Post-diagnostic Zinc Supplement Use and Prostate Cancer Survival Among Men With Nonmetastatic Prostate Cancer

Abstract

Purpose:Biological and experimental evidence support restoration of normal zinc levels in malignant prostate cells as a promising prostate cancer treatment, yet the influence of zinc supplementation after diagnosis on prostate cancer survival in a human population is unknown.Materials and Methods:We prospectively assessed post-diagnostic zinc supplementation in relation to prostate cancer survival among 5,788 men with nonmetastatic prostate cancer in the Health Professionals Follow-up Study (1986-2019). We used Cox regression models to estimate the multivariable hazard ratios and 95% confidence intervals of lethal prostate cancer (distant metastases or prostate cancer–specific death) and all-cause mortality according to post-diagnostic zinc supplement use and dosage.Results:During a median follow-up of 11 years, we documented 527 lethal prostate cancer events and 3,198 all-cause deaths. Fifteen percent of men reported zinc supplement use post-diagnosis. Compared to nonusers, post-diagnostic zinc supplement use was associated suggestively with a lower risk of lethal prostate cancer (HR [95% CI], 0.82 [0.60-1.13]) and significantly with all-cause mortality (0.84 [0.74-0.96]). The inverse association was mostly observed among men who used post-diagnostic zinc supplements of 1-24 mg/d (lethal prostate cancer: 0.55 [0.32-0.96]; all-cause mortality: 0.77 [0.64-0.93]), while higher dosage did not show a lower risk.Conclusions:Post-diagnostic low-dose zinc supplement use among nonmetastatic prostate cancer patients was associated with lower risk of lethal prostate cancer and all-cause mortality. A potential benefit of low-dose post-diagnostic zinc supplement for prostate cancer survival merits further study.

Emerging Perspectives in Zinc Transporter Research in Prostate Cancer: An Updated Review

“…However, the effects of zinc supplementation are controversial, with results varying significantly according to mechanisms that are not well understood. Some studies have suggested that zinc supplementation may benefit prostate cancer patients by reducing the risk of lethal prostate cancer [107][108][109]. In contrast, recent studies, including a 30-year follow-up study and a multi-case control study in Spain, have indicated that zinc supplementation may increase the risk of lethal and aggressive prostate cancer [18,110].…”

“…al. showed that a post-diagnostic low-dose zinc supplementation (1-24 mg/day) in nonmetastatic prostate cancer patients was associated with a lower risk of lethal prostate cancer [109], while high-dose zinc supplementation (>75 mg/day) may increase the risk of lethal and aggressive prostate cancer [18]. Interestingly, a Spanish population of prostate cancer patients receiving zinc supplementation (>10.53 mg/day) may be associated with deleterious effects in those patients with major polygenic risk scores [110], suggesting that a differential effect of zinc supplementation might depend on genetic susceptibility.…”

Correlation between Selenium and Zinc Levels and Survival among Prostate Cancer Patients

“…Molecular and cellular investigations suggest that Se and Zn exhibit reciprocal effects influenced by variations in Zn level [ 22 ]. The low-dose Se and Zn supplementation model can be used to reduce the risk of prostate cancer and overall mortality [ 21 , 23 , 24 ]. However, it should be remembered that supplementation should be performed carefully after studying the level of micronutrients in the patient’s blood/serum.…”

Zinc dampens anti-tumour immunity by promoting Foxp3+ regulatory T cells

“…Studies exploring the relationship between Zn intake and cancer risk have yielded intriguing and, at times, contradictory ndings. Some reports indicated a positive association between high Zn intake and an increased risk of cancer development [19][20][21][22] , while others have pointed towards potential protective effects of Zn against certain cancer types 23,24 . The exact mechanisms underlying of Zn and its association with cancer progression or regression remain elusive, warranting further investigation into the impact of Zn on tumor growth and immune response.…”