viernes, 4 de octubre de 2019

Prostate Cancer, Nutrition, and Dietary Supplements (PDQ®) 3/5 –Health Professional Version - National Cancer Institute

Prostate Cancer, Nutrition, and Dietary Supplements (PDQ®)–Health Professional Version - National Cancer Institute

National Cancer Institute

Prostate Cancer, Nutrition, and Dietary Supplements (PDQ®)–Health Professional Version


Lycopene




Overview

This section contains the following key information:

General Information and History

Lycopene is a phytochemical that belongs to a group of pigments known as carotenoids. It is red and lipophilic. As a natural pigment made by plants, lycopene helps to protect plants from light-induced stress,[1] and it also transfers light energy during photosynthesis.[2] Lycopene is found in a number of fruits and vegetables, including apricots, guavas, and watermelon, but the majority of lycopene consumed in the United States is from tomato-based products.[1]
Lycopene has been investigated for its role in chronic diseases, including cardiovascular disease and cancer. Numerous epidemiological studies suggest that lycopene may help prevent cardiovascular disease. Lycopene may protect against cardiovascular disease by decreasing cholesterol synthesis and increasing the degradation of low-density lipoproteins,[3] although some interventional studies have shown mixed results.[4]
A number of in vitro and in vivo studies suggest that lycopene may also be protective against cancers of the skin, breast, lung, and liver.[5] However, epidemiological studies have yielded inconsistent findings regarding lycopene's potential in reducing cancer risk.
The few human intervention trials have been small and generally focused on intermediate endpoints and not response of clinically evident disease or overall survival and thus have limited translation to practice.[2,6]
On the basis of overall evidence, the association between tomato consumption and reduced risk of prostate cancer is limited.[7]

Preclinical/Animal Studies

In vitro studies

In vitro studies that have examined a link between lycopene and prostate carcinogenesis have suggested several mechanisms by which lycopene might reduce prostate cancer risk. Lycopene is broken down into a number of metabolites that are thought to have various biological effects, including antioxidant capabilities and a role in gap-junction communication.[8]
Treating normal human prostate epithelial cells with lycopene resulted in dose-dependent growth inhibition, indicating that inhibition of prostate cell proliferation may be one way lycopene may lower the risk of prostate cancer.[9]
In addition, treating prostate cancer cells with lycopene resulted in a significant decrease in the number of lycopene-treated cells in the S phase of the cell cycle, suggesting that lycopene may lower cell proliferation by altering cell-cycle progression. Moreover, apo-12’-lycopenal, a lycopene metabolite, reduced prostate cancer cell proliferation and may modulate cell-cycle progression.[10]
Some studies have suggested that cancer cells have altered cholesterol-biosynthesis pathways. Treating prostate cancer cells with lycopene resulted in dose-dependent decreases in 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase (the rate-limiting enzyme in cholesterol synthesis), total cholesterol, and cell growth, and an increase in apoptosis. However, adding mevalonate prevented the growth-inhibitory effects of lycopene, indicating that the mevalonate pathway may be important to the anticancer activity of lycopene.[11] Lycopene may also affect cholesterol levels in prostate cancer cells by activating the peroxisome proliferator-activated receptor gamma (PPARγ)-liver X receptor alpha (LXRα)-ATP-binding cassette, subfamily 1 (ABCA1) pathway, which leads to decreased cholesterol levels and may ultimately result in decreased cell proliferation. ABCA1 mediates cholesterol efflux, and PPARγ has been shown to inhibit the growth and differentiation of prostate cancer cells. In one study, treating prostate cancer cells with lycopene resulted in increased expression of PPARγ, LXRα, and ABCA1 as well as lower total cholesterol. In addition, when the cells were treated with a PPARγ antagonist, cell proliferation increased, whereas treating cells with a combination of the PPARγ antagonist and lycopene decreased cell proliferation.[12]
Adding lycopene to medium containing the LNCaP human prostate adenocarcinoma cell line resulted in decreased DNA synthesis and inhibition of androgen-receptor gene-element activity and expression.[13] In a study that examined the physiologically relevant concentration of lycopene (2 mmol/L) or placebo for 48 hours on protein expression in human primary prostatic epithelial cells, proteins that were significantly upregulated or downregulated following lycopene exposure were those proteins involved in antioxidant responses, cytoprotection, apoptosis, growth inhibition, androgen receptor signaling, and the AKT/mTOR cascade. These data are consistent with previous studies, suggesting that lycopene can prevent malignant transformation in human prostatic epithelial cells at the stages of cancer initiation, promotion, and/or progression.[14]
A study examining the effect of lycopene on multiple points along the nuclear factor-kappa B (NF-kappa B) signaling pathways in prostate cell lines demonstrated a 30% to 40% reduction in inhibitor of kappa B (I-kappa B) phosphorylation, NF-kappa B transcriptional activity and a significant reduction in cell growth at the physiologically relevant concentration of 1.25 μM or higher.[15] These results provided evidence that the anticancer properties of lycopene may occur through inhibition of the NF-kappa B signaling pathway, beginning at the early stage of cytoplasmic IKK kinase activity, which then leads to reduced NF-kappa B–responsive gene regulation. Additionally, these effects in the cancer cells were observed at concentrations of lycopene that are relevant and achievable in vivo.
Some studies have assessed possible beneficial interactions between lycopene and conventional cancer therapies. In one such study, various types of prostate cancer cells were treated with a combination of lycopene and docetaxel, a drug used to treat patients with castration-resistant prostate cancer, or each drug alone. The combination treatment inhibited proliferation in four of five cell lines to a greater extent than did treatment with docetaxel alone. The findings suggest that the mechanism for these effects may involve the IGF-1 receptor (IGF-1R) pathway.[16]

Animal studies

In a chemoprevention study, 59 transgenic adenocarcinoma of the mouse prostate (TRAMP) mice were fed diets supplemented with tomato paste or lycopene beadlets (both preparations contained 28 mg lycopene/kg chow). Mice that received lycopene beadlets exhibited a larger reduction in prostate cancer incidence compared with control mice than mice supplemented with tomato paste, suggesting that lycopene beadlets may provide greater chemopreventive effects than tomato paste.[17]
Ketosamines are carbohydrate derivatives formed when food is dehydrated. In one study, FruHis (a ketosamine in dehydrated tomatoes) combined with lycopene resulted in greater growth inhibition of implanted rat prostate cancer cells than did lycopene or FruHis alone. In addition, in a N-methyl-N-nitrosourea/testosterone-induced prostate carcinogenesis model, rats fed a tomato paste and FruHis diet had longer survival times than rats fed only with tomato paste or tomato powder.[18]
Lycopene has also been studied for potential therapeutic effects in xenograft models. In one study, athymic nude mice were injected with human androgen-independent prostate cancer cells and were treated with either lycopene (4 mg/kg body weight or 16 mg/kg body weight) or beta-carotene (16 mg/kg body weight). Supplementing mice with lycopene or beta-carotene resulted in decreased tumor growth.[19] In an in vitro study, the investigators demonstrated the effect of lycopene in androgen-independent prostate cancer cell lines.[20] In another study, nude mice were injected with human prostate cancer cells and treated with intraperitoneal injections of docetaxel, lycopene (15 mg/kg/d) administered via gavage, or a combination of both. Mice exhibited longer survival times and smaller tumors when treated with a combination of docetaxel and lycopene than when they were treated with docetaxel alone.[16]

Human Studies

Epidemiologic studies

Several epidemiologic studies have assessed potential associations between lycopene intake and prostate cancer incidence.
Epidemiological studies have demonstrated that populations with high intake of dietary lycopene have lower risk of prostate cancer.[7,9-13] Prospective and case-control studies have shown lycopene to be significantly lower in the serum and tissue of patients with cancer than in controls,[7,16-19,21] while other studies have failed to demonstrate such a connection.[22]
An association between lycopene serum concentration and risk of cancer was also examined in men participating in the Kuopio Ischaemic Heart Disease Risk Factor study in Finland. In this prospective cohort study, an inverse association between lycopene levels and overall cancer risk was observed, suggesting that higher concentrations of lycopene may help lower cancer risk overall. Men with the highest levels of serum lycopene had a 45% lower risk of cancer than did men with the lowest levels of lycopene (risk ratio, 0.55; 95% confidence interval (CI), 0.34–0.89; P = .015). However, when the analysis was restricted to specific cancer types, an association was observed for other cancers (risk ratio, 0.43; 95% CI, 0.23–0.79; P = .007) but not prostate cancer.[23]
A 2015 systematic review and meta-analysis of studies investigating dietary lycopene intake/circulating lycopene levels and prostate cancer risk found that when lycopene intake was higher, the incidence of prostate cancer was reduced (P = .078).[24] Similarly, a higher level of circulating lycopene was associated with lower prostate cancer risk. Likewise, a 2017 systematic review and meta-analysis evaluated lycopene dietary intake and circulating lycopene with prostate cancer risk. An inverse association between high levels of both circulating (RR, 0.88; 95% CI, 0.79–0.98; P = .019) and dietary lycopene (RR, 0.88; 95% CI, 0.78–0.98; P = .017) with prostate cancer risk was noted.[25]
The National Cancer Institute's Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial is an ongoing, prospective study that has been a source of subjects for investigations of an association between lycopene intake and prostate cancer risk. A 2006 study examined lycopene and tomato product intakes and prostate cancer risk among PLCO participants who had been followed for an average of 4.2 years. Lycopene and tomato product intakes were assessed via food frequency questionnaires. Overall, no association was found between dietary intake of lycopene or tomato products and the risk of prostate cancer. However, among men with a family history of prostate cancer, increased lycopene consumption was associated with decreased prostate cancer risk.[26] A follow-up study was conducted that examined serum lycopene and risk of prostate cancer in the same group of PLCO participants. The results suggest that there was no significant difference in serum lycopene concentrations between healthy participants and participants who developed prostate cancer.[27]
The Health Professionals Follow-up Study obtained dietary information and ascertained total and lethal prostate cancer cases from 1986 through January 31, 2010. Higher lycopene intake was inversely associated with total prostate cancer risk (hazard ratio [HR], 0.91; 95% CI, 0.84–1.00) and lethal prostate cancer risk (HR, 0.72; 95% CI, 0.56–0.94). A subset analysis was restricted to men who had at least one negative PSA test at the onset, to reduce the influence of PSA screening on the association. The inverse association became markedly stronger (HR, 0.47; 95% CI, 0.29–0.75) for lethal prostate cancer. Levels of tumor markers for angiogenesis, apoptosis, and cellular proliferation and differentiation were monitored. Three of the tumor angiogenesis markers were strongly associated with lycopene intake, so that men with higher intake had tumors that demonstrated less angiogenic potential.[28]
At least two studies examined the effect of lycopene blood levels on the risk of high-grade prostate cancer. The first study examined the associations between carotenoid levels and the risk of high-grade prostate cancer, and also considered antioxidant-related genes and tumor instability. This study demonstrated that plasma carotenoids at diagnosis, particularly among men carrying specific somatic variations, were inversely associated with risk of high-grade prostate cancer. Higher lycopene concentrations were associated with less genomic instability among men with low-grade disease, indicating that lycopene may inhibit progression of prostate cancer early in its natural history.[29]
In another study examining whether carotenoid intake and adipose tissue carotenoid levels were inversely associated with prostate cancer aggressiveness, results suggested that diets high in lycopene may protect against aggressive prostate cancer in white Americans and diets high in beta-cryptoxanthin may protect against aggressive prostate cancer in African Americans.[30]
One study investigated the correlation between lycopene blood levels and the rate of progression of prostate cancer. This study examined plasma carotenoids and tocopherols in relation to PSA levels among men with biochemical recurrence of prostate cancer. This study indicated that the plasma cis-lutein/zeaxanthin level at 3 months was inversely related to PSA level at 3 months (P = .0008), while alpha-tocopherol (P = .01), beta-cryptoxanthin (P = .01), and all-trans-lycopene (P = .004) levels at 3 months were inversely related to PSA levels at 6 months. Percentage increase in alpha-tocopherol and trans-beta-carotene levels from baseline to month 3 was associated with lower PSA levels at 3 and 6 months. Percentage increase in beta-cryptoxanthin, cis-lutein/zeaxanthin and all-trans-lycopene was associated with lower PSA levels at 6 months only.[31]
A study examined the association of prediagnosis and postdiagnosis dietary lycopene and tomato product intake with prostate-cancer specific mortality in a prospective cohort of men diagnosed with nonmetastatic prostate cancer. No association between serum lycopene, tomato products, and prostate-cancer specific mortality was observed. Among men with high-risk cancers (T3–T4, Gleason score 8–10, or nodal involvement), consistently reporting lycopene intake that was at or above the median was associated with lower prostate-cancer specific mortality.[32]
The variability in these epidemiological study results may be related to lycopene source; exposure misclassification; inconsistent measures of intake; differences in absorption; differences in individual lycopene metabolism; lack of a dose response; and confounding lifestyle factors, such as obesity, use of tobacco and alcohol, other dietary differences, varying standardization of quantities and compositions of lycopene, geographical location, and genetic risk factors. Most studies have examined the association of lycopene intake with the risk of all prostate cancers and have not separately considered indolent versus aggressive disease. Given these caveats, results based on epidemiological evidence should be interpreted with caution.

Intervention studies

A number of clinical studies have been conducted investigating lycopene as a chemopreventive agent and as a potential treatment for prostate cancer.
Bioavailability
The bioavailability of lycopene has been examined and demonstrated in several studies relating lycopene to prostate cancer and other diseases. The bioavailability of lycopene is greater in processed tomato products, such as tomato paste and tomato puree, than in raw tomatoes.[4] Lycopene bioavailability has been observed to be highly variable, which may lead to varying biological effects after lycopene consumption. It is postulated that these variations, at least in part, can be attributed to several single nucleotide polymorphisms in genes involved in red-pigment lycopene and lipid metabolism. In a study to define the impact of typical servings of commercially available tomato products on resultant plasma and prostate lycopene concentrations,[33] men scheduled to undergo prostatectomy (n = 33) were randomly assigned to either a lycopene-restricted control group (<5 mg/d) or a tomato soup (2–2¾ cups/d prepared), tomato sauce (142–198 g/d or 5–7 oz/d), or vegetable juice (325–488 mL/d or 11–16.5 fluid oz/d) intervention providing 25 to 35 mg of lycopene per day. The end-of-study prostate lycopene concentration was 0.16 nmol/g (standard error of the mean, 0.02) in the controls, but was 3.5-, 3.6- and 2.2-fold higher in tomato soup (P = .001), sauce (P = .001), and juice (P = .165) consumers, respectively. Prostate lycopene concentration was moderately correlated with postintervention plasma lycopene concentrations (correlation coefficient, 0.60; P = .001), indicating that additional factors have an impact on tissue concentrations. While the primary geometric lycopene isomer in tomato products was all-trans (80%–90%), plasma and prostate isomers were 47% and 80% cis-lycopene, respectively, demonstrating a shift towards cis accumulation. Consumption of typical servings of processed tomato products results in differing plasma and prostate lycopene concentrations. Factors including meal composition and genetics deserve further evaluation to determine their impacts on lycopene absorption, isomerization, and biodistribution.[34]
There is evidence that dietary fat may help increase the absorption of carotenoids, including lycopene. In one experiment, healthy volunteers consumed mixed-vegetable salads with nonfat, low-fat, or full-fat salad dressing. Analysis of blood samples indicated that eating full-fat salad dressing led to more carotenoid absorption than eating low-fat or nonfat dressing.[35] Results of a randomized study published in 2005 demonstrated that cooking diced tomatoes with olive oil significantly increased lycopene absorption compared with cooking tomatoes without olive oil.[36] In another study,[37] there was no difference in plasma lycopene levels following consumption of tomatoes mixed with olive oil or tomatoes mixed with sunflower oil, suggesting that absorption of lycopene may not be dependent on the type of oil used. However, this study found that combining olive oil, but not sunflower oil, with tomatoes resulted in greater plasma antioxidant activity.
Pharmacodynamic studies
Healthy males participated in a crossover design study that attempted to differentiate the effects of a tomato matrix from those of lycopene by using lycopene-rich red tomatoes, lycopene-free yellow tomatoes, and purified lycopene. Thirty healthy men aged 50 to 70 years were randomly assigned to two groups with each group consuming 200 g/d of yellow tomato paste (lycopene, 0 mg) and 200 g/d of red tomato paste (lycopene, 16 mg) as part of their regular diet for 1 week, separated by a 2-week washout period. Then, in a parallel design, the first group underwent supplementation with purified lycopene (16 mg/d) for 1 week, whereas the second group received a placebo. Sera samples collected before and after the interventions were incubated with lymph node cancer prostate cells to measure the expression of 45 target genes. In this placebo-controlled trial, circulating lycopene concentration increased only after consumption of red tomato paste and purified lycopene. Lipid profile, antioxidant status, PSA, and IGF-1 were not modified by consumption of tomato pastes and lycopene. When prostate cancer cells were treated in vitro with sera collected from men after red tomato paste consumption, IGF binding protein-3 (IGFBP-3) and the ratio of Bax to Bcl2 were up-regulated, and cyclin-D1, p53, and Nrf-2 were down-regulated compared with expression levels obtained using sera taken after the first washout period. Intermediate gene expression changes were observed using sera collected from participants after consumption of yellow tomato paste with low carotenoid content. Cell incubation with sera from men who consumed purified lycopene led to significant up-regulation of IGFBP-3, c-fos, and uPAR compared with sera collected after placebo consumption. These findings suggest that lycopene may not be the only factor responsible for the cancer-protective effects of tomatoes.[38]
Prevention/early treatment
In another study, the effect of tomato sauce on apoptosis in benign prostatic hyperplasia (BPH) tissue and carcinomas was examined. Patients who were scheduled for prostatectomy were given tomato sauce pasta entrees (30 mg/day of lycopene) to eat daily for 3 weeks before surgery. Patients scheduled for surgery who did not receive the tomato sauce pasta entrees served as control subjects. Those who consumed the tomato sauce pasta entrees exhibited significantly decreased serum PSA levels and increased apoptotic cell death in BPH tissue and carcinomas.[39]
One study of 40 patients with high-grade prostate intraepithelial neoplasia (HGPIN) received 4 mg of lycopene twice a day or no lycopene supplementation for 2 years. A greater decrease in serum PSA levels was observed in men treated with lycopene supplements, compared with those who did not take the supplementation. During follow-up, adenocarcinomas were diagnosed more often in patients who had not received the supplements (6 of 20) than in men who had received lycopene (2 of 20). These findings suggest that lycopene may be effective in preventing HGPIN from progressing to prostate cancer.[40] In another study, men at high risk of prostate cancer (e.g., HGPIN) were randomly assigned to receive a daily multivitamin (that did not contain lycopene) or the same multivitamin and a lycopene supplement (30 mg/day) for 4 months. No statistically-significant difference was observed in serum PSA levels between the two treatment groups. [41] Another randomized placebo-controlled study of consumption of a lycopene-rich tomato extract that was taken for approximately 6 months in 58 men with HGPIN reported no discernible effect on cell proliferation or cell cycle inhibition in benign prostatic epithelium or in serum PSA levels, despite a substantial increase in serum lycopene.[42]
In another study, 32 men with HGPIN received a lycopene-enriched diet (20–25 mg/day lycopene from triple-concentrated tomato paste) before undergoing a repeat biopsy after 6 months. No overall clinical benefit was seen in decreasing the rate of progression to prostate cancer. Baseline PSA levels showed no significant change. Prostatic lycopene concentration was the only difference between those whose repeat biopsy showed HGPIN, prostatitis, or prostate cancer. Prostatic lycopene concentration below 1 ng/mg was associated with prostate cancer at the 6-month follow-up biopsy (P = .003).[21] Refer to the Multicomponent Therapies section of this summary for more information about trials of multicomponent therapies that include lycopene.
Treatment
A number of clinical trials investigating lycopene as a potential treatment for prostate cancer are listed below in Table 2.
Table 2. Clinical Trials of Lycopene for Prostate Cancer Treatmenta
ENLARGE
Patient Population/Trial Design/Sample SizeAgent/DoseDurationBiomarkersResults
Bid = twice a day; PSA = prostate-specific antigen; RCT = randomized controlled trial.
aRefer to text and the NCI Dictionary of Cancer Terms for additional information and definition of terms.
Preprostatectomy; pilot RCT; N = 26 [43]Tomato oleoresin extract containing lycopene 30 mg/d (15 mg bid) or placebo control3 wkTumor volumeSmaller tumors (80% vs. 45%, less than 4 mL), less involvement of surgical margins and/or extraprostatic tissues with cancer (73% vs. 18%, organ-confined disease), and less diffuse involvement of the prostate by high-grade prostatic intraepithelial neoplasia (33% vs. 0%, focal involvement)
Preprostatectomy; RCT; N = 79 [44]Tomato products containing 30 mg of lycopene daily, tomato products plus selenium, omega-3 fatty acids, soy isoflavones, grape/pomegranate juice and green/black tea, or a control diet3 wkPSANo differences in PSA values between the intervention and control groups. Lower PSA values in men with intermediate-risk prostate cancer with highest increases in lycopene levels
Preprostatectomy; RCT; N = 45 [45]15 mg, 30 mg, or 45 mg lycopene vs. control30 dPSA, steroid hormones, Ki-6730 mg lycopene dose level decrease in free testosterone, significant increases in mean plasma estradiol and in serum sex hormone-binding globulin, and decrease in the percentage of cells expressing Ki-67; at the 45 mg/d dose, serum total estradiol increased
Active surveillance; single arm; N = 40 [46]Whole-tomato supplement containing 10 mg of lycopene (Lycoplus)1 yPSA velocity; PSA doubling timeStatistically significant decrease in PSA velocity after lycopene treatment (P = .0007)
Biochemical relapse after radiation therapy or surgery; RCT; N = 36 [47]15, 30, 45, 60, 90, or 120 mg/d of lycopene (Lyc-O-Mato)1 yPSADid not alter serum PSA levels
Biochemical relapse after radiation therapy or surgery; single-arm study; N = 46 [48]Tomato juice or paste containing lycopene 30 mg/d4 moPSADid not alter serum PSA levels except in one patient
Metastatic, hormone-refractory prostate cancer; open label study; N = 20 [49]Lycopene 10 mg/d (Lycored softules)3 moPSA50% had PSA levels that remained stable, 15% showed biochemical progression, 30% showed a partial response, and one patient exhibited a complete response after treatment
Hormone-refractory prostate cancer; single arm study; N = 17 [50]Lycopene 15 mg/d (pills)6 moPSAPSA stabilization in 5 (29%) of 17 and PSA progression in 12 (71%) of 17
Preprostatectomy
Other studies have examined the potential therapeutic effect of lycopene-containing products in men with prostate cancer. The effects of lycopene supplementation on prostate tissue and prostate cancer biomarkers were investigated in men with localized prostate cancer in a 2002 pilot study. Men received either lycopene supplements (30 mg/d) or no intervention twice daily for 3 weeks before radical prostatectomy. Men in the intervention arm had smaller tumors (80% vs. 45%, less than 4 ml), less involvement of surgical margins and/or extraprostatic tissues with cancer (73% vs. 18%, organ-confined disease), and less diffuse involvement of the prostate by HGPIN (33% vs. 0%, focal involvement) compared with men in the control group. Mean plasma PSA levels were lower in the intervention group compared with the control group.[43] Refer to the Multicomponent Therapies section of this summary for more information on studies with lycopene.
In a phase II, randomized, placebo-controlled trial,[45] 45 men with clinically localized prostate cancer received either 15, 30, or 45 mg of lycopene (Lyc-O-Mato) or no supplement from time of biopsy to prostatectomy (30 days). Plasma lycopene increased from baseline to the end of treatment in all treatment groups, with the greatest increase observed in the 45 mg lycopene-supplemented arm. No toxicity was reported. Overall, men with prostate cancer had lower baseline levels of plasma lycopene, compared with disease-free controls, and similar to levels observed in previous studies in men with prostate cancer.[51,52] At the 30 mg lycopene dose level, a moderate decrease in mean free testosterone and significant increases in mean plasma estradiol and in serum sex hormone-binding globulin (SHBG) (P = .022) were observed. At the 45 mg/d dose, serum total estradiol increased (P = .006) with no significant change in serum testosterone. However, serum testosterone and SHBG levels in the control group remained unchanged. The mean difference between groups who received the lycopene supplementation demonstrated a lower percentage of cells expressing Ki-67, compared with the control group. Notably, 75% of subjects in the 30 mg lycopene-supplemented arm had a decrease in the percentage of cells expressing Ki-67, compared with the subjects in the control group, in which 100% of the subjects observed an increase. These changes were not statistically significant, compared with the changes in the control arm for this sample size and duration of intervention. Although antioxidant properties of lycopene have been hypothesized to be primarily responsible for its beneficial effects, this study suggests that other mechanisms mediated by steroid hormones may also be involved.[45]
In a single-arm study of previously untreated men diagnosed with localized prostate cancer, investigators determined whether PSA velocity was altered by a 1-year intervention with lycopene supplementation (10 mg/d). A statistically significant decrease in PSA velocity after lycopene treatment was observed (P = .0007). Analysis of the PSA-doubling time (pretreatment vs. post-treatment) showed a median increase after supplementation for 174 days; however, this was not statistically significant.[46]
In one study, prostate cancer patients (N = 36) who had biochemical relapse following radiation therapy or surgery received lycopene supplements twice daily for 1 year. There were six cohorts in the study, each receiving a different dose of lycopene (15, 30, 45, 60, 90, or 120 mg/d). Serum PSA levels did not respond to lycopene treatment. Plasma lycopene levels rose and appeared to plateau by 3 months for all doses. The results indicate that, although lycopene may be safe and well tolerated, it did not alter serum PSA levels in biochemically relapsed prostate cancer patients.[47]
In a 2004 open-label study, patients with hormone-refractory prostate cancer (HRPC) (N = 20) received lycopene supplements daily (10 mg/d of lycopene) for 3 months. Of the study's participants, 50% had PSA levels that remained stable, 15% showed biochemical progression, 30% showed a partial response, and one patient (5% of the total sample) exhibited a complete response after treatment.[49] In a phase II study, HRPC patients took lycopene supplements daily (15 mg of lycopene/d) for 6 months. By the end of the study, serum PSA levels had almost doubled in 12 of the 17 patients, and 5 of 17 patients had achieved PSA stabilization. Although this was a small study without a control group, the results suggest that lycopene may not be beneficial for patients with advanced prostate cancer.[50]
In another study, 46 patients with androgen-independent prostate cancer consumed either tomato paste or tomato juice daily (both preparations provided 30 mg of lycopene/d) for at least 4 months. Only one patient in this study exhibited a decrease in PSA level. Several episodes of gastrointestinal side effects were noted after eating the tomato paste or drinking the tomato juice.[48]
On the basis of the available evidence, early randomized clinical trials with lycopene as a single agent, in tomato products, and in combination with other agents (fish oil supplements, tomato products plus selenium, omega-3 fatty acids, soy isoflavones, grape/pomegranate juice and green/black tea) demonstrates bioavailability in serum and modulation of intermediate biomarkers implicated in prostate carcinogenesis and prostate cancer progression in most studies. Perhaps, future clinical trials should include longer duration of consistent lycopene exposure, while accounting for variations in individual absorption of carotenoids and heterogeneity of high-risk (HGPIN, atypical small acinar proliferation) and prostate cancer patient populations (indolent vs. aggressive prostate cancer or androgen-dependent vs. androgen-independent prostate cancer).

Current Clinical Trials

Use our advanced clinical trial search to find NCI-supported cancer clinical trials that are now enrolling patients. The search can be narrowed by location of the trial, type of treatment, name of the drug, and other criteria. General information about clinical trials is also available.

Adverse Effects

Studies evaluating lycopene in randomized clinical trials targeting men at high risk for prostate cancer and populations with prostate cancer have indicated relatively few toxicities at the dose and duration of intervention.[38,40,41,46,49] Doses of lycopene ranging between 8 mg and 45 mg administered over a period ranging from 3 weeks to 2 years have been reported to be safe in randomized clinical trials targeting the prostate. When adverse effects occurred, they tended to present as gastrointestinal symptoms [48] and, in one study, the symptoms resolved when lycopene was taken with meals.[50] Another study reported that one participant withdrew because of diarrhea.[47]
The FDA has accepted the determination by various companies that their lycopene-containing products meet the FDA’s requirements for the designation of GRAS.[53]


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