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Correlation of lycopene measured by HPLC with the L, a, b color readings of a hydroponic tomato and the relationship of maturity with color and lycopene content.

Tomatoes (Lycopersicon esculentum cv. Laura) were separated, according to the ripening stage, by a sensory panel into seven groups, and color was measured on the tomato surface with a Minolta Chroma meter. The L, a, b, hue, chroma, and lycopene content were plotted against the maturity stages of the tomatoes, and several good correlations were found. The a/b ratio and the lycopene content were the parameters that allowed six of seven maturity groups in the tomato to be statistically distinguished. The lycopene content, measured by HPLC, was also correlated with the color measurements, and the a, a/b, and (a/b)(2) color factors produced the best regressions. An estimation of the lycopene content in tomatoes can be achieved by using a portable chroma meter, with a possible field usage application. Equations to calculate the lycopene content of tomatoes based on the color readings are reported.

Carotenoids↗

Lycopene II--effect on osteoblasts: the carotenoid lycopene stimulates cell proliferation and alkaline phosphatase activity of SaOS-2 cells.

We explored the possibility that lycopene, a carotenoid that is abundant in tomatoes, has effects on proliferation and differentiation of osteoblasts, the cells responsible for bone formation. Human osteoblast-like osteosarcoma SaOS-2 cells were cultured for 24 hours, after which varying doses of a water-dispersible microemulsion preparation of lycopene or vehicle of the same dilution were added. The cells were further cultured for 24 to 144 hours, and then the cell numbers were counted. Lycopene at 10(-6) and 10(-5) M had significant stimulatory effects on cell numbers, compared with the corresponding vehicle treatment, at all time points from 24 to 144 hours. The effects of lycopene on activity of the differentiation marker alkaline phosphatase activity in the absence or presence of dexamethasone were shown to be dependent on the stage of cell differentiation. This is the first report on the effects of lycopene on osteoblasts of human origin; the results may have important applications in the prevention of osteoporosis.

Alkaline Phosphatase↗

The biodistribution of a single oral dose of [14C]-lycopene in rats prefed either a control or lycopene-enriched diet.

Lycopene (lyc) has emerged as a primary candidate for dietary interventions of prostate cancer; however, research regarding its absorption, tissue distribution, and metabolism is limited. Previously, we evaluated the biodistribution (3-168 h) of a single oral dose of 14C-lyc in rats prefed lyc for 30 d. The liver was the primary depot for lyc, and the 14C and 14C-polar products appeared in tissues as early as 3 h after dosing. In the current study, F344 rats (n = 48) were randomly assigned to 1 of 4 groups prefed either a control or lyc-enriched diet (0.25 g lyc/kg diet) for 30 d and killed at 5 or 24 h after receiving a single oral dose of 14C-lyc. The percentage of the 14C dose absorbed at 24 h was lower (5.5 +/- 0.5%) in lyc-prefed (LP) rats than in control-prefed (CP) rats (6.9 +/- 0.4%, P < 0.04). Hepatic total 14C and 14C-lyc in CP rats was greater than in LP rats at 24 h (P < 0.005). A portion of 14C was delivered to extrahepatic tissues as early as 5 h, irrespective of diet. Of the tissues analyzed, an increase in the percentage in 14C-polar products occurred between 5 and 24 h only in the prostate and seminal vesicles, suggesting increased accumulation of 14C-polar products in these tissues, irrespective of prior dietary treatment. These data suggest that lyc absorption, tissue uptake, and catabolism were affected by prefeeding and that lyc can be partially taken up by extrahepatic tissues from the postprandial triglyceride-rich fraction.

Absorption↗

Lycopene in tomatoes: chemical and physical properties affected by food processing.

Lycopene is the pigment principally responsible for the characteristic deep-red color of ripe tomato fruits and tomato products. It has attracted attention due to its biological and physicochemical properties, especially related to its effects as a natural antioxidant. Although it has no provitamin A activity, lycopene does exhibit a physical quenching rate constant with singlet oxygen almost twice as high as that of beta-carotene. This makes its presence in the diet of considerable interest. Increasing clinical evidence supports the role of lycopene as a micronutrient with important health benefits, because it appears to provide protection against a broad range of epithelial cancers. Tomatoes and related tomato products are the major source of lycopene compounds, and are also considered an important source of carotenoids in the human diet. Undesirable degradation of lycopene not only affects the sensory quality of the final products, but also the health benefit of tomato-based foods for the human body. Lycopene in fresh tomato fruits occurs essentially in the all-trans configuration. The main causes of tomato lycopene degradation during processing are isomerization and oxidation. Isomerization converts all-trans isomers to cis-isomers due to additional energy input and results in an unstable, energy-rich station. Determination of the degree of lycopene isomerization during processing would provide a measure of the potential health benefits of tomato-based foods. Thermal processing (bleaching, retorting, and freezing processes) generally cause some loss of lycopene in tomato-based foods. Heat induces isomerization of the all-trans to cis forms. The cis-isomers increase with temperature and processing time. In general, dehydrated and powdered tomatoes have poor lycopene stability unless carefully processed and promptly placed in a hermetically sealed and inert atmosphere for storage. A significant increase in the cis-isomers with a simultaneous decrease in the all-trans isomers can be observed in the dehydrated tomato samples using the different dehydration methods. Frozen foods and heat-sterilized foods exhibit excellent lycopene stability throughout their normal temperature storage shelf life. Lycopene bioavailability (absorption) can be influenced by many factors. The bioavailability of cis-isomers in food is higher than that of all-trans isomers. Lycopene bioavailability in processed tomato products is higher than in unprocessed fresh tomatoes. The composition and structure of the food also have an impact on the bioavailability of lycopene and may affect the release of lycopene from the tomato tissue matrix. Food processing may improve lycopene bioavailability by breaking down cell walls, which weakens the bonding forces between lycopene and tissue matrix, thus making lycopene more accessible and enhancing the cis-isomerization. More information on lycopene bioavailability, however, is needed. The pharmacokinetic properties of lycopene remain particularly poorly understood. Further research on the bioavalability, pharmacology, biochemistry, and physiology must be done to reveal the mechanism of lycopene in human diet, and the in vivo metabolism of lycopene. Consumer demand for healthy food products provides an opportunity to develop lycopene-rich food as new functional foods, as well as food-grade and pharmaceutical-grade lycopene as new nutraceutical products. An industrial scale, environmentally friendly lycopene extraction and purification procedure with minimal loss of bioactivities is highly desirable for the foods, feed, cosmetic, and pharmaceutical industries. High-quality lycopene products that meet food safety regulations will offer potential benefits to the food industry.

Antioxidants↗

Lycopene in tomatoes: chemical and physical properties affected by food processing.

Lycopene is the pigment principally responsible for the characteristic deep-red color of ripe tomato fruits and tomato products. It has attracted attention due to its biological and physicochemical properties, especially related to its effects as a natural antioxidant. Although it has no provitamin A activity, lycopene does exhibit a physical quenching rate constant with singlet oxygen almost twice as high as that of beta-carotene. This makes its presence in the diet of considerable interest. Increasing clinical evidence supports the role of lycopene as a micronutrient with important health benefits, because it appears to provide protection against a broad range of epithelial cancers. Tomatoes and related tomato products are the major source of lycopene compounds, and are also considered an important source of carotenoids in the human diet. Undesirable degradation of lycopene not only affects the sensory quality of the final products, but also the health benefit of tomato-based foods for the human body. Lycopene in fresh tomato fruits occurs essentially in the all-trans configuration. The main causes of tomato lycopene degradation during processing are isomerization and oxidation. Isomerization converts all-trans isomers to cis-isomers due to additional energy input and results in an unstable, energy-rich station. Determination of the degree of lycopene isomerization during processing would provide a measure of the potential health benefits of tomato-based foods. Thermal processing (bleaching, retorting, and freezing processes) generally cause some loss of lycopene in tomato-based foods. Heat induces isomerization of the all-trans to cis forms. The cis-isomers increase with temperature and processing time. In general, dehydrated and powdered tomatoes have poor lycopene stability unless carefully processed and promptly placed in a hermetically sealed and inert atmosphere for storage. A significant increase in the cis-isomers with a simultaneous decrease in the all-trans isomers can be observed in the dehydrated tomato samples using the different dehydration methods. Frozen foods and heat-sterilized foods exhibit excellent lycopene stability throughout their normal temperature storage shelf life. Lycopene bioavailability (absorption) can be influenced by many factors. The bioavailability of cis-isomers in food is higher than that of all-trans isomers. Lycopene bioavailability in processed tomato products is higher than in unprocessed fresh tomatoes. The composition and structure of the food also have an impact on the bioavailability of lycopene and may affect the release of lycopene from the tomato tissue matrix. Food processing may improve lycopene bioavailability by breaking down cell walls, which weakens the bonding forces between lycopene and tissue matrix, thus making lycopene more accessible and enhancing the cis-isomerization. More information on lycopene bioavailability, however, is needed. The pharmacokinetic properties of lycopene remain particularly poorly understood. Further research on the bioavalability, pharmacology, biochemistry, and physiology must be done to reveal the mechanism of lycopene in human diet, and the in vivo metabolism of lycopene. Consumer demand for healthy food products provides an opportunity to develop lycopene-rich food as new functional foods, as well as food-grade and pharmaceutical-grade lycopene as new nutraceutical products. An industrial scale, environmentally friendly lycopene extraction and purification procedure with minimal loss of bioactivities is highly desirable for the foods, feed, cosmetic, and pharmaceutical industries. High-quality lycopene products that meet food safety regulations will offer potential benefits to the food industry.

Anticarcinogenic Agents↗

A review of animal model studies of tomato carotenoids, lycopene, and cancer chemoprevention.

There are relatively few reports on the cancer chemopreventive effects of lycopene or tomato carotenoids in animal models. The majority, but not all, of these studies indicate a protective effect. Inhibitory effects were reported in two studies using aberrant crypt foci, an intermediate lesion leading to colon cancer, as an end point and in two mammary tumor studies, one using the dimethylbenz(a)anthracene model, and the other the spontaneous mouse model. Inhibitory effects were also reported in mouse lung and rat hepatocarcinoma and bladder cancer models. However, a report from the author's laboratory found no effect in the N-nitrosomethylurea-induced mammary tumor model when crystalline lycopene or a lycopene-rich tomato carotenoid oleoresin was administered in the diet. Unfortunately, because of differences in routes of administration (gavage, intraperitoneal injection, intra-rectal instillation, drinking water, and diet supplementation), species and strain differences, form of lycopene (pure crystalline, beadlet, mixed carotenoid suspension), varying diets (grain-based, casein based) and dose ranges (0.5-500 ppm), no two studies are comparable. It is clear that the majority of ingested lycopene is excreted in the feces and that 1000-fold more lycopene is absorbed and stored in the liver than accumulates in other target organs. Nonetheless, physiologically significant (nanogram) levels of lycopene are assimilated by key organs such as breast, prostate, lung, and colon, and there is a rough dose-response relationship between lycopene intake and blood levels. Pure lycopene was absorbed less efficiently than the lycopene-rich tomato carotenoid oleoresin and blood levels of lycopene in rats fed a grain-based diet were consistently lower than those in rats fed lycopene in a casein-based diet. The latter suggests that the matrix in which lycopene is incorporated is an important determinant of lycopene uptake. A number of issues remain to be resolved before any definitive conclusions can be drawn concerning the anticancer effects of lycopene. These include the following: the optimal dose and form of lycopene, interactions among lycopene and other carotenoids and fat soluble vitamins such as vitamin E and D, the role of dietary fat in regulating lycopene uptake and disposition, organ and tissue specificity, and the problem of extrapolation from rodent models to human populations.

Animals↗

Bioavailability of synthetic and biosynthetic deuterated lycopene in humans.

Current knowledge of the bioavailability of lycopene in humans is limited due to the inability to distinguish newly administered lycopene from the body reserves of lycopene. A quantitative method to assess the absorption and relative bioavailability of newly absorbed synthetic or natural lycopene was developed using two deuterated lycopene sources, in conjunction with an advanced LC/APCI-MS (liquid chromatography/atmospheric pressure chemical ionization-mass spectrometry) to analyze newly absorbed lycopene in blood samples of study subjects. Two subjects (1 male and 1 female) consumed hydroponically grown tomatoes containing deuterium-enriched lycopene (80-84 g wet weight tomato containing 16.3 and 17.4 micromol lycopene, respectively) and two subjects (1 male, and 1 female) consumed 11 micromol synthetic (2)H(10) lycopene in 6 g of corn oil. Tomatoes were steamed and pureed. The doses were given together with a liquid formulated drink with 25% energy from fat. Our results showed that up to 34 days after taking an oral (2)H(10) lycopene dose (synthetic or from tomato) with a liquid formula drink, the area under the curve of the average serum percent enrichment response of synthetic lycopene reached 33.9 (+/-1.7) nmol-day/micromol lycopene in the dose, whereas that of lycopene from the tomato dose was 11.8 (+/-0.3) nmol-day/mumol lycopene in the dose. Our study provides evidence that the absorption of physiological levels of lycopene in intrinsically labeled tomatoes can be studied in humans. From these preliminary investigations, we find that the bioavailability of synthetic lycopene in oil appears to be about three times higher than that of lycopene from steamed and pureed tomatoes.

Biological Availability↗

Tomato consumption increases lycopene isomer concentrations in breast milk and plasma of lactating women.

OBJECTIVE: To compare plasma and milk lycopene concentrations and the changes in lycopene isomer patterns in lactating women before and after a 3-day dietary intervention with fresh or processed tomato products. DESIGN: Randomized prospective trial. SUBJECTS: 24 lactating women, 4 to 12 weeks postpartum, aged 22 to 39 years. INTERVENTION: Subjects initially consumed a low-lycopene diet for 7 days (washout period) and then were randomly assigned to one of 3 dietary groups (n=8 per group) without any other sources of lycopene: control (low-lycopene), fresh tomatoes, or processed tomato sauce. Subjects in each of the tomato groups consumed approximately 50 mg total lycopene over 3 days. OUTCOME MEASURES: Before and after dietary intervention, plasma and breast milk samples were obtained for high-performance liquid chromotography analysis of lycopene and its geometric isomers (all-trans, 5-cis, all other cis, and total lycopene). STATISTICAL ANALYSIS: Descriptive statistics, analysis of variance to test for differences among intervention groups, and Spearman's correlation coefficients to test for blood-milk relationships. RESULTS: Plasma total lycopene and lycopene isomer concentrations increased in the fresh and processed tomato group but not in the low-lycopene control group during the study. Milk total and cis- and trans-lycopene concentrations (unadjusted for fat) increased in the processed tomato group but did not change in the fresh tomato group. In the control group, milk total and trans-lycopene decreased. Milk total lycopene concentrations were not significantly different from baseline in any group when adjusted for fat content of milk. APPLICATIONS: The results of this study indicate that consumption of a "standard size portion" of tomato products increases plasma and milk lycopene concentrations in lactating women and, therefore, could increase the lycopene status of nursing infants. For dietary recommendations during lactation, the results suggest that consumption of tomato sauce increases milk lycopene concentrations more effectively than consumption of fresh tomatoes.

Adult↗

Liquid chromatography-mass spectrometry of cis- and all-trans-lycopene in human serum and prostate tissue after dietary supplementation with tomato sauce.

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.

Adenocarcinoma↗

cis-trans lycopene isomers, carotenoids, and retinol in the human prostate.

An evaluation of the Health Professionals Follow-Up Study has detected a lower prostate cancer risk associated with the greater consumption of tomatoes and related food products. Tomatoes are the primary dietary source of lycopene, a non-provitamin A carotenoid with potent antioxidant activity. Our goal was to define the concentrations of lycopene, other carotenoids, and retinol in paired benign and malignant prostate tissue from 25 men, ages 53 to 74, undergoing prostatectomy for localized prostate cancer. The concentrations of specific carotenoids in the benign and malignant prostate tissue from the same subject are highly correlated. Lycopene and all-trans beta-carotene are the predominant carotenoids observed, with means +/- SE of 0.80 +/- 0.08 nmol/g and 0.54 +/- 0.09, respectively. Lycopene concentrations range from 0 to 2.58 nmol/g, and all-trans beta-carotene concentrations range from 0.09 to 1.70 nmol/g. The 9-cis beta-carotene isomer, alpha-carotene, lutein, alpha-cryptoxanthin, zeaxanthin, and beta-cryptoxanthin are consistently detectable in prostate tissue. No significant correlations between the concentration of lycopene and the concentrations of any other carotenoid are observed. In contrast, strong correlations between prostate beta-carotene and alpha-carotene are noted (correlation coefficient, 0.88; P < 0.0001), as are correlations between several other carotenoid pairs, which reflects their similar dietary origins. Mean vitamin A concentration in the prostate is 1.52 nmol/g, with a range of 0.71 to 3.30 nmol/g. We further evaluated tomato-based food products, serum, and prostate tissue for the presence of geometric lycopene isomers using high-performance liquid chromatography with a polymeric C30 reversed phase column. All-trans lycopene accounts for 79 to 91% and cis lycopene isomers for 9 to 21% of total lycopene in tomatoes, tomato paste, and tomato soup. Lycopene concentrations in the serum of men range between 0.60 and 1.9 nmol/ml, with 27 to 42% all-trans lycopene and 58 to 73% cis-isomers distributed among 12 to 13 peaks, depending upon their chromatographic resolution. In striking contrast with foods, all-trans lycopene accounts for only 12 to 21% and cis isomers for 79 to 88% of total lycopene in benign or malignant prostate tissues. cis Isomers of lycopene within the prostate are distributed among 14 to 18 peaks. We conclude that a diverse array of carotenoids are found in the human prostate with significant intra-individual variation. The presence of lycopene in the prostate at concentrations that are biologically active in laboratory studies supports the hypothesis that lycopene may have direct effects within the prostate and contribute to the reduced prostate cancer risk associated with the reduced prostate cancer risk associated with the consumption of tomato-based foods. The future identification and characterization of geometric lycopene isomers may lead to the development of novel agents for chemoprevention studies.

Aged↗

Lycopene in serum, skin and adipose tissues after tomato-oleoresin supplementation in patients undergoing haemorrhoidectomy or peri-anal fistulotomy.

Lycopene, the main carotenoid found in tomatoes and tomato-based products, has been reported to be protective against several types of cancer. Assessment of changes in plasma concentration of carotenoids following ingestion of lycopene-rich food sources does not necessarily predict changes in lycopene concentration or distribution of its isomers in other body tissues. Our aim was to determine the relationship between concentrations of lycopene and other tomato carotenoids in human serum and body tissues after tomato-oleoresin supplementation. Tomato lycopene oleoresin (30 mg/d) or a placebo was administered for 1 to 7 weeks to seventy-five volunteers undergoing elective haemorrhoidectomy or peri-anal fistulotomy. Carotenoid concentration and isomer distribution in blood and in the surgically removed skin and adipose tissues was measured by HPLC. The serum concentration of lycopene increased after supplementation from 0.26 (SD 0.12) to 0.52 (SD 0.25) micromol/l (n 35; P<0.0001). In the placebo group (n 40), lycopene serum concentration did not change significantly. Serum lycopene concentration after treatment was 2.2-fold greater in the lycopene group than in the placebo group, a slightly higher ratio than that found in skin and adipose tissue (1.6- and 1.4-fold higher than the placebo, respectively). A significant correlation between serum and tissue concentrations was found for both beta-carotene and lycopene in the placebo group, whereas in the lycopene-supplemented group the correlation between serum and tissues remained the same for beta-carotene but for lycopene was weak. Lycopene supplementation did not significantly change the proportion of all-trans v. cis isomers in the serum and tissues, despite the fact that more than 90 % of the supplemented lycopene was in the all-trans form. These results show that tomato-oleoresin supplementation increases lycopene concentrations in serum and in adipose tissue and skin. The ability to increase lycopene levels in tissues is one of the prerequisites for using it as a food supplement with health benefits.

Adipose Tissue↗

A food-based formulation provides lycopene with the same bioavailability to humans as that from tomato paste.

Lycopene from fresh and unprocessed tomatoes is poorly absorbed by humans. Absorption of lycopene is higher from processed foods such as tomato paste and tomato juice heated in oil. The aim of the present study was to develop a food-grade lycopene formulation that is bioavailable in humans. A formulation of lycopene named "lactolycopene" has been designed in which lycopene is entrapped with whey proteins. Healthy subjects (n = 33; 13 men and 20 women) participated and were allocated randomly to one of the three treatment groups. After a 3-wk deprivation of dietary lycopene, subjects ingested 25 mg lycopene/d for 8 wk from lactolycopene, tomato paste (positive control) or a placebo of whey proteins while consuming their self-selected diets. Plasma lycopene concentrations reached a maximum after 2 wk of supplementation in both lycopene-treated groups and then a plateau was maintained until the end of the treatment. Increases in plasma lycopene at wk 8 were not different between supplemented groups (mean +/- SEM): 0.58 +/- 0.13 micromol/L with lactolycopene and 0.47 plus minus 0.07 micromol/L with tomato paste, although they were different from the control (P < 0.001). Similar time-concentration curves of lycopene incorporation were observed in buccal mucosa cells. Although lycopene was present mainly as all-trans isomers (>90%) in both lycopene supplements, plasma lycopene enrichment consisted of 40% as all-trans and 60% as cis isomers. The precursor of lycopene, phytofluene, was better absorbed than lycopene itself. The lactolycopene formulation and tomato paste exhibited similar lycopene bioavailability in plasma and buccal mucosa cells in humans.

Adult↗

Changes in plasma and oral mucosal lycopene isomer concentrations in healthy adults consuming standard servings of processed tomato products.

The consumption of tomato products is associated with a reduced risk of cardiovascular disease and several cancers. It is hypothesized that lycopene, the major carotenoid in tomato products, may mediate this relationship. We designed a study to examine changes in plasma and buccal mucosal cell (BMC) lycopene concentrations in healthy adults consuming standard daily servings of processed tomato products: spaghetti sauce, tomato soup, or vegetable juice. Thirty-six healthy subjects consumed a lycopene-free diet for 2 wk and were then assigned to one of three (n = 12) intervention groups consuming daily, single servings of sauce (21 mg lycopene per (1/2) cup), soup (12 mg lycopene per 1 cup), or juice (17 mg lycopene per 8 oz) for 4 wk. Fasting blood and BMC samples were evaluated by high-performance liquid chromatography analysis for carotenoids and lycopene isomers. Total plasma lycopene concentrations (Mean +/- SEM) decreased from 1.05 +/- 0.07 to 0.54 +/- 0.05 micromol/l (49%, P < 0.0001) during the 2-wk washout period. Following intervention, plasma lycopene concentrations increased significantly for those consuming sauce, soup, and juice (compared with washout baseline) to 2.08 (192%, P < 0.0001), 0.91 (122%, P < 0.0001), and 0.99 (92%, P < 0.0001) micromol/l, respectively. Plasma isomer concentrations show a 61:39 ratio of cis:all-trans at the start of the study. During the 2-wk washout the decrease in plasma all-trans-lycopene was greater than that for pooled cis isomers (70:30 cis:trans ratio, P < 0.001). After 2 wk of dietary intervention isomer ratios returned to those observed at the start of the study. Total BMC lycopene concentrations did not significantly change during the brief washout. During the 4-wk intervention period, BMC total lycopene concentrations increased (P < 0.005) by 165, 42, and 48% nmol/mg protein for those consuming sauce, soup, and juice, respectively. This study demonstrates that plasma lycopene decreases by 50% after approximately 2 wk on a lycopene-free diet with a decrease in the ratio of all-trans compared with cis isomers. Single, daily servings of processed tomato products significantly increase blood and BMC lycopene for 2 wk. Additional studies of lycopene bioavailability, isomerization, metabolism, and bioactivity will provide greater insight into the potential health benefits suggested by epidemiological studies and laboratory investigations.

Adolescent↗

Synthetic and tomato-based lycopene have identical bioavailability in humans.

BACKGROUND: Bioavailability studies with lycopene have focused on natural sources. A synthetic source has recently become available. AIM OF THE STUDY: To determine the relative bioavailabilities of synthetic and tomato-based lycopene in free living volunteers in a single-blind, randomized, placebo-controlled, parallel trial. METHODS: Three groups (n=12/group) of healthy, normolipemic male and female subjects with a mean baseline serum lycopene concentration of 0.36 micro mol/L took a dose of 15 mg/day total lycopene for 28 days from either Lycovit 10% (beadlets, BASF, Germany) or Lyc-O-Mato (beads, LycoRed Natural Products, Israel) or a placebo (without lycopene) together with the main meal. The increase in serum lycopene from baseline was used as the parameter of bioavailability. RESULTS: Synthetic and tomato-lycopene resulted in significant increases above baseline of serum total lycopene by 0.58 and 0.57 micro mol/L, trans-lycopene by 0.34 and 0.41 micro mol/L, and total-cis-lycopene by 0.24 and 0.16 micro mol/L, whereas no significant changes were found in the placebo treatment. The mean serum total lycopene response to synthetic and natural lycopene was not significantly different. Neither lycopene source affected the other serum carotenoids, viz. alpha-carotene, beta-carotene, beta-cryptoxanthin, zeaxanthin and lutein. CONCLUSION: We conclude that synthetic and natural lycopene are equivalent sources of lycopene and that there is no interaction with other circulating carotenoids.

Adult↗

Lycopene enhances UVA-induced DNA damage and expression of heme oxygenase-1 in cultured mouse embryo fibroblasts.

BACKGROUND: It has been suggested that carotenoids including lycopene may reduce the risk of photodamage. However, carotenoids are unstable under light exposure and may produce prooxidative effects under certain circumstances. AIM OF THE STUDY: We examined whether lycopene inhibits ultraviolet A (UVA)-induced DNA damage and the expression of heme oxygenase-1 (HO-1). We hypothesized that the breakdown of lycopene by UVA irradiation, rather than intact lycopene itself, causes oxidative damage. METHODS: Mouse fibroblasts, C3H10T1/2 (C3H), were first enriched with 10 microM of lycopene in the dark for 2 h before exposure to UVA (22.5 KJ/m2). Then, DNA damage measured by the single-cell gel electrophoretic assay (comet assay) and the expression of HO-1 measured by western blotting were determined. In addition, we exposed lycopene powder to UVA (22.5 KJ/m2) to prepare pre-irradiated lycopene (ILP). Then, C3H cells were incubated with ILP for 2 h, and DNA damage and the expression of HO-1 also were determined. RESULTS: We found that lycopene enrichment did not cause damage to DNA in C3H cells not irradiated with UVA. However, lycopene enrichment strongly induced DNA damage when cells were irradiated with UVA (by ca. 2-fold as compared to control). In addition, lycopene enhanced UVA-induced HO-1 expression by ca. 2.5-fold. UVA irradiation led to a significant loss of lycopene that had been pre-incorporated into C3H cells. When cells were incubated with lycopene that had been pre-irradiated with UVA without subjecting the cells to further UVA irradiation, cellular DNA damage and expression of HO-1 were markedly increased, and these effects of irradiated lycopene were concentration-dependent. CONCLUSIONS: These results demonstrate that lycopene enhances UVA-induced oxidative stress in C3H cells, and they suggest that under UVA irradiation, lycopene may produce oxidative products that are responsible for the prooxidant effects.

Animals↗

Summary of safety studies conducted with synthetic lycopene.

Lycopene belongs to the group of natural carotenoids, which are found in many fruits and vegetables, but predominantly in tomatoes and tomato-based products. This manuscript summarizes the safety of synthetic lycopene as a water-dispersible beadlet formulation containing antioxidants and includes acute and subchronic safety studies, reproductive studies, genotoxicity studies, metabolic studies, and exploratory studies on the hepatic uptake of lycopene. Lycopene has a low order of acute toxicity and no significant toxicity has been observed in rats treated with lycopene beadlet formulations in the diet at doses of up to 500 mg/kg bw/day for 14 weeks or 1000 mg/kg bw/day for 4 weeks. No teratogenic effects were noted in a rat two-generation study (1000 ppm in the diet) or in a teratology study in rats with 1000 mg/kg bw/day lycopene as beadlet formulations. Lycopene accumulates in hepatocytes and to a lesser extent in spleen. In short-term studies with synthetic lycopene, as a beadlet formulation, and natural source lycopene, as tomato concentrate, the accumulation of lycopene in the liver and the presence of pigment deposits in the hepatocytes were similar and neither was associated with any histopathological changes. The pigment deposits in hepatocytes are no longer present after approximately 13 weeks of depletion, demonstrating reversibility for this effect. Unformulated pure crystalline lycopene and lycopene as a 10% beadlet formulation are not genotoxic as determined in a comprehensive battery of tests, however, improperly stored, unformulated crystalline lycopene can degrade to mutagenic products if exposed to light and air. Lycopene is commercially available only in formulated forms, containing antioxidants, which prevent the degradation of lycopene and other excipients that provide for water dispersibility. In the animal studies, there is a large margin of safety based on the repeated dose safety and reproductive/teratology studies in rodents. In humans, there is a very long history of use with respect to dietary exposure, and even in the case of very high exposures from dietary sources, there is no indication of any significant adverse effects.

Animals↗

Variations in plasma lycopene and specific isomers over time in a cohort of U.S. men.

Epidemiologic and laboratory studies suggest a possible role for tomato products, a rich source of the carotenoid lycopene, in the prevention of certain cancers and cardiovascular disease. Lycopene is consumed primarily as the all-trans-isomer, but the majority of lycopene in blood and tissue exists as a variety of cis-isomers. Specific isomers may be involved in different biological reactions, and patterns of isomers may provide insight into the risk or pathogenesis of disease processes. Total lycopene concentration and the concentrations of the cis- and trans-lycopene isomers were measured by HPLC in plasma samples taken 3-4 y apart from 144 mostly nonsmoking male participants in the Health Professionals Follow-up Study. Correlations between plasma concentrations determined 3-4 y apart ranged from 0.55 (all-trans-isomer) to 0.70 (cis-isomer 5 -cis) (P < 0.001). For total lycopene, the correlation was 0.63 (P < 0.001). Total cis-lycopene contributed approximately 67% of total lycopene (range 50-79%). At each time point, the various lycopene isomer concentrations were highly correlated with one another with Spearman correlation coefficients ranging from 0.90 to 0.99 (P < 0.001). Plasma concentrations of total lycopene and its most abundant isomers in samples taken 3-4 y apart were strongly correlated, indicating that dietary patterns and metabolic processes defining lycopene concentrations are stable over time. Because the patterns of lycopene isomers showed limited between-person variability, our results suggest that measuring specific lycopene isomers in epidemiologic studies may not provide additional information beyond that provided by total lycopene concentration. Single plasma samples quantitating plasma lycopene are a valid predictor of long-term exposure for epidemiologic studies.

Carotenoids↗