Vesugen
Summary
Vesugen (Lys-Glu-Asp, KED) is a Khavinson-network tripeptide positioned as a vascular bioregulator. Evidence is in vitro endothelial work (endothelin-1, connexin, sirtuin-1), one 5xFAD mouse Alzheimer study carrying a 2025 correction, and two small uncontrolled Russian human reports. No randomized trial or pharmacokinetic study exists.
Also known as: KED, Lys-Glu-Asp, Vezugen, Lysyl-glutamyl-aspartic acid
Key Findings at a Glance
- • Vesugen is the tripeptide Lys-Glu-Asp (KED); its vascular claims rest on in vitro work showing normalized endothelin-1, restored connexin contacts, and increased sirtuin-1 in atherosclerotic endothelial models.
- • The 5xFAD mouse Alzheimer study (400 mcg/kg daily intraperitoneal) reported prevented dendritic spine loss but carries a January 2025 correction whose content is not specified in the public notice.
- • The two human studies (n=41 and n=32) are uncontrolled Russian-language reports; the n=32 study also detected prooxidant activity and reduced CD34+ progenitor cells.
- • No randomized trial, pharmacokinetic study, or independent replication outside the Khavinson network exists for Vesugen.
Vesugen Overview & Molecular Profile
Vesugen (also spelled Vezugen) is a synthetic tripeptide with the sequence Lys-Glu-Asp (KED), developed at the Saint Petersburg Institute of Bioregulation and Gerontology as a vascular bioregulator and sold in Russia as a dietary supplement. The indexed evidence base is small: in vitro studies in vascular endothelial cells, a 5xFAD mouse Alzheimer model, a molecular-genetic review, and two small uncontrolled Russian-language human studies in elderly patients. Reported endothelial effects include normalization of elevated endothelin-1 expression, restoration of connexin-mediated intercellular contacts, and increased sirtuin-1 expression in atherosclerotic and restenotic cell models. The 2021 mouse Alzheimer paper received a formal correction in January 2025 whose public notice does not specify what changed. Vesugen sits in the same Khavinson short-peptide class as Epithalon, and nearly all of its data originates from that single research network; no randomized trial, pharmacokinetic study, or independent replication has been published.
Mechanism of Action: Gene Expression & Epigenetic Regulation
KED is proposed to act through epigenetic regulation rather than a membrane receptor: molecular modeling from the developing group reports peptide interaction with promoter regions of genes involved in neuronal differentiation and Alzheimer pathogenesis, including GAP43 and APOE. In the same modeling work the related peptide EDR, not KED, is the one credited with binding sites in the CASP3 promoter. In cultured vascular endothelium under atherosclerosis and restenosis conditions, KED normalized elevated endothelin-1 expression, restored connexin expression (re-establishing gap-junction-mediated cell contacts), and increased expression of sirtuin-1, a deacetylase involved in DNA repair. A separate molecular-genetic review attributes to KED regulation of p16 and p21 (cell aging), NES and GAP43 (neuronal differentiation), and SUMO, APOE, and IGF1 (Alzheimer-relevant) genes. No receptor target has been identified at molecular resolution, and no mechanism has been demonstrated outside the originating network.
Vesugen Pharmacokinetics: An Unmeasured Tripeptide
No pharmacokinetic parameter - half-life, Cmax, bioavailability, clearance - has been published for Vesugen (Lys-Glu-Asp) in any species. The only administered-dose information in the indexed literature is the 5xFAD mouse protocol, and a Russian-language review mentions oral use in elderly patients without exposure data.
What Is Known About Exposure
- • In the 5xFAD mouse Alzheimer model, KED was administered intraperitoneally at 400 mcg/kg once daily from 2 to 4 months of age; plasma or brain concentrations were not reported (PMID 34071923).
- • A 2021 review states oral KED improved memory and attention in elderly individuals with functional CNS disorders, implying oral activity, but provides no dose, concentration, or trial data to support exposure claims (PMID 34173097).
Class-Level Expectations
- • As an unmodified tripeptide with two acidic residues, KED is expected to be water-soluble and rapidly degraded by peptidases; no KED-specific measurement confirms this.
- • A 2023 docking analysis of 26 ultrashort peptides from this research network proposed LAT1, LAT2, and PEPT1 transporters as a general cellular uptake route for the class; KED was not among the top-ranked ligands named (PMID 36979488).
Research-Observed Effects
Endothelial Function Markers (In Vitro)
Moderate ResearchIn cultured vascular endothelial and smooth muscle cells under atherosclerosis and restenosis conditions, KED normalized elevated endothelin-1 expression, restored connexin-mediated intercellular contacts, and increased sirtuin-1 expression. Endothelin-1 elevation is a core feature of endothelial dysfunction, and connexins maintain the gap-junction communication lost in atherosclerotic vessels, so the reported direction of effect is biologically coherent; the evidence remains single-network cell culture without independent replication.
Neuroprotection in Alzheimer Models
Preliminary ResearchIn 5xFAD transgenic mice, daily intraperitoneal KED (400 mcg/kg, months 2-4 of age) prevented dendritic spine loss and showed a trend toward improved neuroplasticity, with molecular docking suggesting promoter-level interaction with Alzheimer-relevant genes. This paper received a formal correction in January 2025 whose public notice does not specify the change, so the findings should be read with that caveat; no independent group has replicated them.
Peripheral Blood Flow (Uncontrolled Human Data)
Preliminary ResearchA Russian-language study of 41 patients with vasculogenic erectile dysfunction as a manifestation of atherosclerosis reported improved blood flow in the main penile arteries after KED monotherapy, assessed by clinical and instrumental parameters. The study had no control arm, randomization, or blinding, so placebo effects and natural course cannot be excluded.
Biological Aging Markers (Uncontrolled Human Data)
Preliminary ResearchIn 32 patients aged 41-83 with chronic polymorbidity and organic brain syndrome in remission, Vesugen and the related tripeptide pinealon were reported to shift biological-age indicators in a favorable direction, with Vesugen showing the stronger effect. The same study observed prooxidant activity by chemiluminescence and a significant decrease in circulating CD34+ hematopoietic progenitor cells, which the authors read as inhibited hemopoiesis - a safety-relevant signal, not just a benefit.
Safety & Tolerability
Vesugen's human safety is uncharacterized: two small uncontrolled Russian studies reported no adverse events but had no formal adverse-event protocols, and one of them detected prooxidant activity and a significant decrease in circulating CD34+ hematopoietic progenitor cells. The flagship mouse Alzheimer paper carries a formal 2025 correction. No pharmacokinetic or toxicology study has been published.
Human data: Human evidence is two small, uncontrolled, single-center Russian-language observational reports (n=41 vasculogenic erectile dysfunction; n=32 polymorbidity with organic brain syndrome). No randomized, controlled, or pharmacokinetic human study exists.
Regulatory status: Not approved as a drug by the FDA, EMA, or any major regulator; sold in Russia as a biologically active food supplement (BAFS).
- PubMed 25051774
In 41 patients with vasculogenic erectile dysfunction, KED monotherapy was reported to improve penile artery blood flow with no adverse events mentioned, but the study was uncontrolled and used no formal safety reporting.
Human observational - PubMed 26390612
In 32 elderly patients with polymorbidity, Vesugen shifted biological-age markers favorably but also showed prooxidant activity by chemiluminescence and a significant decrease in circulating CD34+ hematopoietic progenitor cells, interpreted by the authors as inhibition of hemopoiesis.
Human observational - PubMed 34071923
In 5xFAD Alzheimer mice, KED at 400 mcg/kg intraperitoneally daily prevented dendritic spine loss; the paper carries a formal January 2025 correction whose public notice does not specify the change.
Animal - PubMed 39861198
The January 2025 correction to the 2021 Pharmaceuticals mouse study does not disclose, in its public abstract, what was corrected; the mouse neuroprotection findings should be read as corrected-record data.
Theoretical
Research Protocol Doses Reported in Published Literature
Research Disclaimer: Doses reported below are from published preclinical research protocols. Vesugen is not approved by the US FDA for human use; regulatory status can differ in other countries, so see the regulatory status note in the safety section of this page. This information is provided for research reference only and does not constitute a dosing recommendation.
| Route | Dose | Frequency | Notes |
|---|---|---|---|
| Intraperitoneal (mouse) | 400 mcg/kg | Once daily, months 2-4 of age | 5xFAD Alzheimer model (PMID 34071923); no human dosing established |
All doses above are reported from published research protocols using laboratory subjects. Refer to the cited studies in the Research Studies section above for original source data.
Research Studies & References
Molecular aspects of vasoprotective peptide KED activity during atherosclerosis and restenosis
Kozlov KL, Bolotov II, Linkova NS, et al.
Advances in Gerontology (2016)
This Russian-language in vitro study examined KED effects on signal molecule expression in normal, atherosclerotic, and restenotic vascular endothelium. KED normalized endothelin-1 expression (elevated in atherosclerosis and restenosis), restored connexin-mediated intercellular contacts, and increased expression of sirtuin-1, a protein involved in DNA repair. It is the core mechanistic paper behind Vesugen's vasoprotective framing and has not been independently replicated.
Neuroprotective Effects of Tripeptides-Epigenetic Regulators in Mouse Model of Alzheimer's Disease
Khavinson V, Ilina A, Kraskovskaya N, et al.
Pharmaceuticals (Basel) (2021)
In 5xFAD transgenic Alzheimer mice, daily intraperitoneal KED at 400 mcg/kg from 2 to 4 months of age tended to increase neuroplasticity and, together with the EDR peptide, prevented dendritic spine loss; molecular docking proposed DNA-level interaction with Alzheimer-relevant gene promoters. This paper received a formal correction in January 2025 (PMID 39861198) whose public notice does not specify what was corrected, so its findings should be cited with that caveat.
Correction: Khavinson et al. Neuroprotective Effects of Tripeptides-Epigenetic Regulators in Mouse Model of Alzheimer's Disease. Pharmaceuticals 2021, 14, 515
Khavinson V, Ilina A, Kraskovskaya N, et al.
Pharmaceuticals (Basel) (2025)
Formal correction notice for the 2021 Pharmaceuticals 5xFAD mouse study of KED and EDR peptides. The public abstract of the correction does not state what content was changed. Readers and citers of the original mouse Alzheimer findings should treat this notice as part of the record.
The efficacy of peptide bioregulators of vessels in lower limbs chronic arterial insufficiency treatment in old and elderly people
Kitachev KV, Sazonov AB, Kozlov KL, et al.
Advances in Gerontology (2014)
This uncontrolled Russian-language study assessed the vasoactive tripeptide Vezugen in 41 patients with vasculogenic erectile dysfunction as a manifestation of atherosclerosis. Comparative analysis of clinical and instrumental parameters before and after monotherapy found significantly improved blood flow through the main penile arteries. With no control arm, randomization, or blinding, the result is hypothesis-generating only.
Effect of synthetic peptides on aging of patients with chronic polymorbidity and organic brain syndrome of the central nervous system in remission
Meshchaninov VN, Tkachenko EL, Zharkov SV, et al.
Advances in Gerontology (2015)
In 32 patients aged 41-83 with chronic polymorbidity and organic brain syndrome in remission, the tripeptides Vesugen and Pinealon were reported to produce anabolic effects and shift biological-age indicators favorably, with Vesugen the stronger. The same study found prooxidant activity by chemiluminescence and a significant decrease in circulating CD34+ hematopoietic progenitor cells, interpreted as inhibition of hemopoiesis, making this uncontrolled study as relevant to safety assessment as to efficacy.
Peptide KED: Molecular-Genetic Aspects of Neurogenesis Regulation in Alzheimer's Disease
Khavinson VK, Lin'kova NS, Umnov RS
Bulletin of Experimental Biology and Medicine (2021)
This molecular-genetic review of KED in the Alzheimer context states that oral KED improved memory and attention in elderly individuals with functional CNS disorders (no controlled data presented) and that KED restores synaptic plasticity in an in vitro Alzheimer model. It catalogs KED regulation of cell-aging genes (p16, p21), neuronal differentiation genes and proteins (NES, GAP43, nestin), and Alzheimer-relevant genes (SUMO, APOE, IGF1), arguing for formal animal-model efficacy studies.
Frequently Asked Questions
What is Vesugen?
Vesugen (also spelled Vezugen) is the synthetic tripeptide Lys-Glu-Asp (KED), developed at the Saint Petersburg Institute of Bioregulation and Gerontology as a vascular endothelial bioregulator. It is sold in Russia as a dietary supplement. Its indexed literature is small, mostly in vitro and animal work from one research network, with two small uncontrolled human studies.
What human evidence exists for Vesugen?
Two small Russian-language studies, both uncontrolled: 41 patients with vasculogenic erectile dysfunction showed improved penile artery blood flow after KED monotherapy, and 32 elderly patients with polymorbidity showed favorable shifts in biological-age markers but also prooxidant activity and reduced CD34+ progenitor cells. Neither study had a control group, so neither establishes efficacy or safety. No randomized trial has been published.
What is the correction on the Vesugen Alzheimer mouse study?
The 2021 Pharmaceuticals paper reporting that KED prevented dendritic spine loss in 5xFAD Alzheimer mice received a formal correction published in January 2025 (PMID 39861198). The public correction notice does not specify what was changed. The findings remain on the record but should be cited with the correction attached, and no independent group has replicated them.
Is Vesugen safe?
Uncharacterized in humans. The two small human studies reported no adverse events but used no formal adverse-event protocols, and the 32-patient study detected prooxidant activity and a significant drop in circulating CD34+ hematopoietic progenitor cells, which the authors themselves flagged as inhibited hemopoiesis. No pharmacokinetic study, no drug-interaction data, and no pregnancy or organ-impairment data exist.
Related Peptides
View allVilon
Vilon is a synthetic dipeptide (Lys-Glu, KE) identified as an active constituent of the thymus polypeptide complex Thymalin, studied for T-cell differentiation and cytokine modulation.
Pinealon
Pinealon is a synthetic tripeptide (Glu-Asp-Arg) from the Khavinson bioregulator program, studied as a neuroprotective agent that interacts directly with DNA and modulates gene expression in neuronal cells.
Epithalon
Epithalon is a synthetic tetrapeptide based on the natural peptide Epithalamin produced by the pineal gland. It has been studied for effects on telomerase activity and longevity.
Cortagen
Cortagen is a synthetic tetrapeptide (Ala-Glu-Asp-Pro) built from amino acid analysis of the bovine brain cortex preparation Cortexin, studied in nerve regeneration and cerebral ischemia models.
Follow Peptpedia on Google
Add Peptpedia as a Preferred Source and Google can highlight our links with a "preferred" badge in your Top Stories and AI Overviews.