What illnesses cause folate deficiency?

November 14, 2025 •

4 min read

According to the CDC, folate deficiency has become much less common in countries with mandatory food fortification, but it still occurs, particularly due to underlying medical conditions. Several illnesses and health-related factors can disrupt the body's ability to absorb, process, or retain this vital B vitamin.

Quick Summary

Several medical conditions, including malabsorption disorders, inflammatory diseases, and certain genetic mutations, interfere with the body's folate levels. Chronic alcohol use, kidney dialysis, and some medications also contribute to this deficiency, often leading to anemia and other symptoms.

Key Points

Celiac Disease: An autoimmune disorder damaging the small intestine, it causes malabsorption of nutrients, including folate, leading to anemia.
Inflammatory Bowel Disease (IBD): Conditions like Crohn's disease cause chronic inflammation in the gut, hindering folate absorption and increasing deficiency risk.
Chronic Alcoholism: Heavy alcohol use impairs folate absorption, disrupts liver metabolism, and increases excretion, commonly causing deficiency.
Kidney Dialysis: The dialysis process can remove folate from the bloodstream, making regular supplementation necessary for patients with end-stage kidney disease.
Certain Medications: Drugs such as methotrexate and sulfasalazine interfere with folate metabolism and absorption, requiring careful medical monitoring.
MTHFR Gene Mutation: A common genetic variation can reduce the body's ability to convert folate into its active form, potentially causing higher homocysteine levels.
Psoriasis: The rapid turnover of skin cells in this condition increases the body's demand for folate, which can deplete stores if not managed.
Chronic Hemolytic Anemia: The accelerated destruction and replacement of red blood cells significantly increases the body's need for folate, which can cause a deficiency.

Folate, also known as vitamin B9, is a crucial nutrient for DNA synthesis and repair, cell growth, and red blood cell formation. While diet is a primary factor, several underlying illnesses and medical treatments can disrupt the body's folate balance, leading to a deficiency. This comprehensive guide explores the key medical conditions that jeopardize folate status.

Malabsorption Disorders

Chronic illnesses that damage the small intestine can severely hinder the body's ability to absorb nutrients, including folate, which is primarily absorbed in the proximal jejunum.

Celiac Disease

Celiac disease is an autoimmune condition where gluten consumption triggers an immune response that damages the small intestinal lining. This damage, characterized by villous atrophy, reduces the surface area available for nutrient absorption, resulting in deficiencies of iron, vitamin D, vitamin B12, and folate. A strictly gluten-free diet is essential for gut healing and restoring folate levels, although supplementation may still be necessary.

Crohn's Disease

As a form of inflammatory bowel disease (IBD), Crohn's disease causes chronic inflammation of the digestive tract. Inflammation and damage to the small bowel can directly impair folate absorption. Additionally, some medications used to treat Crohn's, such as methotrexate and sulfasalazine, are folate antagonists, further increasing the risk of deficiency.

Alcoholism and Liver Disease

Chronic and excessive alcohol consumption is a significant and common cause of folate deficiency due to a multi-faceted impact on folate metabolism.

Poor Diet: Individuals with alcohol use disorder often have a poor diet, substituting food with alcohol and thus having insufficient folate intake.
Impaired Absorption: Alcohol interferes with the absorption of folate in the small intestine.
Metabolic Disruption: Chronic alcohol exposure disrupts folate metabolism in the liver, the body's primary storage site for folate. It decreases hepatic uptake and storage of folate.
Increased Excretion: Alcohol increases urinary folate excretion, leading to greater loss of the vitamin from the body.

Increased Demand for Folate

Some medical conditions and physiological states increase the body's need for folate beyond normal dietary intake, risking a deficiency if the demand is not met through diet or supplementation.

Chronic Hemolytic Anemia

In conditions like sickle cell anemia, red blood cells are destroyed faster than they can be replaced. The body's increased production of new red blood cells to compensate for the loss requires a higher amount of folate, as it is essential for red blood cell formation.

Psoriasis

Psoriasis is an inflammatory skin condition characterized by rapid turnover of skin cells. The excessive consumption of folate needed for this accelerated cell division can lead to lower folate levels. Psoriasis is also linked to elevated homocysteine levels, which folate helps to metabolize.

Kidney Disease and Dialysis

Patients with end-stage kidney disease who undergo dialysis are at a high risk of folate deficiency. The dialysis process itself can remove folate from the blood, and many patients may have nutritional deficiencies due to dietary restrictions and malnutrition associated with their illness.

Genetic Factors: MTHFR Gene Mutation

The methylenetetrahydrofolate reductase (MTHFR) gene mutation affects an individual's ability to convert folate into its active form, 5-methyl-THF. While many people with this common mutation are asymptomatic, some may have lower serum folate levels and higher homocysteine levels, especially if their diet is low in folate.

Comparison of Folate-Impacting Conditions


Condition	Primary Mechanism	Impact on Folate	Other Key Symptoms
Celiac Disease	Small intestine damage leading to malabsorption.	Decreased absorption from food.	Diarrhea, weight loss, abdominal pain.
Crohn's Disease	Intestinal inflammation and drug side effects.	Impaired absorption and reduced levels due to medication.	Abdominal pain, fatigue, weight loss.
Alcoholism	Impaired absorption, metabolism, and increased excretion.	Significantly reduced folate levels.	Fatigue, neurological issues, liver damage.
Dialysis	Removal of folate during treatment.	Increased folate loss from the body.	Fatigue, anemia, elevated homocysteine.
MTHFR Mutation	Impaired conversion to active folate.	Lower active folate and higher homocysteine.	Often asymptomatic; can be linked to higher homocysteine.

Medications That Cause Folate Deficiency

Certain medications can interfere with folate absorption and metabolism, even in individuals with a balanced diet. It is essential for patients taking these drugs to be monitored by a doctor to prevent deficiency.

Methotrexate: A potent folate antagonist used for autoimmune diseases like psoriasis and Crohn's. It inhibits the enzyme responsible for converting folate to its active form, and supplementation with folic or folinic acid is often required.
Sulfasalazine: Used for inflammatory bowel diseases, this medication is known to impair intestinal folate absorption.
Anticonvulsants: Some anti-seizure medications, including phenytoin, phenobarbital, and carbamazepine, can interfere with folate metabolism.
Metformin: Used to manage blood sugar in type 2 diabetes, metformin can affect vitamin B12 absorption, and by extension, impact folate metabolism through the methylation cycle.

Conclusion

While a poor diet is a common cause, many illnesses and treatments can also lead to folate deficiency by impeding absorption, accelerating utilization, or interfering with metabolism. Conditions like celiac disease, inflammatory bowel disease, chronic alcoholism, and kidney dialysis significantly increase the risk. Additionally, genetic predispositions, such as the MTHFR mutation, can affect folate processing. For those with compromised folate status due to an underlying medical condition, medical supervision and supplementation may be necessary to prevent complications like anemia, fatigue, and other health issues. Addressing the root cause, along with appropriate medical management, is key to restoring healthy folate levels.

Frequently Asked Questions

Early symptoms often include fatigue, weakness, a sore or tender tongue, mouth sores, and pale skin. These can be subtle at first but may worsen over time.

Not always, but it is a common complication due to the small intestine damage that impairs nutrient absorption. Adherence to a gluten-free diet and sometimes supplementation can resolve the issue.

Chronic alcohol consumption interferes with folate absorption in the gut, disrupts its metabolism in the liver, and increases its excretion through the kidneys. Poor diet often associated with heavy drinking also contributes.

Several drugs interfere with folate, including methotrexate, sulfasalazine, certain anticonvulsants (like phenytoin), and metformin. Your doctor should monitor your folate levels if you are on these medications.

Yes, it is common in patients with end-stage kidney disease, particularly those on dialysis. The dialysis process can filter folate from the blood, necessitating regular supplementation.

The MTHFR gene provides instructions for making the MTHFR enzyme, which is needed to convert folate into its active form. A mutation can impair this conversion, potentially leading to lower active folate levels and elevated homocysteine.

Yes, psoriasis can cause folate deficiency due to the accelerated turnover of skin cells. The rapid division of cells consumes more folate, potentially depleting the body's reserves.

Folate is essential for the production of healthy red blood cells. A deficiency leads to the production of abnormally large, immature red blood cells, resulting in a condition called megaloblastic anemia.