Folate, Mood, and Attention: Research and How EnBrace HR/MF Fits In

Folate, also known as vitamin B9, plays a critical role in mental health and cognitive function. It is an essential cofactor in one-carbon metabolism, which is necessary for neurotransmitter synthesis, DNA methylation, and homocysteine regulation (Liwinski & Lang, 2023). When folate is low or when the body struggles to activate folic acid into its usable form, L-methylfolate, mood, cognition, and emotional regulation can suffer (Bender et al., 2017).

Why Folate Matters for the Brain

Inside neurons, folate is required to regenerate tetrahydrobiopterin (BH4), a cofactor needed for producing serotonin, dopamine, and norepinephrine (Liwinski & Lang, 2023). Low folate status is also linked with increased homocysteine, which can impair vascular and brain health (Lukovac et al., 2024). These pathways explain why folate deficiency is associated with depression, cognitive decline, and neurodevelopmental concerns.

Folate and Depression

Low folate increases depression risk

Meta-analyses have consistently shown that people with depression have lower folate levels compared to non-depressed individuals (Bender et al., 2017). An umbrella meta-analysis reported a 35% increased odds of depression in those with low folate status (Gao et al., 2024).

Folate supplementation improves outcomes

Folate supplementation, especially in the form of L-methylfolate, can improve depressive symptoms when added to standard antidepressant therapy (Al Maruf et al., 2022). In clinical trials, L-methylfolate augmentation led to significantly greater symptom improvement compared to placebo, with benefits often seen within 4–8 weeks (Al Maruf et al., 2022).

Key point: For individuals who respond only partially to SSRIs or SNRIs, adding L-methylfolate can enhance treatment outcomes, particularly in those with MTHFR gene variants that impair folate metabolism (Meng et al., 2022).

Folate and ADHD

Biological connection

ADHD has been linked to altered one-carbon metabolism. Some children with ADHD show elevated homocysteine and lower vitamin B12 (Lukovac et al., 2024). MTHFR genetic variants (e.g., C677T and A1298C) that reduce folate activation are modestly associated with ADHD risk (Meng et al., 2022).

Prenatal protection

Maternal folate supplementation before and during pregnancy is associated with reduced ADHD risk in offspring (Chen et al., 2023). This highlights folate’s importance for early brain development.

EnBrace HR/MF

EnBrace HR/MF is a medical food designed to deliver bioactive forms of folate, L-methylfolate and folinic acid, along with B-vitamin cofactors and omega-3 phospholipids. This formulation bypasses MTHFR-related conversion issues and supports methylation and neurotransmitter synthesis (DailyMed, 2025).

For depression: The product’s L-methylfolate content aligns with the dosages and forms used in clinical augmentation trials (Al Maruf et al., 2022), making it a potential adjunct for individuals with low folate status or poor antidepressant response.

For ADHD: While it is not a substitute for stimulant medication or behavioral therapy, it may be beneficial in cases where folate deficiency or MTHFR variants are present, and in preconception/pregnancy for supporting neurodevelopment (Chen et al., 2023).

Practical Takeaways

Test before supplementing: Consider serum folate, RBC folate, vitamin B12, and homocysteine testing before starting.

Adjunct for depression: L-methylfolate can be an evidence-based add-on for treatment-resistant depression.

Support for neurodevelopment: Folate sufficiency before and during pregnancy supports healthy fetal brain development.

ADHD caution: Folate is not a stand-alone ADHD treatment but may be part of a comprehensive wellness plan.

NeuroWell+

We also offer our NeuroWell+ panel here at Well Mind Body, a one-time cheek swab that provides insight into your unique nutrigenomic profile, how your genes influence the way your body processes nutrients critical to brain health. This panel helps us understand how you metabolize key vitamins, minerals, and amino acids involved in mood regulation, focus, and stress response. With this information, we can create a personalized plan to best support your brain, targeting nutritional and lifestyle strategies that align with your biology. By combining advanced genetic insight with compassionate, integrative care, we can address not only your symptoms but also the root factors influencing your mental wellness.We understand that navigating mental health symptoms can feel overwhelming, isolating, and at times discouraging. Whether you are experiencing changes in mood, focus, or overall well-being, it can be difficult to know where to turn or what steps to take next. Learn more here.

At Well Mind Body, we are here to listen without judgment, provide compassionate guidance, and work alongside you to create a personalized plan for support and healing. You don’t have to face these challenges alone. Together, we can move toward clarity, balance, and renewed hope.

If you have any questions or would like to book an appointment, please visit www.wellmindbody.co. We would be happy to help you!

Thanks for being here,

Dr. E

References

Al Maruf, A., Poweleit, E. A., Brown, L. C., Strawn, J. R., & Bousman, C. A. (2022). Systematic review and meta-analysis of L-methylfolate augmentation in depressive disorders. Pharmacopsychiatry, 55(3), 139–147. https://doi.org/10.1055/a-1681-2047

Bender, A., Hagan, K. E., & Kingston, N. (2017). The association of folate and depression: A meta-analysis. Journal of Psychiatric Research, 95, 9–18. https://doi.org/10.1016/j.jpsychires.2017.07.021

Chen, H., Qin, L., Gao, R., Jin, X., Cheng, K., Zhang, S., & Wang, H. (2023). Neurodevelopmental effects of maternal folic acid supplementation: A systematic review and meta-analysis. Critical Reviews in Food Science and Nutrition, 63(19), 3771–3787. https://doi.org/10.1080/10408398.2021.1993781

DailyMed. (2025). ENBRACE HR—levomefolate magnesium, leucovorin, folic acid… (label). Retrieved from https://dailymed.nlm.nih.gov

Gao, S., Khalid, A., Amini-Salehi, E., Radkhah, N., Jamilian, P., Badpeyma, M., & Zarezadeh, M. (2024). Folate supplementation as a beneficial add-on treatment in relieving depressive symptoms: A meta-analysis of meta-analyses. Food Science & Nutrition, 12, 3806–3818. https://doi.org/10.1002/fsn3.4073

Ghanizadeh, A., Sayyari, Z., & Mohammadi, M. R. (2013). Effect of methylphenidate and folic acid on ADHD symptoms, quality of life, and aggression: A randomized, double-blind, placebo-controlled clinical trial. Iranian Journal of Psychiatry, 8(3), 108–114.

Liwinski, T., & Lang, R. (2023). Folate and its significance in depressive disorders and suicidality: A comprehensive narrative review. Nutrients, 15(17), 3859. https://doi.org/10.3390/nu15173859

Lukovac, T., Aleksić Hil, O., Popović, M., Jovanović, V., Savić, T., Pavlović, A. M., & Pavlović, D. (2024). Serum biomarker analysis in pediatric ADHD: Implications of homocysteine, vitamin B12, vitamin D, ferritin, and iron levels. Nutrients, 16(8), 1313. https://doi.org/10.3390/nu16081313

Meng, X., Zheng, J., et al. (2022). Association between MTHFR (677C>T and 1298A>C) polymorphisms and psychiatric disorder: A meta-analysis. PLOS ONE, 17(7), e0271170. https://doi.org/10.1371/journal.pone.0271170

Surman, C., Hammerness, P., et al. (2019). Does L-methylfolate supplement methylphenidate pharmacotherapy in ADHD? A double-blind, randomized clinical trial. Psychiatry Research, 278, 274–281. https://doi.org/10.1016/j.psychres.2019.06.008