Wu Zezhi
Wang Huishu
Li Xiangming- Guangzhou University of Chinese Medicine Affiliated Shantou Hospital of Traditional Chinese Medicine, Shantou, Guangdong, China
by Wang, G., Huang, L., Yue, W., and Feng, J. (2025). Front. Nutr. 12:1579313. doi: 10.3389/fnut.2025.1579313
We, read with great interest the article titled “Joint and independent associations of dietary vitamin intake and prevalence of cardiovascular disease in chronic kidney disease subjects: a cross-sectional analysis” by Wang et al. (1). By leveraging NHANES data, the study provides valuable insights into the protective roles of vitamins B6, E, and multivitamin co-exposure against cardiovascular disease (CVD) in chronic kidney disease (CKD) populations. The authors should be commended for addressing a critical intersection of nutrition, renal disease, and cardiovascular health. While the authors have thoughtfully acknowledged limitations, we offer additional perspectives to contextualize the findings and guide future research.
First, although NHANES provides nationally representative U.S. data, extrapolation to non-U.S. populations may be limited by differences in dietary patterns, genetic predispositions, and healthcare practices. For instance, vitamin D synthesis varies by latitude and skin pigmentation (2), which could influence CKD outcomes. Furthermore, while the study adjusted for key covariates, unmeasured factors such as systemic inflammation (3), or gut microbiota composition (4) might confound the observed associations. Emerging evidence suggests that gut dysbiosis in CKD patients impairs vitamin K metabolism and exacerbates vascular calcification (5)—a pathway not explored here. Future studies should include biomarkers such as homocysteine or markers of oxidative stress, or dietary pattern analysis using the Mediterranean diet score to elucidate these interactions.
Second, the reliance on 24-h dietary recall introduces potential recall bias and may not reflect long-term intake. While the use of Bayesian kernel machine regression (BKMR) to model multivitamin interactions is innovative, The use of supplements such as over-the-counter multivitamins or CKD-specific formulations is excluded, which limits exposure assessment. Additionally, genetic polymorphisms affecting vitamin metabolism (6) might modulate the observed associations. Integrating genomic data or polygenic risk scores could identify subgroups benefiting most from vitamin interventions.
Third, CKD patients often use medications that alter vitamin absorption or metabolism. For example, statins may synergize with vitamin E to reduce oxidative stress (7), while phosphate binders could impair fat-soluble vitamin uptake (8). The study did not address these interactions, nor did it explore comorbidities like diabetes-related oxidative stress, which may exacerbate CVD risk independently of vitamin intake (9, 10). Future analyses incorporating medication histories and comorbidity stratification could refine clinical recommendations.
Fourth, the cross-sectional design precludes causal conclusions, as reverse causality remains plausible. Longitudinal studies tracking vitamin intake and CVD incidence in CKD cohorts would strengthen temporal inferences. Mendelian randomization could also mitigate confounding by leveraging genetic variants as instrumental variables for vitamin exposure. Additionally, sensitivity analyses using propensity score matching or machine learning approaches might enhance robustness.
Finally, this study underscores the need for personalized dietary strategies in CKD management. For instance, vitamin B6 and E intake thresholds may require adjustment based on CKD stage or dialysis status. Public health initiatives should prioritize targeted nutritional education for CKD patients, particularly those with limited healthcare access. Further research should evaluate whether current guidelines sufficiently address skeletal and cardiovascular risks in this population.
In conclusion, Wang et al. have made a significant contribution to understanding dietary vitamin roles in CKD-related CVD. Our suggestions aim to support future investigations into mechanistic pathways, genetic interactions, and real-world clinical applicability. Such efforts will ultimately inform integrated care strategies to improve outcomes in this high-risk population.
Author contributions
WZ: Data curation, Investigation, Methodology, Validation, Writing – original draft. WH: Data curation, Investigation, Methodology, Supervision, Validation, Writing – original draft. LX: Data curation, Investigation, Methodology, Validation, Writing – original draft. XS: Conceptualization, Supervision, Writing – review & editing.
Funding
The author(s) declare that no financial support was received for the research and/or publication of this article.
Conflict of interest
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Generative AI statement
The author(s) declare that no Gen AI was used in the creation of this manuscript.
Publisher's note
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.
References
1. Wang G, Huang L, Yue W, Feng J. Joint and independent associations of dietary vitamin intake and prevalence of cardiovascular disease in chronic kidney disease subjects: a cross-sectional analysis. Front Nutr. (2025) 12:1579313. doi: 10.3389/fnut.2025.1579313
2. Janoušek J, Pilarová V, Macáková K, Nomura A, Veiga-Matos J, Silva DDD, et al. Vitamin D: sources, physiological role, biokinetics, deficiency, therapeutic use, toxicity, and overview of analytical methods for detection of vitamin D and its metabolites. Crit Rev Clin Lab Sci. (2022) 59:517–54. doi: 10.1080/10408363.2022.2070595
3. Kadatane SP, Satariano M, Massey M, Mongan K, Raina R. The role of inflammation in CKD. Cells. (2023) 12:1581. doi: 10.3390/cells12121581
4. Wang X, Yang S, Li S, Zhao L, Hao Y, Qin J, et al. Aberrant gut microbiota alters host metabolome and impacts renal failure in humans and rodents. Gut. (2020) 69:2131–42. doi: 10.1136/gutjnl-2019-319766
5. Ellis JL, Karl JP, Oliverio AM, Fu X, Soares JW, Wolfe BE, et al. Dietary vitamin K is remodeled by gut microbiota and influences community composition. Gut Microbes. (2021) 13:1887721. doi: 10.1080/19490976.2021.1887721
6. Helliwell KE, Wheeler GL, Smith AG. Widespread decay of vitamin-related pathways: coincidence or consequence? Trends Genet. (2013) 29:469–78. doi: 10.1016/j.tig.2013.03.003
7. Cangemi R, Loffredo L, Carnevale R, Pignatelli P, Violi F. Statins enhance circulating vitamin E. Int J Cardiol. (2008) 123:172–4. doi: 10.1016/j.ijcard.2006.11.115
8. Ginsberg C, Zelnick LR, Block GA, Chertow GM, Chonchol M, Hoofnagle A, et al. Differential effects of phosphate binders on vitamin D metabolism in chronic kidney disease. Nephrol Dialysis Transplant. (2020) 35:616–23. doi: 10.1093/ndt/gfaa010
9. Neradova A, Wasilewski G, Prisco S, Leenders P, Caron M, Welting T, et al. Combining phosphate binder therapy with vitamin K2 inhibits vascular calcification in an experimental animal model of kidney failure. Nephrol Dialysis Transplant. (2022) 37:652–62. doi: 10.1093/ndt/gfab314
Keywords: National Health and Nutrition Examination Survey (NHANES), chronic kidney disease (CKD), cardiovascular disease (CVD), cross-sectional analysis, commentary
Citation: Zezhi W, Huishu W, Xiangming L and Shaoting X (2025) Commentary: Joint and independent associations of dietary vitamin intake and prevalence of cardiovascular disease in chronic kidney disease subjects: a cross-sectional analysis. Front. Nutr. 12:1631331. doi: 10.3389/fnut.2025.1631331
Received: 20 May 2025; Accepted: 30 June 2025;
Published: 14 July 2025.
Edited by:
Wenjian Li, Xuzhou Medical University, ChinaReviewed by:
Israel Parra-Ortega, Federico Gómez Children's Hospital, MexicoCopyright © 2025 Zezhi, Huishu, Xiangming and Shaoting. 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: Xie Shaoting, eGllc3QxOTgxQDE2My5jb20=