Mighty methylation: What it means for your healthspan

by | Dec 19, 2023

Key takeaways

  • Methylation is essential for health, affecting cell function, immunity, and gene regulation. Poor methylation is linked to many diseases
  • Methylation patterns are indicators of biological age. Optimising methylation through diet, lifestyle adjustments, and supplements can promote healthier ageing
  • The efficiency of methylation is influenced by genetics, particularly the MTHFR gene, and environmental factors like diet and lifestyle

Methylation is one of the most critical biological processes in the human body, yet rarely gets the credit and attention it deserves.

It quite literally defines you – through the epigenetic expression of your DNA.

Methylation is everywhere, all at once, doing some massive lifting, while being all but invisible.

There are some very deep rabbit holes when it comes to methylation, which as practitioners we find fascinating, but we’ll spare you most of the biochemistry, and instead tell the simplified story of this workhorse of life.

Let’s go!


Methylation 101


Your body is one incredible adaptive, regenerative biological system. It works hard to take raw materials from the nutrients you eat and put those materials through methodical processes to create new, bio-available versions of those nutrients to activate a myriad of cellular processes critical to survival.

Think about crude oil. You cannot place crude oil straight into a petrol tank. It first needs to be refined and processed into a form that a vehicle can use.

Same with solar power. You cannot just beam sunshine into a power plug. The sunlight is converted into electrical energy which can then be received and used as a power source.

A similar process of refinement and conversion happens at a molecular level in your body over and over, billions of times a day. This process is called methylation and it plays a role almost everywhere, notably in the following functions:


  • Cell health
  • Immune health
  • Creating and clearing adrenaline
  • Detoxification
  • Producing energy for cells to use in chemical reactions
  • Clearing out excess oestrogens and histamine
  • Regulating how your genes get expressed (epigenetics)


Methyl (CH3) groups are one of the most basic units of organic chemistry, and are what methylation is all about; attaching and detaching methyl groups to change things like molecules or genes in the body. The process of methylation is controlled by enzymes, whose job is to take one raw material and convert it into another. Without enzymes, methylation comes to a halt.

The thing is, the efficiency of those enzymes can vary wildly between individuals, based on your genetics and nutrient availability. Enzyme efficiency can be compensated for, but not until we have a look at what is going on through testing and nutrigenomic profiling; an important component when embarking on a health optimisation journey.


What happens if methylation is compromised?


Sub-optimal methylation is likely in around 35% of the population thanks to genetic DNA SNPs (Single Nucleotide Polymorphisms, the acronym pronounced “snips”), but more on that topic later. Lifestyle can also impair methylation, even in those without the genetic predisposition.

Poor methylation is a non-trivial matter, having been associated with:



As you can hopefully see, methylation is kind of a big deal. Let’s go a little further.



The biology of methylation


Methylation is a fundamental biochemical process that occurs in every cell of your body, involving the removal or addition of a methyl group to other molecules. This small change can dramatically alter the function and behaviour of these molecules and, consequently, significantly impact the functioning of your body, in almost every way.

Perhaps the most well-known, and significant, role of methylation is in the regulation of genes. This process, known as epigenetics, directly impacts gene expression – the turning on or off of genes by adding or subtracting methyl groups to your DNA at CpG sites (Cytosine-phosphate-Guanine).

The methyl groups are basically saying, ‘play this gene, don’t play this one’.

Think of your DNA like an instrument or code, pretty useless until it is being played/run, all orchestrated epigenetically, by your friend methylation. Epigenetic methylation is like the music of life, determining the notes played, and thus the song of the body.

A poorly tuned instrument, badly played, doesn’t make for easy listening, and in the same way, compromised methylation genetics and nutrients, in combination with lifestyle and environmental factors, make for health issues and poor ageing.


Methylation and biological ageing


DNA methylation patterns are now recognised as reliable biomarkers of biological age, as compared to chronological age. Scientists use ‘epigenetic clocks’ based on these patterns to gauge the ageing process at a molecular level. These ‘clocks’ are developed by analysing methylation at specific DNA sites across the genome. The degree of methylation at these sites correlates with ageing and can reflect the cumulative effect of an individual’s lifestyle, environment, and genetic predispositions.

By measuring these epigenetic changes, we can predict the risk of age-related diseases, offering a window into a person’s true biological age, and providing opportunities for targeted interventions to promote healthier ageing.


Genetics and methylation


What are these MTHFR genes!?


Your genetic blueprint plays a significant role in shaping methylation processes.

A key player in the methylation process is the MTHFR gene (methylenetetrahydrofolate reductase). This gene is responsible for converting folic acid into its active form, 5-MTHF (5-methyltetrahydrofolate).

Genetic variants of the MTHFR gene, most notably C677T and A1298C, can significantly impact its enzyme activity, by up to a 70% reduction in folate enzyme efficiency. The active form of folate (vitamin B9) is a critical player in most methylation reactions throughout the body, and such a significant reduction in efficiency changes the methylation economics of the body. Less methyl groups means less fuel for genetic regulation, and everything else, which makes for a ‘health song’ that isn’t as smooth, including cardiovascular disease and neurological disorders.

The thing is, if you know about your methylation genetics, you can quite simply and effectively compensate for, and accommodate them. You really do need to know what is going on though, as more methyl fuel (5-MTHF), is not always a good thing, potentially creating a different set of problems, including cancer, and mood disturbance. This highlights the importance of genetic testing and personalised interventions to address YOUR particular methylation needs, to optimise YOUR health.



Optimising methylation for healthier ageing


With over 1 in 3 people having MTHFR SNPs (variations), it makes sense to figure out what your MTHFR status is. If you do have a SNP, there are plenty of strategies you can use in your daily life to optimise your methylation. Even if you don’t have any SNPs, it is worth noting that since we all lose methylation capacity as we age, methylation optimisation is a longevity strategy for everyone.


The power of environmental inputs


DNA methylation is a dynamic process, significantly influenced by environmental factors and lifestyle choices. Exposure to environmental toxins, stress, physical activity levels, and even ageing, can alter methylation patterns. This makes sense, as when your environment and life change (for better or worse) your body needs to adapt, and it does this by changing the genes it is playing. For instance, chronic stress has been shown to affect DNA methylation, potentially leading to changes in gene expression related to mood and mental health.

On a positive note, this dynamic nature of methylation means that through healthy lifestyle choices, you can potentially reverse or mitigate negative methylation changes, thereby positively impacting your health and ageing process.


Dietary approaches


Diet plays a pivotal role in influencing methylation patterns, as your diet provides all of the fuel for methyl groups, and enzymes. Nutrients such as folate, vitamin B12, choline, and betaine are required for the conversion of homocysteine to methionine, a key step in the methylation cycle. Diets rich in leafy greens, fruits, nuts, and whole grains provide these vital nutrients, and can therefore help maintain optimal methylation levels. Emerging research suggests that dietary patterns, like the Mediterranean diet, and others with abundant whole foods, may positively influence methylation patterns, thus contributing to healthier ageing, and reduced risk of age-related diseases.

For effective methylation support, a diet rich in natural methyl donors is key. Include the following nutrient-rich food sources:

  • Folate: leafy greens, legumes, and certain fruits
  • Vitamin B12: animal proteins
  • Choline: Eggs, liver, and peanuts

Eating a diet that consists of a wide variety of wholefoods, also provides us with key phytonutrients that work as methyl-adaptogens. Methyl-adaptogens help to regulate how your body uses methyl groups, to turn on the health-promoting genes, turn off the disease-promoting genes and clear out the metabolic waste that builds up day-to-day.


Lifestyle for methylation


Lifestyle factors significantly impact methylation. Regular, moderate exercise has been shown to improve DNA methylation age, suggesting a rejuvenating effect on the body’s cells.

Adequate, high-quality sleep is essential for maintaining healthy methylation patterns, as disrupted sleep can adversely affect methylation processes.

Social connections and stress management, through practices like mindfulness and yoga, can positively influence methylation, potentially reducing the risk of chronic diseases associated with ageing. Even owning a pet has been shown to positively influence gene methylation!


Supplementing for methylation


Supplementation can be an effective strategy for supporting methylation, especially in cases of dietary insufficiency or specific genetic predispositions.

Supplements such as Vitamin B6, B12, folate, choline, and betaine play direct roles in the methylation cycle.

However, it is important that you use supplementation in a targeted way that is appropriate for your unique genetic makeup. A carefully tailored approach ensures that supplementation supports your methylation in a way that promotes overall well-being and healthy ageing.



Monitoring and testing methylation


You can test your methylation genetics, but it’s also important to see what else is playing out in the body. Testing homocysteine (a sulphur-containing amino acid) and methylmalonic acid levels (a marker for vitamin B12 status) can provide helpful additional insights.

Elevated levels of homocysteine can indicate suboptimal methylation, while elevated methylmalonic acid is a specific marker for B12 deficiency, both being useful in establishing what is happening with your methylation ability.

Deciphering these test results provides the information needed for personalising health strategies. It’s important to work with healthcare professionals who understand these results in the context of your overall health, genetics, and lifestyle factors. They can help tailor interventions to optimise methylation, potentially reducing the risk of age-related diseases and enhancing overall well-being.

Methylation plays a pivotal role in your health and ageing. By actively monitoring and optimising methylation patterns, you can take significant steps towards ageing in a healthy way, and reduce the risk of developing chronic disease. The functional medicine practitioners at Melbourne Functional Medicine can help you navigate the latest research and provide valuable guidance and strategies tailored to your individual needs.

Jabe Brown

Jabe holds a Bachelor of Health Science (Naturopathy) and a Masters in Science, Human Nutrition, and Functional Medicine. As the founder of Melbourne Functional Medicine, Jabe's focus in on delivering clinical excellence as well as growth for the business.