Livagen

At a Glance

Classification: Synthetic tetrapeptide; short peptide bioregulator; experimental liver-associated peptide

Livagen is the synthetic tetrapeptide Lys-Glu-Asp-Ala (KEDA). It was developed within the Khavinson short-peptide program from analysis of liver-derived peptide preparations and is commonly described as a liver bioregulator. Unlike several bioregulators we've just covered, Livagen actually has direct experimental work in rat liver cultures and hepatocytes, so the liver association isn't merely a commercial label. Its research nevertheless remains narrow. Much of the literature comes from the same interconnected research network, and there is no convincing modern clinical trial demonstrating that administered Livagen treats human liver disease. A 2020 review describes experimental hepatoprotective findings in animal and in-vitro liver-disease models, but that review also comes from the originating research network. A particularly interesting part of Livagen research isn't liver-specific at all: experiments using cultured lymphocytes from elderly human donors reported changes in chromatin organization and ribosomal-gene activity.

What Is Livagen?

Livagen is a four-amino-acid peptide Lys-Glu-Asp-Ala (KEDA). The peptide was reportedly constructed through analysis of liver peptide preparations. In rat hepatocyte cultures, Livagen increased protein synthesis, with the largest reported effect occurring in cells from older animals. An organotypic rat-tissue study also compared Livagen with Cortagen, Epitalon and Vilon and reported tissue-associated effects, with Livagen stimulating development of liver explants. That's substantially better support for its “liver peptide” identity than we found for some of the other bioregulators. It still doesn't establish a human liver therapy.

What Are Researchers Studying?

How Does It Work?

No single validated Livagen receptor is known. The experimental picture currently looks more like: Livagen / KEDA → cellular uptake → changes involving chromatin organization and/or intracellular signaling → altered gene and protein activity → tissue-level effects under experimental conditions. A broader Khavinson model proposes that short peptides can enter cells and interact with particular DNA sequences. Molecular modeling work assigned KEDA a proposed DNA-binding sequence, but this is a mechanistic model, not proof that orally or systemically administered Livagen reaches human nuclei and selectively regulates those genes in vivo. That's an important Aminodex distinction.

What Does the Research Show?

Notable Studies

What We Still Don't Know

Human pharmacokinetics; Human oral bioavailability; Plasma half-life; Tissue distribution; Whether intact KEDA reaches human liver after administration; Whether proposed DNA interactions occur meaningfully in vivo; Whether it improves ALT/AST or other clinical liver endpoints; Whether it treats hepatitis or fibrosis in humans; Whether it prevents age-related liver dysfunction; Long-term human safety; Reproductive/genotoxic safety; Whether the findings replicate outside the originating research network.

Related Compounds

Sources & References

1. Ryadnova IYu, Filippov SV, Yuzhakov VV. Functional morphology of an organotypic liver culture exposed to the peptide Livagen. Adv Gerontol. 2002.
2. Timofeeva NM, Khavinson VKh, Malinin VV, et al. Effect of peptide Livagen on activity of digestive enzymes in rats of different ages. Adv Gerontol. 2005.
3. 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):389–392.
4. Effect of Livagen and Epitalon on enkephalin-degrading enzymes in human serum.