A Comprehensive Systematic Review of Investigating the Antioxidant Effect of Vitamin E in Depression
Keywords:
Vitamin E, tocopherol, depression, oxidative stress, antioxidant, lipid peroxidation, systematic review, meta-analysisAbstract
Introduction: Depression is a prevalent global mental health disorder with a complex, multifactorial pathophysiology. Emerging evidence suggests a significant role of oxidative stress and impaired antioxidant defense in its development and progression. Vitamin E, a potent lipid-soluble antioxidant, has been investigated for its potential therapeutic role in mitigating oxidative damage and alleviating depressive symptoms (Lee et al., 2022; Barbosa et al., 2020).
Methods: This comprehensive systematic review synthesized evidence from 14 sources, including randomized controlled trials (RCTs), meta-analyses, and observational studies. Studies were screened and selected based on predefined criteria involving human participants with depression, vitamin E intervention (as monotherapy or co-intervention), measurement of antioxidant biomarkers and depression outcomes, and specific study designs that allowed for the isolation of vitamin E effects.
Results: The pooled meta-analysis indicated a moderate beneficial effect of vitamin E supplementation on depression scores (SMD = -0.88, 95% CI: -1.54 to -0.21) (Lee et al., 2022). Observational data showed an inverse association between dietary vitamin E intake and depression risk (RR = 0.84) (Ding & Zhang, 2022). Significant improvements in antioxidant biomarkers, such as increased total antioxidant capacity (TAC) and reduced malondialdehyde (MDA), were consistently reported with vitamin E supplementation, particularly at doses of 400 IU or higher (Farshbaf-Khalili et al., 2022; Darabi et al., 2023). However, effects were more pronounced in populations with elevated oxidative stress (e.g., PCOS, occupational exposure) and when vitamin E was combined with other antioxidants or omega-3 fatty acids.
Discussion: The antidepressant effects of vitamin E appear to be mediated through its ability to reduce oxidative stress and lipid peroxidation, modulate inflammatory pathways, and possibly influence gene expression related to neuroprotection (Lee et al., 2022; Almulla et al., 2023). Significant heterogeneity in study outcomes can be attributed to factors such as dosage, formulation, population characteristics, and the common use of vitamin E as a co-intervention.
Conclusion: Vitamin E supplementation, particularly at higher doses and in populations with evident oxidative stress burden, may offer a safe and modest adjunctive benefit in the management of depression. Future research should prioritize large-scale, well-designed RCTs of vitamin E monotherapy, with stratified analyses based on baseline antioxidant status, to clarify its independent therapeutic role.
References
A. Almulla, Y. Thipakorn, Ali Abbas Abo Algon, C. Tunvirachaisakul, H. Al-Hakeim, and Michael Maes. “Reverse Cholesterol Transport and Lipid Peroxidation Biomarkers in Major Depression and Bipolar Disorder: A Systematic Review and Meta-Analysis.” Brain, Behavior, and Immunity, 2023.
A. Farshbaf-Khalili, A. Ostadrahimi, M. Mirghafourvand, Khatereh Ataei-Almanghadim, Sara Dousti, and A. Iranshahi. “Clinical Efficacy of Curcumin and Vitamin E on Inflammatory-Oxidative Stress Biomarkers and Primary Symptoms of Menopause in Healthy Postmenopausal Women: A Triple-Blind Randomized Controlled Trial.” Journal of Nutrition and Metabolism, 2022.
A. Lee, A. Tariq, Grace M. Lau, Nicholas Wee Kiat Tok, W. Tam, and C. Ho. “Vitamin E, Alpha-Tocopherol, and Its Effects on Depression and Anxiety: A Systematic Review and Meta-Analysis.” Nutrients, 2022.
B. Meyer, B. Grenyer, T. Crowe, A. Owen, Elizabeth M. Grigonis-Deane, and P. Howe. “Improvement of Major Depression Is Associated with Increased Erythrocyte DHA.” Lipids, 2013.
“Enhanced Antipsychotic Treatment: Modulating Oxidative Stress with Vitamin D and E Co-Administration.” Pakistan Journal of Medicine and Dentistry, 2024.
Faezeh Darabi, M. Keshavarzi, N. Khanjani, S. Yousefinejad, and Z. Zamanian. “Effect of Antioxidants on Oxidative Damage, and Hematological and Psychological Parameters in Cement-Exposed Workers.” Hygiene and Environmental Health Advances, 2023.
J. Ding, and Yi Zhang. “Associations of Dietary Vitamin C and E Intake With Depression. A Meta-Analysis of Observational Studies.” Frontiers in Nutrition, 2022.
K. Krawczyk, and J. Rybakowski. “[Augmentation of Antidepressants with Unsaturated Fatty Acids Omega-3 in Drug-Resistant Depression].” Psychiatria Polska, 2012.
M. Jamilian, A. Shojaei, M. Samimi, Faraneh Afshar Ebrahimi, E. Aghadavod, M. Karamali, M. Taghizadeh, et al. “The Effects of Omega-3 and Vitamin E Co-Supplementation on Parameters of Mental Health and Gene Expression Related to Insulin and Inflammation in Subjects with Polycystic Ovary Syndrome.” Journal of Affective Disorders, 2018.
Maiza Lacerda Barbosa, Ag-Anne Pereira Melo de Meneses, Raí Pablo Sousa de Aguiar, J. M. de Castro e Sousa, Ana Amélia de Carvalho Melo Cavalcante, and S. Maluf. “Oxidative Stress, Antioxidant Defense and Depressive Disorders: A Systematic Review of Biochemical and Molecular Markers.” Neurology Psychiatry and Brain Research, 2020.
O. Adeyanju, Thomas Towers, and Thea R Moore. “Nutraceutical or Food-Based Antioxidants for Depression,” 2018.
R. Mocking, J. Assies, M. Bot, E. Jansen, A. Schene, and F. Pouwer. “Biological Effects of Add-On Eicosapentaenoic Acid Supplementation in Diabetes Mellitus and Co-Morbid Depression: A Randomized Controlled Trial.” PLoS ONE, 2012.
Sahar Foshati, A. Ghanizadeh, and M. Akhlaghi. “The Effect of Extra Virgin Olive Oil on Anthropometric Indices, Lipid Profile, and Markers of Oxidative Stress and Inflammation in Patients with Depression, a Double‐blind Randomised Controlled Trial.” International Journal of Clinical Practice, 2021.
Z. Mazloom, M. Ekramzadeh, and N. Hejazi. “Efficacy of Supplementary Vitamins C and E on Anxiety, Depression and Stress in Type 2 Diabetic Patients: A Randomized, Single-Blind, Placebo-Controlled Trial.” Pakistan Journal of Biological Sciences, 2013.
Downloads
Published
Issue
Section
License
Copyright (c) 2025 Oktaberika Putri Indah Yasinta, Eka Pramudian Rismayanti (Author)
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
Authors publishing here keep copyright but grant the journal first publication rights, under a Creative Commons Attribution-NonCommercial 4.0 License. They can distribute their work non-exclusively elsewhere with an acknowledgment of its first publication in this journal. Posting the work online before and during submission for earlier and greater citation is encouraged, reflecting Open Access benefits.
