Livagen

Overview

Livagen is a short synthetic tetrapeptide with the sequence Lys-Glu-Asp-Ala (KEDA). It belongs to the family of "short peptide bioregulators" developed by Vladimir Khavinson and colleagues at the St. Petersburg Institute of Bioregulation and Gerontology — the same school that produced Epitalon and Thymalin. It is marketed by peptide vendors as a liver and anti-aging "bioregulator."

The substantive evidence behind Livagen is very small, older, and almost entirely from one research group. The primary data are a pair of studies (Khavinson, Lezhava et al., Bulletin of Experimental Biology and Medicine, 2002 and 2004) in which the peptide was added to cultured lymphocytes taken from elderly people and reported to cause chromatin decondensation and activation of ribosomal genes. This is ex vivo / in vitro work on human cells in a dish — not in vivo human clinical trials. Effects in living people, clinical endpoints, safety, and dosing are not established in the sources found.

The chemistry is reasonably well defined (molecular formula C18H31N5O9, PubChem CID 87919683), but the CAS number commonly quoted by vendors (195875-84-4) comes from commercial listings and was not confirmed against the PubChem registry record. Livagen has no FDA or EMA approval and is sold as a research-only chemical.

Chemistry and structure

Livagen is a linear tetrapeptide (four amino acids) with the sequence:

Lys-Glu-Asp-Ala (one-letter: KEDA)

The molecule is a small, water-soluble peptide with two acidic residues (Glu, Asp), a basic Lys terminus, and an Ala terminus. As with other Khavinson short peptides, the group has proposed that such peptides interact directly with chromatin; the structural chemistry itself (formula, identity as H-Lys-Glu-Asp-Ala-OH) is well defined in PubChem, but note the CAS discrepancy above.

Mechanism of action

The mechanisms attributed to Livagen should be read as preclinical findings and hypotheses, not established physiology in humans.

• Chromatin decondensation / de-heterochromatinization. Livagen is reported to induce decondensation of pericentromeric structural heterochromatin and general "activation" of chromatin in lymphocytes from elderly people. [In vitro] — cultured human lymphocytes/leukocytes from old donors, ex vivo (Khavinson, Lezhava, Monaselidze et al., Bull. Exp. Biol. Med. 2002, PMID 12533768).
• Ribosomal-gene activation. The peptide is reported to activate ribosomal genes and release genes repressed by age-related chromatin condensation, affecting chromosome 1 (and, per some reports, chromosome 9) structural chromatin. [In vitro] — cultured human lymphocytes from senile subjects (Khavinson, Lezhava, Malinin, Bull. Exp. Biol. Med. 2004, PMID 15085253).
• Lymphocyte-marker / liver "bioregulation." Livagen is claimed to shift lymphocyte marker populations (increase CD3+/CD4+/CD8+, decrease CD22+) and to act as a liver/immune bioregulator. [Hypothesis] — repeated in vendor and secondary summaries only; no primary peer-reviewed source was located for these specific claims, so treat them as unverified.

Research and evidence

The evidence base is small, old, and dominated by a single research group. The two primary studies are ex vivo experiments on human cells; there are no in vivo human trials.

Human evidence. There are no well-established human clinical trials of Livagen. Human involvement is limited to ex vivo / in vitro experiments — the peptide was added to cultured leukocytes/lymphocytes from elderly donors (reported ages roughly 75–88) and chromatin-activation effects were observed. Effects on live human subjects, clinical endpoints, safety, and dosing are not established in the sources found. Pharmacokinetics, bioavailability, and human toxicology are likewise not established in available sources.

Status and regulation

Livagen has no FDA or EMA approval and is not a licensed medicine in the United States or European Union. Wikipedia categorizes it under "drugs with no legal status." It is sold by peptide vendors labeled "research use only / not for human use." Any intended human use would make it an unauthorised / unapproved medicine.

On WADA status: no source located states a prohibited-list class code for Livagen, so its sport-eligibility status is not determinable here — and "unapproved" must not be read as automatically implying any particular WADA class. This is a separate axis from legality. Not medical or legal advice — check your own jurisdiction.

Safety

• No human safety data. No in vivo human trials were found; there is no characterized safety profile, and an absence of reported adverse events reflects a lack of study, not a demonstration of safety.
• Research-grade material. Product sold as "Livagen" is a research chemical; its identity, purity, and contaminant profile cannot be assumed to be controlled.
• Injectable-product risks. Where peptides like this are reconstituted and injected in unregulated settings, the usual risks of non-sterile injectables apply.
• Unverified identity. Even the commonly quoted CAS number is vendor-sourced and unconfirmed, underscoring how loosely such material can be characterized.

Legal status

Livagen is best described by its regulatory classification: a research reagent with no marketing authorisation as a medicine in any major jurisdiction. It has no FDA or EMA approval, and Wikipedia lists it among substances with "no legal status."

The absence of a specific ban is not affirmative permission to use it: a compound becomes an unauthorised medicine the moment it is intended for human use. Sport anti-doping (WADA) is a separate axis and is not determinable for Livagen from the sources found. This is not legal advice and status varies by country — verify the position in your own jurisdiction. (Framing dated 2026-07-08.)

How it compares

Livagen sits within the Khavinson "short peptide bioregulator" family and is best understood next to its better-documented cousins:

• Epitalon (Ala-Glu-Asp-Gly, AEDG) is another synthetic Khavinson tetrapeptide, promoted for telomerase/anti-aging effects. It has a larger — though still weak, single-group-dominated — literature than Livagen, including some animal and (mostly extract-based) human work. Livagen's evidence is thinner still, essentially two in vitro papers.
• Thymalin is a Khavinson-associated thymic peptide extract (a mixture, not a single peptide) registered in Russia as an immunomodulator. It shares the pattern of bold claims resting on a single research school with limited independent replication.

Across all three, the honest reading is the same: bold bioregulator claims, thin and mostly single-group preclinical evidence, and no Western regulatory approval.

Common misconceptions

• "Livagen is a proven liver / anti-aging treatment." It is not. The only substantive evidence is a couple of older, single-group in vitro studies on cultured lymphocytes; there are no in vivo human trials.
• "The chromatin studies were done in living elderly people." No — the peptide was added to cells cultured in a dish (ex vivo lymphocytes from elderly donors). An in vitro chromatin effect does not establish a clinical benefit in a living person.
• "The CAS number 195875-84-4 confirms its identity." That CAS is vendor-cited only and was not found in the PubChem CID 87919683 registry record. The formula (C18H31N5O9) and PubChem CID are the better-verified identifiers.
• "It clearly boosts CD3+/CD4+/CD8+ and lowers CD22+ lymphocytes." These lymphocyte-marker claims appear in vendor/secondary summaries only; no primary peer-reviewed source was located for them, so they are unverified.
• "No specific ban means it's legal to take." No. Absence of a ban is not permission; any intended human use would make it an unauthorised medicine, and it has no FDA/EMA approval.

Russian research

Much of the evidence for Livagen (KEDA, Lys-Glu-Asp-Ala) comes from Russian research — chiefly Khavinson's St. Petersburg Institute of Bioregulation and Gerontology, working in collaboration with the Lezhava/Jokhadze cytogenetics group in Tbilisi, plus a smaller Moscow contribution — and it is surfaced here for completeness and framed honestly for quality. The core body is small, single-school, mostly in vitro, and under-replicated; none of it upgrades the article's existing preclinical evidence level.

The central line of work is a cluster of ex vivo chromatin studies on cultured lymphocytes from elderly human donors. Livagen was reported to activate ribosomal genes, decondense pericentromeric structural heterochromatin, and "release" genes silenced by age-related chromatin condensation — i.e. de-heterochromatinization of chromatin from old people [In vitro] (Khavinson VKh, Lezhava TA, Monaselidze JG, et al. Effects of Livagen peptide on chromatin activation in lymphocytes from old people. Bull Exp Biol Med. 2002;134(4):389-92. PMID 12533768; DOI 10.1023/a:1021924702103). A follow-up pooled Livagen with four other short peptides (Vilon, Epithalon, Prostamax, Cortagen) and concluded that short peptides activate heterochromatinized chromosome regions in senile subjects (aged 75-88) — but Livagen is only one of five and no Livagen-specific effect size is isolated [In vitro] (Khavinson VKh, Lezhava TA, Malinin VV. Bull Exp Biol Med. 2004;137(1):78-81. PMID 15085253; DOI 10.1023/b:bebm.0000024393.40560.05). The same collaboration repeated and extended this chromatin-reactivation finding across nearly two decades — with Epitalon, Livagen and Vilon (Lezhava T, Monaselidze J, Kadotani T, et al. Georgian Med News. 2006;(133):111-5. PMID 16705247); reporting deheterochromatinization plus a modest reduction of cobalt-chloride-induced chromosome aberrations (3.4% vs 4.2% control) [In vitro] (Lezhava T, Jokhadze T. Ann N Y Acad Sci. 2007;1100:387-99. PMID 17460203; DOI 10.1196/annals.1395.043); and most recently confirming decondensation of heterochromatin and ribosomal-gene activation by Lys-Glu-Asp-Ala (Livagen) [In vitro] (Lezhava T, Jokhadze T, Monaselidze J, et al. Georgian Med News. 2023;(335):79-83. PMID 37042594). Importantly, these are the same overlapping authors — repetition by one collaboration, not independent replication — sample sizes are essentially never stated in the abstracts, and every endpoint is cytogenetic (chromatin decondensation, ribosomal-gene activation), not clinical.

Two non-chromatin sources add breadth but not strength. In an in vitro human-serum enzyme assay from the Moscow (Ashmarin/Myasoedov) school, Livagen inhibited enkephalin-degrading enzyme activity with a reported IC50 of ~20 microM, described as more potent than Epitalon (~500 microM) — a biochemical observation only, not a physiological or clinical effect, with the IC50 figures taken from the abstract [In vitro] (Kost NV, Sokolov OIu, Gabaeva MV, et al. Izv Akad Nauk Ser Biol. 2003;(4):427-9. PMID 12942748). The only genuine in vivo Livagen experiment located is a rat study of digestive enzymes, not liver disease: enzyme activity decreased in young rats and increased in old rats (approaching young-rat levels), with a ~50% in vitro reduction of glycyl-L-leucine dipeptidase — a neutral, age-dependent modulation [Animal] (Timofeeva NM, Khavinson VKh, Malinin VV, et al. Adv Gerontol. 2005;16:92-6. PMID 16075683).

The "hepatoprotective in hepatitis and cirrhosis models" claims that vendors attach to Livagen trace to a single 2020 review by Khavinson's own collaborators, which states that KEDA/Livagen "normalized immune and antioxidant status" and showed hepato- and immunoprotective effects [Review, summarizing Animal/In vitro work] (Kuznik BI, Khasanova NB, Ryzhak GA, et al. Adv Gerontol. 2020;33(1):159-164. PMID 32362099). This is a review, not primary data; the underlying animal hepatitis/cirrhosis experiments on the KEDA tetrapeptide could not be located as independently verifiable original articles. Critically, that review also discusses a separate calf-liver polypeptide extract called "Ventvil" (Вентвил) — a different substance from the synthetic KEDA tetrapeptide, which must not be conflated with Livagen. Russian-language sources describe hepatoprotective, immunomodulating and geroprotective effects in acute/chronic hepatitis and cirrhosis models, but no independently verifiable primary citation for those experiments was found. Likewise, vendor/blog claims that Livagen "normalizes cytochrome P450 / glutathione S-transferase / UGT expression," "stimulates HGF / EGF-receptor hepatocyte-proliferation genes," or shows "chromatin relaxation in hepatocytes" have no primary peer-reviewed source — and the verified chromatin studies were done in lymphocytes, not hepatocytes; the hepatocyte framing appears to be vendor extrapolation. Lymphocyte-marker claims (increased CD3+/CD4+/CD8+, decreased CD22+) and the vendor-cited CAS 195875-84-4 likewise lack a verifiable primary source.

On regulation: Livagen (KEDA) is not a registered medicine in Russia or anywhere else that could be verified — no ГРЛС (State Register of Medicines) entry for "Livagen" or KEDA as a finished pharmaceutical was located. It is distributed by peptide vendors as a research/"health" preparation labelled for liver support, i.e. an unlicensed research chemical, with no FDA or EMA approval. Any registration status attaching to the separate liver-extract product "Ventvil" must not be transferred to the synthetic KEDA tetrapeptide. On quality: the Russian primary evidence is small, older, single-school, and mechanistic, with overlapping authorship rather than independent replication, unstated sample sizes, cytogenetic/biochemical rather than clinical endpoints, and no human clinical trials — being studied in Russia is a fact about research activity (and registration, where it exists, is a regulatory fact), not proof of efficacy.