Livagen
Also known as: Lyvagen · KEDA · Lys-Glu-Asp-Ala · K-E-D-A tetrapeptide · synthetic analog of Hepalin/liver cytomedin
Research focus
Liver / hepatocyte support; age-related changes in hepatic protein synthesis; chromatin reactivation in aged cells.
US regulatory status
Not FDA-approved · Not compoundable
Evidence rating
No Human Data
Origin
Synthesized by Vladimir Khavinson's group at the St. Petersburg Institute of Bioregulation and Gerontology as one of the so-called 'Cytogens' — short synthetic peptides built by directed chemical synthesis from the amino-acid analysis of a liver polypeptide extract (the cytomedin 'Hepalin', also rendered 'Ventvil'). It belongs to the same Soviet- and Russian-era gerontology research program that produced Epitalon, Vilon, and Cortagen, in which a tissue extract is profiled and a representative short peptide is then made synthetically and assigned to that organ.
Plain-language summary
Livagen is a four-amino-acid synthetic peptide (Lys-Glu-Asp-Ala, often written KEDA) created in Russian gerontology research as the 'liver' member of a family of short peptides, each matched to an organ. Published work is almost entirely preclinical: rat hepatocyte and rat liver-tissue cultures where it reportedly increased protein synthesis, plus in-vitro enzyme assays and experiments on chromatin in lymphocytes taken from elderly donors. There are no published human clinical trials of Livagen, and almost no work outside the original group and its Tbilisi-based collaborators. It is not FDA-approved and is not legally compoundable in the United States. One housekeeping note: some vendor and secondary sources list the sequence as Lys-Glu-Ala-Ser, but the peer-reviewed studies from the Khavinson group consistently describe Lys-Glu-Asp-Ala — readers should treat the KEDA sequence as the published one and the alternative as unverified.
Claimed mechanism (as reported)
Khavinson-group literature proposes that Livagen acts as a tissue-specific 'peptide bioregulator' for the liver — reportedly raising the rate and rhythm of protein synthesis in cultured hepatocytes (most in cells from old animals) and, in ex-vivo human lymphocytes, inducing decondensation of heterochromatin and reactivation of ribosomal genes, consistent with the group's broader claim that short peptides bind specific DNA regions and modulate gene expression. This mechanism remains at the preclinical-proposal stage, is supported almost entirely by in-vitro and cell-culture work from the originating group and its Tbilisi collaborators, and has not been independently validated.
Evidence summary
Preclinical and ex-vivo only. The Livagen literature is thin and consists mainly of rat hepatocyte and organotypic rat-liver culture studies, in-vitro enzyme-activity assays, and chromatin experiments on lymphocytes from elderly human donors (an ex-vivo cell assay, not a clinical trial). Nearly all of it comes from Khavinson's St. Petersburg institute and the Tbilisi State University group of T. Lezhava, with overlapping authorship. No randomized controlled trials — indeed no in-vivo human efficacy studies of any design — appear in the peer-reviewed English-language literature as of 2026. A sequence ambiguity also persists in secondary sources (KEDA vs. Lys-Glu-Ala-Ser); the published Khavinson-group studies use Lys-Glu-Asp-Ala.
What the research reports
Rhythm of protein synthesis in cultures of hepatocytes from rats of different ages: norm and effect of the peptide Livagen
Grade CBrodskii VYa, Khavinson VKh, Zolotarev YuA, Nechaeva NV, Malinin VV et al. · Izvestiya Akademii Nauk, Seriya Biologicheskaya (Biology Bulletin) · 2001
Reported finding: Livagen (Lys-Glu-Asp-Ala), synthesized from amino-acid analysis of liver polypeptide preparations, reportedly increased the level of protein synthesis in cultured hepatocytes across ages, with the largest effect in cells from old animals; the structurally similar peptide Epitalon did not. Reported by the originating group without independent replication.
Sample: Cultured hepatocytes from rats aged 1-24 months; no human subjects
Methodology: C (preclinical) — in-vitro rat hepatocyte cultures, single research group, no in-vivo or human data
Limitations: Cell-culture only; tissue-specific claim rests on one peptide-vs-peptide comparison; no animal-survival or human endpoints; outcome is a biochemical rate, not a clinical benefit.
Functional morphology of an organotypic liver culture exposed to the peptide Livagen
Grade CRiadnova IYu, Filippov SV, Yuzhakov VV (St. Petersburg Institute of Bioregulation and Gerontology) · Advances in Gerontology (Uspekhi Gerontologii) · 2002
Reported finding: By immunocytochemical and morphometric analysis, the tetrapeptide was reported to stabilize structural and functional homeostasis of liver-culture cell populations and to be associated with cellular and intracellular regeneration markers. A descriptive ex-vivo morphology study, not a controlled efficacy trial.
Sample: Rat liver explant cultures; no human subjects
Methodology: C (preclinical) — organotypic rat liver tissue culture with immunocytochemical/morphometric readouts
Limitations: Descriptive, single-group, no blinding or quantitative clinical outcome; rat tissue; translation to human liver disease unproven.
Effects of the synthetic peptide Livagen on chromatin activation in lymphocytes from old people
Grade CKhavinson VKh, Lezhava TA, Monaselidze JG, Dzhokhadze TA, Malinin VV et al. · Bulletin of Experimental Biology and Medicine · 2002-2008
Reported finding: In cultured lymphocytes from elderly donors, Livagen was reported to activate ribosomal genes and induce de-heterochromatinization (decondensation) of structural and facultative heterochromatin, alongside Epitalon and Vilon. Interpreted by the authors as evidence of a gene-activating bioregulator effect; this is an ex-vivo molecular-cytogenetic observation, not a measure of clinical benefit.
Sample: Lymphocytes from donors aged ~75-88 years; small donor numbers
Methodology: C — ex-vivo human lymphocyte cultures (cell assay, not a clinical trial), single collaborating group
Limitations: Ex-vivo cell assay misread by vendors as 'human data'; small donor pools, no blinding, overlapping St. Petersburg/Tbilisi authorship, no independent replication, no link to any clinical endpoint.
Polypeptide liver complex (Ventvil) and the tetrapeptide KEDA (Livagen) in physiological function in norm and age-related pathology (review)
Grade DKuznik BI, Khasanova NB, Ryzhak GA, Mezsheriakova IE, Khavinson VKh · Advances in Gerontology (Uspekhi Gerontologii) · 2020
Reported finding: Summarizes reported hepatoprotective, immunoprotective and antioxidant effects of the liver complex Ventvil and the KEDA tetrapeptide in experimental animal models of liver fibrosis and hepatitis, with effects said to be greatest in aged animals. A review by the developers, not a source of primary controlled human evidence.
Sample: N/A (review of animal models and in-vitro studies)
Methodology: D — narrative review from the originating group summarizing animal/in-vitro models
Limitations: Author overlap with virtually all primary Livagen literature creates an independence-of-review concern; underlying studies are animal/in-vitro; no human trial data; uses 'hepatoprotector' framing not established by controlled human research.
Administration reported in studies
Most published work exposed cells or tissue directly (rat hepatocyte and organotypic liver cultures, lymphocyte cultures, in-vitro enzyme assays); the few oral-administration animal studies gave Livagen per os over roughly two weeks and reported age-dependent shifts in digestive-enzyme activity. No human dosing regimen, route, or course exists in the peer-reviewed literature, because no human trials have been published. This is a summary of research conditions — not a dosing recommendation and not a protocol endorsed by TPC.
This section reports what published studies describe. It is not a dosing recommendation from TPS.
Safety record
No human safety data are available, because no human clinical trials of Livagen have been published. Within the limited preclinical and in-vitro work, no notable toxicity is described, but follow-up is short and no pharmacokinetic, reproductive, genotoxic, or long-term safety data meeting modern regulatory standards exist. Material sold online as a 'research chemical' is not verified for identity, purity, or potency by TPC — and the lingering KEDA-vs-Lys-Glu-Ala-Ser sequence confusion means buyers cannot be sure which molecule a vendor is even supplying.
US legal status
Not FDA-approved. Not on the 503A compoundable bulk substances list. Not legally compoundable for human clinical use in the United States. Sold online only as a 'research chemical' — vendors in that channel are unregulated and not verified by TPC.
Open research questions
- ? Do the hepatocyte protein-synthesis and liver-culture findings replicate in independent, non-Khavinson-affiliated laboratories, and do they translate to any in-vivo functional liver outcome?
- ? Which sequence is correct in commercial material — the published Lys-Glu-Asp-Ala (KEDA) or the Lys-Glu-Ala-Ser listed by some vendors — and how often does sold product match the studied peptide?
- ? Is there any human pharmacokinetic, bioavailability, or safety data for an orally administered four-amino-acid peptide that would even justify a Phase 1 study?
- ? Are the ex-vivo chromatin/heterochromatin effects in elderly-donor lymphocytes reproducible under blinded conditions, and do they correspond to any measurable clinical benefit rather than a cell-level biochemical change?
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