In short: The MTHFR gene mutation affects how the body processes folate and homocysteine. Whether the mutation is expressed (meaning it impacts enzyme function and biochemical pathways) or not expressed (present but not causing functional changes) determines whether symptoms or health risks appear. Most carriers have no symptoms, but in some cases, elevated homocysteine levels can lead to cardiovascular, neurological, or pregnancy-related complications.
🧬 Understanding Gene Expression
• Gene basics: Genes are segments of DNA that provide instructions for making proteins. The MTHFR gene encodes the enzyme methylenetetrahydrofolate reductase, which helps process folate and regulate homocysteine levels.
• Expression: A gene is expressed when its instructions are actively used to produce a protein. Expression can be influenced by environment, diet, and other genetic factors.
• Mutation vs. variant: A mutation (or variant) is a change in the DNA sequence. Not all mutations are harmful—many are common and benign.
⚖️ Expressed vs. Non-Expressed Mutations
• Expressed mutation: The altered gene produces a protein with reduced or altered function. For MTHFR, this can mean less efficient folate metabolism and higher homocysteine levels.
• Non-expressed mutation: The gene variant exists in DNA but does not significantly change protein function or cause symptoms. Many people carry MTHFR variants without health issues.
🩺 Symptoms and Associated Conditions
Most people with MTHFR mutations are asymptomatic. When expressed, possible outcomes include:
• Elevated homocysteine (hyperhomocysteinemia): Can damage blood vessels and increase clot risk.
• Cardiovascular issues: Higher risk of heart disease, stroke, or thrombophilia (blood clots).
• Neurological effects: Peripheral neuropathy, dementia, or learning difficulties in rare cases.
• Pregnancy complications: Neural tube defects (spina bifida, cleft lip/palate) if folate intake is insufficient.
• Other associations: Depression, certain cancers, and drug sensitivity (e.g., methotrexate toxicity).
🌍 Prevalence and Impact
• The C677T variant is common: up to 40% of White and Hispanic populations carry it.
• The A1298C variant occurs in ~7–12% of North American and European populations.
• Most carriers live normal, healthy lives, especially with adequate folate intake.
🥦 Practical Considerations
• Folate intake matters more than genotype. The CDC emphasizes that 400 mcg of folic acid daily supports healthy folate levels regardless of MTHFR status.
• Testing: Genetic testing is available but not routinely recommended, since most variants don’t cause disease.
• Management: If homocysteine is high, doctors may recommend folic acid, vitamin B6, and B12 supplementation.
✅ Key takeaway: Having an MTHFR mutation doesn’t automatically mean health problems. What matters is whether the mutation is expressed in a way that alters enzyme function and raises homocysteine. With proper folate intake, most people—even those with common variants—remain healthy.
Reasons Someone Might Get Tested
• Unexplained elevated homocysteine: If bloodwork shows high homocysteine, testing can help identify whether MTHFR variants are contributing.
• Family history of clotting disorders: Testing may be considered if relatives have thrombophilia, recurrent blood clots, or early cardiovascular disease.
• Pregnancy complications: Women with recurrent miscarriages, preeclampsia, or a child with a neural tube defect may be tested to see if folate metabolism is impaired.
• Neurological or psychiatric concerns: Some clinicians test when patients have depression, anxiety, or cognitive decline linked to folate metabolism, though evidence is mixed.
• Drug sensitivity: Certain chemotherapy drugs (like methotrexate) interact with folate pathways, so testing may guide treatment.
Reasons Someone Might Not Get Tested
• Variants are common and often harmless: Up to 40% of people carry MTHFR variants, most without symptoms or health risks.
• Limited clinical utility: The CDC and many medical organizations note that MTHFR testing rarely changes treatment, since folate supplementation is recommended for everyone.
• Folate intake matters more: Regardless of genotype, adequate folic acid intake prevents most complications.
• Potential anxiety or confusion: A positive test may cause unnecessary worry if the variant is benign or not expressed.
• Cost and insurance coverage: Testing may not be covered, and results often don’t alter medical management.
🩺 Practical Guidance
• When testing is useful: If someone has unexplained high homocysteine, recurrent clotting, or pregnancy complications, testing may provide context.
• When it’s not: For the general population, routine testing is not recommended. Folate supplementation is the standard preventive measure.
• Alternative approach: Measuring homocysteine directly is often more clinically relevant than genetic testing.
Folate-rich foods include legumes, leafy greens, citrus fruits, and fortified grains—excellent choices for supporting hormone health and reducing homocysteine levels.
Top Natural Sources of Folate
These foods contain folate in its natural form, which is easily absorbed and beneficial for cellular repair and hormone metabolism:
🌿 Leafy Greens
• Spinach (1 cup raw): ~58 mcg
• Kale, arugula, romaine: ~40–60 mcg per cup
• Rich in vitamin K and antioxidants
🫘 Legumes
• Lentils (1 cup cooked): ~358 mcg
• Kidney beans (1 cup cooked): ~131 mcg
• Chickpeas, black beans, peas: ~100–300 mcg per cup
• Also high in fiber and plant protein
Cruciferous & Green Veggies
• Asparagus (½ cup cooked): ~134 mcg
• Broccoli (1 cup cooked): ~84 mcg
• Brussels sprouts: ~47 mcg per ½ cup
🍊 Citrus Fruits
• Oranges (1 medium): ~40 mcg
• Grapefruit, papaya, strawberries: ~20–60 mcg
• Also provide vitamin C for collagen and immune support
Eggs
• 1 large egg: ~22 mcg
• Contains B12 and choline—important for brain and hormone health
References:
- MTHFR Gene Variant and Folic Acid Fact, CDC, May 2025 MTHFR Gene Variant and Folic Acid Facts | Folic Acid | CDC
- MTHFR Gene Mutation: Tests, Treatments, and Symptoms, Web MD, Sept 22,2024 MTHFR Gene Mutations: What You Need to Know
- What is an MTHFR Gene Mutation, Medical News Today Aug 21, 2025 MTHFR mutation: Symptoms, testing, and treatment