How does folate cause anemia?

January 2, 2026 •

3 min read

According to Johns Hopkins Medicine, folate deficiency is a primary cause of megaloblastic anemia. This condition occurs when a lack of vitamin B9 prevents the body from producing healthy red blood cells, leading to a host of health issues.

Quick Summary

A deficiency in folate, also known as vitamin B9, impairs DNA synthesis, leading to the production of abnormally large, immature red blood cells and causing megaloblastic anemia. Excessive folate intake can also mask a co-existing vitamin B12 deficiency.

Key Points

Folate deficiency causes anemia: Contrary to the title, insufficient levels of folate (vitamin B9) are what lead to megaloblastic anemia, not folate itself.
Impaired DNA synthesis: Without enough folate, the body cannot properly synthesize DNA, which is vital for the maturation of red blood cells in the bone marrow.
Megaloblasts are abnormal cells: This defect results in the creation of abnormally large, immature red blood cells called megaloblasts, which are ineffective at transporting oxygen.
Causes are multifactorial: Poor diet, alcoholism, malabsorption issues, certain medications, and increased physiological demand (like pregnancy) are common causes of folate deficiency.
Excess folate can be dangerous: High doses of folic acid can mask a co-existing vitamin B12 deficiency by treating the anemia, but it will not prevent or slow the progression of potentially irreversible nerve damage.
Diagnosis confirms deficiency: A CBC showing abnormally large red blood cells (macrocytosis) and a blood test measuring low serum folate and B12 levels are used for diagnosis.
Treatment is effective: Daily folic acid supplementation, along with dietary changes, is the standard and highly effective treatment for folate deficiency anemia.

The Critical Role of Folate in Red Blood Cell Formation

Folate, or vitamin B9, is an essential water-soluble vitamin involved in DNA and RNA synthesis, a critical process for red blood cell production. Healthy red blood cells originate as stem cells in the bone marrow, where rapid division is necessary for maturation.

How Folate Deficiency Impairs DNA Synthesis

Insufficient folate disrupts DNA synthesis during red blood cell production. This leads to precursors in the bone marrow growing larger but failing to divide properly, resulting in large, immature cells called megaloblasts.

The 'Folate Trap' and Vitamin B12 Connection

Folate and vitamin B12 are interconnected in metabolism. A lack of B12 can trap folate in an unusable form (methyl-THF), causing a functional folate deficiency within cells. This 'folate trap' explains why both deficiencies can cause megaloblastic anemia.

What Happens to Blood Cells in Folate Deficiency?

The presence of malformed megaloblasts characterizes folate-deficiency anemia. Unlike healthy red blood cells, these are large and oval-shaped. Many are destroyed in the bone marrow, and those entering circulation have a short lifespan, reducing oxygen-carrying capacity.

Consequences of Reduced Oxygen Transport:

Fatigue and Weakness: Common symptoms due to insufficient oxygen delivery.
Pallor: Pale skin can result from low red blood cell count.
Shortness of Breath: The body struggles to supply enough oxygen, especially during activity.

Common Causes of Folate Deficiency

Factors leading to low folate include:

Poor Diet: Insufficient intake of folate-rich foods is a primary cause.
Alcoholism: Chronic alcohol use hinders folate absorption and metabolism.
Malabsorption: Conditions like celiac or Crohn's disease impair folate absorption.
Increased Need: Pregnancy increases folate requirements.
Certain Medications: Some drugs interfere with folate.

The Danger of Excessive Folate: Masking a Vitamin B12 Deficiency

High-dose folic acid in those with undiagnosed B12 deficiency is risky. It corrects the anemia but hides the B12 deficiency, allowing irreversible nerve damage to progress undetected. B12 levels are checked before treating suspected folate deficiency.

Comparison of Folate Deficiency Anemia and Iron Deficiency Anemia


Feature	Folate Deficiency Anemia (Megaloblastic)	Iron Deficiency Anemia (Microcytic)
Cause	Lack of vitamin B9 (folate) impairs DNA synthesis.	Lack of iron impairs hemoglobin synthesis.
Red Blood Cells	Abnormally large (macrocytic) and immature.	Abnormally small (microcytic) and pale.
Primary Function Impaired	Cell division and maturation.	Oxygen-carrying capacity of hemoglobin.
Bone Marrow	Produces megaloblasts (large, immature precursors).	Produces microcytes (small, abnormal precursors).
Associated Symptoms	Fatigue, smooth/sore tongue, mouth ulcers, irritability.	Fatigue, weakness, pallor, pica, cold hands/feet.
Neurological Risk	Minimal neurological symptoms unless masking B12 deficiency.	Generally not associated with neurological symptoms.

Symptoms and Diagnosis

Symptoms often appear gradually and include fatigue, lack of energy, pale skin, sore tongue, and mouth ulcers. Diagnosis uses a Complete Blood Count (CBC) showing large red blood cells (high MCV), followed by blood tests for serum folate and B12 levels.

Treatment and Prevention

Treatment involves daily oral folic acid supplements and dietary changes. Ruling out B12 deficiency is crucial. Preventing deficiency involves a diet rich in folate from sources like dark leafy greens, citrus fruits, legumes, and fortified grains.

Conclusion

Folate deficiency, not folate itself, is the cause of megaloblastic anemia. A lack of this vitamin disrupts DNA synthesis, leading to fewer, large, ineffective red blood cells. Diagnosis and treatment, including supplements and diet, are essential. Understanding its interaction with B12 is vital to prevent masking serious neurological issues. Maintaining adequate folate is key to health and preventing this treatable deficiency.

For more information on folate, consult the National Institutes of Health's Office of Dietary Supplements. (https://ods.od.nih.gov/factsheets/Folate-Consumer/)

Frequently Asked Questions

Megaloblastic anemia is a blood disorder where the body produces abnormally large and immature red blood cells. It is most commonly caused by a deficiency in either folate (vitamin B9) or vitamin B12, which are essential for DNA synthesis.

No, excessive folate intake does not cause anemia directly. However, it can mask a vitamin B12 deficiency by correcting the anemia it causes. This is dangerous because the underlying nerve damage from the vitamin B12 deficiency will continue to worsen undetected.

Folate is critical for the synthesis of DNA, a process required for the rapid division and maturation of red blood cells in the bone marrow. Without sufficient folate, these cells cannot develop properly.

Common symptoms include fatigue, weakness, a sore and red tongue, mouth ulcers, pale skin, and shortness of breath. These are caused by the body's reduced ability to transport oxygen effectively.

The 'folate trap' is a metabolic issue that occurs in a vitamin B12 deficiency. It causes folate to become trapped in an unusable form, leading to a functional folate deficiency and causing megaloblastic anemia.

Diagnosis involves a physical examination and blood tests. A Complete Blood Count (CBC) will show large red blood cells, and subsequent tests will measure serum levels of folate and vitamin B12 to determine the specific cause.

Yes, folate is especially important during pregnancy due to the high rate of cell division. A deficiency can lead to severe birth defects, such as neural tube defects, in the developing fetus.

Yes, chronic and heavy alcohol use is a significant cause of folate deficiency. It can lead to poor dietary intake of folate and also impairs its absorption and metabolism in the body.

Treatment involves taking daily oral folic acid supplements to restore folate levels. Additionally, healthcare providers will recommend increasing your intake of folate-rich foods.