Form Comparison

Folic Acid vs Folinic Acid

How folic acid and folinic acid differ in potency, absorption, tolerance, and cost.

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Quick verdict. Folic acid is the form proven to prevent neural tube defects and the right default for anyone who could become pregnant. Folinic acid is a reduced folate that bypasses DHFR, which matters when drugs such as methotrexate or trimethoprim block that enzyme, and it is the prescription rescue drug after methotrexate. Choose folinic acid on a clinician's advice for those drugs or for people who react badly to methylfolate; otherwise folic acid.

Side by Side

Folic Acid Folinic Acid
Absorption High High
How it is absorbed Nearly 100% absorbed on an empty stomach and about 85% with food. Must be reduced by dihydrofolate reductase (DHFR), which is slow in humans, before entering the folate cycle. A reduced folate that bypasses DHFR. It still passes through MTHFR to become methylfolate.
Typical dose 400 mcg daily (all who can become pregnant); 400-800 mcg in prenatals 400-800 mcg daily as a supplement; higher prescription doses
Common uses neural tube defect prevention, fortified foods, prenatal vitamins methotrexate rescue (prescription), people who react to methylfolate
Side effects Unmetabolized folic acid appears in blood above roughly 200-400 mcg per dose; clinical significance unclear. High doses can mask the anemia of B12 deficiency. Well tolerated.
Cost Low Moderate
Also called pteroylmonoglutamic acid leucovorin, calcium folinate, 5-formyltetrahydrofolate
Labels in index 396 11

When to Choose Folic Acid

Choose folic acid when you need the form with proven neural tube defect prevention. The form behind the neural tube defect prevention evidence and US fortification. 1 mcg folic acid with food equals 1.7 mcg DFE.

Folic Acid

The form with the outcome data. For neural tube defect prevention, nothing else has been tested.

What to look for: 400-800 mcg folic acid (680-1,360 mcg DFE) daily, starting at least a month before conception.

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When to Choose Folinic Acid

Choose folinic acid when a clinician wants a reduced folate without the methyl group. Useful when DHFR is inhibited by drugs such as methotrexate or trimethoprim.

Folinic Acid

Choose folinic acid when a clinician wants a reduced folate without the methyl group.

What to look for: Folinic Acid named on the Supplement Facts panel, with the amount per serving stated.

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Products on Titrate

In Titrate's index of NIH label data, 396 labels named as folate products list folic acid and 11 list folinic acid.

Open supplement search

Supplement Search loads one category at a time. Choose the B-Complex tab, then type a form such as "folic acid" under Must contain, or a form to avoid under Must not contain.

Related

References

NIH Office of Dietary Supplements. Folate: Fact Sheet for Health Professionals.

MRC Vitamin Study Research Group. Prevention of neural tube defects: results of the Medical Research Council Vitamin Study. Lancet. 1991;338(8760):131-137.

Williams J, et al. Updated estimates of neural tube defects prevented by mandatory folic acid fortification: United States, 1995-2011. MMWR Morb Mortal Wkly Rep. 2015;64(1):1-5.

Pfeiffer CM, et al. Unmetabolized folic acid is detected in nearly all serum samples from US children, adolescents, and adults. J Nutr. 2015;145(3):520-531.

US Preventive Services Task Force. Folic Acid Supplementation to Prevent Neural Tube Defects: US Preventive Services Task Force Reaffirmation Recommendation Statement. JAMA. 2023;330(5):454-459.