The largest observational study, which primarily focused on dietary patterns and BPH occurrence, was performed by Tavani et al., who included 2820 men. Of this number, 1369 suffered from BPH. The authors concluded that the risk of BPH significantly decreased with an increasing intake of carotene, vitamin C, and iron. The intake of lycopene or zeaxanthin did not impact BPH incidence. These results contradict those of interventional studies conducted so far. However, as the authors noted, no uniform case definition of the disease has been established and only surgically treated men with BPH were included, which is a potential reason for the lack of dependency between lycopene consumption and BPH prevalence [51].

Kristal et al. examined dietary risk factors for incidence of benign prostatic hyperplasia in 4770 Prostate Cancer Prevention Trial placebo-arm participants who were free of BPH at baseline. BPH was assessed in this group of men over a 7-year period. The authors found that a dietary pattern low in vegetables and protein, and high in fat and red meat, was associated with the development of symptomatic BPH. There was also a weak association between lycopene, zinc, and supplemental vitamin D intake and decreased BPH occurrence [52].

A few in vitro studies have shown that lycopene inhibits the proliferation of benign prostate epithelial cells [53] and suppresses inflammatory cascade [54]. The mechanism responsible for this effect might be the inhibition of 5-alpha-reductase and basal inflammatory signaling, assessed in benign prostate tissue of rats. However, a study performed by Herzog et al. did not show the influence of lycopene administration on prostate growth in young rats [21].

An experimental model showed that a combination of Selenium (Se), Serenoa Repens (SeR), and Lycopene (Ly) effectively reduces oxidative stress, prostate inflammatory response, and histological features [54]. Another study performed by Minutoli et al. also investigated the influence of SeR, Se, and Ly on the microscopic effects of supplementation on BPH tissue. Administering SeR, Se, and Ly significantly blunted prostate growth. Moreover, the combination of SeR–Se–Ly was most effective in reducing prostate enlargement and growth by 43.3% in treated animals [55].

Both in vitro and clinical studies indicate that lycopene potentially inhibits BPH progression. Kim et al. administered 30 mg of lycopene per day for three weeks before radical prostatectomy to 32 patients diagnosed with prostate cancer (PCa). Later on, they investigated the impact of lycopene consumption on histopathological changes found in prostate specimens assessed post-surgically. They revealed that lycopene induced apoptosis in cancer-free BPH tissue. Apoptosis affected both epithelial and myoepithelial cells [56].

Lycopene was not the only carotenoid that demonstrates antioxidant properties tested in pre-clinical trials aimed at BPH treatment. Hou et al. investigated astaxanthin (AST) in the BPH rat model. They studied the effects of tested carotenoid on prostate weights, superoxide dismutase (SOD) activity, and testosterone and dihydrotestosterone levels depending on the dose of the administered substance (20 mg/kg, 40 mg/kg and 80 mg/kg). The most pronounced decline in prostate weights was observed after delivering 80 mg/kg of AST, while noticeable changes in hormone levels and SOD activity started from the administered dosage of 40 mg/kg; they concluded that AST has an inhibitory effect on testosterone-induced rats [57].

The suppressive effect of antioxidant supplement (Prosta-Q) on inflammatory processes in prostatitis was assessed by Shahed et al. The product includes zinc, quercetin, cranberry, saw palmetto, bromelain, and papain. It is speculated that oxidative stress may be a key pathway in some men with CPPS, which can be targeted with antioxidant therapy [67]. Lycopene, which downregulates inflammatory regulators such as cytokines, enzymes, and transcription factors in cell culture systems [68], is also known to decrease expression markers for immune cell infiltration in rats’ prostate tissue [21].

The synergistic effect of chronic bladder pain (CBP) treatment with lycopene and fluoroquinolones was demonstrated by Han et al. Their analysis of microbiological cultures of the prostate and urine as well as histological findings showed that the addition of lycopene to antibiotic treatment is associated with a statistically significant decrease in bacterial growth and improved prostatic inflammation compared with the ciprofloxacin group [69].

Morgia et al. evaluated the efficacy of the SeR–Se–LY combination in reducing chronic inflammation in patients with benign prostatic hyperplasia and/or prostate intraepithelial neoplasia or atypical small acinar proliferation (PIN/ASAP). This was a multicenter study involving nine Italian urological centers between January 2009 and December 2010. The influence of the test substances on the inflammatory state was measured by histo-biochemical methods. The anti-inflammatory effects were indirectly measured by evaluating the density of T-cells (CD3, CD8), B-cells (CD20), and macrophages (CD68). At the six-month follow-up, there were statistically significant reductions of extension and grading of inflammatory infiltration, mean values of CD20, CD3, and CD68, and mean PSA value in a group of patients with chronic prostatic inflammation taking SeR–Se–LY compared with the control group. It was concluded that patients with bladder outlet obstruction could benefit from this therapy acting on the inflammatory component of BPH [70].

The effects of SeR–Se–LY on IIIa CPPS were compared to Serenoa repens alone in a randomized study performed by Morgia et al. After eight weeks of treatment, S. repens + selenium and lycopene were found to ameliorate symptoms associated with chronic prostatitis, providing significant improvement in voiding dysfunctions compared to S. repens alone. As the treatment was safe and well tolerated, the authors pointed out its usefulness when long-term therapy is required [71].

Cai et al. assessed the influence of adding Serenoa repens, selenium, lycopene, bromelain, and methyl-sulfonyl-methane extracts to standard levofloxacin therapy for chronic bacterial prostatitis. They found that combination therapy had a significant effect on all three evaluated scores (QoL, NIH-CPSI, and IPSS) compared to antibiotic treatment alone. Moreover, as the authors pointed out, no adverse drug reactions have led to high compliance with the experimental protocol [72].

Based on evidence from observational and experimental studies, lycopene shows therapeutic activity against chronic prostatitis. Although its effect was assessed as a support to standard antibiotic treatment, the results of the studies are encouraging. Taking into account chronicity and the recurrent nature of the disease, which demands long-term drug usage, carotenoid supplementation seems to be a reasonable choice for such patients (Table 2).