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Tomatoes may have beneficial effects on prostate health. Efficacy trials would require long-term adherence to high levels of tomato product (TP) consumption. Therefore, factors that affect adherence in men most at risk and whether increased consumption of TP negatively affects diet and health are important concerns. Cancer-free African–American (AA) men (n 36) with mean serum prostate-specific antigen of 7.4 SD 5.6) ng/ml were randomised to consume one serving of TP/d or a control diet for 3 months. Mean intervention group lycopene intake rose to 464%, with negligible control group increase. Plasma lycopene levels rose by 53 and 40% in the intervention group in months 1 and 3, respectively (P < 0.0001), with no control group change. The intervention group’s barriers to adherence score was inversely associated with both dietary (r -0.49, P = 0.02) and plasma lycopene concentration (r -0.37, P = 0.02). Their TP disadvantage score negatively correlated with the 3-month plasma lycopene concentrations (r -0.37, P = 0.008) and their weekly incentives and impediments were remarkably stable, ‘concern for prostate health’ being the most consistent over time. ‘Liking tomatoes’ and ‘study participation’ decreased in citation frequency at weeks 6 and 9, respectively. No major shifts occurred in dietary cholesterol or saturated fat, with no adverse effects on gastrointestinal complaints, serum total cholesterol, body weight or blood pressure. Lower socio-economic status AA men at higher prostate cancer risk can successfully achieve a whole food intervention goal with a corresponding rise in plasma lycopene concentrations, with no adverse effects on self-selected diet quality or health parameters.

The objective of this study was to determine the influence of thermal processing on the assessment of tocopherols and carotenoids, as well as their isomer formation in tomatoes. The sliced tomatoes were heated in an oven at 100, 130, and 160 °C for 5, 10, and 20 min, then freeze-dried. Freeze-dried samples were finely ground and the analysis was performed on lyophilized samples. The average concentrations of total lycopene, lutein, β-carotene, α-tocopherol, and γ-tocopherol in fresh tomatoes (in 100 g dry weight) were 21.2, 1.1, 2.7, 8.0, and 2.5 mg, respectively. Oven baking of tomato at 160 °C for 20 min led to a significant increase in the apparent measurement of lycopene, β-carotene, and α-tocopherol content by 75%, 81%, and 32%, respectively. Heating induced isomerization of (all-E) to various (Z) isomers of lycopene, and we found that the total (Z)-lycopene proportion in the tomatoes increased with longer heating time. (All-E)-lycopene constituted 75.4% in fresh tomatoes and decreased to 52.5% in oven-baked tomatoes (160 °C, 20 min), while (5Z)-lycopene increased from 9.4% to 17.9% of total lycopene. However, β-carotene release and isomerization was less influenced by the heat treatment than that of lycopene. These results suggested that thermal processes might break down cell walls and enhance the release of carotenoids and tocopherols from the matrix, as well as increase isomerization of lycopene and β-carotene., (© 2012 Institute of Food Technologists®)

Consumption of tomato products is associated with a decreased risk of developing prostate cancer, and lycopene, the red carotenoid in the tomato, is a potent antioxidant that might contribute to this chemoprevention activity. A double-blind, randomized, placebo-controlled trial of 105 African American men veterans, recommended for prostate biopsy to detect cancer, was carried out to investigate whether oral administration of lycopene increases lycopene levels in blood and prostate tissue and lowers markers of oxidative stress. Urology patients were randomly assigned to receive 30 mg/d of lycopene as a tomato oleoresin or placebo for 21 days prior to prostate biopsy for possible diagnosis of prostate cancer. A total of 47 men had a diagnosis of prostate cancer, and 58 men had a diagnosis of benign prostate hyperplasia. Diet, smoking, and drinking habits were assessed. For the men receiving lycopene, the mean lycopene concentration increased from 0.74 ± 0.39 to 1.43 ± 0.61 μmol/L in plasma (P < 0.0001) and from 0.45 ± 0.53 to 0.59 ± 0.47 pmol/mg in prostate tissue (P = 0.005). No significant changes in the DNA oxidation product 8-oxo-deoxyguanosine and the lipid peroxidation product malondialdehyde were observed in prostate tissue and plasma, respectively, as a result of lycopene administration.

Epidemiological evidence associating the decreased risk of prostate cancer with frequent consumption of tomato products inspired us to conduct a small intervention trial among patients diagnosed with prostate adenocarcinoma. Tomato sauce pasta was consumed daily for 3 weeks before their scheduled prostatectomy, and biomarkers of tomato intake, prostate cancer progression and oxidative DNA damage were followed in blood and the available prostate tissue. The whole food intervention was so well accepted by the subjects that the blood lycopene (the primary carotenoid in tomatoes responsible for their red color) doubled and the prostate lycopene concentration tripled during this short period. Oxidative DNA damage in leukocytes and prostate tissues was significantly diminished, the latter mainly in the tumor cell nuclei, possibly due to the antioxidant properties of lycopene. Quite surprising was the decrease in blood prostate-specific antigen, which was explained by the increase in apoptotic death of prostate cells, especially in carcinoma regions. Prostate cancer cell cultures (LNCaP) were also sensitive to lycopene in growth medium, which caused an increased apoptosis and arrested the cell cycle. A possible explanation of these promising results may reside in lycopene effects on the genes governing the androgen stimulation of prostate growth, cytokines and on the enzymes producing reactive oxygen species, all of which were recently discovered by nutrigenomic techniques. Other phytochemicals in tomato may act in synergy with lycopene to potentiate protective effects and to help in the maintenance of prostate health.

Animal and epidemiological studies point to a cancer preventive/therapeutic role for tomato products and its antioxidant, lycopene. It is hypothesized that lycopene will behave as an antioxidant at low concentrations and as a prooxidant at high concentrations in LNCaP human prostate cancer cell culture systems. We characterized the antioxidant, and prooxidant effects of a hexane extract of tomato paste (TP) and water solubilized lycopene at different concentrations using a prostate cancer cell line. Placebo (5% triglyceride, Roche Inc.) was used as a control. After 6, 24 hr and 48 hr incubation, LNCaP cells were harvested and used for each measurement. Cellular proliferation was determined using the MTT colorimetric assay. Lycopene and TP hexane extract inhibited cell growth in a dose-dependent (0.1-50 microM lycopene) manner and growth inhibition was 55% and 35% at 1 microM lycopene and TP hexane extract, respectively after 48 hr incubation. The levels of 8-hydroxydeoxyguanosine/deoxyguanosine (an oxidative DNA damage product) was significantly increased starting at 5 microM lycopene from both TP hexane extract and pure lycopene after 24 and 48 hr incubation with no protection at the lower concentrations. Malondialdehyde formation (a lipid peroxidation product measured by HPLC separation of the MDA-TBA adduct) was significantly reduced at low concentrations (0.1-1 microM) of lycopene in all treatments. Clinically relevant concentrations of lycopene and the tomato fraction containing lycopene significantly reduced LNCaP cancer cell survival which can only be partially explained by increased DNA damage at high lycopene concentrations (> 5 microM). Low concentrations of lycopene acted as a lipid antioxidant but did not protect DNA.

Lycopene is one of the major carotenoids and is found almost exclusively in tomatoes and tomato products. Since tomato consumption is associated with decreased risk of prostate cancer, characterizing the effects of lycopene on cell growth or survival, cell cycle progression, and apoptosis in LCNaP human prostate cancer cells might elucidate the mechanisms of actions of lycopene. To discover the possible anti-cancer mechanism of lycopene, water-soluble lycopene was used, and cell cycle arrest and apoptosis were measured. Placebo formulation at each lycopene dose at 0.1, 1, and 5 microM was used as a control. After 6, 24, and 48 hours of incubation, cells were harvested and measured for cell viability. Lycopene at 1 microM inhibited cell growth by 31%, compared with its placebo formulation after a 48-hour incubation. Lycopene at 5 microM increased the number of cells in the G(2)/M phase of the cell cycle from 13% to 28% and decreased S-phase cells from 45% to 29%, while no shifts in cell cycle were detected in placebo-treated groups. Apoptosis was observed at the 5 microM lycopene formulation at the late stages during the 24- and 48-hour treatments. Lycopene, therefore, deserves further study as a potential chemopreventive/chemotherapeutic agent.

This report details the findings of a single-dose Phase I pharmacokinetic and toxicity study of a food-based formulation of lycopene in healthy adult male subjects. Five dosing groups (n = 5 per group) were sequentially treated with increasing doses of lycopene ranging from 10 to 120 mg. Blood samples were collected for a total of 28 days (672 h) after administration of single doses of lycopene. The mean time (t(max)) to reach maximum total lycopene concentration (C(max)) ranged from 15.6 to 32.6 h. The C(max) for total lycopene ranged between 4.03 and 11.27 microg/dl (0.075-0.210 microm). Mean AUC(0-96) and elimination half-life for total lycopene ranged from 214 to 655 microg h/dl (3.986-12.201 micromol h/l) and 28.1 and 61.6 h, respectively. The changes observed in lycopene exposure parameters (e.g., C(max) and AUC(0-96)) were not proportional to increments in dose, with larger increases observed at the lowest end of the dosing range (10-30 mg). Chylomicron lycopene was measured during the first 12 h with the differences observed among the dosing groups not reaching statistical significance. These findings may reflect a process of absorption that is saturable at very low dosing levels or may be explained by the large interindividual variability in attained lycopene concentrations that were observed within each dosing group. Pharmacokinetic parameters for trans- and cis-lycopene isomers were calculated and are reported here. The formulation was well tolerated with minimal side effects, which were mainly of gastrointestinal nature and of very low grade.

A physiological pharmacokinetic model was developed to describe the disposition of lycopene, delivered as a tomato beverage formulation in five graded doses (10, 30, 60, 90, or 120 mg), for a phase I study in healthy male subjects (five per dose). Blood was collected before dose administration (0 h) and at scheduled intervals until 672 h. Serum concentrations of carotenoids and vitamins were measured by high performance liquid chromatography analysis. The model was comprised of seven compartments: gastrointestinal tract, enterocytes, chylomicrons, plasma lipoproteins, fast-turnover liver, slow-turnover tissues, and a delay compartment before the enterocytes. As predicted, the percent absorption at the 10 mg dose (33.9 +/- 8.1%) was significantly greater than at the higher doses; however, the amount of lycopene absorbed (mg) was not statistically different (mean: 4.69 +/- 0.55 mg) between doses, suggesting a possible saturation of absorptive mechanisms. The slow-turnover tissue compartment served as a slow-depleting reservoir for lycopene, and the liver represented the fast-turnover pool. Independent of dose, 80% of the subjects absorbed less than 6 mg of lycopene. This may have important implications for planning clinical trials with pharmacological doses of lycopene in cancer control and prevention if absorption saturation occurs at levels that are already being consumed in the population.

Consumption of lycopene, the predominant carotenoid in tomatoes and tomato products, is associated with reduced prostate cancer risk. The purpose of this study was to measure the pharmacokinetics and tissue distribution of lycopene after oral administration to male dogs. After single doses of 10, 30 and 50 mg/kg body weight (BW) lycopene to 2 dogs/dose, the mean half-life was 36 h and the plasma systemic exposure levels (AUC(0-)( infinity ), area under the curve) after the 30 and 50 mg/kg BW doses were similar. In a repeat dose study, 30 mg/(kg BW. d) administered orally to six dogs for 28 d resulted in steady-state plasma concentrations between 785 and 997 nmol/L lycopene. Apparent clearance, volume of distribution and apparent elimination half-life were 2.29 L/(h. kg), 96 L/kg and 30.5 h, respectively. Dogs were killed 1 or 5 d after the last dose and 23 tissues were collected for lycopene analysis. Lycopene concentrations were highest in liver, adrenals, spleen, lymph nodes and intestinal tissues. Liver lycopene concentrations were 66 and 91 nmol/g 1 and 5 d after cessation of treatment, respectively. Prostate lycopene concentrations were < 0.2 nmol/g both 1 and 5 d after dosing ceased (<0.4% of liver concentrations). Although 70% trans-lycopene was used in the dosing material, most of the lycopene identified in plasma and tissues was cis-lycopene.

Serum concentrations of several nutrients were measured in 12 captive wild felid species including caracal (Felis caracal), cheetah (Acinonyx jubatus), cougar (Felis concolor), fishing cat (Felis viverrinus), leopard (Panthera pardus), lion (Panthera leo), ocelot (Felis pardalis), pallas cat (Felis manul), sand cat (Felis margarita), serval (Felis serval), snow leopard (Panthera uncia) and tiger (Panthera tigris). Diet information was collected for these animals from each participating zoo (Brookfield Zoo, Fort Worth Zoo, Lincoln Park Zoological Gardens and North Carolina Zoological Park). The nutritional composition of the diets at each institution met the probable dietary requirements for each species except for the pallas cat. Blood samples were collected from each animal (n = 69) and analyzed for lipids (total cholesterol, triacylglycerides, HDL cholesterol and LDL cholesterol), vitamin D metabolites [25-hydroxycholecalciferol (25(OH)D) and 1,25-dihydroxycholecalciferol (1,25(OH)(2)D)], vitamin A (retinol, retinyl stearate and retinyl palmitate), vitamin E (alpha- and gamma-tocopherol) and selected carotenoids. Species differences were found for all except triacylglycerides and 1,25(OH)(2)D. Genus differences were found for retinol, retinyl palmitate, retinyl stearate, gamma-tocopherol and beta-carotene. Circulating nutrient concentrations for many of the species in this study have not been reported previously and most have not been compared with the animals' dietary intakes. The large number of animals analyzed provides a substantial base for comparing the serum nutrient concentrations of healthy animals, for both wild and captive exotic species.

Lycopene, a natural antioxidant found predominantly in tomato products, is attracting attention as a cancer prevention agent. Serum and dietary lycopene levels have been found to be inversely related to the incidence of several types of cancer, including prostate cancer. Although the antioxidant properties of lycopene are thought to be primarily responsible for its apparent beneficial effects, other mechanisms may also be involved. We outline the possible mechanisms of action of lycopene and review the current findings of in vitro and in vivo studies in cancer prevention and to some extent treatment. We examine the epidemiologic evidence regarding consumption of tomato and tomato products with the risk of cancer at various sites. Data suggest lycopene may account for or contribute to chemoprevention, but this hypothesis requires further study. Numerous other potentially beneficial compounds are present in tomatoes and complex interactions among multiple components may contribute to the anticancer properties of tomatoes.

Several epidemiological studies suggest a lower incidence of prostate cancer in men who routinely consume tomato products. Tomatoes are the primary dietary source of lycopene, which is among the most potent antioxidants of the carotenoids. Men with clinical stage T1 or T2 prostate adenocarcinoma were recruited (n = 32) and consumed tomato sauce based pasta dishes for 3 weeks (equivalent to 30 mg of lycopene per day) before radical prostectomy. Prostate tissue from needle biopsy just before intervention and prostectomy after supplementation from a subset of 11 subjects was evaluated for both total lycopene and lycopene geometrical isomer ratios. A gradient HPLC system using a C(18) column with UV-vis absorbance detection was used to measure total lycopene. Because the absorbance detector was insufficiently sensitive, HPLC with a C(30) column and positive ion atmospheric pressure chemical ionization mass spectrometric (LC-MS) detection was developed as a new assay to measure the ratio of lycopene cis/trans isomers in these samples. The limit of detection of the LC-MS method was determined to be 0.93 pmol of lycopene on-column, and a linear response was obtained over 3 orders of magnitude. Total lycopene in serum increased 2.0-fold from 35.6 to 69.9 microg/dL (from 0.664 to 1.30 microM) as a result of dietary supplementation with tomato sauce, whereas total lycopene in prostate tissue increased 3.0-fold from 0.196 to 0.582 ng/mg of tissue (from 0.365 to 1.09 pmol/mg). all-trans-Lycopene and at least 14 cis-isomer peaks were detected in prostate tissue and serum. The mean proportion of all-trans-lycopene in prostate tissue was approximately 12.4% of total lycopene before supplementation but increased to 22.7% after dietary intervention with tomato sauce. In serum there was only a 2.8% but statistically significant increase in the proportion of all-trans-lycopene after intervention. These results indicate that short-term supplementation with tomato sauce containing primarily all-trans-lycopene (83% of total lycopene) results in substantial increases in total lycopene in serum and prostate and a substantial increase in all-trans-lycopene in prostate but relatively less in serum.

Accumulation of carotenoids varies greatly among animal species and is not fully characterized. Circulating carotenoid concentration data in captive wild animals are limited and may be useful for their management. Serum carotenoid concentrations and dietary intakes were surveyed and the extent of accumulation categorized for 76 species of captive wild animals at Brookfield Zoo. Blood samples were obtained opportunistically from 275 individual animals immobilized for a variety of reasons; serum was analyzed for alpha- and beta-carotene, lutein + zeaxanthin, lycopene, beta-cryptoxanthin and canthaxanthin. Total carotenoid content of diets was calculated from tables and chemical analyses of commonly consumed dietary components. Diets were categorized as low, moderate or high in carotenoid content as were total serum carotenoid concentrations. Animals were classified as unknown, high, moderate or low (non-) accumulators of dietary cartenoids. Nonaccumulators had total serum carotenoid concentrations of 0-101 nmol/L, whereas accumulators had concentrations that ranged widely, from 225 to 35,351 nmol/L. Primates were uniquely distinguished by the widest range of type and concentration of carotenoids in their sera. Most were classified as high to moderate accumulators. Felids had high accumulation of beta-carotene regardless of dietary intake, whereas a wide range of exotic birds accumulated only the xanthophylls, lutein + zeaxanthin, canthaxanthin or cryptoxanthin. The exotic ungulates, with the exception of the bovids, had negligible or nondetectable carotenoid serum concentrations despite moderate intakes. Bovids accumulated only beta-carotene despite moderately high lutein + zeaxanthin intakes. Wild captive species demonstrated a wide variety of carotenoid accumulation patterns, which could be exploited to answer remaining questions concerning carotenoid metabolism and function. [ABSTRACT FROM AUTHOR]