Genetics can feel like a complicated puzzle, but sometimes the pieces are surprisingly common. One of the most widespread genetic quirks is a variation in a gene called MTHFR. Estimates suggest that up to 60% of people worldwide carry at least one version of this variant, and most have no idea it’s there.
The name might sound intimidating (methylenetetrahydrofolate reductase, if you want the full version), but what matters is what this gene does. MTHFR is central to a process called methylation, a biochemical pathway that acts a bit like the body’s control panel, switching critical functions on and off.
If your MTHFR gene is less efficient because of a variant, it can change how your body processes key nutrients, how effectively it clears toxins, and even how much energy you feel day to day.
Let’s unpack what this gene does, why so many people have a variant of it, and what you can do if you’re one of them (like using smart supplementation).
What Is the MTHFR Gene?
The MTHFR gene provides instructions for making an enzyme involved in processing folate (vitamin B9). This isn’t just about getting vitamins into your bloodstream, it’s about converting them into the active forms your cells actually use.
Here’s the crucial part: MTHFR helps convert folate into 5-MTHF (5-methyltetrahydrofolate), which is required to recycle homocysteine back into methionine, an amino acid. This reaction powers the methylation cycle, which influences:
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Energy production (supporting mitochondrial function)
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DNA repair and synthesis (keeping cells healthy over time)
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Detoxification (removing harmful compounds from the body)
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Neurotransmitter balance (impacting focus, memory, and mood)
When methylation runs smoothly, these processes hum along in the background. But with certain MTHFR variants, efficiency drops, meaning your body may not be processing folate, B vitamins, and homocysteine as effectively.
How Common Are MTHFR Variants?
Researchers have identified several versions of the MTHFR gene, but two in particular are common: C677T and A1298C.
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About 40% of people carry one copy of C677T, which can reduce enzyme activity by up to 35%.
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Around 10–15% carry two copies, which may lower activity by 70% or more.
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Another 20–30% carry A1298C, which has milder effects but can compound issues if combined with C677T.
Altogether, this means roughly six in ten people have some variation in MTHFR. Most don’t know unless they’ve taken a genetic test, but the downstream effects can influence energy, resilience, and long-term health.
What Happens When MTHFR Doesn’t Work as Well?
Having a variant doesn’t mean you’ll automatically notice symptoms. But over time, less efficient methylation can contribute to imbalances such as:
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Higher homocysteine levels → associated with cardiovascular stress if left unchecked.
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Slower detoxification → the liver struggles to clear byproducts as quickly.
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Lower neurotransmitter production → which may impact focus and cognitive sharpness.
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Reduced glutathione recycling → the body’s master antioxidant, vital for fighting oxidative stress.
This doesn’t mean a variant is a flaw, it’s just a difference that may need nutritional support to keep the system balanced.
How to Support Methylation if You Have an MTHFR Variant
The good news: knowing about MTHFR opens doors to practical solutions. While you can’t change your genes, you can change the environment they work in.
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Optimise Folate Intake
– Choose foods rich in natural folate: leafy greens, legumes, and avocados.
– If supplementing, look for methylated folate (5-MTHF) rather than folic acid, which some people with variants struggle to convert. -
Include Methylation Nutrients
– Vitamin B12 (methylcobalamin): essential partner in recycling homocysteine.
– Vitamin B6 (P5P form): supports amino acid metabolism and neurotransmitter balance.
– Riboflavin (B2): helps MTHFR enzymes function more efficiently. -
Consider Trimethylglycine (TMG)
– TMG, also called betaine, is a methyl donor. It can help “donate” methyl groups directly, bypassing bottlenecks in the MTHFR pathway.
– Studies suggest the best TMG supplement lowers homocysteine and supports liver function, offering an extra layer of resilience. -
Lifestyle Foundations
– Prioritise sleep, since methylation is most active during cellular repair at night.
– Manage stress, as chronic cortisol can interfere with methylation balance.
– Limit alcohol, which increases demands on methylation and depletes B vitamins.
Why Most People Never Realise They Have It
Because MTHFR variants are so common, many people assume their experiences with fatigue, slow recovery, or foggy thinking are “just normal.” Unless someone does a genetic test or checks homocysteine levels, they often won’t connect the dots.
In many ways, that’s the important message: you don’t need to know your exact genetic code to benefit from methylation support. Simple steps like eating more folate-rich foods, choosing methylated B vitamins, and adding TMG can make a noticeable difference for energy, clarity, and long-term wellbeing, variant or not.
Why This Matters for Longevity
Methylation isn’t just about how you feel today. It’s about the processes that protect your cells year after year. Efficient methylation means:
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DNA repairs itself more effectively, reducing errors that accumulate with age.
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Homocysteine stays in check, supporting cardiovascular resilience.
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Neurotransmitters remain balanced, supporting long-term brain function.
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Antioxidants like glutathione recycle efficiently, buffering oxidative stress.
That’s why supporting methylation has become a focus in the field of longevity, because small differences in how your body manages these pathways can ripple into big differences over time.
How Simply Nootropics Can Help
If you’re one of the 60% of people with an MTHFR variant, you don’t need to worry. You simply need to support your body in ways that make methylation run smoothly.
That starts with good nutrition, targeted B vitamins, and additional methyl donors like TMG. Together, these nutrients ensure your methylation “control panel” has the resources it needs to power energy, repair, detoxification, and resilience.
Our TMG B-Complex is designed with this in mind. It combines Trimethylglycine (TMG) with a full spectrum of activated B vitamins, including methylated B12 and folate, to directly support methylation. Whether or not you’ve tested for MTHFR, this formula helps keep the cycle running efficiently so you can think clearer, recover faster, and age better.
