MTHFR, What is it and how does it affect depression?

I am writing a book about depression and deficiencies, and have decided to include a chapter on MTHFR and other mutations having a direct impact on depression. I thought I would share some of my notes here with everyone. We can get lost in all of the medical jargon and our "diagnosis", but I tell people all of the time, our diagnosis does not define us and we shouldn't live under that umbrella. Because for most of us, getting to the root cause of "xzy" will eliminate the symptoms of said disease!

MTHFR & DEPRESSION

MTHFR plays a crucial role in the methylation cycle by converting folate (vitamin B9) into its active form, 5-MTHF (methylfolate), which is necessary for producing neurotransmitters like serotonin, dopamine, and norepinephrine.

• Common MTHFR Variants:

• C677T: Reduces MTHFR activity, leading to lower methylfolate levels and impaired neurotransmitter production.

• A1298C: Also affects methylation but to a lesser extent.

• How It Contributes to Depression:

• Lower serotonin & dopamine levels → Mood regulation problems.

• Elevated homocysteine → Increased oxidative stress and inflammation, which are linked to depression.

• Poor DNA methylation → Impaired gene regulation, affecting mental health.

COMT & DEPRESSION

COMT is an enzyme that breaks down catecholamines, including dopamine, epinephrine, and norepinephrine. It helps regulate how long these neurotransmitters stay active in the brain.

• Common COMT Variants:

• Val158Met (rs4680):

• Val/Val: High COMT activity → Faster breakdown of dopamine → Potential dopamine deficiency (linked to apathy, low motivation).

• Met/Met: Low COMT activity → Higher dopamine levels → Can contribute to anxiety and mood instability.

• How It Contributes to Depression:

• Too much dopamine breakdown (Val/Val) → Low dopamine, which can cause low motivation and anhedonia (lack of pleasure).

• Too little dopamine breakdown (Met/Met) → Dopamine overload in certain brain regions, potentially leading to emotional dysregulation and anxiety-driven depression.

MTHFR + COMT INTERACTION & DEPRESSION

• If someone has an MTHFR mutation and struggles with methylation, they may have reduced neurotransmitter production.

• If they also have a COMT mutation that breaks down neurotransmitters too quickly (Val/Val), they may have dopamine deficiency, increasing depression risk.

• Conversely, if COMT is too slow (Met/Met), excess dopamine may cause mood swings and anxiety.

To summarize: MTHFR and COMT are genes that affect how your brain makes and breaks down important mood-regulating chemicals like serotonin and dopamine. If you have an MTHFR mutation, your body may struggle to activate folate, leading to lower neurotransmitter levels and higher inflammation, which can contribute to depression. COMT, on the other hand, controls how fast dopamine is broken down—if it works too fast, you might feel unmotivated and low; if it’s too slow, you could have mood swings and anxiety. When both genes have mutations, the effects can combine, making depression worse. The good news is that targeted supplements like methylfolate, B12, and lifestyle changes can help balance these issues.

I am of the frame of mind that we should go to food first to try and get our nutritional needs met. What kind of foods specifically? Glad you asked.

To support MTHFR and COMT variations and ease depression symptoms, focus on nutrient-dense foods rich in key vitamins and minerals that optimize methylation, neurotransmitter production, and brain health.

FOR MTHFR SUPPORT (BOOSTING METHYLATION & LOWERING INFLAMMATION)

Folate-Rich Foods (Not Synthetic Folic Acid!)

• Dark leafy greens (spinach, kale, arugula, romaine)

• Liver (beef, chicken) – one of the best natural folate sources

• Asparagus, Brussels sprouts, and avocados

Vitamin B12

• Grass-fed beef, lamb

• Wild-caught fish (salmon, sardines, tuna)

• Pasture-raised eggs

• Dairy (if tolerated)

Other Methylation-Supporting Nutrients

• Choline (helps with neurotransmitter function): Eggs, liver, salmon

• Magnesium (reduces homocysteine, supports mood): Nuts, seeds, dark chocolate, leafy greens

• Zinc (helps serotonin production): Shellfish, pumpkin seeds, beef, chickpeas

FOR COMT SUPPORT (BALANCING DOPAMINE & STRESS HORMONES)

For Slow COMT (Met/Met) – Helps Break Down Dopamine & Reduce Anxiety

• Magnesium-rich foods (calms the nervous system): Pumpkin seeds, almonds, dark leafy greens

• Polyphenols (to regulate dopamine levels): Green tea, berries, dark chocolate, olives

• Sulfur-rich foods (support liver detox of excess dopamine): Garlic, onions, cruciferous vegetables (broccoli, cabbage)

For Fast COMT (Val/Val) – Helps Maintain Dopamine for Motivation & Focus

• Tyrosine-rich foods (boost dopamine production): Eggs, turkey, cheese, fish, nuts

• Adaptogens (to slow dopamine breakdown): Maca, Rhodiola, Ginseng

• Omega-3s (support brain function): Wild salmon, walnuts, flaxseeds, chia seeds

GENERAL MOOD & BRAIN-BOOSTING FOODS

• Fermented foods (probiotics help neurotransmitter production): Sauerkraut, kimchi, yogurt, kefir

• Healthy fats (support brain function & reduce inflammation): Avocados, coconut oil, extra virgin olive oil

• Protein-rich foods (build neurotransmitters): Grass-fed meat, pasture-raised poultry, lentils

By eating a diet rich in these foods, you can naturally support your MTHFR and COMT function, balance neurotransmitters, and improve your mood.

If you feel like getting all of your nutrients from food sources is not ideal or unattainable, try rich whole food derived supplements! Supplement Store