Dimethyl Fumarate’s Potential in Methanol Toxicity: A Critical Perspective on Future Research Directions
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Letter to the Editor
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14 October 2025

Dimethyl Fumarate’s Potential in Methanol Toxicity: A Critical Perspective on Future Research Directions

J Acad Res Med. Published online 14 October 2025.
1. University of Health Sciences Türkiye Başakşehir Çam and Sakura City Hospital, Department of Emergency Medicine, İstanbul, Türkiye
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Received Date: 08.08.2025
Accepted Date: 10.09.2025
E-Pub Date: 14.10.2025
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Dear Editor,

After reading the study by Akyuz Unsal et al. (1) investigating the effects of dimethyl fumarate (DMF) on methanol (MeOH) toxicity, we would like to address an important gap in this research area. As the authors noted, the effects of DMF on organ-level MeOH toxicity have not been previously investigated, particularly considering the significant retinal side effects.

MeOH poisoning causes oxidative stress and retinal ganglion cell damage through its formic acid metabolite. DMF’s proven antioxidant and anti-inflammatory properties in multiple sclerosis and psoriasis treatment may provide protective effects against these toxic processes (2). Indeed, DMF activates the Nrf2 pathway, increasing antioxidant gene expression while suppressing pro-inflammatory cytokines such as interleukin-6 and tumor necrosis factor-alpha (3).

Although the study results were unexpected, the demonstration of DMF’s safety profile is valuable. However, its potential for retinal protection could not be fully evaluated. Literature reports show that DMF exhibits protective effects in age-related macular degeneration, uveitis, and light-induced photoreceptor loss (4). These findings suggest DMF’s therapeutic potential against MeOH’s retinal toxicity.

The study’s limitations, particularly the failure to establish a toxicity model, may have masked DMF’s true effects. Future studies should include specific ophthalmological evaluations such as optical coherence tomography, electroretinography, and retinal ganglion cell counting. Additionally, testing different DMF doses and administration timing would be critical for determining optimal protective protocols.

Given the limited treatment options for MeOH poisoning, investigating multi-target agents like DMF is of great importance. Particularly, DMF’s dual action of reducing oxidative stress and suppressing inflammation offers an ideal protective profile against MeOH’s bidirectional toxic mechanisms (5).

This investigation represents a valuable foundation for exploring DMF’s therapeutic potential in MeOH toxicity, despite methodological challenges encountered. Future research employing more sophisticated toxicity models and comprehensive retinal assessments could provide crucial insights that may ultimately translate into clinical therapeutic strategies for this life-threatening condition (6).

Sincerely,

Keywords:
Dimethyl fumarate, methanol toxicity, retinal protection, oxidative stress, neuroprotection
Author Contributions: Surgical and Medical Practices - M.Ö.; Concept - M.N.S.; Design - M.N.S.; Data Collection and/or Processing - M.Ö.; Analysis and/ or Interpretation - M.N.S.; Literature Search - M.N.S.; Writing - M.N.S.
Conflict of Interest: The authors have no conflicts of interest to declare.
Financial Disclosure: The authors report that no financial support was received for this study.

References

1
Akyuz Unsal AI, Unsal AA, Meteoglu I, Demirci B. The Effect of dimethyl fumarate on tissues in methanol poisoning. J Acad Res Med. 2025; 15: 88-93.
2
Linker RA, Lee DH, Ryan S, van Dam AM, Conrad R, Bista P, et al. Fumaric acid esters exert neuroprotective effects in neuroinflammation via activation of the Nrf2 antioxidant pathway. Brain. 2011; 134: 678-92.
3
Gillard GO, Collette B, Anderson J, Chao J, Scannevin RH, Huss DJ, et al. DMF, but not other fumarates, inhibits NF-κB activity in vitro and in vivo. J Neuroimmunol. 2015; 283: 74-85.
4
Manai F, Govoni S, Amadio M. The challenge of dimethyl fumarate repurposing in eye pathologies. Cells. 2022; 11: 4061.
5
Albrecht P, Bouchachia I, Goebels N, Henke N, Hofstetter HH, Issberner A, et al. Effects of dimethyl fumarate on neuroprotection and immunomodulation. J Neuroinflammation. 2012; 9: 163.
6
Sahin A, Kaya S, Türkcü G, Cingü AK, Yüksel H, Türkcü FM, et al. The effects of caffeic acid phenethyl ester in acute methanol toxicity on rat retina and optic nerve. Cutan Ocul Toxicol. 2013; 32: 263-7.