# Effects of Citicoline-Based Supplementation on Lipid Peroxidation Markers and Sirtuin-1 Expression in Ischemic Stroke

**Authors:** Todorka Sokrateva, Bogdan Roussev, Daniela V. Vankova, Deyana G. Vankova, Diana Ivanova, Mihael Tsalta-Mladenov, Darina Georgieva, Miglena N. Nikolova, Galya Mihaylova, Milka A. Nashar

PMC · DOI: 10.3390/cimb48030314 · 2026-03-15

## TL;DR

This study investigates how a supplement containing citicoline and other ingredients affects oxidative stress and a protective protein in people with ischemic stroke.

## Contribution

The study introduces a new supplement formulation and evaluates its effects on lipid peroxidation and SIRT1 expression in stroke patients.

## Key findings

- Cytodeox™ reduced arachidonic acid and oxidative stress markers in healthy individuals.
- SIRT1 expression increased significantly in stroke patients, especially those with diabetes.
- The supplement showed potential as an antioxidant and membrane stabilizer in early stroke intervention.

## Abstract

Ischemic stroke (IS) is associated with pronounced oxidative stress and lipid peroxidation, which contribute to secondary neuronal damage. This study explored the effects of a six-month intervention with a new formulation containing citicoline, vitamin C, and extracts from green tea and aronia (Cytodeox™) on arachidonic acid (AA) metabolism, lipid peroxidation assessed by total 8-iso-prostaglandin F2α (8-iso-PGF2α), and Sirtuin-1 (SIRT1) expression in healthy controls (n = 43) and patients with IS (n = 53), both with and without comorbidities. AA and 8-iso-PGF2α were quantified in serum using UPLC–MS and ELISA, respectively, and the fold change in SIRT1 expression was assessed in peripheral blood mononuclear cells (PBMCs) by RT-qPCR. In healthy controls, Cytodeox™ significantly lowered AA and 8-iso-PGF2α levels. IS patients showed markedly increased baseline 8-iso-PGF2α, indicating severe oxidative stress. Following supplementation, 8-iso-PGF2α levels increased in patients with comorbidities, particularly diabetes mellitus (DM), whereas an exploratory analysis suggested a decreasing trend in patients without comorbidities. SIRT1 expression was significantly upregulated in IS patients, with the most pronounced increase observed in the DM subgroup, while remaining unchanged in controls. These findings suggest a protective, antioxidant, and membrane stabilising effect of Cytodeox™ under conditions of preserved or moderately impaired redox homeostasis, supporting its potential role as a preventive or early supportive intervention.

## Linked entities

- **Proteins:** SIRT1 (sirtuin 1), SIRT1 (sirtuin 1)
- **Chemicals:** citicoline (PubChem CID 13804), vitamin C (PubChem CID 54670067), arachidonic acid (PubChem CID 444899), 8-iso-prostaglandin F2α (PubChem CID 5282263)
- **Diseases:** ischemic stroke (MONDO:1060198), diabetes mellitus (MONDO:0005015)

## Full-text entities

- **Genes:** SIRT1 (sirtuin 1) [NCBI Gene 23411] {aka SIR2, SIR2L1, SIR2alpha}, ACTB (actin beta) [NCBI Gene 60] {aka BKRNS, BNS, BRWS1, CSMH, DDS1, PS1TP5BP1}, PLA2G1B (phospholipase A2 group IB) [NCBI Gene 5319] {aka PLA2, PLA2A, PPLA2}, SMAD7 (SMAD family member 7) [NCBI Gene 4092] {aka CRCS3, MADH7, MADH8}, TP53 (tumor protein p53) [NCBI Gene 7157] {aka BCC7, BMFS5, LFS1, P53, TRP53}, TBXA2R (thromboxane A2 receptor) [NCBI Gene 6915] {aka BDPLT13, TXA2-R}
- **Diseases:** metabolic disorders (MESH:D008659), brain ischemia (MESH:D002545), cerebrovascular disease (MESH:D002561), malignancies (MESH:D009369), central nervous system trauma (MESH:D020196), hypoxia (MESH:D000860), cystic fibrosis (MESH:D003550), hyperglycemia (MESH:D006943), infectious or (MESH:D003141), neurological deficit (MESH:D009461), hypertension (MESH:D006973), nervous system malignancies (MESH:D010524), endothelial dysfunction (MESH:D014652), allergy (MESH:D004342), chronic inflammation (MESH:D007249), dysphagia (MESH:D003680), neuronal damage (MESH:D009410), traumatic brain injury (MESH:D000070642), impaired consciousness (MESH:D003244), chronic kidney disease (MESH:D051436), ischemic injury (MESH:D017202), subarachnoid haemorrhage (MESH:D013345), IS (MESH:D002544), ischemic attack (MESH:D002546), injury to (MESH:D014947), diabetic vascular complications (MESH:D003925), dyslipidemia (MESH:D050171), Stroke (MESH:D020521), hemorrhagic stroke (MESH:D000083302), metabolic dysregulation (MESH:D021081), infarct (MESH:D007238), vascular injury (MESH:D057772), obesity (MESH:D009765), transient (MESH:C563551), cognitive impairment (MESH:D003072), neuroinflammation (MESH:D000090862), cardiovascular disease (MESH:D002318), small-vessel occlusive disease (MESH:D059345), neurodegeneration (MESH:D019636), gastrointestinal discomfort (MESH:D005767), atherosclerosis (MESH:D050197), mitochondrial dysfunction (MESH:D028361), reperfusion injury (MESH:D015427), DM (MESH:D003920), ischaemia (MESH:D007511)
- **Chemicals:** ROS (MESH:D017382), polyunsaturated fatty acids (MESH:D005231), phosphatidylcholine (MESH:D010713), acetonitrile (MESH:C032159), PBS (MESH:D007854), AA (MESH:D016718), phospholipid (MESH:D010743), methanol (MESH:D000432), prostaglandin F2alpha (MESH:D015237), dichloromethane (MESH:D008752), Polyphenols (MESH:D059808), ATP (MESH:D000255), Vitamin C (MESH:D001205), fibrate (MESH:D058607), choline (MESH:D002794), ammonium formate (MESH:C030544), FFA (MESH:D005230), water (MESH:D014867), isopropanol (MESH:D019840), dopamine (MESH:D004298), hydroxyeicosatetraenoic acid (MESH:D006893), cholesterol (MESH:D002784), 8-iso-PGF2alpharelative (-), nitric oxide (MESH:D009569), Isoprostanes (MESH:D028421), prostaglandins (MESH:D011453), calcium (MESH:D002118), leukotrienes (MESH:D015289), 8-iso-PGF2alpha (MESH:C075750), F2-isoprostanes (MESH:D028441), anthocyanins (MESH:D000872), malondialdehyde (MESH:D008315), oxygen (MESH:D010100), catechins (MESH:D002392), eicosanoid (MESH:D015777), Lipid (MESH:D008055), norepinephrine (MESH:D009638), free-radical (MESH:D005609), Triglyceride (MESH:D014280), Citicoline (MESH:D003566)
- **Species:** Aronia (genus) [taxon 193297], Camellia sinensis (black tea, species) [taxon 4442], Rosa (genus) [taxon 3764], Aronia melanocarpa (black chokeberry, species) [taxon 661339], Homo sapiens (human, species) [taxon 9606]

## Figures

5 figures with captions in the complete paper: https://tomesphere.com/paper/PMC13024967/full.md

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Source: https://tomesphere.com/paper/PMC13024967