Publication Name	World Journal of Diabetes
Manuscript ID	104851
Country	China

Category	Nutrition & Dietetics
Manuscript Type	Letter to the Editor
Article Title	Dose-dependent L-arginine cardiotoxicity in diabetic cardiomyopathy: Mechanisms and clinical implications
Manuscript Source	Invited Manuscript
All Author List	Si-Jun Yang
Funding Agency and Grant Number
Corresponding Author	Si-Jun Yang, Department of Laboratory Medicine, Huangshi Maternity and Children's Health Hospital, Affiliated Maternity and Children's Health Hospital of Hubei Polytechnic University, No. 9 Guilin South Road, Xialu District, Huangshi 435000, Hubei Province, China. yangsijun@ncu.edu.cn
Key Words	L-arginine; Type 2 diabetes; Myocardial injury; Oxidative stress; Inflammation
Core Tip	This letter critiques Mansouri et al's study on L-arginine (L-Arg) in diabetic cardiomyopathy, revealing dose-dependent cardiotoxicity: While low doses (0.5 g/kg) may modestly improve lipid profiles, higher doses (≥ 1 g/kg) exacerbate myocardial injury via prooxidant [nuclear factor E2-related factor (Nrf-2) depletion] and proinflammatory (inducible nitric oxide synthase-driven peroxynitrite) mechanisms. The findings challenge the perception of L-Arg as universally safe, especially in diabetics with endothelial dysfunction. Urgent clinical translation is needed to validate safe thresholds in humans, alongside tailored guidelines for vulnerable populations. Future research should prioritize human trials, combination therapies (e.g., Nrf-2 activators), and regulatory frameworks for supplement standardization.
Citation	Yang SJ. Dose-dependent L-arginine cardiotoxicity in diabetic cardiomyopathy: Mechanisms and clinical implications. World J Diabetes 2025; In press

Received	2025-01-20 10:56
Peer-Review Started	2025-01-20 10:56
To Make the First Decision
Return for Revision	2025-03-05 09:36
Revised	2025-03-12 11:52
Second Decision	2025-03-21 03:16
Accepted by Journal Editor-in-Chief
Accepted by Executive Editor-in-Chief	2025-03-21 08:16
Articles in Press	2025-03-21 08:16
Publication Fee Transferred
Edit the Manuscript by Language Editor	2025-03-23 23:36
Typeset the Manuscript	2025-03-30 15:52

ISSN	1948-9358 (online)
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