Methylation: What It Is, Why It Matters, and Why It's Not All About MTHFR
Methylation is a word that’s thrown around a lot in functional and integrative health circles—and more recently, on TikTok and Instagram by wellness influencers pushing methylated B vitamins like they’re magic pills. But methylation is far more nuanced (and powerful) than a single gene or supplement.
Let’s break it down.
What Is Methylation?
Methylation is a biochemical process that happens in every cell of your body, millions of times per minute. It involves transferring a methyl group (one carbon and three hydrogen atoms) onto a molecule. While that sounds simple, its ripple effects are huge.
Methylation helps your body:
Make neurotransmitters like dopamine, serotonin, and melatonin
Regulate gene expression (epigenetics; turning genes on and off)
Detoxify hormones, medications, and environmental toxins
Recycle homocysteine into methionine (key for cardiovascular health)
Clear excess histamine
Repair DNA and support immune function
If methylation is under-functioning, these systems don’t work efficiently, and that can impact everything from your mood and sleep to hormone balance, detoxification, and energy.
Why It’s About More Than Just MTHFR
The MTHFR gene has been centre stage in wellness circles for the past decade, often blamed for everything from fatigue to fertility issues. While variations in the MTHFR gene (such as C677T and A1298C) can influence how well you activate folate, they are just one small piece of a much larger picture.
Other important genes involved in the methylation cycle include:
• COMT – impacts how you clear dopamine and oestrogen
• MAO-A / MAO-B – involved in serotonin and other neurotransmitter metabolism
• MTR & MTRR – influence how well you recycle and utilise B12
• BHMT & CBS – manage alternative methylation pathways
• GST, SOD2, PEMT – affect antioxidant function and detoxification, especially in phase 2 liver support
Focusing only on MTHFR and jumping straight to high-dose methylated folate or B12 can be counterproductive—and in some cases, make people feel worse (think: anxiety, insomnia, headaches).
The Health Impacts of Poor Methylation
When methylation isn’t functioning well, symptoms can show up in many different ways, including:
• Anxiety, low mood, or irritability
• Brain fog and poor memory
• Sleep disturbances
• Chemical sensitivity
• Histamine intolerance
• Heavy periods, PMS, acne and oestrogen dominance
• Fatigue and poor recovery
• Skin issues and delayed wound healing
• Speech and language delays in children
• Fertility struggles and recurrent miscarriage
• Behavioural and developmental challenges
• Increased sensitivity to medications or supplements
Methylation also plays a key role in phase 2 liver detoxification—specifically in processing:
• Heavy metals like arsenic, mercury, and lead
• Oestrogen, adrenaline, noradrenaline, and histamine
• Medications and environmental toxins
• Phenolic compounds from foods like tea, wine, berries, and spices
This means poor methylation can impact how well you clear not just what comes from your body, but also what comes into it.
Why Testing (Properly) Matters
Supporting methylation isn’t about guessing or self-diagnosing based on one gene result. It requires a comprehensive understanding of:
• Genetic variations across multiple genes—not just MTHFR
• Blood markers like B12, folate, homocysteine, and liver enzymes
• Symptom history and medication use
• Gut function, nutrient absorption, and detox capacity
This is not something you should be taking advice on from a TikTok bro with a six-pack and a supplement code.
High-dose methylated vitamins are often unnecessary and, in some people, can do more harm than good. Especially if other detox pathways (like sulfation, glucuronidation, and glutathione conjugation) are underfunctioning.
Bottom Line? Methylation Matters—But It’s Complicated
Methylation is a critical biochemical process, but supporting it properly requires nuance, testing, and a personalised approach. This is not the place for one-size-fits-all protocols or trendy stacks.
Food-first, test-based, and gently-supported wins every time.