# The association between urinary nitrate and prostate specific antigen without prostatic disease: a cohort study

## TL;DR

This study finds that higher urinary nitrate levels are linked to lower prostate-specific antigen (PSA) ratios in men without prostate disease, which could help improve cancer screening accuracy.

## Contribution

This is the first study to explore the relationship between urinary nitrate and the PSA ratio in a general population without prostate disease.

## Key findings

- Urinary nitrate shows a significant negative correlation with the PSA ratio in the gray zone (4–10 ng/mL).
- The association remains significant after adjusting for confounders, suggesting potential for improved prostate cancer screening.
- A nonlinear relationship between urinary nitrate and PSA was observed, with minimal changes at lower levels followed by a decline.

## Abstract

The carcinogenic effects of nitrate reduction to nitrite are well established, and nitrate has been closely linked to various diseases. However, research on its effects on the urinary system remains limited, and its association with PSA remains unclear. This study aims to investigate the relationship between urinary nitrate and PSA.

We employed weighted generalized linear models, weighted univariate analysis, forest plots, weighted multivariable analysis, and generalized additive models (GAM) to investigate the relationship between urinary nitrate and PSA. Subgroup analyses were conducted to further validate the stability of this association across different groups. GAM was utilized to provide a more intuitive representation of the specific relationships between PSA and urinary nitrate.

TPSA, FPSA, and the prostate specific antigen ratio (%, 4 ng/mL ≤ TPSA ≤ 10 ng/mL) showed negative correlations with urinary nitrate. After adjusting for confounders, only the prostate-specific antigen ratio maintained a significant negative association (β = -632.7; 95% CI: -1094.9, -170.6; P = 0.011), while correlations with TPSA and FPSA were not statistically significant. A nonlinear relationship was observed, where urinary nitrate initially remained stable or changed minimally before gradually declining.

This study identifies a negative correlation between urinary nitrate and the prostate-specific antigen ratio in individuals with gray-zone TPSA. These findings enhance our understanding of urinary nitrate’s impact and may help reduce overtreatment in this population.

This study is the first to investigate the relationship between urinary nitrate and the prostate-specific antigen (PSA) ratio in a general population without prostatic disease, providing novel insights into the potential impact of urinary nitrate on PSA screening.Our findings reveal a significant negative correlation between urinary nitrate and the PSA ratio in the gray zone (4–10 ng/mL), suggesting that urinary nitrate may improve the accuracy of prostate cancer screening and reduce overtreatment.The study highlights the importance of exploring urinary biomarkers in prostate cancer screening, potentially leading to more precise risk assessment and fewer unnecessary biopsies.

This study is the first to investigate the relationship between urinary nitrate and the prostate-specific antigen (PSA) ratio in a general population without prostatic disease, providing novel insights into the potential impact of urinary nitrate on PSA screening.

Our findings reveal a significant negative correlation between urinary nitrate and the PSA ratio in the gray zone (4–10 ng/mL), suggesting that urinary nitrate may improve the accuracy of prostate cancer screening and reduce overtreatment.

The study highlights the importance of exploring urinary biomarkers in prostate cancer screening, potentially leading to more precise risk assessment and fewer unnecessary biopsies.