How much do genetics really matter?
Is nature more important than nurture? Should I do genetic testing or will it just tell me what my bloodwork already shows?
I get these questions a lot. What we know about our genes is like a snowflake on the tip of an iceberg. That said, there are a few genetic variants I see matter a lot in daily practice. The one I hear patients and friends talking about the most is APOE for Alzheimer’s. But the gene I see having perhaps a more frequent impact, on everything from mental health to fertility, is MTHFR.
MTHFR is an acronym for a gene in the body, and it’s a mouthful: methylenetetrahydrofolate reductase. Like all genes, you have two copies of MTHFR. Variants on one or both copies mean the resulting MTHFR enzyme is significantly less active, which can impair the body’s ability to process folate and increase levels of the amino acid homocysteine.
MTHFR variants are wildly common—more people in the United States have one or two variants than don’t, according to the CDC. (Certain variations are more common in certain geographic regions. In Australia, for example, as many as 60-70% of people have at least one of the most common MTHFR variations. Globally, an estimated 25% of people have at least one MTHFR gene variation.)
If MTHFR variations have the potential to cause health issues, why are they so common? At a certain point in our evolutionary history, they must have been adaptive. One hypothesis: certain MTHFR variations might have protected our ancestors from solar radiation.
In our modern environment, however, MTHFR mutations are complicated.
I personally have a double variant in one of my MTHFR genes. I know this because I did genetic testing when I was first training in functional medicine and it’s changed the way I approach my health. Here’s how:
The research says
A lot of genetic markers aren’t actionable. Variations on the ACTN3 (Alpha-Actinin-3) gene, for example, can influence whether your body is better suited to endurance exercise or power-based sports like sprinting. It’s good to know, but there’s likely nothing you can do to change that predisposition.
But a lot of genetic variations are actionable. Knowing your genes can help you lower your disease risk, improve metabolic health, and overhaul your mental health.
At Parsley we use advanced genetic tests to analyze how your genes affect metabolism and nutrient absorption, thyroid function and hormone metabolism, and anxiety and mood.
Knowing you have an MTHFR variation is not only actionable, it can be hugely impactful for optimizing your nutrient intake and—potentially—lowering your disease risk.
MTHFR variations can cause:
- Low levels of folate. Folate is essential for making and repairing DNA, neurotransmitter production, and supporting fetal development. Studies suggest that people with the C677T MTHFR polymorphism may have lower levels of folate and benefit from supplementation. (More on that later.) Folate deficiency can be the cause of fatigue, weakness, depression, and gastro issues.
- High levels of homocysteine. Low serum folate levels can lead to undesirably high levels of the amino acid homocysteine, which may cause two issues: increased inflammation, which is linked to a greater risk of heart disease, and impaired function of neurotransmitters (including serotonin, dopamine, and GABA), which is linked to decreased mood and cognitive function.
- Reduced methylation capacity. Methylation is your body’s ability to turn genes on and off, which is crucial for cell function, the proper absorption of nutrients, and your cells’ ability to process and eliminate toxins like heavy metals.
Beyond these three issues, a large body of research has explored the downstream effects of MTHFR variations on increased risk of disease. But the evidence is often conflicting or inconclusive.
So, what does that mean for your health? The following associations shouldn’t cause panic but could be a nudge to work with a functional medicine practice to assess your risk of certain diseases that may be impacted by MTHFR.
For example, there is evidence that MTHFR mutations may play a role in:
- Preventable cardiovascular disease. The C677T MTHFR mutation is correlated with increased blood pressure and higher total cholesterol, LDL cholesterol and triglycerides. A 2021 study found these links plus an increase in markers of inflammation—all risk factors for cardiovascular disease.
- The development of certain types of cancers. Including breast cancer, colon cancer, and cervical cancer.
- Impaired fertility. At least some evidence has linked MTHFR mutations to recurrent pregnancy loss, male infertility, impaired IVF outcomes (including reduced oocyte maturation potential and poorer embryo quality), and diminished ovarian reserve. The evidence is not considered conclusive enough at present to warrant testing for MTHFR before trying to conceive. If you have concerns about a family history or recurrent losses, talk to your doctor about whether testing might make sense for you.
- Cognitive decline including Alzheimer’s and dementia. Elevated homocysteine levels have been associated in some studies with a higher risk of cognitive disease. But most meta-analyses find the link between MTHFR and long-term brain health to be either inconsistent or to vary widely across populations.
- Psychiatric disorders. Researchers are also investigating MTHFR mutations—specifically the C677T and A1298C polymorphisms—and psychiatric disorders. But again, the results aren’t consistent across all groups. One review of 81 studies published in Frontiers in Neuroscience in 2022, for example, found links between MTHFR mutations and major depressive disorder, bipolar disorder, and schizophrenia in Asian populations but not caucasians.
Here’s what I take away:
MTHFR is actionable and impacts your body’s ability to regulate mood, fully absorb nutrients, and rid itself of common toxins. When it comes to supporting optimal cell function, cognitive health, heart health, and fertility, MTHFR can have real-time impact for many of us.
MTHFR may impact your risk of disease but that risk is highly individualized and is best assessed with the help of a functional medicine physician who can help you understand the whole picture of your health.
What I’m doing for my own body
Here’s how I used the knowledge of my MTHFR variants to improve my personal health:
Detoxing heavy metals
In my 30s as I was preparing to get pregnant, I learned I had bioaccumulated a lot of mercury (I was a big tuna eater in my 20s). I was taking in all this mercury, but likely because of my sluggish MTHFR-influenced detox pathways, I was not able to safely process and eliminate it (and other toxic heavy metals).
I went through heavy metal detox, aka chelation therapy, before getting pregnant to help safely remove these metals from my system.
Taking methylated supplements
When I was in college, I took Zoloft for a year for mild depression. I haven’t taken medication since then, a shift I attribute mostly to my yoga and spirituality practice. But I also use what I’ve learned about the MTHFR variant to support my mental wellbeing.
People with MTHFR variants have trouble converting inactive forms of folate and B12 found in many foods and supplements into their active, usable forms. Taking a methylated (i.e. active) form of these micronutrients bypasses any sluggishness of the MTHFR enzyme so that your body can use it.
Most supplements on the market aren’t (including multivitamins) methylated. I take Parsley’s Daily Dose Multivitamin plus 1 milligram of methylated folate and 1mg of methylated B12 every day.
When I don’t take the latter, the difference in my mood is remarkable. It helps with better focus, better clarity, and positivity.
What I recommend for you
The only way to know if you have an MTHFR variation is through a genetic blood test that looks for variations in the MTHFR gene. Come test with us at Parsley.
Here’s what I recommend:
Test your homocysteine levels
This is another way to make an educated guess about your MTHFR gene. If your homocysteine levels are high, you likely have an MTHFR variant and would benefit from methylated supplementation for heart health.
Optimize folate intake
Supplementing with folic acid can help increase blood folate levels in patients with MTHFR variants. I recommend supplementing with 1 mg of a methylated form of folate (L-5-MTHF) to bypass the conversion issue.
Support methylation pathways
To support methylation pathways in the body (key for cell function, detoxing, and nutrient absorption) take B-complex vitamins with active forms of B12 (methylcobalamin or adenosylcobalamin). I recommend 1 mg for patients with MTHFR mutations.
Since B12 is water soluble, you can take a higher dose—some people find 5 mg is even better for their mental clarity and mood while others find the higher dose agitating or too energizing. I don’t personally find that, but I also don’t find massive benefits from taking 5 mg vs. 1 mg.
If you don’t know your MTHFR status, there is little downside to taking a methylated multi or prenatal vitamin and seeing how you feel. Occasionally, people report feeling agitated with methylated B vitamins, but it’s rare in my experience. If you feel that way, you can simply stop and take a non-methylated version.
Make a prenatal plan
I bias towards getting more information over less pre-pregnancy. I want to help patients optimize outcomes and have the healthiest pregnancies possible. So because MTHFR may have implications for fertility, I want to know about it as a physician.
I recommend working with a functional medicine practitioner or fertility specialist to make a prenatal plan. That might include higher doses of methylfolate, which a lot of general prenatals don’t include. (One of the many reasons I love Ritual’s prenatal, which includes 1 mg 6S-5-methyltetrahydrofolate and 8 mcg methylcobalamin.)
Set up a free consult call with my team at Parsley to learn about the genetic tests we offer as well as specialty tests to measure homocysteine levels and inflammation. Use my code RBMDCREW for $150 off your membership.
As always, this newsletter is for informational and educational purposes only and is not intended as medical advice. Always consult your healthcare provider before making any health decisions or changes to your treatment plan.