Lycopene is a carotenoid that forms the red pigment in fruit, such as tomatoes or apricots.
Lycopene has been suggested to exhibit antioxidant activities, inhibit cell proliferation and induct apoptosis, thus protecting against cancer (in particular prostate cancer) and providing health benefits for cancer patients. The additional intake of processed tomato products (juice), functional foods enriched with lycopene, or nutritional supplements is marketed based on such claims. This summary concerns the supranutritional intake (i.e. in addition to the content of the daily diet) of lycopene in the form of supplements or functional foods.
For the treatment of prostate cancer, clinical evidence is available from one systematic review (SR) and one additional randomized controlled trial (RCT); for the prevention of prostate cancer, clinical evidence is available from two SRs and one additional RCT for prevention. There are also three RCTs for oral submucous fibrosis and one for cisplatin-induced nephrotoxicity.
- Prostate specific antigen (PSA) levels: There is insufficient high-quality evidence for lycopene as a cancer treatment from one systematic review and one good-quality RCT assessing PSA levels.
- Cisplatin-induced nephrotoxicity: Lycopene may decrease complications due to cisplatin-induced nephrotoxicity but evidence from one RCT is very limited.
Prostate cancer: There is insufficient evidence to support the recommendation of lycopene for prostate cancer prevention based on two SRs and one additional RCT.
Oral submucous fibrosis: Three RCTs provide some evidence for lycopene reducing the symptoms of oral submucous fibrosis but the trials are small and of poor quality.
In men, the ingestion of lycopene seems to be generally safe.
Ava Lorenc, Gabriele Dennert, CAM Cancer Consortium. Lycopene [online document], November 9th, 2020.
Fully updated and revised in October 2020 by Ava Lorenc
Fully updated and revised in September 2018 by Ava Lorenc
Summary first published in July 2013, authored by Gabriele Dennert.
Lycopene forms the red pigment in fruit such as tomatoes, apricots, guavas, pink grapefruits, rosehips or watermelons (Diener 2008) and is involved in the photosynthesis of plants, algae and other organisms that actively generate energy through photosynthesis. It is chemically a carotenoid, but is not an essential food ingredient for humans. Lycopene was named after the fruit from which it was first isolated, namely the tomato (Lycopersicum esculentum), by the chemist C.A. Schunck in 1903 (Schunck 1904).
In Western countries, tomatoes and tomato products have been found to be the major nutritional source of lycopene for humans. Lycopene supplements or lycopene-enriched functional foods are marketed by various companies. In a US sample of prostate cancer patients, 11% of men used lycopene or tomato products (Wang 2016). Intake in the general population has been estimated at 4·1mg/d in Belgium (Vandevijvere 2013) and 3.1 mg/d in Spain (Esèvez- Santiago 2016) .
Ingredient and quality issues
Lycopene is a lipophilic, acyclic (C40H56) carotenoid with no provitamin-A activity, which means it is not metabolized to vitamin A in the body. It is insoluble in water and exists naturally in an all-trans isoform and several cis-isoforms.
Application and dosage
The level of intake optimal for human health has not been established. This summary concerns the supplemental intake of lycopene. Supporters of the supranutritional intake of lycopene often recommend adding between 15 and 40 mg to their daily diet. Lycopene is obtained from processed tomato products (juice), functional foods enriched with lycopene or as nutritional supplements. Nutritional supplements contain pure lycopene, extracted from either natural or synthetic sources, at doses of between 5 and 25mg per tablet or capsule. Tomato juice or sauce contains about 9mg of lycopene per100g (Rao 2007). For safe use of tomato leaf extract the authors of an animal study recommend lower doses (250 and 500 mg/kg) for prolonged use (Nguenang 2020).
Lycopene is intestinally absorbed. Some studies found that absorption is higher in the presence of dietary lipids, and from processed tomato products, than from raw tomatoes. (overview in Diener 2008). Several studies have shown that the additional intake of lycopene (between 20 and 40mg/day) in the form of tomato products or nutritional supplements increased the plasma lycopene level. (overview in Basu 2007). One pharmacokinetic study found peak plasma levels of lycopene at 0.5–6 hours after oral ingestion and an elimination half-life of between two and five days. Lycopene and its metabolites were transported to the skin in this study, where it remained detectable for up to 42 days (Ross 2011). Various novel delivery systems have been shown in animal studies to improve bioavailability, e.g. green tea catechin derivatives, protein nanoparticles or lipid based solid dispersion (Li 2017, Jain 2018, Faisal 2013). Lycopene seems to be eliminated and excreted via the bile duct and the kidneys.
Lycopene has been proposed as being active in the prevention of cancer, in particular prostate cancer, and other disease, e.g. cardiovascular diseases. As well as exhibiting beneficial effects in prostate cancer and lung cancer patients, it has been suggested as helpful in protecting against the adverse effects of chemotherapy (Sahin 2010).
Systematic reviews of epidemiologic studies show that higher intake of lycopene is associated with a reduced risk of developing prostate cancer (although not advanced prostate cancer) (Catano 2018, Chen 2015, Rowles 2017, Wang 2015, Giovannucci 1999) as well as cardiovascular diseases (Cheng 2017). Lycopene has therefore been promoted for cancer prevention and general health improvement.
To date, there is contradictory epidemiologic evidence regarding the association of lycopene intake and the risk of other cancers: meta-analyses showed consumption of large amounts of tomato products is associated with a reduced risk of gastric cancer (Yang 2013), and lycopene intake is marginally associated with reduced risk of pancreatic cancer (Chen 2016), but lycopene intake is not significantly associated with the risk of ovarian cancer (Li 2014), colorectal cancer (Wang 2016), colon cancer (Slattery 2000), or non-Hodgkin lymphoma (Chen 2016) . Individual studies are also contradictory: for lung cancer (Michaud 2000), Michaud et al found a reduced risk associated with higher lycopene levels or intake. For breast cancer one 20 year follow up study found a reduced risk (Eliassen 2015) but a previous 9.9 year follow up study found no protective association (Sesso 2005).
Mechanisms of action
Several biological mechanisms of lycopene and its metabolites have been described and suggested as linked to cancer development and prevention in humans (Mein 2008), including: growth inhibition and induction of apoptosis G0/G1 cell cycle arrest (Rotelli 2015), inhibition of MMP-7 expression and leptin-mediated cell invasion (Rotelli 2015), decreased genomic instability in low grade prostate cancer, suggesting inhibition of disease progression early on (Nordstrom 2015), and decreased tumour angiogenesis (Zu 2014). However, much of this data s from in vitro studies, and the metabolism and biological effects of lycopene are still not fully understood as, to date, studies have yielded discrepant results.
Some studies with healthy volunteers found that the intake of additional lycopene decreased the level of biomarkers of oxidative stress, while other investigations showed no effect (Basu 2007). A systematic review concludes that lycopene supplementation significantly decreases the DNA tail length, but does not significantly prolong the lag time of low-density lipoprotein (Chen 2013). In one randomized clinical trial (RCT) involving male African American urology patients, no antioxidant effect of lycopene supplementation prior to prostate biopsy (30 mg/day for 21 days) could be seen (van- Breemen 2011) . Llanos et al (Llanos 2014) conducted a crossover trial of 70 women at risk of breast cancer who were put on a tomato-based diet (>25 mg lycopene daily) for 10 weeks, compared to a soy-based diet. They found that the tomato-based diet may beneficially increase serum adiponectin concentrations. Another investigation with healthy volunteers suggested that the intake of lycopene (30 mg/day) increased serum insulin-like growth factor (ILGF)-binding protein-1 and -2 concentrations (Vrieling 2007) , which might lower ILGF-levels and prevent its possible cancer-promoting effects. Lycopene has also been linked to androgen metabolism and has been found to lower testosterone levels in mice mediated by genetic variations of enzymes of the carotenoid-metabolism (Ford 2012).
Some animal and in-vitro studies found a protective effect of lycopene against smoke carcinogen-induced injury (Aizawa 2016, Mustra 2019)Acar 2014, Kulhan 2019, Stokiljkovic 2019, Zhu 2019, Celik 2020), e.g. nephron- and cardiotoxicity of cisplatin or adriamycin, while others did not (Anjos Ferreira 2007, overview in Sahin ). Mice/rat studies found that lycopene reduces hepatic tumours, through inhibiting NF-kappaB and mTOR pathways and reducing hepatic proinflammatory signalling and inflammatory foci (Sahin 2014, Ip 2013, Ip 2014, Xia 2018). An SR found evidence to support the biological plausibility that lycopene interacts with the androgen axis in prostate cancer (Applegate 2019) and an in-vitro study found tomato products increase apoptosis in prostate cancer cells (Soares 2019). Lycopene has been shown to reduce gene expression in gastric cancer cells in-vitro (Han 2019, Kim 2019), in pancreatic cancer in-vitro (Jeong 2019), in cutaneous tumors (Wang 2020), in ovarian cancer in vitro (Xu 2019) and in prostate cancer in TRAMP mice (Wan 2014). Other mechanisms identified in animal studies include antioxidant and anti-inflammatory mechanisms (ovarian cancer and prostate cancer)(Jiang 2018) (Sahin 2018) , reduction of growth factors (Tjahjodjati 2020) and antioxidant defence (cutaneum carcinoma) (Shen 2014). An in-vitro study found that LYC-oxidation derivatives or metabolites in lycopene are involved in growth inhibition of breast cancer cells (Arathi 2018). (via autophagy)(Bi 2019) and chemotherapy/radiotherapy-induced toxicities such as cardiotoxicity, neuropathy, kidney and ovarian injury (Lopez- Jornet 2016,
In-vitro studies found that lycopene may enhance the effects of treatment of lung cancer (Jiang 2019) and melanoma (Zhu 2019)
In an in-vitro model, lycopene at a physiological level did not show a significant effect on the proliferation of normal and malignant cells (Burgess 2008), and two animal studies found that lycopene did not reduce carcinogenesis in TRAMP mice (Rowles 2020) (Conlon 2015).
For functional foods and nutritional supplements, EU and national regulations apply.
Costs and expenditures
Thirty tablets (15–25 mg lycopene each) – one-month’s supply – are available in Europe for around €25 via internet sellers.
For prostate cancer clinical evidence is available from one systematic review (SR) and one additional randomized controlled trial (RCT) for treatment as well as two SRs and one additional RCT for prevention. There are also three RCTs for oral submucous fibrosis and one for cisplatin-induced nephrotoxicity.
- Prostate specific antigen (PSA) levels: There is insufficient high-quality evidence for lycopene as a cancer treatment from one systematic review and one good-quality RCT assessing PSA levels.
- Prostate cancer: There is insufficient evidence to support the recommendation of lycopene for prostate cancer prevention based on two SRs and one additional RCT.
- Oral submucous fibrosis: Three RCTs provide some evidence for lycopene reducing the symptoms of oral submucous fibrosis but the trials are small and of poor quality.
- Cisplatin-induced nephrotoxicity: Lycopene may decrease complications due to cisplatin-induced nephrotoxicity but evidence from one RCT is very limited.
Description of included studies
Haseen and colleagues (2009) identified eight intervention studies for their systematic review of lycopene supplementation in men with prostate cancer (Haseen 2009). Two of them were RCTs (Ansari 2003, Kucuk 2001). One was a non-randomized clinical trial (Kim 2003) and five were uncontrolled intervention studies (Ansari 2004, Barber 2006, Chen 2001, Jatoi 2007, Clark 2006).
All studies reported on changes of PSA level as the surrogate parameter for prostate cancer progression. Only one RCT (Ansari 2003) investigated clinical outcomes: 54 men with metastasized prostate cancer were randomized to orchidectomy or orchidectomy plus lycopene (4 mg/day). After two years, clinical response of bone metastases (as measured in bone scan) and overall survival were higher in the lycopene plus orchiectomy group, suggesting a beneficial effect of lycopene. However, due to shortcomings in methods and reporting of this trial, these findings need to be replicated in larger RCTs before any generalized recommendations for men with advanced prostate cancer can been made. Moreover, as stated by the reviewers, ‘orchidectomy is now rarely performed in Western countries as a prostate cancer treatment and it is unclear whether the results of this study can be generalized to patients receiving medical castration therapy’ (Haseen 2009). In summary, reviewers concluded that there is not sufficient evidence to recommend the use of lycopene supplements in routine care for prostate cancer patients.
Since the systematic review, one RCT on PSA levels (Paur 2016) has been published. Paur et al (Paur 2016) randomised 79 patients with prostate cancer to either tomato products containing 30mg lycopene per day, tomato products plus other supplements, or control diet for 3 weeks. They found no difference in PSA levels between groups in the overall sample, but sub-analysis suggests tomato products may reduce PSA levels in intermediate risk prostate cancer patients. This was a high-quality study, although patients were not blinded.
In addition to the epidemiologic evidence described above (see ‘Claims of efficacy’), two systematic reviews of RCTs of lycopene for prostate cancer prevention (Llanos 2014, Cui 2017) and three RCTs for the precancerous condition oral submucous fibrosis (OSMF) (Saran 2018, Karemore 2012, Beenakumary 2019) are included in this summary.
Two systematic reviews and one subsequently published RCT (Beynon 2018) have looked at lycopene for prostate cancer prevention. A Cochrane systematic review (2011) concluded that ‘there is insufficient evidence to either support, or refute, the use of lycopene for the prevention of prostate cancer” (Ilic 2011). The review identified three RCTs investigating lycopene for prostate cancer prevention (Mohanty 2005, Bunker 2007, Schwarz 2008). Two RCTs used prostate specific antigen (PSA) levels as surrogate parameters for prostate cancer development but only one study (Mohanty 2005) assessed the incidence of prostate cancer. The latter RCT reported a lower rate of prostate cancer (10% in the lycopene group versus 30% in the comparison group) but was very small (40 participants) and considered to be of unclear risk of bias by the review authors. A larger systematic review (n=13) with meta-analysis published in 2017 of high-grade prostatic intraepithelial neoplasia (precursor or premalignant form of prostate cancer) concluded that lycopene decreased the risk of prostate cancer but not significantly (Cui 2017). Beynon et al (Beynon 2018) subsequently conducted a high quality, powered RCT of 128 men with raised PSA levels comparing tomato products, tomato products plus supplements and standard care. They found no differences in PSA except for subgroup analysis of intermediate risk prostate cancer patients.
Oral submucous fibrosis
Three RCTs have tested lycopene supplementation for oral submucous fibrosis (OSMF), a potentially malignant disorder (Saran 2018, Karemore 2012). Beenakumary et al (Beenakumary 2019) randomised 60 patients with OSMF to lycopene supplement, lycopene supplement + dexamethasone or dexamethasone + hyaluronidase. They found that lycopene was not as effective as dexamethasone + hyaluronidase. Saran et al (Saran 2018) randomised 60 patients to receive 4 mg of lycopene or 300 mg of curcumin thrice daily for 3 months. Lycopene showed better results than curcumin in improving mouth opening; both the drugs were equally effective in decreasing burning sensation in OSMF patients. Lycopene significantly reduced the signs and symptoms of OSMF. Karemore and Motwani (Karemore 2012) randomised 92 patients to either 4mg of Lycopene or placebo tablet twice a day. Lycopene was found significantly efficacious reducing the signs and symptoms of OSMF. However all three studies may be subject to detection bias and underpowered samples.
Nephrotoxic side effects of cancer treatment
Mahmoodnia et al randomised 120 patients with cancer (candidates for cisplatin-based chemotherapies) to either 25mg lycopene each 12 hours from 24 hours before to 72 hours after cisplatin administration or standard care. (Mahmoodnia 2017) They found lycopene decreased the complications due to cisplatin-induced nephrotoxicity through affecting some markers of renal function but not all. The study was double-blind and adequately randomised but lacks information on the sample and follow up and the authors recommend additional studies using other nephrotoxicity outcomes.
Supranutritional intake (10 mg/day) of lycopene seems to be generally safe in men and non-pregnant women (Norwegian Scientific Committee for Food Safety).
Authors of a systematic review of lycopene for prostate cancer patients found no indication that the use of lycopene was harmful in these men (Haseen 2009). Also Shao and Hathcock claimed that the ‘absence of any pattern of adverse effects related to lycopene consumption in any of the published human trials provides support for a high level of confidence in the safety of this substance’ (Shao 2008).
One RCT in pregnant women indicated a higher rate of adverse effects (preterm labour, low birth weight) in the lycopene group (2mg/day) as compared to placebo (Banerjee 2009).
Datta et al (Datta 2013) evaluated the tolerance and acceptance of three different amounts (4, 8, or 12 oz) of tomato juice during radiotherapy in 20 men with localized prostate cancer and found it was well tolerated with no gastrointestinal side effects. An animal study found that high doses of tomato leaf extract (1000mg/kg) increased urea levels and total serum proteins (Nguenang 2020).
There are no known contraindications.
One animal study reported a possible interaction between lycopene and alcohol intake, with the enzyme cytochrome P450 2E1 being induced by this combination (Veeramachaneni 2008) However, the relevance of this finding for humans is unclear.
One recent in-vitro study (Sunaga 2012) 35 found that tomato products, but not lycopene alone, had an inhibitory effect on cytochrome P450 3A4 (CYP3A4)-mediated metabolism, the magnitude of which differed between substrates. As CYP3A4 is involved in the metabolization of multiple drugs, including antibiotics, cytostatic and psychotropic drugs, these findings support caution when large quantities of tomato products are concomitantly taken with CYP3A4-dependent drugs.
The actual content of lycopene in commercially available nutritional supplements seems to vary and may differ by as much as +/-38–42% from the stated content (Feifer 2002).
Other problems or complications
It is possible that the intake of high amounts of lycopene leads to a discoloration of the skin, because of an accumulation of the yellow-orange pigment this carotenoid contains (Linus Pauling Institute).
Acar DE, Acar U, Yumusak N, Korkmaz M, Acar M, Atilgan HI, et al. Reducing the histopathological changes of radioiodine to the lacrimal glands by a popular anti-oxidant: lycopene. Current eye research. 2014;39(7):659-65.
Aizawa K, Liu C, Tang S, Veeramachaneni S, Hu KQ, Smith DE, et al. Tobacco carcinogen induces both lung cancer and non-alcoholic steatohepatitis and hepatocellular carcinomas in ferrets which can be attenuated by lycopene supplementation. International journal of cancer. 2016;139(5):1171-81.
Anjos Ferreira AL, Russell RM, Rocha N, Placido Ladeira MS, Favero Salvadori DM, Oliveira Nascimento MC, et al. Effect of lycopene on doxorubicin-induced cardiotoxicity: an echocardiographic, histological and morphometrical assessment. Basic Clin PharmacolToxicol. 2007;101(1):16-24.
Ansari MS, Gupta NP. A comparison of lycopene and orchidectomy vs orchidectomy alone in the management of advanced prostate cancer. BJU Int. 2003;92(4):375-8.
Ansari MS, Gupta NP. Lycopene: a novel drug therapy in hormone refractory metastatic prostate cancer. Urol Oncol. 2004;22(5):415-20.
Applegate CC, Rowles JL, 3rd, Erdman JW, Jr. Can Lycopene Impact the Androgen Axis in Prostate Cancer?: A Systematic Review of Cell Culture and Animal Studies. Nutrients. 2019;11(3).
Arathi BP, Raghavendra-Rao Sowmya P, Kuriakose GC, Shilpa S, Shwetha HJ, Kumar S, et al. Fractionation and Characterization of Lycopene-Oxidation Products by LC-MS/MS (ESI)(+): Elucidation of the Chemopreventative Potency of Oxidized Lycopene in Breast-Cancer Cell Lines. Journal of agricultural and food chemistry. 2018;66(43):11362-71.
Banerjee S, Jeyaseelan S, Guleria R. Trial of lycopene to prevent pre-eclampsia in healthy primigravidas: results show some adverse effects. The journal of obstetrics and gynaecology research. 2009;35(3):477-82.
Barber NJ, Zhang X, Zhu G, Pramanik R, Barber JA, Martin FL, et al. Lycopene inhibits DNA synthesis in primary prostate epithelial cells in vitro and its administration is associated with a reduced prostate-specific antigen velocity in a phase II clinical study. Prostate Cancer Prostatic Dis. 2006;9(4):407-13.
Basu A, Imrhan V. Tomatoes versus lycopene in oxidative stress and carcinogenesis: conclusions from clinical trials. Eur J Clin Nutr. 2007;61(3):295-303.
Beenakumary T, Gopinathan A, Varghese M, Raghavan R, Najeer M, Pius A. Evaluation of Therapeutic Efficacy of Different Treatment Modalities in Oral Submucous Fibrosis: a Comparative Study. Journal of contemporary dental practice. 2019;20(3):390‐4.
Beynon RA, Richmond RC, Santos Ferreira DL, Ness AR, May M, Smith GD, et al. Investigating the effects of lycopene and green tea on the metabolome of men at risk of prostate cancer: The ProDiet randomised controlled trial. International journal of cancer. 2018;144(8):1918-28.
Bi S, Li L, Gu H, Li M, Xu S, Bu W, et al. Lycopene upregulates ZO-1 and downregulates claudin-1 through autophagy inhibition in the human cutaneous squamous cell carcinoma cell line COLO-16. Journal of Cancer. 2019;10(2):510-21.
Bunker CH, McDonald AC, Evans RW, de-la RN, Boumosleh JM, Patrick AL. A randomized trial of lycopene supplementation in Tobago men with high prostate cancer risk. Nutrition and cancer. 2007;57:130-7.
Burgess LC, Rice E, Fischer T, Seekins JR, Burgess TP, Sticka SJ, et al. Lycopene has limited effect on cell proliferation in only two of seven human cell lines (both cancerous and noncancerous) in an in vitro system with doses across the physiological range. ToxicolIn Vitro. 2008;22(5):1297-300.
Catano JG, Trujillo CG, Caicedo JI, Bravo-Balado A, Robledo D, Marino-Alvarez AM, et al. [Efficacy of lycopene intake in primary prevention of prostate cancer: a systematic review of the literature and meta-analysis.]. Archivos espanoles de urologia. 2018;71(2):187-97.
Celik H, Kucukler S, Ozdemir S, Comakli S, Gur C, Kandemir FM, et al. Lycopene protects against central and peripheral neuropathy by inhibiting oxaliplatin-induced ATF-6 pathway, apoptosis, inflammation and oxidative stress in brains and sciatic tissues of rats. Neurotoxicology. 2020;80:29-40.
Chen F, Hu J, Liu P, Li J, Wei Z, Liu P. Carotenoid intake and risk of non-Hodgkin lymphoma: a systematic review and dose-response meta-analysis of observational studies. Annals of hematology. 2016;96(6):957-65.
Chen J, Jiang W, Shao L, Zhong D, Wu Y, Cai J. Association between intake of antioxidants and pancreatic cancer risk: a meta-analysis. International journal of food sciences and nutrition. 2016;67(7):744-53.
Chen J, Song Y, Zhang L. Effect of lycopene supplementation on oxidative stress: an exploratory systematic review and meta-analysis of randomized controlled trials. Journal of medicinal food. 2013;16(5):361-74.
Chen L, Stacewicz-Sapuntzakis M, Duncan C, Sharifi R, Ghosh L, van BR, et al. Oxidative DNA damage in prostate cancer patients consuming tomato sauce-based entrees as a whole-food intervention. J NatlCancer Inst. 2001;93(24):1872-9.
Chen P, Zhang W, Wang X, Zhao K, Negi DS, Zhuo L, et al. Lycopene and Risk of Prostate Cancer: A Systematic Review and Meta-Analysis. Medicine. 2015;94(33):e1260.
Cheng HM, Koutsidis G, Lodge JK, Ashor AW, Siervo M, Lara J. Lycopene and tomato and risk of cardiovascular diseases: A systematic review and meta-analysis of epidemiological evidence. Critical Reviews in Food Science and Nutrition. 2017:1-18.
Clark PE, Hall MC, Borden LS, Jr., Miller AA, Hu JJ, Lee WR, et al. Phase I-II prospective dose-escalating trial of lycopene in patients with biochemical relapse of prostate cancer after definitive local therapy. Urology. 2006;67(6):1257-61.
Conlon LE, Wallig MA, Erdman JW, Jr. Low-lycopene containing tomato powder diet does not protect against prostate cancer in TRAMP mice. Nutrition research (New York, NY). 2015;35(10):882-90.
Cui K, Li X, Du Y, Tang X, Arai S, Geng Y, et al. Chemoprevention of prostate cancer in men with high-grade prostatic intraepithelial neoplasia (HGPIN): a systematic review and adjusted indirect treatment comparison. Oncotarget. 2017;8(22):36674-84.
Datta M, Taylor ML, Frizzell B. Dietary and serum lycopene levels in prostate cancer patients undergoing intensity-modulated radiation therapy. Journal of medicinal food. 2013;16(12):1131-7.
Diener R, Christian M. Lycopene Overview: What It Is and What It Does. In: VR P, RR W, editors. Lycopene: nutritional, medicinal and therapeutic properties. Enfield: Science Publishers; 2008. p. 3-16.
Eliassen AH, Liao X, Rosner B, Tamimi RM, Tworoger SS, Hankinson SE. Plasma carotenoids and risk of breast cancer over 20 y of follow-up. The American journal of clinical nutrition. 2015;101(6):1197-205.
Estévez-Santiago R, Beltrán-de-Miguel B, Olmedilla-Alonso B. Assessment of dietary lutein, zeaxanthin and lycopene intakes and sources in the Spanish survey of dietary intake (2009–2010). International journal of food sciences and nutrition. 2016;67(3):305-13.
Faisal W, Ruane-O'Hora T, O'Driscoll CM, Griffin BT. A novel lipid-based solid dispersion for enhancing oral bioavailability of Lycopene--in vivo evaluation using a pig model. International journal of pharmaceutics. 2013;453(2):307-14.
Feifer AH, Fleshner NE, Klotz L. Analytical accuracy and reliability of commonly used nutritional supplements in prostate disease. J Urol. 2002;168(1):150-4; discussion 4.
Ford NA, Moran NE, Smith JW, Clinton SK, Erdman JW, Jr. An interaction between carotene-15,15'-monooxygenase expression and consumption of a tomato or lycopene-containing diet impacts serum and testicular testosterone. Int J Cancer. 2012;131(2):E143-E8.
Giovannucci E. Tomatoes, tomato-based products, lycopene, and cancer: review of the epidemiologic literature. J NatlCancer Inst. 1999;91(4):317-31.
Han H, Lim JW, Kim H. Lycopene Inhibits Activation of Epidermal Growth Factor Receptor and Expression of Cyclooxygenase-2 in Gastric Cancer Cells. Nutrients. 2019;11(9).
Haseen F, Cantwell MM, O'Sullivan JM, Murray LJ. Is there a benefit from lycopene supplementation in men with prostate cancer? A systematic review (Structured abstract). Prostate Cancer and Prostatic Diseases. 2009;12:325-32.
Ilic D, Forbes KM, Hassed C. Lycopene for the prevention of prostate cancer. Cochrane Database SystRev. 2011(11):CD008007.
Ip BC, Hu KQ, Liu C, Smith DE, Obin MS, Ausman LM, et al. Lycopene metabolite, apo-10'-lycopenoic acid, inhibits diethylnitrosamine-initiated, high fat diet-promoted hepatic inflammation and tumorigenesis in mice. Cancer prevention research (Philadelphia, Pa). 2013;6(12):1304-16.
Ip BC, Liu C, Ausman LM, von Lintig J, Wang XD. Lycopene attenuated hepatic tumorigenesis via differential mechanisms depending on carotenoid cleavage enzyme in mice. Cancer prevention research (Philadelphia, Pa). 2014;7(12):1219-27.
Jain A, Sharma G, Ghoshal G, Kesharwani P, Singh B, Shivhare US, et al. Lycopene loaded whey protein isolate nanoparticles: An innovative endeavor for enhanced bioavailability of lycopene and anti-cancer activity. International journal of pharmaceutics. 2018;546(1-2):97-105.
Jatoi A, Burch P, Hillman D, Vanyo JM, Dakhil S, Nikcevich D, et al. A tomato-based, lycopene-containing intervention for androgen-independent prostate cancer: results of a Phase II study from the North Central Cancer Treatment Group. Urology. 2007;69(2):289-94.
Jeong Y, Lim JW, Kim H. Lycopene Inhibits Reactive Oxygen Species-Mediated NF-kappaB Signaling and Induces Apoptosis in Pancreatic Cancer Cells. Nutrients. 2019;11(4).
Jiang LN, Liu YB, Li BH. Lycopene exerts anti-inflammatory effect to inhibit prostate cancer progression. Asian journal of andrology. 2018.
Jiang X, Wu H, Zhao W, Ding X, You Q, Zhu F, et al. Lycopene improves the efficiency of anti-PD-1 therapy via activating IFN signaling of lung cancer cells. Cancer cell international. 2019;19:68.
Karemore TV, Motwani M. Evaluation of the effect of newer antioxidant lycopene in the treatment of oral submucous fibrosis. Indian journal of dental research : official publication of Indian Society for Dental Research. 2012;23(4):524-8.
Kim HS, Bowen P, Chen L, Duncan C, Ghosh L, Sharifi R, et al. Effects of tomato sauce consumption on apoptotic cell death in prostate benign hyperplasia and carcinoma. NutrCancer. 2003;47(1):40-7.
Kim M, Kim SH, Lim JW, Kim H. Lycopene induces apoptosis by inhibiting nuclear translocation of beta-catenin in gastric cancer cells. Journal of physiology and pharmacology : an official journal of the Polish Physiological Society. 2019;70(4).
Kucuk O, Sarkar FH, Sakr W, Djuric Z, Pollak MN, Khachik F, et al. Phase II randomized clinical trial of lycopene supplementation before radical prostatectomy. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsoredbythe American Society of Preventive Oncology. 2001;10:861-8.
Kulhan NG, Kulhan M, Turkler C, Ata N, Kiremitli T, Kiremitli S, et al. Effect of lycopene on oxidative ovary-damage induced by cisplatin in rats. General physiology and biophysics. 2019;38(3):253-8.
Li W, Yalcin M, Lin Q, Ardawi MM, Mousa SA. Self-assembly of green tea catechin derivatives in nanoparticles for oral lycopene delivery. Journal of controlled release: official journal of the Controlled Release Society. 2017;248:117-24.
Li X, Xu J. Meta-analysis of the association between dietary lycopene intake and ovarian cancer risk in postmenopausal women. Scientific reports. 2014;4:4885.
Linus Pauling Institute. Carotenoids. Alpha-Carotene, Beta-Carotene, Beta-Cryptoxanthin, Lycopene, Lutein, and Zeaxanthin.
Llanos A, Peng J, Pennell M, Krok J, Vitolins M, Degraffinreid C, et al. Effects of tomato and soy on serum adipokine concentrations in postmenopausal women at increased breast cancer risk: a cross-over dietary intervention trial. Journal of clinical endocrinology and metabolism. 2014; 99(2):[625-32 pp.]
Lopez-Jornet P, Gomez-Garcia F, Garcia Carrillo N, Valle-Rodriguez E, Xerafin A, Vicente-Ortega V. Radioprotective effects of lycopene and curcumin during local irradiation of parotid glands in Sprague Dawley rats. The British journal of oral & maxillofacial surgery. 2016;54(3):275-9.
Mahmoodnia L, Mohammadi K, Masumi R. Ameliorative effect of lycopene effect on cisplatin-induced nephropathy in patient. Journal of nephropathology. 2017;6(3):144-9.
Mein JR, Lian F, Wang XD. Biological activity of lycopene metabolites: implications for cancer prevention. NutrRev. 2008;66(12):667-83.
Michaud DS, Feskanich D, Rimm EB, Colditz GA, Speizer FE, Willett WC, et al. Intake of specific carotenoids and risk of lung cancer in 2 prospective US cohorts. Am J Clin Nutr. 2000;72(4):990-7.
Mohanty NK, Saxena S, Singh UP, Goyal NK, Arora RP. Lycopene as a chemopreventive agent in the treatment of high-grade prostate intraepithelial neoplasia. Urologic Oncology. 2005;23:383-5.
Mustra Rakic J, Liu C, Veeramachaneni S, Wu D, Paul L, Chen CO, et al. Lycopene Inhibits Smoke-Induced Chronic Obstructive Pulmonary Disease and Lung Carcinogenesis by Modulating Reverse Cholesterol Transport in Ferrets. Cancer prevention research (Philadelphia, Pa). 2019;12(7):421-32.
Nguenang GS, Ntyam ASM, Kuete V. Acute and Subacute Toxicity Profiles of the Methanol Extract of Lycopersicon esculentum L. Leaves (Tomato), a Botanical with Promising In Vitro Anticancer Potential. Evidence-based complementary and alternative medicine : eCAM. 2020;2020:8935897.
Nordstrom T, Van Blarigan EL, Ngo V, Roy R, Weinberg V, Song X, et al. Associations between circulating carotenoids, genomic instability and the risk of high-grade prostate cancer. The Prostate. 2015;76(4):339-48.
Norwegian Scientific Committee for Food Safety. Risk assessment of "other substances" – Lycopene. Opinion of the Panel on Food Additives, Flavourings, Processing Aids, Materials in Contact with Food and Cosmetics of the Norwegian Scientific Committee for Food Safety,. Oslo; 2016.
Paur I, Lilleby W, Bohn SK, Hulander E, Klein W, Vlatkovic L, et al. Tomato-based randomized controlled trial in prostate cancer patients: Effect on PSA. Clinical nutrition (Edinburgh, Scotland). 2016;36(3):672-9.
Rao AV, Rao LG. Carotenoids and human health. Pharmacol Res. 2007;55(3):207-16.
Ross AB, Vuong le T, Ruckle J, Synal HA, Schulze-Konig T, Wertz K, et al. Lycopene bioavailability and metabolism in humans: an accelerator mass spectrometry study. Am J Clin Nutr. 2011;93(6):1263-73.
Rotelli MT, Bocale D, De Fazio M, Ancona P, Scalera I, Memeo R, et al. IN-VITRO evidence for the protective properties of the main components of the Mediterranean diet against colorectal cancer: A systematic review. Surgical oncology. 2015;24(3):145-52.
Rowles JL, 3rd, Ranard KM, Smith JW, An R, Erdman JW, Jr. Increased dietary and circulating lycopene are associated with reduced prostate cancer risk: a systematic review and meta-analysis. Prostate cancer and prostatic diseases. 2017;20(4):361-77.
Rowles JL, Smith JW, Applegate CC, Miller RJ, Wallig MA, Kaur A, et al. Dietary Tomato or Lycopene Do Not Reduce Castration-Resistant Prostate Cancer Progression in a Murine Model. The Journal of nutrition. 2020;150(7):1808-17.
Sahin K, Orhan C, Tuzcu M, Sahin N, Ali S, Bahcecioglu IH, et al. Orally administered lycopene attenuates diethylnitrosamine-induced hepatocarcinogenesis in rats by modulating Nrf-2/HO-1 and Akt/mTOR pathways. Nutrition and cancer. 2014;66(4):590-8.
Sahin K, Sahin N, Kucuk O. Lycopene and chemotherapy toxicity. NutrCancer. 2010;62(7):988-95.
Sahin K, Yenice E, Tuzcu M, Orhan C, Mizrak C, Ozercan IH, et al. Lycopene Protects Against Spontaneous Ovarian Cancer Formation in Laying Hens. Journal of cancer prevention. 2018;23(1):25-36.
Saran G, Umapathy D, Misra N, Channaiah SG, Singh P, Srivastava S, et al. A comparative study to evaluate the efficacy of lycopene and curcumin in oral submucous fibrosis patients: A randomized clinical trial. Indian journal of dental research : official publication of Indian Society for Dental Research. 2018;29(3):303-12.
Schunck CA. The xanthophyll group of yellow colouring matters. Proceedings of the Royal Society of London. 1904;72(477-486):165-76.
Schwarz S, Obermller-Jevic UC, Hellmis E, Koch W, Jacobi G, Biesalski HK. Lycopene inhibits disease progression in patients with benign prostate hyperplasia. The Journal of nutrition. 2008;138:49-53.
Sesso HD, Buring JE, Zhang SM, Norkus EP, Gaziano JM. Dietary and plasma lycopene and the risk of breast cancer. Cancer EpidemiolBiomarkers Prev. 2005;14(5):1074-81.
Shao A, Hatchcock J. Risk Assessment of Lycopene. In: VR Preedy RW, editor. Lycopene : nutritional, medicinal and therapeutic properties Enfield: Science Publishers; 2008. p. 83-104.
Shen C, Wang S, Shan Y, Liu Z, Fan F, Tao L, et al. Chemomodulatory efficacy of lycopene on antioxidant enzymes and carcinogen-induced cutaneum carcinoma in mice. Food & function. 2014;5(7):1422-31.
Slattery ML, Benson J, Curtin K, Ma KN, Schaeffer D, Potter JD. Carotenoids and colon cancer. Am J Clin Nutr. 2000;71(2):575-82.
Soares N, Elias MB, Lima Machado C, Trindade BB, Borojevic R, Teodoro AJ. Comparative Analysis of Lycopene Content from Different Tomato-Based Food Products on the Cellular Activity of Prostate Cancer Cell Lines. Foods (Basel, Switzerland). 2019;8(6).
Stojiljkovic N, Ilic S, Stojanovic N, Stojanovic S, Stoiljkovic M. Lycopene improves methotrexate-induced functional alterations of the Madin-Darby kidney cells in a concentration-dependent manner. Can J Physiol Pharmacol. 2019;98(2):111-6.
Sunaga K, Ohkawa K, Nakamura K, Ohkubo A, Harada S, Tsuda T. Mechanism-based inhibition of recombinant human cytochrome P450 3A4 by tomato juice extract. Biological & pharmaceutical bulletin. 2012;35(3):329-34.
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. Research and reports in urology. 2020;12:137-43.
van-Breemen RB, Sharifi R, Viana M, Pajkovic N, Zhu D, Yuan L, et al. Antioxidant effects of lycopene in African American men with prostate cancer or benign prostate hyperplasia: a randomized, controlled trial. Cancer Prevention Research. 2011;4:711-8.
Vandevijvere S, Cucu T, Vinkx C, Huvaere K, Huybrechts I, Van Loco J. Dietary intake of lycopene by the Belgian adult population. Public Health Nutrition. 2013;17(2):248-55.
Veeramachaneni S, Ausman LM, Choi SW, Russell RM, Wang XD. High dose lycopene supplementation increases hepatic cytochrome P4502E1 protein and inflammation in alcohol-fed rats. J Nutr. 2008;138(7):1329-35.
Vrieling A, Voskuil DW, Bonfrer JM, Korse CM, van DJ, Cats A, et al. Lycopene supplementation elevates circulating insulin-like growth factor binding protein-1 and -2 concentrations in persons at greater risk of colorectal cancer. The American journal of clinical nutrition. 2007;86:1456-62.
Wan L, Tan HL, Thomas-Ahner JM, Pearl DK, Erdman JW, Jr., Moran NE, et al. Dietary tomato and lycopene impact androgen signaling- and carcinogenesis-related gene expression during early TRAMP prostate carcinogenesis. Cancer prevention research (Philadelphia, Pa). 2014;7(12):1228-39.
Wang R, Lu X, Yu R. Lycopene Inhibits Epithelial-Mesenchymal Transition and Promotes Apoptosis in Oral Cancer via PI3K/AKT/m-TOR Signal Pathway. Drug design, development and therapy. 2020;14:2461-71.
Wang X, Yang HH, Liu Y, Zhou Q, Chen ZH. Lycopene Consumption and Risk of Colorectal Cancer: A Meta-Analysis of Observational Studies. Nutrition and cancer. 2016;68(7):1083-96.
Wang Y, Cui R, Xiao Y, Fang J, Xu Q. Effect of Carotene and Lycopene on the Risk of Prostate Cancer: A Systematic Review and Dose-Response Meta-Analysis of Observational Studies. PloS one. 2015;10(9):e0137427.
Xia H, Liu C, Li CC, Fu M, Takahashi S, Hu KQ, et al. Dietary Tomato Powder Inhibits High-Fat Diet-Promoted Hepatocellular Carcinoma with Alteration of Gut Microbiota in Mice Lacking Carotenoid Cleavage Enzymes. Cancer prevention research (Philadelphia, Pa). 2018;11(12):797-810.
Xu J, Li Y, Hu H. Effects of lycopene on ovarian cancer cell line SKOV3 in vitro: Suppressed proliferation and enhanced apoptosis. Molecular and cellular probes. 2019;46:101419.
Yang T, Yang X, Wang X, Wang Y, Song Z. The role of tomato products and lycopene in the prevention of gastric cancer: a meta-analysis of epidemiologic studies. Medical hypotheses. 2013;80(4):383-8.
Zhou X, Burke KE, Wang Y, Wei H. Dietary Lycopene Protects SKH-1 Mice Against Ultraviolet B-Induced Photocarcinogenesis. Journal of drugs in dermatology : JDD. 2019;18(12):1244-54.
Zhu J, Hu Q, Shen S. Enhanced antitumor efficacy and attenuated cardiotoxicity of doxorubicin in combination with lycopene liposomes. J Liposome Res. 2019;30(1):37-44.
Zu K, Mucci L, Rosner BA, Clinton SK, Loda M, Stampfer MJ, et al. Dietary lycopene, angiogenesis, and prostate cancer: a prospective study in the prostate-specific antigen era. Journal of the National Cancer Institute. 2014;106(2):djt430.