Citation: Lin, H.-Y.; Zhu, X.; Aucoin, A.J.; Fu, Q.; Park, J.Y.; Tseng, T.-S. Dietary and Serum Antioxidants Associated with Prostate-Specific Antigen for Middle-Aged and Older Men. Nutrients 2023, 15, 3298. https://doi.org/10.3390/nu15153298 Academic Editor: Giorgio Ivan Russo Received: 8 July 2023 Revised: 22 July 2023 Accepted: 22 July 2023 Published: 25 July 2023 Copyright: © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). nutrients Article Dietary and Serum Antioxidants Associated with Prostate-Specific Antigen for Middle-Aged and Older Men Hui-Yi Lin 1, * , Xiaodan Zhu 1 , Alise J. Aucoin 2 , Qiufan Fu 1 , Jong Y. Park 3 and Tung-Sung Tseng 4 1 Biostatistics Program, School of Public Health, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA 2 School of Medicine, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA; aauco4@lsuhsc.edu 3 Department of Cancer Epidemiology, Moffitt Cancer Center & Research Institute, Tampa, FL 33612, USA; jong.Park@moffitt.org 4 Behavior and Community Health Sciences Program, School of Public Health, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA; ttseng@lsuhsc.edu * Correspondence: hlin1@lsuhsc.edu; Tel.: +1-504-568-6083 Abstract: High prostate-specific antigen (PSA) levels can indicate potential prostate problems and are a warning sign of prostate cancer. The impact of antioxidants on the PSA of generally healthy men is understudied. This study aims to evaluate 14 dietary and endogenous antioxi- dants associated with PSA levels for United States (US) men. We assessed 7398 men using the 2003–2010 US population-based National Health and Nutrition Examination Survey (NHANES). The PSA levels were categorized into three groups: Normal, borderline, and elevated levels. We performed analyses for middle-aged and older groups aged 40–64.9 and ≥65, respectively. The weighted multinomial regressions were performed to evaluate antioxidants associated with the PSA status. For results, 0.3% and 3.4% of middle-aged and older men, respectively, had elevated PSA (>10 ng/mL). Men with a higher serum albumin level had a lower risk of an elevated PSA, adjusting for age. The magnitude of albumin’s impact on PSA is larger in middle-aged men than in older men (OR of elevated PSA = 0.82 and 0.90, respectively, interaction p = 0.002). Other antioxidants are not associated with PSA. Our findings support men with low serum albumin tend to have an elevated PSA level, so related interventions can be considered to decrease PSA for maintaining prostate health. Keywords: PSA; prostate cancer; oxidative stress; antioxidant; albumin; vitamin D 1. Introduction The Prostate-Specific Antigen (PSA), a serine protease secreted by prostatic epithe- lial cells, is the most commonly used biomarker in detecting and monitoring prostate health [1]. An elevated PSA level in the blood can indicate prostate-related diseases, such as prostatitis, benign prostatic hyperplasia (BPH), and prostate cancer. Prostate cancer cells often produce higher levels of PSA, resulting in elevated levels in the blood. It is well-known that the probability of prostate cancer increases with the level of PSA. It has been shown that men whose PSA falls within the borderline range (4–10 ng/mL) have an approximate 25% chance of having prostate cancer, and men with a PSA level exceeding 10 ng/mL have a probability greater than 50% [2]. In addition, high PSA levels could be affected by other factors, such as aging, infection, genetics, dietary factors, and antioxidants [3,4]. It is commonly known that aging plays an essential role in increasing serum PSA levels [5–8]. For instance, a study compared PSA levels in men aged 60 and above and found a significant increase in PSA levels with increasing age [5,6]. The serum PSA level increases by approximately 0.04 ng/mL per year in healthy men over 60 [5]. Nutrients 2023, 15, 3298. https://doi.org/10.3390/nu15153298 https://www.mdpi.com/journal/nutrients