pe
pep-10941 v1 CC-BY-SA-4.0

Liver-protecting peptide Livagen (KEDA): a Khavinson bioregulator supplement

A small synthetic peptide studied in animals for protecting the liver and restoring digestive function; sold as a supplement in Russia, experimental and not an approved drug.

statusdesigned target? length4 aa refs1
snapshot preclinical 0% confidence
Class
Synthetic bioregulator tetrapeptide (Khavinson series)
Status
Not approved as a medicine in any major regulatory jurisdiction; sold in Russia as an oral dietary supplement; available in Western markets as a research chemical only
Best-supported effect
Chromatin decondensation and ribosomal gene activation in aged human lymphocytes (ex vivo, Khavinson group only); hepatoprotective and digestive enzyme restoration effects in rodent models
Main caveat
No human clinical trials of any kind; all evidence originates exclusively from one Khavinson-affiliated research group in primarily Russian-language literature; no independent Western replication of any finding
status 1 / 5
sequence4 aa
14
KEDA
overview readme

Snapshot

Class: Synthetic bioregulator tetrapeptide (Khavinson series)
Evidence tier: Animal-only evidence
Status: Not approved as a medicine in any major regulatory jurisdiction; sold in Russia as an oral dietary supplement; available in Western markets as a research chemical only
Best-supported effect: Chromatin decondensation and ribosomal gene activation in aged human lymphocytes (ex vivo, single research group); hepatoprotective and digestive enzyme restoration effects in rodent models
Main caveat: No human clinical trials of any kind; all evidence originates exclusively from one Khavinson-affiliated research group in primarily Russian-language literature; no independent Western replication of any finding


What this is

Livagen is a synthetic tetrapeptide with the sequence Lys-Glu-Asp-Ala (KEDA), developed by Vladimir Khavinson at the Saint Petersburg Institute of Bioregulation and Gerontology as part of the Cytogen / Cytomax bioregulator series. It was proposed as the chemically defined synthetic counterpart to a bioactive fraction derived from porcine liver tissue extract. The Khavinson framework assigns it specificity for liver, gastrointestinal, and immune tissue.

Livagen shares its first three amino acids with Vesugen (Lys-Glu-Asp / KED), differing only at the C-terminal alanine. The originating research group claims distinct tissue tropism for each peptide — liver and immune cells for KEDA versus vascular endothelium for KED — but no molecular basis for this specificity has been established. Among Khavinson bioregulators, Livagen has some of the more developed mechanistic characterization due to ex vivo cytogenetic experiments in primary human lymphocytes, though the entire published evidence base originates from a single research network with no independent replication.


Evidence map

Evidence layerGradeWhat it supports
Human clinicalNoneNo human clinical trials are identifieds available literature
Ex vivo (human tissue)Moderate — single groupChromatin decondensation and ribosomal gene activation in lymphocytes from elderly donors (ages 75–88); two published studies; both from the originating group only
AnimalModerate — single groupDigestive enzyme restoration in aged rats; protein synthesis enhancement in aged hepatocyte cultures; hepatoprotective and immunomodulatory effects in rodent hepatitis models; tissue-specific effects confirmed in liver, GI, and immune tissue
In vitro / cellWeak — single groupProtein synthesis effects in aged rat hepatocyte cultures; tissue culture work across liver, GI, and immune lines
ComputationalNone identifiedNo computational or structural prediction data identified in available literature
MechanismPlausible — not independently verifiedDeheterochromatinization (heterochromatin to euchromatin conversion) proposed as primary mechanism; ex vivo cytogenetic observations provide concrete but unverified support; no binding target identified

Evidence concentration caveat: Substantially all published evidence originates from one research network (Khavinson-affiliated investigators, Saint Petersburg Institute of Bioregulation and Gerontology), predominantly in Russian-language literature. Independent replication of the chromatin-decondensation finding by Western cytogenetics laboratories has not occurred. Confidence in claims derived from this evidence base reflects the absence of independent replication.


Claim check

ClaimVerdictEvidence layerConfidence
Chromatin decondensation and ribosomal gene reactivation in aged human lymphocytes ex vivoSupported (ex vivo, single group)In vitro / ex vivo (primary human cells)Medium — single research group; no independent Western replication
Digestive enzyme restoration in aged animalsSupported (animal)Animal (aged rat model)Medium — rodent model only; no human translation established
Hepatoprotective effectsSupported (animal — rodent hepatitis model)AnimalLow — rodent models and a single-group 2020 review; no human clinical evidence
Immune cell reactivation in elderlyPartially supported (ex vivo / animal)In vitro / ex vivo + animalLow — ex vivo lymphocyte data and rodent tissue work; no clinical immune-endpoint trial
Treatment for hepatitis or diagnosed liver disease in humansNot establishedNoneHigh confidence in verdict — no human clinical trials in any hepatic indication
Anti-aging or longevity benefit in humansNot establishedNoneHigh confidence in verdict — no human clinical endpoint data of any kind

Experimental exposure

This section reports exposure used in animal experiments and ex vivo assays described in the available literature. It does not establish human dosing.

ContextSystemExperimental exposure / conditionDurationEndpointLimitation
Animal experimentAged rats (oral administration)Oral Livagen; exact dose not individually extracted from sourceMulti-day to multi-week; not individually extractedDigestive enzyme activity (dipeptidases) in GI tissue vs. young-animal baselineRodent only; no human equivalent; dose regimen not extractable from source
Ex vivo assayLymphocytes from elderly human donors (ages 75–88)Livagen applied to isolated lymphocyte cultures; exact concentration not individually extractedAssay duration not individually extractedHeterochromatin decondensation; ribosomal gene activation on chromosomes 1 and 9Ex vivo, not a clinical intervention; single research group only; no independent replication
In vitro assayHepatocyte cultures from aged ratsLivagen applied to hepatocyte culture medium; exact concentration not individually extractedCulture duration not individually extractedProtein synthesis rhythm and intensity vs. young-cell controlsIn vitro; no human hepatocyte or clinical data
Animal experimentRodent hepatitis modelSource describes hepatoprotective effects; exact model, dose, and regimen not individually extractedNot individually extractedAntioxidant markers, liver function indicatorsRodent model; exact experimental parameters not extractable from review; no human clinical equivalence

Community and commercial dosing conventions described in available literature (Khavinson oral capsule schedules, injectable research-chemical conventions) are not rendered in this section. These involve routes and patterns not represented in the published experimental evidence.


Preclinical safety signals

SignalSystemNotes
No adverse effects reported in published studiesAnimal models and ex vivo tissuePublished reports describe the peptide as well-tolerated; formal toxicology studies are absent; surveillance quality is limited
Theoretical: unintended gene activation concernMechanistic concern — not observed in published studiesThe proposed mechanism (chromatin reactivation and ribosomal gene activation in aged cells) operates in the same biology where unintended growth-promoting effects would be a concern; no formal genotoxicity or carcinogenicity study is present in available literature
Theoretical: lymphocyte hyperactivity concernMechanistic concernClaimed immune-cell reactivation is mechanistically a concern in conditions driven by lymphocyte hyperactivity (autoimmune disease context); no controlled safety study in this population
One Khavinson-program multi-peptide study found no chromatin condensation abnormalities in elderly subjectsHuman tissue / multi-peptide studyPer available sources, this as a safety-relevant observation; it is not a dedicated Livagen safety trial
Long-term safetyNot established in any systemNo chronic exposure data across repeated courses; effects on oncogene-suppressor balance over multi-year use are unknown

Source-noted cautions without clinical safety data: Research active or recent malignancy, active autoimmune disease, pregnancy, breastfeeding, and pediatric use as populations for which no data exist and for which the proposed mechanism raises theoretical concerns. No reproductive toxicology, developmental, or pediatric safety studies are identified. These are source-noted precautions, not label exclusions from a clinical trial or approved label.

Theoretical interaction context from source: Research theoretical mechanistic concerns about concurrent use with anticancer chemotherapy and radiation (due to claimed transcriptional reactivation working against treatment intent) and with immunosuppressive regimens (due to claimed lymphocyte reactivation). No controlled drug-interaction data are present; these are mechanistic concerns only, not clinical pharmacovigilance findings.

No human pharmacovigilance data are present in available literature.


Regulatory status

Region / bodyStatusNotes
US (FDA)Not approvedPer available sources, not FDA-approved for any indication; not recognized as a dietary supplement ingredient; not on the FDA compounding-eligible peptide list; available in Western markets as a research chemical — not an authorized clinical channel
EU (EMA / MHRA)Not authorizedPer available sources, no EMA or MHRA authorization; not independently verified in this card
Canada (Health Canada)Not authorizedPer available sources, no Health Canada authorization; not independently verified in this card
RussiaSold as dietary supplement / functional foodPer available sources, availability under the Peptides.ru / Khavinson Peptides brand as an oral peptide bioregulator capsule; positioned as a dietary supplement, not a registered prescription medicine; this does not constitute regulatory approval by a major stringent regulatory authority
WADAProbable S0 coverage — per available sourcesSource states Livagen is not specifically named on the WADA Prohibited List but may fall under the S0 catch-all for substances not currently approved by any governmental regulatory health authority for human therapeutic use; per available sources only; current list status not independently verified in this card

No approved therapeutic status identified in major regulatory jurisdictions. This card describes a research and commercially sold peptide, not an approved medicine.


Mechanism

Livagen (Lys-Glu-Asp-Ala) is proposed to act through chromatin remodeling: specifically, inducing deheterochromatinization — the conversion of condensed, transcriptionally silent heterochromatin back to open, transcriptionally active euchromatin. In aging cells, portions of the genome are progressively silenced by chromatin compaction; the Khavinson group's core claim is that the KEDA tetrapeptide reverses this process, reactivating ribosomal genes and other age-silenced programs.

Published cytogenetic evidence from the originating group (PMIDs 12533768, 15085253) shows direct ex vivo visualization of heterochromatin decondensation in lymphocytes from elderly donors (ages 75–88), including decondensation of pericentromeric structural heterochromatin on chromosomes 1 and 9 and activation of ribosomal RNA genes. In aged rat hepatocyte cultures, Livagen was reported to enhance protein synthesis rhythm and intensity with larger effects in older cells. Oral administration in aged rats was reported to restore dipeptidase activity in GI tissue toward young-animal levels. A 2020 review from the same research group describes hepatoprotective and immunomodulatory effects in rodent hepatitis models, including normalization of antioxidant markers.

The proposed oral activity is attributed by published research to resistance of the KEDA tetrapeptide to degradation by small intestinal peptidases; human pharmacokinetic characterization does not exist.

Mechanism limitations: No molecular binding target or receptor has been identified. Mechanism is inferred from ex vivo cytogenetic end-states only. The entire mechanistic evidence base originates from a single research group with no independent replication. The tissue tropism of KEDA for liver and immune tissue — as distinct from the related KED (Vesugen) for vascular endothelium — has no established molecular explanation. Ex vivo chromatin effects in isolated lymphocytes may not translate to in vivo or clinical outcomes.


Chemistry

FieldValue
Amino-acid sequenceLys-Glu-Asp-Ala (KEDA)
Length4 amino acids
TopologyLinear
ModificationsNone described in source
Molecular weightNot individually extracted from source
FormulaNot individually extracted from source
CASNot individually extracted from source
Salt formNot individually extracted from source
Sequence confidenceConsistent throughout the available literature

Relation to Vesugen: Livagen (Lys-Glu-Asp-Ala) shares its first three residues with Vesugen (Lys-Glu-Asp / KED). The originating research group claims distinct tissue tropism; they are not interchangeable based on published research literature, though the molecular basis for this distinction has not been independently validated.


Open questions

  • Independent replication of the chromatin-decondensation finding: The defining mechanistic claim — heterochromatin decondensation and ribosomal gene activation in aged human lymphocytes — has not been replicated by any laboratory outside the originating Khavinson group. This is the foundational gap before any clinical translation argument can be made.
  • Human pharmacokinetics: Oral and parenteral bioavailability of the KEDA tetrapeptide in humans is uncharacterized. The oral capsule is the dominant commercial form, claimed to exploit peptidase resistance, but no human absorption, distribution, metabolism, or excretion data are identifieds source.
  • Tissue-specificity mechanism: The molecular basis for why Lys-Glu-Asp-Ala preferentially affects liver and immune tissue while the near-identical Lys-Glu-Asp (Vesugen) is claimed to target vascular endothelium has no established explanation. Without this, the tissue-tropism claim cannot be independently assessed.
  • Blinded randomized controlled trials in any indication: No controlled clinical trial in any liver, immune, or aging indication is identified in available literature. Evidence remains dominated by ex vivo human-tissue work and rodent models. The step from preclinical to any human clinical endpoint has not been taken.
  • Long-term safety of repeated chromatin-reactivation cycles: The proposed mechanism operates in biology adjacent to oncogene and tumor-suppressor regulation. Formal genotoxicity, carcinogenicity, and chronic-exposure studies do not exist in available literature. The theoretical concern about unintended gene activation in aged cells has not been evaluated.
  • Comparative efficacy versus established interventions: No head-to-head data comparing Livagen to established hepatoprotective agents or standard interventions exists. The clinical magnitude and relevance of animal-model effects is uncharacterized.
Hypotheses1 direction▾ collapse

Research directions for this peptide, selected from the current sources — hypotheses you can explore and model. None of it is proven yet; tap any one to see the full thinking.

openupdated 2026-06-05

Could KEDA organise itself into microscopic beads or gels that act as natural packaging for delivering drugs that are normally too fragile to survive digestion?

Short therapeutic peptides are almost always destroyed before they can be absorbed. If KEDA forms its own stable nano-carriers, it could solve this delivery problem cheaply and safely, benefiting the development of many peptide drugs, not just Livagen itself.

The hypothesis
The Lys-Glu-Asp-Ala (KEDA) sequence functions as a minimal self-assembling zwitterionic hydrogel unit at physiological pH and ionic strength because the Lys basic amine and the tandem Glu-Asp acid pairs produce alternating charge complementarity sufficient for beta-sheet-like hydrogen-bonded stacking, enabling KEDA to form nanostructures at millimolar concentrations that could serve as depot matrices for co-delivered therapeutic peptides.
Why it’s plausible
Ionic self-assembling peptides (ISAPs) based on alternating charged residues form stable hydrogels. KEDA has K(+), E(-), D(-), A(neutral) giving a charge pattern of (+)(-)(-)(0), providing partial alternating complementarity. Short Ala-terminated sequences promote backbone hydrogen bonding. If KEDA forms even transient beta-sheet oligomers it could serve as a structural component for nanoparticle formulation of the Khavinson peptide family or other short therapeutic peptides, a role entirely unrelated to its proposed bioregulatory function.
Why it matters
Repurposing KEDA as a biocompatible self-assembling scaffold would convert a poorly characterised supplement into a functional excipient for peptide drug delivery, solving the oral bioavailability problem that limits the entire Khavinson series without requiring expensive chemical modification.
Plausibility.35
Novelty.65
Impact.55
Basis · grounding1 paper · 2 computed/notes
[1]
sequenceKEDA: charge sequence (+)(-)(-)( neutral); partial alternating complementarity; C-terminal Ala supports backbone stacking; sequence length of 4 residues is within the range of minimal ISAP units described in the literature.
[2]
sourceSolid-phase synthesis of short peptides is well established and cost-effective; KEDA-based self-assembly scaffolds would be scalable at low cost.
[3]
paper
Alternative peptide delivery strategies including self-assembling nanostructures are expanding the formulation toolbox for peptide therapeutics with poor intrinsic stability.
doi: 10.1039/d5ra03731j
details expand to inspect
3-letter notation
Lys-Glu-Asp-Ala
citationbibtex
peptidemodel (2026). Liver-protecting peptide Livagen (KEDA): a Khavinson bioregulator supplement (pep-10941, v1). PeptideModel. https://peptidemodel.com/card/pep-10941
@peptide{pep10941,
  sequence = {KEDA},
  target   = {},
  author   = {peptidemodel},
  year     = {2026},
  status   = {designed}
}
clinical trials 0 trials · checked 2026-05-09
0
no registered clinical trials as of 2026-05-09; we'll re-check periodically
references 1 papers
discussion no comments
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