The newly developed WTFS is a mixture of whole tomato powder and a polyphenolic extract from olives. The original tomato powder was firstly used to produce food for special medical purposes (FSMP) and investigated as adjuvant therapy in subjects affected by chronic hepatitis C. This FSMP was effective in preventing carotenoid serum depletion and improving the oxidative status during antiviral therapy . Then, the anti-tumor activity of the tomato powder was evaluated in a transgenic mouse model of prostate carcinogenesis (TRAMP) . In this model, feeding mice with the tomato powder significantly delayed tumor progression and decreased both the incidence of poorly differentiated carcinoma and mortality. Additionally, in agreement with several other reports, tomato supplementation was found to reduce the levels of circulating inflammatory/angiogenic cytokines as VEGF, TNF alpha, and IL-6 in several experimental models [24-26]. The patented method to produce the WTFS leads to a final product enriched in bioactive compounds, i.e. olive’s polyphenols which have been found more active than the tomato powder alone in reducing serum levels of IL-6 and VEGF in TRAMP mice . Serum measurement of a panel of inflammatory cytokines in the pretreatment sera did not show any significant derangement (data not shown). This does not come unexpectedly since the prostate inflammation in BPH patients is unlikely to be mirrored in circulation.
Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a urinary disorder that afflicts patients due to various discomforts. It is pressing and meaningful to develop novel and effective treatments because of the uncertain etiology and dismal therapeutic effect of CP/CPPS. In the absence of a standard treatment , the use of substances like antioxidants that may stop or potentially reverse the deleterious effects of inflammation is particularly attractive. Tomatoes and olives are the sources of complexes of micronutrients endowed with well-known strong antioxidants and anti-inflammatory activity, with properties potentially useful in protecting DNA and other cell constituents from oxidation [28,29].
Here we demonstrate that the new WTFS determines a significant improvement of urinary tract symptoms and quality of life in BPH patients, thus representing a suitable alternative option to the pharmacological treatment of this age-related pathology. Although the molecular mechanisms underlying this clinical benefit remains to be investigated, in a rat model lycopene was found to attenuate chronic prostatitis/chronic pelvic pain syndrome by inhibiting oxidative stress and inflammation via the interaction of NF-κB, MAPKs, and Nrf2 signaling pathways .
Indeed, in addition to lycopene, tomatoes contain within their matrix other bioactive compounds that are responsible for the health effects associated with the constant consumption of the fruit, which cannot be accounted for solely by lycopene [18, 31]. The patented WTFS production method, not only generates more bioavailable cis-lycopene and increased tomato phenolic components but produces frus-his compounds that further increase tomato health-preserving properties . Thus this WTFS is likely to possess a spectrum of cooperative mechanisms. In view that the increase of the epithelial and stromal components in BPH is not paralleled by noticeable proliferation, the hyperplastic lesions have been interpreted as the result of impaired programmed cell death mechanism [32, 33]. In this regard, tomato sauce has been reported to increased apoptosis in different experimental models [34, 35]. Stromal cells are responsible for the androgen-mediated glandular epithelium growth. Although a defined molecular pathway has not been yet defined, tomato and lycopene have been reported to down-regulate androgen metabolism and signaling .
Inflammation is a common histopathological finding in BPH, in absence of prostatic cancer or clinical prostatitis. It is a condition of which subclinical inflammation may be associated with a rise in serum PSA levels . However weak is the correlation between PSA levels and the active or chronic inflammation and no significant correlation exists between the active or chronic histopathological inflammation and IPSS . Also, in this regard nutritional interventions with tomato-products reduced PSA levels in subgroups of prostate patients, while lycopene supplements or extracts were found to be less effective [39-42].
Also, the mix of polyphenols from tomatoes and olive vegetation water can certainly contribute to the anti-inflammatory properties of the WTFS [43, 44].
This new food supplement can modulate the total PSA concentrations even in patients with BPH. We have observed an increasing total PSA trend in the placebo group (P=0.080), probably as the consequence of the biopsy procedure. Indeed, cystoscopy can increase serum PSA levels fourfold, while needle biopsies and transurethral resection can temporarily increase PSA levels up to fiftyfold, all as a result of increased PSA leakage into the serum. Besides, the relatively long half-life of PSA may lead to a consistent delay before serum PSA returns to a baseline level after TURP, biopsy, or infection . On the contrary, a trend toward a reduction of total PSA levels was observed in WTFS treated patients (P=0.096), which was sustained by the significant reduction of total PSA concentrations seen in the patients with high basal levels (>10 ng/ml; P = 0.009).
Although BPH and prostate cancer (PCa) share features such as hormone-dependent growth and response to treatment with anti-androgen therapy, BPH is not considered a premalignant lesion. However, in a nationwide cohort study involving over 3 million men followed for up to 27 yr, clinical BPH was associated with a two- to three-fold increased risk of PCa incidence and with a two- to eight-fold increased risk of PCa mortality . Because PSA determinations when properly utilized may contribute to the diagnosis and follow-up of prostate cancer , the effect of tomato treatment on total PSA serum levels could interfere with clinical management. However, the determination of the percentage of free PSA and free/total PSA ratio appears to be a helpful method for enhancing the specificity of total PSA evaluation [48-49] and WTFS does not change free PSA and free/total PSA values.
The overall tomato consumption may bear harmful effects on human health such as gastroesophageal reflux disease, irritable bowel syndrome, kidney stones, and some urinary problems . In this context, it is worthy to be noted that, due to the preparation procedures, this WTFS does not contain organic acids (citric and malic acids), significant potassium/oxalate concentration and tomato skin/seeds, responsible for these side effects.
Based on recent human experimentation  this novel dietary supplement, which is phytosterols-free may help to maintain prostate health and can contribute to the beneficial effect of adhering to the WCRF/AICR recommendations , by itself, when complemented with current treatments  and by adopting healthy lifestyles. Furthermore, because of its high deliverable antioxidant activity, the consumption of the WTFS can be advantageous in contrasting the unhealthy effects of the excess production of free radicals induced by a variety of risk factors, including the metabolic syndrome often associated with BPH [25, 54].
Although tomatoes provide most of the dietary antioxidants in the Mediterranean-style diet, their culinary use is often associated with the consumption of carbohydrates rich meals (e.g. pasta, pizza), and high calories uptake (olive oil), thus representing a risk factor for individuals with excessive body mass, obesity, and metabolic syndrome. In this regard, the WTFS is an exemplary source of a complex of antioxidants. Furthermore, this food supplement may represent an ideal candidate to develop a variety of tomato-based enriched foods to delay the onset and/or to attenuate the course of age-related chronic degenerative disease [55,56].