Blood samples were collected for a total of 28 days (672 h) after administration of single doses . Effects of lycopene supplementation in patients with localized prostate cancer. Walfisch S., Walfisch Y., Kirilov E., Linde N., Mnitentag H., Agbaria R., Sharoni Y., Levy J. Tomato lycopene extract supplementation decreases insulin-like growth factor-I levels in colon cancer patients. Lycopene has been investigated in clinical trials for its antioxidant, anti-inflammatory, and CNS effects, as well as for use in cancer prevention, cardiovascular disease, dental hygiene, and diabetes. and transmitted securely. Tomato sauce and ketchup treatment for 96 hours decreased the percentage of cells in the G0/G1 phase but increased the percentage of cells in the S and G2/M phases. (McEneny 2013) In another study, low lycopene concentrations were associated with carotid atherosclerosis in 220 asymptomatic individuals. (Tang 2009) Another study documented activity against a liver adenocarcinoma cell line and a noncancerous lung cell line. This information relates to an herbal, vitamin, mineral or other dietary supplement. (Kuhad 2008b) Lycopene may also be useful in type 2 diabetes by reducing fasting blood glucose levels, suppressing oxidative stress, enhancing innate immunity or serum levels of immunoglobulin M, and attenuating inflammation. Schwenke C., Ubrig B., Thrmann P., Eggersmann C., Roth S. Lycopene for advanced hormone refractory prostate cancer: A prospective, open phase II pilot study. Only 5 of the 39 studies about the anti-cancer role of lycopene in tumours other than prostate cancer had negative results. Amounts typically found in food are considered safe. Association between selenium and lycopene supplementation and incidence of prostate cancer: Results from the post-hoc analysis of the procomb trial. In present review the dose range of lycopene varied from 16 . Watanabe S., Kitade Y., Masaki T., Nishioka M., Satoh K., Nishino H. Effects of lycopene and Sho-saiko-to on hepatocarcinogenesis in a rat model of spontaneous liver cancer. There is no consensus regarding recommended dosing of lycopene. (Mozos 2018) The 11 conjugated double bonds give lycopene the ability to interact with reactive oxygen species. This information should not be used to decide whether or not to take this product. Careers, Unable to load your collection due to an error. Ansari M.S., Gupta N.P. (Cano-Carrillo 2014) Another study of 45 patients with oral submucous fibrosis found that lycopene with and without hyaluronidase injections for 3 months significantly changed mouth opening and burning sensation compared with placebo. However, lycopene supplementation in African Americans lowered the levels of oxidation markers in patients diagnosed with benign prostatic hyperplasia, but not to a statistically significant degree [43]. Licensee MDPI, Basel, Switzerland. What are antioxidants and should you take supplements. All the studies about lycopene in head and neck cancer confirmed its anti-cancer activity. 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. In the cited intervention studies, lycopene was supplied as a dietary component (tomato paste) or as ready-made supplements available in the countries where the studies were conducted (see Supplements). Moody L., Crowder S.L., Fruge A.D., Locher J.L., Demark-Wahnefried W., Rogers L.Q., Delk-Licata A., Carroll W.R., Spencer S.A., Black M., et al. The daily per capita . Here are some excellent sources of lycopene: 1 cup of canned tomato sauce: 37 milligrams. However, clinical trial data are lacking to recommend use for any indication. It was shown that lycopene improved the treatment outcomes of locally advanced prostate cancer [25,49], reduced prostate cancer-specific mortality in men at high risk for prostate cancer [30], delayed the progression of recurrent prostate cancer regardless of hormone sensitivity status [19], improved the response to docetaxel chemotherapy in advanced castrate-resistant prostate cancer [33], and stabilised the effect of orchidectomy in a group of patients with advanced metastatic prostate cancer [51]. The identification of human and animal studies was performed according to PRISMA guidelines [9]. (Roohbakhsh 2017), In a cross-sectional study evaluating dietary carotenoid intake of pregnant women (N=1,978), the authors determined that each 1 mg increase in lycopene intake was associated with a 5% reduction in the risk for gestational diabetes (95% CI, 0.91 to 0.99; P=0.02). ; methodology, A.K. A very important aspect in the design of clinical trials with lycopene is appropriate population selection and attention to racial differences, which affect pharmacodynamics and are associated with different baseline levels of lycopene in populations with different diets [26]. Sheriff S.A., Devaki T. Lycopene stabilizes lipoprotein levels during D-galactosamine/lipopolysaccharide induced hepatitis in experimental rats. Although dietary lycopene may offer protection against cancers of the lung, breast, bladder, stomach, mouth or prostate, supplemental lycopene may worsen the effects of prostate cancer in men who already have the disease, MedlinePlus notes. The studies were retrospective and prospective, with a follow-up period of 6 months to 23 years. ; data curation, M.S., A.K. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (, GUID:7CE97761-0D47-4D69-B76F-A5260504B150, lycopene, cancer, in vivo study, nutraceuticals. Liu C., Russell R.M., Wang X.-D. Lycopene supplementation prevents smoke-induced changes in p53, p53 phosphorylation, cell proliferation, and apoptosis in the gastric mucosa of ferrets. Kucuk O., Sarkar F.H., Djuric Z., Sakr W., Pollak M.N., Khachik F., Banerjee M., Bertram J.S., Wood D.P. Lycopene intake ~ 10 mg per day. Eating a variety of brightly colored fruits and vegetables each day may be a more effective way to prevent chronic disease than taking lycopene in supplement form, the American Cancer Society notes. The Observed Safe Level methodology indicates up to 75 mg/day of lycopene is safe. Dietary and plasma lycopene and the risk of breast cancer. Rydn M., Leanderson P., Kastbom K.-O., Jonasson L. Effects of simvastatin on carotenoid status in plasma. (Chandra 2007) A randomized, double-blind, placebo-controlled trial (N=50) found no difference between groups receiving lycopene-enriched olive oil or placebo (water) for treatment of burning mouth syndrome or its symptoms. Fat also enhances the absorption of lycopene. Lycopene in the form (Lyc-O-Mato ) 6 mg per day (n = 41 men); 15 mg per day (n = 37 men) for 8 weeks; Control placebo capsule with soya oil and normal diet for 8 weeks: Supplementation with lycopene in the amount of 15 mg/day for 8 weeks in the group of tested men had a positive effect on endothelial function. Sengngam K., Hoc T.H., Hang D.V., Tran Ngoan L. Trans-Lycopene and -Cryptoxanthin Intake and Stomach Cancer in Vietnamese Men: A Pilot Case-Control Study. (Voskuil 2008) In a longitudinal study in which serum levels of various carotenoids and micronutrients were measured in a subset of women from the Women's Health Initiative clinical trials (N=5,450), higher baseline levels of lycopene were associated with an increased risk of invasive breast cancer during a median follow-up of 8 years. Vogt T.M., Mayne S.T., Graubard B.I., Swanson C.A., Sowell A.L., Schoenberg J.B., Swanson G.M., Greenberg R.S., Hoover R.N., Hayes R.B., et al. The data collected from the papers included the size of the studied population, the type of study and intervention, the source and doses of supplemented lycopene, the exact endpoints, and the most important findings. Lycopene is a common carotenoid compound found in fruits and vegetables. (Karppi 2009) Lycopene not only achieves high concentrations in the prostate, but also in the testes and adrenal glands. (Wang 2018) In an animal model of neuroinflammation, lycopene improved spatial learning and memory impairment, suggesting a potential role in Alzheimer disease. All authors have read and agreed to the published version of the manuscript. In a 2016 Cochrane review of interventions used to prevent oral cancer in patients with oral leukoplakia, lycopene improved some histologic features of oral leukoplakia. No significant changes were seen in arterial stiffness or blood pressure between the lycopene- and placebo-treated groups. Taking beta carotene supplements in high doses could make the skin appear yellow or orange ( carotenemia ). Possible Side Effects. (Cheng 2019) Similarly, another 2017 meta-analysis of 14 studies found that lycopene was associated with a reduced risk of cardiovascular disease (pooled RR, 0.83; 95% CI, 0.76 to 0.9). It has low and variable bioavailability. Di Franco R., Calvanese M., Murino P., Manzo R., Guida C., Di Gennaro D., Anania C., Ravo V. Skin toxicity from external beam radiation therapy in breast cancer patients: Protective effects of Resveratrol, Lycopene, Vitamin C and anthocianin (Ixor). Thus, such references were the secondary sources of papers. Human epidemiological evidence indicates that diets high in tomatoes may reduce the risk of cervical, colon, esophageal, oral, rectal, prostate, and stomach cancers. An interesting feature of lycopene is its dual effect on oxidative processes. HHS Vulnerability Disclosure, Help The mechanisms that were studied and confirmed in the analysed in vivo studies are presented in Table 1. Effects of a lycopene-rich diet on spontaneous and benzo[a]pyrene-induced mutagenesis in prostate, colon and lungs of the lacZ mouse. According to MayoClinic.com, recommended doses of lycopene generally range from 2 to 30 mg per day for up to six months. (Nkondjock 2005, Singh 2008). Zhuang E., Uchio E., Lilly M., Zi X., Fruehauf J.P. A phase II study of docetaxel plus lycopene in metastatic castrate resistant prostate cancer. [ 74 ] administered 30 mg/day lycopene (in the form of a tomato oleoresin) plus a multivitamin or just a . Velmurugan B., Bhuvaneswari V., Burra U.K., Nagini S. Prevention of N-methyl-N-nitro-N-nitrosoguanidine and saturated sodium chloride-induced gastric carcinogenesis in Wistar rats by lycopene. In addition to the aforementioned antioxidant capacity, in the process of oncogenesis, lycopene may show an opposite pro-oxidative effect that supports the elimination of pathological cells. Improvement in forearm blood flow from baseline, as measured by endothelium-dependent vasodilatation (EDV), was significant in cardiovascular disease patients (63% higher; P=0.008), with values approximating those of healthy volunteers at baseline. Saini R.K., Rengasamy K.R.R., Mahomoodally F.M., Keum Y.-S. In breast cancer, complex supplementation containing lycopene and other antioxidants reduced skin toxicity during radiotherapy used in radical treatment [75]. (Fuhrman 1997) In a 6-week clinical trial, 24 patients receiving fresh tomato and tomato juice twice daily reported reduced triglyceride levels and LDL cholesterol as well as increased HDL cholesterol. 1 By automation tools based on PubMed ID (PMID). ; visualization, M.S. Kim D.J., Takasuka N., Nishino H., Tsuda H. Chemoprevention of lung cancer by lycopene. Antioxidant response element or stimulation of cells to produce enzymes to protect against free radicals. Aizawa K., Liu C., Tang S., Veeramachaneni S., Hu K.-Q., Smith D.E., Wang X.-D. Tobacco carcinogen induces both lung cancer and non-alcoholic steatohepatitis and hepatocellular carcinomas in ferrets which can be attenuated by lycopene supplementation. Lycopene gives tomatoes, pink grapefruit, watermelon, apricots and other red, pink or orange fruits and vegetables their vivid colors. We comply with the HONcode standard for trustworthy health information. Another study identified a population of head and neck cancer survivors with high lycopene serum levels. Large molecules such as pectins hinder lycopene absorption, while fat facilitates it. Publ. (Petyaev 2016) Lycopene consists of only hydrogen and carbon atoms, and is 1 of 600 carotenoids synthesized by plants and photosynthetic microorganisms. (Grabowska 2019), In a murine model of benign prostatic hyperplasia, lycopene supplementation was found to ameliorate testosterone-induced increases in prostate weight. (Grabowska 2019, Tvrd 2016), One study involving 20 patients showed a significant correlation between skin roughness and lycopene dietary concentration, with higher levels of antioxidants leading to lower levels of skin roughness. Sahin K., Tuzcu M., Sahin N., Akdemir F., Ozercan I., Bayraktar S., Kucuk O. Inhibitory effects of combination of lycopene and genistein on 7,12- dimethyl benz(a)anthracene-induced breast cancer in rats. (Grabowska 2019, Tvrd 2016), In a study of bovine sperm, lycopene exhibited significant reactive oxygen speciesscavenging and antioxidant properties, which may prevent spermatozoa alterations caused by oxidative stress and preserve the functionality of male reproductive cells; lycopene administration resulted in preservation of spermatozoa motion parameters, mitochondrial function, and antioxidant characteristics. Kucuk O., Sarkar F.H., Sakr W., Khachik F., Djuric Z., Banerjee M., Pollak M.N., Bertram J.S., Wood D.P. 1 tablespoon . The average reported daily lycopene intake is 1.1 mg/day in the United Kingdom, 1.6 mg/day in Spain, 3.8 mg/day in Australia, 4.8 mg/day in France, and 4.9 mg/day in the Netherlands (Porrini & Riso 2005). Subgroup analysis results showed that a higher dosage of lycopene supplement (greater than 12 mg/day) could lower SBP more significantly, especially for participants with baseline SBP greater than 120 mm Hg or Asian participants. (Grabowska 2019, Petyaev 2016) Lycopene is available in various doseforms (eg, capsule, softgel) and is also incorporated in multivitamin and multimineral products. XRCC1 protein; Form and function. Gann P.H., Ma J., Giovannucci E., Willett W., Sacks F.M., Hennekens C.H., Stampfer M.J. Lower prostate cancer risk in men with elevated plasma lycopene levels: Results of a prospective analysis. Additionally, no dose relationship was observed. the contents by NLM or the National Institutes of Health. For example, in a recent study of nearly 50,000 male health professionals, dietary lycopene was associated with a reduced risk of lethal prostate cancer and a dose-response meta-analysis of 34 studies suggested that the risk was reduced by 3% per 1 mg/day increment of dietary lycopene intake . Additionally, for every 2 mg of lycopene consumed, the investigators found a 1% decrease in prostate cancer risk. The Observed Safe Level methodology indicates up to 75 mg/day of lycopene is safe. In contrast, interventions such as dietary advice or a lycopene-rich diet are not specific enough to be reliably analysed. A Food-Based Formulation Provides Lycopene with the Same Bioavailability to Humans as That from Tomato Paste. 41 Bioavailability of lycopene can be affected by a number of factors with only 10-30% of the total ingested lycopene being absorbed by the human body. None of the studies compared the anti-cancer effect depending on the form of lycopene supply. 8. This is why there is a lot of research interest in lycopene's role, if any, in preventing cancer. Based on results of 5 relevant studies with no substantial heterogeneity, lycopene intake showed no significant association with cataract risk. Apoptotic activity was observed and may have been caused by lycopene. (Saawarn 2011), Antioxidant effects (eg, decreased hydrogen peroxide and lipid peroxidation) may explain some of lycopene's effects in diabetes. (Kuhad 2008a) A diabetic mouse model suggests lycopene may also attenuate diabetic neuropathic pain via its inhibitory action on tumor necrosis factor alpha (TNF-alpha) and nitric oxide release. (Hu 2008) In a rat model of atherosclerosis, lycopene 50 mg/kg daily administered for 45 days significantly lowered total cholesterol, LDL cholesterol, VLDL cholesterol, and triglyceride levels, and increased HDL cholesterol levels. Huang C.-S., Liao J.-W., Hu M.-L. Lycopene inhibits experimental metastasis of human hepatoma SK-Hep-1 cells in athymic nude mice. Lycopene has been reported to improve treatment outcomes in prostate cancer when used with docetaxel, soy isoflavones, and orchidectomy to treat advanced prostate cancer [19,33,36,51]. Jatoi A., Burch P., Hillman D., Vanyo J.M., Dakhil S., Nikcevich D., Rowland K., Morton R., Flynn P.J., Young C., et al. Puah B.P., Jalil J., Attiq A., Kamisah Y. Also, the intake should be moderate during pregnancy or breastfeeding. (Kanetsky 1998) Plasma levels of lycopene and other carotenoids were lower in women with cervical intraepithelial neoplasia and cervical cancer, suggesting a possible protective effect of higher lycopene concentrations. In a rat model of hepatocellular carcinoma (HCC), the long-term administration of lycopene did not reduce the risk of hepatocarcinogenesis [60]. Correlates of serum lycopene in older women. Allen N.E., Key T.J., Appleby P.N., Travis R.C., Roddam A.W., Rinaldi S., Egevad L., Rohrmann S., Linseisen J., Pischon T., et al. Luo C., Wu X.-G. Lycopene enhances antioxidant enzyme activities and immunity function in N-methyl-N-nitro-N-nitrosoguanidine-enduced gastric cancer rats. Two independent studies confirmed the role of lycopene in inhibiting colorectal carcinogenesis via an insulin-like growth factor (IGF)-dependent mechanism [61,76]. Wang Y., Jacobs E.J., Newton C.C., McCullough M.L. Further population-specific studies are needed to quantify the anti-tumour role of lycopene. Serum lycopene concentration and prostate cancer risk: Results from the Prostate Cancer Prevention Trial. Lycopene also resulted in better histological findings (fewer foam cells, no naked fatty streaks, and only initial lesions of atherosclerosis [instead of fatty streaks and intermediate lesions]). Tomato sauces, pastes, soups and juices contain more lycopene than the fresh vegetable. Are there Adverse Effects of Lycopene Exposure? However, there is currently no recommended daily intake for lycopene. Weroha S.J., Haluska P. The insulin-like growth factor system in cancer. In a lung cancer mouse model, lycopene improved the efficiency of anti-PD-1 therapy [79]. Conceptualization, A.K. We found 20 papers on lycopene and the risk of prostate carcinogenesis in humans (Supplement Table S2). In humans, neither higher dietary levels nor higher plasma lycopene levels were shown to be associated with a reduced risk of breast cancer [59]. Beilby J., Ambrosini G.L., Rossi E., de Klerk N.H., Musk A.W. Lycopene is lipophilic and insoluble in water. Serum lycopene, other carotenoids, and prostate cancer risk: A nested case-control study in the prostate, lung, colorectal, and ovarian cancer screening trial. Lycopene co-supplementation with vitamin E also showed an improvement in the results of prostate cancer treatment, and in one of the studies the beneficial effect of lycopene was observed only in the case of such combined supplementation [28,36]. Gene expression and biological pathways in tissue of men with prostate cancer in a randomized clinical trial of lycopene and fish oil supplementation. You should talk with your health care provider for complete information about the risks and benefits of using this product. According to MayoClinic.com, most clinical studies have focused on the amount of lycopene-containing foods that participants ate rather than on the specific quantities of lycopene they consumed. Materials and methods: Current study was conducted on 52 BPH patients, who were randomly assigned into four groups of treatments: lycopene plus FruHis ( n = 11, 25 mg/day lycopene and 10 mg/day FruHis), lycopene ( n = 12, 25 mg/day lycopene), FruHis ( n = 12, 10 mg/day FruHis), and placebo ( n = 13). The easiest way to lookup drug information, identify pills, check interactions and set up your own personal medication records. Lu Y., Edwards A., Chen Z., Tseng T.-S., Li M., Gonzalez G.V., Zhang K. Insufficient Lycopene Intake Is Associated With High Risk of Prostate Cancer: A Cross-Sectional Study From the National Health and Nutrition Examination Survey (20032010). (Roohbakhsh 2017) In some animal models, lycopene reduced diabetes-induced learning and memory impairment by decreasing oxidative stress and inflammation. Only one study reported incidence of prostate cancer (10% vs 30% in the lycopene vs control groups). It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this product. Exp. (Grabowska 2019), In North America, nearly 85% of dietary lycopene is derived from tomatoes and tomato-based products. Avoid use. The levels of lycopene were inversely associated with incidence and mortality in these cancers [64,67]. Nutritional supplements, COX-2 and IGF-1 expression in men on active surveillance for prostate cancer. Lycopene levels in serum were similar after 3 month dosages of 15, 30, 45, 60, or 90 mg/day, and no change in serum PSA was detected as a result of intervention. (Costa-Rodrigues 2018), Lycopene suppressed tissue factor activation in vascular thrombosis in human endothelial cells. (Li 2018) In an animal study of sodium fluoride toxicity, oral lycopene administered for 5 weeks exerted antioxidant effects, causing a reduction in ameloblast apoptosis. This information is not specific medical advice and does not replace information you receive from your health care provider. Data sources include IBM Watson Micromedex (updated 14 May 2023), Cerner Multum (updated 28 May 2023), ASHP (updated 10 Apr 2023) and others. (Polidori 2003, Steinberg 1998) In another study, lycopene administration positively impacted the chance of successful pregnancy with in vitro fertilization; while donor sperm freezing can increase oxidative stress on the sperm, lycopene can increase sperm motility and reduce DNA damage. government site. The search keywords were cancer and lycopene, and results were limited to original papers published in English until June 2022. Fraser G.E., Jacobsen B.K., Knutsen S.F., Mashchak A., Lloren J.I. Combinations of tomato and broccoli enhance antitumor activity in dunning r3327-h prostate adenocarcinomas. In 2000, the Food and Nutrition Board of the Institute of Medicine determined that clinical evidence did not justify the need for a recommended dietary allowance or an adequate intake for lycopene or other carotenoids. Consuming at least 12 mg per day of lycopene has shown a blood pressure-lowering effect in people with high blood pressure. A randomized trial of lycopene supplementation in Tobago men with high prostate cancer risk. Histology of the pancreas was also improved in the lycopene group. 1 wedge of raw watermelon: 13 milligrams. (Kulhan 2019, Mahmoodnia 2017) However, more studies are needed to fully understand these effects. The PubMed, Scopus and Web of Science databases were comprehensively screened for papers about lycopene in cancer. (Lodi 2016) A compounded lycopene gel administered for 1 month was beneficial in reducing the size of oral leukoplakia lesion caused by tobacco use. See specific indications in Uses and Pharmacology section. No toxic effects were observed in rats treated with lycopene 2,000 mg/kg/day for 28 days, an intake similar to a human lycopene dosage of approximately 200 mg/kg of body weight per day. Inverse associations between plasma lycopene and other carotenoids and prostate cancer. Although dietary lycopene may offer protection against cancers of the lung, breast, bladder, stomach, mouth or prostate, supplemental lycopene may worsen the effects of prostate cancer in men who already have the disease, MedlinePlus notes. Clark P.E., Hall M.C., Borden L.S.J., Miller A.A., Hu J.J., Lee W.R., Stindt D., DAgostino R.J., Lovato J., Harmon M., et al. The daily per capita intake value of total phenolics was highest in raw tomatoes (7.21 mg/capita/day), followed by watermelons (1.72 mg/capita/day), tomato ketchup (1.41 mg/capita/day), and tomato juice (0.80 mg/capita/day). Some GI complaints (eg, diarrhea, dyspepsia, gas, nausea, vomiting) are documented. and M.S. Prostate carcinogenesis in N-methyl-N-nitrosourea (NMU)-testosterone-treated rats fed tomato powder, lycopene, or energy-restricted diets. In a study about lycopene in prostate cancer treatment, the supplementation did not alter the IGF1 and IGFBP3 levels [97]. Lycopene is a carotenoid nutraceutical that enhances protection against cancer, cardiovascular disease, hypertension, and neurodegenerative and inflammatory diseases [1]. (Lee 2006) Additional studies found that lycopene reduced expression of cell surface adhesion molecules and binding of monocytes. (Song 2017) Beneficial cardiovascular effects noted with lycopene may be due in part to its antiplatelet effects. Helzlsouer K.J., Comstock G.W., Morris J.S. Another candidate for the role of predictive factors is single nucleotide polymorphisms in -carotene oxygenase 1, associated with plasma lycopene responses to lycopene supplementation [13], which was independently confirmed by a large genome-wide association study [125]. Cell-cycle arrest or induction of cell death at the G1 phase, Effect on growth factors and signaling pathways critical for cancer cell growth, and, Antimetastatic and anti-invasion activity. Patients treated with the tomato extract also had reduced sputum neutrophil elastase activity. Lycopene's efficient absorption from tomato products facilitates its antioxidant effects and may also play an important role in cancer prevention. Our research provided ample evidence for the anti-cancer role of lycopene in the prostate and breast cancer cell lines. The daily dietary allowance of lycopene is 0.5-27 g per person per day. A European Food Safety Authority panel recommends a lycopene intake of 0.5 mg/kg body weight per day, at most 75 mg per day, but some reviews have shown that a dietary or formulated lycopene consumption of even up to 3 g per day is safe [96,128,129]. Getting at least 10 milligrams of lycopene per day appears helpful. However, the data from in vivo studies indicate the need for further research on the role of lycopene in tumours dependent on IGF stimulation, such as thyroid, breast, ovary, colon and lung cancer, as well as in gliomas and sarcomas [105]. Natural sources primarily contain the all-trans form of lycopene, the most thermodynamically stable form; when exposed to heat, light, and chemical reactions, lycopene is converted to the cis form, which is more bioavailable and less likely to precipitate and form crystals. (Banerjee 2009, Sharma 2003) Amounts typically found in food are considered safe. The standard serving size of Lycopene is 200 mg once or twice a day unless a physician recommends otherwise. (Singh 2017) Lycopene 8 mg twice daily administered for 6 months was found to improve mouth opening, burning sensation, tongue protrusion, and cheek flexibility in patients with oral submucous fibrosis. In addition, lycopene improved the quality of life, and provided relief from bone pain and control of lower urinary tract symptoms [50,51]. (Salman 2007) Lycopene and eicosapentaenoic acid also suppressed signal transduction pathways in human colon cancer cells, thus inhibiting cancer cell growth. (Kohlmeier 1997) Plasma LDL cholesterol concentrations were reduced by 14% in 6 men consuming dietary supplements of lycopene 60 mg/day for a 3-month period. Similarly, in animal studies, lycopene supplementation attenuated renal cell carcinogenesis [58]. Al-Yafeai A., Bhm V. In Vitro Bioaccessibility of Carotenoids and Vitamin E in Rosehip Products and Tomato Paste as Affected by Pectin Contents and Food Processing. Avoid use in individuals with hypersensitivity to lycopene or any of its food sources, especially tomatoes. In a large case-control study (N=4,721) taking place over 3 years, the risk of pancreatic cancer for men consuming lycopene was reduced by 31%. (Grabowska 2019). The Epidemiology of Prostate Cancer. https://creativecommons.org/licenses/by/4.0/, https://www.mdpi.com/article/10.3390/nu14235152/s1, Lower degree of angiogenesis in the tumour, vascular endothelial growth factor (VEGF), oxidative injury ( HIF-1, Cyr61, NDRG1, BNIP3, STAT2 mRNA); antioxidant enzyme activities (SOD, CAT and GPx), activity of enzymic antioxidants (superoxide dismutase, catalase, and glutathione peroxidase) and reduced levels of nonenzymic antioxidants (glutathione, vitamins E and C), level of malondialdehyde, NRF2 and its major target protein (heme oxygenase 1), serum thiobarbituric acid-reactive substances, Hypomethylation of CD8A and CD8 and CD8+ T cells, Accumulation of tumour cells in the G(0)/G(1) phase and further apoptosis, Inhibition of proliferation: downregulation of, cell cycle inhibitors p21(CIP1/WAF1) and p27(Kip1); factors for DNA division (PCNA, -catenin, cyclin D1, and, STAT3 by inducing the protein inhibitor, p21 and Bax1; factors for DNA division (cyclin 1, PCNA), Inhibition of hormone-dependent carcinogenesis, steroid target genes (cystatin-related protein 1 and 2, prostatic spermine-binding protein, prostatic steroid-binding protein C1, C2, and C3 chain, probasin). Inclusion in an NLM database does not imply endorsement of, or agreement with, van der Gaag M.S., van den Berg R., van den Berg H., Schaafsma G., Hendriks H.F. Moran N.E., Erdman J.W.J., Clinton S.K. Lycopene is available in various doseforms (eg, capsule, softgel) and is also incorporated in multivitamin and multimineral products. Serum lycopene, other serum carotenoids, and risk of prostate cancer in US Blacks and Whites. Epigenetic stratification of head and neck cancer survivors reveals differences in lycopene levels, alcohol consumption, and methylation of immune regulatory genes. Tomato consumption increases lycopene concentrations in the breast milk and plasma of lactating women. Lycopene supplements may have unknown side effects or medication interactions when taken in high doses. The references of the latter were screened to identify the papers that met the inclusion criteria but were not found in the database search. With regard to cancers of the digestive system, lycopene intake showed a strong protective effect against stomach cancer, regardless of H. pylori status [82]. TMPRSS2:ERG-positive disease appears to be particularly sensitive to the anti-cancer effects of tomato sauce [44]. More research is needed to explore whether doses higher than 25-44 mg/day of lycopene, provide additional beneficial effects on blood lipids compared with control, . Received 2022 Nov 2; Accepted 2022 Nov 29. (Shen 2007) In studies conducted in overweight individuals, both dietary and supplemental lycopene led to an increase in HDL cholesterol levels(Cuevas-Ramos 2013) and a reduction in HDL-associated inflammation. Shi J., Maguer M. Le Lycopene in Tomatoes: Chemical and Physical Properties Affected by Food Processing. Most of the studies concerned prostate cancer, reflecting the number of in vitro studies. An association between lycopene intake and decreased stomach cancer risk has been observed. Lycopene is a nutraceutical with health-promoting and anti-cancer activities, but due to a lack of evidence, there are no recommendations regarding its use and dosage. It is naturally found mainly as the trans isomer in varying concentrations in tomatoes, but also in other red fruits and vegetables such as red carrots, watermelons, grapefruits, and papayas [2]. FASEB J. Pooled data as well as subgroup analysis (ie, study design, smoking history, alcohol consumption, gender, geographical location) revealed no association between consumption of lycopene and risk of colorectal cancer. Although these results are sometimes seemingly inconsistent, they show the effect of lycopene on different stages of angiogenesis. Following this exposure and treatment period, the findings illustrated that the high dose of lycopene decreased the incidence of NNK/cigarette smoke-induced bronchiolitis and emphysema in ferrets [ 41 ]. Low plasma lycopene concentration is associated with increased mortality in a cohort of patients with prior oral, pharynx or larynx cancers. In addition, lycopenegenistein co-supplementation showed a protective effect against mammary carcinogenesis in an animal model [68]. Radhakrishnan V.K., Ravikumar V., Shivashangari K., Sattu K., Devaki T. Chemopreventive Role of Lycopene and D-arginine in Benzo(a) Pyrene Induced Lung Cancer with Reference to Lipid Peroxidation, Antioxidant and Tumor Marker Enzymes. (Graydon 2007, Vrieling 2007) A meta-analysis of observational studies explored the association between lycopene consumption and risk of colorectal cancer. Lycopene also modulates production of the antioxidant enzymes superoxide dismutase and catalase. However, research has not confirmed that lycopene offers greater preventive benefits than potassium, vitamin C or other nutrients found in these foods. Mariani S., Lionetto L., Cavallari M., Tubaro A., Rasio D., De Nunzio C., Hong G.M., Borro M., Simmaco M. Low prostate concentration of lycopene is associated with development of prostate cancer in patients with high-grade prostatic intraepithelial neoplasia. van Het Hof K.H., West C.E., Weststrate J.A., Hautvast J.G. Ansari M.S., Gupta N.P. Meta-analysis revealed no difference in prostate-specific antigen levels or in lycopene levels with and without lycopene supplementation. Tang L., Jin T., Zeng X., Wang J.-S. Lycopene inhibits the growth of human androgen-independent prostate cancer cells in vitro and in BALB/c nude mice. (Kumar 2017) In a murine study, supplementation with lycopene and tomato powder with a high-fat diet decreased adiposity index, organ weights, serum triglycerides, and free fatty acids, and improved glucose homeostasis with no impact on body weight. A prospective study of lycopene and tomato product intake and risk of prostate cancer. Ferrucci L., Perry J.R.B., Matteini A., Perola M., Tanaka T., Silander K., Rice N., Melzer D., Murray A., Cluett C., et al. (Stice 2018) Tomato sauce and ketchup contain 33 to 68 mg of lycopene per 100 g, while raw tomatoes contain 3.1 mg of lycopene per 100 g.(Murray 1996, van Breemen 2008) Mechanical treatment with heat helps release lycopene from the tomato matrix, improving bioavailability, as seen with processed commercial tomato products versus fresh tomatoes. Boileau T.W.-M., Liao Z., Kim S., Lemeshow S., Erdman J.W.J., Clinton S.K. How Does It Work? (Jian 2008) Additionally, lycopene 100 mg daily was not associated with adverse effects in volunteers. and A.K. The majority of body lycopene is found in the adipose tissue, with most of the remaining lycopene being found in the liver (17-23%) and . Rao A.V., Waseem Z., Agarwal S. Lycopene content of tomatoes and tomato products and their contribution to dietary lycopene. The population of patients who could benefit from the anti-cancer properties of lycopene can be found by identifying the predictive factors for lycopene supplementation. Kirkegrd J., Mortensen F.V., Cronin-Fenton D. Chronic Pancreatitis and Pancreatic Cancer Risk: A Systematic Review and Meta-analysis. (Malekiyan 2019), In a murine model of 3-nitropropionic acidinduced Huntington disease, lycopene 10 mg/kg administered for 15 days ameliorated mitochondrial dysfunction. Rowles J.L., Smith J.W., Applegate C.C., Miller R.J., Wallig M.A., Kaur A., Sarol J.N., Musaad S., Clinton S.K., OBrien W.D., et al. (Rowles 2017) In a Cochrane review of randomized controlled trials of lycopene for the prevention and treatment of benign prostatic hyperplasia and prostate cancer, only 3 of 64 published studies (n=154) met inclusion criteria. Moroni M., Pirovano M., Brugnatelli S., Zucca M., Morreale M., Rizzo V., Ferrari A., Tinelli C., De Silvestri A., Meregalli M., et al. However, for lung cancer the trend was different depending on sex, with a statistically insignificant reduction of risk in males [74,87,95]. Because carotenoids are fat-soluble nutrients, cooking tomatoes with oil or eating cooked tomatoes with small amounts of fat increases the amount of lycopene that your body can absorb. The animal studies had inconclusive results regarding the preventive role of lycopene in prostate cancer (Supplement Table S4). Limpens J., Schrder F.H., de Ridder C.M.A., Bolder C.A., Wildhagen M.F., Obermller-Jevic U.C., Krmer K., van Weerden W.M. Seren S., Mutchnick M., Hutchinson D., Harmanci O., Bayraktar Y., Mutchnick S., Sahin K., Kucuk O. (Gupta 2007) In 997 middle-aged men, an inverse association was found between serum lycopene levels and overall cancer incidence, but no association was found between lycopene levels and prostate cancer risk. Lycopene is available in various doseforms (eg, capsule, softgel) and is also incorporated in multivitamin and multimineral products. In general, tomato-based products and lycopene supplements are well tolerated. (Wang 2016), Suggested mechanisms of lycopene in cardiovascular disease include reduced LDL cholesterol, increased HDL functionality, reduced arterial thickness, decreased platelet aggregation, increased vasodilation, anti-inflammatory effects, and reduced proinflammatory cytokines. Investigating the effects of lycopene and green tea on the metabolome of men at risk of prostate cancer: The ProDiet randomised controlled trial. Clinical research has not verified that taking lycopene in supplement form can reduce your risk of cancer or heart disease. The anti-cancer effect, non-toxicity, safety and preventive or therapeutic roles of lycopene have been investigated in several studies. (Johny 2019), In an in vitro study, lycopene exerted a corrective effect in photodamaged keratinocytes. Role of the TMPRSS2-ERG gene fusion in prostate cancer. (Eliassen 2012), Lycopene's protective role in the early stages of cervical carcinogenesis was noted in one study. Lycopene is a potent antioxidant and possible mechanisms by which lycopene may prevent cancer may include (i) inhibition of growth and induction of differentiation in prostate cancer cells; 14,. Mazidi M., Ferns G.A., Banach M. A high consumption of tomato and lycopene is associated with a lower risk of cancer mortality: Results from a multi-ethnic cohort. Serum levels of folate, lycopene, -carotene, retinol and vitamin E and prostate cancer risk. Most of them (n = 15) were observational studies in which the incidence of prostate cancer was assessed in relation to the declared amount of consumed products containing lycopene. (Ye 2016) In vitro data also showed that lycopene exerts activity against pancreatic cancer cells. (Riso 2006) Asthmatic adults receiving lycopene treatment experienced improvement in airway inflammation. Relationship between cigarette smoking and nutrient intakes and blood status indices of older people living in the UK: Further analysis of data from the National Diet and Nutrition Survey of people aged 65 years and over, 1994/95. Lycopene in the prevention of renal cell cancer in the TSC2 mutant Eker rat model. Of the 15 studies that met inclusion criteria, 11 were case controlled and 4 were cohort studies, with heterogeneity found among the studies. We have deliberately not limited this review to high-quality studies because the available data on intervention studies are too little and heterogeneous to be used in statistical analyses. (Paran 2009) In a meta-analysis of 6 blinded intervention studies (N=494) evaluating the effects of lycopene or lycopene-containing products on blood pressure, lycopene supplementation significantly decreased SBP (P=0.012) but not DBP. (Tong 2016), In 19 subjects, dietary lycopene supplementation in the form of tomato juice, spaghetti sauce, and tomato oleoresin decreased serum lipid peroxidation and LDL oxidation, suggesting potential use in decreasing risk of coronary heart disease. Kitamura Y., Tanaka K., Kiyohara C., Hirohata T., Tomita Y., Ishibashi M., Kido K. Relationship of alcohol use, physical activity and dietary habits with serum carotenoids, retinol and alpha-tocopherol among male Japanese smokers. (Erdman 2009, Godsey 2016, Rao 2006, Singh 2008, van Breemen 2008) Several molecular mechanisms of action(Grabowska 2019) are proposed for lycopene's anticancer activity, including the following: Antioxidant activity or reduction of free radicals. Trivia Effects of lycopene on the insulin-like growth factor (IGF) system in premenopausal breast cancer survivors and women at high familial breast cancer risk. Calcium-containing products: Lycopene decreases the bioavailability of calcium. 1. One of the first investigations to suggest a possible relationship between lycopene use and prostate cancer risk was a case-control study published in the late 1970s. As a result, we confirmed that in vivo lycopene exhibits anti-cancer effects previously observed in in vitro studies. Stice C.P., Xia H., Wang X.-D. Tomato lycopene prevention of alcoholic fatty liver disease and hepatocellular carcinoma development. Although significant, these effects were less than those achieved in the atorvastatin group. Chen P., Xu S., Qu J. Lycopene Protects Keratinocytes Against UVB Radiation-Induced Carcinogenesis via Negative Regulation of FOXO3a through the mTORC2/AKT Signaling Pathway. Doses ranged from 4.5 to 15 mg/day (mean, 12.4 mg/day) for a duration of 4 to 16 weeks (mean, 8.3 weeks); average net change in SBP ranged from 11.5 to 2.4 mm Hg, with an overall pooled estimate of 4.95 mm Hg. Caution Excess intake might cause skin discoloration. Modulatory effect of lycopene on oxidative injury, related proteins and gene expression in gastric cancer tissue. Sesso H.D., Buring J.E., Zhang S.M., Norkus E.P., Gaziano J.M. Consult your health-care provider before taking lycopene in supplement form. Richelle M., Bortlik K., Liardet S., Hager C., Lambelet P., Baur M., Applegate L.A., Offord E.A. Therefore, the mechanism of angiogenesis is more important in tumour development and metastasis than in tumour initiation, which explains the negative results of the mentioned study in mice. Lycopene is the carotenoid with the greatest antioxidant action, i.e., it helps our body fight oxidative stress, a pathological condition caused by an excess of free radicals that the body cannot dispose of naturally. In in vitro studies, lycopene has shown anti-neoplastic activity by interfering with cancer cell migration, invasion, vessel formation, and microenvironment regulation, and by enhancing apoptosis [8]. For example, the average daily lycopene intake is 4.9 mg/day in the Netherlands and 1.6 mg/day in Spain. 8600 Rockville Pike (Lee 2008) Lycopene may also have a role in reducing rhinovirus-induced airway inflammation by potentially inhibiting the formation of reactive oxygen species and decreasing viral replication. ; funding acquisition, A.K. (El-Ashmawy 2018) Lycopene was also found to improve neurological function from spinal cord ischemia injury in a murine model; specifically, it attenuated cyclooxygenase-2 and nuclear factor kappaB levels. (Neyestani 2007, Ozmen 2016, Zheng 2019) In a murine model, lycopene reduced biomarkers of diabetic nephropathy. Thus, specific formulation used may impact potential outcomes. 42 Singh D et al. Jian L., Du C.-J., Lee A.H., Binns C.W. Prevention and treatment of cancer According to epidemiologic studies, lycopene has antioxidant and anticancer properties, which suggests that a high intake of lycopene-rich foods can reduce the risk of developing cancer. The Observed Safe Level methodology indicates up to 75 mg/day of lycopene is safe. (Salman 2007) There is a large body of evidence documenting lycopene's health benefits, as well as its biological activity in numerous conditions. The preventive potential of lycopene in female cancers was demonstrated in an animal model of ovarian cancer with predominant antioxidant and anti-inflammatory mechanisms [58]. Kirsh V.A., Mayne S.T., Peters U., Chatterjee N., Leitzmann M.F., Dixon L.B., Urban D.A., Crawford E.D., Hayes R.B. Tjahjodjati, Sugandi S., Umbas R., Satari M. The Protective Effect of Lycopene on Prostate Growth Inhibitory Efficacy by Decreasing Insulin Growth Factor-1 in Indonesian Human Prostate Cancer Cells. Shao A., Hathcock J.N. Alison M.R., Nicholson L.J., Lin W.-R. Xu Y.F., Zhou S.K., Feng X.J., Jiang L.X. To our knowledge, the present study is the only one to date that has comprehensively assessed the anti-tumour role of lycopene in humans and animals in a clinical setting. Lycopene minimizes skin toxicity and oxidative stress in patients treated with panitumumab-containing therapy for metastatic colorectal cancer. Last updated on Jan 23, 2023. The conclusions about the role of lycopene in colorectal cancer were uncertain, but the growth of colon cancer in mice supplemented with lycopene alone or with lycopene and fish oil was inhibited [63]. Conlon L.E., Wallig M.A., Erdman J.W.J. These nutritious foods also provide vitamin C, potassium, folate and other antioxidant pigments. Only one study indirectly concluded that the pyruvate-lowering effect of lycopene might be causally related to a reduced risk of prostate cancer [55]. The accumulation of lycopene also depends on other factors, such as age, body weight, gastrointestinal status, lifestyle habits, or food intake [5]. Phase I-II prospective dose-escalating trial of lycopene in patients with biochemical relapse of prostate cancer after definitive local therapy. Methods: Twenty selected prostate cancer patients were given whole-tomato supplement lycopene 10 mg per day for about 6 months. There is no consensus regarding recommended dosing of lycopene. In addition, in humans, lycopene seemed not to have reduced the risk of colorectal, skin, or lung cancer. Bohn T., Desmarchelier C., Dragsted L.O., Nielsen C.S., Stahl W., Rhl R., Keijer J., Borel P. Host-related factors explaining interindividual variability of carotenoid bioavailability and tissue concentrations in humans. Kim M.J., Kim H. Anticancer Effect of Lycopene in Gastric Carcinogenesis. Prostate Cancer Prevention. Lycopene: Food Sources, Biological Activities, and Human Health Benefits. The hallmark of this population was hypermethylation of mediators and signalling genes, which caused decreased oxidative damage and reduced T-cell activation and might have been the benefit of lycopene [66]. Although lycopene may offer numerous health benefits, a recommended intake for this plant pigment has not been established. The site is secure. The levels of both proteins were lowered after prostatectomy regardless of lycopene supplementation, which was inconsistent with the hypothesis based on the observation that in in vitro and ex vivo studies, lycopene caused a decrease in IGF1 (with mitogenic and anti-apoptotic properties) and an increase in IGFBP3 (with an opposite effect) [100,101]. Unlu N.Z., Bohn T., Francis D.M., Nagaraja H.N., Clinton S.K., Schwartz S.J. (Saedisomeolia 2009), Epidemiological studies have found that lycopene decreases the inflammation marker C-reactive protein. Supplement Facts Active Ingredient (s): Lycopene Alternate Name (s): ,-Carotene Legal Status: "Grandfathered" dietary ingredient (legally marketed before 1994) Suggested Dose: No formal recommendation for lycopene intake. (Ried 2011), Effects of oral lycopene supplementation on vascular function were investigated in a randomized, double-blind, placebo-controlled trial with parallel arms, including statin-treated patients with cardiovascular disease (n=36) and healthy volunteers (n=36). (Rao 1998). (Kabat 2009) A pooled analysis of 8 prospective studies on carotenoids and breast cancer demonstrated a statistically significant inverse association between carotenoid levels, including lycopene concentrations, and the risk of breast cancer. Available for Android and iOS devices. Chronic inflammation and hepatocellular carcinoma. From this observation, it may be concluded that there are at least two populations of patients with prostate cancer, and between them, those with a preserved prostate storage capacity may benefit from the anti-cancer properties of lycopene. (Hua 2019) In a murine model of asthma, lycopene suppressed infiltration of inflammatory mediators and cells into the lung, decreased airway hyperresponsiveness, and inhibited cell infiltration and invasion. sharing sensitive information, make sure youre on a federal Bhatia N., Gupta P., Singh B., Koul A. Lycopene Enriched Tomato Extract Inhibits Hypoxia, Angiogenesis, and Metastatic Markers in early Stage N-Nitrosodiethylamine Induced Hepatocellular Carcinoma. (Burgess 2008, Jackson 2008, Mozos 2018, Stice 2018, van Breemen 2008) The double bonds are necessary for lycopene's antioxidant properties. Lycopene supplementation elevates circulating insulin-like growth factor binding protein-1 and -2 concentrations in persons at greater risk of colorectal cancer. (Murray 1996), Processed tomato products (eg, tomato paste) are a better source of lycopene than fresh tomatoes,(New study 1997) and provide greater bioavailability. Vaishampayan U., Hussain M., Banerjee M., Seren S., Sarkar F.H., Fontana J., Forman J.D., Cher M.L., Powell I., Pontes J.E., et al. The use of nutraceuticals and dietary supplements in the prevention and treatment of cancers is highly controversial due to the likely additive effect of many substances from the daily diet and the difficulty of designing selective studies identifying the specific substances and doses at which the nutraceuticals and dietary supplements exhibit anti-cancer effects. Publishers Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. A separate 12-week study showed that those taking between 8 and 16 mg of lycopenefrom food or supplementshad a 40 to 50 percent reduction in skin redness after UV . The average lycopene intake of male and female were 1.98 and 1.92 mg/capita/day, respectively. There are limited data on the role of lycopene in urological neoplasms other than prostate cancer. van Breemen R.B., Sharifi R., Viana M., Pajkovic N., Zhu D., Yuan L., Yang Y., Bowen P.E., Stacewicz-Sapuntzakis M. Antioxidant effects of lycopene in African American men with prostate cancer or benign prostate hyperplasia: A randomized, controlled trial. PSA velocity slope, which reflects the change of PSA, and the degree of change were also calculated. Another questionable result is the effect of lycopene on the IGF-mediated pathway. The relationships between race, lycopene, and carcinogenesis have been studied only in prostate cancer. (Peng 2017) In another in vitro study, lycopene increased apoptosis in a cell line of human head and neck squamous carcinoma. In vitro, lycopene has been found to inhibit human colon carcinoma, myeloid leukemia, and lymphoma cell lines in a dose-dependent manner. This pigment belongs to the class of carotenoids, antioxidant compounds that counteract the cellular damage that can lead to heart disease, cancer, macular degeneration and other diseases. Bethesda, MD 20894, Web Policies Off. This is only a brief summary of general information about this product. A Tomato-Based, Lycopene-Containing Intervention for Androgen-Independent Prostate Cancer: Results of a Phase II Study from the North Central Cancer Treatment Group. Lycopene dosage per day Duration (treatment phase) Participants, m/f, age Sample size; Sakamoto 94, Japan: . Although no established authority has offered official recommendations regarding lycopene dosage, Dr. Edward Giovannucci, a professor of nutrition and epidemiology at the Harvard School of Public Health, recommends getting at least 10 milligrams of lycopene per day. Our research aimed to assess whether the successes of in vitro studies are reflected in human and animal studies where the final effect of lycopene depends on other factors, such as its absorption and distribution, the influence of the microenvironment, and drug interactions. Additionally, each 1 mg increase in lycopene was associated with a 0.09 mg/dL decrease in fasting blood glucose. Serological precursors of cancer: Malignant melanoma, basal and squamous cell skin cancer, and prediagnostic levels of retinol, beta- carotene, lycopene, alpha-tocopherol, and selenium. Perhaps this population would benefit from prophylactic lycopene supplementation or from popularising a lycopene-rich diet [119]. 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