5/29/2025
Last update
5/29/2025
Reviewed By
Overview
SCIENTIFIC SCORE
Possibly Effective
Based on 29 Researches
7.1
USERS' SCORE
Good
Based on 4 Reviews
8.6
Supplement Facts
Serving Size: 1 Tablet
Amount Per Serving
%DV
Folate
1,360 mcg DFE** (800 mcg folic acid)
340%
Vitamin B-12 (as Cyanocobalamin)
25 mcg
1042%
Top Medical Research Studies
2
We assessed the effect of vitamin B12 supplementation on depressive symptoms by reviewing several randomized controlled trials (RCTs). Our analysis focused on participants who may experience mild cognitive impairment, an area where low vitamin B12 levels could potentially raise the risk of depression.
After a thorough examination of studies, we found that the included trials did not support a significant benefit of vitamin B12 for alleviating depressive symptoms. In our evaluation of three studies focusing specifically on depression, the average difference in symptoms was negligible, indicating no real effect.
This outcome reflects that while vitamin B12 is essential for various bodily functions, its role in improving mood and reducing depression symptoms may not be as effective as some might hope. Further exploration is still warranted to better understand the contexts in which vitamin B12 could be beneficial.
After a thorough examination of studies, we found that the included trials did not support a significant benefit of vitamin B12 for alleviating depressive symptoms. In our evaluation of three studies focusing specifically on depression, the average difference in symptoms was negligible, indicating no real effect.
This outcome reflects that while vitamin B12 is essential for various bodily functions, its role in improving mood and reducing depression symptoms may not be as effective as some might hope. Further exploration is still warranted to better understand the contexts in which vitamin B12 could be beneficial.
9.5
We explored the impact of vitamin B12 supplementation on patients experiencing symptoms like depression, fatigue, and neuropathic pain—often linked with rheumatic diseases. Through our review of three case studies, we found that when these patients received vitamin B12 treatment, many of their depressive symptoms significantly improved.
The findings suggest that vitamin B12 may play a crucial role in alleviating not just physical discomfort, but also mental health issues like depression, which can accompany rheumatic conditions. Despite the patients initially presenting normal vitamin B12 levels in lab tests, the supplementation showed almost complete resolution of their symptoms, highlighting that clinical evaluations should not solely depend on blood test results.
In summary, we recommend that healthcare professionals consider assessing vitamin B12 levels early on when diagnosing rheumatic diseases and think about supplementation even if serum levels appear adequate. This approach might offer a straightforward and effective option for improving patients' quality of life.
The findings suggest that vitamin B12 may play a crucial role in alleviating not just physical discomfort, but also mental health issues like depression, which can accompany rheumatic conditions. Despite the patients initially presenting normal vitamin B12 levels in lab tests, the supplementation showed almost complete resolution of their symptoms, highlighting that clinical evaluations should not solely depend on blood test results.
In summary, we recommend that healthcare professionals consider assessing vitamin B12 levels early on when diagnosing rheumatic diseases and think about supplementation even if serum levels appear adequate. This approach might offer a straightforward and effective option for improving patients' quality of life.
9
We examined the effects of folic acid as an add-on treatment for major depression alongside traditional medications like SSRIs and SNRIs. After reviewing six randomized control trials, we found that patients receiving folic acid showed better progress.
Specifically, their depression scores improved significantly, with higher response and remission rates as well. This suggests that adding folic acid might enhance the benefits of standard depression therapies, giving hope to those looking for more effective treatment options.
Specifically, their depression scores improved significantly, with higher response and remission rates as well. This suggests that adding folic acid might enhance the benefits of standard depression therapies, giving hope to those looking for more effective treatment options.
Most Useful Reviews
9
Less severe illness
88 people found this helpful
After using this vitamin for over a year, I've noticed a significant improvement in my quality of life. Not only do I feel healthier and get sick less often, but it has noticeably improved my mood. Given my family history of depression, I am very grateful for this change.
9
Winter depression relief
5 people found this helpful
Living in a northern climate, I've struggled with winter depression. After starting this vitamin, I experienced significant improvement. Initially, I relied on it daily, but now I can manage without it, thanks to its cumulative effect. It has made winter much more bearable.
9
Effective for depression
Folic acid supports the formation of the nervous system. I take it for its benefits in alleviating mental depression and lethargy, and it genuinely seems effective. Additionally, it aids in preventing dementia and improving brain health and immunity, so I'll continue taking it alongside green vegetables rich in folic acid.
Medical Researches
SCIENTIFIC SCORE
Possibly Effective
Based on 29 Researches
7.1
- All Researches
9.5
We explored the impact of vitamin B12 supplementation on patients experiencing symptoms like depression, fatigue, and neuropathic pain—often linked with rheumatic diseases. Through our review of three case studies, we found that when these patients received vitamin B12 treatment, many of their depressive symptoms significantly improved.
The findings suggest that vitamin B12 may play a crucial role in alleviating not just physical discomfort, but also mental health issues like depression, which can accompany rheumatic conditions. Despite the patients initially presenting normal vitamin B12 levels in lab tests, the supplementation showed almost complete resolution of their symptoms, highlighting that clinical evaluations should not solely depend on blood test results.
In summary, we recommend that healthcare professionals consider assessing vitamin B12 levels early on when diagnosing rheumatic diseases and think about supplementation even if serum levels appear adequate. This approach might offer a straightforward and effective option for improving patients' quality of life.
The findings suggest that vitamin B12 may play a crucial role in alleviating not just physical discomfort, but also mental health issues like depression, which can accompany rheumatic conditions. Despite the patients initially presenting normal vitamin B12 levels in lab tests, the supplementation showed almost complete resolution of their symptoms, highlighting that clinical evaluations should not solely depend on blood test results.
In summary, we recommend that healthcare professionals consider assessing vitamin B12 levels early on when diagnosing rheumatic diseases and think about supplementation even if serum levels appear adequate. This approach might offer a straightforward and effective option for improving patients' quality of life.
9
We explored the effects of chlorzoxazone and folic acid on anxiety, depression, and memory using a mouse model of Spinocerebellar Ataxia type 3 (SCA3).
The combination of these treatments showed promising results, particularly in reducing signs of anxiety and depression while enhancing recognition memory in SCA3-84Q mice.
This suggests that a combined therapy might be beneficial for managing both motor and cognitive symptoms related to ataxia, highlighting the potential of folic acid in improving mood.
The combination of these treatments showed promising results, particularly in reducing signs of anxiety and depression while enhancing recognition memory in SCA3-84Q mice.
This suggests that a combined therapy might be beneficial for managing both motor and cognitive symptoms related to ataxia, highlighting the potential of folic acid in improving mood.
9
Folic acid mitigates depression symptoms
We examined how maternal vitamin D deficiency (VDD) impacts depression-like behaviors in offspring and the potential role of folic acid in this process.
Female mice were fed a VDD diet during pregnancy, leading to clear depression-like behaviors in their adult offspring.
However, when folic acid was given, it reversed certain negative changes, like DNA methylation, and reduced symptoms of depression.
This suggests that folic acid could be a significant factor in mitigating depression-related issues associated with maternal vitamin D deficiency.
Female mice were fed a VDD diet during pregnancy, leading to clear depression-like behaviors in their adult offspring.
However, when folic acid was given, it reversed certain negative changes, like DNA methylation, and reduced symptoms of depression.
This suggests that folic acid could be a significant factor in mitigating depression-related issues associated with maternal vitamin D deficiency.
9
We examined the effects of folic acid as an add-on treatment for major depression alongside traditional medications like SSRIs and SNRIs. After reviewing six randomized control trials, we found that patients receiving folic acid showed better progress.
Specifically, their depression scores improved significantly, with higher response and remission rates as well. This suggests that adding folic acid might enhance the benefits of standard depression therapies, giving hope to those looking for more effective treatment options.
Specifically, their depression scores improved significantly, with higher response and remission rates as well. This suggests that adding folic acid might enhance the benefits of standard depression therapies, giving hope to those looking for more effective treatment options.
9
This research delves into the question of how vitamin B12 impacts stress resilience and depression. Utilizing a chronic variable stress mouse model, we identified changing gene activity linked to stress resilience after vitamin B12 treatment. By employing advanced techniques like RNA sequencing, we found that vitamin B12 plays a role in altering the way certain genes, particularly one called Ttr, are expressed under stress.
We specifically observed that Ttr, or transthyretin, is influenced by vitamin B12 in a way that appears distinct for different sexes. Our findings indicated that postmortem samples from male patients with depression showed elevated levels of TTR in their brains, while no similar difference was noted in females. Further experimentation demonstrated that manipulating Ttr in the brains of stressed mice led to changes in behavior associated with stress and depression, along with alterations in brain structure and the expression of other related genes.
Notably, when stressed mice received vitamin B12, it appeared to reduce DNA methylation (a chemical modification that can regulate gene activity) in the region controlling Ttr. This led us to establish a clear connection between Ttr’s regulation and behaviors associated with chronic stress. Overall, our work suggests that vitamin B12 supplementation may stimulate mechanisms tied to stress resilience, sparking interest in dietary interventions as a means to combat mood disorders.
We specifically observed that Ttr, or transthyretin, is influenced by vitamin B12 in a way that appears distinct for different sexes. Our findings indicated that postmortem samples from male patients with depression showed elevated levels of TTR in their brains, while no similar difference was noted in females. Further experimentation demonstrated that manipulating Ttr in the brains of stressed mice led to changes in behavior associated with stress and depression, along with alterations in brain structure and the expression of other related genes.
Notably, when stressed mice received vitamin B12, it appeared to reduce DNA methylation (a chemical modification that can regulate gene activity) in the region controlling Ttr. This led us to establish a clear connection between Ttr’s regulation and behaviors associated with chronic stress. Overall, our work suggests that vitamin B12 supplementation may stimulate mechanisms tied to stress resilience, sparking interest in dietary interventions as a means to combat mood disorders.
User Reviews
USERS' SCORE
Good
Based on 4 Reviews
8.6
- All Reviews
- Positive Reviews
- Negative Reviews
9
Less severe illness
88 people found this helpful
After using this vitamin for over a year, I've noticed a significant improvement in my quality of life. Not only do I feel healthier and get sick less often, but it has noticeably improved my mood. Given my family history of depression, I am very grateful for this change.
9
Winter depression relief
5 people found this helpful
Living in a northern climate, I've struggled with winter depression. After starting this vitamin, I experienced significant improvement. Initially, I relied on it daily, but now I can manage without it, thanks to its cumulative effect. It has made winter much more bearable.
9
Effective for depression
Folic acid supports the formation of the nervous system. I take it for its benefits in alleviating mental depression and lethargy, and it genuinely seems effective. Additionally, it aids in preventing dementia and improving brain health and immunity, so I'll continue taking it alongside green vegetables rich in folic acid.
7.5
Mood improvement
NOW Foods Folic Acid, 800 mcg, 250 Tablets, is known to boost the immune system and contribute to overall health. It also positively affects mood stabilization and helps in the prevention of depression.
Frequently Asked Questions
9
Less severe illness
88 people found this helpful
After using this vitamin for over a year, I've noticed a significant improvement in my quality of life. Not only do I feel healthier and get sick less often, but it has noticeably improved my mood. Given my family history of depression, I am very grateful for this change.
9
Winter depression relief
5 people found this helpful
Living in a northern climate, I've struggled with winter depression. After starting this vitamin, I experienced significant improvement. Initially, I relied on it daily, but now I can manage without it, thanks to its cumulative effect. It has made winter much more bearable.
9
Effective for depression
Folic acid supports the formation of the nervous system. I take it for its benefits in alleviating mental depression and lethargy, and it genuinely seems effective. Additionally, it aids in preventing dementia and improving brain health and immunity, so I'll continue taking it alongside green vegetables rich in folic acid.
7.5
Mood improvement
NOW Foods Folic Acid, 800 mcg, 250 Tablets, is known to boost the immune system and contribute to overall health. It also positively affects mood stabilization and helps in the prevention of depression.
7
We investigated how effective combining low-dose methylfolate with standard antidepressants is for treating depressive disorder.
In an open-label trial involving 44 patients, one group received traditional antidepressants while the other received the same medications along with methylfolate for four weeks.
We found that this combination therapy could be a safe and effective approach, potentially improving patient outcomes.
In an open-label trial involving 44 patients, one group received traditional antidepressants while the other received the same medications along with methylfolate for four weeks.
We found that this combination therapy could be a safe and effective approach, potentially improving patient outcomes.
8
We conducted an umbrella meta-analysis to explore how folate affects depression. By sifting through various studies up to October 2023 from multiple databases like PubMed and Scopus, we wanted to find a clear answer regarding folate supplementation's role in alleviating depressive symptoms.
Our analysis included 11 relevant studies, out of which 8 underwent a quantitative review. The findings were promising: folate supplementation showed a significant reduction in depressive symptoms, with results suggesting an effect size that indicates moderate improvement. Specifically, the standardized mean difference was -0.42, and the weighted mean difference was -3.20, demonstrating a notable benefit with very little variability between studies.
Additionally, we found that those with low folate levels had a 35% higher chance of experiencing depression compared to their counterparts with adequate levels. This suggests a strong link between folate insufficiency and depressive symptoms.
Overall, our findings support the idea that folate supplementation could be an effective adjunct treatment when combined with standard depression therapies, providing individuals with another tool to manage their mental health.
Our analysis included 11 relevant studies, out of which 8 underwent a quantitative review. The findings were promising: folate supplementation showed a significant reduction in depressive symptoms, with results suggesting an effect size that indicates moderate improvement. Specifically, the standardized mean difference was -0.42, and the weighted mean difference was -3.20, demonstrating a notable benefit with very little variability between studies.
Additionally, we found that those with low folate levels had a 35% higher chance of experiencing depression compared to their counterparts with adequate levels. This suggests a strong link between folate insufficiency and depressive symptoms.
Overall, our findings support the idea that folate supplementation could be an effective adjunct treatment when combined with standard depression therapies, providing individuals with another tool to manage their mental health.
9
We examined the effects of folic acid as an add-on treatment for major depression alongside traditional medications like SSRIs and SNRIs. After reviewing six randomized control trials, we found that patients receiving folic acid showed better progress.
Specifically, their depression scores improved significantly, with higher response and remission rates as well. This suggests that adding folic acid might enhance the benefits of standard depression therapies, giving hope to those looking for more effective treatment options.
Specifically, their depression scores improved significantly, with higher response and remission rates as well. This suggests that adding folic acid might enhance the benefits of standard depression therapies, giving hope to those looking for more effective treatment options.
References
- Siddique A, Khokhar MM, Waheed A, Naeem U, Aziz SA. Effect of combination therapy of methylfolate with antidepressants in patients with depressive disorder. BMC Pharmacol Toxicol. 2025;26:14. 10.1186/s40360-025-00846-x
- Guo Q, Wang Y, Guo L, Xu K, Shang S. Association of serum total folate and serum vitamin D concentrations with W-shape in depressed older adults with cognitive dysfunction: A cross-sectional observational study. Clin Nutr ESPEN. 2025;65:50. 10.1016/j.clnesp.2024.11.021
- Marinina KS, Bezprozvanny IB, Egorova PA. A combination of chlorzoxazone and folic acid improves recognition memory, anxiety and depression in SCA3-84Q mice. Hum Mol Genet. 2024;33:1406. 10.1093/hmg/ddae079
- Lagzi N, Bateni A, Goli R, Talebiazar N. The effect of multivitamins on anxiety and depression in patients undergoing methadone maintenance treatment: A double-blind randomized controlled trial. Int J Psychiatry Med. 2023;58:576. 10.1177/00912174231179320
- Tuo LJ, Song XY, Zhu YY, He HN, Song YP, et al. Gestational folic acid supplement prevents vitamin D deficiency-induced depression-like behavior by reversing cortical DNA hypomethylation in adult offspring. J Steroid Biochem Mol Biol. 2023;231:106313. 10.1016/j.jsbmb.2023.106313
- Pan LA, Segreti AM, Wrobleski J, Shaw A, Hyland K, et al. Metabolomic disorders: confirmed presence of potentially treatable abnormalities in patients with treatment refractory depression and suicidal behavior. Psychol Med. 2023;53:6046. 10.1017/S0033291722003233
- Jin X, Cheng Z, Yu X, Tao Q, Huang R, et al. Continuous supplementation of folic acid in pregnancy and the risk of perinatal depression-A meta-analysis. J Affect Disord. 2022;302:258. 10.1016/j.jad.2022.01.080
- Lam NSK, Long XX, Li X, Saad M, Lim F, et al. The potential use of folate and its derivatives in treating psychiatric disorders: A systematic review. Biomed Pharmacother. 2022;146:112541. 10.1016/j.biopha.2021.112541
- Maruf AA, Poweleit EA, Brown LC, Strawn JR, Bousman CA. Systematic Review and Meta-Analysis of L-Methylfolate Augmentation in Depressive Disorders. Pharmacopsychiatry. 2022;55:139. 10.1055/a-1681-2047
- Altaf R, Gonzalez I, Rubino K, Nemec EC. Folate as adjunct therapy to SSRI/SNRI for major depressive disorder: Systematic review & meta-analysis. Complement Ther Med. 2021;61:102770. 10.1016/j.ctim.2021.102770
- Budni J, Moretti M, Freitas AE, Neis VB, Ribeiro CM, et al. Behavioral and neurochemical effects of folic acid in a mouse model of depression induced by TNF-α. Behav Brain Res. 2021;414:113512. 10.1016/j.bbr.2021.113512
- Saxena PP, Kyomen H. Leucovorin as an Antidepressant Adjunct in Elderly Inpatients With Treatment-resistant Depression. Prim Care Companion CNS Disord. 2021;23. 10.4088/PCC.20m02767
- Mahdavifar B, Hosseinzadeh M, Salehi-Abargouei A, Mirzaei M, Vafa M. Dietary intake of B vitamins and their association with depression, anxiety, and stress symptoms: A cross-sectional, population-based survey. J Affect Disord. 2021;288:92. 10.1016/j.jad.2021.03.055
- Falade J, Onaolapo AY, Onaolapo OJ. Evaluation of the Behavioural, Antioxidative and Histomorphological Effects of Folic Acid-supplemented Diet in Dexamethasone-induced Depression in Mice. Cent Nerv Syst Agents Med Chem. 2021;21:73. 10.2174/1871524921666210114125355
- Yang Y, Qi H, Zhang J, Jia J, Yang Y, et al. Evaluating the association of depressive symptoms on serum folate and erythrocyte folate levels based on the 2017-2020 NHANES database. Front Nutr. 2025;12:1505700. 10.3389/fnut.2025.1505700
- Xiong Y, Zhou G, Zhou L, Guo M, Lu H. Serum molecules of the folate-driven one-carbon cycle as indicators of depressive tendencies in the elderly. Heliyon. 2024;10:e36980. 10.1016/j.heliyon.2024.e36980
- Liu M, Wang G, Jiang C. Independent and combined effect of serum copper and folate on depression: cross-sectional data from the NHANES 2011-2016. Front Nutr. 2024;11:1389480. 10.3389/fnut.2024.1389480
- Gao S, Khalid A, Amini-Salehi E, Radkhah N, Jamilian P, et al. Folate supplementation as a beneficial add-on treatment in relieving depressive symptoms: A meta-analysis of meta-analyses. Food Sci Nutr. 2024;12:3806. 10.1002/fsn3.4073
- Lv P, Xiang F, Zhang S, Lei D, Zhou C, et al. Valeriana jatamansi jones improves depressive behavior in CUMS mice by modulating vitamin B12-related ileal homeostasis. J Ethnopharmacol. 2025;342:119392. 10.1016/j.jep.2025.119392
- Alzahrani H. Assessment of Vitamin B12 Efficacy on Cognitive Memory Function and Depressive Symptoms: A Systematic Review and Meta-Analysis. Cureus. 2024;16:e73350. 10.7759/cureus.73350
- Zhang J, Liao Q, Chen H, Liu F, Sun D, et al. Association of Vitamin B12 and Polymorphism of with Early-Onset Post-Stroke Depression. Neuropsychiatr Dis Treat. 2024;20:2289. 10.2147/NDT.S480417
- Stein G, Aly JS, Manzolillo A, Lange L, Riege K, et al. Transthyretin Orchestrates Vitamin B12-Induced Stress Resilience. Biol Psychiatry. 2025;97:54. 10.1016/j.biopsych.2024.07.009
- Hui J, Zhang N, Kang M, Gou Y, Liu C, et al. Micronutrient-Associated Single Nucleotide Polymorphism and Mental Health: A Mendelian Randomization Study. Nutrients. 2024;16. 10.3390/nu16132042
- Harikaran S, Basu S, Mukherjee MP, Kar R, Nair S, et al. Vitamin B12 and homocysteine in patients with major depressive disorder. J Family Med Prim Care. 2024;13:2049. 10.4103/jfmpc.jfmpc_1460_23
- Gao Y, Yang J, Sun H, Zhou H. Efficacy of Danzhixiaoyao tablets combined with methylcobalamin tablets in the treatment of burning mouth syndrome: an open-label, randomized controlled trial. BMC Oral Health. 2024;24:603. 10.1186/s12903-024-04318-2
- Cruz-Rodríguez J, Canals-Sans J, Hernández-Martínez C, Arija V. Association between of vitamin B12 status during pregnancy and probable postpartum depression: the ECLIPSES study. J Reprod Infant Psychol. 2024. 10.1080/02646838.2024.2324043
- Reis da Silva T. Can supplementing vitamin B12 improve mental health outcomes?: a literature review. Br J Community Nurs. 2024;29:137. 10.12968/bjcn.2024.29.3.137
- Dułak NA, Rytlewska M, Jaskólska M, Chmielewski M. A new perspective on vitamin B12 deficiency in rheumatology: a case-based review. Rheumatol Int. 2024;44:737. 10.1007/s00296-024-05539-y
- Tan Y, Zhou L, Gu K, Xie C, Wang Y, et al. Correlation between Vitamin B12 and Mental Health in Children and Adolescents: A Systematic Review and Meta-analysis. Clin Psychopharmacol Neurosci. 2023;21:617. 10.9758/cpn.22.1040
