Can Folate Cause Neutropenia? Separating Fact from Deficiency

December 14, 2025 •

3 min read

While most are familiar with the benefits of folate, a lesser-known fact is that a deficiency can impair the body's ability to produce new blood cells, including neutrophils. This raises a key question: can folate itself, in excess, cause neutropenia? The evidence shows the opposite is true for healthy individuals.

Quick Summary

Folate deficiency is a direct cause of neutropenia, while excess folate is not considered a direct cause in healthy individuals. Concerns primarily relate to excess masking a vitamin B12 deficiency.

Key Points

Folate Deficiency is the Cause: Low folate, not high folate, is a recognized cause of neutropenia due to impaired DNA synthesis in bone marrow.
No Evidence for Excess Folate: Medical consensus and recent guidelines state there is no evidence that excess folate causes neutropenia in otherwise healthy people.
B12 Deficiency Masking: The primary risk of excess folic acid is its ability to mask a concurrent vitamin B12 deficiency, which can have severe neurological consequences.
Chemotherapy Interactions: Some studies suggest that high serum folate might exacerbate chemotherapy-induced reductions in neutrophil counts, though this is not a direct cause.
Supplementation Corrects It: In cases of folate deficiency, appropriate supplementation can reverse the neutropenia and other cytopenias.
High Dose ≠ Toxicity: Oral administration of folate in recommended dosages is generally considered non-toxic, with excess being excreted in urine.

What is Neutropenia?

Neutropenia is a condition characterized by an abnormally low count of neutrophils, a type of white blood cell crucial for fighting infections. The severity of neutropenia varies and can be temporary or chronic. A low neutrophil count leaves the body vulnerable to bacterial and fungal infections. Various factors can cause neutropenia, including genetic conditions, infections, autoimmune disorders, and certain nutritional deficiencies.

The Surprising Truth: Folate Deficiency Causes Neutropenia

Folate is a B vitamin essential for DNA synthesis and cell division. The bone marrow, responsible for blood cell production, is particularly sensitive to folate levels. A deficiency impairs DNA synthesis, leading to megaloblastic anemia, where abnormally large, immature red blood cells are produced. This impairment affects the production of all blood cells, including neutrophils, leading to neutropenia. Treating folate deficiency with folic acid supplementation is a standard way to correct this.

The Misconception: Can Excess Folate Cause Neutropenia?

For the general population, the idea that excess folate causes neutropenia is largely a misconception. Scientific reviews find no evidence that high folate intake directly causes neutropenia in healthy people. Concerns about excess folate are usually related to other issues.

The Critical Danger of Masking Vitamin B12 Deficiency

High intake of synthetic folic acid can mask a vitamin B12 deficiency. Both deficiencies can cause megaloblastic anemia and low blood counts, but only B12 deficiency leads to irreversible nerve damage. High-dose folic acid can correct the anemia without addressing the B12 deficiency, allowing neurological damage to worsen. Therefore, checking B12 levels before high-dose folic acid therapy is crucial.

Limited Evidence from Animal Studies and Contextual Findings

Some research has explored very high folate levels. A mouse study in 2017 suggested that excessive folic acid might impair blood cell production pathways but did not show a direct causation of neutropenia. Animal study results don't always apply to humans.

Another study in 2004 found that women receiving chemotherapy with higher serum folate levels experienced a greater drop in neutrophil count during treatment. This indicates a potential interaction exacerbating the effects of chemotherapy, not that high folate independently causes neutropenia.

Comparison Table: Folate Deficiency vs. Excess Folate


Feature	Folate Deficiency	Excess Folate (Synthetic Folic Acid)
Effect on Neutrophils	A known cause of neutropenia due to impaired blood cell production.	Not a direct cause of neutropenia in healthy individuals; some studies show it can exacerbate chemotherapy effects.
Mechanism of Action	Impaired DNA synthesis leads to megaloblastic anemia and decreased production of all blood cell types in the bone marrow.	At high levels, can mask an underlying vitamin B12 deficiency, potentially allowing neurological damage to worsen.
Associated Condition	Megaloblastic anemia; can present with pancytopenia.	Can worsen or hide a vitamin B12 deficiency.
Resolution	Symptoms resolve with appropriate folate supplementation.	No evidence of reversal for neutropenia since it does not cause it.

Conclusion

In summary, folate deficiency is a well-established cause of neutropenia and megaloblastic anemia. There is no evidence that excess folate directly causes neutropenia in healthy individuals. The main risk of excessive synthetic folic acid intake is masking a concurrent vitamin B12 deficiency, which can lead to serious neurological damage. While interactions exist in specific scenarios like chemotherapy, excess folate isn't considered an independent cause of neutropenia. If you are concerned about your blood counts, a healthcare provider can perform tests to identify the cause. Maintaining a balanced diet or following recommended supplementation is advised. An authoritative source on folate and B vitamin intake can be found at the NIH Office of Dietary Supplements.

Frequently Asked Questions

Yes, folate deficiency can lead to neutropenia by impairing the production of blood cells, including neutrophils, within the bone marrow.

Folate is crucial for DNA synthesis. A deficiency leads to impaired cell division, particularly in rapidly dividing cells like those in bone marrow, causing megaloblastic anemia and other low blood counts, including neutrophils (neutropenia).

While excess folate from food is harmless, very high doses from supplements can have side effects, most notably masking a vitamin B12 deficiency. It is not established as a direct cause of neutropenia.

High-dose folate can correct the anemia caused by B12 deficiency, but it will not fix the underlying neurological damage, allowing it to progress unnoticed and potentially become irreversible.

The tolerable upper intake level (UL) for synthetic folic acid from supplements and fortified foods is 1,000 mcg per day for adults, according to the NIH Office of Dietary Supplements.

Some older studies, particularly concerning chemotherapy, have observed that higher folate levels were associated with a greater decrease in neutrophil count during treatment. This is a specific context, not a general causation.

Following folate supplementation, leukopenia and thrombocytopenia generally resolve within 2 to 4 weeks as bone marrow function recovers.