How is Folate Absorbed in the Body?

December 21, 2025 •

3 min read

Over 50% of the naturally occurring folate in food can be destroyed by cooking and processing, underscoring the importance of understanding absorption. This process of how is folate absorbed in the body is a complex journey, relying on a sequence of enzymatic actions and specialized transport systems within the gastrointestinal tract and liver.

Quick Summary

The absorption of dietary folate involves enzymatic breakdown into monoglutamate forms, primarily in the jejunum, before transport into intestinal cells via the proton-coupled folate transporter (PCFT) and, to a lesser extent, the reduced folate carrier (RFC). Once absorbed, it is metabolized in the liver and distributed throughout the body.

Key Points

Absorption Site: Folate absorption occurs primarily in the proximal small intestine (duodenum and jejunum), where a slightly acidic environment facilitates transport.
Enzymatic Conversion: Dietary folate, which is in polyglutamate form, must first be hydrolyzed into monoglutamate form by intestinal enzymes (folyl conjugases) before absorption can occur.
Primary Transporter (PCFT): The proton-coupled folate transporter (PCFT) is the main transporter responsible for absorbing folate across the intestinal brush-border membrane at a low pH.
Folic Acid Absorption: Synthetic folic acid is more readily absorbed (85%) than natural food folate (50%) and doesn't require enzymatic digestion.
Liver Metabolism: Once absorbed, folate travels to the liver, where it is converted into active forms like 5-methyl-THF and stored for future use.
Colonic Absorption: The large intestine also contributes to folate status by absorbing folate synthesized by gut bacteria, although this is a slower process.
Inhibitory Factors: Alcohol consumption, certain medications (e.g., methotrexate), and intestinal disorders like celiac disease can all inhibit folate absorption.

The Journey of Folate: From Plate to Cell

Folate, or vitamin B9, is an essential nutrient crucial for cellular growth, DNA synthesis, and red blood cell formation. Unlike synthetic folic acid, naturally occurring folates in foods are sensitive and less bioavailable, making the absorption process a key determinant of overall folate status. The journey begins in the digestive tract, primarily the small intestine, and involves multiple biochemical steps and transport mechanisms.

Preliminary Digestion and Hydrolysis

Before folate can be absorbed, it must be broken down into its transportable form. Dietary folates exist mainly as polyglutamates, which are multiple glutamate molecules attached to the folate structure. For intestinal absorption:

Intestinal enzymes, specifically glutamate carboxypeptidase II, cleave the excess glutamate residues.
This results in monoglutamate folate, which can be transported across the intestinal wall.
This enzymatic activity is concentrated in the jejunum.

Intestinal Absorption via Specialized Transporters

Monoglutamate folate enters enterocytes (intestinal cells) through specific transporters, a process highly dependent on pH. Absorption mainly occurs in the duodenum and jejunum.

The Proton-Coupled Folate Transporter (PCFT) is the primary mechanism for folate absorption under physiological conditions. It has a high affinity for monoglutamate folates, especially at a slightly acidic pH, operating optimally in the acidic environment (pH ~5.5) of the proximal small intestine. PCFT transports folate into the cell along with protons.

The Reduced Folate Carrier (RFC) also plays a role, though less significant in initial intestinal uptake. RFC has lower affinity at acidic pH compared to PCFT and functions optimally at a more neutral pH. It is primarily involved in delivering folates to cells from systemic circulation.

The Role of the Liver and Metabolism

After intestinal absorption, folate travels via the portal vein to the liver for metabolic conversion. In the liver, absorbed folate is converted into active forms, including 5-methyl-THF. The liver stores large amounts and re-secretes folate into the bile for reabsorption in the intestine (enterohepatic circulation), helping maintain steady levels.

Factors Influencing Folate Absorption

Several factors can impact folate absorption and metabolism:

Alcohol: Chronic alcohol consumption interferes with intestinal absorption and increases excretion.
Genetics: Genetic variations like in the MTHFR gene can impair conversion to active forms.
Medications: Certain drugs, such as some anti-seizure medications and sulfasalazine, interfere with absorption or metabolism.
Gut Health: Conditions causing intestinal malabsorption, like celiac disease, can limit folate uptake.

Comparison Table: Folate vs. Folic Acid Absorption


Feature	Natural Folate (from food)	Folic Acid (synthetic)
Molecular Structure	Polyglutamate chains, needs enzymatic breakdown.	Monoglutamate structure, no enzymatic cleavage needed.
Absorption Site	Primarily absorbed in the jejunum and duodenum.	Absorbed throughout the small intestine.
Absorption Efficiency	Generally less bioavailable, and influenced by food processing.	Better absorbed (about 85% compared to 50% for food folate).
Metabolism	Metabolized into active forms within the intestinal cells and liver.	Requires conversion in the liver; can lead to unmetabolized folic acid in the bloodstream at high doses.

The Compensatory Role of the Colon

While the small intestine is the primary site, the large intestine also contributes to folate status. Intestinal bacteria synthesize folate, which can be absorbed slowly, making a significant contribution due to longer transit time.

Conclusion

Understanding how folate is absorbed is key to maintaining adequate levels. From enzymatic hydrolysis of dietary polyglutamates to high-affinity transport via PCFT in the jejunum, a complex, coordinated process ensures the body receives vitamin B9. Factors like diet, alcohol intake, certain medications, and genetic variations can impact this. Natural folate and synthetic folic acid are absorbed differently, with folic acid showing higher efficiency. Sufficient intake, managing lifestyle factors, and consulting a healthcare professional are essential for optimal folate absorption. For further reading, explore the detailed review from PubMed Central on intestinal folate absorption.

Frequently Asked Questions

The primary site for folate absorption is the proximal small intestine, specifically the duodenum and jejunum. This is where the specialized transport systems are most active.

Yes, they absorb differently. Folic acid is synthetic and absorbed more efficiently (around 85%) than natural folate (around 50%) because it does not require enzymatic breakdown into its monoglutamate form before absorption.

The liver is crucial for folate metabolism. After intestinal absorption, folate is transported to the liver, where it is converted into active coenzyme forms, stored, and re-circulated through the enterohepatic pathway.

Yes, intestinal bacteria can synthesize folate. While most absorption occurs in the small intestine, the colon can absorb this bacterially-produced folate, making a small but significant contribution to the body's folate status.

The most important transporter for absorbing dietary folate is the proton-coupled folate transporter (PCFT), which functions optimally in the acidic environment of the proximal small intestine.

Excessive alcohol consumption hinders folate absorption, impairs liver storage, and increases folate excretion. This makes chronic alcohol use a significant risk factor for folate deficiency.

After absorption and metabolic use, excess folate is excreted. Most metabolic products are eliminated through urine within 24 hours after an oral dose.