Genetics can be a bitch. Or a savior. I guess it depends on which cards you’re dealt. The Human Genome Project was completed in 2003, and we now have $2.7 billion dollars worth of data that may or may not be useful to know. Since we can’t change our genes….that we know of – gene testing largely leaves us hanging in the lurch of ‘is this a hand to hold or a hand to fold.’ Got me? Some gene testing certainly seems to fall into the category of ‘well, I’m not so sure I wanted to know that,’ but that’s not true of all of it. More and more, we’re learning that specific gene testing is useful. It is useful in the sense you may not be able to change the genes your parents are solely responsible for giving you, but you might be able to make some simple, inexpensive lifestyle changes to maximize what you got.
There’s no shortage of internet buzz about ‘methylation’ or something called ‘MTHFR’ status these days. What it means for your health, your diet, and how your individual physiology manages what you put in your body. Today, I want to do a – hopefully short – overview of a popular topic in functional medicine. A topic requested by many. One you may or may not be familiar with.
MTHFR status.
Methylation is something your liver does as part of detoxification. It’s a pretty important step – one that can affect everything from your mood to your gut function. This MTHFR situation can dramatically impact a person’s ability to do this important methylation step. If learning more about the infamous methylenetetrahydrofolate reductase or, more colloquially known as the ‘motherfucker’ gene mutation sounds interesting, then today’s topic is for you. Let’s get into it.
What is MTHFR, and Why Should You Care?
Let’s start with the basics: MTHFR stands for methylenetetrahydrofolate reductase—a mouthful, I know. From here on out, we’re calling it MTHFR. But just by looking at it you can see why people prefer to just call it the mother*er gene. MTHFR is a gene that produces an enzyme with a critical job: converting folate and folic acid, which is the synthetic version of vitamin B9, into its usable form called ‘methylfolate.’ Methylfolate is a powerhouse. It’s the active form of folate that your body uses for DNA production, detoxification, neurotransmitter synthesis, and energy metabolism.
Folate is an essential nutrient in the human body. Folate is necessary for the body to produce new cells, particularly red blood cells, and is essential for healthy cell growth and function, especially during early pregnancy to prevent neural tube defects in the developing baby; it’s found in leafy green vegetables and legumes, but we get most of our folate from grains.
Here in the US, we spray the chemical or synthetic form of folate, called folic acid, on basically all grains – wheat, corn, rice. We also ‘enrich’ foods containing grains with folic acid – things like bread, pasta, bagels, and cereal. The government started doing this in the 1980s to make sure folks were getting plenty of folic acid. That’s how important it is. Insufficient folate levels are linked to birth defects, heart disease, stroke, Alzheimer’s disease, and even cancer. Sounds like a nice gesture from the government, right?
Well…
Here’s the problem. Your body can’t actually use folic acid. It’s not a real nutrient. They engineer it in a lab somewhere. Sound familiar? What? They do! Too soon? The only way your body is able to use this synthetic nutrient is by converting it into actual folate, which it does by using an enzyme called MTHFR.
But here’s the problem: not everyone’s MTHFR gene functions at 100%. Variants—or mutations—in the gene can reduce the efficiency of this enzyme, making it difficult or damn near impossible for a person to methylate folic acid and other B vitamins properly. This might not sound like a big deal, but it can be. Too much folic acid floating around and not enough methylated folate can snowball into a whole host of issues.
- Increased homocysteine levels.
If you’re a patient at LFM, you’ve definitely seen this on your labs. Homocysteine is an amino acid that is a byproduct of protein metabolism, specifically the breakdown of methionine. It plays a crucial role in methylation pathways. You need homocysteine, but too much is no good. Normally, homocysteine is converted into other beneficial compounds, such as glutathione – the most important antioxidant in the body. When methylation is impaired—such as in individuals with MTHFR mutations—homocysteine can accumulate in the blood. Elevated homocysteine levels are associated with an increased risk of cardiovascular disease, stroke, cognitive decline, and inflammation. This is why testing homocysteine levels can be an important marker for methylation efficiency and overall health. - Impaired detoxification, making it harder for your body to clear out heavy metals, environmental toxins, and excess hormones.
- Neurotransmitter imbalances, potentially contributing to anxiety, depression, brain fog, ADHD, and mood swings.
- Chronic fatigue and energy depletion, since methylation plays a role in mitochondrial function.
- Hormonal imbalances, including PMS, PCOS, and estrogen dominance.
- Digestive dysfunction, since methylation influences gut motility and microbiome balance.
- Pregnancy complications, including miscarriage, neural tube defects, and preeclampsia.
In my clinical experience, the most commonly reported symptoms seem to hit people in the head and in the gut. Adults report lifelong anxiety, brain fog, unpredictable digestive issues, and food sensitivities. Kids often exhibit hyperactivity and difficulty concentrating in school. These issues can certainly be related to other problems, but identifying and managing symptoms related to MTHFR gene mutations are easy to diagnose and inexpensive to manage.
If you’re struggling with any of these symptoms and have tried everything without success, your methylation status might be worth investigating.
How Many People Are Affected?
Estimates suggest that up to 44% of the population has an MTHFR mutation. 44%! 44% of the population can’t process folic acid well, or not at all, and we’re ‘enriching and fortifying’ the food supply with synthetic folic acid for 100% of us. Once you go down the rabbit hole, you learn that MTHFR isn’t the only gene that can be broken in the process of methylation and detox. There’s a bunch. I’m really trying not to rabbit hole today. The two most notable MTHFR gene breaks are:
C677T – Linked to elevated homocysteine levels and increased cardiovascular risk.
A1298C – Associated with mood disorders, chronic pain, and detoxification issues.
Everyone has two copies of each of these genes – you got one from your mom and one from your dad. Some folks inherit one bad copy of a gene – we call that situation ‘heterozygous’. Others inherit two bad copies – we call that homozygous. You would be correct in assuming that having two bad copies is worse than just having one. And you’d be right again in assuming that if you have bad copies in both MTHFR genes, it’s a bigger deal than if just one of them is affected.
‘Bad’ copies of genes are called ‘SNPs’ in my business. SNP stands for ‘single nucleotide polymorphism’. Why do doctors do this fancy verbiage situation? You’ll also hear them referred to as ‘gene breaks’. More gene breaks means more impact on methylation efficiency.
Why Should You Get Tested for Methylation Issues?
Most people only find out about MTHFR after years of unexplained symptoms. The reality? Many chronic health issues—including those your doctor might brush off as “just stress” or “all in your head”—can actually be tied to inefficient methylation. Here are some reasons why testing might be a game-changer:
For Adults:
Anxiety, Depression & ADHD
Methylation is essential for making serotonin and dopamine, so dysfunction can wreak havoc on your mental health.
Brain Fog & Memory Issues
Struggling to focus? Your body may not be detoxing properly, leaving you in a fog.
Chronic Fatigue
If you feel exhausted no matter how much you sleep, your mitochondria may be struggling.
GI Dysfunction
IBS, leaky gut, and food intolerances can all be influenced by methylation status.
Cardiovascular Risk
High homocysteine levels are a warning sign for heart disease and strokes.
Infertility or recurrent miscarriages
Appropriate levels of methylated folate are required for healthy pregnancies and healthy babies. The American College of Obstetrics and Gynecology acknowledges the high incidence of MTHFR mutations in the population of childbearing women. In spite of this, their recommendation is to supplement with folic acid and not check for methylation status or use methylated folate supplements in affected women instead. Curious. If you’re a woman experiencing difficulty getting pregnant or maintaining pregnancy, consider having your methylation status evaluated. Just sayin.
For Children:
ADHD & Behavioral Issues
MTHFR mutations are associated with lower levels of dopamine, potentially affecting focus and impulse control.
Autism Spectrum Disorders (ASD)
Research suggests that methylation and detoxification play a role in neurodevelopmental conditions.
Frequent Illnesses
A sluggish detox system can make kids more susceptible to infections and toxin buildup.
Birth Defects
Again, proper methylation is critical during pregnancy, affecting everything from neural tube formation to placental health.
If you or your child have struggled with any of these issues, testing for MTHFR and homocysteine levels could offer some long-overdue answers.
The Folic Acid Trap
Now, here’s where things get spicy. The synthetic version of folate, folic acid, is found in fortified foods and most multivitamins. But if you have an MTHFR mutation, folic acid is not your friend. Instead of converting efficiently into methylfolate, it can build up in your system as unmetabolized folic acid (UMFA). This can block your body’s ability to use natural folate and even suppress immune function.
In functional medicine, we’re big fans of the whole ‘test not guess’ philosophy. Countless companies offer testing for MTHFR status. Because it’s a gene test, it only needs to be done once in your whole life. Unless we get into the business of genetic modification with experimental gene therapies or injections. That’s obviously an editorial theoretical. Anyway – If you happen to have one or more of these MTHFR gene breaks, you can bypass the problem altogether by taking supplements that contain methylated folate and B vitamins. And maybe some magnesium, B2, B6, and TMG. Sorry – too far in the weeds here. These methylated supplements are already in their active form, so your body doesn’t have to do the work that it is genetically incapable of doing. It’s like getting a pre-peeled orange—you’re skipping the heavy lifting.
Practical Takeaways for MTHFR Mutations
If you’ve tested positive for an MTHFR mutation (or suspect you might have one), here are some actionable steps:
Get Tested
As previously mentioned, there are many companies that do methylation testing with blood or saliva. Since your genes don’t change, this is a once in your lifetime test. They’re not a million dollars – money well spent in my opinion.
Upgrade Your Supplements
Swap out folic acid for methylated folate (5-MTHF). Pair it with methylcobalamin (B12) for maximum benefit. And magnesium – everyone is deficient in magnesium and this helps the whole detox system work better.
One more thing about B12 – or cobalamin. Most commercially available B12 comes in the form of something called ‘cyanocobalamin’, which is code word for we made this B12 supplement with hydrogen cyanide. And we snuck it in your multivitamin, your protein powder, your kids’ cereal, and your energy drinks just to see if it would kill you. Just kidding, Cyanocobalamin is the only synthetic form of B12. They make it with hydrogen cyanide (an industrial waste product) because it’s cheap. The Redditors will tell those of us in the wellness space to stop blathering on about this, citing ‘there’s only a little bit of poison’ in cyanocobalamin. OK – we agree on this. Poison has a dose. But don’t you get enough poison in your life? These poisons accumulate over time, and a little bit of poison suddenly becomes a hell of a strain on your detox system. Do your liver a favor, and don’t consume anything with ‘cyanocobalamin’ in it.
Methylcobalamin, hydroxocobalamin, and adenosylcobalamin are way safer alternatives and just plain easier for your body to assimilate. Enough ranting on that – moving on.
Eat Folate-Rich Foods
Focus on leafy greens, asparagus, avocado, and lentils. Read labels and don’t buy grain containing foods labeled as ‘fortified’ or ‘enriched’.
Check Your Homocysteine Levels
This simple, inexpensive blood test is a pretty good proxy indicator for whether your methylation pathways are struggling. If you’re supplementing with B vitamins and your homocysteine level is over 8 or 10, there’s a high likelihood that you have one or more methylation gene breaks.
Support Detox Pathways
Use practices like infrared sauna, Epsom salt baths, and liver-supportive foods (beets, artichokes, dandelion greens).
Manage Stress
Methylation is closely tied to stress, so incorporating meditation, yoga, or deep breathing can make a real difference. Adrenal support with adaptogens and CBD oil are also extremely beneficial.
Conclusion: Your Genes Aren’t the Boss of You
Understanding your MTHFR status is empowering. Knowledge is power. With an easy test and a few supplement and dietary tweaks, you can support your body, prevent disease, and optimize health. Your genes may set the stage, but your daily choices determine the outcome. Small, intentional changes can have a profound impact on how you feel, how you function, and your long-term well-being.
So, if you’ve been wondering whether those “folic acid-free” labels on supplements are just marketing—spoiler alert: they’re not. The right form of nutrients matters. Take control of your health, work with your genetics, and unlock your body’s full potential.
