Efficacy and Safety of Lycoprozen®, a Novel Tomato-Based Food Supplement in Patients with Benign Prostatic Hyperplasia

Benign prostatic hyperplasia BPH affects aging men and represents the most common urologic disease among elderly men¹. BPH is a growth of both epithelial and stromal cells from both the transition zone and periurethral areas, and typically develops after the age of 40 years, ranging in prevalence from >50% at 60 years to as high as 90% by 85 years of age².

The diagnosis of BPH is often in response to the development of lower urinary tract obstructive, irritative, and post-micturition symptoms (LUTS), including urinary hesitancy, urgency, frequency and post void dribble. Medical treatment options include α-adrenergic antagonists or 5-α reductase inhibitors, however about one-third of men with LUTS do not respond to either treatment approach³. Patients who are resistant to treatment, or who become resistant to treatment over time, will become candidates for surgical intervention to reduce LUTS severity.

Further understanding the causes of LUTS will guide interventions to prevent LUTS or increase sensitivity to medical treatment. To date, there are multiple theories on the cellular and molecular processes underlying the pathogenesis of BPH leading to a symptomatic disease. In addition to androgens, both chronic and acute inflammation can lead to events that can cause proliferation within prostatic tissue through a variety of mechanisms, notably oxidative stress ^{4, 5}. At present, non-steroidal anti-inflammatory drugs are used to improve urinary symptoms and flow measures, but their long-term effectiveness and safety are not known⁶.

BPH is also associated with obesity and related pathologies. However, the biological pathways linking obesity and BPH are poorly understood. Centralized adipose deposition was associated with the severity of prostate tissue inflammation and LUTS and an approach to minimize centralized fat deposition may reduce LUTS severity in BPH patients⁷.

A large number of anti-inflammatory compounds has been identified in tomato extracts⁸;moreover, tomato consumption reduces inflammation by decreasing inflammatory cytokines in overweight and obese humans ^{9, 10}.

We have also observed that a feed enriched with a 10% whole tomato preparation versus a tomato-free control feed is able to increase the anti-oxidant serum activity and to reduce serum levels of inflammatory biomarkers in the TRAMP mouse model of prostate carcinogenesis, even before the appearance of cancer¹¹.

Recently, a novel food supplement named Lycoprozen® was developed by Janus Pharma, Roma, Italy. It consists of whole tomatoes specially processed for make their antioxidant and anti-inflammatory micronutrients highly bioavailable, and a small percentage of olive’s vegetation water. In the present study, we have evaluated the effects of Lycoprozen® on the LUTS severity in subjects affected by BPH.

Lycoprozen® is available as food supplement on the Italian market since 2017 with the Ministry of Health registration number 68843. The patented multi-step production process results into an increased bioavailability of antioxidant and anti-inflammatory tomato micronutrients, which include carotenoids (mainly lycopene), flavonoids, and ketosamines¹². Lycoprozen® is made of two components, a whole tomato powder and an olive water waste¹².

The compositions of the tomato powder and polyphenolic extract from olive vegetation water are reported in Table 1 and in Table 2, respectively.

All patients successfully completed treatment with no side effects.

The IPSS is based on the answer to seven questions concerning urinary symptoms, and is the only questionnaire validated by WHO in Italian language. Each question is assigned points from 0 to 5, indicating increasing severity of a particular symptom. The total score can therefore range from 0 to 35 (asymptomatic to very symptomatic). Although there are presently no standard recommendations into grading patients with mild, moderate or severe symptoms, patients can be tentatively classified as follows: 0 - 7 = mildly symptomatic; 8 - 19 = moderately symptomatic; 20 - 35 = severely symptomatic.

In this preliminary study, we have found that Lycoprozen® significantly reduced the LUTS severity (paired t-test, two-tailed p value < 0.0001). Following the treatment, IPSS value decreased in 17 out of 20 patients, independently of the starting level, while remained unchanged in the remaining three cases (Figure 1). The IPSS mean values before and after the treatment were 16.95+6.0 SD (range 31-6) and 12.2+4.9 SD (range 20-2), respectively.

Figure 1.Urinary symptoms, evaluated according the IPSS* score, in patients with benign prostatic hyperplasia before(blue) and after (red) Lycoprozen®treatment

As reported above, Lycoprozen® is a mixture of two components, tomato powder and a polyphenolic extract from olives.

The original tomato powder was firstly developed to produce a food for special medical purposes (FSMP) and investigated as an adjuvant therapy in patients with chronic hepatitis C infection. Our results showed that this FSMP was effective in improving carotenoid status in healthy subjects, whereas in patients with hepatitis, it prevented carotenoid serum depletion and improved the oxidative status during antiviral therapy¹⁴.

Next, the anti-neoplastic activity of tomato preparation was analyzed in the transgenic adenocarcinoma of the mouse prostate (TRAMP) model¹¹. The TRAMP mouse is a model for progressive prostate cancer that mirrors the stages of the human form. Tomato diet significantly increased overall survival, delayed progression from prostatic intraepithelial neoplasia to adenocarcinoma, and decreased the incidence of poorly differentiated carcinoma. Biochemical data disclosed an increase in serum antioxidant activity and a reduction of serum inflammation/angiogenesis biomarkers of particular relevance in prostate carcinogenesis.

The patented method to produce Lycoprozen® leads to a final product enriched in bio-active compounds which have been found more active in reducing serum levels of IL-6 and VEGF in TRAMP mice¹².

The present observational study revealed that a once-daily intake of Lycoprozen® for two months significantly improved urinary symptoms and quality of life in patients with BPH.

BPH has been shown to be associated with an inflammatory environment, which is known to sustain proliferative programs resulting in nodules of BPH ^{4, 5, 15} and the anti-angiogenic/anti-inflammatory activities of tomato could represent the basis of its beneficial effect on BPH ^{8, 9, 10, 11}.

Based on these preliminary data, Lycoprozen® may be a suitable alternative option for the treatment of symptomatic BPH patients. The treatment was without side effects and acceptance among patients was high.

1. 1.McVary K T. (2006) BPH: epidemiology and comorbidities. , Am J Manag Care 12, 122-128.
   PubMed·Search at Google Scholar

1. 2.Roehrborn C G. (2008) BPH progression: concept and key learning from. , MTOPS, ALTESS, COMBAT, and ALF-ONE. BJU Int 101, 17-21.
   Search at Google Scholar

1. 3.McConnell J D, Roehrborn C G, Bautista O M, Andriole GL Jr, Dixon C M. (2003) The Long- Term Effect. of Doxazosin, Finasteride, and Combination Therapy on the Clinical Progression of Benign Prostatic Hyperplasia. New EnglandJ Med 349, 2387-2398.
   Search at Google Scholar

1. 4.Chughtai B, Lee R, Te A, Kaplan S. (2011) . Role of Inflammation in Benign Prostatic Hyperplasia. Rev Urol 13, 147-150.
   PubMed·Search at Google Scholar

1. 5.Ficarra V, Rossanese M, Zazzara M, Giannarini G, Abbinante M. (2014) The role of inflammation in lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH) and its potential impact on medical therapy. , Curr Urol Rep 15, 463-469.
   PubMed·View article·Search at Google Scholar

1. 6.Kahokehr A, Vather R, Nixon A, Hill A G. (2013) Non-steroidal anti-inflammatory drugs for lower urinary tract symptoms in benign prostatic hyperplasia: Systematic review and meta-analysis of randomized controlled trials. , BJU Int 111, 304-311.
   PubMed·View article·Search at Google Scholar

1. 7.Fowke J H, Koyama T, Fadare O, Clark P E. (2016) Does inflammation mediate the obesity and BPH relationship? An epidemiologic analysis of body composition and inflammatory markers in blood, urine, and prostate tissue, and the relationship with prostate enlargement and lower urinary tract symptomssPloS. One.11: 6-0156918.
   PubMed·View article·Search at Google Scholar

1. 8.Mohri S, Takahashi H, Sakai M, Takahashi S, Waki N. (2018) Wide-range screening of anti-inflammatory compounds in tomato using LC-MS and elucidating the mechanism of their functions. , PLoS One 12, 13-0191203.
   PubMed·View article·Search at Google Scholar

1. 9.Ghavipour M, Saedisomeolia A, Dialali M, Sotoudeh G, M R Eshraghyan. (2013) Tomato juice consumption reduces systemic inflammation in overweight and obese females. , BrJ Nutr109 2031-2035.
   PubMed·View article·Search at Google Scholar

1. 10.Li Y F, Chang Y Y, Huang H C, Y C Wu, Yang M D. (2015) Tomato juice supplementation in young women reduces inflammatory adipokine levels independently of body fat reduction. , Nutrition 31, 691-696.
   PubMed·View article·Search at Google Scholar

1. 11.Pannellini T, Iezzi M, Liberatore M, Sabatini F, Iacobelli S. (2010) . , Cancer Prev Res 10, 1284-1291.
   Search at Google Scholar

1. 12.Fogliano V, Iacobelli S, Piantelli M. (2016) Tomato powder-based composition”. US Patent App.15/024,165
   Search at Google Scholar

1. 13.Badia X, Garcia-Losa M, Dal-Re R. (1997) Ten-lenguage translation and harmonization of the International Prostate Symptom Score: developing methodology for multinational clinical trials. , Eur Urol 31, 129-140.
   Search at Google Scholar

1. 14.Vitaglione P, Fogliano V, Stingo S, Scalfi L, Caporaso N. (2007) Development of a tomato-based food for special medical purposes as therapy adjuvant for patients with HCV infection. , Eur J Clin Nutr 61, 906-915.
   Search at Google Scholar

1. 15.Krušlin B, Tomas D, Džombeta T, Milković-Periša M, Ulamec M. (2017) Inflammation in prostatic Hyperplasia and carcinoma. Basic scientific approach. Frontiers in Oncology. 7(77).
   Search at Google Scholar

1. 1.Quiros-Roldan Eugenia, Carriero Canio, Paghera Simone, Degli Antoni Melania, Fiorini Chiara, et al, 2021, Symptoms and quality of life in HIV-infected patients with benign prostatic hyperplasia are improved by the consumption of a newly developed whole tomato-based food supplement. A phase II prospective, randomized double-blinded, placebo-controlled study, Journal of Functional Foods, 82(), 104495, 10.1016/j.jff.2021.104495

1. 2.Natali Pier Giorgio, Piantelli Mauro, Minacori Marco, Eufemi Margherita, Imberti Luisa, 2023, Improving Whole Tomato Transformation for Prostate Health: Benign Prostate Hypertrophy as an Exploratory Model, International Journal of Molecular Sciences, 24(6), 5795, 10.3390/ijms24065795

1. 3.Cormio Luigi, Calò Beppe, Falagario Ugo, Iezzi Manuela, Lamolinara Alessia, et al, 2021, Improvement of urinary tract symptoms and quality of life in benign prostate hyperplasia patients associated with consumption of a newly developed whole tomato-based food supplement: a phase II prospective, randomized double-blinded, placebo-controlled study, Journal of Translational Medicine, 19(1), 10.1186/s12967-020-02684-3