001) risk of the acute coronary event or stroke as compared with others. In the second study, we assessed the association between plasma concentration of lycopene and intima-media thickness of the common carotid artery wall (CCA-IMT) in a cross-sectional analysis of the Antioxidant Supplementation in the Atherosclerosis Prevention (ASAP) study data in 520 asymptomatic men and women. In a covariance analysis adjusting for common cardiovascular risk factors, low plasma levels of lycopene were associated with an 18% increase of IMT in men as compared with men in whom plasma levels were higher than median (P = 0.003 for difference). In women, the difference did not remain significant after the adjustments. On the basis of these works, it is evident that the circulating levels of lycopene play some role with regard to cardiovascular health in Finland, at least in men. We conclude that circulating levels of lycopene, a biomarker of tomato-rich food, may play a role in early stages of atherogenesis and may have clinical and public health relevance.     

Plasma iron is associated with lipid peroxidation in an elderly population

Epidemiological evidence has raised concern that a moderate elevation in body iron stores may increase oxidative stress and risk of heart disease. We examined the cross-sectional association between plasma iron and factors that could affect its levels (antioxidant enzymes, diet), with the concentration of plasma malondialdehyde (MDA) as a marker of lipid peroxidation. Participants were 162 non-smoking institutionalised elderly. Our results show that those in the highest tertile of plasma iron were at least twice as likely to have higher plasma MDA levels. Among the factors affecting plasma iron levels, we found that the upper tertile of erythrocyte-superoxide dismutase (E-SOD) was inversely associated with higher plasma iron, and potato intake explained a sizeable proportion of the variation in plasma iron levels. In addition to potatoes, eggs, wine, fruit in men and green vegetables in women showed a positive association with plasma iron levels. Only potatoes in both sexes, wine in men and eggs in women had an independent effect on plasma MDA. Potatoes, wine, plasma lycopene and plasma iron accounted for 43% of the variability in plasma MDA for males, and E-SOD, potatoes, eggs, plasma lycopene and plasma iron explained 45% for women. A longitudinal study should confirm, whether these MDA levels are related to morbidity and mortality.     

The effect of an acute phase response on tissue carotenoid levels of growing chickens (Gallus gallus domesticus)

Plasma, liver and skin carotenoids decrease following infectious disease challenges. Since these challenges often involve substantial host pathology and chronic immune responses, the mechanism underlying altered carotenoid deposition is unclear. Therefore, changes in tissue carotenoid levels were examined during an acute phase response induced by lipopolysaccharide (LPS) or interleukin-1 (IL-1). In two experiments, chicks were hatched from carotenoid-deplete eggs (n=28, n=64, respectively) and fed 0, 8 or 38 mg carotenoids (lutein+canthaxanthin)/kg diet. For chicks fed 38 mg carotenoids, but not those fed 0 or 8 mg, LPS generally reduced plasma lutein, canthaxanthin and total carotenoids (P<0.05), and liver lutein, zeaxanthin, canthaxanthin and total carotenoids (P<0.05). Additionally, LPS reduced thymic total carotenoids (P=0.05) and increased thymocyte lutein (P=0.07), zeaxanthin (P=0.07) and total carotenoids (P=0.07). Finally, LPS increased bursal canthaxanthin (P<0.01), but had no effect on shank carotenoids (P>0.5). In chicks hatched from carotenoid-replete eggs (n=36) and fed dietary lutein (38 mg/kg diet), LPS reduced plasma and liver zeaxanthin and liver total carotenoids (P<0.05); IL-1 reduced plasma and liver lutein, zeaxanthin and total carotenoids (P<0.05). Therefore, an acute phase response plays a role in reduced tissue carotenoids during infectious disease.     

Independent and interactive association of blood antioxidants and oxidative damage in elderly people

Oxidative stress is recognized as one of the major contributors to the increased risk of several diseases. Many recent population studies have established a close link between antioxidant defense and lowered risk of morbidity and mortality from cancer and heart disease, but little is known about the cooperative interactions of antioxidants. We examined the cross-sectional independent and interactive association of serum lipid-soluble antioxidant levels and free radical scavenging enzymes to serum malondialdehyde (MDA) levels, as a marker of oxidative damage. The participants were 160 nonsmoker institutionalized elderly. Upper tertile values of erythrocyte-superoxide-dismutase (E-SOD) constituted the strongest-associated single compound with a 74% decreased risk of high MDA. Upper tertiles of carotenoids and alpha-tocopherol independently showed a similar lowering of risk of about 57%. The highest tertiles of lycopene and either beta-carotene or alpha-tocopherol simultaneously reveal a higher decreased risk for oxidative damage (74 and 71%, respectively), very similar to those in the upper tertiles of all these three vitamins (75%). This study represents one of the few attempts to date to understand the interactive effect between antioxidants and suggests that lipid-soluble antioxidants act not individually, but rather cooperatively with each other. The efficacy of this interaction is more effective when lycopene is present.     

Absorption and metabolism of dietary carotenoids

A number of carotenoids with diverse structures are present in foods and have beneficial effects on human health due to their common antioxidant activity and their respective biological activities. The major carotenoids found in human tissues, however, are limited to several including such as β-carotene, lycopene, and lutein. We have little knowledge of whether carotenoids are selectively absorbed in intestine and metabolized discriminately in the body. Moreover, the metabolic transformation of carotenoids in mammals other than vitamin A formation has not been fully elucidated. Here, the intestinal absorption and oxidative metabolism of dietary carotenoids are reviewed with a focus on dietary xanthophylls.     

Longitudinal Survey of Carotenoids in Human Milk from Urban Cohorts in China,Mexico, and the USA

Emerging evidence indicates that carotenoids may have particular roles in infant nutrition and development, yet data on the profile and bioavailability of carotenoids from human milk remain sparse. Milk was longitudinally collected at 2, 4, 13, and 26 weeks postpartum from twenty mothers each in China, Mexico, and the USA in the Global Exploration of Human Milk Study (n = 60 donors, n = 240 samples). Maternal and neonatal plasma was analyzed for carotenoids from the USA cohort at 4 weeks postpartum. Carotenoids were analyzed by HPLC and total lipids by Creamatocrit. Across all countries and lactation stages, the top four carotenoids were lutein (median 114.4 nmol/L), β-carotene (49.4 nmol/L), β-cryptoxanthin (33.8 nmol/L), and lycopene (33.7 nmol/L). Non-provitamin A carotenoids (nmol/L) and total lipids (g/L) decreased (p<0.05) with increasing lactation stage, except the provitamin A carotenoids α- and β-cryptoxanthin and β-carotene did not significantly change (p>0.05) with lactation stage. Total carotenoid content and lutein content were greatest from China, yet lycopene was lowest from China (p<0.0001). Lutein, β-cryptoxanthin, and β-carotene, and lycopene concentrations in milk were significantly correlated to maternal plasma and neonatal plasma concentrations (p<0.05), with the exception that lycopene was not significantly associated between human milk and neonatal plasma (p>0.3). This enhanced understanding of neonatal exposure to carotenoids during development may help guide dietary recommendations and design of human milk mimetics.     

Interaction of peroxynitrite with carotenoids in human low density lipoproteins

Interaction of peroxynitrite, the product of the reaction between nitric oxide and superoxide, with carotenes (lycopene, alpha-carotene, and beta-carotene) and oxocarotenoids (beta-cryptoxanthin, zeaxanthin, and lutein) was studied both in homogeneous solution and in human low-density lipoproteins (LDL). All carotenoids prevented the formation of rhodamine 123 from dihydrorhodamine 123 caused by peroxynitrite, suggesting that the carotenoids react with peroxynitrite. Oxocarotenoids were as effective as biothiols, known scavengers of peroxynitrite, whereas lycopene, alpha-carotene, and beta-carotene exhibited a considerably more pronounced effect. Moreover, peroxynitrite caused a loss of carotenoids in LDL as was revealed by HPLC. The concentration of peroxynitrite causing half-maximal loss of carotenoids in LDL ranged from 13 +/- 3 to 68 +/- 3 microM for lycopene and lutein, respectively. Again, oxocarotenoids were less reactive in this system. A correlation between efficiency of carotenoids in the competitive assay with dihydrorhodamine 123 and the concentration of peroxynitrite causing half-maximal loss of carotenoids in LDL was observed (r(2) = 0.91). These findings suggest that carotenoids can efficiently react with peroxynitrite and perform the role of scavengers of peroxynitrite in vivo.     

Differential effects of carotenoids on lipid peroxidation due to membrane interactions: X-ray diffraction analysis

The biological benefits of certain carotenoids may be due to their potent antioxidant properties attributed to specific physico-chemical interactions with membranes. To test this hypothesis, we measured the effects of various carotenoids on rates of lipid peroxidation and correlated these findings with their membrane interactions, as determined by small angle X-ray diffraction approaches. The effects of the homochiral carotenoids (astaxanthin, zeaxanthin, lutein, β-carotene, lycopene) on lipid hydroperoxide (LOOH) generation were evaluated in membranes enriched with polyunsaturated fatty acids. Apolar carotenoids, such as lycopene and β-carotene, disordered the membrane bilayer and showed a potent pro-oxidant effect (> 85% increase in LOOH levels) while astaxanthin preserved membrane structure and exhibited significant antioxidant activity (40% decrease in LOOH levels). These findings indicate distinct effects of carotenoids on lipid peroxidation due to membrane structure changes. These contrasting effects of carotenoids on lipid peroxidation may explain differences in their biological activity.