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The presence of chronic inflammation in an aging prostate may lead to two primary diseases: benign prostatic hyperplasia (BPH) and cancer (PCa). BPH may severely impair the quality of life in one-third of adults older than 50 years and is reported in about 90% of individuals reaching 80 years of age. PCa is the most frequently diagnosed cancer in men, with an annual incidence of nearly 1.5 million new cases. Although significant differences in PCa incidence and mortality across ethnic groups have been reported, this malignancy represents an alarming public health issue worldwide because of the increasing incidence in young patients and the growing frequency of advanced disease cases. Given the global augmented life expectancy, both BPH and PCa embody an ever-increasing economic burden for wealthy societies and patients' direct and indirect costs.
Because of their late age, BPH and PCa are suitable for preventive interventions since even a modest delay in their development can substantially reduce the incidence of clinically identifiable lesions. Primary prevention of BPH and PCa relies on healthy choices, such as regular exercise, low fat intake, and high vegetable and fruit consumption. The latter recommendations, often inclusively described as adherence to the Mediterranean diet, advocate the regular uptake of various antioxidants and anti-inflammatory complexes in fresh vegetables and fruits. In this regard, tomatoes and olives are of great nutritional importance as they represent the primary source of such complexes. Accordingly, their consumption is associated with a low overall mortality rate.
It is still unclear what molecular processes underlie the pathophysiology of BPH that result in a condition with symptoms. It has been suggested that aging-related vascular and endocrine alterations and unchecked oxidative stress from acute and chronic inflammation cause the stromal and cellular compartments of the gland's transition zone to increase excessively. Nonetheless, BPH has been explained as the outcome of compromised systems for programmed cell death as a low level of proliferation of both stromal and epithelial cells has been found. Interestingly, new molecular profiling of BPH has shown discrete subgroups that may benefit from more specialised therapy, such as those with altered mTOR signalling associated with a poor prognosis.
Urinary hesitancy, urgency, frequency, and post-void dribbling are examples of lower urinary tract obstructive symptoms (LUTSs) typically used to diagnose BPH. People with BPH have a lower incidence of "in situ" PCa, indicating that treating BPH or reducing risk factors may postpone the emergence of PCa in some instances.
Because chronic inflammation has a decreased response to therapy, it has also been demonstrated to increase the chance of a disease progressing quickly. As a result, one of the main goals of BPH therapy is inflammation. However, the current state of BPH medication development is stagnant. It is limited to alpha-blockers, 5-alpha reductase inhibitors, and phosphodiesterase type 5 inhibitors, often employed in BPH lesions because their underlying heterogeneity is used successively. About one-third of patients still have uncontrolled LUTSs despite these treatments, and a variety of adverse consequences, including reduced libido, erectile dysfunction, dizziness, and hypotension, may manifest. To lessen the severity of LUTSs, surgical intervention is always necessary when medicinal therapy fails.
Guidelines for BPH treatment choices also include phytotherapy. The use of phytocompounds—in plant parts, derived extracts, or pure molecules—in treating individuals suffering from moderate to severe BPH is growing. An extensive collection of research on the prevention of BPH or amelioration of its associated symptoms, including experimental, clinical, and epidemiological studies, has concentrated on tomato lycopene, an open-chain beta carotenoid with a red colour and no retinoid activity that is found in varying amounts in foods derived from tomato cultivars. All dietary sources of tomatoes include lycopene, primarily in the low-accessible trans-isomeric form. Lycopene has many biological functions, many of which are preserved by its metabolites.
Comparative research, however, has unequivocally shown that tomatoes' health benefits cannot be solely attributed to their high lycopene concentration. The fruit contains a variety of compounds with a wide range of biological activities, or these compounds are formed during the fruit's heat processing; as a result, the complex plays a part in the fruit's anti-androgenic and in vivo anti-proliferative, anti-inflammatory, and pro-apoptotic activities. As a result, experimental and clinical research have demonstrated that whole tomatoes have healthier benefits than lycopene alone.
It is widely established that olive oil is a source of nutrients that help prevent cancer. Because these compounds can influence the molecular signalling involved in the growth and proliferation of altered cells in inflammation (e.g., MAPK, PI3K, and NF-κB) and angiogenesis, its polyphenol concentration reduces PCa development and invasiveness. Specifically, it has been observed that hydroxytyrosol inhibits the growth of human PCa cells in vitro and induces apoptosis.
The tomato is especially appealing for maintaining prostate health among the various preparations made from roots, seeds, pollen, bark, or fruits. Because they function both systemically and inside the gland, the fruit's antioxidant and anti-inflammatory compounds may also help protect prostate cells from the degenerative changes associated with aging. Regarding elderly patients who frequently get several pharmacologic treatments, it is essential to note that there is no scientific proof of drug-tomato interaction. Initially, efforts to enhance tomato antioxidant activity involved heating a concentrated whole ripe fruit puree at 95°C for 5 minutes while adding 10% extra-virgin olive oil. Cooking the fruit and adding fats, mainly olive virgin oil, dramatically increases the bioavailability of lycopene, the main antioxidant found in tomatoes.
10% of FSMP added to the diet of transgenic mice used in the human prostate carcinogenesis model (TRAMP) dramatically reduced the development of poorly differentiated tumours and the animals' deaths. Furthermore, a thorough serological examination of the animals during therapy showed that the FSMP may lower circulating angiogenic/inflammatory cytokines, including IL-6, TNF-α, and vascular endothelial growth factor (VEGF). Since lower lycopene content tomato-based supplemented meals failed to alter the clinical course of cancer in the TRAMP animals, these effects were dose-dependent. Following this enquiry, an inventive whole tomato, solvent-free processing was developed to create a more refined and standardised "whole tomato food supplement" (WTFS) that may be utilised in clinical trials. The availability of the standardised WTFS product allowed for its assessment in a clinical pilot study, which demonstrated that following the daily assumption of 6 gr of the WTFS containing 22 mg of total carotenoids for two months, 80% of symptomatic BPH patients showed a decrease in LUTSs.
Links between BPH and PCa
PCa and BPH share genetic characteristics. Particularly for Asian patients, epidemiologic and pathologic connections between BPH and the development of PCa have been identified; these connections coincide with the findings of a long-term, large cohort study conducted in Europe. Like BPH, PCa may be linked to insulin resistance and metabolic syndrome, indicating a possible dietary component for this class of illnesses. The correlation between a high body mass index—a component of the metabolic syndrome—and the advancement of prostate cancer, as well as its mortality, further supports this.
While the molecular underpinnings of the two diseases remain poorly understood, common deranged molecular pathways include
chronic inflammation, hormone dependence, and downstream signalling pathways involving cytokines like IL-12, TNF-α, IL-1, IL-1β, and IL-6.
Downstream signalling pathways mediated by NF-κB, which contribute to tumour progression.
angiogenesis modulated by IGF1R; and
IL-6/JAK/STAT signalling, which promotes cell growth and inhibits apoptosis.
The data above suggests that complexes of phytonutrients, like those found in tomatoes and olives, may treat several molecular targets associated with the two illnesses in adjuvant contexts.
Phytotherapies are becoming increasingly popular in PCa care for preventative, therapeutic, and palliative purposes because of the links above. Epidemiology studies first suggested a connection between the consumption of tomatoes and lycopene and the incidence of PCa. A prospective analysis of tomato products validated the negative relationship between tomato sauce consumption and PCa risk. Significantly, individuals with over two servings of tomatoes per week instead of less than one serving per month showed a 66% lower incidence of PCa metastatic cancer. More recently, scholars discovered that among individuals with high-risk tumours, a continuously high tomato diet was linked to a considerably decreased chance of specific death following PCa diagnosis.
Additionally, in patients with high-risk prostatic intraepithelial tumours, decreased lycopene concentrations in the prostate favour the formation of PCa. In summary, a meta-analysis established that the protective effects of eating raw and processed tomatoes (cooked tomatoes and sauces) on the risk of PCa are dose dependent. It also found that consistent tomato consumption, which complies with dietary guidelines specific to PCa, is linked to a lower risk of PCa.
The TRAMP murine carcinoma model of progressive prostate cancer, which replicates the phases of human illness, including the androgen-independent stage, provides early evidence that WTBS can disrupt the carcinogenesis of prostate cancer. The FSMP diet in these animals delayed the advancement of prostatic intraepithelial neoplasia to adenocarcinoma. It reduced the prevalence of poorly differentiated cancer, all associated with a substantial improvement in overall survival (p < 0.01). According to biochemical studies, animal sera showed lower levels of antioxidant activity and circulating biomarkers related to prostate carcinogenesis, such as TNF-α and IL-6, which were found to significantly correlate with PCa grade and VEGF, which is linked to prognosis, metastasis, and tumour grade. The TRAMP murine carcinoma model of progressive prostate cancer, which replicates the phases of human illness, including the androgen-independent stage, provides early evidence that WTBS can disrupt the carcinogenesis of prostate cancer. The FSMP diet in these animals delayed the advancement of prostatic intraepithelial neoplasia to adenocarcinoma. It reduced the prevalence of poorly differentiated cancer, all associated with a substantial improvement in overall survival (p < 0.01). According to biochemical studies, animal sera showed lower levels of antioxidant activity and circulating biomarkers related to prostate carcinogenesis, such as TNF-α and IL-6, which were found to significantly correlate with PCa grade and VEGF, which is linked to prognosis, metastasis, and tumour grade.
The signal transducer and activator of transcription 3 (STAT3), a major regulator in the expression of a variety of neoplastic genes and a contributor to prostate cancer's energy, is the IL-6/STAT axis, which links inflammation with prostate cancer's development.
Additionally, recent research using the androgen-sensitive human prostate epithelial cell line LNCaP exposed to an environmental carcinogen has shown that WTFS exhibits pro-apoptotic and anti-proliferative properties, protects DNA from oxidative stress damage, and blocks pathways involved in the development of prostate cancer, such as STAT3 activation androgen receptor signalling.
In general, it is healthy and wise to check your health for 'prevention is better than cure', and early detection saves lives.
To your health,
Nwabekee.
Reference
Natali, P. G., Piantelli, M., Minacori, M., Eufemi, M., & Imberti, L. (2023). Improving whole tomato transformation for prostate health: Benign prostate hypertrophy as an exploratory model. International Journal of Molecular Sciences, 24(6), 5795.
Thanks for sharing
Informative! This is a good read.
Ride on!