For men whose prostate-specific antigen (PSA) levels begin to rise again after local treatment, indicating a biochemical recurrence, androgen deprivation therapy (ADT) is a common next step. However, ADT carries potential side effects that can impact quality of life. Particularly for men whose PSA levels are rising slowly (indicated by a long PSA doubling time, or PSADT), there’s often a period of watchful waiting before starting hormone therapy. This window presents an opportunity to explore less intensive interventions.

Researchers recently investigated one such potential intervention: Grape Seed Extract (GSE), a natural phytochemical known for its tolerability. A Phase II clinical trial,the results of which were presented at ACCR 2025 explored whether a specific, highly bioavailable formulation of GSE could impact PSA progression in men experiencing this early, non-metastatic recurrence. Forty-one eligible men, all with rising PSA levels after maximal local therapy, took 150mg of the specialized GSE orally twice a day for twelve months, or until their cancer progression necessitated other treatments.

The results offer a note of optimism. The study found that, on average, GSE significantly slowed the rate of PSA rise. The participants’ average PSADT increased from 5.71 months before starting GSE to 6.86 months while on the treatment. This indicates a slowing of cancer progression for the group as a whole. Notably, a large majority of the men, 32 out of 41 (78%), experienced some lengthening of their PSADT. Furthermore, 15 men (37%) achieved the study’s primary goal: a substantial increase in PSADT of 30% or more. While most men benefited, nine participants (22%) did see their PSADT decrease during the study period.

Intriguingly, the researchers observed that men who responded positively to GSE, showing an increased PSADT, tended to have higher PSA and testosterone levels at the start of the trial compared to those whose PSADT decreased. This suggests certain patient characteristics might predict a better response to this natural extract. Importantly, the GSE supplement was well-tolerated; only one participant discontinued the study due to side effects (hypertension and rash).

While encouraging, these findings need confirmation through larger, placebo-controlled clinical trials before GSE can be routinely recommended for this purpose.

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