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Life Extension Magazine December 2012
Abstracts

Lycopene

Lycopene Content of Tomato Products: Its Stability, Bioavailability and In Vivo Antioxidant Properties.

Lycopene is a bioactive carotenoid present in many fruits and vegetables. Tomatoes constitute the major dietary source of lycopene. Recent evidence shows lycopene to be associated with several health benefits. However, very little information is available about the stability of lycopene and its bioavailability. Because tomatoes undergo extensive processing and storage before consumption, a study was conducted to evaluate the stability, isomeric form, bioavailability, and in vivo antioxidant properties of lycopene. Total lycopene and isomers were measured by spectrophotometry and high-performance liquid chromatography, respectively. Lycopene content of tomatoes remained unchanged during the multistep processing operations for the production of juice or paste and remained stable for up to 12 months of storage at ambient temperature. Moreover, subjecting tomato juice to cooking temperatures in the presence of corn oil resulted in the formation of the cis isomeric form, which was considered to be more bioavailable. Lycopene was absorbed readily from the dietary sources. Serum lipid and low-density lipoprotein oxidation were significantly reduced after the consumption of tomato products containing lycopene.

Med Food. 2001 Spring;4(1):9-15

Processed tomato products as a source of dietary lycopene: bioavailability and antioxidant properties.

Oxidative stress is one of the major contributors to increased risk of chronic diseases. A diet rich in tomatoes and tomato products containing lycopene, a carotenoid antioxidant, has been found to protect against these chronic diseases by mitigating oxidative damage. The study aim was to evaluate the effects of a long-term tomato-rich diet, consisting of various processed tomato products, on bioavailability and antioxidant properties of lycopene. Seventeen healthy human subjects (ten men, seven non-pregnant women) participated in the study. Following a two-week washout period during which subjects avoided foods containing lycopene, all subjects consumed test tomato products including tomato juice, tomato sauce, tomato paste, ketchup, spaghetti sauce, and ready-to-serve tomato soup providing 30 mg of lycopene a day for four weeks. At the end of treatment, serum lycopene level increased significantly (p <0.05), from 181.79 +/- 31.25 to 684.7 +/- 113.91 nmol/L. Similarly, total antioxidant potential increased significantly (p <0.05), from 2.26 +/- 0.015 to 2.38 +/- 0.17 mmol/L Trolox equivalent. Lipid and protein oxidation was reduced significantly (p <0.05). The results suggest that a tomato-rich diet containing different sources of lycopene can increase serum lycopene levels and reduce oxidative stress effectively.

Can J Diet Pract Res. 2004 Winter;65(4):161-5

Bioavailability and in vivo antioxidant properties of lycopene from tomato products and their possible role in the prevention of cancer.

Oxidative stress is recognized as one of the major contributors of increased risk of cancer. Many recent population studies have established a close link between dietary intake of tomatoes, a major source of the carotenoid antioxidant lycopene, and lowered risk of cancer. A study was conducted on 19 healthy human subjects to evaluate the uptake and in vivo antioxidant properties of lycopene, using a randomized, crossover design. Dietary lycopene was provided by tomato juice, spaghetti sauce, and tomato oleoresin for a period of one week each. Blood samples were collected at the end of each treatment. Serum lycopene was extracted and measured by high-performance liquid chromatography using an absorbance detector. Serum thiobarbituric acid-reactive substances, protein thiols, and 8-oxodeoxyguanosine contents of lymphocyte DNA were assayed to measure lipid, protein, and DNA oxidation. Lycopene was the major carotenoid present in the serum. Dietary supplementation of lycopene resulted in a significant increase in serum lycopene level and diminished amounts of serum thiobarbituric acid-reactive substances. Although not statistically significant, a tendency of lowered protein and DNA oxidation was observed. There was also indication that the lycopene levels increased in a dose-dependent manner in the case of spaghetti sauce and tomato oleoresin. These results indicate that lycopene is readily absorbed from tomato products and may act as an in vivo antioxidant. It may, therefore, play an important role in the prevention of cancer.

Nutr Cancer. 1998;31(3):199-203

Lycopene.

Lycopene is a carotenoid found in grapefruit, watermelons, and papaya in addition to tomatoes. It is obtained only through diet. Lycopene exhibits antioxidant and anticancer properties. Results from several epidemiologic studies suggest a strong association between high intake of lycopene-rich foods and reduced risk of several cancers, notably prostate cancer. However, few well designed clinical trials have been conducted, and data remain inconclusive. Because lycopene supplementation is associated with strong antioxidant effects, it has the potential to interfere with chemotherapy and radiation therapy. Cancer patients should use caution if considering an increase in their lycopene intake.

Oncology (Williston Park). 2010 Mar;24(3):296

Update on prostate cancer chemoprevention.

BACKGROUND: Prostate cancer is the most common type of cancer and the second leading cause of cancer-related deaths in American men. Its high rate of occurrence and long lead time to clinically significant disease make prostate cancer an ideal disease for pharmacologic or nutritional chemoprevention. METHODS: To identify the various chemoprevention strategies for prostate cancer, a MEDLINE search (from 1967-2005) and bibliographic search of the English-language literature were conducted. RESULTS: Epidemiologic and retrospective studies have assessed the effect of carotenoids (e.g., lycopene), vitamins, selenium, and nonsteroidal antiinflammatory drugs (NSAIDs) on the rate of occurrence of prostate cancer. The few published prospective trials evaluated prostate cancer as a secondary end point. Lycopene (as beta-carotene) and selenium supplementation have been associated with a reduced risk of prostate cancer in nested case-control studies, but only in subgroups of men with low baseline plasma lycopene (or beta-carotene) and selenium levels respectively. The Prostate Cancer Prevention Trial prospectively evaluated finasteride, a 5-alpha-reductase inhibitor, as chemoprevention. The results showed a 25% relative risk reduction in prostate cancer, albeit at an increased risk of invasive tumors. CONCLUSION: Data regarding lycopene, vitamin E, and selenium as chemoprevention for prostate cancer appear promising. Prospective trials such as the Selenium and Vitamin E Cancer Prevention Trial (SELECT) will clarify the role of these agents in prostate cancer prevention. The role of NSAIDs is unclear, and the long-term toxicity associated with NSAIDs may limit their usefulness. Although finasteride has decreased overall prostate cancer occurrence, the risk of invasive tumors may outweigh the benefit of this agent. The continuing Reduction by Dutasteride of Prostate Cancer Events (REDUCE) trial may help define a role for the 5-alpha-reductase inhibitors in cancer chemoprevention. At this time, nothing has been proven effective as chemoprevention against clinically significant prostate cancer.

Pharmacotherapy. 2006 Mar;26(3):353-9

Micronutrients attenuate progression of prostate cancer by elevating the endogenous inhibitor of angiogenesis, platelet factor-4.

BACKGROUND: Longstanding evidence implicates an inadequate diet as a key factor in the onset and progression of prostate cancer. The purpose herein was to discover, validate and characterize functional biomarkers of dietary supplementation capable of suppressing the course of prostate cancer in vivo. METHODS: The Lady transgenic mouse model that spontaneously develops prostate cancer received a diet supplemented with a micronutrient cocktail of vitamin E, selenium and lycopene ad libitum. A proteomic analysis was conducted to screen for serum biomarkers of this dietary supplementation. Candidate peptides were validated and identified by sequencing and analyzed for their presence within the prostates of all mice by immunohistochemistry. RESULTS: Dietary supplementation with the combined micronutrients significantly induced the expression of the megakaryocyte-specific inhibitor of angiogenesis, platelet factor-4 (P = 0.0025). This observation was made predominantly in mice lacking tumors and any manifestations associated with progressive disease beyond 37 weeks of life, at which time no survivors remained in the control group (P < 0.0001). While prostates of mice receiving standard chow were enlarged and burdened with poorly differentiated carcinoma, those of mice on the supplemented diet appeared normal. Immunohistochemical analysis revealed marked amplifications of both platelet binding and platelet factor-4 within the blood vessels of prostates from mice receiving micronutrients only. CONCLUSION: We present unprecedented data whereby these combined micronutrients effectively promotes tumor dormancy in early prostate cancer, following initiation mutations that may drive the angiogenesis-dependent response of the tumor, by inducing platelet factor-4 expression and concentrating it at the tumor endothelium through enhanced platelet binding.

BMC Cancer. 2010 Jun 4;10:258

Effects of lycopene supplementation in patients with localized prostate cancer.

Epidemiological studies have shown an inverse association between dietary intake of lycopene and prostate cancer risk. We conducted a clinical trial to investigate the biological and clinical effects of lycopene supplementation in patients with localized prostate cancer. Twenty-six men with newly diagnosed prostate cancer were randomly assigned to receive a tomato oleoresin extract containing 30 mg of lycopene (n = 15) or no supplementation (n = 11) for 3 weeks before radical prostatectomy. Biomarkers of cell proliferation and apoptosis were assessed by Western blot analysis in benign and cancerous prostate tissues. Oxidative stress was assessed by measuring the peripheral blood lymphocyte DNA oxidation product 5-hydroxymethyl-deoxyuridine (5-OH-mdU). Usual dietary intake of nutrients was assessed by a food frequency questionnaire at baseline. Prostatectomy specimens were evaluated for pathologic stage, Gleason score, volume of cancer, and extent of high-grade prostatic intraepithelial neoplasia. Plasma levels of lycopene, insulin-like growth factor-1, insulin-like growth factor binding protein-3, and prostate-specific antigen were measured at baseline and after 3 weeks of supplementation or observation. After intervention, subjects in the intervention group had smaller tumors (80% vs 45%, less than 4 ml), less involvement of surgical margins and/or extra-prostatic tissues with cancer (73% vs 18%, organ-confined disease), and less diffuse involvement of the prostate by high-grade prostatic intraepithelial neoplasia (33% vs 0%, focal involvement) compared with subjects in the control group. Mean plasma prostate-specific antigen levels were lower in the intervention group compared with the control group. This pilot study suggests that lycopene may have beneficial effects in prostate cancer. Larger clinical trials are warranted to investigate the potential preventive and/or therapeutic role of lycopene in prostate cancer.

Exp Biol Med (Maywood). 2002 Nov;227(10):881-5

Role of lycopene and tomato products in prostate health.

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.

Biochim Biophys Acta. 2005 May 30;1740(2):202-5

Gene signature of breast cancer cell lines treated with lycopene.

Among the micronutrients studied in relation between nutrition and cancer, lycopene appears to be a breast cancer preventive phytochemical candidate found in raw tomatoes and tomato-derived products. In order to investigate the responsiveness of breast cancer genes to lycopene and to better understand the molecular mechanisms underlying the effects of lycopene, we used an oligonucleotide microarray approach. Human breast cancer cell lines (MCF-7 and MDA-MB-231) and a fibrocystic breast cell line (MCF-10a) were either exposed or not exposed to 10 microM lycopene for 48 h. Microarrays comprising 202 genes were used to identify genes responsive to lycopene supplementation. Hierarchical clustering revealed a cell line-specific lycopene modulation of breast cells. Based on the observed results, lycopene seems to exert regulation on apoptosis, cell cycle and DNA repair mechanisms according to estrogen and retinoic acid receptor cell status.

Pharmacogenomics. 2006 Jul;7(5):663-72

Chemopreventive effect of lycopene alone or with melatonin against the genesis of oxidative stress and mammary tumors induced by 7,12 dimethyl(a)benzanthracene in sprague dawely female rats.

Breast cancer is the principle cause of death among women worldwide. In this study, we investigated the anti-tumor potential of lycopene (Lyco) alone or combined with melatonin (Lyco + Mel) for 120 days against a single oral dose of (50 mg/kg B.W.) 7,12-dimethylbenz(a)anthracene (DMBA)-induced oxidative stress and mammary carcinogenesis in female rats. The treatment protocol started from the day immediately after DMBA administration. Results obtained indicated that there was an elevation in the levels of malondialdhyde and nitric oxide in serum and breast tissues of DMBA injected rats. The combined treatment (Lyco + Mel) group showed a potential reduction of these parameters more than lyco individually. The activities of SOD, CAT, and GPx were found to be significantly high than lyco alone treated rats. In DMBA group a negative significant correlation between weight and serum nitric oxide (r = -0.59), and a positive significant correlation between NO and MDA (r = 0.81) was observed. Histopathological examination revealed the formation of tumor and angiogenesis in DMBA-induced rats and these abnormal changes were ameliorated by combined treatment with Lyco + Mel. In conclusion, these results suggested that supplementation of diet with lycopene with melatonin provided antioxidant defense with strong chemo preventive activity against DMBA-induced mammary tumors.

Mol Cell Biochem. 2008 Dec;319(1-2):175-80