What medical conditions cause low folic acid?

November 14, 2025 •

4 min read

According to the Cleveland Clinic, one of the most common causes of folate deficiency, or low folic acid, is not eating a balanced diet rich in fruits and vegetables, but underlying medical conditions also play a significant role. These health issues can interfere with the body’s ability to absorb, metabolize, and utilize this crucial B vitamin, leading to a host of health problems.

Quick Summary

Several medical issues can lead to folic acid deficiency, primarily affecting absorption, increasing demand, or interfering with metabolism. Key contributors include intestinal disorders like celiac disease, chronic alcohol misuse, liver disease, kidney dialysis, certain genetic mutations, and medications.

Key Points

Malabsorption is a primary cause: Disorders affecting the small intestine, like celiac disease and Crohn's, significantly reduce the body's ability to absorb folic acid, even with adequate dietary intake.
High demand can cause deficiency: Rapid cell turnover, such as during pregnancy or in chronic hemolytic anemias like sickle cell disease, increases the body’s need for folate, leading to depletion.
Chronic alcohol use is a major factor: Long-term heavy drinking impairs absorption, metabolism, and storage of folate, while also often coinciding with a poor diet.
Liver function is critical for storage: As the main site of folate storage, a compromised liver due to conditions like cirrhosis or fatty liver disease can lead to low folic acid levels.
Certain medications deplete folate: Several common drugs, including methotrexate, some anticonvulsants, and sulfasalazine, can interfere with folate metabolism or absorption.
Genetic factors play a role: Mutations in the MTHFR gene or conditions like hereditary folate malabsorption can hinder the body's conversion and transport of folate.
Kidney dialysis removes folate: The dialysis process removes folate from the blood, requiring regular supplementation for patients to prevent deficiency.

Folic acid, or folate (its natural form), is a vital B vitamin essential for DNA synthesis, cell growth, and red blood cell production. When medical conditions disrupt the body's folate balance, it can lead to deficiency and a type of anemia called megaloblastic anemia. Understanding these underlying health issues is crucial for proper diagnosis and treatment.

Malabsorption Disorders

Many gastrointestinal conditions can impair the small intestine's ability to absorb nutrients, including folate, leading to a deficiency even with adequate dietary intake.

Celiac Disease

This autoimmune disorder triggers an immune response to gluten, which damages the lining of the small intestine. The resulting inflammation and villous atrophy (flattening of the finger-like projections that absorb nutrients) severely impede the absorption of vitamins and minerals, including folic acid. Studies confirm a high prevalence of folic acid deficiency among patients with active celiac disease.

Inflammatory Bowel Disease (IBD)

Chronic inflammation of the digestive tract is the hallmark of IBD, which includes Crohn's disease and ulcerative colitis. Malabsorption is common in IBD due to bowel inflammation, surgical removal of parts of the intestine (especially the ileum where folate is absorbed), and a reduced appetite due to symptoms like diarrhea and abdominal pain. Some studies show that nearly 30% of Crohn's disease patients and 9% of ulcerative colitis patients can develop folic acid deficiency.

Tropical Sprue

This condition causes the small intestine's lining to flatten and not absorb nutrients properly. Although the exact cause is unknown, it is a significant cause of folate malabsorption in tropical regions.

Conditions Involving Increased Cellular Turnover

Certain conditions cause the body to produce or turn over cells at an accelerated rate, dramatically increasing the demand for folate, which can quickly deplete the body's reserves.

Pregnancy

During pregnancy, the demand for folate increases significantly to support rapid fetal growth and cell division. The Centers for Disease Control and Prevention (CDC) recommends that women who are pregnant or planning to become pregnant take a daily folic acid supplement to reduce the risk of neural tube defects like spina bifida.

Chronic Hemolytic Anemia

This group of disorders involves the premature destruction of red blood cells, forcing the bone marrow to work overtime to produce replacements. The high demand for folate in this accelerated erythropoiesis can lead to a deficiency. Sickle cell disease is a prime example where chronic hemolytic anemia is a major factor contributing to low folic acid levels, necessitating lifelong supplementation.

Certain Cancers

Some cancers, especially those with rapid cell division, can increase the body's folate demand. This can be further exacerbated by cancer treatments and associated complications like poor nutrition.

Psoriasis

This chronic inflammatory skin condition is characterized by rapid turnover of skin cells. This process increases the body's use of folate, leading to lower-than-normal levels in some patients, though the link to deficiency is still under investigation.

Diseases Affecting Folate Metabolism and Storage

The liver is the primary storage site for folate in the body, and its proper function is critical for folate metabolism.

Chronic Alcoholism

Excessive alcohol consumption is a major cause of folate deficiency. Alcohol disrupts folate absorption, interferes with its metabolism, and increases folate excretion through the kidneys. Many individuals with alcohol use disorder also have a poor diet, further contributing to the deficiency.

Liver Disease

Conditions like non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), and cirrhosis can lead to reduced folate storage and metabolism. As liver disease progresses, serum folate levels tend to decrease.

Genetic Mutations

Polymorphisms in the MTHFR gene, which encodes the enzyme methylenetetrahydrofolate reductase, can impair the body's ability to convert folic acid into its active, usable form (5-MTHF). This affects approximately 25% of the Hispanic population, 10% of white and Asian populations, and 1% of the Black population. Hereditary folate malabsorption is a rarer genetic disorder that directly impacts the transport of folate.

Other Causes and Contributing Factors

Kidney Dialysis

Patients undergoing hemodialysis for kidney failure are at risk of folate deficiency because the procedure removes folate from the blood. Regular supplementation is typically needed for these patients to prevent complications.

Medications

Several prescription drugs are known to interfere with folate absorption or metabolism, including:

Methotrexate: Used for cancer, rheumatoid arthritis, and psoriasis, it is a folate antagonist.
Anticonvulsants: Some seizure medications like phenytoin, phenobarbital, and primidone.
Sulfasalazine: Used for ulcerative colitis and Crohn's disease.
Trimethoprim: An antibiotic.

Comparison Table of Folic Acid Deficiency Causes


Cause Category	Specific Condition/Factor	Mechanism of Deficiency	Risk Level
Malabsorption	Celiac Disease	Damage to small intestine lining prevents absorption.	High
	Crohn's Disease	Intestinal inflammation and surgical resections reduce absorptive surface.	High
Increased Demand	Pregnancy/Lactation	Rapid fetal and maternal cell growth increases folate requirements.	High
	Hemolytic Anemia	High red blood cell turnover rate depletes folate stores.	High
Metabolic/Storage	Chronic Alcoholism	Impaired absorption, metabolism, and liver storage.	High
	Liver Disease	Decreased liver storage and metabolic function.	Moderate to High
	MTHFR Polymorphism	Genetic mutation impairs conversion of folate to active form.	Variable
Other	Kidney Dialysis	Folate is filtered out of the blood during the process.	High
	Certain Medications	Drugs like methotrexate interfere with absorption or metabolism.	Moderate to High

Conclusion

While a poor diet is a common cause, low folic acid is frequently a consequence of underlying medical conditions that affect how the body absorbs, uses, or stores this vital nutrient. Malabsorption disorders like celiac and Crohn's disease, heightened demands from conditions such as pregnancy and hemolytic anemia, and factors that impair metabolism and storage like chronic alcohol use and liver disease are all major contributors. Certain medications and genetic predispositions can also significantly deplete folate levels. It is essential for individuals experiencing symptoms of deficiency, such as fatigue or megaloblastic anemia, to consult a healthcare professional to identify the root cause and determine the appropriate treatment. For more information on folate deficiency, refer to authoritative sources such as Cleveland Clinic on Folate Deficiency.

Frequently Asked Questions

Celiac disease is an autoimmune condition where ingesting gluten causes inflammation and damage to the lining of the small intestine. This damage reduces the surface area available for absorbing nutrients like folic acid, leading to a deficiency over time.

Yes, several medications can interfere with the body's ability to absorb or utilize folic acid. Noted examples include methotrexate (used for cancer and autoimmune diseases), some anticonvulsants (epilepsy medications), and sulfasalazine (used for inflammatory bowel disease).

Chronic excessive alcohol consumption is a significant cause of folate deficiency because it interferes with folate absorption, inhibits metabolism, and reduces the liver's ability to store the vitamin. Alcohol misuse is also often associated with a poor diet, which further depletes folate stores.

During pregnancy, the body's demand for folic acid increases dramatically to support the rapid growth and development of the fetus's cells, including the brain and spinal cord. This elevated need can lead to deficiency if not adequately supplemented.

Yes, genetic mutations can impact folate levels. For instance, a common polymorphism in the MTHFR gene can impair the enzyme responsible for converting inactive folic acid into its active form, leading to lower usable folate. A rare inherited disorder called hereditary folate malabsorption also affects folate transport.

The liver is the main storage organ for folate. In liver diseases like cirrhosis and non-alcoholic fatty liver disease, impaired liver function reduces its capacity to store and metabolize folate, leading to lower levels in the body.

Some research suggests that patients with psoriasis have lower folate levels, potentially due to the rapid turnover of skin cells. This increased cellular activity may heighten the body's demand for folate, though further study is needed to fully understand this connection.