Methylation: is the adding on of a methyl group.

Methylation is not just an MTHFR ‘thing’.  Neither is it as simple as taking methyl-folate.

MTHFR is not the only enzyme involved, and there isn’t just one form of folate either.

Now, if you are asking, “What on earth is MTHFR?”, then we have a few more blogs coming.

But simply, for now, all you need to know is that MTHFR is ONE enzyme involved in the broader folate and methionine cycles that support methylationMethylation is one of the body's most important ‘behind-the-scenes’ processes. Happening millions of times every second, it helps regulate everything from energy production and hormone balance to detoxification, neurotransmitters, DNA repair, and how we respond to stress. Yes, it is literally involves in every reaction in your body. At its heart, methylation is the process of transferring tiny chemical tags, called methyl groups (one carbon with 3 hydrogens if you like a bit of chemistry), from one molecule to another. To do this efficiently, the body relies on nutrients such as folate, vitamin B12, vitamin B6, zinc, choline, methionine and more. Together, these nutrients help produce a molecule called SAMe, which acts as one of the body's main methyl donors.Referenced in 13 articlesClick to read more →.

Methylation occurs constantly throughout the body.

Dys-regulation in methylation can result in a series of pathologies such as (only a few listed below):

• Auto-immune conditions such as Multiple Sclerosis
• Birth Defects
• Oestrogen related issues such as PCOS, fibroids, menopausal mayhem
• Alzheimer’s Disease
• Psychiatric conditions

What exactly is methylation? 

Methylation is one of the body’s important ‘behind-the-scenes’ biochemical processes. It is involved in an extraordinary number of functions, from neurotransmitter metabolismMetabolism is not a calorie-burning furnace that sits somewhere near your belly button, deciding whether you can fit into last year's jeans. Metabolism is the set of chemical processes taking place inside your body every second of every day, keeping you alive.Referenced in 31 articlesClick to read more → and hormone metabolism to gene regulation, phospholipid synthesis and many other cellular processes.

Methylation is the transfer of a methyl group, a tiny chemical group consisting of one carbon and three hydrogens (CH₃), if you like a bit of chemistry, from one molecule to another.

Think of methylation like a relay race, where the baton being passed from one molecule to another is the methyl group (CH₃).

But where do those methyl groups come from?

This is where the folate and methionine cycles come in.

This is the kind of biochemistry we dip into at the New School of Nutritional Medicine. It is not about memorising pathways, or bringing back childhood school science nightmares, but about understanding the science when you have a real person sitting in front of you wanting support on their health journey.

These interconnected pathways (more commonly known as cycles) rely on nutrients including  folate (not folic acid), vitamin B12, vitamin B6, choline, methionine, and others. The folate cycle provides methyl groups that feed into the methionine cycle, ultimately enabling the production of SAMe (S-adenosylmethionine). SAMe is one of the body’s main methyl donor.

SAMe can then donate its methyl group to another molecule and THAT is methylation. 

When these interconnected pathways are disrupted, the effects can potentially reach many different areas of our biology. The folate cycle and methionine cycle are interconnected pathways within one-carbon metabolism.

They work closely together, with one supporting the other. Imagine, two cogs working together, what happens in one can impact the other. Together, these pathways help us produce SAMe (S-adenosylmethionine), remember, one of the body’s major methyl donors.

And remember our relay race? SAMe is carrying the CH₃ baton ready to pass it on.

Folate: Vitamin B9

Folate isn’t actually one molecule. We often hear, that ‘Folic acid is vitamin B9’. This is an oversimplification. Folate is the umbrella term for a family of compounds with vitamin B9 activity.

Within that family, we have several different molecules. These include:

• Folic acid 
• Tetrahydrofolate (THF)
• 5,10-methylene-THF
• 5-formyl-THF (folinic acid)
• 5-methyl-THF (methylfolate)

and several other folate derivatives.

They are related, but they are NOT interchangeable molecules. Importantly, they don’t all enter our biochemistry at exactly in the same place. This is important because there is a popular theory that MTHFR is the main issue (more on this later).

The beauty of food is that it can contain a mixture of naturally occurring folates, including methylfolate, folinic acid and tetrahydrofolate. The proportions differ between foods and can also change with the variety, growing conditions, storage and preparation.  For more folate-rich foods, check out the NIH folate fact sheet HERE.

Sprouting and fermenting: Sprouting legumes for four days causes a 3- to 4-fold increase in total folate, a near-complete conversion of the folate to methylfolate, AND a spike in vitamin C content that protects the methylfolate. 

Bacteria and yeasts are folate factories, and hence fermented foods are excellent sources of active folate.

Ultimately, we need folate for two enormous jobs:

1. Making DNA and new cells: 10-formyl-THF helps make purines, and 5,10-methylene-THF helps make thymidylate. These are building blocks of DNA, and DNA is required to make new cells. This is particularly important during neural-tube formation.
2. Supporting methylation: 5-methyl-THF (5-MTHF, or methylfolate) works with vitamin B12 to help recycle homocysteine into methionine, which can then be used to make SAMe, one of the body’s main methyl donors. This supports gene regulation and many other developmental processes.

And then there is folinic acid (5-formyl-THF). This is another reduced form of folate that can be converted into other folate forms, supporting both DNA synthesis and methylation. It differs from the 10-formyl-THF mentioned above and is not the same as folic acid or methylfolate.

In order for synthetic ‘folic acid’ to do the above, it needs to be converted into the usable folate forms involved in these pathways, and that is another story for a later blog.

In a nutshell, you need different forms of folate, each with a different job. Not just methylfolate or folic acid.

Why is methylation such a big deal?

So folate metabolism feeds into methylation, and methylation is involved in:

• Brain & mood: methylation is involved in neurotransmitter metabolism and nervous-system function. When these pathways are disrupted, we might see mood changes, anxiety, poor concentration, brain fog, changes in behaviour or difficulties with attention.
• Hormones: methylation is one of the pathways involved in processing oestrogens. When this isn’t working efficiently, we might think about how oestrogen metabolites are being handled, particularly in someone experiencing heavy periods, PMS, breast tenderness or other symptoms associated with hormonal imbalance.
• Immunity: methylation helps regulate immune-cell function and gene expression. When immune regulation is disrupted, we might think of frequent infections, poor immune resilience, chronic inflammation, or inappropriate immune responses.
• DNA and gene regulation: methyl groups help regulate which genes are switched on or off, while folate metabolism is also essential for DNA synthesis and repair. When these processes go ‘off line’, think  abnormal cell growth, ageing, and diseases such as cancer, in which abnormal DNA methylation patterns are commonly found.
• Homocysteine: methylation helps recycle homocysteine back into methionine. When that pathway isn’t working efficiently, homocysteine can rise, something we measure in a blood test and when elevated, is associated with cardiovascular and neurological disease risk.
• Detoxification: methylation is one of several pathways the body uses to process certain hormones, chemicals and other compounds. When assessing someone’s overall detoxification capacity, we may also consider their exposure to environmental chemicals, medications, alcohol, and potentially toxic metals, alongside the liver’s other detoxification and elimination pathways. More in detox HERE.
• Cell membranes & the brain: methylation helps produce phosphatidylcholine, an important component of cell membranes. When these pathways are compromised, we’re potentially thinking about cellular communication, liver function, nervous system health, and cognitive function.
• Digestive system: methylation supports one of the pathways that makes phosphatidylcholine, an important component of bile. Bile helps us digest fats, absorb vitamins A, D, E and K, and eliminate certain waste products. When bile delivery to the gut is impaired, we might see poor fat digestion, greasy stools and reduced absorption of these fat-soluble vitamins (more HERE)
• Growth, repair and pregnancy: folate metabolism provides the building blocks required to make DNA and, therefore, new cells. This becomes particularly important during pregnancy, foetal development, childhood growth, tissue repair and anywhere cells are rapidly dividing.
• That in ‘bite-size’ chunks is the function of methylation. Nearly every biochemical process is impacted by methylation. Some more than others.

Can you see why we don’t teach the body in isolated systems at the New School? 

You cannot get to grips with understanding hormones, fertility, cancer, digestive issues, autoimmune diseases, nervous system regulation etc. And let’s just admit it, we cannot talk about the nervous system as though nutrition sits somewhere in the ‘corner’. The vagus nerve communicates largely through a neurotransmitter called acetylcholine. Neurotransmitters have to be synthesised and metabolised, cell membranes have to be built, genes regulated and nervous-system cells maintained. Folate and methylation sit within that much bigger biochemical picture.

It all connects and learning to see those connections is where nutritional medicine and psychological coaching gets super exciting.

Folate is not just about methylation: it is also essential for making DNA and new cells.

Folate metabolism provides the one-carbon units needed to make purines and thymidylate. These are essential building blocks of DNA. If DNA synthesis isn’t working efficiently, cells that need to divide rapidly can be particularly affected.

• Pregnancy & foetal development: enormous numbers of new cells are being produced during early development. When folate-dependent DNA synthesis is compromised, consider impaired cell division, disrupted neural tube formation, and an increased risk of neural tube defects such as spina bifida and anencephaly.
• Growth and development: babies, children and adolescents are continually building new tissue. When DNA synthesis and cell division are compromised, we might think about poor growth, developmental problems and impaired tissue renewal.
• Blood cells: our bone marrow is constantly producing new blood cells. When DNA synthesis is impaired, we can see megaloblastic anaemia, large immature red blood cells, fatigue, weakness, pallor and shortness of breath.
• Gut: cells lining the gastrointestinal tract turn over rapidly. When cell renewal is compromised, we might consider changes to the gut lining, gastrointestinal symptoms, and impaired intestinal function.
• Skin, hair & nails: these tissues also depend on continual cell division and renewal. When this isn’t happening efficiently, we might see changes in skin integrity, poor wound healing, hair changes, or slower tissue renewal.
• Immune system: activated immune cells need to proliferate rapidly. When DNA synthesis is compromised, we might think about impaired immune-cell proliferation and a reduced ability to mount an effective immune response.
• Repair & recovery: healing requires cells to divide, rebuild and replace damaged tissue. When new-cell production is compromised, we might see slower wound healing, impaired tissue repair, and slower recovery.

Maybe this is the year you stop just reading about this stuff.

At the New School of Nutritional Medicine, this is how we teach. We don’t teach nutrients, pathways, genetics, psychology and physiology as isolated subjects. We teach you how they connect, and importantly, how to take all that science and apply it to the WHOLE person. We are not into one nutrient, one SNP, one symptom. 

If you find yourself reading blogs like this and thinking, I want to understand this properly, perhaps it is time to stop sitting on the sidelines.

Our next two-year Nutritional Medicine programme begins 19th September 2026, and applications are still open. APPLY NOW 

To WHOLEness!

From the team at the New School of Nutritional Medicine.

If you want to dive deeper,  here are a few links:

1. Mentch SJ & Locasale JW (2016). One-Carbon Metabolism and Epigenetics: Understanding the Specificity.
2. Anderson OS et al., (2012) . Nutrition and epigenetics: an interplay of dietary methyl donors, one-carbon metabolism and DNA methylation.

Learn about the Founder & Principal of the New School of Nutritional Medicine, Dr Khush Mark PhD HERE.