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. With a healthy vitamin B status, homocysteine can properly convert into methionine, a critical amino acid for the proper functioning of neurotransmitters, proteins, and DNA. 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. 

Elevated homocysteine can have numerous adverse effects on the body. It is associated with cellular dysfunction and unhealthy inflammatory responses and may be associated with dysregulated blood sugar metabolism and neurodegenerative diseases. Specifically relating to mental health, elevated homocysteine may hinder the normal synthesis of catecholamines, including dopamine, norepinephrine, and epinephrine, and non-catecholamines, such as serotonin, due to decreased S-adenosyl methionine (SAMe) availability. It may also lead to the production of neurotoxic compounds that may have harmful effects on dopaminergic neurons. 

One small clinical study evaluated 46 inpatients diagnosed with severe depression. 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. 

Maintaining a healthy homocysteine status is also clinically relevant for children and adolescents. A cross-sectional study 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. Compared to students with low anxiety levels, those with moderate to high anxiety levels were significantly positively associated with elevated serum homocysteine levels. 

Certain genetic polymorphisms, such as the ones involving the methylenetetrahydrofolate reductase (MTHFR) enzyme that regulates methylation and homocysteine clearance, may hinder normal homocysteine status. A common MTHFR polymorphism is C677T, and it is associated with a 50% reduction in MTHFR enzyme activity. Another common polymorphism is A1298C. Both C677T and A1298C polymorphisms are associated with elevated homocysteine. 

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) to help maintain proper homocysteine clearance. 

By Danielle Moyer, MS, CNS, LDN