Introduction
We read the article by Jin et al. (1) regarding the Composite Dietary Antioxidant Index (CDAI) and “high-risk prostate cancer” with great interest. While utilizing NHANES data offers valuable insights into nutritional epidemiology, we write to discuss potential methodological limitations that may affect the clinical applicability of their conclusions. Specifically, defining “high-risk prostate cancer” solely based on a serum tPSA > 10 ng/mL threshold in a cancer-free screening population raises concerns regarding oncological specificity.
Distinction between clinical diagnosis and epidemiological surrogates
A primary concern lies in the definition of the outcome. In clinical practice, standard risk stratification requires histopathological confirmation (e.g., Gleason grading) and clinical staging (2). We acknowledge that in population-based research, biomarkers are often used as surrogate endpoints when pathological data is unavailable. However, even within an epidemiological framework, using a PSA threshold of >10 ng/mL as a sole proxy for “high-risk cancer” in older men is problematic. The 2023 AUA/SUO Guideline notes that PSA is a continuous variable that increases with both age and benign prostatic hyperplasia (BPH) (3). The EAU Guidelines also state that PSA’s continuous nature limits the utility of a single threshold for cancer detection (4). Consequently, without exclusion of benign causes, this surrogate endpoint likely captures a mixed signal of both malignancy and benign prostatic growth, potentially reducing the specificity of the findings.
The anti-inflammatory hypothesis
The observed association between CDAI and PSA levels may also be interpreted through an alternative mechanism: the anti-inflammatory effect. Biological evidence suggests that inflammation modulates PSA levels in benign conditions. Cross-sectional data from Weng et al. (2023) indicate that pro-inflammatory diets are associated with PSA elevation (5). Furthermore, interventional studies, such as Schwarz et al. (2008), have observed that lycopene supplementation reduced serum PSA in patients with BPH (6). Similarly, Kutwin et al. (2022) highlighted how natural antioxidants may mitigate the oxidative stress driving BPH (7). We hypothesize that the inverse association reported by Jin et al. might plausibly reflect the efficacy of antioxidants in suppressing prostatic inflammation and lowering BPH-associated PSA, rather than exclusively indicating a protective effect against tumorigenesis.
Epidemiological context and confounding factors
Finally, the prevalence of benign conditions in this demographic warrants consideration. The authors noted in their Introduction that PSA elevation is not specific to malignancy (1). Epidemiological data from the GBD 2019 study indicate that the prevalence of BPH in men aged 60 and older is substantial, often exceeding 50% (8), whereas the prevalence of prostate cancer is comparatively lower (<5%) in the general population. Given this prevalence gap, it is plausible that the “High-Risk” group (PSA > 10 ng/mL) includes a significant proportion of individuals with undiagnosed BPH. If BPH status was not fully adjusted for (potentially due to data limitations in NHANES), the study essentially compares a high-antioxidant group against a group with elevated PSA of mixed etiology.
Discussion
In conclusion, while the CDAI is a valuable construct, the findings regarding “cancer prevention” should be interpreted with caution due to the non-specific nature of the PSA endpoint. We suggest that the results could be re-interpreted as an association between antioxidants and benign prostatic health or general PSA reduction. Future research utilizing NHANES data for oncological outcomes would benefit from integrating available diagnostic codes or specifying the limitations of biochemical surrogates to avoid potential misclassification.
Statements
Author contributions
YD: Writing – original draft. SL: Writing – original draft. CW: Investigation, Writing – review & editing. HZ: Writing – review & editing, Validation. PS: Writing – review & editing.
Funding
The author(s) declared that financial support was not received for this work and/or its publication.
Conflict of interest
The author(s) declared that this work was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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References
1
JinXTongWSunLLuSSunPLiHet al. Association of composite dietary antioxidant index with high risk of prostate cancer in middle-aged and elderly men: insights from NHANES. Front Immunol. (2025) 16:1530174. doi: 10.3389/fimmu.2025.1530174
2
CooperbergMRMeeksWFangRGaylisFDCatalonaWJMakarovDV. Time trends and variation in the use of active surveillance for management of low-risk prostate cancer in the US. JAMA Netw Open. (2023) 6:e231439. doi: 10.1001/jamanetworkopen.2023.1439
3
WeiJTBarocasDCarlssonSCoakleyFEggenerSEtzioniRet al. Early detection of prostate cancer: AUA/SUO guideline part I: prostate cancer screening. J Urol. (2023) 210:46–53. doi: 10.1097/JU.0000000000003491
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MottetNvan den BerghRCNBriersEVan den BroeckTCumberbatchMGDe SantisMet al. EAU-EANM-ESTRO-ESUR-SIOG guidelines on prostate cancer—2020 update. Part 1: Screening, diagnosis, and local treatment with curative intent. Eur Urol. (2021) 79:463–79. doi: 10.1016/j.eururo.2020.09.042
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WengXTanWWeiBYangSGuCWangS. Interaction between drinking and dietary inflammatory index affects prostate specific antigen: A cross-sectional study. BMC Geriatr. (2023) 23:537. doi: 10.1186/s12877-023-04151-2
6
SchwarzSObermüller-JevicUCHellmisEKochWJacobiGBiesalskiH-K. Lycopene inhibits disease progression in patients with benign prostate hyperplasia. J Nutr. (2008) 138:49–53. doi: 10.1093/jn/138.1.49
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KutwinPFalkowskiPŁowickiRBorowiecka-KutwinMKoneckiT. Are we sentenced to pharmacotherapy? Promising role of lycopene and vitamin a in benign urologic conditions. Nutrients. (2022) 14:859. doi: 10.3390/nu14040859
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GBD 2019 Benign Prostatic Hyperplasia Collaborators. The global, regional, and national burden of benign prostatic hyperplasia in 204 countries and territories from 2000 to 2019: A systematic analysis for the global burden of disease study 2019. Lancet Healthy Longev. (2022) 3:e754–76. doi: 10.1016/S2666-7568(22)00213-6
Summary
Keywords
benign prostatic hyperplasia (BPH), composite dietary antioxidant index(CDAI), diagnostic misclassification, NHANES, prostate cancer, prostate-specific antigen (PSA)
Citation
Dai Y, Liu S, Wang C, Zhang H and Shang P (2026) Commentary: Association of composite dietary antioxidant index with high risk of prostate cancer in middle-aged and elderly men: insights from NHANES. Front. Immunol. 17:1799402. doi: 10.3389/fimmu.2026.1799402
Received
29 January 2026
Revised
13 February 2026
Accepted
16 February 2026
Published
02 March 2026
Volume
17 - 2026
Edited by
José Antonio Estrada, Universidad Autónoma del Estado de México, Mexico
Reviewed by
Mojtaba Yousefi, Yasuj University of Medical Sciences, Iran
Updates
Copyright
© 2026 Dai, Liu, Wang, Zhang and Shang.
This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Panfeng Shang, shangpf@lzu.edu.cn
†These authors have contributed equally to this work and share first authorship
Disclaimer
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.