Circulating Carotenoid Concentrations Research Articles

Plasma carotenoid concentrations of incubating American kestrels (Falco sparverius) show annual, seasonal, and individual variation and explain reproductive outcome.

In wild birds, the proximate and ultimate factors that affect circulating carotenoid concentrations remain poorly understood. We studied variation in plasma carotenoid concentrations across several scales: annual, seasonal, pair, territory and individual, and evaluated whether carotenoid levels explained reproductive outcome of wild American kestrels (Falco sparverius). We sampled plasma carotenoid concentrations of 99 female and 80 male incubating kestrels from April-June in 2008-2012. Plasma carotenoid concentrations were explained by an interaction between year and sex, date, and random effects for pair and individual identity. In general, plasma carotenoid concentrations of males were significantly higher than females, but this depended on year. Within a breeding season, earlier nesting kestrels had higher carotenoid concentrations than later nesting kestrels, a pattern that is coincident with seasonal trends in local fitness. Pair and individual identity explained variation in carotenoid concentrations suggesting that carotenoid concentrations of mated birds were correlated, and some individuals consistently maintained higher carotenoid levels than others. Male carotenoid concentrations were positively associated with number of young fledged per pair. These results are consistent with the hypothesis that higher quality individuals have higher carotenoid levels compared to lower quality individuals, despite annual variations in carotenoid availability.

The effect of carotenoid supplementation on immune system development in juvenile male veiled chameleons (Chamaeleo calyptratus)

IntroductionNutrient availability, assimilation, and allocation can have important and lasting effects on the immune system development of growing animals. Though carotenoid pigments have immunostimulatory properties in many animals, relatively little is known regarding how they influence the immune system during development. Moreover, studies linking carotenoids to health at any life stage have largely been restricted to birds and mammals. We investigated the effects of carotenoid supplementation on multiple aspects of immunity in juvenile veiled chameleons (Chamaeleo calyptratus). We supplemented half of the chameleons with lutein (a xanthophyll carotenoid) for 14 weeks during development and serially measured multiple aspects of immune function, including: agglutination and lysis performance of plasma, wound healing, and plasma nitric oxide concentrations before and after wounding.ResultsThough lutein supplementation effectively elevated circulating carotenoid concentrations throughout the developmental period, we found no evidence that carotenoid repletion enhanced immune function at any point. However, agglutination and lysis scores increased, while baseline nitric oxide levels decreased, as chameleons aged.ConclusionsTaken together, our results indicate that body mass and age, but not carotenoid access, may play an important role in immune performance of growing chameleons. Hence, studying well-understood physiological processes in novel taxa can provide new perspectives on alternative physiological processes and nutrient function.

Foraging for carotenoids: do colorful male hihi target carotenoid-rich foods in the wild?

Dietary access to carotenoids is expected to determine the strength of carotenoid-based signal expression and potentially to maintain signal honesty. Species that display carotenoid-based yellow, orange, or red plumage are therefore expected to forage selectively for carotenoid-rich foods when they are depositing these pigments during molt, but whether they actually do so is unknown. We set out to address this in the hihi (Notiomystis cincta), a New Zealand passerine where males, but not females, display yellow carotenoid-based plumage. We measured circulating carotenoid concentrations in male and female hihi during breeding and molt, determined the nutritional content of common foods in the hihi diet, and conducted feeding observations of male and female hihi during molt. We found that although male and female hihi do not differ significantly in plasma carotenoid concentration, male hihi have a greater proportion of carotenoid-rich foods in their diet than do females. This is a consequence of a greater fruit and lower invertebrate intake than females and an avoidance of low-carotenoid content fruit. By combining behavioral observations with quantification of circulating carotenoids, we present evidence that colorful birds forage to maximize carotenoid intake, a conclusion we would not have drawn had we examined plasma carotenoids alone.

Plasma Carotenoid- and Retinol-Weighted Multi-SNP Scores and Risk of Breast Cancer in the National Cancer Institute Breast and Prostate Cancer Cohort Consortium

Dietary and circulating carotenoids have been inversely associated with breast cancer risk, but observed associations may be due to confounding. Single-nucleotide polymorphisms (SNPs) in β-carotene 15,15'-monooxygenase 1 (BCMO1), a gene encoding the enzyme involved in the first step of synthesizing vitamin A from dietary carotenoids, have been associated with circulating carotenoid concentrations and may serve as unconfounded surrogates for those biomarkers. We determined associations between variants in BCMO1 and breast cancer risk in a large cohort consortium. We used unconditional logistic regression to test four SNPs in BCMO1 for associations with breast cancer risk in 9,226 cases and 10,420 controls from the National Cancer Institute Breast and Prostate Cancer Cohort Consortium (BPC3). We also tested weighted multi-SNP scores composed of the two SNPs with strong, confirmed associations with circulating carotenoid concentrations. Neither the individual SNPs nor the weighted multi-SNP scores were associated with breast cancer risk [OR (95% confidence interval) comparing extreme quintiles of weighted multi-SNP scores = 1.04 (0.94-1.16) for β-carotene, 1.08 (0.98-1.20) for α-carotene, 1.04 (0.94-1.16) for β-cryptoxanthin, 0.95 (0.87-1.05) for lutein/zeaxanthin, and 0.92 (0.83-1.02) for retinol]. Furthermore, no associations were observed when stratifying by estrogen receptor status, but power was limited. Our results do not support an association between SNPs associated with circulating carotenoid concentrations and breast cancer risk. Future studies will need additional genetic surrogates and/or sample sizes at least three times larger to contribute evidence of a causal link between carotenoids and breast cancer.

Serum β-Carotene in Relation to Risk of Prostate Cancer: The Kuopio Ischaemic Heart Disease Risk Factor Study

Results from epidemiologic studies on the association between circulating carotenoid concentrations and the risk of prostate cancer are still inconsistent. We studied whether serum concentrations of carotenoids were associated with the risk of developing prostate cancer. The study population consisted of 997 middle-aged Finnish men (56.1 ± 6.6 yr) in the Kuopio Ischaemic Heart Disease Risk Factor (KIHD) cohort. Serum concentrations of carotenoids were measured by high-performance liquid chromatography. Subjects were classified into tertiles according to their serum concentrations of antioxidants. Relative risks (RRs) were estimated by using the Cox proportional hazard models. During the mean follow-up time of 15 yr, a total of 68 prostate cancer cases occurred. After adjusting for age, examination yr, family history of cancer, BMI, pack-yr of smoking, alcohol consumption, education, physical activity, serum total cholesterol, and serum α-linolenic acid, men in the highest tertile of serum concentrations of β-carotene had 2.3-fold higher risk of prostate cancer as compared to those in the lowest tertile (RR = 2.29, 95% CI: 1.12–4.66; P = 0.023). α-Tocopherol and retinol were not associated with prostate cancer. This prospective study suggests that high-serum β-carotene concentrations may increase the risk of prostate cancer in middle-aged men.

The effect of capture-and-handling stress on carotenoid-based beak coloration in zebra finches

Stress can have widespread effects on animal behaviors and phenotypes, including sexually selected traits. Ornamental colors have long been studied as honest signals of condition, but few studies have been conducted on how the physiological stress response (i.e., corticosterone (CORT) elevation) impacts color expression. We used a traditional capture-and-restraint technique to examine the effect of repeated handling stress on carotenoid-dependent beak coloration in male and female zebra finches (Taeniopygia guttata). Birds subjected to daily, 10-min handling treatments, which elevated circulating CORT levels, for a four-week period displayed deeper orange/red beak coloration than did control animals. Stressed males lost body mass during the experiment and marginally decreased in circulating carotenoid concentrations. Hence, handling stress may have reduced food intake or induced mobilization of body stores (i.e., fat) of carotenoids. In contrast to males, stressed females maintained orange beak color, while control females faded in color. This study highlights sex- and pigment-specific mechanisms by which stress may temporarily enhance the expression of sexual traits, but at the expense of other key fitness traits (e.g., body mass maintenance, reproduction).

Cigarette smoke and human plasma lycopene depletion

It is known that smokers have a higher risk of developing cardiovascular disease and lung cancer. Plasma carotenoid concentrations in smokers are generally lower than in non-smokers and this may be due to modifications in diet or a direct or indirect action of cigarette smoke on carotenoids in the plasma. Recently it was reported that reactive nitrogen species derived from cigarette smoke could diffuse across the lung alveolar cell wall into the plasma. Such species may modify circulating low density lipoprotein (LDL) and in the process reduce circulating carotenoid concentrations. In an effort to address this rational we have treated lycopene solutions, human plasma and isolated LDL with cigarette smoke and monitored all-(E)-lycopene, 5(Z )-lycopene and β-carotene depletion. In plasma, the depletion of all-(E)-lycopene (15.0 ± 11.0%, n = 10) was greater than 5(Z )-lycopene (10.4 ± 9.6%) or β-carotene (12.4 ± 10.5%). In LDL, both all-(E)- and 5(Z)-lycopene were more susceptible than β-carotene (20.8 ± 11.8%, 15.4 ± 11.5% and 11.5 ± 12.5%, n = 3 respectively). The effects have been compared with Sin-1 reactions and isomerization of all-(E) lycopene is common to both treatments. The results clearly indicate that low plasma lycopene may be a direct consequence of smoke inhalation.

Sexual, seasonal, and environmental variation in plasma carotenoids in great tits, Parus major

In many birds, carotenoids have dual functions as irreversible plumage pigments and as physiologically essential vitamins and antioxidants. They must be obtained through the diet and may therefore be a limiting resource, a constraint that is likely to vary with factors such as sex, habitat, and time of year. In the present study, we investigated signs of carotenoid limitation in great tits, Parus major, in relation to sex, season, year, and within an urban versus a rural habitat. The two main carotenoids, lutein and zeaxanthin, were analysed by high-performance liquid chromatography in the plasma and in the yellow carotenoid-based breast feathers. We found that plasma carotenoid concentrations were significantly influenced by sex, season, and year, but not by urban versus rural habitat. At moult, plasma concentration was positively correlated with feather pigmentation, independent of body condition and sex. During the breeding season, however, circulating carotenoid concentrations were negatively related to the feather pigmentation (i.e. from previous autumn moult). We suggest that great tits are carotenoid deprived before leaf emergence, and that carotenoid utilization and limitations are sex-specific, but that there are neither any obvious honesty-maintaining costs of pigmentation, nor any fitness consequences of the colour variation. © 2007 The Linnean Society of London, Biological Journal of the Linnean Society, 2007, 92, 521–527.

Relationships of Circulating Carotenoid Concentrations with Several Markers of Inflammation, Oxidative Stress, and Endothelial Dysfunction: The Coronary Artery Risk Development in Young Adults (CARDIA)/Young Adult Longitudinal Trends in Antioxidants (YALTA) Study

Serum carotenoid concentrations relate inversely to cardiovascular disease incidence. To clarify the effect of carotenoids on atherosclerotic risk factors, we examined the association of circulating carotenoids with inflammation, oxidative stress, endothelial dysfunction, and smoking. Black and white men and women in the Coronary Artery Risk Development in Young Adults study, ages 18 to 30 years at recruitment (1985-1986) from 4 US cities, were investigated over 15 years. We included 2048 to 4580 participants in analyses of the sum of serum alpha-carotene, beta-carotene, zeaxanthin/lutein, and beta-cryptoxanthin concentrations and of lycopene at year 0 and at year 7. The year 0 sum of 4 carotenoids was inversely associated (all P <0.05) with year 0 leukocyte count (slope per sum carotenoid SD, -0.17); year 7 fibrinogen (slope, -0.10); year 7 and year 15 C-reactive protein (slope, -0.12 and -0.09); and year 15 F(2)-isoprostanes (slope, -13.0), soluble P-selectin (slope, -0.48), and soluble intercellular adhesion molecule-1 (sICAM1; slope, -5.1). Leukocyte counts and sICAM1 and F(2)-isoprostane concentrations had stronger associations in smokers than in nonsmokers, and sICAM1 concentrations were higher in the highest carotenoid quartile in smokers than in the lowest carotenoid quartile in nonsmokers. Superoxide dismutase was positively associated with the sum of 4 carotenoids (slope, 0.12; P <0.01). Lycopene was inversely associated only with sICAM1. The year 7 carotenoid associations with these markers were mostly similar to those at year 0. Circulating serum carotenoids were associated, some interactively with smoking, in apparently beneficial directions with markers of inflammation, oxidative stress, and endothelial dysfunction.

Increases in Plasma Carotenoid Concentrations in Response to a Major Dietary Change in the Women's Healthy Eating and Living Study

Cohort studies suggest that higher circulating carotenoid concentrations through food sources may reduce breast cancer events. Other intervention studies have not achieved the level of change in circulating carotenoids required to properly test this hypothesis. In a randomized trial of 2,922 breast cancer survivors, we examined blood and self-reported diet at baseline and 1 year. Intensive telephone counseling encouraged a plant-based diet in the intervention group. Diet was measured via 24-hour recalls, and a panel of plasma carotenoid concentrations was assessed at both time points. The study intervention was associated with a 51% increase in total carotenoid concentration, from 2.272 +/- 1.294 to 3.440 +/- 2.320 micromol/L, achieved mainly by marked increases in targeted carotenoids: alpha-carotene, beta-carotene, and lutein. For each of these targeted carotenoids, the proportion of the intervention sample remaining below the cutpoint for the lowest baseline quartile decreased by one third to one half. After 1 year of study, half of the intervention group was in the highest baseline quartile. No change in distribution was observed in comparison group. Intervention participants achieved this change by both dietary pattern and vegetable juice consumption. Participants who chose to change dietary pattern without consuming significant quantities of vegetable juice achieved 75% of the level of change observed in other intervention participants. Innovative telephone counseling intervention and dietary targets in the Women's Healthy Eating and Living study were associated with the level of change in circulating carotenoid concentration necessary to test the diet and breast cancer hypothesis suggested by cohort studies.

Olestra is associated with slight reductions in serum carotenoids but does not markedly influence serum fat-soluble vitamin concentrations

The 1996 Food and Drug Administration approval of the fat substitute olestra (sucrose polyester) called for active postmarketing surveillance because preapproval studies showed that olestra may lower circulating concentrations of fat-soluble nutrients such as vitamins and carotenoids. The objective of the Olestra Post-Marketing Surveillance Study was to examine whether customary consumption of olestra-containing savory snacks was associated with changes in serum fat-soluble vitamin and carotenoid concentrations among free-living persons in geographically and ethnically distinct US cities. Adults (n = 2535) and their children aged 12-17 y (n = 272) in Baltimore, Minneapolis, and San Diego attended clinic visits during which data were collected on diet, savory snack consumption, lifestyle, and anthropometric indexes. Blood samples were drawn to assay carotenoids and vitamins A, D, E, and K. Data and blood samples were collected both before and after the nationwide introduction of olestra. General estimating equations were used in multivariate-adjusted models that examined olestra's association with the specified serum nutrients. Compared with no intake, the top 2 tertiles of olestra use in adults were associated with circulating carotenoid concentrations that were modestly but significantly lower (4.3% to 22.4%). There were no significant associations of olestra with any serum nutrients among adolescents. This active postmarketing surveillance study of a food additive suggests that small decreases in serum fat-soluble nutrients are attributable to olestra use. Although health outcomes were not measured here, it is unlikely that these small changes in nutrient measures would adversely affect health.

A randomized trial of the effect of a plant-based dietary pattern on additional breast cancer events and survival:: the Women's Healthy Eating and Living (WHEL) Study

The Women's Healthy Eating and Living (WHEL) Study is a multisite randomized controlled trial of the effectiveness of a high-vegetable, low-fat diet, aimed at markedly raising circulating carotenoid concentrations from food sources, in reducing additional breast cancer events and early death in women with early-stage invasive breast cancer (within 4 years of diagnosis). The study randomly assigned 3088 such women to an intensive diet intervention or to a comparison group between 1995 and 2000 and is expected to follow them through 2006. Two thirds of these women were under 55 years of age at randomization. This research study has a coordinating center and seven clinical sites. Randomization was stratified by age, stage of tumor and clinical site. A comprehensive intervention program that includes intensive telephone counseling, cooking classes and print materials helps shift the dietary pattern of women in the intervention. Through an innovative telephone counseling program, dietary counselors encourage women in the intervention group to meet the following daily behavioral targets: five vegetable servings, 16 ounces of vegetable juice, three fruit servings, 30 g of fiber and 15–20% energy from fat. Adherence assessments occur at baseline, 6, 12, 24 or 36, 48 and 72 months. These assessments can include dietary intake (repeated 24-hour dietary recalls and food frequency questionnaire), circulating carotenoid concentrations, physical measures and questionnaires about health symptoms, quality of life, personal habits and lifestyle patterns. Outcome assessments are completed by telephone interview every 6 months with medical record verification. We will assess evidence of effectiveness by the length of the breast cancer event-free interval, as well as by overall survival separately in all the women in the study as well as specifically in women under and over the age of 55 years.

Identification and quantitation of major carotenoids in selected components of the Mediterranean diet: green leafy vegetables, figs and olive oil.

To characterize the carotenoid content of selected components of the Mediterranean diet commonly eaten by Greek migrants to Melbourne, a population group maintaining a traditional dietary regimen, and who exhibit relatively high circulating carotenoid concentrations and low cardiovascular disease mortality. DESIGN AND SPECIMENS: Opportunistic sampling of wild (sow thistle, amaranth, purslane and dandelion, collected from roadsides and home gardens) and commercially available (chicory, endive) green leafy vegetables and figs in season. Foods were selected on the basis that they are commonly eaten by Greek migrants but not by Anglo-Celtic persons, and had not previously been well-characterized with respect to their carotenoid contents. Extra virgin, cold-pressed olive oil and 'extra light' olive oil were obtained from commercial sources. Specimens were extracted with tetrahydrofuran (or chloroform:methanol for olive oil) and carotenoid contents were quantified using HPLC with UV detection. Two to six specimens of greens and figs were analysed. Dietary intake was assessed by food frequency questionnaire. Wild green vegetables contained high concentrations of lutein (sow thistle>amaranth>purslane>dandelion) and beta-carotene (sow thistle>amaranth>purslane=dandelion). Sow thistle and amaranth contained lutein (15 and 13 mg/100 g, respectively) and beta-carotene (3.3 and 4.0 mg/100 g, respectively) at concentrations greater than that seen in the commercially available species of chicory and endive. Figs contained all major carotenoids appearing in plasma, albeit at low concentrations. Extra virgin cold-pressed olive oil contained substantial quantities of lutein and beta-carotene, but the more-refined 'extra light' olive oil did not. These components of the traditional Mediterranean diet contribute to the higher circulating concentrations of carotenoids in Greek migrants compared to Anglo-Celtic Australians. This study largely funded by the National Health and Medical Research Council of Australia (grant no. 974098). Extra virgin olive oil donated by Picuba Foods, Marrickville, NSW, Australia.

Effect of β-carotene supplementation and lactation on carotenoid metabolism and mitogenic T lymphocyte proliferation

Information is lacking regarding the effects of beta-carotene supplementation, early lactation, or both on circulating carotenoid concentrations and T lymphocyte proliferation. This study investigated the effects of short-term beta-carotene supplementation (30 mg/d for 28 d) during early lactation (days 4-32 postpartum) on circulating carotenoid concentrations and on the T lymphocyte proliferative response to phytohemagglutinin. Subjects aged 19-39 y were paired [lactating (4 d postpartum) and nonlactating (never pregnant, healthy women)] and randomly assigned to receive either beta-carotene or a placebo. During the study, subjects provided eight 24-h food records for analysis with the NUTRITIONIST IV and US Department of Agriculture carotenoid databases. Nonfasting blood samples were collected at baseline and at 28 d. Plasma analysis included quantification of alpha-carotene, beta-carotene, lutein, lycopene, retinol, and alpha-tocopherol, complete differential blood cell counts, and lymphocyte proliferative activity. beta-Carotene supplementation increased beta-carotene (P < 0.001) and alpha-carotene (P < 0.05) concentrations but did not affect lycopene concentrations significantly. Supplemented women showed significant decreases in plasma lutein (P < 0.03), as did lactating subjects (P < 0.02). Neither lactation nor beta-carotene supplementation affected the T lymphocyte proliferative response to phytohemagglutinin. Our results suggest that beta-carotene supplementation as well as some events related to parturition, initiation of lactation, or both alter circulating concentrations of lutein. beta-Carotene supplementation does not enhance T lymphocyte immune competence in healthy women.

Serum carotenoid concentrations and their reproducibility in children in Belize

Suggestions that carotenoid-containing foods are beneficial in maintaining health have led to several studies of circulating carotenoid concentrations of adults. Because few data are available for children, we report serum carotenoid concentrations of 493 children in Belize. Carotenoid concentrations were determined as part of a survey of vitamin A status of children, most between 65 and 89 mo of age. Reproducibility was tested by collecting a second blood sample 2 wk after the first collection from a subset of children (n = 23) who consumed their habitual diet with no treatment during the interim. Predominant serum carotenoids were lutein/zeaxanthin and beta-carotene, which accounted for 26% and 24% of median total carotenoids, respectively. The three provitamin A carotenoids, alpha- and beta-carotene and beta-cryptoxanthin, constituted 51% of median total carotenoid concentrations. Partial correlations of each carotenoid with fasting retinol concentration indicated that beta-carotene had the highest correlation. Concordance correlation coefficients (rc) for fasting carotenoid concentrations determined 2 wk apart were > or = 0.89 for lycopene, beta-cryptoxanthin, and alpha- and beta-carotene. The rc for lutein/zeaxanthin and total carotenoids was lower, 0.59 and 0.68, respectively, because of higher lutein/zeaxanthin concentrations at the second sampling than at the first. The reproducibility of the concentrations suggests both that individuals have characteristic profiles and that serum carotenoid concentrations can be measured randomly over > or = 2 wk without significant bias.