Lycopene-rich Tomato Research Articles

Study on Effect of Lycopene Rich Tomato Puree Supplementation on Wellbeing/Healthiness in Hyperlipidemic Wistar Rats

Background: The red-colored tomatoes are characterised as a mine of lycopene to manufacture food grade ingredient and projected its placement in a specialty class where nutrient with pharmaceutical value justifies dietary status. Tomato lycopene has justified its status as a potential antioxidant compensating with nutraceutical importance and provided an option for endorsing specialty nutrition. The diversity epidemiological experiments recorded noteworthy modulations in lipid profile and projected risk reduction potential of lycopene against non-communicable diseases. The progressive research efforts to monitor haematological parameters to justify efficacy of tomato lycopene against adverse effects on wellbeing of human body is required for precision governance. The present research work aims to assess the potential of lycopene rich tomato puree in monitoring the haematological parameters in hyperlipidemic Wistar rats. Methods: Wistar rats (Healthy control, high fat diet fed, HFD-Stain treated and HFD-tomato puree treated) were examined for physiological, haematological and blood biochemical parameters on 0, 14 and 28th day of experiment to assess effect of tomato puree administration on wellbeing of rats against healthy, hyperlipidemic and standard drug status. Result: The increased haemoglobin and total erythrocyte count on 14th and 28th day of experiment justifies the erythropoiesis stimulatory effect of tomato puree lycopene. Moreover, increased total leukocyte count in high fat diet-tomato puree fed rats on 14th and 28th day validates the positive effect of tomato puree lycopene to monitor healthiness in Wistar rats. The regulatory mechanism based on haematological specialty features that monitors the risk of physiological disorders and diseases outlined through animal study experimental data provided a logistic option to confirm the efficacy of tomato puree lycopene to protect wellbeing/healthiness of live entity (Wistar rats).

Protective Effect of Lycopene Rich Tomato Puree on the Development of Atherosclerosis/Heart Diseases in Animal Models

Background: Lycopene as an aliphatic carotenoid promulgated from tomato has gained the attention of new generation food and pharma scientists on the ground of its nutraceutical efficacy. It is a preeminent antioxidant known for its singlet oxygen quenching ability that reduces oxidative stress responsible for non-communicable diseases. In present investigation the health claim exploration ability of lycopene rich tomato puree as a dietary supplement was assessed by animal studies to project its hypolipidemic efficacy effective in reducing risk of heart diseases.
 Aim: The present investigation aims to determine efficacy of tomato puree lycopene in monitoring atherogenesis mechanism through synergic mode of action of notified specialty features (total cholesterol, serum triglycerides, LDL cholesterol and HDL cholesterol) in Wistar rats.
 Study Design: Wistar rats (Positive control, high fat diet fed, HFD-Stain fed and HFD-tomato puree fed) were examined for general examinations (behavioural changes and body weight), Lipid profile (total cholesterol, triglyceride, LDL and HDL cholesterol) on 0, 14 and 28th day of experiment to assess effect of tomato puree administration on wellbeing of rats against healthy, hyperlipidemic and standard drug status.
 Place and Duration of Study: MIT School of Food Technology in collaboration with Department of Pharmacology and Toxicology, College of Veterinary and Animal Sciences, Parbhani (MAFSU, Nagpur), Maharashtra. The overall study duration was for 3 months.
 Methodology: The experimental rats (Wistar) employed in present study were acquired from authorized breeder after the approval of the experimental protocol by Institutional Animal Ethical Committee (IAEC approval resolution no.: IAEC 58/19, Date 20/08/2019). Acclimatization of the animals was undertaken for 20 days during which they were provided with natural diet, pure and safe drinking water. CPCSEA (Committee for the purpose of control and supervision of experiments on animals) guidelines were followed while handling the experimental animals throughout the complete study duration. The experimental animals (32 Wistar rats) were segregated into four different groups (Positive control, high fat diet fed, HFD-Stain fed and HFD-tomato puree fed), containing 8 rats (4 male and 4 female). Animals from four distinguished groups were monitored regularly for general observations (body weights, behavioural changes and mortality changes) throughout the experimental period. The lipid profile (total cholesterol, triglyceride, HDL, LDL) of blood serum samples was recorded using auto analyser on 0, 14th and 28th day of experiment.
 Results: The data analysis, interpretation and reviewed literature infusion collectively underlined the efficacy of lycopene (tomato puree) in monitoring atherogenesis mechanism through synergic mode of action of notified specialty features (total cholesterol, serum triglycerides, LDL cholesterol and HDL cholesterol) and projected an effective gateway to support disease infused health claim. The cumulative decrease in total cholesterol (159.99 to 126.40mg/dl), serum triglycerides (114.81 to 107.34mg/dl), LDL cholesterol (40.19 to 32.90mg/dl) and increase in HDL cholesterol (19.99 to 23.87mg/dl) of treated rats represents hypolipidemic efficacy of tomato puree lycopene.
 Conclusion: The tomato puree mass being a viable lycopene source with innate antiatherogenic efficacy has rationally updated the review base critical appraisal leading to development of prototype of CVD to launch health claim. The human clinical study as a confirmation tool, may be the best option for next generation research.

The effectiveness of tomato extract on superoxide dismutase (SOD) and severity degree of patients with melasma.

Melasma is present in 40% of cases in Southeast Asia. The condition is often unresponsive to therapy; treatment has variable success rates, and melasma has high recurrence rates. Lycopene-rich tomato extract is needed to avoid oxidative stress due to ultraviolet rays that cause melasma through the melanogenesis pathway. The aim of this study was to evaluate the effectiveness of an oral tomato extract supplement as an adjuvant for melasma therapy. The study recruited 62 subjects with melasma to a true-experimental clinic with a double-blind, randomized, pre and post-test control design over 12 weeks at the Diponegoro National Hospital, Indonesia. The subjects received an oral tomato extract supplement contains lycopene 30 mg (placebo). All subjects applied topical sunscreen and hydroquinone-4%-cream. Subjects were assessed by superoxide dismutase (SOD) and melasma area and severity index (MASI). Fifty-nine patients completed the research. The serum SOD levels in the treatment group (tomato extract supplementation) were higher than in the control group given the placebo, with delta SOD (P<0.05). The difference in MASI Scores after therapy in the treatment group had a significant decrease compared to the control group, with statistical review results suggesting that the difference was significant (P<0.05). Supplementation of tomato extract as an adjuvant therapy can increase serum SOD levels and improve melasma severity.

Tomato Oil Encapsulation by α-, β-, and γ-Cyclodextrins: A Comparative Study on the Formation of Supramolecular Structures, Antioxidant Activity, and Carotenoid Stability.

Cyclodextrins (CDs) are oligosaccharides, comprising 6 (α), 7 (β), or 8 (γ) glucose residues, used to prepare oil-in-water emulsions and improve oil stability towards degradation. In this research, the aptitude of α-, β-, and γ-CDs to form complexes with a supercritical CO2 extracted lycopene-rich tomato oil (TO) was comparatively assessed. TO/CD emulsions and the resulting freeze-dried powders were characterized by microscopy, Fourier transform infrared-attenuated total reflection (FTIR-ATR), and differential scanning calorimetry (DSC), as well as for their antioxidant activity. Furthermore, carotenoid stability was monitored for 90 days at 25 and 4 °C. Confocal and SEM microscopy revealed morphological differences among samples. α- and β-CDs spontaneously associated into microcrystals assembling in thin spherical shells (cyclodextrinosomes, Ø ≈ 27 µm) at the oil/water interface. Much smaller (Ø ≈ 9 µm) aggregates were occasionally observed with γ-CDs, but most TO droplets appeared “naked”. FTIR and DSC spectra indicated that most CDs did not participate in TO complex formation, nevertheless structurally different interfacial complexes were formed. The trolox equivalent antioxidant capacity (TEAC) activity of emulsions and powders highlighted better performances of α- and β-CDs as hydrophobic antioxidants-dispersing agents across aqueous media. Regardless of CDs type, low temperature slowed down carotenoid degradation in all samples, except all-[E]-lycopene, which does not appear efficiently protected by any CD type in the long storage period.

Production of (Z)-Lycopene-Rich Tomato Concentrate: A Natural Catalyst-Utilized and Oil-Based Study for Practical Applications.

Since lycopene Z-isomers exhibit greater bioavailability and biological activity than the naturally occurring all-E-isomer, efficient manufacturing methods for (Z)-lycopene-rich materials are urgently needed. Herein, a method was developed for Z-isomerization of (all-E)-lycopene in tomato oleoresin using heat treatment and a natural catalyst, viz. allyl isothiocyanate (AITC). For practical application of this isomerization technology, no organic solvents were used, and instead, oils and fats were used as the reaction medium. The Z-isomerization of (all-E)-lycopene was promoted by heating (>120 °C) even when oil and fat media were used. Allyl isothiocyanate enhanced thermal Z-isomerization and improved the (5Z)-lycopene content, which shows higher biological activity compared to the other Z-isomers. The thermal isomerization efficiency with AITC was further improved by using certain vegetable oils such as argan and olive oils. In addition, the storage stability of (Z)-lycopene-rich tomato concentrates dispersed in olive oil was evaluated. The total Z-isomer ratio and lycopene concentration decreased with longer storage periods, and it was revealed that (5Z)-lycopene showed excellent storage stability among the mono-Z-isomers.

Lycopene and bone: an in\xa0vitro\xa0investigation and a\xa0pilot prospective\xa0clinical\xa0study

BackgroundThere are several effective therapies for osteoporosis but these agents might cause serious adverse events. Lycopene intake could prevent bone loss, however studies on its effects on bone are scarce. Our aim was to investigate the effects of lycopene on osteoblast cells as well as bone mineral density and bone turnover markers in postmenopausal women.MethodsWe investigated the effect of lycopene on the Wnt/β-catenin and ERK 1/2 pathways, RUNX2, alkaline phosphatase, RANKL and COL1A of Saos-2. We also carried out a pilot controlled clinical study to verify the feasibility of an approach for bone loss prevention through the intake of a lycopene-rich tomato sauce in 39 postmenopausal women.ResultsLycopene 10 µM resulted in higher β-catenin and phERK1/2 protein Vs the vehicle (p = 0.04 and p = 0.006). RUNX2 and COL1A mRNA was induced by both 5 and 10 µM doses (p = 0.03; p = 0.03 and p = 0.03; p = 0.05) while RANKL mRNA was reduced (p < 0.05). A significant bone density loss was not detected in women taking the tomato sauce while the control group had bone loss (p = 0.002). Tomato sauce intake resulted in a greater bone alkaline phosphatase reduction than the control (18% vs 8.5%, p = 0.03).ConclusionsLycopene activates the WNT/β-catenin and ERK1/2 pathways, upregulates RUNX2, alkaline phosphatase, COL1A and downregulates RANKL Saos-2. These processes contributed to prevent bone loss in postmenopausal women.

Randomised Clinical Trial: Calorie Restriction Regimen with Tomato Juice Supplementation Ameliorates Oxidative Stress and Preserves a Proper Immune Surveillance Modulating Mitochondrial Bioenergetics of T-Lymphocytes in Obese Children Affected by Non-Alcoholic Fatty Liver Disease (NAFLD).

Fatty liver disease is a serious complication of childhood obesity. Calorie-restricted regimen (RCR) is one of the effective therapy for this condition. Aim of the study was to evaluate the effect of lycopene-rich tomato sauce with oregano and basil extracts in obese children with fatty liver on RCR. 61 obese children with fatty liver were enrolled, 52 completed the study. A randomized cross over clinical trial was performed. Participants were assigned to RCR alone or with a supplement of lycopene-rich tomato juice for 60 days; subsequently, the groups were switched to the alternative regimen for the next 60 days. Reduction in BMI, HOMA-IR, cholesterol, triglycerides, liver size, and steatosis was more profound in tomato-supplemented group. Leptin decreased in both groups whereas adiponectin raised only after tomato supplementation. RCR is associated with the impaired engagement of T-cells glycolysis and proliferation, tomato-supplementation resulted in glycolytic metabolic activation of T-cells. Tomato juice ameliorates glucose and lipid metabolism in obese children, improve oxidative and inflammatory state and modulates the mitochondrial metabolism of T-cells contributing to a maintenance of a proper immune surveillance in children, impaired by RCR. The addition of tomato to RCR could be considered a protective and preventive support to obese child.

Consumption of lycopene-rich tomatoes improved glucose homeostasis in rats via an increase in leptin levels.

The lycopene content of tomatoes is important because of its effects on vital physiological functions such as improvement of glucose tolerance and non-alcoholic fatty liver disease. To investigate the influence of the lycopene content of tomatoes on glucose tolerance and hepatic lipid content, homogenates of lycopene-rich (LR) or lycopene-free negative control (NC) tomato varieties were administrated to normal rats for 4weeks. At the end of the experiment, an oral glucose tolerance test (OGTT) was performed. Rats were fed once and then dissected. According to the OGTT results, plasma glucose levels in the LR group were 10% and 9% lower at 15min and 30min, respectively, than those in the NC group, whereas plasma insulin levels did not differ between the groups at either time point. Upon dissection, plasma leptin levels in the LR group were higher than those in the NC group, while plasma adiponectin levels did not differ between groups. With the exception of retinol palmitate, no carotenoids were detected in the liver by HPLC analysis. Hepatic retinol palmitate levels and hepatic triacyl glyceride levels did not differ between the groups. We concluded that in normal rats, a lycopene-rich tomato variety improved glucose tolerance via an increase in plasma leptin levels that enhanced insulin sensitivity but did not affect carotenoid accumulation or lipid metabolism.

Tomato Phytonutrients Balance UV Response: Results from a Double-Blind, Randomized, Placebo-Controlled Study

Background: Our previous double-blinded, placebo-controlled cross-over study indicated that a nutritional supplement named lycopene-rich tomato nutrient complex (TNC) can protect from UVA1-induced (340–400 nm) and UVA- (320–400 nm)/UVB-induced (280–320 nm) upregulation of molecular markers associated with oxidative stress, inflammation, and ageing. Objectives: in the current double-blind, randomized, placebo-controlled multicenter study, we analyze whether a similar, synergistic carotenoid-rich TNC can protect from broadband UVB-induced threshold erythema formation assessed as increase in minimal erythemal dose (MED) reading, the intensity of erythema formation, and the upregulation of molecular markers associated with inflammation and immunosuppression, and whether this correlates with carotenoid blood levels. Methods: One hundred and forty-nine healthy volunteers were randomized to two groups and subjected to a 5-week washout phase, followed by a 12-week treatment phase receiving either 15 mg lycopene, 5.8 mg phytoene and phytofluene, 0.8 mg β-carotene, 5.6 mg tocopherols from tomato extract, and 4 mg carnosic acid from rosemary extract per day or placebo made from medium-chain triglycerides. At the end of each phase, MED determination, UVB irradiation, chromametry, biopsies, and blood samples were undertaken. Results: The active supplement was well tolerated. Interestingly, no significant difference was seen in the MED between the active-supplement and placebo groups, as determined by visual grading by expert assessors. Of note, the carotenoid-containing supplement significantly protected against UVB-induced erythema formation measured as Δa* after the intervention minus Δa* after the washout phase as compared to the placebo. Moreover, intake of the active supplement significantly protected against UVB-induced upregulation of IL6 and TNFα as compared with the intake of placebo. Lastly, carotenoid plasma levels were significantly increased. Conclusion: This well-tolerated carotenoid-containing supplement significantly protected against UVB-induced erythema formation and upregulation of proinflammatory cytokines in healthy volunteers.

Dietary Tomato Powder Inhibits High-Fat Diet–Promoted Hepatocellular Carcinoma with Alteration of Gut Microbiota in Mice Lacking Carotenoid Cleavage Enzymes

Both incidence and death rate due to liver cancer have increased in the United States. Higher consumption of lycopene-rich tomato and tomato products is associated with a decreased risk of cancers. β-Carotene-15, 15'-oxygenase (BCO1), and β-carotene-9', 10'-oxygenase (BCO2) cleave lycopene to produce bioactive apo-lycopenoids. Although BCO1/BCO2 polymorphisms affect human and animal lycopene levels, whether dietary tomato consumption can inhibit high-fat diet (HFD)-promoted hepatocellular carcinoma (HCC) development and affect gut microbiota in the absence of BCO1/BCO2 is unclear. BCO1/BCO2 double knockout mice were initiated with a hepatic carcinogen (diethylnitrosamine) at 2 weeks of age. At 6 weeks of age, the mice were randomly assigned to an HFD (60% of energy as fat) with or without tomato powder (TP) feeding for 24 weeks. Results showed that TP feeding significantly decreased HCC development (67%, 83%, and 95% reduction in incidence, multiplicity, and tumor volume, respectively, P < 0.05). Protective effects of TP feeding were associated with (1) decreased hepatic inflammatory foci development and mRNA expression of proinflammatory biomarkers (IL1β, IL6, IL12α, monocyte chemoattractant protein-1, and inducible NO synthase); (2) increased mRNA expression of deacetylase sirtuin 1 and nicotinamide phosphoribosyltransferase involving NAD+ production; and (3) increased hepatic circadian clock genes (circadian locomotor output cycles kaput, period 2, and cryptochrome-2, Wee1). Furthermore, TP feeding increased gut microbial richness and diversity, and significantly decreased the relative abundance of the genus Clostridium and Mucispirillum, respectively. The present study demonstrates that dietary tomato feeding independent of carotenoid cleavage enzymes prevents HFD-induced inflammation with potential modulating gut microbiota and inhibits HFD-promoted HCC development.

Microencapsulation by spray drying of a lycopene-rich tomato concentrate: Characterization and stability

The objective of this study was to evaluate the effect of different encapsulating agents (maltodextrin, whey protein isolate and the modified starch Capsul®) on the physicochemical properties and lycopene stability of a tomato concentrate microencapsulated by spray drying. Different formulations were produced according to an experimental mixture simplex-lattice design, where the independent variables were the concentrations of each encapsulating agent. Physical properties (moisture content, solubility and hygroscopicity), lycopene concentration and the antioxidant capacity of particles immediately after drying, as well as lycopene stability during storage, were analyzed as responses. Particles presented initial lycopene content between 333 and 494 μg/g. The powders produced with maltodextrin and modified starch presented the highest concentrations of this carotenoid and greater antioxidant capacity. These two responses showed high degree of correlation with each other. Maltodextrin and modified starch also led to lower lycopene degradation rates during storage and, therefore, these encapsulating agents were considered the most suitable for the tomato concentrate encapsulation.

The Combined Anti-Inflammatory Effect of Astaxanthin, Lyc-O-Mato and Carnosic Acid In Vitro and In Vivo in a Mouse Model of Peritonitis

Inflammation has an important role in the pathogenesis of many diseases. The aims of the present research were to assess the effectiveness of a combination of Astaxanthin, Lycopene rich Tomato extract (Lyc-O-Mato®) and Carnosic acid, at low concentrations, to prevent the release of the inflammatory mediators from LPS stimulated macrophages in vitro an in vivo using a mouse model of peritonitis. Addition of low concentrations of Astaxanthin Lyc-O-Mato® and Carnosic acid to peritoneal mouse macrophages 1 h before addition of LPS for 24 h caused a synergistic inhibition of NO, PGE2 and TNFα secretion. The supplementation of a nutrient combination in drinking water resulted in attenuation of basal, but not stimulated, superoxide production by recruited neutrophils to the peritoneal cavity and in inhibition of inflammatory mediators production by peritoneal macrophages. Our results indicate a potential use of these combinations in many inflammatory states.

Molecular evidence that oral supplementation with lycopene or lutein protects human skin against ultraviolet radiation: results from a double-blinded, placebo-controlled, crossover study.

Increasing evidence suggests photoprotection by oral supplementation with β-carotene and lycopene. To examine the capacity of lycopene-rich tomato nutrient complex (TNC) and lutein, to protect against ultraviolet (UV)A/B and UVA1 radiation at a molecular level. In a placebo-controlled, double-blinded, randomized, crossover study two active treatments containing either TNC or lutein were assessed for their capacity to decrease the expression of UVA1 the radiation-inducible genes HO1, ICAM1 and MMP1. Sixty-five healthy volunteers were allocated to four treatment groups and subjected to a 2-week washout phase, followed by two 12-week treatment phases separated by another 2 weeks of washout. Volunteers started either with active treatment and were then switched to placebo, or vice versa. At the beginning and at the end of each treatment phase skin was irradiated and 24 h later biopsies were taken from untreated, UVA/B- and UVA1-irradiated skin for subsequent reverse transcriptase polymerase chain reaction analysis of gene expression. Moreover, blood samples were taken after the washout and the treatment phases for assessment of carotenoids. TNC completely inhibited UVA1- and UVA/B-induced upregulation of heme-oxygenase 1, intercellular adhesion molecule 1 and matrix metallopeptidase 1 mRNA, no matter the sequence (anova, P < 0·05). In contrast, lutein provided complete protection if it was taken in the first period but showed significantly smaller effects in the second sequence compared with TNC. Assuming the role of these genes as indicators of oxidative stress, photodermatoses and photoageing, these results might indicate that TNC and lutein could protect against solar radiation-induced health damage.

DNA and mitochondrial protective effect of lycopene rich tomato (Solanum lycopersicum L.) peel extract prepared by enzyme assisted extraction against H2O2 induced oxidative damage in L6 myoblasts

Lycopene rich extracts (ETE) were prepared by enzyme assisted extraction of tomato peel. Oxidative damage was induced in L6 myoblasts by exposing cells to H2O2 in presence and absence (control) of ETE. The potential of ETE to protect cells from oxidative damage was investigated in terms of cytotoxicity (MTT assay), Reactive oxygen species (ROS) by 2′, 7′-dichlorofluorescindiacetate (H2DCFDA), DNA damage (ladder assay, 8-oxo-dG), Hoechst 33342 nuclear staining, mitochondrial stability by ATP production and mitochondrial membrane potential by Rhodamine 123 staining. It was observed that treatment of cells with ETE significantly increased cell viability, decreased ROS production, reduced DNA fragmentation, chromatin condensation & 8-oxo-dG, increased ATP levels and mitochondrial membrane potential. Results indicated that ETE could protect cells from H2O2 induced oxidative damage significantly as compared to control. These results depicted the antioxidant potential of tomato peel extract which can counteract the redox imbalance in cells induced by oxidative stress condition.

Carotenoid profiling, in silico analysis and transcript profiling of miRNAs targeting carotenoid biosynthetic pathway genes in different developmental tissues of tomato

Carotenoid biosynthetic pathway is one of the highly significant and very well elucidated secondary metabolic pathways in plants. microRNAs are the potential regulators, widely known for playing a pivotal role in the regulation of various biological as well as metabolic processes. miRNAs may assist in the metabolic engineering of the secondary metabolites for the production of elite genotypes with increased biomass and content of various metabolites. miRNA mediated regulation of carotenoid biosynthetic genes has not been elucidated so far. To illustrate the potential regulatory role of miRNAs in carotenoid biosynthesis, transcript profiling of the known miRNAs and their possible target carotenoid genes was undertaken at eight different developmental stages of tomato, using stem-loop PCR approach combined with quantitative RT-PCR. The inter-relationship amongst carotenoid content, biosynthetic genes and miRNAs was studied in depth. Comparative expression profiles of miRNA and target genes showed variable expression in different tissues studied. The expression level of miRNAs and their target carotenoid genes displayed similar pattern in the vegetative tissues as compared to the reproductive ones, viz. fruit (different stages), indicating the possibility of regulation of carotenoid biosynthesis at various stages of fruit development. This was later confirmed by the HPLC analysis of the carotenoids. The present study has further enhanced the understanding of regulation of carotenoid biosynthetic pathway in plants. The identified miRNAs can be employed to manipulate the biosynthesis of different carotenoids, through metabolic engineering for the production of lycopene rich tomatoes.

Tomato-based randomized controlled trial in prostate cancer patients: Effect on PSA

The effect of lycopene-containing foods in prostate cancer development remains undetermined. We tested whether a lycopene-rich tomato intervention could reduce the levels of prostate specific antigen (PSA) in prostate cancer patients. Prior to their curative treatment, 79 patients with prostate cancer were randomized to a nutritional intervention with either 1) tomato products containing 30mg lycopene per day; 2) tomato products plus selenium, omega-3 fatty acids, soy isoflavones, grape/pomegranate juice, and green/black tea (tomato-plus); or 3) control diet for 3 weeks. The main analysis, which included patients in all risk categories, did not reveal differences in changes of PSA-values between the intervention and control groups. Post-hoc, exploratory analyses within intermediate risk (n=41) patients based on tumor classification and Gleason score post-surgery, revealed that median PSA decreased significantly in the tomato group as compared to controls (-2.9% and+6.5% respectively, p=0.016). In separate post-hoc analyses, we observed that median PSA-values decreased by 1% in patients with the highest increases in plasma lycopene, selenium and C20:5 n-3 fatty acid, compared to an 8.5% increase in the patients with the lowest increase in lycopene, selenium and C20:5 n-3 fatty acid (p=0.003). Also, PSA decreased in patients with the highest increase in lycopene alone (p=0.009). Three week nutritional interventions with tomato-products alone or in combination with selenium and n-3 fatty acids lower PSA in patients with non-metastatic prostate cancer. Our observation suggests that the effect may depend on both aggressiveness of the disease and the blood levels of lycopene, selenium and omega-3 fatty acids.

A Phase II Randomized Trial of Lycopene-Rich Tomato Extract Among Men with High-Grade Prostatic Intraepithelial Neoplasia

A diverse body of evidence suggests that lycopene might inhibit prostate cancer development. We conducted a 6-mo repeat biopsy randomized trial among men with high-grade prostatic intraepithelial neoplasia (HGPIN). Here we report results for serum lycopene, prostate specific antigen (PSA) and insulin-like growth factor (IGF) proteins, histopathological review, and tissue markers for proliferation [minichromosome maintenance protein 2 (MCM-2)] and cell cycle inhibition (p27). Participants consumed placebo or tomato extract capsules containing 30 mg/day lycopene. Pre- and posttreatment biopsies were immunostained and digitally scored. Serum lycopene was determined by LC-MS-MS. In secondary analyses, pathologists blindly reviewed each biopsy to score histological features. Fifty-eight men completed the trial. Serum lycopene increased 0.55 μmol/L with treatment and declined 0.29 μmol/L with placebo. We observed no meaningful differences in PSA, IGF-1, or IGF binding protein 3 concentrations between groups, nor any differences in expression of MCM-2 or p27 in epithelial nuclei. Prevalences of cancer, HGPIN, atrophy, or inflammation posttreatment were similar; however, more extensive atrophy and less extensive HGPIN was more common in the lycopene group. Despite large differences in serum lycopene following intervention, no treatment effects were apparent on either the serum or benign tissue endpoints. Larger studies are warranted to determine whether changes observed in extent of HGPIN and focal atrophy can be replicated.Trial registration: ClinicalTrials.gov identifier: NCT00416325.

Lycopene-rich tomato oleoresin modulates plasma adiponectin concentration and mRNA levels of adiponectin, SIRT1, and FoxO1 in adipose tissue of obese rats.

To investigate whether lycopene can modulate adiponectin levels and SIRT1 and FoxO1 gene expression in the adipose tissue of diet-induced obese rats. Male Wistar rats were first fed with hypercaloric diet (HD, n = 12) for 6 weeks, and afterward, these rats were randomly assigned to receive HD (n = 6) or HD with lycopene-rich tomato oleoresin (equivalent to lycopene 10 mg/kg body weight (BW)/day, HD + L, n = 6) by gavage for additional 6 weeks. Plasma lycopene and adiponectin levels were analyzed by high-performance liquid chromatography and immunoassay, respectively. The messenger RNA (mRNA) expressions of adiponectin, Sirtuin 1 (SIRT1), Forkhead box O 1 (FoxO1), fatty acid translocase/cluster of differentiation 36 (FAT/CD36), and PPARγ in adipose tissues were determined by quantitative polymerase chain reaction. Lycopene was detected in the plasma of rats in HD + L group but not in the HD group. Although both BW and adiposity were not different between the two groups, there was a significant increase in both plasma concentration and mRNA expression of adiponectin in the adipose tissue of the HD + L group. In addition, the lycopene supplementation upregulated mRNA expressions of SIRT1, FoxO1, and FAT/CD36 but downregulated PPARγ in adipose tissue of obese rats. These data suggest that lycopene, in the concentration used, is not toxic and also its health benefits in adipose tissue may play a role against obesity-related complications.

Changes in Selected Quality Attributes of Greenhouse Tomato Fruit as Affected by Pre- and Postharvest Environmental Conditions in Year-round Production

‘Durinta’ tomatoes were grown hydroponically using rockwool substrate in greenhouses to assess the seasonal and postharvest changes of selected quality attributes including lycopene and total soluble solids (TSS, % Brix) concentrations in fruit when grown under varied electrical conductivity (EC) in the nutrient solution. Two levels of EC examined in this study were 2.4 and 4.8 dS·m−1 for standard low EC and high EC treatments, respectively. All fruits at light-red and red ripeness stages were harvested and weighed every week, and nine fruits visually representing the median group of red fruits were selected from each EC treatment and subject to measurements of lycopene and TSS concentrations. Of 53 harvest weeks (Dec. 2005 to Dec. 2006), 45 weeks were subject to fruit quality analyses at harvest and 3 weeks were subject to postharvest quality analyses. Lycopene concentration and TSS showed seasonal differences with larger variation in lycopene, but the high EC treatment induced an overall average of 18% greater lycopene concentration and a 20% greater TSS. The regression analyses indicated that efflux solution EC (EEC) was the most influential factor for both lycopene and TSS concentrations, but secondary influential factors were greenhouse temperature for lycopene and daily light integral for TSS. Postharvest storage test showed that selected fruit quality attributes (lycopene, TSS, ascorbic acid, and total phenolics) changed minimally or not at all for 10 days when stored at 12 °C, a widely recommended tomato postharvest storage temperature. Overall, we consider that producing lycopene-rich tomato by controlling EC of nutrient solution was feasible during year-round greenhouse production using a high-wire rockwool culture system.

Abstract 3564: A Phase II randomized trial of lycopene-rich tomato extract among men with high-grade prostatic intraepithelial neoplasia (HGPIN)

Abstract Evidence from observational epidemiology, animal models and cell culture experiments suggest that tomato foods or other sources of lycopene might inhibit the development of prostate cancer. Clinical trial data, however, is thus far sparse, especially in relation to effects on benign prostate tissue. We conducted a 6-month repeat biopsy trial in men with HGPIN who were randomly assigned to consume either placebo or capsules of Lyco-Mato®, a tomato oleoresin containing 30 mg/day of lycopene. All participants were encouraged to avoid lycopene containing foods and supplements while on-study. Here we report results for serum lycopene, PSA and IGF proteins, and initial results for immunohistochemical analysis of markers for proliferation (minichromosome maintenance protein 2, MCM-2) and cell cycle inhibition (p27). Biopsy slides were stained using monoclonal antibodies for both markers and scoring was performed using an Aperio whole-slide digital microscope and scoring algorithms plus Genie® pattern recognition software for defining the epithelial compartment. Serum lycopene was determined by LC-MS-MS; PSA, IGF-1 and IGFBP3 were measured by enzyme immunoassay. Primary analyses compared treatment groups using a paired t test for the change in each endpoint. A total of 58 men completed the trial (26 active, 32 placebo); assignment groups were equivalent at baseline in terms of age, race, serum lycopene, PSA, IGF-1 and IGFBP3. Serum lycopene increased by 0.550 μmol/L (77%) in the active treatment group and declined by 0.288 μmol/L (19%) in the placebo group. We observed no meaningful differences in serum PSA, IGF-1 or IGFBP3 concentrations between groups. There were also no differences between groups in the percentages of epithelial nuclei expressing MCM-2 or the scoring index combining percentage with nuclear stain intensity. Similar null results were seen for staining with the CDK2 inhibitor p27. We conclude that despite a large difference in serum lycopene concentrations following intervention, no effects were apparent at 6 months on PSA or IGF proteins. The IHC results, although preliminary, suggest that treatment had no effect on epithelial cell proliferation or cell cycle inhibition via p27. Further analyses, including analysis of additional IHC markers, are currently underway. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3564. doi:1538-7445.AM2012-3564