Understanding What Underlying Conditions Cause Low Folate? Beyond Simple Dietary Intake

October 11, 2025 •

4 min read

According to the National Institutes of Health, folate is a water-soluble B vitamin essential for numerous bodily functions, including DNA synthesis and cell growth. When dietary intake is adequate but folate levels remain low, it is crucial to investigate what underlying conditions cause low folate, as the reasons often extend beyond simple malnutrition.

Quick Summary

Low folate levels can be caused by various underlying conditions that impair absorption or metabolism, including digestive disorders like celiac and Crohn's disease, genetic mutations, specific medications, and chronic alcohol use. A diagnosis requires professional medical evaluation.

Key Points

Malabsorption Diseases: Conditions like celiac and Crohn's disease can damage the intestinal lining, preventing adequate folate absorption even with sufficient dietary intake.
Genetic Mutations: A common genetic mutation in the MTHFR gene can impair the body's ability to convert folate into its active form, leading to functional deficiency.
Medication Interference: Certain drugs, including methotrexate and some anticonvulsants, are known to interfere with how the body absorbs or utilizes folate, requiring special medical management.
Chronic Alcohol Use: Excessive alcohol consumption significantly impacts folate absorption, metabolism, and excretion, often contributing to deficiency in individuals with alcohol use disorder.
Physiological Stress: Increased demand for folate during pregnancy, lactation, or due to conditions like hemolytic anemia can deplete the body's reserves if not met with increased intake.
Professional Diagnosis is Key: Given the complexity of potential causes, a healthcare provider should always diagnose low folate through blood tests and identify the specific underlying reason before starting supplementation.

Why Diet Alone Isn't the Whole Story

While a diet lacking in folate-rich foods is a primary cause of deficiency, relying solely on dietary adjustments may not be enough for some individuals. In many cases, an underlying medical issue prevents the body from properly absorbing, metabolizing, or retaining this essential B vitamin. Folate (or vitamin B9) is vital for forming healthy red blood cells and for producing DNA and RNA. When levels are insufficient due to an internal condition, it can lead to various health problems, including megaloblastic anemia, fatigue, and other neurological symptoms.

Malabsorption Syndromes and Digestive Diseases

Your digestive system is where folate is absorbed, and any condition that damages the small intestine can significantly impair this process. These are some of the most common underlying causes:

Celiac Disease: An autoimmune disorder where consuming gluten leads to damage in the small intestine's lining. This villous atrophy reduces the surface area available for nutrient absorption, including folate.
Crohn's Disease: A type of inflammatory bowel disease (IBD) that causes chronic inflammation of the digestive tract. This inflammation can interfere with the gut's ability to absorb nutrients, leading to deficiencies over time.
Tropical Sprue: A condition characterized by damage to the small intestine lining, resulting in malabsorption. It is most common in tropical climates and often requires antibiotics and nutritional supplements for treatment.
Intestinal Surgery: Surgical procedures that involve removing or bypassing large portions of the intestines, such as bariatric surgery, can reduce the body's ability to absorb folate.

Genetic and Metabolic Conditions

Some people are predisposed to low folate levels due to their genetic makeup or inherited metabolic disorders. These conditions affect how the body processes folate even when sufficient amounts are consumed.

MTHFR Gene Mutation: A mutation in the methylenetetrahydrofolate reductase (MTHFR) gene affects about 25% of Hispanic people and 10% of white people, and it can significantly hinder the body's ability to convert folate to its active, usable form (5-MTHF). This is one of the most common genetic causes of low folate.
Hereditary Folate Malabsorption: This is a rare, inherited disorder that specifically affects the body's ability to absorb folate from the intestines and transport it into the brain and other tissues.
Enzyme Deficiencies: Various congenital enzyme deficiencies can impact folate metabolism, preventing the body from utilizing it correctly.

Medications that Interfere with Folate

Certain medications can interfere with folate absorption and metabolism. If you are taking any of the following, your doctor may recommend monitoring your folate levels or taking a supplement:

Methotrexate: Used to treat certain cancers and autoimmune diseases like rheumatoid arthritis, methotrexate is a folate antagonist that blocks the enzyme needed to use folate effectively. Patients on this medication are often prescribed folic acid supplements to mitigate side effects.
Anticonvulsants: Drugs used to treat epilepsy, such as phenytoin (Dilantin), can interfere with folate absorption.
Trimethoprim: An antibiotic that can act as a folate antagonist.
Sulfasalazine: Used to treat ulcerative colitis and rheumatoid arthritis, this medication can also hinder folate absorption.

Chronic Conditions and Lifestyle Factors

Beyond genetic and digestive issues, other conditions and lifestyle choices can increase the risk of folate deficiency.

Excessive Alcohol Use: Chronic, heavy alcohol consumption interferes with folate absorption and increases its excretion through urine, while also often leading to a poor diet.
Kidney Dialysis: The process of kidney dialysis can result in the loss of folate, necessitating supplementation for those undergoing treatment.
Hemolytic Anemia: This blood disorder involves the premature destruction of red blood cells, which increases the body's demand for folate to produce new cells rapidly.
Pregnancy and Lactation: The demand for folate increases significantly during pregnancy to support fetal growth, and again during lactation. Without increased intake, deficiency can occur.
Chronic Liver Disease: Conditions affecting the liver can disrupt folate storage and metabolism.

A Comparative Look at Folate-Related Conditions


Condition Category	Specific Examples	Impact on Folate	Other Relevant Symptoms
Malabsorption	Celiac Disease, Crohn's Disease	Damages intestinal lining, reducing absorption	Diarrhea, abdominal pain, weight loss
Genetic/Metabolic	MTHFR Mutation	Impairs conversion to active folate	Elevated homocysteine, possible anemia
Medication-Induced	Methotrexate, Phenytoin	Blocks folate utilization or absorption	Can be dose-dependent, may lead to anemia
Lifestyle/Other	Chronic Alcoholism, Kidney Dialysis	Impairs absorption, increases excretion	Malnutrition, poor diet, chronic fatigue

The Importance of a Professional Diagnosis

If you experience symptoms such as fatigue, weakness, a sore tongue, or changes in cognitive function, it is essential to consult a healthcare provider for a proper diagnosis. Blood tests can measure serum folate and red blood cell folate levels to assess your status. Do not self-treat with supplements without medical guidance, as high doses of folic acid can mask a coexisting vitamin B12 deficiency, potentially allowing neurological damage to progress. Treating the underlying condition is the most effective approach to correcting folate deficiency and restoring long-term health.

Addressing the Underlying Cause

Depending on the diagnosis, treatment will vary. For malabsorption issues, managing the primary digestive disease is key. For genetic conditions, specialized supplements containing the active form of folate may be recommended. In cases involving medication, a doctor may adjust the dosage or recommend supplementation. For individuals with chronic alcohol use disorder, addressing the addiction is crucial. The CDC provides valuable resources on nutrition and fortified foods to support overall intake.

Conclusion In summary, while a lack of folate-rich foods can cause a deficiency, it is often deeper than that. Digestive disorders, specific genetic mutations, prescription medications, and chronic health issues can all prevent the body from properly utilizing vitamin B9. Understanding what underlying conditions cause low folate is the first step toward a correct diagnosis and effective treatment plan. Always work with a healthcare professional to identify the root cause of the deficiency and manage it appropriately to prevent serious complications.

Frequently Asked Questions

Yes, it is possible to have a folate deficiency despite a healthy diet. Underlying conditions such as malabsorption diseases, certain genetic mutations, or specific medications can prevent your body from properly absorbing or utilizing the folate you consume.

Diseases like Celiac and Crohn's damage the lining of the small intestine, where folate is absorbed. This inflammation and damage reduce the intestine's ability to extract and process nutrients, leading to malabsorption and subsequent deficiency.

The MTHFR gene provides instructions for making an enzyme that converts folate into its active form. A mutation in this gene can compromise this process, meaning the body cannot efficiently use the folate it absorbs.

Yes, several medications can interfere with folate. Drugs like methotrexate, some anticonvulsants, and sulfasalazine can block folate metabolism or absorption, leading to lower levels in the body.

Common symptoms of folate deficiency include fatigue, weakness, a sore and red tongue, mouth sores, irritability, and shortness of breath. Severe or prolonged deficiency can also lead to anemia.

Checking vitamin B12 levels is crucial because a B12 deficiency can also cause a form of anemia similar to folate deficiency. Taking high doses of folic acid can mask the B12 deficiency, potentially allowing neurological damage from the B12 issue to progress unnoticed.

Excellent food sources of folate include dark leafy greens like spinach and kale, legumes (beans and peas), citrus fruits, eggs, liver, and enriched grain products like bread, pasta, and cereals.