MTHFR & Miscarriage Risk

The secret factor you need to know about

For many women, the journey to motherhood is not as straightforward as they expected. One of the hidden culprits behind recurrent miscarriage, failed implantation, or even unexplained infertility may be a little-known gene mutation: MTHFR.

You may have heard of it in passing or had it flagged on a genetic test — but what does it really mean for your fertility, and what can you do about it?

Let’s break down what the science says.

What Is MTHFR?

MTHFR (methylenetetrahydrofolate reductase) is an enzyme responsible for converting inactive folic acid into 5-MTHF (methylfolate) — the usable form of folate your body needs for:

• DNA and RNA synthesis

• Detoxification

• Neurotransmitter production

• Homocysteine metabolism

• Cell division and placental development

There are two common MTHFR mutations:

• C677T – More strongly associated with high homocysteine and pregnancy loss

• A1298C – Has milder effects, though still impactful in combination with C677T

Depending on whether you carry one or two mutations (heterozygous or homozygous), your enzyme activity may be reduced by 30–70%, making it harder for your body to methylate properly.

MTHFR and Miscarriage Risk: What the Research Shows

The Connection Lies in Homocysteine

Women with MTHFR mutations often have elevated homocysteine levels, especially if they are:

• Not supplementing with the right form of folate

• Under chronic stress

• Deficient in B vitamins (B2, B6, B12)

• Exposure to folic acid (which is what is in “enriched/fortified foods")

High homocysteine can cause:

• Poor placental development

• Impaired blood flow to the uterus

• Increased clotting (thrombophilia)

• DNA damage during embryo development

What the Studies Say:

• A 2020 meta-analysis involving 1,125 women found that homozygous MTHFR C677T mutations significantly increased the risk of recurrent pregnancy loss (RPL)
  Source: He Y et al. "Association between MTHFR polymorphisms and risk of recurrent pregnancy loss." Genet Test Mol Biomarkers. 2020

• A study of over 200 women with recurrent miscarriage found elevated homocysteine in 43% of cases. The risk was reduced in women who took methylated folate and B12.
  Source: Nelen WL et al. "Hyperhomocysteinemia and recurrent early pregnancy loss: a meta-analysis." Fertil Steril. 2000

• Women with high homocysteine had a 2-3x higher risk of miscarriage, preeclampsia, and intrauterine growth restriction (IUGR).
  Source: Walker MC et al. "Elevated plasma homocysteine levels in early pregnancy and subsequent adverse pregnancy outcomes." Am J Obstet Gynecol. 1999

Labs to Run If You Suspect MTHFR or Miscarriage Risk

1. Genetic Testing

• MTHFR C677T and A1298C – Can be run through blood, saliva, or functional panels (DUTCH, 3x4, etc.)

2. Homocysteine

• Ideal range for fertility: <8 μmol/L

• 10 is considered elevated and can increase risk for miscarriage and cardiovascular disease

3. CRP (C-Reactive Protein)

• A marker of systemic inflammation

• Ideal: <1.0 mg/L

• Levels between 1–3 suggest mild inflammation; >3 indicates higher risk of miscarriage, especially with MTHFR or high homocysteine

4. B12 and Folate (Serum and Functional)

• Methylmalonic acid (MMA) – Functional marker of B12 deficiency

• Serum folate doesn’t distinguish between folic acid and 5-MTHF; a methylation panel may be more helpful

What To Look For in Standard Labs

Even if you haven’t done genetic testing yet, traditional labs can offer clues:

• Homocysteine<8 μmol/L, >10 indicates methylation issues

• CRP <1.0 mg/L>3 = chronic inflammation

• B12- 600–1,000 pg/mL (functional), <500 often shows symptoms despite being “normal”

• Folate- Replete with 5-MTHF, Serum folate may be falsely elevated with unmetabolized folic acid

• MCV (from CBC)- 82–92 fL, High MCV can hint at B12/folate deficiency

How to Reduce Homocysteine & CRP

Target Methylation Support:

• 5-MTHF (not folic acid): 400–800 mcg daily

• Methylcobalamin (B12): 1,000 mcg sublingual or IM/IV as needed

• P5P (active B6): 25–50 mg daily

• Riboflavin (B2): 10–50 mg, especially with C677T mutation

• TMG (Trimethylglycine) or Betaine: Helps convert homocysteine to methionine

We offer the Seeking Health Homocysteine Support and the Mind, Body, Green B Complex.

Lower Inflammation (CRP):

• Omega-3s (DHA/EPA): 1–3 g daily

• Magnesium glycinate or threonate: 300–500 mg

• Curcumin (liposomal or BCM-95): 500–1,000 mg

• Vitamin D3/K2: Aim for 50–80 ng/mL

• Address root causes: Gut dysbiosis, mold, chronic infections, insulin resistance, and unresolved trauma can elevate CRP

We offer all of these as supplement brands we trust and use ourselves.

Signals Rather Than Sentences

MTHFR mutations are not a sentence — they are a signal.
They tell us where we need to support the body more intentionally.

If you’ve experienced recurrent loss or unexplained fertility struggles, testing for MTHFR and homocysteine could reveal crucial pieces of the puzzle.

We’ve had MULTIPLE clients who either tested positive for MTHFR or presented symptoms/labs to indicate they had MTHFR, with diet changes, the right supplements, and adjustments to lifestyle they have have ALL been able to conceive naturally, and carry to term beautiful healthy babies. This may be the piece of the puzzle you are missing, we’d rather eliminate as a factor before jumping in to invasive fertility treatments.

With the right testing, nutrients, and lifestyle changes, you can dramatically reduce miscarriage risk and create the best possible environment for a healthy pregnancy and baby.