Folinic acid

Clinically proven in methotrexate rescue. Increasingly used as an alternative to folic acid for individuals with MTHFR variants, though methylfolate is the more direct bypassing form.

A rough internal score reflecting quantity, quality, and consistency of human evidence. Not a clinical recommendation.

Standard of care for leucovorin rescue in methotrexate chemotherapy. Provides a reduced folate that doesn't require DHFR for activation. Used in autism research (Frye et al.) with positive preliminary results in cerebral folate deficiency.

• Bypasses DHFR reduction step
• Clinical standard for methotrexate rescue
• Alternative folate for MTHFR polymorphism carriers

400–800 mcg/day as a folate supplement. Medical doses for methotrexate rescue are much higher (mg range, under physician guidance).

• Generally well-tolerated
• Rare allergic reactions
• May mask B12 deficiency

Prescription-strength leucovorin is different from supplement-grade folinic acid. Do not self-manage methotrexate rescue.

For MTHFR support, methylfolate (5-MTHF) is often preferred as it is the final active form. Folinic acid still requires one conversion step.

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