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Can beta-sitosterol lower PSA?

Results. Subjects treated with β-sitosterol enriched saw palmetto oil showed significant decrease in IPSS, AMS and ADAM scores along with reduced postvoiding residual volume (p < 0.001), PSA (p < 0.01) and 5α-reductase from baseline to end of 12-week treatment as compared to placebo.

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A total of 118 human volunteers were screened of which 99 subjects meeting the inclusion criteria were enrolled in the study. Of the 99 subjects randomized to three treatment groups (n = 33 in each group), 91 subjects completed the study. There were 8 dropouts in the study (reason: lost to follow up). The intention-to-treat (ITT) analysis was used to assess the outcome of the study. The participant flow through the study is presented in Fig. 2. The demographic characteristics of subjects between the groups were not significantly different (Table 2). The efficacy and safety analysis were performed using ITT population.

Fig. 2 Subject participant flow chart Full size image

Table 2 Demographic characteristics of subjects Full size table

The comparative efficacy of VISPO against the conventional saw palmetto oil was evaluated primarily using IPSS, ADAM and AMS scores assessed at visit 1 (baseline), visit 2 (6 weeks) and visit 3 (12 weeks) of the study. At baseline there was no significant difference in the IPSS score between the groups while the values were decreased in VISPO and SPO groups during the study (Table 3). There was a significant decrease in the IPSS score from baseline value of 20.00 ± 4.41 to 18.06 ± 4.14 at visit 2 (p < 0.001) and 16.82 ± 4.03 at visit 3 (p < 0.001). The values were not significant for SPO group. In the placebo group there was a slight increase in IPSS score during the intervention period. The change in IPSS value from baseline to the end of treatment (visit 3) was significant in saw palmetto oil treated groups as compared to placebo (p < 0.001). Table 3 Summary of International Prostate Symptom Score (IPSS) by visit and treatment Full size table In the present study ADAM questionnaire was used to screen for the severity of androgen deficiency in men (Table 4). The ITT population analysis revealed that VISPO group subjects showed a significant reduction of ADAM score from baseline (4.33 ± 1.67) to the end of study (3.73 ± 1.74) (p < 0.001) while SPO and placebo groups showed an increase in the mean ADAM score. The change in the score from baseline to visit 3 of VISPO group (− 0.61 ± 1.06) was significant (p < 0.01) compared to placebo (0.15 ± 0.94). Further AMS scale was used to assess the symptoms of ageing and to measure the changes in severity of symptoms pre- and post-intervention (Table 5). AMS scale has three dimensions (sub-scales) i.e., psychological, somatic, and sexual subscale. The composite scores for each of the three sub-scales is based on adding up the scores of the items of the respective dimensions. The AMS total score from baseline to end of treatment decreased considerably in VISPO group (p < 0.001). SPO group showed non-significant reduction in the mean score. The change in total AMS score from baseline to visit 3 of VISPO (− 3.64 ± 4.76) and SPO (− 1.12 ± 4.14) groups were significant (p < 0.001) when compared to placebo (1.70 ± 3.37). Similar trend was observed in the AMS subscale analyses (Table 6). Importantly, there was a significant reduction (p < 0.001) in the AMS sexual subscale from baseline to the end of treatment in VISPO (− 1.24 ± 1.84) and SPO (− 0.12 ± 1.47) groups as compared to placebo (0.73 ± 1.26).

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Table 5 Summary of total Aging male symptoms (AMS) score by visit and treatment Full size table Table 6 Summary of Aging male symptoms (AMS) subscale analysis Full size table Table 7 shows the urodynamic measurements obtained before and after the intervention period. The residual urine volume decreased significantly (p < 0.001) in VISPO group (from 112.55 ± 36.19 mL to 99.79 ± 29.27 mL) after the 12-week treatment. SPO group showed a slight improvement in residual urine volume, though not to a significant extent (110.12 ± 34.71 mL to 108.24 ± 33.22 mL). A significant improvement (p < 0.001) of Qmax was observed in the VISPO group (from 11.85 ± 2.06 mL/s to 14.27 ± 2.54 mL/s). In the SPO group a non-significant increase in the Qmax was recorded from 12.33 ± 1.61 mL/s to 12.82 ± 1.72 mL/s. Table 7 Summary of urodynamic measurements by visit and treatment Full size table Assessment of serum BPH markers are presented in Table 8. Serum levels of PSA was decreased in the VISPO group from 2.77 ± 0.56 ng/mL to 2.70 ± 0.59 ng/mL while it was increased in SPO and placebo groups after the treatment. The subjects in VISPO group showed an increase in free testosterone levels (6.23 ± 1.16 to 6.46 ± 1.43) after treatment (p < 0.05). On the contrary there was a reduction of serum levels of free testosterone in SPO and placebo groups. The change in free testosterone from baseline to end of treatment was significant in VISPO group as compared to placebo (p < 0.05). There was a reduction in total testosterone noted in all the treatment groups. However, the data were not significant. 5α-reductase activity was non-significantly reduced in VISPO group from baseline to the end of 12-week treatment (445.90 ± 105.40 ng/L to 438.24 ± 98.56). However, it was noticed that unexpectedly, the enzyme activity was increased in SPO group towards the end of study.

Table 8 Summary of BPH marker analysis Full size table

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The Short-Form Health Survey (SF-12) is one of the most widely used questionnaire for assessing self-reported health-related quality of life. VISPO group subjects demonstrated a significant improvement (p < 0.001) in the quality of life as evident from the increase in the mean total score. Comparatively, SPO group showed moderate increase in the SF-12 total score. Both VISPO and SPO groups showed significant change in mean score from visit 1 to visit 3 as compared to placebo. The subset analysis revealed that VISPO group also showed significant improvement in PCS-12 and MCS-12 scores after 12-week treatment (p < 0.001), Fig. 3 shows the change in SF-12 scores from baseline to the end of treatment. Fig. 3 Mean change in SF-12 score of the study participants. The changes from baseline (visit 1) to the end of treatment (visit 3) in SF-12 total score (a), physical health composite (PCS-12) score and mental health composite (MCS-12) score (b) . The values are represented as mean ± SD (n = 33 in each group). The data were analysed by one way ANOVA followed by Scheffe test. ***p < 0.001 vs. placebo Full size image No serious adverse events (SAEs) were recorded during the study. The investigational products were well tolerated among the subjects. There were no significant alterations in the biochemical and haematological parameters among the subjects during the intervention period. The results of safety assessment are provided in supplementary file 4.

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