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What is considered very low folate?

4 min read

According to the Cleveland Clinic, a serum folate level of less than 2 nanograms per milliliter (ng/mL) is considered deficient. Understanding what is considered very low folate is critical, as a severe deficiency can lead to significant health complications, including megaloblastic anemia and birth defects.

Quick Summary

Very low folate levels are clinically defined by specific blood test results, with serum folate levels under 2 ng/mL indicating deficiency. Symptoms can include fatigue and neurological issues, caused by poor diet, medical conditions, or medications. Treatment involves supplementation and addressing the root cause. This information helps differentiate folate from B12 deficiency.

Key Points

  • Serum Levels: A serum folate level under 2 ng/mL is considered deficient, while 2-4 ng/mL is borderline.

  • Long-Term Status: Red Blood Cell (RBC) folate is a more reliable indicator of long-term status, with levels below 140 ng/mL indicating inadequate status.

  • Diverse Symptoms: Very low folate can cause megaloblastic anemia, fatigue, weakness, mouth sores, diarrhea, and neurological or psychological symptoms in severe cases.

  • Varied Causes: Common causes include poor diet, chronic alcohol use, malabsorption issues from conditions like celiac or Crohn's disease, and increased physiological needs during pregnancy.

  • Treatment Approach: Treatment involves folic acid supplements and dietary improvements, but requires careful diagnosis to differentiate from vitamin B12 deficiency.

  • B12 Distinction: Unlike folate deficiency, vitamin B12 deficiency often causes neurological damage; treating with folate alone can mask and worsen this B12-related damage.

In This Article

Defining Very Low Folate

Clinically defining very low folate depends on the type of blood test used. A serum folate test measures the amount of folate circulating in the blood, reflecting recent dietary intake. A red blood cell (RBC) folate test, on the other hand, provides a longer-term assessment of the body's folate status, as it measures the level of folate stored within the red blood cells.

Interpreting Folate Test Results

For serum folate, a value of less than 2 ng/mL is typically considered a definite deficiency, while a level between 2 and 4 ng/mL is viewed as borderline. For the more reliable long-term indicator, RBC folate, a level below 140 ng/mL is considered inadequate. Healthcare providers interpret these results alongside a complete blood count (CBC) to check for megaloblastic anemia and other markers like homocysteine and methylmalonic acid (MMA).

Symptoms of Very Low Folate

Symptoms often develop gradually and can be subtle at first, becoming more severe as the deficiency progresses.

  • Anemia Symptoms: This can include extreme fatigue, paleness, lethargy, shortness of breath, heart palpitations, and headaches, all caused by a shortage of red blood cells to transport oxygen.
  • Oral Manifestations: A sore, red, and swollen tongue (glossitis) and mouth ulcers or sores are common signs.
  • Gastrointestinal Issues: Reduced sense of taste, weight loss, loss of appetite, and diarrhea can occur.
  • Neurological and Psychological Symptoms: In severe cases, particularly if an underlying vitamin B12 deficiency is also present, symptoms can extend to memory loss, confusion, irritability, depression, or a decline in cognitive function. Nerve-related issues like tingling in the hands and feet can also develop.

Causes of Low Folate Levels

A variety of factors can contribute to low folate levels, from dietary choices to underlying health conditions.

  • Dietary Factors: The most common cause is inadequate intake of folate-rich foods, often seen in those with an unbalanced diet, excessive alcohol consumption, or specific restrictive diets. Overcooking vegetables can also destroy folate.
  • Increased Need: The body requires more folate during certain periods, such as pregnancy, breastfeeding, and infancy, due to rapid cell growth. Chronic conditions like cancer and blood disorders like sickle cell anemia also increase folate needs.
  • Malabsorption: Conditions affecting the digestive system, including celiac disease and Crohn's disease, can impair the body's ability to absorb folate.
  • Medications: Some drugs, such as certain anticonvulsants (e.g., phenytoin) and chemotherapy drugs (e.g., methotrexate), can interfere with folate absorption and metabolism.
  • Genetics: An inherited mutation in the MTHFR gene can hinder the body's ability to convert folate to its active form, potentially requiring supplementation with a different type of folate.

Diagnosis and Treatment

Diagnosis begins with a blood test to measure serum and, if necessary, RBC folate levels. It is crucial to also test for vitamin B12 deficiency, as the two can present with similar symptoms, and treating with only folate in the presence of an underlying B12 deficiency can worsen neurological damage.

Treatment for low folate typically involves:

  • Folic Acid Supplements: Oral folic acid supplements are the primary treatment for addressing the deficiency. The dosage and duration depend on the severity of the deficiency and its cause, often lasting several months.
  • Dietary Improvements: Incorporating more folate-rich foods is essential for long-term management. These include dark leafy greens, legumes, nuts, citrus fruits, eggs, and fortified grain products. Cooking methods that preserve folate, such as steaming instead of boiling, can also help.
  • Treating the Underlying Cause: If a health condition or medication is the root cause, treating that issue or adjusting medication dosages under medical supervision is necessary.

Folate vs. Vitamin B12 Deficiency: A Comparison

Feature Folate Deficiency Vitamin B12 Deficiency
Lab Findings (shared) Macrocytic anemia (large red blood cells), elevated homocysteine levels. Macrocytic anemia, elevated homocysteine levels.
Lab Findings (unique) Normal methylmalonic acid (MMA) levels. Elevated methylmalonic acid (MMA) levels.
Primary Symptoms Fatigue, weakness, mouth sores, gastrointestinal issues, irritability. Fatigue, weakness, neurological symptoms (pins and needles, memory loss, walking changes), psychiatric issues.
Neurological Impact Typically absent unless a co-existing B12 deficiency exists. Significant risk of permanent neurological damage if untreated.
Treatment Caution Folic acid supplementation can mask a co-existing B12 deficiency, worsening neurological issues. Treatment with B12 supplements or injections is required; folate alone is insufficient and dangerous.
Risk Groups Pregnant women, alcohol users, individuals with malabsorption disorders. Vegans/vegetarians, older adults, people with autoimmune conditions like pernicious anemia.

Conclusion

Understanding what is considered very low folate is vital for timely diagnosis and management. A serum level below 2 ng/mL or an RBC folate level under 140 ng/mL indicates a significant deficiency, though a healthcare provider's interpretation is essential. Symptoms range from mild fatigue to severe anemia and neurological issues, with particular risk during pregnancy. Treatment is generally straightforward with folic acid supplements and dietary changes, but it is critical to rule out vitamin B12 deficiency first. Consulting a healthcare provider for proper diagnosis and treatment is always the best course of action.

For further information on folic acid, the synthetic form of folate, and its role in pregnancy, visit the March of Dimes website.

Frequently Asked Questions

Serum folate reflects recent dietary intake and provides a short-term picture of folate levels. RBC folate, found within red blood cells, is a more accurate measure of the body's long-term folate stores, similar to how HbA1c measures long-term blood sugar.

While neurological symptoms like irritability, forgetfulness, and cognitive decline can occur with folate deficiency, severe nerve damage (peripheral neuropathy) is more characteristic of vitamin B12 deficiency. It is crucial to test for B12, as folate treatment can hide the signs of a coexisting B12 deficiency and allow nerve damage to progress.

Folic acid supplements can raise folate levels, often showing improvement within a few months of treatment. A healthcare provider will determine the appropriate dosage based on the severity of the deficiency. Additionally, eating folate-rich foods and addressing any underlying causes contribute to a quicker recovery.

The most common causes include poor diet, excessive alcohol consumption, and malabsorption syndromes like celiac disease. Increased physiological demand during pregnancy, certain medications, and some genetic mutations can also lead to deficiency.

Severe deficiency can cause symptoms such as megaloblastic anemia, extreme fatigue, paleness, glossitis (red, sore tongue), mouth ulcers, depression, and confusion. Pregnant women with severe deficiency risk serious birth defects like spina bifida.

In countries with mandatory folic acid fortification of grains, like the US and Canada, folate deficiency is relatively rare. However, it remains a concern in populations with poor dietary intake, individuals with malabsorption disorders, or those with specific genetic variations.

Yes, excessive folic acid intake can be a concern. High doses can mask a co-existing vitamin B12 deficiency, potentially worsening neurological symptoms. There are also concerns about high intake accelerating the progression of preneoplastic lesions, though more research is needed.

References

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Medical Disclaimer

This content is for informational purposes only and should not replace professional medical advice.