Safety Profile
Known Safety Concerns
- Can still mask vitamin B12 deficiency at high doses
- Clinically used to counteract methotrexate -- interaction with methotrexate therapy
- Check B12 status before supplementing with any high-dose folate form
- No established UL for folinic acid specifically
Contraindications
- Can still mask vitamin B12 deficiency at high doses
- Clinically used to counteract methotrexate -- interaction with methotrexate therapy
Interactions
Information not yet available for this ingredient profile.
Evidence and Scientific Findings
Ingredient Overview
Folinic acid is an active reduced form of folate that bypasses the MTHFR enzyme step and does not accumulate as unmetabolised folic acid. Used clinically as leucovorin to rescue from methotrexate toxicity. As a supplement it is preferred for MTHFR variant individuals. High doses can still mask vitamin B12 deficiency. Generally well tolerated with excellent safety profile.
Biological and Chemical Classification
- Scientific Name
- 5-formyl-tetrahydrofolic acid
Mechanism of Action
Information not yet available for this ingredient profile.
Clinical Evidence of Effectiveness
Information not yet available for this ingredient profile.
Pharmacokinetics
Information not yet available for this ingredient profile.
Recommended Dosage
Information not yet available for this ingredient profile.
SETI — Scientific Evidence Transparency Index
Executive Summary — Ingredient Assessment
- 3 studies reviewed
- 0 high-quality studies (meta-analysis or RCT)
- Main clinical benefit observed: Vitamin
- Evidence consistency: High consistency across studies (100%)
- Can still mask vitamin B12 deficiency at high doses
- Clinically used to counteract methotrexate -- interaction with methotrexate therapy
- Check B12 status before supplementing with any high-dose folate form
- No established UL for folinic acid specifically
The available scientific evidence for Vitamin B9 (Folinic Acid) indicates notable safety signals that warrant caution. Use should be considered carefully and monitored, particularly in sensitive populations or alongside other medications.
Total SETI Score
High risk| Evidence quality | 3/40 |
| Evidence consistency | 20/20 |
| Safety signals | 14/20 |
| Study recency | 10/10 |
| Evidence transparency | 10/10 |
Evidence Summary
- 3 studies reviewed
- 0 high-quality studies (meta-analysis or systematic review)
- 0 studies identified benefits or no safety concern (GREEN)
- 3 studies reported limited or advisory safety evidence (YELLOW)
Evidence Policy
Only peer-reviewed scientific literature indexed in PubMed or comparable databases is included in this evaluation. Commercial websites, blogs, and marketing materials are excluded. All references include direct traceable links to source documents.
Last updated: 30 მარ 2026, 19:31
Evidence Distribution
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Observational / other LOW evidence YELLOWFolinic Acid. ↗Gristan YD et al.. Folinic Acid.. 2026. PMID:31424816.PMID 31424816 ↗Year 2026Study type Observational / otherEvidence strength LOW evidencePubMed link https://pubmed.ncbi.nlm.nih.gov/31424816/
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Observational / other LOW evidence YELLOWFluorescence spectroscopy combined with molecular docking to study the interaction between folic acid derivatives from wheat grains and bovine trypsin. ↗Tian P et al.. Fluorescence spectroscopy combined with molecular docking to study the interaction between folic acid derivatives from wheat grains and bovine trypsin.. Sci Rep. 2025. PMID:41290973.PMID 41290973 ↗Journal Sci RepYear 2025Study type Observational / otherEvidence strength LOW evidencePubMed link https://pubmed.ncbi.nlm.nih.gov/41290973/
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Observational / other LOW evidence YELLOWNaturally occurring folates in selected traditionally prepared foods in Southern India. ↗Vishnumohan S et al.. Naturally occurring folates in selected traditionally prepared foods in Southern India.. J Food Sci Technol. 2017. PMID:29184222.PMID 29184222 ↗Journal J Food Sci TechnolYear 2017Study type Observational / otherEvidence strength LOW evidencePubMed link https://pubmed.ncbi.nlm.nih.gov/29184222/
Score Transparency
0 of 10 approved references (score saturates at 10). More peer-reviewed studies = stronger evidence base.
Method: Q = number of approved references ÷ 10 (capped at 1.0)
Limited — mostly case reports or animal studies
Method: L = mean study-level weight across approved references. Level 1 (meta-analysis / systematic review) = 1.0; Level 2 (RCT) = 0.8; Level 3 (cohort/case-control) = 0.6; Level 4 (case report) = 0.4; Level 5 (animal / in-vitro) = 0.2.
Mixed or neutral — roughly equal benefit and risk signals
Method: D = (sum of risk-scored references − sum of benefit-scored references) ÷ total evidence score, then scaled from [−1, 1] to [0, 1]. 0.0 = pure benefit; 0.5 = neutral; 1.0 = pure risk.
One or more monitoring-level safety signals active
Method: S = 0.5 (neutral baseline) + sum of active signal severity deltas ÷ 10. Severity deltas: Critical = +2.0, High = +1.5, Moderate = +1.0, Low = +0.5. Capped at 1.0.
Final GIRI Score for Vitamin B9 (Folinic Acid). Risk level thresholds: Low 0–3.0 · Moderate 3.0–5.5 · High 5.5–7.5 · Critical 7.5–10.
Full methodology & data sources
The GIRI Score is computed entirely from structured data — no editorial scoring or subjective weighting is applied at any step.
- References: Only approved references are counted. Each reference is assigned an evidence level (L1–L5) and a direction (risk / neutral / benefit) by the reference manager or AI classifier.
- Safety Signals: Sourced from regulatory agencies (FDA, EMA, Health Canada, TGA, and others) and pharmacovigilance databases. Only active signals count toward the score.
- Formula version: GIRI Score v3.7.0 — Q × L × D × S × 10.
- Limitations: The score reflects published evidence and recorded signals as of the last update date. It is not a clinical risk assessment and should not replace advice from a qualified healthcare professional.
Risk Level Classification
Based on available regulatory signals and scientific evidence, this ingredient presents a low safety concern under normal conditions of use.
0–3.0
3.0–5.5
5.5–7.5
7.5–10
The score pin shows exactly where this ingredient falls on the fixed risk scale.
What drove the Low classification for Vitamin B9 (Folinic Acid)
A score of 2.5 places this ingredient in the Low band. Thresholds: Low 0–3.0 · Moderate 3.0–5.5 · High 5.5–7.5 · Critical 7.5–10.
0 approved references.
Limited — mostly case reports or animal studies (Level 4–5).
Neutral or mixed — benefit and risk signals roughly balanced.
No active signals — S component is at neutral baseline (0.5), contributing no extra risk weight.
No major regulatory restrictions or advisories recorded across monitored jurisdictions (FDA, EMA, Health Canada, TGA, and others).
How are the Low / Moderate / High / Critical thresholds defined?
The four risk levels are fixed score bands. A score is assigned to exactly one level based on where it falls:
| Level | Score | Meaning |
|---|---|---|
| LOW | 0.0 – 2.9 | Sparse or predominantly beneficial evidence. No active safety alerts. |
| MODERATE | 3.0 – 5.4 | Mixed signals — some risk alongside benefit. Caution at high doses or in sensitive groups. |
| HIGH | 5.5 – 7.4 | Multiple studies or regulatory alerts documenting adverse effects. Professional oversight recommended. |
| CRITICAL | 7.5 – 10 | Regulatory restrictions in one or more major jurisdictions. Serious documented harm. Avoid without specialist supervision. |
Thresholds are fixed constants (GIRI_Score_Utils::LEVEL_THRESHOLDS). They do not change per ingredient and are never subject to editorial adjustment.