Effects of riboflavin in the treatment of brain damage caused by oxygen deprivation: an integrative systematic review

ABSTRACT

Brain oxygen deprivation causes morphological damage involved in the formation of serious pathological conditions such as stroke and cerebral palsy. Therapeutic methods for post-hypoxia/anoxia injuries are limited and still have deficiencies in terms of safety and efficacy. Recently, clinical studies of stroke have reported the use of drugs containing riboflavin for post-injury clinical rehabilitation, however, the effects of vitamin B2 on exposure to cerebral oxygen deprivation are not completely elucidated. This review aimed to investigate the potential antioxidant, anti-inflammatory and neuroprotective effects of riboflavin in cerebral hypoxia/anoxia. After a systematic search, 21 articles were selected, 8 preclinical and 12 clinical studies, and 1 translational study. Most preclinical studies used B2 alone in models of hypoxia in rodents, with doses of 1–20 mg/kg (in vivo) and 0.5–5 µM (in vitro). Together, these works suggested greater regulation of lipid peroxidation and apoptosis and an increase in neurotrophins, locomotion, and cognition after treatment. In contrast, several human studies have administered riboflavin (5 mg) in combination with other Krebs cycle metabolites, except one study, which used only B2 (20 mg). A reduction in lactic acidosis and recovery of sensorimotor functions was observed in children after treatment with B2, while adults and the elderly showed a reduction in infarct volume and cognitive rehabilitation. Based on findings from preclinical and clinical studies, we conclude that the use of riboflavin alone or in combination acts beneficially in correcting the underlying brain damage caused by hypoxia/anoxia and its inflammatory, oxidative, and behavioral impairments.

KEYWORDS:

• Brain hypoxia
• riboflavin
• vitamin B2
• oxidative stress
• neuroinflammation
• neuroprotection; metabolic stress; brain ischemia

Declaration of interests

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Author contributions

Silva-Araújo, ER: Conceptualization, Methodology, Software, Writing. Manhães-de-Castro, R: Supervision, Funding acquisition. Pontes, PB: Methodology, Software, Writing. Visco, DB: Visualization, Supervision. Lacerda, DC: Visualization, Supervision. Gouveia, HJ: Methodology, Software. Toscano, AE: Supervision, Project administration, Funding acquisition.

Data availability statement

The data that support the findings of this study were evaluated by the corresponding author (A.E.T) and are available in this article.

Additional information

Funding

This work was supported by Conselho Nacional de Desenvolvimento Científico e Tecnológico [grant number: #402426/2021-5]; Fundação de Amparo à Ciência e Tecnologia do Estado de Pernambuco [grant number: #1471-4.05/22]; Fundação de Amparo à Ciência e Tecnologia do Estado de Pernambuco [grant number: #0989-4.05/22]; Coordenação de Aperfeiçoamento de Pessoal de Nível Superior [grant number: Finance Code 001].

Notes on contributors

Eulália Rebeca da Silva-Araújo

Eulália Rebeca da Silva-Araújo: Bachelor in Nutrition, Master's student in the Graduate Program in Neuropsychiatry and Behavioral Sciences and Member of the Studies in Nutrition and Phenotypic Plasticity Unit, Federal University of Pernambuco.

Raul Manhães-de-Castro

Raul Manhães-de-Castro: Professor emeritus at UFPE, PhD in Sciences from Université Pierre et Marie Curie (France), Master of Nutrition, Federal University of Pernambuco.

Paula Brielle Pontes

Paula Brielle Pontes: Bachelor in Nutrition, Master in Nutrition, PhD student at the in the Graduate Program in Neuropsychiatry and Behavioral Sciences, Member of the Studies in Nutrition and Phenotypic Plasticity Unit, Federal University of Pernambuco.

Diego Bulcão Visco

Diego Bulcão Visco: PhD in Nutrition, Federal University of Pernambuco, Assistant Professor at Neurofunctional Laboratory - Department of Biological Sciences and Health, Physiotherapy Course, Federal University of Amapá, Leader of the research group “Neurosciences and Functionality in Health”, Federal University of Amapá.

Diego Cabral Lacerda

Diego Cabral Lacerda: PhD in Nutrition, Substitute Professor of Anatomy at the Nursing Unit, Federal University of Pernambuco, Member of the Studies in Nutrition and Phenotypic Plasticity Unit, Federal University of Pernambuco.

Henrique José Cavalcanti Bezerra Gouveia

Henrique J C B Gouveia: Postdoctoral student in Nutrition (UFPE), Member of the Studies in Nutrition and Phenotypic Plasticity Unit, Federal University of Pernambuco.

Ana Elisa Toscano

Ana Elisa Toscano: PhD in Nutrition, Federal University of Pernambuco in co-supervision with Université de Technologie de Compiegne - UTC, France, Coordinator of the Studies in Nutrition and Phenotypic Plasticity Unit, Coordinator of Graduate Program in Neuropsychiatry and Behavioral Sciences for the training os masters and doctors in the area of neuroscience, Federal University of Pernambuco.