Initial Presentation

Lindsay initially presented to my office with complaints of low mood, significant irritability, and brain fog. She also reported low energy despite getting adequate sleep and exercising regularly. And while she worked as an accountant and would ultimately meet her work deadlines, she described how the brain fog and fatigue doubled the time it would normally take her to complete most tasks.

Three years prior to the onset of her symptoms, she had become vegan, eating a lot of vegan junk food with only small amounts of protein from tofu and beans. While she ate some fruit, she rarely consumed vegetables. Upon further questioning, she wasn’t opposed to expanding her diet to include eggs and seafood.

Lindsey hadn’t been diagnosed with any other medical conditions and wasn’t taking any medications. She denied substance use outside of one or two drinks per month consumed on social occasions. She had no prior history of psychiatric hospitalizations, or symptoms of mania. Since she was adopted, she could not provide any family medical or psychiatric history.

Initial Relevant Labs

• Vitamin B12 low at 244 pg/mL
• Compound heterozygous for methylenetetrahydrofolate reductase (MTHFR) single nucleotide polymorphisms: one copy of each C677T (rs1801133) and A1298C (rs1801131) variants
• Homocysteine elevated at 15.7 µmol/L
• Complete blood count (CBC), comprehensive metabolic panel (CMP), hemoglobin A1c, lipid panel, ferritin, serum folate, and vitamin D were within normal limits

Working Diagnosis:

• Vitamin B12 Deficiency
• Elevated homocysteine likely due to B12 deficiency and MTHFR variants

Initial Treatment

• Vitamin B12 as methylcobalamin, 1,000 µg intramuscular injections once weekly for eight weeks
• Methylated vitamin-B complex, one capsule daily in the morning that includes 800 µg of L-methylfolate
• Add eggs and seafood to the diet
• Increase intake of folate-rich foods, including leafy greens, broccoli, avocado, and lentils

Explanation

MTHFR is an enzyme involved in the metabolism of folate and homocysteine (Dean, 2012). Variants in the MTHFR gene can affect enzyme activity and have been associated with various health conditions, including depression, anxiety disorders, and bipolar disorder (Zhang et al., 2022). MTHFR mutations, particularly C677T and A1298C, decrease enzyme function, reducing the conversion of folic acid to its active form, 5-methyltetrahydrofolate (5-MTHF). This active form is crucial for the methylation cycle, which affects the production of neurotransmitters such as serotonin, dopamine, and norepinephrine.

Low levels of vitamin B12 can exacerbate the effects of MTHFR mutations, leading to elevated homocysteine levels (Shiran et al., 2015). High homocysteine is neurotoxic and has been linked to cognitive decline, depression, and fatigue (Bisschops et al., 2004). Correcting vitamin B12 deficiency helps normalize homocysteine levels, supporting neurotransmitter synthesis and improving mood, energy, and cognitive function (Clarke et al., 2007). By ensuring adequate levels of B12 and active folate, the methylation cycle functions more efficiently, promoting overall mental health.

Follow-up Presentation

A few weeks after the vitamin B12 injections, Lindsay’s serum B12 was 675 pg/mL, well within the optimal range. She reported improved mood and less irritability. At work, she was feeling clearer-minded and more focused. Since starting the B12 injections, she noted increases in her overall energy. Even after transitioning off injections and fully onto oral supplementation, her energy levels remained significantly improved.

Follow-up Testing

• Vitamin B12 normalized, 675 pg/mL
• Homocysteine improved, 8 µmol/L

Follow-up Treatment

• Continue methylated vitamin-B complex twice daily
• Recheck vitamin B12 and homocysteine in three to six months

Explanation

After just a few months, Lindsay was reporting significant improvements in various facets of her mental and physical health. Additionally, she appeared calmer with a brighter affect. Even loved ones had commented on the changes.

CASE SUMMARY: The Importance of Vitamin B12 and Folate and the Potential Pitfalls of Vegan Diets for Mental Health

Vitamin B12 and folate are critical for brain function and mental health due to their essential roles in the methylation cycle. This biochemical process is necessary for the production of neurotransmitters, DNA synthesis, and cellular repair. Methylation impacts mood, cognition, and energy levels (Liu et al, 2018). Deficiencies in B12 and folate can lead to elevated homocysteine levels, which are associated with neurotoxicity and increased risk of mental health disorders such as depression, anxiety, obsessive-compulsive disorder, and cognitive decline among other mental health conditions. Correcting these deficiencies supports proper methylation, leading to enhanced neurotransmitter synthesis and improved brain function.

It is important to note that vegan and vegetarian diets can pose potential pitfalls for mental health if not well formulated. Key micronutrients such as vitamin B12, iron, omega-3 fatty acids, zinc, and iodine are often missed, leading to deficiencies that can adversely affect brain function and mood (Bali & Naik, 2023). In this case, Lindsay was willing to expand her diet to include eggs and seafood, but other patients may be unwilling to implement dietary changes. In such cases, supplementing the missing nutrients may be a long-term necessity.