Dietary intervention in prostate cancer patients: PSA response in a randomized double‐blind placebo‐controlled study

Abstract

The objective of this study was to show or to exclude an effect of dietary supplement on rising prostate-specific antigen (PSA) levels. We have studied the effect of a dietary supplement (verum, administered for 6 weeks) containing plant estrogens, antioxidants, including carotenoids, selenium and other putative prostate cancer inhibiting substances in a randomized placebo-controlled double-blind crossover study in 37 hormonally untreated men with prostate cancer and increasing PSA levels. Outcome measures were changes in the rates of change of serum concentrations of total and free PSA and changes in male sex hormone levels. Male sex hormone levels were significantly lower during the verum phase (DHT: ؊0.11 nmol/L, p ‫؍‬ 0.005; testosterone: ؊1 nmol/L, p ‫؍‬ 0.02). Total PSA doubling time was unaffected. Free PSA, which increased during the placebo phase (average doubling time of 68 weeks), decreased during the verum period (average half-life of 13 weeks; p ‫؍‬ 0.02). In those men in whom the free androgen index decreased (21 out of 32), a significant decrease in the slopes of both total and free PSA was observed (p ‫؍‬ 0.04). Overall total PSA doubling times did not increase significantly during verum. However, the study demonstrates that this dietary intervention reduces DHT and testosterone levels and increases free PSA doubling time (and total PSA doubling time in a relevant subgroup). If future studies confirm that these observations translate into a slowing of disease progression, a dietary intervention may become an attractive option for prostate cancer treatment and prevention.

Lycopene inhibits DNA synthesis in primary prostate epithelial cells in vitro and its administration is associated with a reduced prostate-specific antigen velocity in a phase II clinical study

“…29 Interestingly, a recent study examining the effect of a dietary supplement ('verum' -containing numerous potentially active compounds, including carotenoids, selenium and phyto-estrogens) in a group of patients not dissimilar to those included in this study describes a significant reduction in serum-free PSA but not in total PSA nor any increase in total PSA doubling times. 30 The period of supplementation was only 6 weeks; however, this was a randomized, doubleblind placebo-controlled study. 30 The clinical study described here reinforces the positive findings of these previous trials and demonstrates an ongoing and real effect upon serum PSA and perhaps therefore possibly on the behavior of established CaP in men receiving no other form of treatment.…”

“…30 The period of supplementation was only 6 weeks; however, this was a randomized, doubleblind placebo-controlled study. 30 The clinical study described here reinforces the positive findings of these previous trials and demonstrates an ongoing and real effect upon serum PSA and perhaps therefore possibly on the behavior of established CaP in men receiving no other form of treatment. Indeed, while the overall effect was to demonstrate a statistically significant shallowing of the gradient of PSA, there was also a large increase in estimated PSA doubling time.…”

Human xenograft models as useful tools to assess the potential of novel therapeutics in prostate cancer

“…In Rotterdam, we have evaluated a strategy of parallel testing of new compounds using preclinical xenograft studies and experimental, PSA-based, short-term clinical phase II studies (Kranse et al, 2005;Schroder et al, 2005). The xenograft studies were used to confirm efficacy of the compound as well as to validate PSA as a surrogate biomarker for therapy response.…”

“…Two randomised double-blind and placebo-controlled PSA-based phase II studies have been performed in Rotterdam with two different oral supplements constituted of several dietary nutrients including soy isoflavones, lycopene, selenium and antioxidants. Both studies showed prolongation of PSA doubling time when patients received the supplement, suggesting reduction in tumour progression (Kranse et al, 2005;Schroder et al, 2005). In a third preclinical study, the antitumour effect of two dietary nutrients, synthetic lycopene and vitamin E, was tested.…”

Serum prostate-specific antigen but not testosterone levels decrease in a randomized soy intervention among men

“…It was proposed that the estrogen-like structure of isoflavones may interact with male steroid hormones and alter circulating sex hormone levels (Makela et al, 1991). A randomized double-blind intervention study of a dietary supplement containing soy isoflavones, phytosterols, and other nutrients noted a significant reduction in circulating testosterone, dihydrotestosterone (DHT), and free prostate-specific antigen (PSA) levels among prostate cancer patients (Kranse et al, 2005). An intervention with soy protein isolate showed significantly lower serum DHT levels and a decreased DHT/testosterone ratio at the end after a low soy and a high soy diet as compared to the control diet (Dillingham et al, 2005).…”