Lycopene

Brand names: All-trans-lycopene, Lycopene, Psi,psi-carotene, Psi-carotene

Usage of Lycopene

Lycopene exerts antioxidant effects, induces apoptosis and cell-cycle arrest, and modulates cyclooxygenase pathways.(Heber 2002)

Alcoholic liver disease

A review suggests lycopene inhibits alcohol-induced CYP2E1, an effect that may be associated with decreased development of alcoholic liver disease.(Stice 2018)

Anti-inflammatory effects

Animal and in vitro data

In a murine model of acute pancreatitis, lycopene reduced TNF-alpha, myeloperoxidase activity, and gene expression of inducible nitric oxide synthase. Histology of the pancreas was also improved in the lycopene group.(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.(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.(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.(Saedisomeolia 2009)

Clinical data

Epidemiological studies have found that lycopene decreases the inflammation marker C-reactive protein.(Erdman 2009) The production of inflammatory mediators, such as TNF-alpha, was reduced in patients consuming a tomato-based drink.(Riso 2006) Asthmatic adults receiving lycopene treatment experienced improvement in airway inflammation. Patients treated with the tomato extract also had reduced sputum neutrophil elastase activity.(Wood 2008)

Antioxidant effects

In a review examining the mechanisms linking lycopene in the human diet and vascular changes, lycopene was 2- to 10-fold more efficient in quenching singlet oxygen than beta-carotene and alpha-tocopherol, respectively. Lycopene also modulates production of the antioxidant enzymes superoxide dismutase and catalase.(Mozos 2018) The 11 conjugated double bonds give lycopene the ability to interact with reactive oxygen species.(Grabowska 2019, Tvrdá 2016)

In vitro data

In a study of bovine sperm, lycopene exhibited significant reactive oxygen species–scavenging 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.(Grabowska 2019, Tvrdá 2016)

Clinical data

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.(Darvin 2008) In an 8-week, double-blind, randomized, placebo-controlled trial, purified lycopene supplementation decreased DNA oxidative damage.(Devaraj 2008) Lycopene may also ameliorate the oxidative stress of cigarette smoke, including according to a study in 15 healthy, normolipidemic subjects in whom plasma antioxidant levels were measured before and 4 weeks after smoking cessation.(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.(Grabowska 2019)

Benign prostatic hyperplasia

Animal data

In a murine model of benign prostatic hyperplasia, lycopene supplementation was found to ameliorate testosterone-induced increases in prostate weight.(Zou 2014)

Bone mineral density

Clinical data

In the European Prospective Investigation into Cancer and Nutrition (EPIC)-Norfolk cohort, lycopene intake was associated with an increase in heel bone mineral density in women (P=0.005).(Hayhoe 2017)

Cancer

Oxidative stress is recognized as a major contributor to increased cancer risk. Lycopene's efficient absorption from tomato products facilitates its antioxidant effects and may also play an important role in cancer prevention.(Rao 1998)

Human epidemiological evidence indicates that diets high in tomatoes may reduce the risk of cervical, colon, esophageal, oral, rectal, prostate, and stomach cancers.(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,
  • Antioxidant response element or stimulation of cells to produce enzymes to protect against free radicals,
  • Apoptosis or elimination of unhealthy abnormal cells,
  • 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

    • Lycopene has shown some benefit in reducing cisplatin-induced nephropathy and ovarian damage.(Kulhan 2019, Mahmoodnia 2017) However, more studies are needed to fully understand these effects.

    Animal and in vitro data

    In vitro, lycopene has been found to inhibit human colon carcinoma, myeloid leukemia, and lymphoma cell lines in a dose-dependent manner.(Salman 2007) Lycopene and eicosapentaenoic acid also suppressed signal transduction pathways in human colon cancer cells, thus inhibiting cancer cell growth.(Tang 2009) Another study documented activity against a liver adenocarcinoma cell line and a noncancerous lung cell line.(Burgess 2008) Lycopene prevented chemically induced DNA and chromosome damage as well as tumor-promoting activity in liver cells through antioxidant activity and inhibition of growth factors and signaling pathways.(Huang 2007, Scolastici 2008, Tharappel 2008) Decreased insulin growth factor 1 contributed to reduced growth in human prostate cancer cells treated with lycopene.(Tjahjodjati 2020) A comparative analysis assessed the impact of various tomato-based food products on prostate cancer cell lines. Decreased cell viability and increased apoptosis occurred after treatment with all tomato-based products tested. There was a decrease in the percentage of prostate cancer cells in G0/G1 and G2/M phases after 96 hours of treatment with tomato paste and tomato extract. 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.(Soares 2019) Lycopene decreased cell proliferation and increased apoptosis in MCF-7 human breast cancer cells.(Peng 2017) In another in vitro study, lycopene increased apoptosis in a cell line of human head and neck squamous carcinoma.(Ye 2016) In vitro data also showed that lycopene exerts activity against pancreatic cancer cells.(Jeong 2019) In a murine model of ovarian cancer, lycopene given intralesionally reduced tumor burden and metastatic load.(Holzapfel 2017)

    Clinical data

    Breast

    In a clinical trial, tomato-derived lycopene supplementation (30 mg/day for 2 months) had beneficial effects in healthy women with a high risk of breast cancer (n=36) but not in breast cancer survivors (n=24).(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. However, after exclusion of breast cancer cases diagnosed during the first 2 years of follow-up, the association was no longer statistically significant.(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.(Eliassen 2012)

    Cervical

    Lycopene's protective role in the early stages of cervical carcinogenesis was noted in one study.(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.(Cho 2009, Palan 1996)

    Oral

    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.(Lodi 2016) A compounded lycopene gel administered for 1 month was beneficial in reducing the size of oral leukoplakia lesion caused by tobacco use.(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.

    Pancreatic

    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%. Lycopene protected against cancer by activating cancer-preventive phase 2 enzymes.(Nkondjock 2005, Singh 2008)

    Prostate

    Growing evidence exists for the use of lycopene in prostate cancer prevention. Although numerous animal studies exist,(van Breemen 2008) only clinical evidence was reviewed in the following studies. In a 2017 systematic review and meta-analysis including 42 studies, 43,851 cases of prostate cancer were reported in 692,012 participants. Dietary intake (relative risk ratio [RR], 0.88; 95% CI, 0.78 to 0.98; P=0.017) and circulating concentrations of lycopene (RR, 0.88; 95% CI, 0.79 to 0.98; P=0.019) were associated with a reduced risk of prostate cancer. Additionally, for every 2 mg of lycopene consumed, the investigators found a 1% decrease in prostate cancer risk.(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. Meta-analysis revealed no difference in prostate-specific antigen levels or in lycopene levels with and without lycopene supplementation. Only one study reported incidence of prostate cancer (10% vs 30% in the lycopene vs control groups).(Ilic 2011) In another review of 8 randomized controlled trials, varying quality of the studies made conclusions regarding use of lycopene for prevention or treatment of benign prostatic hyperplasia or prostate cancer impossible.(Illic 2012) In another study, lycopene concentrations changed rapidly in men with prostate cancer given lycopene supplements for several weeks prior to radical prostatectomy. Apoptotic activity was observed and may have been caused by lycopene. Prostate volume was reduced in prostate cancer patients taking lycopene extract 30 mg/day for 3 weeks prior to radical prostatectomy.(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.(Karppi 2009) Lycopene not only achieves high concentrations in the prostate, but also in the testes and adrenal glands.

    Stomach/Colon

    An association between lycopene intake and decreased stomach cancer risk has been observed.(Gerster 1997, Kim 2018) Lycopene was more efficient than any carotenoid in inhibiting insulinlike growth factor type 1 (high levels of this growth factor are related to an increased risk of cancer) in patients with a higher risk of colorectal cancer.(Graydon 2007, Vrieling 2007) A meta-analysis of observational studies explored the association between lycopene consumption and risk of colorectal cancer. Of the 15 studies that met inclusion criteria, 11 were case controlled and 4 were cohort studies, with heterogeneity found among the studies. 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. Additionally, no dose relationship was observed.(Wang 2016)

    Cardiovascular disease/Cardiometabolic syndrome

    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.(Costa-Rodrigues 2018)

    Animal and in vitro data

    Lycopene suppressed tissue factor activation in vascular thrombosis in human endothelial cells.(Lee 2006) Additional studies found that lycopene reduced expression of cell surface adhesion molecules and binding of monocytes.(Hung 2008, Martin 2000) Lycopene also bound and inhibited platelet-derived growth factor, which is associated with the development and progression of cardiovascular disease in rat smooth muscle cells.(Lo 2007) One nutritional study in rabbits compared lycopene's action in reducing the formation of atherosclerotic plaques in the aorta with that of fluvastatin; similar to fluvastatin, lycopene significantly attenuated atherogenesis in rabbits fed a high-fat diet.(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. Although significant, these effects were less than those achieved in the atorvastatin group. 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]).(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. Lycopene and tomato powder exerted inflammatory effects, as noted by a reduction in cytokine and chemokine expression in adipose tissue.(Fenni 2017) In mice, intravenous lycopene reduced myocardial ischemia-reperfusion injury through suppression of reactive oxygen species accumulation and consequent inflammation.(Tong 2016)

    Clinical data

    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.(Agarwal 1998) An epidemiological study in 10 European countries also showed beneficial effects on the heart correlating with lycopene lipid levels and reduced risk of myocardial infarction.(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.(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.(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.(McEneny 2013) In another study, low lycopene concentrations were associated with carotid atherosclerosis in 220 asymptomatic individuals.(Riccioni 2008)

    In a study of 50 moderately hypertensive individuals, tomato extract supplementation for 6 weeks was associated with reduced systolic and diastolic blood pressure (SBP and DBP) and increased serum lycopene levels.(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. 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. 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.(Li 2013) Similar results were found in a meta-analysis of 4 intervention trials published between 1955 and 2010.(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). Participants received lycopene 7 mg or placebo daily for 2 months. 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. No significant changes in EDV were observed with placebo. Post hoc analysis demonstrated a positive dose-response correlation between lycopene concentration and absolute change in EDV response between visits (P=0.019). No significant changes were seen in arterial stiffness or blood pressure between the lycopene- and placebo-treated groups. Lycopene was well tolerated; no serious adverse events were reported.(Gajendragadkar 2014) In a clinical trial of 142 patients with coronary vascular disease, ingestion of lycosome-formulated lycopene 7 mg daily for 30 days increased flow-mediated dilation (FMD) and oxygen saturation but had no effect on ankle-brachial index test, pulse rate, or systemic blood pressure. Such increases in FMD and oxygen saturation were not noted in patients taking a lactolycopene formulation. Thus, specific formulation used may impact potential outcomes.(Petyaev 2018)

    In a 2019 systematic review and meta-analysis of 25 studies (N=211,704), high lycopene intake or serum levels were associated with a significant decrease in the risk of stroke (26%; hazard ratio [HR], 0.74; 95% CI, 0.62 to 0.89; P=0.02), mortality (37%; HR, 0.63; 95% CI, 0.49 to 0.81; P<0.001), and cardiovascular disease (14%; HR, 0.86; 95% CI, 0.77 to 0.95; P=0.003). No significant associations were noted for myocardial infarction, atherosclerosis, heart failure, or atrial fibrillation.(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). This result remained consistent when the authors reviewed dietary studies (RR, 0.87; 95% CI, 0.79 to 0.96) and biomarker studies (RR, 0.74; 95% CI, 0.62 to 0.87).(Song 2017) Beneficial cardiovascular effects noted with lycopene may be due in part to its antiplatelet effects.(Mozos 2018)

    Cataracts

    Clinical data

    A meta-analysis of 13 observational studies (N=18,999) evaluated the association between blood levels of antioxidants and vitamins and the risk of age-related cataracts. Based on results of 5 relevant studies with no substantial heterogeneity, lycopene intake showed no significant association with cataract risk.(Cui 2013)

    CNS effects

    Lycopene has been studied for its neuroprotective effects; potential mechanisms include inhibition of oxidative stress, neuroinflammation, and neuronal apoptosis, as well as restoration of mitochondrial dysfunction.(Chen 2019)

    Animal data

    In a murine model of lipopolysaccharide-induced memory loss, lycopene attenuated cognitive impairment, neuroinflammation, oxidative stress, and formation and accumulation of amyloid plaques.(Wang 2018) In an animal model of neuroinflammation, lycopene improved spatial learning and memory impairment, suggesting a potential role in Alzheimer disease.(Sachdeva 2015)

    In a rat model of diabetes, lycopene alone and in combination with insulin exerted neuroprotective effects and attenuated apoptosis in the hippocampal regions of the brain.(Malekiyan 2019)

    In a murine model of 3-nitropropionic acid–induced Huntington disease, lycopene 10 mg/kg administered for 15 days ameliorated mitochondrial dysfunction.(Sandhir 2010)

    In mice with Parkinson disease, lycopene 5 to 20 mg/kg/day attenuated oxidative stress and motor abnormalities and reversed apoptosis.(Prema 2015)

    In an epilepsy animal model, lycopene in combination with valproate sodium exerted neuroprotective effects.(Bhardwaj 2016)

    Clinical data

    In a systematic review, lycopene was associated with maintaining cognition. One study in the review showed an association between low levels of lycopene and higher rates of Alzheimer disease.(Crowe-White 2019)

    The Austrian Stroke Prevention Study found that certain concentrations of lycopene and other antioxidants may protect against cognitive impairment.(Schmidt 1998)

    Dental hygiene

    Animal data

    In a model of ovariectomized rats with osteopenia, lycopene improved titanium implant osseointegration and bone formation 12 weeks after implantation.(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.(Li 2017)

    Clinical data

    Clinical studies suggest lycopene may be effective as a first-line therapy in treating oral submucous fibrosis(Kumar 2007) and in combination with other therapies in treating gingivitis.(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.(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.(Johny 2019)

    Dermatologic effects

    In vitro data

    In an in vitro study, lycopene exerted a corrective effect in photodamaged keratinocytes.(Ascenso 2016)

    Clinical data

    Reports exist of positive outcomes with beta-carotene in skin disorders, including cancer, pigment imbalance, and photodermatoses(Beta carotene 1991, Pietzcker 1977, Pietzcker 1979, Pollitt 1975); however, lycopene may not share these effects because of its structural configuration. One report found beta-carotene to be active in wound healing, while lycopene was inactive.(Lee 1970) Other studies document that lycopene or tomato-derived products rich in lycopene provide photoprotective effects against ultraviolet light–induced erythema.(Grether-Beck 2017, Rizwan 2011, Stahl 2001, Stahl 2006) Higher levels of lycopene antioxidants in the skin have effectively led to lower levels of skin roughness.(Darvin 2008) In a placebo-controlled study, lycopene effectively managed oral lichen planus.(Saawarn 2011)

    Diabetes

    Animal and in vitro data

    Antioxidant effects (eg, decreased hydrogen peroxide and lipid peroxidation) may explain some of lycopene's effects in diabetes.(Roohbakhsh 2017) In some animal models, lycopene reduced diabetes-induced learning and memory impairment by decreasing oxidative stress and inflammation.(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.(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.(Neyestani 2007, Ozmen 2016, Zheng 2019) In a murine model, lycopene reduced biomarkers of diabetic nephropathy.(Roohbakhsh 2017)

    Clinical data

    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). Additionally, each 1 mg increase in lycopene was associated with a 0.09 mg/dL decrease in fasting blood glucose.(Gao 2019)

    Lycopene side effects

    Tomato-based products and lycopene supplements are generally well tolerated. The literature documents some GI complaints, such as diarrhea, dyspepsia, gas, nausea, and vomiting. One trial documented a cancer-related hemorrhage in a patient taking lycopene, but causality was unclear.(Jatoi 2007) Tomato-based products are acidic and may irritate stomach ulcers.

    Before taking Lycopene

    Avoid use. Information regarding safety and efficacy in pregnancy and lactation is lacking. Clinical studies evaluating the effects of supplemental lycopene in preeclampsia have produced conflicting results regarding benefit, and some evidence of harm has been reported.(Banerjee 2009, Sharma 2003) Amounts typically found in food are considered safe. Tomato consumption increases lycopene concentrations in the breast milk and plasma of lactating women.(Alien 2002)

    How to use Lycopene

    There is no consensus regarding recommended daily dosing and duration of lycopene. The Observed Safe Level methodology indicates up to 75 mg/day of lycopene is safe.(Grabowska 2019) In the United States, reported daily intake ranges from 3.7 to 16.2 mg/day.(Grabowska 2019, Petyaev 2016) Lycopene is available in various doseforms (eg, capsule, softgel) and is also incorporated in multivitamin and multimineral products.

    Warnings

    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.(Jian 2008) Additionally, lycopene 100 mg daily was not associated with adverse effects in volunteers.(Petyaev 2016)

    What other drugs will affect Lycopene

    Calcium-containing products: Lycopene decreases the bioavailability of calcium by 84%.(Grabowska 2019)

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