Folinic Acid
Also known as: Leucovorin, 5-formyltetrahydrofolate
Randomized controlled trials in children with ASD reported improvements in verbal communication and reductions in autism severity scores with oral folinic acid (2 mg/kg/day up to 50 mg/day) versus placebo; benefits were often greater in participants positive for folate receptor autoantibodies. Other large trials and reviews that mention folinic acid relate to its use in oncology regimens (intravenous folinic acid with chemotherapy) and are not evidence for oral supplementation as a dietary ingredient.
Last reviewed: 2026-10-14 · 3 indexed studies
Set your location for accurate regulatory status
Saved on this device — no sign-in needed.
Overview
Folinic acid (leucovorin) is a reduced folate used to provide bioactive folate without requiring dihydrofolate reductase. Clinical RCT evidence in children with autism spectrum disorder (ASD) suggests symptomatic benefit on communication and overall autism rating scales when given as an add-on at doses up to 2 mg/kg/day (maximum 50 mg/day).
Mechanism & Function
Mechanism of Action
Folinic acid is a reduced form of folate that bypasses dihydrofolate reductase and can replenish intracellular folate pools and one‑carbon metabolism. In ASD trials, response may be linked to overcoming impaired folate transport related to folate receptor autoantibodies and restoring folate-dependent neurotransmitter and methylation pathways.
Physiological Role
Donor and carrier within one‑carbon metabolism, supporting DNA synthesis, methylation reactions and neurotransmitter synthesis.
Primary Pathways
Performance / Health Relevance
Direct performance or athletic benefits are not supported by the provided human RCT abstracts; available human RCT evidence pertains primarily to symptomatic outcomes in children with ASD.
Evidence Review
Practical Use & Dosage
- Minimum Effective Dose
- 2 mg/kg/day (used in ASD trials; up to a maximum of 50 mg/day in children)
- Optimal Range
- Not established for general use; clinical trials in children used 2 mg/kg/day (max 50 mg/day)
- Upper / Caution Level
- Not established for long-term supplementation in healthy adults from these abstracts
- Timing
- As administered in trials: daily oral dosing
- Best Format
- Oral tablets or oral solution (form used in RCTs)
- Bioavailability
- Folinic acid is a bioactive reduced folate and does not require metabolic reduction by dihydrofolate reductase.
- Absorption Considerations
- Oral folinic acid is systemically bioavailable; response in some studies correlated with folate receptor autoantibody status.
Safety & Interactions
Side Effects
- •No adverse reactions reported in the provided ASD RCTs
Contraindications
- Not established from provided abstracts; caution when used with folate‑sensitive chemotherapy regimens without specialist advice
Drug Interactions
- •May interact with antifolate chemotherapy (note: folinic acid is used intentionally to modulate effects of some chemotherapies)
Who Should Avoid
- •People receiving antifolate cancer chemotherapy without oncology guidance
- •Use in pregnancy or other clinical states not addressed by provided abstracts should follow clinical guidance
Monitoring
Consider testing for folate receptor autoantibodies or folate status in contexts similar to the ASD trials; monitor clinical response and standard safety parameters as guided by a clinician.
Frequently Asked Questions
Auto-generated from indexed evidence — dosage, safety, interactions, and more.
When is Folinic Acid typically used or indicated?
Folinic Acid is most commonly used for: Support for folate-dependent metabolism, Adjunctive therapy in children with autism spectrum disorder (investigational), To bypass folic acid metabolic blocks in deficiency states. Donor and carrier within one‑carbon metabolism, supporting DNA synthesis, methylation reactions and neurotransmitter synthesis.
How does Folinic Acid work?
Folinic acid is a reduced form of folate that bypasses dihydrofolate reductase and can replenish intracellular folate pools and one‑carbon metabolism. In ASD trials, response may be linked to overcoming impaired folate transport related to folate receptor autoantibodies and restoring folate-dependent neurotransmitter and methylation pathways.
What is the recommended dose of Folinic Acid?
The optimal range is Not established for general use; clinical trials in children used 2 mg/kg/day (max 50 mg/day). with a minimum effective dose of 2 mg/kg/day (used in ASD trials; up to a maximum of 50 mg/day in children). Best taken: As administered in trials: daily oral dosing. Upper / caution level: Not established for long-term supplementation in healthy adults from these abstracts.
What are the side effects of Folinic Acid?
Reported side effects include: No adverse reactions reported in the provided ASD RCTs. Monitoring: Consider testing for folate receptor autoantibodies or folate status in contexts similar to the ASD trials; monitor clinical response and standard safety parameters as guided by a clinician.
Does Folinic Acid interact with medications?
Known or theoretical interactions: May interact with antifolate chemotherapy (note: folinic acid is used intentionally to modulate effects of some chemotherapies). Always check with a clinician before combining with prescription medication.
Who should avoid Folinic Acid?
Folinic Acid is generally not recommended for: People receiving antifolate cancer chemotherapy without oncology guidance; Use in pregnancy or other clinical states not addressed by provided abstracts should follow clinical guidance; and Not established from provided abstracts; caution when used with folate‑sensitive chemotherapy regimens without specialist advice.
How strong is the evidence for Folinic Acid?
Evidence level: Moderate (overall score 57/100), based on 3 indexed studies on SuppIndex.
Research & References (3)
Efficacy of oral folinic acid supplementation in children with autism spectrum disorder: a randomized double-blind, placebo-controlled trial.
Double‑blind, placebo‑controlled RCT in children with ASD aged 2–10 years comparing oral folinic acid (2 mg/kg/day, max 50 mg/day) with placebo over 24 weeks as add‑on therapy.
Folinic acid improves verbal communication in children with autism and language impairment: a randomized double-blind placebo-controlled trial.
Randomized double‑blind placebo‑controlled trial of high‑dose oral folinic acid (2 mg/kg/day, max 50 mg/day) for 12 weeks in children with non‑syndromic ASD and language impairment.
Pharmacological and dietary-supplement treatments for autism spectrum disorder: a systematic review and network meta-analysis.
Systematic review and network meta‑analysis of pharmacological and dietary‑supplement treatments for ASD that included folinic acid among many interventions.
Related Ingredients
Other top-rated ingredients in Vitamins.
Vitamin D3
91/100A secosteroid prohormone converted to calcitriol (1,25-dihydroxyvitamin D), functioning as a nuclear hormone receptor ligand regulating >1000 genes.
Vitamin B3 (Niacin)
80/100Niacin is a precursor to nicotinamide adenine dinucleotide (NAD+) and nicotinamide adenine dinucleotide phosphate (NADP+), two critical coenzymes involved in over 400 enzymatic reactions in the body. These reactions are central to energy metabolism, DNA repair, and antioxidant defense. Pharmacological doses of nicotinic acid have a well-established role in lowering LDL cholesterol and triglycerides and raising HDL cholesterol, primarily through inhibiting hepatic VLDL synthesis and reducing fatty acid mobilization. Nicotinamide, while also a source of NAD+, does not exert the same hypolipidemic effects but is crucial for various cellular processes and has shown promise in certain dermatological conditions and neurological contexts at higher doses.
Vitamin B9 (L-Methylfolate / 5-MTHF)
75/100L-Methylfolate is the principal circulating form of folate and the only form that can cross the blood-brain barrier. It plays a critical role as a coenzyme in one-carbon metabolism, particularly in the methylation cycle. Its direct bioavailability makes it a preferred supplemental form, especially when addressing folate deficiencies or supporting processes requiring efficient methylation, such as neurotransmitter synthesis and homocysteine regulation. Research indicates its efficacy in supporting mood, cardiovascular health, and cognitive function, particularly in populations with impaired folate metabolism.
Research Overview
Moderate EvidenceCite this ingredient
One-click citation export in APA, MLA, Chicago, BibTeX, or HTML. The URL below is stable and safe to link.
Stable URL
https://thesuppindex.com/ingredients/folinic-acid
SuppIndex. (2026). Folinic Acid: Evidence summary, dosage and clinical studies. Retrieved October 16, 2026, from https://thesuppindex.com/ingredients/folinic-acid
Based on 3 indexed studies · Evidence level: Moderate.
Goal Ratings
Stack Compatibility
May be used with other B‑vitamins and folate interventions; interactions with chemotherapy agents require oncology oversight.