Poplar Propolis Improves Insulin Homeostasis in Non-Diabetic Insulin-Resistant Volunteers with Obesity: A Crossover Randomized Controlled Trial.

Propolis, a natural resinous mixture rich in polyphenols, produced by bees from a variety of plant sources, has shown significant therapeutic effects and may prevent the development of certain chronic diseases like type 2 diabetes mellitus (T2DM). The objective of this study was to evaluate the effect of supplementation with standardized poplar propolis extract powder (PPEP) on insulin homeostasis in non-diabetic insulin-resistant volunteers with obesity. In this randomized, controlled, crossover trial, nine non-diabetic insulin-resistant volunteers with obesity, aged 49 ± 7 years, were subjected to two periods of supplementation (placebo and PPEP) for 3 months. Blood samples and anthropomorphic data were collected at baseline and at the end of each phase of the intervention. PPEP supplementation improved insulin sensitivity by significantly decreasing the percentage of insulin-resistant subjects and the insulin sensitivity Matsuda index (ISI-M). According to this study, supplementation with standardized PPEP for 3 months in non-diabetic insulin-resistant volunteers with obesity led to an improvement in insulin homeostasis by its effect on insulin resistance and secretion. This study suggests that poplar propolis has a preventive effect on the physiopathological mechanisms of T2DM and, therefore, that it can help to prevent the development of the disease.

Botanic Origin of Propolis Extract Powder Drives Contrasted Impact on Diabesity in High-Fat-Fed Mice.

Propolis extracts are considered as nutraceutical products with potentialities towards obesity and comorbidities management. Nevertheless, propolis extracts composition is highly variable and depends on the botanic origin of plants used by the bees to produce propolis. This study aims to evaluate the differential effect of poplar propolis extract powder (PPEP), Baccharis propolis extract powder (BPEP), and/ or Dalbergia propolis extract powder (DPEP) on obesity and glucose homeostasis in high-fat-fed mice. PPEP supplementation reduced high-fat (HF)-mediated body weight gain, adiposity index, and improved glucose homeostasis in male C57Bl/6J mice that were submitted to a high-fat diet for 12 weeks, whereas BPEP, DPEP, or a mix of the three PEPs did not modify those parameters. Adipose tissue (AT) gene expression profiling highlighted an induction of mRNA related to lipid catabolism and an inhibition of mRNA coding for inflammatory markers. Several Nrf2 target genes, coding for antioxidant enzymes, were induced in AT under PPEP effect, but not by other PEP. Interestingly, representative PPEP polyphenols mediated the induction of Nrf2 target genes cell-autonomously in adipocytes, suggesting that this induction may be related to the specific polyphenol content of PPEP. Whereas PPEP supplementation has demonstrated a clear potential to blunt the onset of obesity and associated comorbidities, other PEPs (from Baccharis and Dalbergia) were inefficient to support their role in preventive nutrition.

Poplar Propolis Ethanolic Extract Reduces Body Weight Gain and Glucose Metabolism Disruption in High-Fat Diet-Fed Mice.

SCOPE: Current evidence supports the beneficial effect of polyphenols on the management of obesity and associated comorbidities. This is the case for propolis, a polyphenol-rich substance produced by bees. The aim of the present study is to evaluate the effect of a poplar propolis ethanolic extract (PPEE) on obesity and glucose homeostasis, and to unveil its putative molecular mechanisms of action. METHODS AND RESULTS: Male high-fat (HF) diet-fed mice are administered PPEE for 12 weeks. PPEE supplementation reduces the HF-mediated adiposity index, adipocyte hypertrophy, and body weight gain. It also improves HOMA-IR and fasting glucose levels. Gene expression profiling of adipose tissue (AT) shows an induction of mRNA related to lipid catabolism and mitochondrial biogenesis and inhibition of mRNA coding for inflammatory markers. Interestingly, several Nrf2-target genes are induced in AT following administration of PPEE. The ability of PPEE to induce the expression of Nrf2-target genes is studied in adipocytes. PPEE is found to transactivate the Nrf2 response element and the Nrf2 DNA-binding, suggesting that part of the effect of PPEE can be mediated by Nrf2. CONCLUSION: PPEE supplementation may represent an interesting preventive strategy to tackle the onset of obesity and associated metabolic disorders.

Antifungal activity of Brazilian red propolis extract and isolation of bioactive fractions by thin-layer chromatography-bioautography.

OBJECTIVES: This study set out to highlight the in vitro and in vivo antifungal activity of an Ethanolic Extract of Red Brazilian Propolis (EERBP) and identify bioactive fractions effective against Colletotrichum musae. METHODS: Active fractions were detected by the thin-layer chromatography-bioautography method and characterised by HPLC-MSn. RESULTS: The in vitro results showed that EERBP had strong antifungal properties againstC. musae (81 ± 1% inhibition at 1.6 g GAE L-1). Medicarpin, (3S)-vestitol and (3S)-neovestitol were the main compounds identified in the EERBP extract (45% of all detected peaks). Two isolated fractions displayed inhibition percentages of 35 ± 4 and 42 ± 1%, respectively, on C. musae mycelial growth compared to the EERBP extract. The biological activity of the two fractions displayed an additive effect. CONCLUSION: A further in vivo investigation revealed that EERBP is a potential natural alternative for controlling banana crown rot.

Bee pollen improves muscle protein and energy metabolism in malnourished old rats through interfering with the Mtor signaling pathway and mitochondrial activity.

Although the management of malnutrition is a priority in older people, this population shows a resistance to refeeding. Fresh bee pollen contains nutritional substances of interest for malnourished people. The aim was to evaluate the effect of fresh bee pollen supplementation on refeeding efficiency in old malnourished rats. Male 22-month-old Wistar rats were undernourished by reducing food intake for 12 weeks. The animals were then renourished for three weeks with the same diet supplemented with 0%, 5% or 10% of fresh monofloral bee pollen. Due to changes in both lean mass and fat mass, body weight decreased during malnutrition and increased after refeeding with no between-group differences (p < 0.0001). Rats refed with the fresh bee pollen-enriched diets showed a significant increase in muscle mass compared to restricted rats (p < 0.05). The malnutrition period reduced the muscle protein synthesis rate and mTOR/p70S6kinase/4eBP1 activation, and only the 10%-pollen diet was able to restore these parameters. Mitochondrial activity was depressed with food restriction and was only improved by refeeding with the fresh bee pollen-containing diets. In conclusion, refeeding diets that contain fresh monofloral bee pollen improve muscle mass and metabolism in old, undernourished rats.

LDL-cholesterol-lowering effect of a dietary supplement with plant extracts in subjects with moderate hypercholesterolemia.

PURPOSE: Red yeast rice (RYR), sugar cane-derived policosanols (SCdP) and artichoke leaf extracts (ALEs) are currently incorporated alone or in combination into dietary supplements for their potential low-density-lipoprotein cholesterol (LDL-cholesterol)-lowering effects. Yet, there is no information supporting the efficacy of this association on the reduction in LDL-cholesterol. The main objective of this study was to investigate the effects of a new dietary supplement (DS) with RYR, SCdP and ALEs on LDL-cholesterol. METHODS: In a double-blind, randomized, parallel controlled study, 39 subjects from 21 to 55 years with moderate hypercholesterolemia without drug treatment were assigned to 2 groups and then consumed either a DS containing RYR, SCdP and ALEs or a placebo over a 16-week period. Plasma concentrations of lipids [LDL-cholesterol, total cholesterol (TC), high-density-lipoprotein cholesterol (HDL-cholesterol), triacylglycerols (TG)] and plasma levels of vitamins C and E, total polyphenols and malondialdehyde were determined at baseline and after 4, 8, 12 and 16 weeks. RESULTS: LDL-cholesterol and TC were reduced by, respectively, 21.4 % (95 % CI, -13.3 to -24.9 %, p < 0.001) and 14.1 % (95 % CI, -10.1 to -18.0 %, p < 0.001) at week 16 in the DS group compared with baseline. Similar results were obtained at weeks 4, 8 and 12. TG decreased by 12.2 % after 16 weeks in the DS group (95 % CI: -24.4 to -0.1 %, p < 0.05). For the vitamin E/TC ratio, a difference was observed between groups at week 16 (p < 0.05). Other parameters were not modified. CONCLUSIONS: Daily consumption of this new DS decreased LDL-cholesterol and TC and is therefore an interesting, convenient aid in managing mild to moderate hypercholesterolemia.

Comparable reduction in cholesterol absorption after two different ways of phytosterol administration in humans.

PURPOSE: Consumption of phytosterols is a nutritional strategy to reduce cholesterol absorption, but the efficacy of various phytosterol intake modalities remains uncertain. The main objective was to investigate the effects of phytosterol esters (PE) provided either as a spread (dispersed in fat) during a mixed meal or as a minidrink (micro-dispersed in liquid form) after a meal. METHODS: In a randomized, single-blinded crossover design, 12 healthy intubated volunteers tested three different liquid meal sequences with and without PE. The liquid meal (500 mL, Fortisip) contained an oral dose (80 mg) of deuterium-enriched cholesterol (D7C). The intubation was stopped at 240 min, and the fate of sterols was determined in the different phases of duodenal content samples as function of time. A second solid fat-containing meal without sterols was consumed at 270 min. D7C was quantified in chylomicrons and plasma for 8 h. The conditions tested were as follows: (1) no PE added (control), (2) PE in a spread added into a liquid meal (PE-spread meal) and (3) PE given 30 min after a liquid meal as 100-g yoghurt drink (PE-minidrink meal). RESULTS: Addition of PE decreased the incorporation of cholesterol into the duodenum aqueous phase including micelles. PE added as a spread or as a minidrink significantly and comparably lowered meal cholesterol occurrence in chylomicrons (-40 % for PE-spread and -54 % for PE-minidrink, p < 0.0001) compared with the control meal. CONCLUSIONS: PE either dispersed in fat during a meal or micro-dispersed in a liquid form after a meal resulted in a markedly reduced occurrence of meal-derived cholesterol in the circulation at a comparable extent.

Phytosterol ester processing in the small intestine: impact on cholesterol availability for absorption and chylomicron cholesterol incorporation in healthy humans.

Phytosterols (plant sterols and stanols) can lower intestinal cholesterol absorption, but the complex dynamics of the lipid digestion process in the presence of phytosterol esters (PEs) are not fully understood. We performed a clinical experiment in intubated healthy subjects to study the time course of changes in the distribution of all lipid moieties present in duodenal phases during 4 h of digestion of meals with 3.2 g PE (PE meal) or without (control meal) PE. In vitro experiments under simulated gastrointestinal conditions were also performed. The addition of PE did not alter triglyceride (TG) hydrolysis in the duodenum or subsequent chylomicron TG occurrence in the circulation. In contrast, cholesterol accumulation in the duodenum aqueous phase was markedly reduced in the presence of PE (-32%, P < 0.10). In vitro experiments confirmed that PE reduces cholesterol transfer into the aqueous phase. The addition of PE resulted in a markedly reduced presence of meal-derived hepta-deuterated cholesterol in the circulation, i.e., in chylomicrons (-43%, PE meal vs. control; P < 0.0001) and plasma (-54%, PE meal vs. control; P < 0.0001). The present data show that addition of PE to a meal does not alter TG hydrolysis but displaces cholesterol from the intestinal aqueous phase and lowers chylomicron cholesterol occurrence in humans.

Vitamin E decreases endogenous cholesterol synthesis and apo-AI-mediated cholesterol secretion in Caco-2 cells.

Intestine is the gateway for newly absorbed tocopherols. This organ also plays a crucial role in cholesterol metabolism. Because tocopherols are known to impact cholesterol metabolism in the liver, we hypothesized that tocopherols could also modulate cholesterol metabolism in the intestine. This study aimed to verify this hypothesis and to unveil the mechanisms involved, using Caco-2 cells as a model of the human intestinal cell. Both α- and γ-tocopherol significantly (P<.05) decreased endogenous cholesterol synthesis and apo-AI-mediated cholesterol secretion in Caco-2 cells. Tocopherols down-regulated (P<.05) up to half of the genes involved in the cholesterol synthesis pathway, together with CYP27A1, which is involved in oxysterol production. The activity of this enzyme, as well as the levels of intracellular oxysterols, was significantly diminished by tocopherols. Finally, tocopherols significantly reduced ABCA1 mRNA levels in Caco-2 cells. We conclude that tocopherols impair the endogenous synthesis and apo-AI-mediated secretion of cholesterol in Caco-2 cells. This effect involves a down-regulation of genes involved in the cholesterol synthesis pathway, resulting in down-regulation of CYP27A1 which, in turn, diminishes oxysterol concentrations. The outcome is a decrease of LXR activity, resulting in down-regulation of ABCA1. These data reinforce the effect of α- and γ-tocopherol on cholesterol metabolism via gene expression regulation.

Purified low-density lipoprotein and bovine serum albumin efficiency to internalise lycopene into adipocytes.

Epidemiological studies have suggested that lycopene has protective effects against various diseases including cardiovascular diseases. However, mechanistic studies to understand these effects are difficult due to the insolubility of lycopene in aqueous culture medium. The objective of the present study was to use LDL or BSA as physiological vehicles for lycopene and to compare them with various classical vehicles. Among tested vehicles, only LDL, BSA, THF/BHT, beadlets, and liposomes were able to solubilise lycopene. No cytotoxicity was observed with these vehicles. LDL and BSA allowed good stability of lycopene during incubation (52% and 43% for 2microM lycopene solutions), but remained less efficient than THF/BHT or beadlets (67% and 62%). Incubation of adipocytes (3T3-L1) with the different vehicles for 24 and 48h showed that beadlets best delivered lycopene to cells. Finally, whatever the vehicle used, intracellular localization of lycopene was the same: lipid droplets (32-51%), plasma membrane (32-37%) and nuclear membrane (19-29%). As a conclusion, LDL or BSA display comparable properties to THF/BHT or beadlets. It is the first time that lycopene carried by physiological vehicles is shown to reach different subcellular compartments supporting molecular effects in adipocyte, such as cell signaling or nuclear receptor interacting.

Increased concentrations of circulating vitamin E in carriers of the apolipoprotein A5 gene - 1131T>C variant and associations with plasma lipids and lipid peroxidation.

The aim of this study was to investigate the effects of the apolipoprotein A5 (APOA5) 1131T>C gene variant on vitamin E status and lipid profile. The gene variant was determined in 297 healthy nonsmoking men aged 20-75 years and recruited in the VITAGE Project. Effects of the genotype on vitamin E in plasma, LDL, and buccal mucosa cells (BMC) as well as on cholesterol and triglyceride (TG) concentrations in plasma and apolipoprotein A-I (apoA-I), apoB, apoE, apoC-III, and plasma fatty acids were determined. Plasma malondialdehyde concentrations as a marker of in vivo lipid peroxidation were determined. C allele carriers showed significantly higher TG, VLDL, and LDL in plasma, higher cholesterol in VLDL and intermediate density lipoprotein, and higher plasma fatty acids. Plasma alpha-tocopherol (but not gamma-tocopherol, LDL alpha- and gamma-tocopherol, or BMC total vitamin E) was increased significantly in C allele carriers compared with homozygote T allele carriers (P = 0.02), but not after adjustment for cholesterol or TG. Plasma malondialdehyde concentrations did not differ between genotypes. In conclusion, higher plasma lipids in the TC+CC genotype are efficiently protected against lipid peroxidation by higher alpha-tocopherol concentrations. Lipid-standardized vitamin E should be used to reliably assess vitamin E status in genetic association studies.

Lycopene but not lutein nor zeaxanthin decreases in serum and lipoproteins in age-related macular degeneration patients.

BACKGROUND: Epidemiological studies have established that a low serum concentration of carotenoids was associated with risk of Age-Related Macular Degeneration (ARMD). The aim of this study was to determine carotenoid levels in serum and in different lipoprotein fractions in patients diagnosed for ARMD and in matched control group. METHOD: Thirty-four ARMD patients and 21 control subjects from Brest area (France) have been included to this study. Lipoproteins have been separated from serum by gradient density ultracentrifugation. We measured concentration of carotenoids and tocopherols in serum and in different lipoprotein fractions by HPLC. RESULTS: No difference was observed between ARMD patients and control subjects in total serum carotenoids. Individual carotenoid levels showed that only lycopene was decreased significantly in serum, LDL and HDL fractions in patients (P<0.05). Concentrations in serum and lipoparticle fractions of lutein and zeaxanthin, the major pigments present in macula were not modified between both groups. CONCLUSIONS: Lycopene, as liposoluble antioxidant nutrient, is the only carotenoid altered in ARMD patients. It cannot be excluded that this effect is related to different dietary habits, but we hypothesise that lower lycopene status could result also from specific antioxidant protection of lutein and zeaxanthin by lycopene.

In vivo and in vitro evidences that carotenoids could modulate the neutrophil respiratory burst during dietary manipulation.

BACKGROUND: The primary role of polymorphonuclear neutrophils (PMNs) is to destroy pathogenic microorganisms after phagocytosis by producing reactive oxygen species (ROS) and toxic molecules. However, PMNs produce sufficient amounts of ROS during an oxidative burst to be autotoxic and detrimental to their own functions and to possibly cause DNA damage, protein and lipid oxidation and cell membrane destructuration. OBJECTIVE: The aim of this study was to investigate in vivo the role of the antioxidant capacities of carotenoids in modulating ROS content in PMNs during oxidative burst. Moreover to investigate the direct or indirect effect of carotenoids, the modification of PMN ROS content was explored after in vitro supplementation with beta-carotene or lycopene, chosen taking account of their vitamin A and no vitamin A precursor effect, respectively. DESIGN: In vivo study: Venous blood was collected from 10 healthy male volunteers and ROS production from phorbol myristate acetate (PMA)-stimulated PMNs was determined, by flow cytometry using the fluorescent dye dihydrorhodamine 123, at baseline, after 3 weeks of carotenoid depletion (carotenoid intake limited to 25% of usual intake) and after 5 weeks of carotenoid repletion (30 mg beta-carotene, 15 mg lycopene and 9 mg lutein per day). In vitro study: ROS content in PMA-stimulated PMNs isolated from carotenoid depleted subjects and controls was quantified after an in vitro enrichment with beta-carotene (1 micromol/L) or lycopene (0.3 micromol/L). RESULTS: In vivo carotenoid depletion increased PMN H2O2 content after PMA activation by 38% (p < 0.05 vs baseline),while supplementation for 5 weeks restored basal H2O2 generation (p < 0.05 vs depletion). Although H2O2 measurement in PMNs from non-depleted subjects was not affected by an in vitro supply with beta-carotene or lycopene, a significant decrease in H2O2 content by 78.9 % and 81.2%, respectively, was observed in PMNs from carotenoid depleted subjects (p < 0.01 vs depleted control subjects). CONCLUSIONS: The carotenoid ROS quenching capacities control both in vivo and in vitro the PMNs ROS generation and probably protect these cells against DNA, membrane lipid and protein damages during oxidative burst. Moreover, these effects appear independent from the metabolic conversion of carotenoids to vitamin A.

Health effect of vegetable-based diet: lettuce consumption improves cholesterol metabolism and antioxidant status in the rat.

BACKGROUND & AIMS: It is often assumed that fruits and vegetables contribute to protect against degenerative pathologies such as cardiovascular diseases. Besides epidemiological observations, scientific evidences for their mechanism of action are scarce. In the present study, we investigated the mean term and post-prandial effects of lettuce ingestion on lipid metabolism and antioxidant protection in the rat. RESULTS: Feeding rats a 20% lettuce diet for 3 weeks resulted in a decrease cholesterol LDL/HDL ratio and a marked decrease of liver cholesterol levels (-41%). Concurrently, fecal total steroid excretion increased (+44%) and apparent absorption of dietary cholesterol was significantly depressed (-37%) by the lettuce diet. Lettuce diet also displayed an improvement of vitamin E/TG ratio in plasma and limited lipid peroxidation in heart as evidenced by TBARS. In post-prandial experiment, lettuce intake significantly increased both ascorbic acid and alpha-tocopherol plasma levels which contribute to improve plasma antioxidant capacity within 2 h of consumption. Other lipid-soluble antioxidants (lutein and vitamin E) may also improve the plasma antioxidant capacity. CONCLUSION: Lettuce consumption increases the total cholesterol end-products excretion and improves antioxidant status due to the richness in antioxidants (vitamins C, E and carotenoids). In our model, lettuce clearly shows a beneficial effect on lipid metabolism and on tissue oxidation. Therefore regular consumption of lettuce should contribute to improve protection against cardiovascular diseases.

Does aging affect the response of vitamin E status to vitamin E depletion and supplementation?

A vitamin E depletion/supplementation study was conducted in 100 healthy 20-75-year-old volunteers. The responses of vitamin E status to 3-week dietary vitamin E restriction to approximately 25% of recommended intake and 2-month unrestricted dietary intake plus 800 IU/d of RRR-alpha-tocopherol were studied as a function of age. Plasma alpha-tocopherol concentrations were closely related to cholesterol concentrations, which increased with age (P < 0.001). Upon dietary restriction, plasma alpha-tocopherol concentrations decreased significantly (P < 0.001) but independently of age. Plasma alpha-tocopherol responses to supplementation increased significantly with age, but this effect disappeared after standardization for cholesterol. gamma-Tocopherol concentrations decreased to less than 30% of baseline.

Comparison of the postprandial chylomicron carotenoid responses in young and older subjects.

BACKGROUND: The plant carotenoids may contribute to the beneficial health effect of fruits- and vegetables-rich diet. Epidemiological studies consistently associated high plasma carotenoids status with reduced age-related diseases. However, the data concerning the bioavailability of carotenoids in the elderly are scarce. OBJECTIVE: To test whether there is an age effect on carotenoid bioavailability. DESIGN: Eight young (20-35 y) and eight older (60-75 y) healthy adults ingested three different meals containing 40 g triacylglycerols (TG) and vegetable sources of carotenoids. These sources were either 188 g carrot purée which provided 30 mg betacarotene as the main carotenoid, or 61 g tomato purée providing 30mg lycopene, or 260 g cooked chopped spinach providing 30 mg lutein. TG and carotenoids were assayed in chylomicrons (CM) collected for 9 h postprandially. RESULTS: There was no major effect of age on the postprandial CM/TG response (0-9 h area under the curve (AUC)). There was no major effect of age on the postprandial CM all- trans beta-carotene, cis betacarotene, alpha-carotene, and lutein responses. Adjustment of these responses by the CM TG responses did not reveal any age effect. While there was no significant effect of age on the CM lycopene response, the CM TG-adjusted lycopene response was significantly lower (-40 %) in the older than in the younger subjects (P < 0.04). The cis-trans ratios of CM betacarotene were not significantly different between the old and the young subjects. There was no significant effect of age on the ratio of CM retinyl-palmitate to the sum of alpha-carotene and beta-carotene measured after the carrot meal. CONCLUSIONS: The bioavailability of lycopene is apparently impaired in the old,while there is no major difference in the bioavailability of beta-carotene, alpha-carotene and probably lutein. There is also no major effect of age on the cis-trans isomerization of beta-carotene during absorption, and in the intestinal conversion of provitamin A carotenoids into vitamin A.

Effect of carrot intake on cholesterol metabolism and on antioxidant status in cholesterol-fed rat.

BACKGROUND: Vegetables are major dietary sources of fibers and antioxidants such as carotenoids, polyphenols and vitamin C which contribute to explain their protective effects against cardiovascular diseases. AIM OF THE STUDY: We investigated in the rat the effects of a 3-week supplementation of the diet with carrot (15% dry matter) on lipid metabolism and antioxidant status. RESULTS: A significant decrease of cholesterol level in liver (-44%; P= 0.0007) was observed together with a reduction of the level of liver triglycerides (-40%; P= 0.0005). Fecal total steroids excretion increased by 30% upon feeding the carrot diet as compared to the control. The secretion of bile acids was maintained, whereas the cholesterol apparent absorption was reduced in rats fed carrot diet. Carrot consumption also improved the antioxidant status. It significantly decreased the urinary excretion of thiobarbituric acid reactive substances (TBARS), reduced the TBARS levels in heart, increased the vitamin E plasmatic level and tended to increase the ferric reducing ability of plasma (FRAP) as compared to the controls. The carrot diet provided carotenoid antioxidants: 5.1 mg beta-carotene, 1.6 mg alpha-carotene and 0.25mg lutein per 100 g diet. No carotenoids were found in plasma whereas the three carotenoids were detected in the plasma of the rats fed the carrot diet at 125, 41, 43 nmol/L respective concentrations. beta-Carotene was also detected in liver and heart. CONCLUSION: Carrot consumption modifies cholesterol absorption and bile acids excretion and increases antioxidant status and these effects could be interesting for cardiovascular protection.

Short-term supplementation with lutein affects biomarkers of lutein status similarly in young and elderly subjects.

There is evidence that lutein may protect against age-related macular degeneration, cataract, cancers and cardiovascular diseases, but no data have been published on the effect of age on lutein status. The purpose of this work was to determine whether there are major differences in the status of this carotenoid between young and elderly subjects. Initial lutein status and the effect of a 5-week lutein supplementation (9 mg/d) on the most common markers of lutein status were compared in 12 young (26.9+/-0.8yr) and 17 older subjects (67.3+/-1.1yr). Lutein was measured by HPLC in fasting serum, adipose tissue and buccal mucosa cells (BMC) before and after supplementation. Macular pigment optical density (MPOD), which partly depends on retina lutein concentration, was measured by reflectometry before and after supplementation. Initial lutein status was not significantly different between the two groups, irrespective of the lutein status marker. Plasma and BMC lutein concentrations significantly increased in both groups after lutein supplementation, but not MPOD or adipose tissue lutein. Plasma and BMC responses to lutein supplementation (percent variation from initial values) were not significantly different between the two groups. These results suggest that there is no major effect of age on lutein status in healthy subjects.

Feedback regulation of beta,beta-carotene 15,15'-monooxygenase by retinoic acid in rats and chickens.

beta,beta-Carotene 15,15'-monooxygenase (formerly termed beta,beta-carotene 15,15'-dioxygenase, EC 1.13.11.21) catalyzes the conversion of provitamin A carotenoids to retinal in vertebrate tissues. In the present study, we investigated whether preformed vitamin A or beta-carotene and its direct metabolites can regulate the enzyme activity in vivo. We found dose-dependent decreases in intestinal beta,beta-carotene monooxygenase activity after oral administration to rats of retinyl acetate (up to -79%), beta-carotene (up to -79%), apo-8'-carotenal (up to -56%), all-trans retinoic acid (up to -88%), and 9-cis retinoic acid (up to -67%). Liver beta,beta-carotene 15,15'-monooxygenase (betaCMOOX) activity was not affected. Apo-12'carotenal and the retinoic acid receptor (RAR) alpha antagonist Ro 41-5253 significantly increased the intestinal enzyme activity by 55 and 94%, respectively. When beta-carotene was administered to rats pretreated with the two cytochrome P(450) (CYP) inducers, pentobarbital and naphthoflavone, the intestinal betaCMOOX activity increased by 39%. In a transcriptional study in chickens, treatment with retinoic acid resulted in low expression of the intestinal betaCMOOX. Our data suggest that retinoids and carotenoids might regulate betaCMOOX expression by a transcriptional feedback mechanism via interaction with members of the RAR family.

Vegetable-borne lutein, lycopene, and beta-carotene compete for incorporation into chylomicrons, with no adverse effect on the medium-term (3-wk) plasma status of carotenoids in humans.

BACKGROUND: The results of epidemiologic studies have consistently shown associations between dietary intake or plasma carotenoid status and incidence of cancers and cardiovascular and eye diseases. OBJECTIVE: The aim was to assess whether vegetable-borne carotenoids (lycopene, lutein, and beta-carotene) compete for intestinal absorption and whether this affects the plasma status of carotenoids in the medium term (ie, after 3 wk). DESIGN: During 3-wk periods separated by 3-wk washout periods, 20 women were supplemented with either 96 g tomato purée/d (14.98 mg lycopene + 1.50 mg beta-carotene), 92 g cooked chopped spinach/d (11.93 mg lutein + 7.96 mg beta-carotene), 96 g tomato purée/d + 92 g chopped spinach/d, 96 g tomato purée/d + 2 lutein pills (12 mg lutein), or 92 g chopped spinach/d + 1 lycopene pill (15 mg lycopene). Plasma carotenoids were measured before and after each supplementation period. The subjects also participated in postprandial experiments in which they ingested meals containing double amounts of the supplements described above. Carotenoids were measured in chylomicrons to assess the interaction of carotenoids on absorption. RESULTS: Adding a second carotenoid to a meal that provided a first carotenoid diminished the chylomicron response to the first carotenoid. However, cosupplementation with a second carotenoid of a diet supplemented with a first carotenoid did not diminish the medium-term plasma response to the first carotenoid. CONCLUSION: Consumption of carotenoids from different vegetable sources does not diminish plasma carotenoid concentrations in the medium term, despite the finding in postprandial testing of competitive inhibitory interactions among different carotenoids.