Plasma Lycopene Concentrations Research Articles

Plasma Lycopene and Lutein Concentrations Are Associated With Reduced Adiposity and Improved Metabolic Health in Healthy Infants

Plasma Lycopene and Lutein Concentrations Are Associated With Reduced Adiposity and Improved Metabolic Health in Healthy Infants

Association of dietary and nutritional factors with cognitive decline, dementia, and depressive symptomatology in older individuals according to a neurogenesis-centred biological susceptibility to brain ageing.

Hippocampal neurogenesis (HN) occurs throughout the life course and is important for memory and mood. Declining with age, HN plays a pivotal role in cognitive decline (CD), dementia, and late-life depression, such that altered HN could represent a neurobiological susceptibility to these conditions. Pertinently, dietary patterns (e.g., Mediterranean diet) and/or individual nutrients (e.g., vitamin D, omega 3) can modify HN, but also modify risk for CD, dementia, and depression. Therefore, the interaction between diet/nutrition and HN may alter risk trajectories for these ageing-related brain conditions. Using a subsample (n= 371) of the Three-City cohort-where older adults provided information on diet and blood biobanking at baseline and were assessed for CD, dementia, and depressive symptomatology across 12years-we tested for interactions between food consumption, nutrient intake, and nutritional biomarker concentrations and neurogenesis-centred susceptibility status (defined by baseline readouts of hippocampal progenitor cell integrity, cell death, and differentiation) on CD, Alzheimer's disease (AD), vascular and other dementias (VoD), and depressive symptomatology, using multivariable-adjusted logistic regression models. Increased plasma lycopene concentrations (OR [95% CI] = 1.07 [1.01, 1.14]), higher red meat (OR [95% CI] = 1.10 [1.03, 1.19]), and lower poultry consumption (OR [95% CI] = 0.93 [0.87, 0.99]) were associated with an increased risk for AD in individuals with a neurogenesis-centred susceptibility. Increased vitamin D consumption (OR [95% CI] = 1.05 [1.01, 1.11]) and plasma γ-tocopherol concentrations (OR [95% CI] = 1.08 [1.01, 1.18]) were associated with increased risk for VoD and depressive symptomatology, respectively, but only in susceptible individuals. This research highlights an important role for diet/nutrition in modifying dementia and depression risk in individuals with a neurogenesis-centred susceptibility.

Postprandial Micronutrient Variability and Bioavailability: An Interventional Meal Study in Young vs. Old Participants.

This study explores age- and time-dependent variations in postprandial micronutrient absorption after a micronutrient-rich intervention meal within the Biomiel (bioavailability of micronutrients in elderly) study. Comprising 43 healthy participants, the study compares young (n = 21; mean age 26.90 years) and old (n = 22; mean age 66.77 years) men and women, analyzing baseline concentrations and six-hour postprandial dynamics of iron (Fe), copper (Cu), zinc (Zn), selenium (Se), iodine (I), free zinc (fZn), vitamin C, retinol, lycopene, β-carotene, α-tocopherol, and γ-tocopherol, along with 25(OH) vitamin D (quantified only at baseline). Methodologically, quantifications in serum or plasma were performed at baseline and also at 90, 180, 270, and 360 min postprandially. Results reveal higher baseline serum Zn and plasma lycopene concentrations in the young group, whereas Cu, Se, Cu/Zn ratio, 25(OH) vitamin D, α-tocopherol, and γ-tocopherol were higher in old participants. Postprandial variability of Zn, vitamin C, and lycopene showed a strong time-dependency. Age-related differences in postprandial metabolism were observed for Se, Cu, and I. Nevertheless, most of the variance was explained by individuality. Despite some limitations, this study provides insights into postprandial micronutrient metabolism (in serum/plasma), emphasizing the need for further research for a comprehensive understanding of this complex field. Our discoveries offer valuable insights for designing targeted interventions to address and mitigate micronutrient deficiencies in older adults, fostering optimal health and well-being across the lifespan.

Dietary Tomato Varieties Similarly Inhibit Prostate Carcinogenesis in the TRAMP Model in Association with Distinct Transcriptomic and Metabolomic Profiles

Abstract Objectives Lycopene intake is associated with reduced risk of prostate cancer, especially lethal disease. Tangerine tomatoes contain highly bioavailable lycopene isomers, compared to red tomatoes, but impact of isomers on cancer preventive bioactivity are unknown. Our goals are: (1) to determine if feeding tomato containing diets with differing lycopene isomers inhibit transgenic adenocarcinoma of the mouse prostate (TRAMP) carcinogenesis, and (2) to determine key early metabolic and transcriptional pathways through which tomatoes act to prevent carcinogenesis. Methods We examine prostate carcinogenesis in the TRAMP model, comparing two tomatoes with distinct lycopene isomer profiles: all-trans-lycopene-rich red tomatoes and cis-lycopene-isomer-rich tangerine tomatoes. Weanling TRAMP and wild type (WT) mice were fed AIN-93 G control, 10% tangerine tomato + AIN-93 G (w/w), or 10% red tomato + AIN-93 G (w/w) diet until 10 or 18 wks. At 10 wks., prostate RNA-seq and plasma metabolomics were performed on TRAMP and WT samples. At 18 wks., plasma carotenoid analysis and histopathology was performed on TRAMP mice. Results At 18 wks., plasma lycopene concentrations were 2.84-fold greater in tangerine tomato-fed mice than red tomato-fed mice (p < 0.0001), yet both red and tangerine tomato diets similarly prevent carcinoma incidence compared to the control diet by 43% and 36% respectively (p < 0.001, both vs. control). Our investigation of early carcinogenesis (10 wks.) shows that both tomato diets similarly impact the plasma metabolome, and we define prostate transcriptomic profiles mediated by TRAMP genotype, such as inflammation- and immune-regulated pathways, that are inhibited by dietary tomato. We identify an inflammatory gene panel (Olr1, Il1a, Cscl9, and Ccl22) which is inhibited by tomato diets. In a human prostate cancer database, higher expression of this gene panel is associated with a more aggressive phenotype. Conclusions Together, our results implicate red and tangerine tomatoes as potentially beneficial for the inhibition of early prostate carcinogenesis through the modulation of transcriptional programs centered on inflammation and the immune response. Our findings support efforts to test novel tomato products for the inhibition of human prostate carcinogenesis. Funding Sources AICR, NIH P30, USDA NNF.

Lycopene Reduces Skin Toxicity in Patients Treated with Panitumumab-Containing Therapy for Metastatic Colorectal Cancer – A Randomized Double-Blind Placebo-Controlled Pilot Study

Background: EGFR inhibition leads to the production of reactive oxygen metabolites, causing skin inflammatory reactions. Lycopene has an extreme antioxidant activity and, due to its hydrophobic structure, accumulates specifically in the skin. Methods: To assess lycopene effectiveness in reducing skin toxicity induced by panitumumab, 28 patients received lactolycopene or placebo in a phase-II PASTO study. Patients were evaluated at the beginning of each cycle and data were analyzed as the difference in mean grade of skin toxicity, frequency and duration of > G2 skin toxicity and frequency of tetracyclines administration. Lycopene, β-carotene and malondialdehyde plasma concentrations were analyzed to measure antioxidant consumption and oxidative stress. Findings: In the placebo group, ten out of 15 patients (66·67%), developed a > G2 skin toxicity, during 36 out of 92 cumulative cycles (39·1%), versus 3 out of 13 (23·08%), during 8 out of 64 cumulative cycles (12·5%) in the lactolycopene group. The time to the appearance of > G2 skin toxicity was different in the two groups (p= 0.0007 logrank test). Mean value of skin toxicity during treatment was 2·4 and 1·4 for placebo and lactolycopene group, respectively. Tetracyclines were administered for > G2 skin toxicity according to the protocol. Mean plasma concentration of lycopene and β-carotene decreased during treatment compared to day 0 (-141·94% and -157·22% respectively) in the placebo group, with a +109·36% mean malondialdehyde concentration increase. In contrast, in the lactolycopene group, mean plasma lycopene concentration increased during treatment (+94·18%), with a mean malondialdehyde concentration decrease (-68·83%) and a mean β-carotene concentration decrease (-105·5%) smaller than in the placebo group . Interpretation: Despite the limited number of patients, results clearly show lycopene effectiveness in reducing skin toxicity in patients treated with panitumumab. In our series lactolycopene administration was able to protect tissues from oxidative stress and to replenish antioxidants consumption. Trial Registration: registered in ClinicalTrials.gov (PaSTo – Clinicaltrials.gov: NCT 03167268) Funding Statement: AMOlavitaONLUS, Indena Spa. Declaration of Interests: MM1 is the vice-president and MP the treasurer of AMOlavitaONLUS. AMOlavitaONLUS is the sole owner and it holds all the ownership rights on the international patent application entitled “Use of carotenoid derivatives to reduce the toxicity and increase the efficacy of antiEGFR antitumor treatments” (N°PCT/IB2018/050229). MM1 and MP are exclusively inventors of the patent and they have no ownership right on the patent. Indena Spa, who supplied free of charge lactolycopene for the Pasto Clinical Trial, is not the owner of the patent for lactolycopene production. All other authors declare no competing interest. Ethics Approval Statement: The protocol was approved by the ethics committees of all participating institutions. Written informed consent was obtained from all patients.

Regular Intake of Tomato Juice by Egyptian Male Preadolescents was Associated with Significant Increase in the Plasma Lycopene Concentration and Modest Changes in the Blood Glutathione and Plasma Immunoglobulin E Levels

Regular Intake of Tomato Juice by Egyptian Male Preadolescents was Associated with Significant Increase in the Plasma Lycopene Concentration and Modest Changes in the Blood Glutathione and Plasma Immunoglobulin E Levels

Single Nucleotide Polymorphisms in β-Carotene Oxygenase 1 are Associated with Plasma Lycopene Responses to a Tomato-Soy Juice Intervention in Men with Prostate Cancer

Human plasma and tissue lycopene concentrations are heterogeneous even when consuming controlled amounts of tomato or lycopene. Our objective is to determine whether single nucleotide polymorphisms (SNPs) in or near known or putative carotenoid metabolism genes [β-carotene 15,15' monooxygenase 1 (BCO1), scavenger receptor class B type 1 (SCARB1), ATP-binding cassette transporter subfamily A member 1 (ABCA1), microsomal triglyceride transfer protein (MTTP), apolipoprotein B-48, elongation of very long chain fatty acids protein 2 (ELOVL2), and ATP-binding cassette subfamily B member 1 (ABCB1), and an intergenic superoxide dismutase 2, mitochondrial-associated SNP] are predictive of plasma lycopene responses to steady state tomato juice consumption. Secondary linear regression analyses of data from a dose-escalation study of prostate cancer patients [n=47; mean ± SEM age: 60±1 y; BMI (in kg/m2): 32±1] consuming 0, 1, or 2 cans of tomato-soy juice/d (163 mL/can; 20.6 mg lycopene 1.2 mg β-carotene/can) for 24±0.7 d before prostatectomy were conducted to explore 11 SNP genotype effects on the change in plasma lycopene and plasma and prostate tissue concentrations of lycopene, β-carotene, phytoene, and phytofluene. Two BCO1 SNP genotypes were significant predictors of the change in plasma lycopene, with SNP effects differing in magnitude and direction, depending on the level of juice intake (rs12934922×diet group P=0.02; rs6564851×diet group P=0.046). Further analyses suggested that plasma β-carotene changes were predicted by BCO1 rs12934922 (P<0.01), prostate lycopene by trending interaction and main effects of BCO1 SNPs (rs12934922×diet group P=0.09; rs12934922 P=0.02; rs6564851 P=0.053), and prostate β-carotene by BCO1 SNP interaction and main effects (rs12934922×diet group P=0.01; rs12934922 P<0.01; rs7501331 P=0.02). In conclusion, SNPs in BCO1 and other genes may modulate human plasma and prostate tissue responses to dietary lycopene intake and warrant validation in larger, human controlled feeding intervention and cohort studies. Genetic variants related to carotenoid metabolism may partially explain heterogeneous human blood and tissue responses and may be critical covariates for population studies and clinical trials. This trial was registered at clinicaltrials.gov as NCT01009736.

Dyslipidemia and Other Risk Factors Among Egyptian Patients with Type-2 Diabetes Mellitus and the Impact of Dietary Intervention with Thermally Treated Tomato Juice

The increase in the plasma level of lycopene following the drinking of tomato juice is a valid biomarker reflecting lowering in the oxidative stress and improving glycemic control among patients with type 2 Diabetes Mellitus (T2 DM). The aim of the study is to characterize the overall health of a small sample of typical patients with type 2 DM and to test the effectiveness of dietary intervention with tomato juice against the oxidative stress of diabetes. Design: The study consisted of 29 diabetic men and women with mean age of 61 years and median duration of diabetes of 12 years. Blood samples were collected for biochemical analysis of 14 blood biomarkers. The participants were then divided into two groups, one arm served as control and the second received daily 240 ml of thermally treated tomato juice providing 22 mg of lycopene. At days zero and at the end of the 3 week dietary intervention, blood samples were collected for HPLC measurement of plasma carotenoids and retinol concentrations. Results: The fasting plasma glucose (FPG) concentrations of 46.7 % of the diabetic men and 40% of the diabetic women were ≤ 7.0 implying good management. The use of HbA1c as criteria of good control of glycemic index, 78.6 % of the diabetic men and 88.9% of the diabetic women were presented with poorly glycemic control. Prevalences of obesity (BMI > 30 kg/ m2) accounted for 44 % and 87.5% among the diabetic men and women, respectively. Prevalences of total cholesterol high density lipoprotein ratio above the acceptable upper limit were 33.3 and 25 % among diabetic men and women, respectively. Prevalences of hyper triglyceridemia were 69.2 and 60% among the diabetic men and women, respectively. After the 3 week dietary intervention with thermally treated tomato juice, plasma lycopene concentration increased on average by 161% fold excess over the respective baseline level, reflecting lowering in the oxidative stress and improving glycemic control of T2 DM pathogenesis. The preliminary data recommends the regular intakes of tomato lycopene rich diets as a safe adjunct to glucose-lowering drugs among diabetics with poor glycaemic control and with increased levels of oxidative stress biomarkers.

Possible benefits of tomato juice consumption: a pilot study on irradiated human lymphocytes from healthy donors

BackgroundReactive oxygen species (ROS) mediate much of the DNA damage caused by ionizing radiation. Among carotenoids, lycopene and β-carotene, present in tomato juice, are known to be strong radical scavengers. The aim of the study was to investigate the effect of tomato juice intake on the levels of DNA damage and oxidative stress in human whole blood induced by in vitro exposure to X-rays.MethodsTen healthy adults were asked to drink 190 g of tomato juice, containing 17 mg lycopene and 0.25 mg β-carotene, per day for 3 weeks and then refrain from drinking it for 3 weeks. Peripheral whole blood samples were collected before and after the intake period of tomato juice and after the washout period. The blood samples were exposed in vitro to X-ray doses of 0, 0.1, 0.5, and 2 Gy. Cytogenetic damage was measured using the cytokinesis-block micronucleus (CBMN) assay and the dicentrics (DIC) assay. The level of oxidative stress was determined using serum 8-oxo-7, 8-dihydro-2-deoxyguanosine (8-oxo-dG) and plasma reactive oxygen metabolite-derived compounds (d-ROMs). The concentration of carotenoids in plasma was measured at the three time points.ResultsThe levels of 8-oxo-dG tended to decrease during the intake period and increase during the washout period. A non-significant inverse correlation was noted between the plasma concentration of lycopene plus β-carotene and the level of 8-oxo-dG (P = 0.064). The radiation-induced MN and DIC frequencies increased in a dose-dependent manner, and when compared at the same dose, the MN and DIC frequencies decreased during the intake period compared with those at baseline and then increased during the washout period. The results suggest that continuous tomato juice consumption non-significantly decreases extracellular 8-oxo-dG, d-ROMs, and MN. Tomato juice intake had minimal or no effect on radiation-induced 8-oxo-dG and d-ROMs. For most radiation doses, continuously tomato juice intake lowered the levels of MN and DIC.ConclusionTomato juice consumption may suppress human lymphocyte DNA damage caused by radiation, but further examination is required.Trial registration2014-001 and 2014-R06.

Effect of dry tomato peel supplementation on glucose tolerance, insulin resistance, and hepatic markers in mice fed high-saturated-fat/high-cholesterol diets

Many studies have investigated the effect of crude tomato peel in vivo, but no studies have determined the dose-effect of dry tomato peel (DTP) on glucose intolerance, insulin resistance, and atherogenic dyslipidemia induced by a high-saturated-fat (HSF) diet in vivo. The aim of this study was to investigate the effects of different doses of DTP on the levels of oxidative stress in mice fed an HSF and cholesterol-rich diet for 12 weeks. The main outcomes are glucose and insulin tolerance, plasma lipids, and hepatic steatosis and inflammation. BALB/c male mice (n=40) (8 weeks old, weighing 22.2±1.0 g) were divided into four treatment groups (10 mice/group): (a) high-fat control diet (HF Ctrl), which contains sunflower oil as a sole source of fat; (b) HSF/high-cholesterol (HC) diet; (c) HSF/HC diet supplemented with 9% DTP and (d) HSF/HC diet supplemented with 17% DTP. The HSF/HC diet significantly increased body weight gain, adipose tissue weight, fasting plasma glucose, fasting plasma insulin and lipid peroxidation and caused the development of liver steatosis and inflammation. Supplementation with DTP increased plasma lycopene concentration and reduced the development of indicators of metabolic syndrome, with no consistent effect of the DTP dose. Hepatic steatosis and inflammation were not reversed with DTP supplementation. Among mice fed the HSF/HC diet, DTP supplementation appears to have a beneficial effect on insulin resistance, which confirms the antiatherogenic effect of DTP.

Plasma Lycopene Is Associated with Pizza and Pasta Consumption in Middle-Aged and Older African American and White Adults in the Southeastern USA in a Cross-Sectional Study.

BackgroundThe role of dietary lycopene in chronic disease prevention is not well known.MethodsThis study examined intake of lycopene and other antioxidants from lycopene-rich foods (e.g., pizza and pasta) simultaneously with plasma levels of lycopene and other antioxidants in a representative cross-sectional sample (187 Blacks, 182 Whites, 40–79 years old) from the Southern Community Cohort Study (SCCS). The SCCS is an ongoing study conducted in populations at high risk for chronic diseases living in Southeastern United States. Dietary intake was assessed using a validated food frequency questionnaire (FFQ), and plasma levels of lycopene and other antioxidants were measured at baseline (2002–2005). The participants were classified into tertiles according to consumption of pizza and pasta food groups.ResultsLycopene dietary intake and plasma lycopene concentrations were significantly higher in the highest (tertile 3) compared to tertiles 1 and 2 (both P < 0.01). Total energy intake ranged from 1964.3 ± 117.1 kcal/day (tertile 1) to 3277.7 ± 115.8 kcal/day (tertile 3) (P<0.0001). After adjusting for age and energy intake, total dietary fat, saturated fatty acids, trans-fatty acids, and sodium intakes were significantly higher in tertile 3 than tertiles 2 and 1 (all P <0.01). Vitamin C intake was significantly lower in tertile 3 than tertiles 1 and 2 (P = 0.003). Except for γ-tocopherol being higher in tertile 3 than tertiles 1 and 2 (P = 0.015), the plasma concentrations of antioxidants were lower in tertile 3 than tertiles 1 and 2 (β-carotene, α-carotene, lutein and zeaxanthin, all P<0.05).ConclusionsIn the SCCS population, pizza and pasta were the main sources of dietary lycopene and their intake was associated with plasma lycopene concentration. Diets with frequent pizza and pasta consumption were high in energy, saturated fatty acids, trans-fatty acids, sodium and low in other antioxidants. Future studies of lycopene as a protective dietary factor against chronic disease should consider the overall nutritional quality of lycopene-containing foods.

Consumption of canned citrus fruit meals increases human plasma β-cryptoxanthin concentration, whereas lycopene and β-carotene concentrations did not change in healthy adults

Several studies suggest that β-cryptoxanthin has a greater plasma response from its common food sources than other carotenoids such as β-carotene and lycopene. The hypothesis of this study is that changes in plasma β-cryptoxanthin concentrations will be greater than changes in plasma β-carotene or lycopene concentrations even if these carotenoids are fed in a similar food matrix, such as citrus fruit. We tested this hypothesis by measuring changes in plasma concentrations of β-cryptoxanthin, lycopene, and β-carotene after feeding measured amounts of canned tangerines and pink grapefruit to healthy nonsmoking adult humans. Volunteers served as their own controls and received both citrus fruit treatments randomly. In the first study, 8 subjects ate single meals of 234-304g of tangerines or 60-540g of pink grapefruit. The second study compared changes in plasma carotenoid concentration caused by feeding 234g of tangerines or 540g of pink grapefruit to 11 subjects. Blood was collected 5 times within 24hours after each citrus meal. Carotenoid concentrations were analyzed by reversed-phase high-performance liquid chromatography. Plasma β-cryptoxanthin concentrations increased within 5hours and then stabilized, remaining high throughout the 24hours measured. Plasma concentrations of lycopene and β-carotene did not change. These results show that β-cryptoxanthin concentrations increased after a citrus fruit meal, but lycopene and β-carotene concentrations did not change after a similar citrus fruit meal. These results support our hypothesis that changes in plasma β-cryptoxanthin are greater than changes in plasma lycopene or β-carotene, even when these carotenoids are fed in a similar food matrix.

Lycopene Deficiency in Ageing and Cardiovascular Disease.

Lycopene is a hydrocarbon phytochemical belonging to the tetraterpene carotenoid family and is found in red fruit and vegetables. Eleven conjugated double bonds predetermine the antioxidant properties of lycopene and its ability to scavenge lipid peroxyl radicals, reactive oxygen species, and nitric oxide. Lycopene has a low bioavailability rate and appears in the blood circulation incorporated into chylomicrons and other apo-B containing lipoproteins. The recent body of evidence suggests that plasma concentration of lycopene is not only a function of intestinal absorption rate but also lycopene breakdown via enzymatic and oxidative pathways in blood and tissues. Oxidative stress and the accumulation of reactive oxygen species and nitric oxide may represent a major cause of lycopene depletion in ageing, cardiovascular disease, and type 2 diabetes mellitus. It has been shown recently that low carotenoid levels, and especially decreased serum lycopene levels, are strongly predictive of all-cause mortality and poor outcomes of cardiovascular disease. However, there is a poor statistical association between dietary and serum lycopene levels which occurs due to limited bioavailability of lycopene from dietary sources. Hence, it is very unlikely that nutritional intervention alone could be instrumental in the correction of lycopene and carotenoid deficiency. Therefore, new nutraceutical formulations of carotenoids with enhanced bioavailability are urgently needed.

A randomized double‐blind placebo controlled phase I–II study on clinical and molecular effects of dietary supplements in men with precancerous prostatic lesions. Chemoprevention or “chemopromotion”?

Antioxidants effectiveness in prostate cancer (PCa) chemoprevention has been severely questioned, especially after the recent results of the Selenium and Vitamin E Cancer Prevention Trial. We present the results of a double-blind randomized controlled trial (dbRCT) on the pharmacokinetic, clinical, and molecular activity of dietary supplements containing lycopene, selenium, and green tea catechins (GTCs) in men with multifocal high grade prostatic intraepithelial neoplasia (mHGPIN) and/or atypical small acinar proliferation (ASAP). From 2009 to 2014, we conducted a dbRCT including 60 patients with primary mHGPIN and/or ASAP receiving daily lycopene 35 mg, selenium 55 µg, and GTCs 600 mg, or placebo for 6 months. Pharmacokinetic analysis were performed with UV-Visible spectrophotometric assay under standard (SC) and accelerated (AC) conditions. Upon plasma lycopene concentrations falling within the expected range (1.2-90 mcg/l) and no side-effects of grade >1, study proceeded to phase II (n = 50). After unblinding of results, eight men (4 per arm, 2 without and 2 with PCa, respectively) were randomly selected and totRNA extracted from "non-pathological" tissues. MicroRNA profiling was performed with the Agilent platform. Raw data processing used R-statistical language and linear models for microarray analysis. Samples were stable except for lycopene, showing significant degradation (SC = 56%, AC = 59%) and consequently stabilized under vacuum in a dark packaging. Mean plasmatic lycopene concentration was 1,45 ± 0,4 μM. At 6 months, 53 men underwent re-biopsy and 13 (24.5%) were diagnosed with PCa (supplementation n = 10, placebo n = 3 [P = 0.053]). At a mean 37 months follow-up, 3 additional PCa were found in the placebo group. No significant variations in PSA, IPSS, and PR25 questionnaires were observed. Stronger modulation of miRNAs was present on re-biopsy in the supplementation group compared to the placebo, including: (i) overexpression of miRNAs present in PCa versus non-cancer tissue; (ii) underexpression of miRNAs suppressing PCa proliferation; (iii) detection of 35 miRNAs in PCa patients versus disease-free men, including androgen-regulated miR-125b-5p and PTEN-targeting miR-92a-3p (both upregulated). Administration of high doses of lycopene, GTCs, and selenium in men harboring HGPIN and/or ASAP was associated with a higher incidence of PCa at re-biopsy and expression of microRNAs implicated in PCa progression at molecular analysis. The use of these supplements should be avoided.

A Dietary Guideline Adherence Score Is Positively Associated with Dietary Biomarkers but Not Lipid Profile in Healthy Children ,

Background: Whether dietary indexes are associated with biomarkers of children’s dietary intake is unclear.Objective: The study aim was to examine the relations between diet quality and selected plasma biomarkers of dietary intake and serum lipid profile.Methods: The study sample consisted of 130 children aged 4–13 y (mean ± SD: 8.6 ± 2.9 y) derived by using baseline data from an intervention study. The Dietary Guideline Index for Children and Adolescents (DGI-CA) comprises the following 11 components with age-specific criteria: 5 core food groups, whole-grain bread, reduced-fat dairy foods, discretionary foods (nutrient poor; high in saturated fat, salt, and added sugar), healthy fats/oils, water, and diet variety (possible score of 100). A higher score reflects greater compliance with dietary guidelines. Venous blood was collected for measurements of serum lipids, fatty acid composition, plasma carotenoids, lutein, lycopene, and α-tocopherol. Linear regression was used to examine the relation between DGI-CA score (independent variable) and concentrations of biomarkers by using the log-transformed variable (outcome), controlling for confounders.Results: DGI-CA score was positively associated (P < 0.05) with plasma concentrations of lutein (standardized β = 0.17), α-carotene (standardized β = 0.28), β-carotene (standardized β = 0.26), and n–3 (ω-3) fatty acids (standardized β = 0.51) and inversely associated with plasma concentrations of lycopene (standardized β = −0.23) and stearic acid (18:0) (standardized β = −0.22). No association was observed between diet quality and α-tocopherol, n–6 fatty acids, or serum lipid profile (all P > 0.05).Conclusion: Diet quality, conceptualized as adherence to national dietary guidelines, is cross-sectionally associated with plasma biomarkers of dietary exposure but not serum lipid profile. This trial was registered with the Australia New Zealand Clinical Trial Registry (www.anztr.org.au) as ACTRN12609000453280.

Plasma Carotenoids and Retinol and Overall and Breast Cancer Risk: A Nested Case-Control Study

Experimental studies suggest that carotenoids and retinol may play a role in carcinogenesis, but epidemiological evidence is lacking. We investigated the prospective associations between plasma concentrations of major carotenoids and retinol, and overall and breast cancer risk. A nested case-control study included all first incident cancer cases diagnosed in the SU.VI.MAX cohort between 1994 and 2002 (n = 159 cases, 1 matched control/case). Baseline plasma concentrations of carotenoids and retinol were measured by high-performance liquid chromatography. Conditional logistic regression was used to assess odds ratios for an increase of 0.1 μmol/L [odds ratio (OR)] and 95% confidence intervals (CI). Plasma β-carotene (OR = 0.95, 95% CI = 0.90–0.99, Ptrend = 0.04) and β-cryptoxanthin concentrations (OR = 0.89, 95% CI = 0.81–0.99, Ptrend = 0.03) were inversely associated with overall cancer risk. Plasma β-cryptoxanthin concentration was inversely associated with breast cancer risk (OR = 0.83, 95% CI = 0.71–0.96, Ptrend = 0.02). The OR between plasma lycopene concentration and overall cancer risk was 1.07 (0.99–1.15), Ptrend = 0.06. This association turned significant (Ptrend = 0.01) when excluding cancer cases diagnosed during the first year of follow-up. This prospective study suggests an inverse association between plasma concentrations of β-cryptoxanthin and both overall and breast cancer risk, and an inverse association between β-carotene and overall cancer risk. The direct association between lycopene concentration and cancer risk deserves further investigation.

Independent positive association of plasma β-carotene concentrations with adiponectin among non-diabetic obese subjects.

Many epidemiological studies find an inverse correlation between carotenoids intake or carotenoids plasma concentrations and body mass index (BMI), insulin resistance or metabolic syndrome in the general population. However, it is not clear whether these relationships occur in obese population. We conducted a cross-sectional study in 108 obese non-diabetic patients. There was an inverse correlation between plasma levels of pro-vitamin A carotenoids (α-carotene, β-carotene and β-cryptoxanthin) and both BMI and insulin resistance (estimated by the HOMA-IR). No correlation between plasma concentrations of lycopene or lutein/zeaxanthin and BMI or insulin resistance was found. The inverse association between the three pro-vitamin A carotenoids and HOMA-IR disappeared after adjustment for BMI and waist circumference. Interestingly, we identified a positive association between concentrations of β-carotene and adiponectin in plasma that was independent of sex, age, smoking status, BMI and waist circumference. To our knowledge, such association has never been described in obese patients. These results suggest the existence of a favourable effect of β-carotene on insulin sensitivity in obese individuals that could involve a positive regulation of adiponectin, either directly or via its pro-vitamin A activity. The demonstration of the potential benefits of β-carotene towards insulin sensitivity would open the way to dietary strategies to prevent metabolic syndrome.

Lycopene up‐regulates mRNA expressions of SIRT and adiponectin and down‐regulates PPARγ and IL‐6 in adipose tissue of hypercaloric diet‐fed rats

ObjectiveTo evaluate the effect of lycopene supplementation on inflammation in adipose tissue of obese rats.MethodsMale Wistar rats were first fed control diet (C, n=6) or hypercaloric diet (HD, n=12) for 6 wks. Afterwards, the HD rats were randomized into two groups: HD [placebo (corn oil)] or HD+L [lycopene (10 mg/Kg BW/day in corn oil)] by gavage for 6 wks. Plasma lycopene concentration was analyzed by a HPLC system. The mRNA expressions of SIRT1, FoxO1, adiponectin, PPARγ, MCP‐1 and IL‐6 in adipose tissue were determined by real time PCR.ResultsLycopene was detected in plasma (24 nmol/L) from HD+L group only. The mRNA expressions of adiponectin, SIRT1 and FoxO1 decreased significantly but PPARγ, MCP‐1 and IL‐6 increased significantly in adipose tissue from HD group, as compared with those of C group. Although there was no difference in adiposity index between the HD and HD+L group, lycopene supplementation restored the reduced expressions of SIRT1 and FoxO1 to the levels of the C group and inhibited the up‐regulations of PPARγ, MCP‐1 and IL‐6 mRNA expressions in the HD+L group.ConclusionLycopene modulates several key inflammatory genes in adipose tissue indicating its potential protective effect against obesity‐related inflammation.Financial Support: FAPESP (2010/06100–9; 2010/19746–4; 2011/22786–0)

Pharmacokinetics of 13C‐Lycopene in Healthy Adults

Higher plasma lycopene (LYC) concentrations are associated with lower risk of several cancers. (All‐E)‐LYC is the predominant geometrical isomer in tomatoes, yet most plasma and tissue LYC isomers are Z, suggesting greater bioavailability of Z and/or endogenous isomerization of E to Z. To study human LYC pharmacokinetics and isomerization, ~10 mg of 13C‐LYC isolated from tomato cell cultures was consumed with breakfastby 6 healthy adults. The dose was 85% (all‐E)‐LYC, and ~30% uniformly labeled. Plasma was collected at 1–10, 24, 72, and 672 hrs post‐dosing. Native and 13C‐LYC was analyzed by HPLC‐PDA, and LC‐MS (QToF), respectively. No adverse effects of 13C‐LYC were observed. 13C‐LYC Cmax= 0.13±0.03 μM which occurred at 32±8 hr, T1/2 = 6.5 ± 0.3 d, and area‐under‐the‐curve (AUC0–672) = 36.9±7 μM*h. Plasma 13C‐all‐E‐LYC Cmax =0.10 ±0.02 μM at 29±9 h post‐dosing, T1/2 = 5.5±0.3 d, and it constituted 67% of total 13C‐LYC AUC. Total 13C‐Z‐LYC isomers Cmax =0.03 ± 0.005 μM at 56±10 hr post‐dosing with a subsequent T1/2 = 9.3±0.6 days, and constituted 32% of the total 13C‐LYC AUC. Initial plasma 13C‐LYC was 73–87% all‐E, but by 672 hr, had decreased to 46%. The later Z isomer Cmax and longer T1/2 relative to all‐E suggests that endogenous conversion is a source of circulating Z‐LYC isomers. Understanding LYC pharmacokinetics assists in designing anti‐cancer dietary interventions.Grant Funding Source: NCCAM R21AT005166, Pelotonia, OSUCCC NPASR

Plasma carotenoid concentrations of infants are increased by feeding a milk‐based infant formula supplemented with carotenoids

Human milk is the gold standard of infant nutrition and is a source of important substances, including carotenoids. Infant formulas are designed to mimic the composition and/or performance of human milk, although currently carotenoids are not routinely added to US infant formulas. The aim of this study was to assess plasma concentrations of β-carotene, lutein and lycopene 56 days after feeding infants milk-based infant formula without (CTRL) or with different concentrations of added carotenoids (L1 and L2). Plasma carotenoid concentrations increased in infants fed carotenoid-supplemented formulas as compared with the control formula with no added carotenoids. At study day 56, infants fed the supplemented formulas (L1 and L2) had mean plasma lutein, β-carotene and lycopene concentrations that were within the range of a concurrent group of human milk-fed infants (HM). Anthropometric measurements were comparable among all study groups. Plasma carotenoid concentrations of infants fed the supplemented formulas were within the range of the HM group and are consistent with reported plasma carotenoid ranges in human milk-fed infants. The experimental formulas were well tolerated and anthropometric measurements were comparable among all study groups.