News
Exploring the Advantages of 5-MTHF and Folinic Acid over Synthetic Folic Acid
2 December 2025
A groundbreaking study published in Nutrition Reviews has explored the key differences between various folate compounds and their clinical relevance.
Understanding how these forms differ in absorption, bioavailability, and physiological effects is essential—especially for individuals planning pregnancy, pregnant women, and those with specific genetic or metabolic conditions.
Avoidance of Unmetabolized Folic Acid Accumulation and Improved Metabolic Support
Folate compounds play a crucial role in various biological processes, including DNA and RNA synthesis, homocysteine regulation, and epigenetic methylation. However, natural folate forms such as 5-methyltetrahydrofolate (5-MTHF) and folinic acid (CHO-THF) behave differently in the body compared to synthetic folic acid (sFA).
The study‘s comparative analysis has demonstrated that the natural folate forms, 5-methyltetrahydrofolate (5-MTHF) and folinic acid (CHO-THF), offer significant advantages over synthetic folic acid (sFA).
These natural folate compounds help to reduce the buildup of unmetabolized folic acid and provide more efficient metabolic support. These benefits are particularly relevant for individuals with genetic variants that affect folate metabolism or those with impaired folate transport. Additionally, both 5-MTHF and CHO-THF have shown promising results in high-dose therapies for patients with folate receptor autoantibodies or transport dysfunction.
Enhanced Brain Health and Cognitive Function
The review also shows that 5-MTHF can effectively cross the blood–brain barrier, supporting brain development during fetal and neonatal stages. Beyond early development, 5-MTHF may also contribute to improved cognitive function and reductions in depressive symptoms.
Folinic acid (CHO-THF) demonstrates potential benefits as well, particularly in addressing neurological and developmental concerns. It has shown promise in supporting individuals with autism spectrum disorders by influencing neurotransmission and neurometabolic pathways.
