How the MTHFR Gene Affects Your Ability to Use B Vitamin

If your B-vitamin levels are “normal” but you still feel foggy, tired, or irritable, this could be why.

If you're taking B vitamins and still feel mentally off, you're not imagining it. Your labs might say things are fine, but your brain knows otherwise. One of the most common reasons we see for this mismatch is a gene variant called MTHFR.

MTHFR is short for methylenetetrahydrofolate reductase. It’s an enzyme that helps convert folate (B9) and B12 into active, usable forms through a process called methylation. If you have a mutation in this gene, your body struggles to complete that conversion.

That means you might have plenty of B vitamins in your system, but your brain and nervous system can’t actually use them.

Why This Matters

Methylation is critical for mood, focus, memory, energy, and detox. It affects how your brain makes neurotransmitters, clears inflammation, and repairs damage. So when methylation slows down due to an MTHFR issue, your brain function slows down with it.

This is why people with MTHFR mutations often report symptoms like:

• Mood swings or persistent anxiety

• Brain fog that doesn’t respond to supplements

• Fatigue, even with decent sleep

• Hormonal imbalances or poor stress recovery

• Higher sensitivity to toxins or medications

And these issues don’t always show up on standard bloodwork. However, we've had a lot of success figuring out when a patient has the MTHFR mutation by using a specialized Cyrex blood panel. The ease and accuracy of this test makes it incredibly worth it, especially when patients haven't been able to find answers anywhere else.

The MTHFR Research

In a meta-analysis published in Molecular Psychiatry, individuals with the common C677T mutation in the MTHFR gene were significantly more likely to experience depression and treatment-resistant mood disorders. Their brains lacked the methylated B vitamins needed to maintain proper neurotransmitter levels and mood regulation (Gilbody et al. 2007).

And another study in Nutrients found that people with MTHFR mutations showed improved mood, energy, and cognition after switching to methylated folate and B12 supplements (Hoepner et all 2021). This supports what we see clinically: when the right forms are used, symptoms often begin to shift quickly.

What to Do if You Think This Is You

First, don’t guess. We offer MTHFR testing in the clinic, and it’s one of the most helpful tools for explaining why “normal labs” don’t line up with how people actually feel. Second, if you do have the mutation, standard B-complex supplements may not work for you. In some cases, they can even make symptoms worse. That’s why we recommend methylated B vitamins, which bypass the need for MTHFR and go directly to work. We carry several methylated B-complex options at The Neuro Clinic that we’ve vetted for purity and neurological compatibility. Ask about them at your next visit.

If you’ve been doing everything right but still feel off, this may be the missing piece.

Download Our Brain Nutrition Guide to get our full breakdown of what to look for and what actually works.

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Key Take-away:

MTHFR affects how your body activates B vitamins. Without that activation, your brain can’t function at full capacity. Testing for this mutation and using methylated supplements can be a turning point in getting your energy, focus, and mood back.