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what is methylation and who needs methylated vitamins?

by Dr Nina Bailey BSc (Hons), MSc, PhD, RNutr
& Rose Glover BSc (Hons), mBANT, CHNC

Methylation is a natural process that happens inside your cells every second of every day. It helps to keep your systems running smoothly, from how you produce energy to how your body handles toxins and supports brain health.

As nearly half of Europeans have some form of gene variation affecting methylation, this process doesn’t always function as it should. The result? A large proportion of the population feels tired, has a low mood, or experiences brain fog. Luckily, there’s an easy solution if you know which form of vitamins to take.

what is methylation?

Put simply, methylation involves adding small chemical compounds called methyl groups to other molecules. These groups act like “activation tags,” switching certain processes on or off.


You can picture methylation as a kind of relay race, where each nutrient passes an ‘activation’ baton - the methyl group - to the next. When this handover runs well, you feel balanced, focused, and energised. When the process doesn’t run so well, it has the potential to lead to more serious health concerns (1). 

This process relies on key nutrients, with folate (B9) and vitamin B12 playing central roles, while B6, B2 and betaine (produced from dietary choline) support the cycle to keep it running efficiently.


When this system becomes imbalanced due to stress, poor diet, or genetics, the body struggles to efficiently recycle key compounds. As a result, harmful substances such as homocysteine can build up, affecting heart, brain, and liver health.


Methylation works alongside other key pathways in the body, such as the folate cycle and the transsulfuration pathway. Together, they help convert nutrients into usable forms, support detoxification, and keep your body functioning smoothly.

How Methylation Supports Key Body Functions

1.    Detoxification and Liver Health
Methylation supports your liver’s ability to neutralise and remove toxins. It’s also key in producing glutathione, one of the body’s most powerful antioxidants. When methylation is sluggish, toxins can build up, leading to fatigue, inflammation, and poor liver function.(2)
 

2.    Energy and Cellular Health
A large proportion of methyl groups is used to produce fats that form healthy cell membranes and energy molecules such as creatine. When methylation falters, cells may lose structure and energy production can drop, potentially leaving you feeling drained.(1)
 

3.    Liver health
The liver is rich in mitochondria, the tiny powerhouses within cells that generate energy. The fats that are created by methylation are not only a major component of mitochondrial membranes, but are also needed to make other specialised forms of fats (called lipoproteins) that play a role in the healthy transport of triglycerides and cholesterol away from the liver to other parts of the body. Triglycerides transported by lipoproteins provide energy to muscles and other tissues, while cholesterol is needed for functions such as bile production for fat digestion and the production of vital hormones. When methylation is impaired, it negatively affects mitochondrial health, leading to low energy and the storage of unhealthy levels of triglycerides by the liver, a major contributor to fatty liver disease.(3)
 

4.    Brain and Mood
Methylation helps produce neurotransmitters such as serotonin, dopamine, and norepinephrine, which are essential for focus, mood, and emotional balance. Poor methylation has been linked to low mood, anxiety, and cognitive decline.(4,5)
 

5.    Heart and Circulatory Health
High levels of homocysteine, caused by inefficient methylation, are associated with a higher risk of heart disease and stroke. Supporting methylation helps maintain healthy homocysteine levels, protecting both the heart and brain.(6)
 

6.    Immune Balance and Inflammation 
Proper methylation helps regulate the immune system and reduces unnecessary inflammation, promoting resilience and balanced immune responses.(7)

Choosing the Right B-Vitamins for Methylation

Two B-vitamins are especially important for methylation because they act as methyl donors, which are able to transfer methyl groups (‘activation tags’): folate (vitamin B9) and vitamin B12. 
However, not all forms of these B vitamins work the same way in your body.

For example, vitamin B9 comes in several forms:

folate from food (like leafy greens)

methylfolate (the active form found in well-formulated supplements)

folic acid (the synthetic form in many supplements)

Folic acid must first be converted into methylfolate to be used, and many people with genetic variations struggle with this conversion. 
 

Vitamin B12 also comes in different forms. The active form methylcobalamin can be used directly as a methyl donor. Other forms, such as cyanocobalamin, need to be converted first, a process that can be less efficient for some people.


While methylfolate and methylcobalamin directly support methylation, vitamins B6 and B2 help indirectly—but only in their active coenzyme forms, pyridoxal 5'-phosphate and riboflavin-5′-phosphate. 

 

In summary, using a supplement containing the active forms, methylfolate and methylcobalamin, alongside B6 and B2 as 5'-phosphates, helps ensure your body has the nutrients it needs to support methylation, energy, and overall health.

The MTHRF Gene, and how it influences Methylation

Genetics can influence how efficiently your body methylates. One well-known gene is MTHFR, which helps convert the nutrient folate into its active form, methylfolate, a crucial step in methylation. 

 

As mentioned, some people carry variations in this gene, called SNPs (single-nucleotide polymorphisms), which can reduce the efficiency of this conversion. 

For these individuals, taking folic acid supplements - the synthetic form of folate - can be less effective, because their bodies struggle to convert it into the active form. This reduced conversion can lead to a build-up of unmetabolised folic acid (UMFA), a form the body cannot use and one that may be associated with potential health risks.(8)


Using supplements that provide methylfolate rather than folic acid can help bypass this step and support healthy methylation. 

While some genetic variations affecting methylfolate production are well known, many others exist in related pathways. Having several of these variations together can influence health in different ways. For example, some SNPs make it harder for the body to activate regular B6, so taking pyridoxal 5'-phosphate avoids that problem—just like methylfolate helps people with MTHFR variants.(9)

 

If you’re curious about your own genetic makeup, practitioner-led genetic testing (for example, through Lifecode Gx® in the UK) can help identify these variations and guide personalised nutritional support.

How to Support Healthy Methylation

A nutrient-rich diet provides the building blocks your body needs for methylation. Focus on foods high in: 

Maintain Adequate Protein Intake
Proteins provide amino acids such as methionine and cysteine, which are essential for methylation and detoxification.


Limit Alcohol and Environmental Toxins
Excess alcohol and exposure to toxins can impair methylation and deplete cofactors such as B vitamins and glutathione.


Consider Targeted Supplementation
Additional support with methylated nutrients may be beneficial, especially for individuals with genetic variations or higher nutrient demands. 

Look for supplements containing methylated nutrients such as methylfolate (L-MTHF) and methylcobalamin (B12), as well as active B6 and B2 in their 5′-phosphate forms.

The Takeaway

Methylation is a core process that underpins many aspects of health, from energy and mood to detoxification and immune function. Supporting it is about providing the body with the nutrients and cofactors it needs to function properly.

REFERENCES

1.    Bertolo RF, McBreairty LE. The nutritional burden of methylation reactions. Curr Opin Clin Nutr Metab Care. 2013 Jan;16(1):102-8.   https://pubmed.ncbi.nlm.nih.gov/23196816/
2.    Townsend DM et al., The importance of glutathione in human disease. Biomed Pharmacother. 2003 May-Jun;57(3-4):145-55.  https://pubmed.ncbi.nlm.nih.gov/12818476/
3.    Mansouri A et al., Mitochondrial Dysfunction and Signaling in Chronic Liver Diseases. Gastroenterology. 2018 Sep;155(3):629-647. https://pubmed.ncbi.nlm.nih.gov/30012333/
4.    Miller AL The methylation, neurotransmitter, and antioxidant connections between folate and depression. Altern Med Rev. 2008 Sep;13(3):216-26.  https://pubmed.ncbi.nlm.nih.gov/18950248/
5.    Mirkovic B et al., Epigenetics and Attention-Deficit/Hyperactivity Disorder: New Perspectives? Front Psychiatry. 2020 Jun 17;11:579. https://pubmed.ncbi.nlm.nih.gov/32625125/
6.    Joshi SM & Jadavji NM. Deficiencies in one-carbon metabolism led to increased neurological disease risk and worse outcome: homocysteine is a marker of disease state 
Front Nutr. 2024 Fe 2121;11:1285502 https://pmc.ncbi.nlm.nih.gov/articles/PMC10915003/

7.    Alimohammadi et al., 2022 DNA methylation changes and inflammaging in aging-associated diseases. Epigenomics. 2022 Aug;14(16):965-986. https://pubmed.ncbi.nlm.nih.gov/36043685/

8.    Fardous AM, Heydari AR. Uncovering the Hidden Dangers and Molecular Mechanisms of Excess Folate: A Narrative Review. Nutrients. 2023 Nov 6;15(21):4699. https://pubmed.ncbi.nlm.nih.gov/37960352/

9.    Carter TC et al. Common Variants at Putative Regulatory Sites of the Tissue Nonspecific Alkaline Phosphatase Gene Influence Circulating Pyridoxal 5'-Phosphate Concentration in Healthy Adults. J Nutr. 2015 Jul;145(7):1386-93. https://pubmed.ncbi.nlm.nih.gov/25972531/

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