The study investigated the efficacy of folinic acid versus l-methylfolate in lowering total homocysteine (tHcy) levels in healthy Greek adults.
Clin Nutr ESPEN · 2023 · PMID 38056998 · DOI 10.1016/j.clnesp.2023.09.002
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.
What they tested
The study aimed to compare the effectiveness of folinic acid and l-methylfolate in reducing tHcy levels.
How they did it
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.
What they found
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.
What it means
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.
Where the published abstract does not list limitations, we say so rather than inventing them. Read the full paper on PubMed before drawing conclusions.
The paper at a glance
| Magellan’s evidence label | active folate, methylation cofactor (our label for this citation — see PubMed for the paper’s own title and authors) |
|---|---|
| Journal | Clin Nutr ESPEN |
| Year | 2023 |
| PMID | 38056998 ↗ |
| DOI | 10.1016/j.clnesp.2023.09.002 ↗ |
| Topic | Cardiovascular & vascular aging |
Read the source: PubMed record (authors, abstract, full citation) ↗ · Publisher via doi.org ↗
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L-Methylfolate (5-MTHF)
In human trials, both L-5-MTHF and folic acid raise blood folate and lower total homocysteine, an amino acid whose elevation is linked to cardiovascular and cognitive risk; head-to-head studies find L-5-MTHF at least as effective as folic acid, and sometimes better, at improving folate status.
L-Methylfolate (also called 5-methyltetrahydrofolate, 5-MTHF, or levomefolic acid) is the biologically…
Research describes the compound or intervention studied. It is not a claim about any specific product.
Molecules & mechanisms in this paper
Each of these is named in the paper’s own words above. Open the monograph for the full mechanism and its other citations.
Cite this page
These citations point at this summary. To cite the original paper with its full author list, use the PubMed record or doi.org.
Magellan Longevity. (2026). The study investigated the efficacy of folinic acid versus l-methylfolate in lowering total homocysteine (tHcy) levels in healthy Greek adults. [Plain-English summary of Clin Nutr ESPEN 2023, PMID 38056998, DOI 10.1016/j.clnesp.2023.09.002]. Magellan Longevity. https://magellanlongevity.com/study/s130.html@misc{magellan_s130,
title = {The study investigated the efficacy of folinic acid versus l-methylfolate in lowering total homocysteine (tHcy) levels in healthy Greek adults.},
author = {{Magellan Longevity}},
year = {2026},
howpublished = {\url{https://magellanlongevity.com/study/s130.html}},
note = {Plain-English summary of PubMed PMID 38056998; DOI 10.1016/j.clnesp.2023.09.002; Clin Nutr ESPEN 2023. Reviewed by Gabriel Radu, DO},
urldate = {2026-08-11}
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