---
title: Supporting Mental Health with Healthy Homocysteine
description: Elevated homocysteine, driven by low B vitamin status, has been linked to depression and anxiety in adults and children, per multiple clinical studies.
image: https://www.casi.org/hubfs/casi/featured/adobestock_583954251.jpeg
---

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# Supporting Mental Health with Healthy Homocysteine

DM Danielle C. Male, MS, CNS, LDN Jul 06, 2023

![Supporting Mental Health with Healthy Homocysteine](https://www.casi.org/hs-fs/hubfs/casi/featured/adobestock_583954251.jpeg?width=960)

The B vitamins work interconnectedly in the body, with [folate and vitamins B2, B6, and B12 acting as cofactors in DNA methylation and homocysteine clearance](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4772032/). With a healthy vitamin B status, homocysteine can properly convert into [methionine](https://pubmed.ncbi.nlm.nih.gov/25449138/), a critical amino acid for the proper functioning of [neurotransmitters, proteins, and DNA](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7564482/). A deficiency in one or more of these B vitamins can potentially lead to an accumulation of homocysteine, which has been [deemed a risk factor for poor mood and mental health.](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6770181/) 

[Elevated homocysteine](https://pubmed.ncbi.nlm.nih.gov/25449138/) can have numerous adverse effects on the body. It is associated with [cellular dysfunction](https://pubmed.ncbi.nlm.nih.gov/25449138/) and [unhealthy inflammatory responses](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8703276/) and may be associated with [dysregulated blood sugar metabolism](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8703276/) and [neurodegenerative diseases](https://onlinelibrary.wiley.com/doi/full/10.1111/bcpt.12424). Specifically relating to mental health, elevated homocysteine may hinder the [normal synthesis of catecholamines](https://onlinelibrary.wiley.com/doi/10.1111/fcp.12145), including dopamine, norepinephrine, and epinephrine, and [non-catecholamines](https://onlinelibrary.wiley.com/doi/10.1111/fcp.12145), such as serotonin, due to decreased S-adenosyl methionine (SAMe) availability. It may also lead to the production of [neurotoxic compounds](https://onlinelibrary.wiley.com/doi/10.1111/fcp.12145) that may have harmful effects on [dopaminergic neurons.](https://onlinelibrary.wiley.com/doi/10.1111/fcp.12145) 

One [small clinical study evaluated 46 inpatients diagnosed with severe depression](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1737050/). The researchers observed that the mean total plasma homocysteine value was significantly increased in the depressed group compared to the control groups, with 24 (52.1%) of the patients having a total plasma homocysteine concentration above the normal range. Similar findings were concluded in a [systematic review and meta-analysis of observational studies.](https://pubmed.ncbi.nlm.nih.gov/33423269/) 

Maintaining a healthy homocysteine status is also clinically relevant for [children and adolescents](https://pubmed.ncbi.nlm.nih.gov/32304285/). A [cross-sectional study](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5566365/) examined the homocysteine status in a community sample of students aged 6 to 13 (n = 649). Among the 7th-grade boys, the rates of both [depression and anxiety were independently associated with increased homocysteine levels](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5566365/). Compared to students with low anxiety levels, those with [moderate to high anxiety levels were significantly positively associated with elevated serum homocysteine levels](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5566365/). 

Certain genetic polymorphisms, such as the ones involving the [methylenetetrahydrofolate reductase (MTHFR) enzyme](https://pubmed.ncbi.nlm.nih.gov/36562046/) that regulates methylation and homocysteine clearance, may hinder normal homocysteine status. A common MTHFR polymorphism is [C677T](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8703276/), and it is associated with a [50% reduction in MTHFR enzyme activity](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8703276/). Another common polymorphism is [A1298C](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8703276/). Both C677T and A1298C polymorphisms are associated with [elevated homocysteine](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8703276/). 

Maintaining a healthy homocysteine status may support mental health. Daily intake of B vitamins, such as folate, vitamin B2, B6, and B12, may help promote healthy homocysteine metabolism. Individuals with MTHFR polymorphisms may benefit from supplementing with [methylated folate (as 5-MTHF)](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7564482/) to help maintain proper homocysteine clearance. 

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### Danielle C. Male, MS, CNS, LDN

Clinical Application

## Clinical Considerations in Practice

 In clinical practice, practitioners considering the topics discussed above may also weigh nutrient form, delivery and formulation, alongside individual patient variability.

### Practitioner Formulation Example

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Methylfolate, NAC, TMG, B6, B12 and riboflavin · Capsules

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