What Causes Low Folic Acid? A Comprehensive Guide to Deficiency

According to the World Health Organization, folate insufficiency affects over 40% of women of reproductive age globally. So, what causes low folic acid levels, and who is most at risk of this deficiency? The causes range from controllable factors like diet to unavoidable genetic conditions and medical treatments.

Quick Summary

Low folic acid, or folate deficiency, can be caused by inadequate dietary intake, excessive alcohol consumption, and malabsorption disorders like celiac disease. Increased physiological needs during pregnancy or lactation also significantly contribute, as do certain medications and genetic mutations.

Key Points

• Poor Diet: Not eating enough leafy green vegetables, fruits, and fortified grains is a primary cause of low folic acid.

• Malabsorption Issues: Conditions such as celiac and Crohn's disease, or bariatric surgery, can prevent the body from properly absorbing folate.

• Increased Demand: Pregnancy, lactation, and certain health conditions like hemolytic anemia and cancer drastically increase the body's need for folate.

• Medications: Drugs like methotrexate, anticonvulsants, and sulfasalazine can interfere with folate metabolism and absorption.

• Genetic Factors: A mutation in the MTHFR gene can impair the conversion of folic acid into its active form, leading to a functional deficiency.

• Alcohol Use: Excessive alcohol consumption interferes with folate absorption and increases its excretion from the body.

• Vitamin B12 Link: An untreated vitamin B12 deficiency can prevent the body from using available folate effectively, creating a functional folate deficiency.

Dietary Factors and Poor Absorption

One of the most common reasons for low folic acid is simply not consuming enough folate-rich foods. Folate, the natural form of vitamin B9, is a water-soluble vitamin and cannot be stored by the body for long periods, meaning a consistent daily intake is necessary. This is a particular risk for individuals with unbalanced or restrictive diets, as well as chronic alcohol users who often substitute alcohol for food.

Food Preparation

How food is prepared also plays a significant role. Folate is sensitive to heat and can be easily destroyed during cooking. Prolonged boiling or overcooking fruits and vegetables can deplete their folate content by 50% to 95%. This makes raw or lightly cooked foods, such as fresh salads and steamed vegetables, much better sources of this essential nutrient.

Alcohol Misuse

Chronic and excessive alcohol consumption directly interferes with folate absorption and metabolism in the liver. It also increases the excretion of folate through the urine, further depleting the body's stores.

Malabsorption Syndromes

Several gastrointestinal conditions can prevent the body from properly absorbing folate, even if intake is sufficient. These malabsorption syndromes disrupt the normal function of the small intestine, where folate is absorbed.

• Celiac Disease: An autoimmune disorder where consuming gluten damages the small intestine lining, hindering nutrient absorption, including folate.
• Crohn's Disease: A chronic inflammatory bowel disease that causes inflammation in the digestive tract, which can impair nutrient uptake.
• Tropical Sprue: A disease affecting the small intestine that leads to malabsorption and nutrient deficiencies.
• Bariatric Surgery: Surgical procedures like gastric bypass can reduce the area available for nutrient absorption.

Increased Physiological Needs

Certain life stages and medical conditions increase the body's demand for folate, which can lead to a deficiency if not met through diet or supplementation.

• Pregnancy and Lactation: Rapid cell division and fetal development significantly elevate the need for folate, making pregnant and breastfeeding individuals a high-risk group. A deficiency during pregnancy is linked to a higher risk of neural tube defects like spina bifida.
• Infancy and Adolescence: Periods of rapid growth also require higher amounts of folate to support accelerated cellular development.
• Hemolytic Anemia: This blood disorder involves the premature destruction of red blood cells, which increases the body's demand for folate to produce new ones.
• Chronic Dialysis: Individuals undergoing long-term kidney dialysis can lose folate during the procedure, necessitating higher intake.

Genetic and Medical Causes

Beyond dietary and absorption issues, some genetic factors and pharmaceutical treatments can interfere with folate metabolism.

MTHFR Gene Mutation

Some individuals have a genetic variant in the methylenetetrahydrofolate reductase (MTHFR) gene, such as the C677T mutation. This mutation impairs the body's ability to convert folic acid into its active, usable form, 5-MTHF. Individuals with this mutation may benefit from supplements containing the active form of folate directly.

Medications

Certain drugs interfere with folate utilization or absorption, lowering levels in the body.

• Methotrexate: An anti-cancer and anti-inflammatory drug that is a powerful folate antagonist.
• Anticonvulsants: Medications used to treat epilepsy, such as phenytoin, primidone, and phenobarbital, can reduce folate levels.
• Sulfasalazine: Used for inflammatory conditions like Crohn's disease and ulcerative colitis.
• Trimethoprim: An antibiotic that can interfere with folate metabolism.
• Metformin: A medication for type 2 diabetes that can lower both B12 and folate levels over time.

Comparison of Major Causes

Cause	Mechanism	At-Risk Population	Dietary Impact	Management Approach
Dietary Insufficiency	Inadequate intake of folate-rich foods and overcooking.	Elderly, individuals with unbalanced diets, alcohol users.	Significant. Lack of intake is the primary issue.	Increase consumption of fresh leafy greens, fruits, and fortified grains.
Malabsorption	Conditions like celiac or Crohn's disease damage the intestinal lining.	Individuals with underlying gastrointestinal disorders.	Can be high even with good diet. Impaired absorption is the issue.	Address the underlying medical condition and may require high-dose supplementation.
Increased Requirement	Periods of rapid cell growth or high cell turnover.	Pregnant/lactating individuals, infants, those with hemolytic anemia.	Can occur even with adequate intake if demand is high.	Supplementation is often necessary to meet the higher demand.
Medications	Certain drugs interfere with folate's function or absorption.	Patients on methotrexate, anticonvulsants, or sulfasalazine.	Variable. Can occur regardless of dietary intake.	Medical supervision and supplementation may be needed while on medication.
Genetic Factors	Mutations like MTHFR limit the body's ability to activate folate.	Individuals with a specific genetic polymorphism.	High. Normal folic acid may not be converted properly.	Use of supplements containing the active form of folate (5-MTHF) may be beneficial.

The Crucial Link with Vitamin B12

An often-overlooked cause is a coexisting vitamin B12 deficiency. Folate and B12 work together in metabolic processes, and a severe B12 deficiency can trap folate in an inactive form, rendering it unusable by the body. This is known as the "folate trap." This can present as a high folic acid level in the blood despite a functional deficiency. Therefore, it is critical to test for both B12 and folate levels when diagnosing a deficiency to ensure correct treatment.

Conclusion

Understanding what causes low folic acid is the first step toward prevention and treatment. While dietary factors like insufficient intake and poor food preparation are common culprits, underlying medical conditions such as celiac disease, certain medications, and genetic mutations can also significantly impact folate status. Increased physiological demand during pregnancy, growth, and specific illnesses creates additional risk. By addressing these varied causes through dietary improvements, targeted supplementation, and appropriate medical management, individuals can effectively prevent and resolve a folic acid deficiency. For anyone concerned about their folate levels or experiencing related symptoms, consulting a healthcare provider is the best course of action. The proper diagnosis will ensure a treatment plan that addresses the specific cause, such as high-dose oral supplementation or addressing an underlying malabsorption disorder.

Resources

For additional information on folate deficiency, symptoms, and treatment options, the Cleveland Clinic offers a helpful overview.

Frequently Asked Questions

What is the fastest way to increase my folic acid levels?

The fastest way to increase folic acid levels is typically through oral supplements, which your healthcare provider may prescribe, along with dietary changes to include more folate-rich and fortified foods.

Can overcooking vegetables reduce my folate intake?

Yes, folate is very sensitive to heat. Overcooking fruits and vegetables can destroy a significant amount of the folate they contain, sometimes up to 95%.

How does alcohol cause low folic acid?

Excessive alcohol intake interferes with the body's absorption and metabolism of folate, and it also increases the rate at which folate is excreted through urine.

Does celiac disease cause low folic acid?

Yes, celiac disease can cause low folic acid. As a malabsorption syndrome, it damages the lining of the small intestine, which impairs the body's ability to absorb nutrients like folate from food.

What is the MTHFR gene mutation?

The MTHFR gene mutation is a genetic variation that affects the body's ability to convert folic acid into its active, usable form. Individuals with this mutation may benefit from special supplements with the active form of folate.

Should I take folic acid supplements during pregnancy?

Yes, women who are pregnant or planning to become pregnant are advised to take folic acid supplements. This is because pregnancy increases the body's folate demand significantly, and adequate intake helps prevent neural tube defects in the baby.

How does vitamin B12 deficiency affect folic acid levels?

A vitamin B12 deficiency can trap folate in an inactive form, preventing the body from using it effectively. This is why a B12 deficiency must be ruled out before treating a folate deficiency with supplements.