MTHFR Mutations: What They Mean & How They Can Affect Your Health.
I talk about MTHFR gene mutations with clients all the time, and they also get mentioned in the holistic health space quite often. So let’s go through what it actually is, and what it means for your health.
What is MTHFR?
MTHFR (aka methylenetetrahydrofolate reductase) is an enzyme that is involved in our folate-methylation cycle. This is a crucial process that facilitates the metabolism of folate into its active form (5-MTHF), while also creating our body’s universal methyl donor, SAMe. We rely on this process to be able to convert folate into a form that our body can actually use. It also supports methylation reactions throughout the whole body, thanks to SAMe. Methylation reactions are involved in so many different processes throughout the body, including detoxification and hormone metabolism, neurotransmitter production, DNA synthesis and gene regulation, immune system regulation, and many other cellular processes.
What are the most common MTHFR variants?
An MTHFR genetic variant is an inherited genetic SNP. We receive 1 copy of the gene from each parent.
There are two common MTHFR mutations: C677T and A1298C. You can have either a homozygous (2 copies), heterozygous (1 copy) or compound heterozygous (1 copy of each) mutation. Typically, heterozygous mutations will not have a huge impact on health, as long as dietary, lifestyle and environmental factors are kept in check. The C677T mutation generally has a more profound impact than A1298C, though everybody is different!
MTHFR and homocysteine
MTHFR mutations can cause an increase in homocysteine, as the MTHFR enzyme supports the recycling of homocysteine back into methionine. This is especially noted with the C677T variant.
This is problematic as persistently elevated homocysteine is associated with increased oxidative stress and inflammation, and may negatively impact cardiovascular health. It has also been associated with fertility issues, pregnancy complications, and neurological health concerns, including depression.
However - it is important to note that homocysteine levels can still be managed with an MTHFR variant. Nutrient status, lifestyle, and other genetic factors can also influence levels.
Does having an MTHFR mutation mean you can’t methylate?
The answer to this is no. You can absolutely still methylate - the process may just be down-regulated and less efficient.
There are a list of epigenetic factors that can significantly interfere with MTHFR-functioning. Individuals with MTHFR mutations may need to keep on top of overall health to ensure the folate-methylation cycle continues to run smoothly.
These factors can include:
Nutrient deficiencies: folate, vitamins B12, B6, B2, choline
Inadequate protein and methionine intake
Chronic stress
Poor gut health
Overexposure to environmental toxins
Alcohol intake
Certain medications
Other genetic SNPs that impact the folate-methylation cycle or other methylation processes in the body.
Should I take methyl-folate, folinic acid or folic acid?
You do not necessarily need to take a folate supplement at all, unless specifically required. Adding more folate to the picture can actually make your symptoms worse if the folate-methylation cycle’s capacity is impaired.
Folic acid is the synthetic form of folate that cannot be efficiently processed by our folate-methylation cycle. Doses exceeding 200-400mcg can cause the folate-methylation cycle to become blocked - in individuals with MTHFR mutations, this dose is likely to be lower.
Folinic acid may be a better starting point for individuals who are sensitive to methylated supplements or for those who have folate receptor autoantibodies in the brain (as sometimes seen in autism).
Methyl-folate should be used under practitioner guidance, once the folate-methylation cycle has been “opened”.
Signs you may have an MTHFR genetic variant
History of mental health complaints
Personal or family history of cardiovascular disease
Neurodevelopmental delays in children
Immune system over- or under-activity
Chronic fatigue
Unexplained infertility
Sensitivity to environmental toxins
Sensitivity to supplements or medications
Note: these symptoms cannot diagnose MTHFR SNPs, and can have many other underlying causes.
You may also have an MTHFRn genetic variation and experience no symptoms at all.
Remember: your genes are not your destiny.
The MTHFR gene is one small piece of your individual biology. Understanding your genetic makeup can provide valuable information about how your body may process certain nutrients or how you may respond to lifestyle and environmental factors - but the goal is not to “fix” your genes... that would be impossible!
The goal is to create a stable internal environment that supports optimal enzyme function and reduces the potential impact of genetic variations on your health. This is done by understanding your individual needs and making changes to your diet, lifestyle and environment to support your body functioning at its best.