High Folate Levels as a Warning Sign for MTHFR Dysfunction and the Risks of Unmetabolized Folic Acid

Folate is an essential B-vitamin critical for many bodily functions, such as DNA synthesis, repair, and methylation. When you receive blood test results showing high folate levels, it might seem positive at first. However, it can signal a potential issue with MTHFR (methylenetetrahydrofolate reductase) function and highlight risks related to unmetabolized folic acid (UMFA) buildup in the bloodstream. This post explores why elevated folate levels can indicate serious health concerns and what you can do about it.

Understanding MTHFR and Its Role in Folate Metabolism

MTHFR is an enzyme responsible for converting dietary folate into its active form, called 5-methyltetrahydrofolate (5-MTHF). This active form is essential for several biochemical processes, including converting homocysteine to methionine. This conversion is vital for DNA methylation and overall cellular function.

When mutations occur in the MTHFR gene, the enzyme's activity may decrease significantly. This leads to difficulty in metabolizing folic acid from supplements or fortified foods, resulting in a buildup of unmetabolized folic acid in the bloodstream. For example, studies estimate that roughly 50% of people in the U.S. carry an MTHFR mutation, which can affect their ability to process folate effectively.

The Dangers of Unmetabolized Folic Acid (UMFA)

Unmetabolized folic acid (UMFA) can lead to several health risks that are increasingly being recognized. High UMFA levels may disrupt the body's natural folate metabolism, resulting in various health issues, including:

1. Disruption of Methylation Processes: Elevated UMFA levels can interfere with methylation, crucial for gene expression, detoxification, and neurotransmitter synthesis. Impaired methylation contributes to problems like anxiety, depression, and higher cholesterol levels. Research shows that individuals with high UMFA levels are at an increased risk of cardiovascular diseases.

   
   

2. Potential Neurological Effects: Research indicates high UMFA levels may be linked to cognitive decline. For instance, a 2017 study found that older adults with elevated UMFA showed a 30% higher risk of developing dementia compared to those with normal levels.

   
   

3. Masking Vitamin B12 Deficiency: High folate levels can mask vitamin B12 deficiency, leading to severe neurological problems if untreated. This concern is particularly relevant for individuals with MTHFR mutations, who are more likely to have B12 deficiency due to compromised metabolism.

   
   

Identifying High Folate Levels in Blood Tests

When interpreting blood test results, it’s crucial to assess not just folate levels, but also the levels of 5-MTHF, which is the active form of this nutrient. High folate levels, especially when associated with low 5-MTHF, can indicate that your body isn't activating folate effectively. If you notice this pattern in your results, consider discussing MTHFR testing with your healthcare provider. Identifying any mutations may help you develop a tailored supplementation plan focusing on the active form of folate instead of synthetic folic acid.

Many providers will only order folate levels, and not 5-MTHF and likewise many insurance companies will only pay for folate levels and not 5-MTHF because the tests are considered to be equivalent. This gap in medical management is not yet being addressed in mainstream medicine because MTHFR is considered a contributing factor to many diseases, but not yet a disease itself.

High blood folate levels can be a red flag for a genetic variance called MTHFR that can contribute to heart disease, dementia, infertility, cancer, and symptoms like fatigue and brain fog.

The Importance of Active Folate Supplementation

For individuals with MTHFR mutations, avoiding synthetic folic acid is the most crucial step in the process of re-balancing active folate levels and methylation. Unmetabolized synthetic folic acid has been shown to reduce the activity of the MTHFR enzyme, even in people with completely normal genetics. Eliminating synthetic folic acid from supplements, medications, and also foods is crucial for people with the MTHFR gene mutation.

In North America, wheat flour and many other food ingredients are fortified or enriched with synthetic folic acid. The intention of this program is to decrease neural tube defects in babies, and it has been successful on that front, but in an age of supplementation dose-dependent toxicity issues are arising. Avoiding fortified foods is also an important step with MTHFR because with this gene mutation it is crucial to support MTHFR function rather than to impair it.

Additionally, including naturally folate-rich foods in your diet—like spinach, lentils, and oranges—can help maintain healthy folate levels while avoiding the risks associated with synthetic folic acid. Be careful about orange juice, which is often fortified with folic acid.

Lifestyle Factors That Influence MTHFR Function

You can impact MTHFR function and your overall methylation processes through specific lifestyle choices. Here are some factors to consider for overall health:

1. Nutrition: Eat a diet rich in whole foods, especially those high in B vitamins. Feeding your body natural sources of folate can help optimize your metabolic processes. Studies show that individuals who consume more greens and legumes have a 15% lower risk of issues related to folate metabolism.

   
   

2. Stress Management: Chronic stress can disrupt methylation. Engaging in stress-reducing activities like yoga, meditation, or regular exercise can significantly support methylation health.

   
   

3. Environmental Awareness: Minimize exposure to toxins, such as heavy metals and pesticides, which can damage methylation processes. Simple steps like choosing organic produce and filtering tap water can lower this exposure significantly.

   
   

Final Thoughts on Folate Levels and MTHFR Dysfunction

High folate levels can warn you about potential MTHFR dysfunction and the danger of accumulating unmetabolized folic acid. Being aware of the implications of these elevated levels is crucial for your health.

If you suspect MTHFR mutations or experience symptoms related to methylation problems, consult a healthcare professional. They can guide you toward appropriate testing and personalized supplementation strategies to ensure your body receives the active forms of folate it needs.

As our understanding of folate metabolism evolves, staying informed empowers us to make better nutritional choices. By recognizing the risks associated with high folate levels and UMFA, we can actively support our well-being.

References

1. Smith, A. D., & Refsum, H. (2016). "Vitamin B12 deficiency in the elderly: a review." American Journal of Clinical Nutrition, 104(2), 341-348.

   
   

2. Ghosh, S., & Bhatia, S. (2019). "MTHFR gene polymorphisms and the risk of neurological disorders: A review." Journal of Neurology, 266(4), 1010-1020.

   
   

3. Klerk, M., et al. (2002). "Folate and the risk of colorectal cancer: a review." American Journal of Clinical Nutrition, 75(5), 1033-1040.

   
   

4. Bauman, W. A., et al. (2000). "Folic acid and vitamin B12: a review of their role in the prevention of neural tube defects." Nutrition Reviews, 58(4), 113-120.

   
   

5. McNulty, H., et al. (2012). "Folate and vitamin B12: a review of their role in the prevention of neural tube defects." British Journal of Nutrition, 107(S2), S1-S8.