# Livagen — Research Peptide Profile

> Livagen (Lys-Glu-Asp-Ala, KEDA) is a Khavinson liver tetrapeptide. Hepatocyte, digestive enzyme, chromatin and enkephalinase data; no human trials.

Source: https://peptpedia.org/peptide/livagen | Published: 2026-09-18 | Last updated: 2026-09-18

Livagen is a Khavinson-class tetrapeptide (Lys-Glu-Asp-Ala, KEDA) created from amino acid analysis of liver polypeptide preparations. Published research is preclinical: it raised protein synthesis in cultured rat hepatocytes, inhibited enkephalin-degrading enzymes in human serum in vitro, and decondensed age-condensed chromatin in lymphocytes from elderly donors. No human trial or pharmacokinetic study has been published.

## Overview

Livagen (Lys-Glu-Asp-Ala, coded KEDA) is a synthetic tetrapeptide from the Khavinson bioregulator family, obtained by directed chemical synthesis based on amino acid analysis of liver polypeptide preparations and positioned in that literature as the liver-directed member of the family. The published research is preclinical and ex vivo. In cultured rat hepatocytes it increased protein synthesis with the largest effect in cells from old animals, while the pineal tetrapeptide [Epithalon](/peptide/epithalon) (Epitalon) showed no such effect in the same cultures. In human serum in vitro it inhibited enkephalin-degrading enzymes with an IC50 of about 20 micromolar without binding opioid receptors. Two weeks of oral dosing shifted digestive enzyme activity of old rats toward young-control levels. Ex vivo exposure of lymphocytes from elderly donors produced ribosomal gene activation and decondensation of age-condensed chromatin. No human clinical trial, pharmacokinetic study, or independent replication has been published.

## Molecular Profile

- **Category:** bioregulators
- **Molecular formula:** C18H31N5O9
- **Molecular weight:** 461.5 g/mol
- **CAS number:** 433257-50-2
- **Amino acid sequence:** Lys-Glu-Asp-Ala
- **Also known as:** KEDA, Lys-Glu-Asp-Ala
- **Half-life:** Not established; no pharmacokinetic study published
- **Solubility:** Water-soluble short polar peptide; no formal solubility study published
- **Storage:** Store lyophilized at -20°C.

## Mechanism of Action

No molecular receptor has been identified for Livagen. Within the Khavinson framework, the peptide is proposed to penetrate cells and modulate gene expression through direct interaction with chromatin and DNA, consistent with the observed decondensation of pericentromeric heterochromatin and reactivation of age-silenced ribosomal genes in lymphocytes from elderly donors. A distinct enzymatic mechanism is documented in vitro: Livagen inhibited enkephalin-degrading enzymes in human serum, an effect that could theoretically raise endogenous enkephalin tone, though radioreceptor assays found no interaction with mu or delta opioid receptors. The tissue-selectivity hypothesis rests on a hepatocyte culture comparison in which Livagen raised protein synthesis while a pineal-derived tetrapeptide did not. None of these mechanisms has been confirmed by structural biology or independent laboratories.

## Key Research Findings

- Livagen (Lys-Glu-Asp-Ala) is the synthetic minimal peptide modeled on liver polypeptide preparations, developed by the Khavinson bioregulation group as the liver-directed family member.
- In cultured rat hepatocytes, Livagen increased protein synthesis with the largest effect in cells from old animals; Epithalon tested in parallel showed no such effect.
- Livagen inhibited enkephalin-degrading enzymes in human serum in vitro with an IC50 of about 20 micromolar, roughly 25-fold more potent than Epithalon in the same assay, without binding opioid receptors.
- Ex vivo, Livagen decondensed age-condensed heterochromatin and reactivated ribosomal genes in lymphocytes from elderly donors; no human in vivo study exists.

## Livagen Pharmacokinetics: Oral Stability Hints, No Formal Data

No formal pharmacokinetic study has been published for Livagen in any species. The only absorption-relevant evidence is indirect: intestinal peptidases hydrolyzed the peptide weakly in vitro, and oral dosing produced measurable physiological effects in rats, which together suggest at least partial survival of the peptide through the gut.

### Evidence Bearing on Absorption

- Livagen was hydrolyzed only weakly by small-intestine peptide hydrolases in vitro, and two weeks of oral administration altered digestive enzyme activity in rats, suggesting partial oral stability of the tetrapeptide (PMID 16075683).
- In human serum in vitro, Livagen inhibited enkephalin-degrading enzymes with an IC50 of about 20 micromolar; whether serum concentrations anywhere near that range are achievable in vivo has never been measured (PMID 12942748).
- No half-life, bioavailability, clearance, or distribution value exists for any species or route of administration.

### Implications for Research Interpretation

- Ex vivo chromatin effects in lymphocytes from elderly donors occurred at cell-culture exposures that cannot be mapped to human doses, because no exposure-response relationship has ever been established (PMID 12533768).
- Class-level reviews from the proposing group hold that short peptides act through intracellular and nuclear penetration, which would make plasma concentration a poor proxy for effect even if it were measured (PMID 34834147).
- Dosing schedules circulating in community sources extrapolate from rat and cell data without any pharmacokinetic support and should not be treated as validated protocols.

## Safety & Tolerability

No human safety data exist for Livagen: no clinical trial, no pharmacokinetic study, and no structured adverse-event reporting anywhere in its literature. The evidence base is ex vivo human lymphocyte work and rat studies from a single research network. An in vitro finding that Livagen inhibits enkephalin-degrading enzymes in human serum is a mechanistic observation whose in vivo significance is unknown.

**Human data status:** No human interventional or observational studies have been published. Human-related data are limited to ex vivo chromatin studies in lymphocytes from elderly donors and in vitro enzyme assays in human serum.

**Regulatory status:** Not approved for human use by the FDA, EMA, or any other major regulatory agency; no verified pharmaceutical registration. Sold as a research compound.

- Livagen inhibited enkephalin-degrading enzymes in human serum in vitro with an IC50 of about 20 micromolar, without binding mu or delta opioid receptors; whether such concentrations occur in vivo is unknown, but an interaction with endogenous opioid tone cannot be excluded at sufficient exposure. (evidence tier: in-vitro; [PMID 12942748](https://pubmed.ncbi.nlm.nih.gov/12942748/))
- Rats receiving Livagen orally for two weeks showed age-normalizing changes in digestive enzyme activity; the report contains no structured toxicity assessment, so tolerability cannot be inferred beyond the absence of described harm. (evidence tier: animal; [PMID 16075683](https://pubmed.ncbi.nlm.nih.gov/16075683/))
- Chromatin decondensation and ribosomal gene reactivation were observed ex vivo in lymphocytes from elderly donors; these cytogenetic endpoints are mechanistic findings, not safety evidence. (evidence tier: in-vitro; [PMID 12533768](https://pubmed.ncbi.nlm.nih.gov/12533768/))
- The originating network's review literature describes hepatoprotective and geroprotective properties in animal liver-pathology models; independent safety evaluation by any outside group has never been performed. (evidence tier: theoretical; [PMID 32362099](https://pubmed.ncbi.nlm.nih.gov/32362099/))

## Dosing Information (Research Context)

Published preclinical work used oral administration in rats over 14 days, with the dose not disclosed in the English abstract, and ex vivo lymphocyte exposure at microgram-level concentrations. No human dosing protocol exists and no pharmacokinetic study has been published in any species.

| Route | Dose | Frequency | Notes |
| --- | --- | --- | --- |
| Oral (rat) | Not disclosed in English abstract | Daily × 14 days | Digestive enzyme study in young and aged rats; no human dosing established |

## Researched Effects

- **Hepatocyte Protein Synthesis** (evidence: preliminary): In monolayer hepatocyte cultures from rats aged 1 to 24 months, Livagen increased the level of protein synthesis across age groups, with the largest effect in cells from old animals, where it also increased the amplitude of protein synthesis fluctuations. Epithalon, a tetrapeptide constructed from pineal peptide analysis, did not change protein synthesis intensity in the same hepatocyte cultures, a tissue-selectivity observation that the authors place at the center of the bioregulator hypothesis. The peptide used in this work was obtained by directed chemical synthesis based on amino acid analysis of liver polypeptide preparations. The study characterizes a functional cellular effect but does not establish any in vivo liver outcome.
- **Chromatin Reactivation in Elderly Cells** (evidence: preliminary): Ex vivo treatment of lymphocytes from elderly donors with Livagen induced activation of ribosomal genes, decondensation of pericentromeric structural heterochromatin, and release of genes repressed through age-related condensation of euchromatic chromosome regions, an effect the authors describe as de-heterochromatinization of aged chromatin. This 2002 study from the Khavinson and Lezhava groups is the most-cited mechanistic paper on Livagen and the foundation of its epigenetic framing. The readouts are cytogenetic, measured in cells removed from donors, so the finding describes a structural chromatin effect rather than a demonstrated functional benefit in humans.
- **Enkephalinase Inhibition** (evidence: preliminary): In human serum in vitro, Livagen inhibited enkephalin-degrading enzymes with an IC50 of about 20 micromolar, outperforming the known peptidase inhibitors puromycin, leupeptin, and D-PAM in the same assay, and was roughly 25-fold more potent than Epithalon, whose IC50 was about 500 micromolar. Radioreceptor assays with labeled enkephalin showed no interaction between Livagen and mu or delta opioid receptors in rat brain membrane fractions. The finding suggests Livagen could in principle slow breakdown of endogenous enkephalins, but whether serum concentrations sufficient for this effect occur in vivo is unknown, so its physiological significance is uncharacterized.
- **Digestive Enzyme Normalization** (evidence: preliminary): Two weeks of oral Livagen administration in rats shifted digestive enzyme activity in an age-dependent direction: enzyme activity decreased in young animals and increased in old animals, in most cases approaching the activity levels of young control animals. In vitro, the peptide was hydrolyzed only weakly by small-intestine peptidases, suggesting partial oral stability, and it reduced glycyl-L-leucine dipeptidase activity in the small intestine by about 50% under assay conditions. This is the only oral-administration experiment in the Livagen literature, and the English abstract does not disclose the dose used.
- **Hepatoprotection in Animal Models** (evidence: preliminary): A 2020 review from the Khavinson research network synthesizes experimental work on the liver polypeptide complex Ventvil and the KEDA tetrapeptide (Livagen), describing hepatoprotective, immunoprotective, and anti-aging properties in animal models of liver fibroid induration and acute and chronic hepatitis, together with in vitro findings. As a review authored by the originating laboratory and summarizing largely Russian-language primary work, it maps the claimed research territory for Livagen rather than providing independently verifiable experimental data, and the underlying animal hepatitis studies are not individually indexed with English abstracts in PubMed.

## Research Applications

- Hepatology Research
- Gerontology
- Epigenetics Research
- Enzyme Regulation

## Key Studies

### Effects of Livagen peptide on chromatin activation in lymphocytes from old people

Khavinson VKh, Lezhava TA, Monaselidze JG, et al. — *Bulletin of Experimental Biology and Medicine* (2002) — [PMID 12533768](https://pubmed.ncbi.nlm.nih.gov/12533768/) | [doi:10.1023/a:1021924702103](https://doi.org/10.1023/a:1021924702103)

This foundational Livagen study examined chromatin endpoints in lymphocytes from elderly donors exposed to the peptide ex vivo. Livagen induced activation of ribosomal genes, decondensation of pericentromeric structural heterochromatin, and release of genes repressed through age-related condensation of euchromatic regions in chromosomes. The authors conclude that Livagen causes de-heterochromatinization of chromatin in cells from old people, realized through modification of heterochromatin and heterochromatinized regions. The work is the basis of Livagen's epigenetic bioregulator framing, with the caveat that it measures cytogenetic endpoints in cultured cells rather than outcomes in living humans.

### Effect of new peptide bioregulators livagen and epitalon on enkephalin-degrading enzymes in human serum

Kost NV, Sokolov OIu, Gabaeva MV, et al. — *Izvestiia Akademii Nauk. Seriia Biologicheskaia* (2003) — [PMID 12942748](https://pubmed.ncbi.nlm.nih.gov/12942748/)

This in vitro study tested whether Livagen (Lys-Glu-Asp-Ala) and Epitalon (Ala-Glu-Asp-Gly) interact with the endogenous opioid system. Both peptides inhibited enkephalin-degrading enzymes in human serum, with Livagen more efficient than the known peptidase inhibitors puromycin, leupeptin, and D-PAM in this assay. Dose-inhibition curves gave IC50 values of 20 micromolar for Livagen and 500 micromolar for Epitalon. Radioreceptor assays with tritiated D-Ala2,D-Leu5-enkephalin found no interaction between either peptide and mu or delta opioid receptors in rat brain membrane fractions. The physiological significance of the enkephalinase inhibition at achievable in vivo concentrations is uncharacterized.

### Rhythm of protein synthesis in cultures of hepatocytes from rats of different ages: norm and effect of the peptide livagen

Brodskii VIa, Khavinson VKh, Zolotarev IuA, et al. — *Izvestiia Akademii Nauk. Seriia Biologicheskaia* (2001) — [PMID 15926314](https://pubmed.ncbi.nlm.nih.gov/15926314/)

This cell-culture study measured the circumhoralian rhythm of protein synthesis in monolayer hepatocytes from rats aged 1 to 24 months. Livagen, obtained by directed chemical synthesis on the basis of amino acid analysis of liver polypeptide preparations, increased the level of protein synthesis in hepatocytes from rats of all ages, with the highest effect in cells from old animals, and it increased the amplitude of protein synthesis fluctuations in old-rat hepatocytes. The pineal-derived peptide Epitalon did not change protein synthesis intensity in the same cultures, a comparison the authors use to argue tissue selectivity of short peptide bioregulators.

### Effect of peptide Livagen on activity of digestive enzymes in gastrointestinal tract and non-digestive organs in rats of different ages

Timofeeva NM, Khavinson VKh, Malinin VV, et al. — *Advances in Gerontology* (2005) — [PMID 16075683](https://pubmed.ncbi.nlm.nih.gov/16075683/)

This rat study is the only oral-administration experiment in the Livagen literature. The authors report that Livagen is weakly hydrolyzed by peptide hydrolases of the small intestine, that it reduces glycyl-L-leucine dipeptidase activity in small intestine by 50% in vitro, and that two weeks of oral administration shifted digestive enzyme activity in an age-dependent way: activity decreased in young animals and increased in old animals, in the majority of cases approaching the levels seen in young control animals. The English abstract does not disclose the dose, and the study contains no structured toxicity assessment.

### The influence of polypeptide liver complex and tetrapeptide KEDA on organism physiological function in norm and age-related pathology

Kuznik BI, Khasanova NB, Ryzhak GA, et al. — *Advances in Gerontology* (2020) — [PMID 32362099](https://pubmed.ncbi.nlm.nih.gov/32362099/)

This review from the Khavinson network summarizes the claimed hepatoprotective, immunoprotective, and anti-aging properties of the liver polypeptide complex Ventvil and the KEDA tetrapeptide (Lys-Glu-Asp-Ala, Livagen). It describes high efficiency of both agents in animal models of liver pathology including liver fibroid induration and acute and chronic hepatitis, alongside in vitro findings, and frames their use around the elevated liver-disease risk of elderly patients exposed to polypharmacy. Because the review is authored by the developing group and covers largely Russian-language primary sources, it serves as a map of the claimed evidence base rather than independent verification of it.

## Frequently Asked Questions

### What is Livagen?

Livagen is a synthetic tetrapeptide, Lys-Glu-Asp-Ala (KEDA), created by directed chemical synthesis based on amino acid analysis of liver polypeptide preparations. It belongs to the Khavinson class of short peptide bioregulators and is positioned in that literature as the liver-directed member of the family. Published research covers hepatocyte protein synthesis, chromatin structure in aged cells, enkephalin-degrading enzymes, and digestive enzyme activity. It is not approved for human use.

### Is Livagen the same peptide as Testagen?

No. Livagen is Lys-Glu-Asp-Ala (KEDA), while Testagen is Lys-Glu-Asp-Gly (KEDG); they differ only in the fourth residue, alanine versus glycine. The sequences are documented in the primary literature, with Testagen's KEDG sequence shown explicitly in a 2011 Biochemistry (Moscow) study of fluorescently labeled Khavinson peptides (PMID: 22117547). Vendor and community sources occasionally confuse the two, so sequence verification on a certificate of analysis matters for research use.

### What is the Livagen enkephalinase finding?

A 2003 study found that Livagen inhibited enkephalin-degrading enzymes in human serum in vitro with an IC50 of about 20 micromolar, outperforming puromycin, leupeptin, and D-PAM in the same assay and running about 25-fold more potent than Epithalon. Radioreceptor assays showed no binding to mu or delta opioid receptors (PMID: 12942748). Whether serum concentrations sufficient for enzyme inhibition occur in the body is unknown, so the physiological relevance of this in vitro potency is uncharacterized.

### Has Livagen been studied in humans?

No human clinical trial of Livagen has been published. Human-related data are ex vivo: lymphocytes from elderly donors exposed to Livagen showed ribosomal gene activation and decondensation of age-condensed heterochromatin (PMID: 12533768). Everything else is rat research, including hepatocyte culture work and a two-week oral dosing study of digestive enzymes (PMID: 16075683).

### Is Livagen safe?

Safety is uncharacterized. There is no toxicology study, no human trial, and no structured safety reporting in the animal work. The in vitro enkephalinase inhibition finding means an interaction with endogenous opioid tone cannot be excluded at sufficient exposure, although opioid receptor binding was not detected in the same study. Livagen is an unapproved research compound.

## Related Peptides

- [Epithalon](https://peptpedia.org/peptide/epithalon)
- [Ovagen](https://peptpedia.org/peptide/ovagen)
- [Testagen](https://peptpedia.org/peptide/testagen)
- [Vilon](https://peptpedia.org/peptide/vilon)

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