In our latest episode of “Ask NP Deidre,” I had the opportunity to discuss a critical yet often overlooked risk factor for cardiovascular disease and Peripheral Artery Disease (poor leg circulation) with Nurse Practitioner Deidre Arms from Aspire Wellness and Integrative Health. Our conversation revealed why homocysteine testing should be a standard consideration for anyone concerned about their heart health or with a family history of cardiovascular issues.

Homocysteine is an amino acid produced in our bodies when we break down methionine, which is found in protein-rich foods like eggs, meat, and dairy. Normally, our bodies recycle homocysteine using B vitamins, particularly B6, B12, and folate (B9). However, when this process doesn’t work efficiently, homocysteine can build up in the bloodstream.

“When homocysteine becomes elevated, it can become dangerous to the arteries and damage blood vessel walls,” explains NP Deidre. “It can trigger inflammation and make your blood more likely to clot.”

Think of elevated homocysteine as “nails on your artery walls,” causing damage that leads to plaque buildup and stiffening of the arteries. This damage significantly increases the risk of coronary artery disease (blocked arteries in the heart) and peripheral artery disease (blocked arteries in the legs).

Why Isn’t This Tested More Often?

Despite being listed on the American Heart Association website as something that should be checked, homocysteine testing isn’t typically included in routine labs. When I asked NP Deidre why this enzyme isn’t more well-known, she responded, “I think it doesn’t fall into a routine lab, but it’s easy for us to check. Many people aren’t aware of what this enzyme does in the body.”

In my own casual experiment, I asked ten people to get their homocysteine levels checked, and nine out of ten had elevated levels. This striking result raises questions about why testing isn’t more widespread, particularly for individuals with risk factors for heart disease.

What Causes Elevated Homocysteine?

Several factors can contribute to high homocysteine levels:

1. B Vitamin Deficiencies: Insufficient levels of B6, B12, and folate are primary causes.
2. Genetic Mutations: Approximately 40% of the population carries a genetic variant called MTHFR (methylenetetrahydrofolate reductase) that affects how the body processes folate and regulates homocysteine levels. Recent research has confirmed that MTHFR gene mutations can lead to hyperhomocysteinemia, a known risk factor for venous thromboembolism and cardiovascular disease.
3. Poor Absorption: Even with normal B vitamin levels in blood tests, those with the MTHFR gene mutation may not be able to convert folate into its active form (5-MTHF), impairing methylation and leading to elevated homocysteine.

NP Deidre explains: “If you are somebody who has that genetic mutation MTHFR gene, that reduces your ability to convert folic acid into the active form of 5-MTHF, the methyl form. This impairs methylation, leading to homocysteine levels becoming elevated.”

Early Warning Signs

Elevated homocysteine is what NP Deidre calls “the canary in the coal mine” - an early warning signal that your body is under metabolic stress. However, many people dismiss potential symptoms as just part of life or stress.

Common symptoms of high homocysteine can include:

• Brain fog
• Fatigue
• Hormone imbalances (potentially affecting fertility)
• Joint issues (particularly after eating enriched products)
• Cognitive issues (seen in people with Alzheimer’s or cognitive decline)

Testing and Treatment

The good news is that once identified, elevated homocysteine levels can be addressed effectively. NP Deidre recommends checking homocysteine levels alongside B vitamin levels, as this provides a more complete picture of your methylation status.

“You can have a normal looking B vitamin level but have an elevated homocysteine. That lets us know you’re not methylating properly, and you probably have that genetic mutation in MTHFR, which is very common,” she explains.

For treatment, NP Deidre recommends:

1. Methylated B Vitamins: Using the methyl form of B vitamins, which are better absorbed, especially for those with MTHFR mutations.
2. Dietary Changes: Working with a dietitian to eliminate foods with fortified or synthetic folate, particularly in enriched bread and cereal products.
3. Early Detection: “If the homocysteine level is elevated, it’s giving you an early warning sign that your body is under metabolic stress. And then we have action to take,” says NP Deidre.

Special Considerations for Pregnancy

Our conversation took an important turn toward pregnancy considerations. With approximately 40% of people carrying the MTHFR gene mutation, prenatal nutrition becomes even more critical.

NP Deidre cautions: “When you’re taking prenatals, what you’re looking for is one with the form of methylfolate that is better absorbed. But if you are eating fortified folates in your food, it’s like mopping your floor with dirty boots - you are literally negating the good stuff that you’re doing.”

For women with recurrent pregnancy loss, testing for MTHFR mutations and homocysteine levels can be particularly important. While medical guidelines typically recommend such testing after three pregnancy losses, NP Deidre often considers these tests earlier, especially when family history suggests a genetic predisposition.

Taking Action

If you’re concerned about your homocysteine levels, NP Deidre suggests having an open conversation with your healthcare provider. Explain that this is a modifiable risk factor for heart disease that can be easily tested and treated.

For those whose providers are hesitant, functional health lab testing is an alternative option that often includes homocysteine markers at a reasonable cost.

The ideal homocysteine level according to functional medicine standards is 7 or below, though conventional medicine often sets the cutoff at 10.

Why This Matters

Catching elevated homocysteine early could potentially prevent or delay the onset of atherosclerosis and reduce your risk of heart disease and peripheral artery disease. As someone who discovered my own MTHFR mutation and elevated homocysteine levels in my 40s (while my father wasn’t diagnosed until his late 70s), I can attest to the importance of early detection. My primary care physician has me on a regular methylated B vitamin and I’ve already met with a Cardiologist to establish a baseline.

By addressing this “little known enzyme” now, you might be preventing serious cardiovascular complications later in life. As NP Deidre puts it, “There’s actionable things that we can do when we know.”

Want to learn more? Visit AspireWIH.com to learn about Nurse Practitioner Deidre Arms and her telemedicine services available in multiple states. Follow her YouTube channel @NPDeidre for more health insights.

Are you experiencing leg cramps, leg pain, neuropathy, diabetes, leg numbness and tingling, or burning feet? These could be signs of peripheral artery disease. Call the Global PAD Association’s Leg Saver Hotline at 1-833-PAD-LEGS to discuss your symptoms, find a testing site for poor circulation, and get help finding a doctor who treats advanced peripheral artery disease.

Sources:

1. Liu F, Silva D, Viteri Malone M, Seetharaman K. MTHFR A1298C and C677T Polymorphisms Are Associated with Increased Risk of Venous Thromboembolism: A Retrospective Chart Review Study. Acta Haematol. 2017.
2. Bhatt RD, Karmacharya BM, Shrestha A, et al. Prevalence of MTHFR C677T polymorphism and its association with serum homocysteine and blood pressure among different ethnic groups: insights from a cohort study of Nepal. BMC Cardiovasc Disord. 2025.
3. Yu Y, Shao L, Zhang M, et al. MTHFR variant links homocysteine metabolism and endothelial cell dysfunction by targeting mitophagy in human thoracic aortic dissection patient induced pluripotent stem cell (iPSC) models. Journal of Advanced Research. 2025.
4. American Heart Association. “Homocysteine, Folic Acid and Cardiovascular Disease.” heart.org.

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