Reviewed By
Overview
SCIENTIFIC SCORE
Possibly Effective
Based on 18 Researches
7.1
USERS' SCORE
Good
Based on 26 Reviews
8.1
Supplement Facts
Serving Size: 1 Capsule
Amount Per Serving
%DV
Folate (400 mcg as (6S)-5-MTHF [(6S)-5-Methyltetrahydrofolate Glucosamine Salt)
680 mcg DFE‡
170%
Top Medical Research Studies
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.
Read More
8
Folic acid shows promise against depression
We evaluated how folic acid supplementation affects depression-related behaviors and brain health in a mouse model. Over eight weeks, mice received either a standard diet or one supplemented with folic acid.
Those on the folic acid diet showed improved behavior, including increased activity and reduced signs of despair in stress tests. Moreover, they exhibited better antioxidant levels and healthier brain structures.
Overall, the findings suggest that folic acid may help counteract depression and support cognitive function.
Those on the folic acid diet showed improved behavior, including increased activity and reduced signs of despair in stress tests. Moreover, they exhibited better antioxidant levels and healthier brain structures.
Overall, the findings suggest that folic acid may help counteract depression and support cognitive function.
Read More
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.
Read More
Most Useful Reviews
9
Potential depression aid
86 people found this helpful
Methylfolate, or (6S)-5-MTHF, is the most effective form of folate, easily absorbed and critical for human health. It helps control homocysteine levels, supports cell growth, and reduces risks of developmental defects in infants. Methylfolate also positively influences cognitive functions, making it valuable for depression treatment. Studies show it can lower homocysteine levels, which, when elevated, is linked to cardiovascular diseases. It's crucial to choose methylfolate over standard folic acid, which is poorly absorbed and can hinder essential nutrient absorption from food.
Read More
9
Supports depression recovery
5 people found this helpful
Jarrow Formulas' Methyl Folate is one of the most active forms of folic acid. It’s crucial for human health but is poorly absorbed in its raw form, requiring transformation by enzymes. A B9 deficiency raises homocysteine levels, damaging cells, particularly in the nervous and cardiovascular systems. Women considering pregnancy should take folate supplements before conception to lower homocysteine levels. Methylfolate helps prevent pregnancy-related health issues and supports men’s health as well.
Read More
7.5
Critical for pregnancy
3 people found this helpful
The active form of vitamin B9 is essential for pregnancy. A deficiency in the mother can lead to severe fetal malformations. It’s crucial to address this deficiency at least three months before conception. B9 absorption affects iron, and deficits can lead to anaemia, resulting in apathy or depression. Men must also consider methylfolate to reduce homocysteine levels, especially smokers. I've felt balanced and noticed significant improvements in my hair health since taking B vitamins.
Read More
Medical Researches
SCIENTIFIC SCORE
Possibly Effective
Based on 18 Researches
7.1
- All Researches
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.
Read More
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.
Read More
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.
Read More
8
Multivitamins reduce depression symptoms
We conducted a double-blind, randomized controlled trial with 70 male patients undergoing Methadone Maintenance Treatment (MMT), to see how multivitamins affect anxiety and depression. Participants received either multivitamins or a placebo for 12 weeks. While we found no notable improvement in anxiety, there's encouraging news: the multivitamin group experienced significant reductions in depression levels. This suggests that certain vitamins, including folic acid, can positively influence mood among those in MMT.
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8
This study focused on whether folic acid can help reduce depressive-like behaviors triggered by inflammation in mice.
We observed that folic acid significantly lowered immobility in tail suspension tests and improved behaviors affected by tumor necrosis factor (TNF-α).
Even at low doses, folic acid combined with common antidepressants showed positive effects. We found that it also influenced specific brain signaling pathways, possibly helping to balance mood by acting on certain neurotransmitter systems.
Overall, folic acid appears to be effective against inflammation-induced depression in this model.
We observed that folic acid significantly lowered immobility in tail suspension tests and improved behaviors affected by tumor necrosis factor (TNF-α).
Even at low doses, folic acid combined with common antidepressants showed positive effects. We found that it also influenced specific brain signaling pathways, possibly helping to balance mood by acting on certain neurotransmitter systems.
Overall, folic acid appears to be effective against inflammation-induced depression in this model.
Read More
User Reviews
USERS' SCORE
Good
Based on 26 Reviews
8.1
- All Reviews
- Positive Reviews
- Negative Reviews
9
Potential depression aid
86 people found this helpful
Methylfolate, or (6S)-5-MTHF, is the most effective form of folate, easily absorbed and critical for human health. It helps control homocysteine levels, supports cell growth, and reduces risks of developmental defects in infants. Methylfolate also positively influences cognitive functions, making it valuable for depression treatment. Studies show it can lower homocysteine levels, which, when elevated, is linked to cardiovascular diseases. It's crucial to choose methylfolate over standard folic acid, which is poorly absorbed and can hinder essential nutrient absorption from food.
Read More
9
Supports depression recovery
5 people found this helpful
Jarrow Formulas' Methyl Folate is one of the most active forms of folic acid. It’s crucial for human health but is poorly absorbed in its raw form, requiring transformation by enzymes. A B9 deficiency raises homocysteine levels, damaging cells, particularly in the nervous and cardiovascular systems. Women considering pregnancy should take folate supplements before conception to lower homocysteine levels. Methylfolate helps prevent pregnancy-related health issues and supports men’s health as well.
Read More
7.5
Critical for pregnancy
3 people found this helpful
The active form of vitamin B9 is essential for pregnancy. A deficiency in the mother can lead to severe fetal malformations. It’s crucial to address this deficiency at least three months before conception. B9 absorption affects iron, and deficits can lead to anaemia, resulting in apathy or depression. Men must also consider methylfolate to reduce homocysteine levels, especially smokers. I've felt balanced and noticed significant improvements in my hair health since taking B vitamins.
Read More
9
Mood improvement
2 people found this helpful
Methylfolate is essential for producing happiness hormones and improving mood. It's crucial for cell division, growth, and immune function. A deficiency can lead to symptoms like depression, anxiety, and memory issues. I find methylfolate to be one of the best forms for assimilation.
Read More
7.5
Mood regulation
2 people found this helpful
Methylfolate is a key cofactor for producing neurotransmitters like serotonin, dopamine, and norepinephrine, which are vital for mood regulation; low levels are linked to depression.
Read More
Frequently Asked Questions
9
Effective against anxiety
1 people found this helpful
I quickly noticed that this methylfolate helped with my anxiety and depression. I felt its positive effects within a couple of weeks.
7.5
Combats depression
1 people found this helpful
This product is excellent! Methylfolate has noticeably improved my mood and helped combat depression. It also detoxifies the body effectively; I take one capsule a day.
9
Life-changing
Methylfolate has transformed my life. I struggled with depression and fatigue, but after taking it, I noticed a significant boost in my mood and energy. I highly recommend it!
7.5
Essential for anxiety
Quality Methyl Folate is essential for addressing anxiety disorders and depression.
7.5
Reduces anxiety symptoms
3 people found this helpful
Methylfolate pairs well with vitamin B12, significantly helping my anxiety and alleviating my depression symptoms.
8
Treatment for depression
1 people found this helpful
This folate has a convenient capsule size and is easily digestible. It's important for maintaining cardiovascular and nervous system health. I recommend it for anyone dealing with depression, chronic fatigue, or low immunity. You will feel the difference!
7.5
Boosts mood
I took it alongside vitamin B12, and the capsules are small and easy to swallow. This vitamin effectively helps with managing depression. Stay healthy!
7.5
Mood regulation
2 people found this helpful
Methylfolate is a key cofactor for producing neurotransmitters like serotonin, dopamine, and norepinephrine, which are vital for mood regulation; low levels are linked to depression.
4
L-methylfolate shows modest antidepressant benefit
We systematically explored the effect of L-methylfolate, a form of folic acid, as an add-on treatment for adults suffering from major depressive disorder. By reviewing studies involving 6,707 patients, we found that L-methylfolate may enhance the effectiveness of antidepressants to a modest extent.
Specifically, our analysis indicated a small but significant improvement in treatment response. While L-methylfolate isn’t widely endorsed in clinical guidelines yet, these findings suggest it could be beneficial for those who need additional support in managing their depression.
Specifically, our analysis indicated a small but significant improvement in treatment response. While L-methylfolate isn’t widely endorsed in clinical guidelines yet, these findings suggest it could be beneficial for those who need additional support in managing their 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.
7
We aimed to understand how levels of serum folate and vitamin D relate to depression and cognitive decline in older adults. By analyzing data from over 2,000 participants aged 60 and up, we found that adequate levels of these nutrients may play a role in preventing and managing these issues.
Interestingly, our results hinted at a W-shaped relationship, indicating that folic acid might be beneficial within a certain range. However, more clinical studies are needed to confirm these findings and truly understand how folic acid supplementation could help.
Interestingly, our results hinted at a W-shaped relationship, indicating that folic acid might be beneficial within a certain range. However, more clinical studies are needed to confirm these findings and truly understand how folic acid supplementation could help.
4
We aimed to understand how folate affects depression, considering its interaction with copper levels in the body. Using data from a large national health survey, we focused on adults aged 18 to 80 and assessed their depression using a standard questionnaire.
Our analysis highlighted a potential relationship between low folate levels and increased depression risk, especially when accompanied by high copper levels. While folate alone appears to play a part, the combined effect with copper is particularly noteworthy.
However, we also observed that the study doesn’t conclusively prove that folate treatment will resolve depressive symptoms. It suggests a need for further research, especially regarding folic acid supplementation for individuals with higher copper levels.
Overall, the findings imply that addressing nutritional factors like folate could be an interesting path for managing depression, but more evidence is needed before we can fully endorse it.
Our analysis highlighted a potential relationship between low folate levels and increased depression risk, especially when accompanied by high copper levels. While folate alone appears to play a part, the combined effect with copper is particularly noteworthy.
However, we also observed that the study doesn’t conclusively prove that folate treatment will resolve depressive symptoms. It suggests a need for further research, especially regarding folic acid supplementation for individuals with higher copper levels.
Overall, the findings imply that addressing nutritional factors like folate could be an interesting path for managing depression, but more evidence is needed before we can fully endorse it.
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
