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Nutrients
Volume 17
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10.3390/nu17010040
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Review

Hyperhomocysteinemia: Underlying Links to Stroke and Hydrocephalus, with a Focus on Polyphenol-Based Therapeutic Approaches

by
Carmen Ortiz-Salguero
1,
Marina Romero-Bernal
1,
Ángela González-Díaz
1,
Elaheh Sobh Doush
1,
Carmen del Río
1,*,
Miriam Echevarría
1 and
Joan Montaner
2,3,*
1
Instituto de Biomedicina de Sevilla, IBiS, Hospital Universitario Virgen del Rocío, CSIC, Universidad de Sevilla, 41013 Sevilla, Spain
2
Instituto de Biomedicina de Sevilla, IBiS, Hospital Universitario Virgen Macarena, CSIC, Universidad de Sevilla, 41004 Sevilla, Spain
3
Department of Neurology, Hospital Universitario Virgen Macarena, 41004 Sevilla, Spain
*
Authors to whom correspondence should be addressed.
Nutrients 2025, 17(1), 40; https://doi.org/10.3390/nu17010040
Submission received: 22 November 2024 / Revised: 19 December 2024 / Accepted: 23 December 2024 / Published: 26 December 2024
(This article belongs to the Section Proteins and Amino Acids)
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Highlights

  • Mutations (e.g., MTHFR) and B-vitamin deficiencies elevate homocysteine (HCys) levels.
  • Elevated HCys levels induce oxidative stress, inflammation and neurodegeneration.
  • HCys modulates endothelial dysfunction and fluid dynamics, with implications for stroke and hydrocephalus pathogenesis.
  • Polyphenols can reduce HCys levels by enhancing key metabolic enzymes and counteracting oxidative and inflammatory damage, offering neurovascular protection.
  • Polyphenol-rich diets and supplementation show potential in mitigating neurovascular damage.

Abstract

Hyperhomocysteinemia (HHcy), characterized by elevated homocysteine (HCys) levels, is associated with increased risks of neurovascular diseases such as stroke or hydrocephalus. HHcy promotes oxidative stress, neuroinflammation, and endothelial dysfunction, disrupting the blood–brain barrier and accelerating neurodegeneration. These processes highlight HCys as both a biomarker and a potential therapeutic target in vascular-related neurological disorders. Current research suggests that polyphenols, known for their antioxidant and anti-inflammatory properties, may reduce HCys levels and offer neuroprotection. Polyphenols have demonstrated effectiveness in modulating oxidative stress and inflammatory pathways triggered by HHcy. These compounds may also upregulate enzymatic functions involved in HCys metabolism, thus reducing neurotoxicity. Furthermore, polyphenol-rich diets, like the Mediterranean diet, have been linked to lower HCys levels and a reduced incidence of neurovascular disorders. This review provides an overview of HHcy’s role in neurovascular pathologies and examines the therapeutic potential of polyphenols in managing HCys levels and preventing HCys-induced neurovascular damage.
Keywords: small vessel; homocysteine; polyphenols; hydrocephalus; stroke small vessel; homocysteine; polyphenols; hydrocephalus; stroke

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MDPI and ACS Style

Ortiz-Salguero, C.; Romero-Bernal, M.; González-Díaz, Á.; Doush, E.S.; del Río, C.; Echevarría, M.; Montaner, J. Hyperhomocysteinemia: Underlying Links to Stroke and Hydrocephalus, with a Focus on Polyphenol-Based Therapeutic Approaches. Nutrients 2025, 17, 40. https://doi.org/10.3390/nu17010040

AMA Style

Ortiz-Salguero C, Romero-Bernal M, González-Díaz Á, Doush ES, del Río C, Echevarría M, Montaner J. Hyperhomocysteinemia: Underlying Links to Stroke and Hydrocephalus, with a Focus on Polyphenol-Based Therapeutic Approaches. Nutrients. 2025; 17(1):40. https://doi.org/10.3390/nu17010040

Chicago/Turabian Style

Ortiz-Salguero, Carmen, Marina Romero-Bernal, Ángela González-Díaz, Elaheh Sobh Doush, Carmen del Río, Miriam Echevarría, and Joan Montaner. 2025. "Hyperhomocysteinemia: Underlying Links to Stroke and Hydrocephalus, with a Focus on Polyphenol-Based Therapeutic Approaches" Nutrients 17, no. 1: 40. https://doi.org/10.3390/nu17010040

APA Style

Ortiz-Salguero, C., Romero-Bernal, M., González-Díaz, Á., Doush, E. S., del Río, C., Echevarría, M., & Montaner, J. (2025). Hyperhomocysteinemia: Underlying Links to Stroke and Hydrocephalus, with a Focus on Polyphenol-Based Therapeutic Approaches. Nutrients, 17(1), 40. https://doi.org/10.3390/nu17010040

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