Is an MTHFR Test Worth Your Time and Money?

Why Your MTHFR Gene Status May Not Offer Much Clinical Value

New genetic test technology has made it possible to order your own MTHFR test through consumer-based gene testing services. MTHFR gene variants have been proposed as a cause of symptoms from fatigue to brain fog, to hormonal imbalances, and more. But is this test really necessary?

At best, the consensus about how to use MTHFR gene testing is controversial and still being debated [1 Trusted SourcePubMedGo to source, 2 Trusted SourcePubMedGo to source, 3 Trusted SourcePubMedGo to source, 4 Trusted SourcePubMedGo to source]. In this article, we’ll cover what the MTHFR gene is and what it does, what an MTHFR test tells you, and why MTHFR testing likely isn’t necessary. We’ll also discuss how to address health issues you think may be caused by MTHFR.

MTHFR test: DNA strand inside a test tube filled with red liquid

What Is the MTHFR Gene?

MTHFR (methylene-tetra-hydro-folate reductase) refers to a gene and the enzyme created by that gene. The MTHFR enzyme helps convert dietary folate (vitamin B9) into methylfolate, the usable form

Specific variations in your MTHFR genes have been proposed as risk factors for certain health conditions, like cardiovascular disease, chronic pain, depression, and even autism. However, the best available evidence suggests that having specific MTHFR gene variants doesn’t increase your risk factors for these health conditions [5].

What Does An MTHFR Test Tell You?

You may have turned to MTHFR testing in an attempt to explain persistent symptoms, like fatigue or brain fog. So let’s consider what you can learn from an MTHFR test.

An MTHFR genetic test tells you which MTHFR gene variants you have. MTHFR tests are either a simple blood test collected in a lab or run on a saliva sample collected at home. 

But what do the possible gene variants do, and what do they mean?

What Are Gene Variants?

You inherit one copy of each gene from your parents. You might receive the same variant from both of your parents (homozygous) or different variants from each parent (heterozygous).

Common MTHFR Variants

Most genetic tests check for the following common MTHFR variants. There is very little evidence to suggest having one of these variants leads to symptoms.

MTHFR C677T is the most common variant. Those who have two copies of the C677T  variant may have a 70% reduction in normal MTHFR enzyme production [6 Trusted SourcePubMedGo to source].

The MTHFR A1298C variant is less common. Those who have two copies of this variant have 40% less MTHFR enzyme production [6 Trusted SourcePubMedGo to source].

Combined variants: People can also have one copy of the C677T gene and one copy of the A1298C gene; they are considered “double heterozygous” and may have reduced MTHFR enzyme production as well [6 Trusted SourcePubMedGo to source].

A note about “MTHFR mutations”: These MTHFR gene variations are often referred to in the media as genetic mutations. But researchers note that the C677T and A1298C variants are more accurately “polymorphisms” or normal gene variants. Gene variants mildly affect gene function and generally don’t cause noticeable health problems, while mutations drastically affect function, and may cause congenital health problems, nutrient deficiencies, or birth defects. 

People with true MTHFR gene mutations can have a condition called homocystinuria, which can cause neurological defects, gait problems, and psychiatric disorders. These are extremely rare and are not caused by C677T or A1298C variants [7]. 

MTHFR test: Tired woman rubbing her eyes

Should You Get an MTHFR Test?

Testing for MTHFR variants has limited usefulness and should be considered for informational purposes only. Two separate literature reviews, which included meta-analyses, found, at best, a minimal clinical utility for MTHFR polymorphism testing [6 Trusted SourcePubMedGo to source, 8 Trusted SourcePubMedGo to source].

This is because knowing which gene variants you have tells you very little about what is actively contributing to your symptoms. Your genes never change, but their function is heavily influenced by your diet and lifestyle habits.

A more useful way to test for the possible effects of MTHFR variants is to first run blood tests to measure:

If these tests show elevated homocysteine levels or very low folate values, there are plenty of diet and lifestyle options for addressing these imbalances. Running a genetic test won’t provide any additional specific recommendations.

Can MTHFR Variants Cause Symptoms?

Many people want to do an MTHFR test because they think it will explain symptoms such as fatigue, brain fog, or hormone imbalances, or it will recommend particular dietary or supplementation advice. 

The truth is that there is very little data to suggest that MTHFR gene polymorphisms cause any noticeable symptoms or health conditions [5]. Many of the attributed symptoms are caused by much more common problems, such as gut imbalances or a poor diet.

Though much has been written about the risks of MTHFR variants, research suggests that 85% of people have at least one variant, which implies that having MTHFR gene variants may be normal [5].

MTHFR ‘Symptoms’ May Be Coming From Your Gut

You can’t change your genes, but you can affect your health with diet and lifestyle interventions. 

Research shows many symptoms commonly attributed to MTHFR variants may be affected by your gut health and/or diet. For example, fatigue and brain fog are often associated with MTHFR variants. However, studies show these symptoms strongly correlate with gut imbalances.

Consider fatigue. A meta-analysis found that 40% of IBS patients had fatigue [11 Trusted SourcePubMedGo to source], and fatigue is also common for people with non-celiac gluten sensitivity [12 Trusted SourcePubMedGo to source] and leaky gut [13 Trusted SourcePubMedGo to source, 14 Trusted SourcePubMedGo to source]. Brain fog is also associated with IBS, celiac disease, and non-celiac gluten sensitivity [15, 16, 17]. 

Before assuming your symptoms are caused by your genes, doing a comprehensive health assessment with a skilled functional medicine healthcare provider can help you determine your root causes and help you avoid chasing red herrings. (Learn more about becoming a patient in our clinic.)

Smiling woman leaning on a wooden table with a bowl of salad and fresh ingredients in front of her

Diet To Support MTHFR Function

A whole foods diet rich in healthy sources of proteins, fats, fiber, and carbohydrates, like the paleo diet, can improve your gut health, and reduce the risk of inflammatory health conditions, like heart disease, that are often associated with MTHFR variants [18 Trusted SourcePubMedGo to source].

A healthy diet is also rich in dietary sources of folate, which can support your body’s ability to produce adequate MTHFR enzymes. Common folate sources include [6 Trusted SourcePubMedGo to source]:

  • Fruits
  • Green leafy vegetables
  • Fortified breads and cereal grains
  • Lentils, chickpeas, and most beans
  • Asparagus
  • Spinach 

MTHFR and Methylfolate

Proponents of MTHFR testing claim that those with MTHFR variants should avoid supplementation with the more-common folic acid and should instead use methyl-folate. This reasoning is often used as a justification for doing genetic testing to uncover MTHFR variants.

Supplementing folate may be helpful, as low folate levels do indeed contribute to an increased risk of [19]:

  • Neural tube defects and spina bifida during pregnancy
  • Certain types of anemia
  • Dementia
  • Stroke and thrombosis (blood clots)
  • Certain types of cancer, including colorectal, prostate, and breast cancer
  • High levels of homocysteine, an amino acid that is associated with cardiovascular disease and high blood pressure [6 Trusted SourcePubMedGo to source, 20 Trusted SourcePubMedGo to source]

Folate deficiencies are especially concerning to expecting mothers. Because supplementation with folic acid can take upwards of nine months to get to sufficient levels [10 Trusted SourcePubMedGo to source, 21 Trusted SourcePubMedGo to source, 22 Trusted SourcePubMedGo to source], supplementation should start long before trying to conceive.

However, a 2016 literature review concluded that there is no significant evidence that MTHFR gene variants have a clinically relevant effect on your folate metabolism [23].

While it’s true that neural tube defects appear to be slightly more common for women who have two copies of an MTHFR variant [24], the American College of Medical Genetics recommends 0.4 mg of folic acid per day for all women of childbearing age, regardless of MTHFR status [25 Trusted SourcePubMedGo to source].

Similarly, a large Chinese study that showed folic acid supplementation reduced the risk of stroke by 30% indicated that special supplementation is not necessary for those with MTHFR variants to enjoy the benefits of folate [26 Trusted SourcePubMedGo to source].

In short, the evidence suggests that folic acid supplementation is enough to protect you against folate deficiencies [3 Trusted SourcePubMedGo to source, 27]. There is no need to take special methylfolate supplements. 

Probiotics Supplements and MTHFR

Triple probiotic therapy can be a powerful reset for your gut health, which is a more likely source of your MTHFR symptoms than your gene variants

Probiotics have been shown in many studies to reduce leaky gut [28 Trusted SourcePubMedGo to source, 29 Trusted SourcePubMedGo to source, 30 Trusted SourcePubMedGo to source] and inflammation [31 Trusted SourcePubMedGo to source], crowd out bad bacteria [32 Trusted SourcePubMedGo to source, 33 Trusted SourcePubMedGo to source, 34 Trusted SourcePubMedGo to source], and improve symptoms such as diarrhea [35 Trusted SourcePubMedGo to source, 36 Trusted SourcePubMedGo to source], constipation [37 Trusted SourcePubMedGo to source, 38 Trusted SourcePubMedGo to source], and bloating [39 Trusted SourcePubMedGo to source, 40 Trusted SourcePubMedGo to source]. 

Probiotics have also been shown to reduce homocysteine levels and increase B vitamin levels [41 Trusted SourcePubMedGo to source].

The Bottom Line About MTHFR Tests

There is very little evidence to suggest that knowing your MTHFR gene status is important for your day-to-day health. Though MTHFR status may affect your folate levels, the folic acid you consume through dietary intake and supplementation should be adequate. Meanwhile, improving your gut health and diet are shown by research to improve supposed MTHFR symptoms.

If you have questions about how to work with your MTHFR status, get qualified medical advice from your healthcare provider, or apply to become a patient at our clinic.

➕ References
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