Livagen

What it is. Livagen is Lys-Glu-Asp-Ala (KEDA), one of the tetrapeptides in the Khavinson short-peptide family, designated as the liver bioregulator on the programme's organ-specific principle [5].

What its literature is actually about. Chromatin, in white blood cells, from old people, in a dish. The 2002 study found Livagen activated ribosomal genes, decondensed pericentromeric structural heterochromatin, and released genes repressed by the age-related condensation of euchromatic regions [1]. A 2006 paper compared Epitalon, Livagen and Vilon on the same measures and found Livagen behaved like Epitalon - decondensing pericentromeric heterochromatin - where Vilon did not [2]. A 2007 study added that Livagen reduced the chromosomal aberrations cobalt ions induce in cells from old donors, from 4.2% to 3.4% [3]. A further study looked at short peptides and lymphocyte chromatin in senile subjects generally [6].

What is conspicuously absent. Anything about the liver. There is one rat study of digestive enzyme activity across the gastrointestinal tract and non-digestive organs [4]. There is no model of liver injury, no measure of liver function, no hepatic histology. For a compound whose entire identity is "the liver peptide", that is the most important fact on this page.

There is also no lifespan study, no tumour study and no human trial - all of which Vilon has at least some of.

How to read the chromatin work. It is real laboratory work with a consistent finding, from a group in Tbilisi collaborating with the St Petersburg institute. What it shows is that adding these peptides to aged lymphocytes in culture changes how condensed their chromatin is. It does not show that this happens in a person, that it would be beneficial if it did, or that the peptide reaches a cell nucleus after a dose.

The proposed mechanism is the family mechanism: small peptides entering the nucleus and interacting with DNA or chromatin to change gene accessibility [7][8]. Livagen's specific contribution to that case is the deheterochromatinisation work - chromatin in aged cells is more condensed, condensation silences genes, and these peptides reverse some of it [1][2].

The comparative detail matters more than the individual result. In the same experiments, Epitalon and Livagen decondensed pericentromeric structural heterochromatin while Vilon did not [2]. Different sequences, different effects - which is what you would expect if the interaction is sequence-specific, and not what you would expect from a generic charge effect.

What the mechanism does not explain is the organ designation. Nothing in the chromatin work is liver-specific, and no published study connects Livagen's chromatin effects to hepatic tissue. The organ assignment comes from the design principle - derived from liver extract amino acid composition - rather than from a demonstrated tropism.

The free tetrapeptide Lys-Glu-Asp-Ala, supplied lyophilised. Injected in the rat work; oral products are sold without a published absorption study.

No adverse effects are reported, and no safety study has been done. There is no toxicology publication, no pharmacokinetic study, and no human exposure data.

The one finding that bears on safety runs favourably: Livagen reduced cobalt-induced chromosomal aberrations rather than increasing them [3], which at least argues against a genotoxic effect in that assay.

Set against that, a compound whose proposed mechanism is decondensing chromatin and releasing silenced genes is doing something that warrants more scrutiny than it has received. Heterochromatin silences genes for reasons, including the suppression of transposable elements, and nothing in this literature examines what else gets derepressed.

No interaction studies exist. Livagen has been studied side by side with Epitalon and Vilon on the same chromatin measures [2], as a comparison rather than a combination.