Cited by 112Folate and B Vitamins ResearchTreatment of Major DepressionTryptophan and brain disorders

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Folate and B12 serum levels in association with depression in the aged: a systematic review and meta-analysis

Petridou, Eleni Th., Kousoulis, Antonis A., Michelakos, Theodoros, Papathoma, Paraskevi, Dessypris, Nick, Papadopoulos, Fotios C., Stefanadis, Christodoulos·2016·Aging & Mental Health

DOI 10.1080/13607863.2015.1049115

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Abstract

OBJECTIVES: To systematically review and meta-analyse existing evidence on the association between folate/B12, and depression among the aged people. METHODS: Following PRISMA/STROBE guidelines, the Medline abstracts were retrieved using an algorithm comprising relevant MeSH terms. Publications on the association of folate/B12 serum measurements with depression were abstracted independently by two reviewers and included in both gender and gender-specific meta-analyses, following recarculations of published data as appropriate. The Newcastle-Ottawa scale was used to evaluate the quality of included studies. RESULTS: Both gender data were contributed by 11 folate-related (7949 individuals) and 9 B12-related studies (6308 individuals), whereas gender-specific data by 4 folate-related (3409 individuals) and 3 B12-related studies (1934 individuals). A statistically significant overall association between both exposures of interest (low folate and B12 levels) and depression was observed (ORfolate:1.23, 95%CI:1.07-1.43, ORB12:1.20, 95%CI:1.02-1.42). Gender-specific estimates pointed to a statistically significant positive association between low B12 levels and depression only among women (OR:1.33, 95%CI:1.02-1.74); the gender specific associations of low folate levels with depression were, however, non-significant and of counter-direction (ORfemales:1.37, 95%CI:0.90-2.07; ORmales:0.84, 95%CI:0.57-1.25). CONCLUSION: Low folate and B12 serum levels seem to be associated with depression in the aged. The gender-specific analyses are confined to a positive association of low B12 with depression among older women and call for further research in this direction.

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“In addition, Petridou et al. conducted a systematic review and meta-analysis revealing a significant association between low vitamin B12 levels and depression in older adults, focusing on the importance of maintaining adequate levels to support mood regulation and reduce depressive symptoms [6].”
Say hello to my little friend… micronutraceuticals in neuroenergetics, neuronal health, and neurodegenerative diseases
Mason, S. (2025) · Frontiers in Neuroscience · doi:10.3389/fnins.2025.1498655 · Cited by 2
The association of reproductive hormones, thyroid function, and vitamin levels with premature ejaculation: A prospective case-control study
Pazır, Y., Güler, H., Bulut, T. B., Arı, E., Aktas, S., & Kadıhasanoğlu, M. (2024) · Korean journal of urology · doi:10.4111/icu.20230213 · Cited by 2
“Various studies have reported that vitamin B 12 and folic acid deficiency are significantly associated with depression because of their negative effects on 5-HT synthesis [16].”
Background
Toward Better Science-Based Advice on Nutrition
Forsan, H. F., El-Hak, A. E. A., Ahmad, E., Alswerky, E. M., Elagezy, F. K., Yassin, M., Fayed, M. R., Elkheir, M. A., Safwat, M.-A., Fouda, M. A., et al. (2024) · Nutritional neurosciences · doi:10.1007/978-981-97-2681-3_8 · Cited by 2
Serum folate concentration and health-related quality of life among the elderly in South Korea
Lee, E., & Park, S. (2021) · Health and Quality of Life Outcomes · doi:10.1186/s12955-021-01899-2 · Cited by 2
Testing and Prescribing Vitamin B12 in Swiss General Practice: A Survey among Physicians
Bardheci, K., Jäger, L., Risch, L., Rosemann, T. J., Burgstaller, J. M., & Markun, S. (2021) · Nutrients · doi:10.3390/nu13082610 · Cited by 2
Consultation-Liaison Case Conference: Psychiatric Care of Patients Who Undergo Bariatric Surgery
Andrade, N. L., Shenouda, R., Sockalingam, S., & Fipps, D. C. (2023) · Journal of the Academy of Consultation-Liaison Psychiatry · doi:10.1016/j.jaclp.2023.02.001 · Cited by 2
Effects of Vitamin B12 Deficiency on Ejaculation Time in Patients with Chronic Gastritis
Gökçen, K., & Gökçen, P. (2019) · Journal of Urological Surgery · doi:10.4274/jus.galenos.2019.2591 · Cited by 1
Üniversite Öğrencilerinin Depresyon Düzeyi Üzerinde Bazı B Grubu Vitaminleri ile D Vitamininin Etkisinin İncelenmesi
Karataş, E., & Uçar, A. (2023) · Adnan Menderes Üniversitesi Sağlık Bilimleri Fakültesi Dergisi · doi:10.46237/amusbfd.1114257 · Cited by 1
Association between neck circumference and depressive mood among Korean adults
Park, S. J., Hwang, I. C., & Ahn, H. Y. (2023) · Obesity Research & Clinical Practice · doi:10.1016/j.orcp.2023.05.011 · Cited by 1
Increase in the folate level can decrease the intensity of disorder in patients with depression who use citalopram: a randomized clinical trialPreprint
Morovati, M., Morsali, Y., Rezaee, S., Pezeshki, A., Esmaeilzadeh, A., Ranjbar, H., & Islambulchilar, M. (2020) · doi:10.21203/rs.3.rs-18168/v1 · Cited by 1
“Low level of blood folate was associated with higher prevalence of depression [14-16].”
Background
Altered Microbiota Composition Mediates Depressive Behavior During Chronic Stress
Marin, I. A. (2017) · doi:10.18130/v3h92t
Nutrition in Neurocognition and Mental Health
Katrinak, M., Irani, F., Armstrong, C. L., & Kerr, S. (2019) · Springer eBooks · doi:10.1007/978-3-030-14895-9_28
DEFICIÊNCIA DE VITAMINA B12 E DOENÇAS DO SISTEMA NERVOSO
Lopes, A. J. R., Boaventura, I. T., Teixeira, B. G. G. B., Boaventura, J. M. T., Oliveira, F. D. S. R., Parreira, E. D. S., Silva, D. N., Pereira, M. A. D. S., & de Mendonça, E. D. (2022) · Editora Pasteur eBooks · doi:10.29327/547549.1-6
Clinical Laboratories and Their Role in Anti-Aging Strategies
Sitar, M. E. (2023) · Springer eBooks · doi:10.1007/978-981-19-7443-4_13
Chapter 22. Neurocognitive Disorders
Merideth, F. L., Vahia, I. V., & Jeste, D. V. (2020) · American Psychiatric Association Publishing eBooks · doi:10.1176/appi.books.9781615378869.lg22
Chapter 2. The Neurological Examination for Neuropsychiatric Assessment
Benjamin, S., & Lauterbach, M. D. (2020) · American Psychiatric Association Publishing eBooks · doi:10.1176/appi.books.9781615378869.lg02
Chapter 25. Somatic Symptom and Related Disorders
Dickerman, A. L., & Muskin, P. R. (2020) · American Psychiatric Association Publishing eBooks · doi:10.1176/appi.books.9781615378869.lg25
Chapter 1. An Internist’s Approach to the Neuropsychiatric Patient
Rencic, J. J., & Salem, D. N. (2020) · American Psychiatric Association Publishing eBooks · doi:10.1176/appi.books.9781615378869.lg01
Chapter 4. Neuroimaging, Electroencephalography, and Lumbar Puncture in Medical Psychiatry
Talmasov, D., & Klein, J. P. (2020) · American Psychiatric Association Publishing eBooks · doi:10.1176/appi.books.9781615378869.lg04
Chapter 6. Cardiovascular Disease
Shapiro, P. A. (2020) · American Psychiatric Association Publishing eBooks · doi:10.1176/appi.books.9781615378869.lg06
Chapter 7. Endocrine Disorders and Their Psychiatric Manifestations
Gagliardi, J. P. (2020) · American Psychiatric Association Publishing eBooks · doi:10.1176/appi.books.9781615378869.lg07
Chapter 24. Insomnia
Doghramji, K. (2020) · American Psychiatric Association Publishing eBooks · doi:10.1176/appi.books.9781615378869.lg24
Chapter 23. Chronic Pain
McCarron, R. M., Sheth, S. J., Mesa, C. D., & Parish, M. B. (2020) · American Psychiatric Association Publishing eBooks · doi:10.1176/appi.books.9781615378869.lg23
Chapter 3. The Bedside Cognitive Examination in Medical Psychiatry
Glass, S. P. (2020) · American Psychiatric Association Publishing eBooks · doi:10.1176/appi.books.9781615378869.lg03
Chapter 17. Psychotic Disorders Due to Medical Illnesses
Brown, H. E., Mukerji, S., & Freudenreich, O. (2020) · American Psychiatric Association Publishing eBooks · doi:10.1176/appi.books.9781615378869.lg17
Chapter 10. Gastroenterological Disease in Patients With Psychiatric Disorders
Nadkarni, A., & Silbersweig, D. (2020) · American Psychiatric Association Publishing eBooks · doi:10.1176/appi.books.9781615378869.lg10
Index
(2020) · American Psychiatric Association Publishing eBooks · doi:10.1176/appi.books.9781615378869.index
Chapter 16. Neurodevelopmental Disorders
Hauptman, A. J., & Benjamin, S. (2020) · American Psychiatric Association Publishing eBooks · doi:10.1176/appi.books.9781615378869.lg16
Chapter 18. Catatonia in the Medically Ill Patient
Beach, S. R., & Fricchione, G. L. (2020) · American Psychiatric Association Publishing eBooks · doi:10.1176/appi.books.9781615378869.lg18
Chapter 12. Neurological Conditions and Their Psychiatric Manifestations
Fogel, B. S., Baslet, G. C., Safar, L. T., Raynor, G., & Silbersweig, D. (2020) · American Psychiatric Association Publishing eBooks · doi:10.1176/appi.books.9781615378869.lg12
Chapter 20. Anxiety and Related Disorders: Manifestations in the General Medical Setting
Hebert, C. L., Banayan, D. J., Forcén, F. E., Perticone, K., Guttikonda, S., & Pollack, M. (2020) · American Psychiatric Association Publishing eBooks · doi:10.1176/appi.books.9781615378869.lg20
Chapter 13. Cancer: Psychiatric Care of the Oncology Patient
Fernandez-Robles, C. G., & Glass, S. P. (2020) · American Psychiatric Association Publishing eBooks · doi:10.1176/appi.books.9781615378869.lg13
Chapter 19. Mood Disorders Due to Medical Illnesses
Mauer, S., Querques, J., & D, P. S. M. (2020) · American Psychiatric Association Publishing eBooks · doi:10.1176/appi.books.9781615378869.lg19

Authors: Petridou, E. T., Kousoulis, A. A., Michelakos, T., Papathoma, P., Dessypris, N., Papadopoulos, F. C., & Stefanadis, C.
Affiliations: National and Kapodistrian University of Athens (GR)
Uppsala University (SE)
Corresponding author: Petridou, Eleni Th.
ORCID: Petridou, Eleni Th.
Kousoulis, Antonis A.
Michelakos, Theodoros
Papadopoulos, Fotios C.
Stefanadis, Christodoulos
Venue: Aging & Mental Health
Publisher: Informa UK Limited
Published: 2015-06-08
Volume: 20
Issue: 9
Pages: 965-973
ISSN: 1360-7863 (ISSN-L)
1364-6915
DOI: 10.1080/13607863.2015.1049115
OpenAlex: W2215638520
Cited by: 112
References: 57
Citations by year: 2025: 2 · 2024: 14 · 2023: 8 · 2022: 6 · 2021: 9 · 2020: 41 · 2019: 12 · 2018: 7 · 2017: 6 · 2016: 6 · 2015: 1
FWCI: 1.03
Type: journal article
Language: en
Open access: closed
Locations: Aging & Mental Health (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Nursing › Nutrition and Dietetics › Folate and B Vitamins Research
Health Sciences › Medicine › Pharmacology (medical) › Treatment of Major Depression
Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
Keywords: folic acid, vitamin B12, serum folate, serum vitamin B12, depression, older adults, aging, sex differences, vitamin deficiency
MeSH terms: Aged, Aged, 80 and over, Depressive Disorder, Female, Folic Acid, Humans, Male

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Folate and B12 serum levels in association with depression in the aged: a systematic review and meta-analysis

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