Livagen
Also known as: KEDA, Lys-Glu-Asp-Ala, Lyvagen
Evidence: Preclinical
Overview
Khavinson-series synthetic tetrapeptide (KEDA) designed from liver peptide preparations; studied mainly in cultured lymphocytes from elderly donors and in rat hepatocytes.
Livagen (KEDA, Lys-Glu-Asp-Ala) was made by the St. Petersburg Institute of Bioregulation and Gerontology from the amino acid make-up of liver peptide preparations (Brodskii 2001). In lymphocytes from people over 75 it activated ribosomal genes and decondensed heterochromatin (Khavinson 2002; Lezhava 2007). It raised protein synthesis in rat hepatocytes, most in cells from old rats, inhibited enkephalin-degrading enzymes in human serum (IC50 20 microM; Kost 2003), and given orally to rats moved digestive enzyme activity in old animals toward young values (Timofeeva 2005). A 2020 review from the group reports liver protection in animal hepatitis and fibrosis models (Kuznik 2020). No human trial has been published.
Benefits
Chromatin decondensation in lymphocytes from elderly donors (in vitro), higher protein synthesis in rat hepatocytes (in vitro), enkephalinase inhibition in human serum (in vitro), digestive enzyme changes in old rats (rodent, oral)
Dosing reference
- Research dose
- 100 to 200 mcg daily: vendor/community range, no published human dose
- Range
- 100 to 200 mcg, 1x daily
Sold as oral capsules and as lyophilized powder for injection. Rats received it orally for two weeks; the abstract does not state the dose (Timofeeva 2005). Community protocols run 10 to 20 day courses two or three times a year; no study compared schedules.
Mechanism
Proposed, from in vitro work. In lymphocytes from elderly donors it activated ribosomal genes, decondensed pericentromeric heterochromatin and released genes silenced by age-related condensation (Khavinson 2002); it also reduced cobalt-induced chromosome aberrations (Lezhava 2007). It inhibited enkephalin-degrading enzymes in human serum with an IC50 of 20 microM, without binding mu or delta opioid receptors (Kost 2003). In rat hepatocyte cultures it raised protein synthesis and the amplitude of its rhythm (Brodskii 2001). The old claim that it regulates cytochrome P450 genes has no published source.
Evidence
Preclinical: animal or in vitro data only
- Activated ribosomal genes and decondensed heterochromatin in cultured lymphocytes from elderly donors (Khavinson et al., 2002)
- Reversed age-related heterochromatin condensation and reduced cobalt-induced chromosome aberrations in lymphocytes from people aged 80 to 91 (Lezhava et al., 2007)
- Inhibited enkephalin-degrading enzymes in human serum (IC50 20 microM) without binding opioid receptors (Kost et al., 2003)
- Raised protein synthesis in rat hepatocyte cultures, most in cells from old animals (Brodskii et al., 2001)
- Resisted rat small-intestine peptidases; two weeks of oral dosing moved digestive enzyme activity in old rats toward young values (Timofeeva et al., 2005)
- Human-trial status: no published human trial; liver claims rest on animal models summarized in a review by the developer (Kuznik et al., 2020)
References
- Effects of Livagen peptide on chromatin activation in lymphocytes from old people. Khavinson VKh, Lezhava TA, Monaselidze JG, Dzhokhadze TA, et al., Bulletin of Experimental Biology and Medicine, 2002
- Activation of pericentromeric and telomeric heterochromatin in cultured lymphocytes from old individuals. Lezhava T, Jokhadze T, Annals of the New York Academy of Sciences, 2007
- Effect of new peptide bioregulators livagen and epitalon on enkephalin-degrading enzymes in human serum (in Russian). Kost NV, Sokolov OIu, Gabaeva MV, Zolotarev IuA, et al., Izvestiia Akademii Nauk. Seriia Biologicheskaia, 2003
- Rhythm of protein synthesis in cultures of hepatocytes from rats of different ages. Norm and effect of the peptide livagen (in Russian). Brodskiĭ VIa, Khavinson VKh, Zolotarev IuA, Nechaeva NV, et al., Izvestiia Akademii Nauk. Seriia Biologicheskaia, 2001
- Effect of peptide Livagen on activity of digestive enzymes in gastrointestinal tract and non-digestive organs in rats of different ages (in Russian). Timofeeva NM, Khavinson VKh, Malinin VV, Nikitina AA, et al., Advances in Gerontology (Uspekhi Gerontologii), 2005
- The influence of polypeptide liver complex and tetrapeptide KEDA on organism physiological function in norm and age-related pathology (in Russian). Kuznik BI, Khasanova NB, Ryzhak GA, Mezsheriakova IE, et al., Advances in Gerontology (Uspekhi Gerontologii), 2020
Side effects
No controlled safety study has been published in any species, and the animal and cell studies, almost all from the developing institute, were not designed to detect harm. Commonly reported (anecdotal): injection-site irritation with injectable forms; oral capsules draw few complaints.
Storage
- Storage
- Room temperature
- Lyophilized
- 24+ months
Pharmacology
- Half-life
- No published pharmacokinetic data in any species
- Bioavailability
- Not measured. Resists hydrolysis by rat small-intestine peptidases and was active orally in rats (Timofeeva 2005)
- Molecular weight
- 461.47 Da
- Sequence
- KEDA (Lys-Glu-Asp-Ala)