--- title: "Evidence: active folate, methylation cofactor" description: "Folinic acid and l-methylfolate both lower homocysteine, but folinic acid may be more beneficial for individuals with the MTHFR 677CT genotype." url: "https://magellanlongevity.com/study/s130.md" canonical: "https://magellanlongevity.com/study/s130.html" html: "https://magellanlongevity.com/study/s130.html" type: "study" study_key: "s130" journal: "Clin Nutr ESPEN" year: 2023 pmid: "38056998" doi: "10.1016/j.clnesp.2023.09.002" citations: 1 updated: 2026-09-02 author: "Gabriel Radu, DO" author_credentials: "Physiatrist (PM&R). NY medical license 275110. NPI 1376861765." publisher: "Magellan Longevity" content_format: "markdown" --- # Evidence: active folate, methylation cofactor [Home](https://magellanlongevity.com/) › [Research map](https://magellanlongevity.com/longevity-research-map.html) › Evidence: active folate, methylation cofactor **HTML version:** https://magellanlongevity.com/study/s130.html · **In the Magellan app:** https://magellanlongevity.com/#/study/s130 ## Citation | Field | Value | | --- | --- | | Journal | Clin Nutr ESPEN | | Year | 2023 | | PMID | [38056998](https://pubmed.ncbi.nlm.nih.gov/38056998/) | | DOI | [10.1016/j.clnesp.2023.09.002](https://doi.org/10.1016/j.clnesp.2023.09.002) | | Study key | s130 | ## Takeaway Folinic acid and l-methylfolate both lower homocysteine, but folinic acid may be more beneficial for individuals with the MTHFR 677CT genotype. ## The question The study investigated the efficacy of folinic acid versus l-methylfolate in lowering total homocysteine (tHcy) levels in healthy Greek adults. ## Hypothesis The study aimed to compare the effectiveness of folinic acid and l-methylfolate in reducing tHcy levels. ## Methods Two hundred and seventy-two healthy Greek adults with tHcy levels ≥10 μmol/L were randomized to receive either folinic acid or l-methylfolate orally for three months. Participants with low cobalamin also received hydroxycobalamine. Serum folate, cobalamin, and tHcy levels were measured at the beginning and end of the study, and MTHFR C677T and A1298C gene polymorphisms were genotyped. ## Results Both folinic acid and l-methylfolate significantly increased serum folate and cobalamin, and significantly decreased tHcy levels. Individuals with the MTHFR 677TT genotype showed a greater reduction in tHcy. While folinic acid led to a higher increase in serum folate than l-methylfolate, the reduction in tHcy levels between the two groups was not substantially different overall. However, individuals with the MTHFR 677CT genotype experienced a statistically significant higher reduction in tHcy when supplemented with folinic acid compared to l-methylfolate. ## Conclusion Folinic acid resulted in a greater increase in serum folate levels than l-methylfolate, but there was no overall difference in tHcy reduction between the two treatments. The MTHFR C677T gene polymorphism, but not MTHFR A1298C, influenced tHcy reduction, with MTHFR 677CT individuals benefiting more from folinic acid. ## Limitations The abstract does not explicitly state any limitations of the study. ## Verbatim from the abstract > serum folate increased while total homocysteine decreased significantly ## Where this study is used on Magellan This paper is one of the citations behind the evidence grade on the pages below. Grades are assigned from the published research and are independent of affiliate commissions. | Compound or device | Evidence grade | Graded pages | | --- | --- | --- | | L-Methylfolate (5-MTHF) | Moderate evidence | [L-Methylfolate (5-MTHF)](https://magellanlongevity.com/p/130.md) | ## Reference 1. **Evidence: active folate, methylation cofactor** Clin Nutr ESPEN 2023 · [PMID 38056998](https://pubmed.ncbi.nlm.nih.gov/38056998/) · [DOI 10.1016/j.clnesp.2023.09.002](https://doi.org/10.1016/j.clnesp.2023.09.002) > serum folate increased while total homocysteine decreased significantly ## Structured data ```json {"@context":"https://schema.org","@graph":[{"@type":"MedicalWebPage","@id":"https://magellanlongevity.com/study/s130.html#page","url":"https://magellanlongevity.com/study/s130.html","name":"Evidence: active folate, methylation cofactor","description":"Folinic acid and l-methylfolate both lower homocysteine, but folinic acid may be more beneficial for individuals with the MTHFR 677CT genotype.","inLanguage":"en","isPartOf":{"@type":"WebSite","name":"Magellan Longevity","url":"https://magellanlongevity.com/"},"author":{"@type":"Person","name":"Gabriel Radu, DO","jobTitle":"Physiatrist (PM&R)","identifier":[{"@type":"PropertyValue","name":"NPI","value":"1376861765"},{"@type":"PropertyValue","name":"NY medical license","value":"275110"}]},"publisher":{"@type":"Organization","name":"Magellan Longevity","url":"https://magellanlongevity.com/"},"encoding":{"@type":"MediaObject","encodingFormat":"text/markdown","contentUrl":"https://magellanlongevity.com/study/s130.md"},"dateModified":"2026-09-02"},{"@type":"BreadcrumbList","itemListElement":[{"@type":"ListItem","position":1,"name":"Home","item":"https://magellanlongevity.com/"},{"@type":"ListItem","position":2,"name":"Research map","item":"https://magellanlongevity.com/longevity-research-map.html"},{"@type":"ListItem","position":3,"name":"Evidence: active folate, methylation cofactor","item":"https://magellanlongevity.com/study/s130.html"}]},{"@type":"ScholarlyArticle","@id":"https://magellanlongevity.com/study/s130.html#study","name":"Evidence: active folate, methylation cofactor","headline":"Evidence: active folate, methylation cofactor","datePublished":"2023","isPartOf":{"@type":"Periodical","name":"Clin Nutr ESPEN"},"identifier":"PMID:38056998","url":"https://pubmed.ncbi.nlm.nih.gov/38056998/","sameAs":"https://doi.org/10.1016/j.clnesp.2023.09.002","abstract":"Folinic acid and l-methylfolate both lower homocysteine, but folinic acid may be more beneficial for individuals with the MTHFR 677CT genotype."}]} ``` ## Related on Magellan Longevity - [L-Methylfolate (5-MTHF)](https://magellanlongevity.com/p/130.md) — product graded on this and related evidence - [Effect of adjunctive L-methylfolate 15 mg among inadequate responders to SSRIs in…](https://magellanlongevity.com/study/d24813065.md) - [Longevity research map](https://magellanlongevity.com/longevity-research-map.html) - [Evidence-based longevity supplements](https://magellanlongevity.com/longevity-supplements.md) ## Scope and disclosures Educational information, not medical advice. Nothing here is intended to diagnose, treat, cure, or prevent any disease. Talk to your physician before starting any supplement or device, especially if you are pregnant, nursing, or taking medication. Editorial firewall: evidence grades are assigned from the published research and are independent of any affiliate commission. As an Amazon Associate, Magellan Longevity earns from qualifying purchases. Reviewed for accuracy by a board-certified physician (DO).