Ovagen peptide: the Glu-Asp-Leu bioregulator, what has been studied and what has not

Ovagen, or the EDL peptide, is a three-amino-acid peptide: glutamic acid, aspartic acid and leucine. It is one of the synthetic short peptides, sometimes called cytogens, from the Khavinson group in St Petersburg, which designed them as fragments of the organ extracts it had studied since the 1970s. A 2022 review from the institute lists Ovagen (EDL) with the stated activities of nephroprotector and hepatoprotector, and its supporting citations are kidney studies ^[1]. In the institute’s cell-culture papers the same peptide appears under the code T-35 ^[6].

The name causes confusion. Some suppliers list ovagen as an ovarian or female reproductive peptide, presumably from the name; others list it as a liver peptide; the peer-reviewed research is almost entirely about the kidney. We found no study of Glu-Asp-Leu in ovarian tissue, and the liver claim rests on a patent cited in the institute’s review rather than on a published experiment ^[1]. A related tetrapeptide, Lys-Glu-Asp-Ala, is the institute’s liver peptide sold as livagen, and Ala-Glu-Asp is its kidney and cartilage peptide sold as cartalax; the two are often studied alongside EDL.

Ovagen belongs with the other Khavinson tripeptides on this site that share its Glu-Asp core: chonluten (Glu-Asp-Gly), crystagen (Glu-Asp-Pro), pinealon (Glu-Asp-Arg) and vesugen (Lys-Glu-Asp). What is true of the evidence for one of them is largely true of the others: a small number of papers from one institute, several in Russian, and no human trials.

The St Petersburg programme began in the 1970s with extracts of animal organs, the best known being thymalin from calf thymus and epithalamin from calf pineal gland. In 2002 Khavinson and Morozov reported that 266 elderly people given thymalin, epithalamin or both for the first two to three years of a six-to-eight-year follow-up had fewer acute respiratory infections, less ischaemic heart disease, hypertension and osteoporosis, and lower mortality than a control group, with a 4.1-fold fall in mortality in the group treated with both preparations every year ^[9]. That study is the foundation of the group’s claim that peptide bioregulators are geroprotectors. It was not blinded, the control group is not described in the abstract, and it has never been replicated outside the group.

The synthetic short peptides came later. Khavinson and Malinin set out the reasoning in a 2002 review: in their model, peptides normalise the synthesis of tissue-specific proteins and regulate the genes responsible for cell proliferation and differentiation, and in doing so maintain physiological function and slow ageing ^[10]. Under that model the institute produced a dipeptide or tripeptide for almost every organ, each named for its target and sold as a supplement: ovagen for the kidneys and liver, vesugen for blood vessels, pinealon for the brain, cartalax for cartilage and so on. These are the Khavinson peptides sold today. The synthetic peptides are called cytogens; the original extracts are called cytomaxes.

When reading claims about ovagen bioregulator products, three features of this literature matter. Almost every paper comes from one institute or its collaborators; many are in Russian in the institute’s own journal, Advances in Gerontology, with only an abstract in English; and the English-language papers are mostly in the Bulletin of Experimental Biology and Medicine, a translated Russian journal that is indexed in PubMed but does not amount to independent replication. None of this makes the findings wrong, but it means the evidence for ovagen has never been tested by anyone with no stake in the result.

The Khavinson group’s hypothesis is that its short peptides enter cells, bind particular DNA sequences and change the expression of tissue-specific genes. For EDL the group has published a version of that argument for kidney cells. In a 2014 Russian-language paper, the peptides AED and EDL increased proliferation in young and aged renal cell cultures, reduced the expression of the ageing markers p16, p21 and p53, and increased expression of SIRT6; the authors built computer models in which both peptides formed their most favourable complexes with an alternating AT sequence in the minor groove of DNA, and concluded that DNA binding was the cause of the expression changes ^[5]. The DNA binding was modelled, not measured.

A 2015 paper in the Bulletin of Experimental Biology and Medicine reported that a polypeptide complex from calf kidney and the short peptides T-31 (AED) and T-35 (EDL) increased the proliferation marker Ki-67 and reduced the pro-apoptotic protein p53 in organotypic kidney cultures from young and old rats, with the short peptides having a weaker effect than the whole extract ^[6]. The institute’s transporter papers propose that di- and tripeptides enter cells through the PEPT family and the LAT1 and LAT2 carriers, and include EDL among 26 peptides docked to those transporters ^{[1] [7]}. These are models; no experiment has measured EDL entering a cell.

Searches for ovagen benefits usually concern ovagen liver effects, fertility or the ovaries, and anti-ageing. The published research supports none of those directly. What exists is a consistent set of rat kidney studies from the Khavinson institute with collaborators in Chernivtsi, Ukraine, and they are the reason the institute calls EDL a nephroprotector.

Acute kidney injury: in 2015, Zamorskii and colleagues gave rats cisplatin to induce acute renal failure and treated them with a kidney polypeptide complex or with the short peptides AED, EDL or AEDG. EDL and AEDG normalised urine output, creatinine excretion, glomerular filtration rate and sodium reabsorption and reduced protein in the urine; the authors described EDL as having a potent nephroprotective effect ^[3]. In 2017 the same group reported that EDL prevented oliguria, retained nitrogen waste, proteinuria and sodium loss in rats with gentamicin nephropathy and with ischaemia-reperfusion kidney injury, and prevented the fall in antioxidant enzyme activity and the rise in lipid peroxidation ^[2].

Ageing kidneys: a 2018 Russian-language paper gave old rats the kidney complex or AED, EDL or AEDG. AED and EDL increased urine output by 1.2 to 1.4 times and distal sodium transport by 1.2 to 1.3 times, EDL increased sodium excretion 1.6-fold, antioxidant enzyme activity in kidney tissue rose, and the authors saw no signs of nephrotoxicity ^[4]. Together with the cell-culture work ^{[5] [6]}, these are the entirety of the EDL evidence: rat kidneys, rat kidney cells, one research network.

Liver: the institute’s review lists EDL as a hepatoprotector but cites a patent rather than a study ^[1]. We found no published experiment on Glu-Asp-Leu in liver cells or in animals with liver injury. Ovaries and fertility: we found nothing at all. Anti-ageing: the cell-culture papers report changes in ageing markers in kidney cells ^[5], which is not evidence of any effect on ageing in an animal or a person.

We found no clinical trial, case series or case report of ovagen or Glu-Asp-Leu in people in PubMed, and no registered study on ClinicalTrials.gov. The Khavinson group’s 2013 summary of its clinical work lists thymalin, thymogen, vilon, epithalamin, prostatilen, cortexin and retinalamin, and does not mention ovagen ^[8]. Supplier statements that ovagen has been used in patients with liver disease, hepatitis or infertility do not correspond to any paper we could locate.

For a Khavinson peptide that has been given to people, see thymogen, which is a registered medicine in Russia and was tested in US cancer trials as IM862, or epitalon, the pineal tetrapeptide with the largest literature in the family.

In rats, EDL was given during the days of an acute kidney injury model and the protective effects were measured at the end of the model ^{[2] [3]}; in old rats, the changes in urine output were measured after a course of injections ^[4]. There is no human timeline because there are no human studies, and none of the rat timings applies to a person taking a supplement.

No human dose exists because there are no human studies. The rat kidney-injury papers gave EDL by injection over the course of the injury model; the abstracts do not state the dose per kilogram ^{[2] [3] [4]}. In cell culture, the tripeptides were used at nanogram-per-millilitre concentrations ^{[5] [6]}. Suppliers sell ovagen as 20 mg vials of lyophilised powder or as capsules and quote course lengths copied from the institute’s supplement marketing; those regimens have not been tested in any published study and are not recommendations. To convert vial contents to a concentration for laboratory use, see the ovagen calculator or the general peptide calculator.

The published animal work gave EDL by injection ^{[2] [3] [4]}, and the cell work added it to culture medium ^{[5] [6]}. Research suppliers sell ovagen as a freeze-dried powder for reconstitution with bacteriostatic water and as oral capsules. No data exist on the absorption of Glu-Asp-Leu by mouth in animals or people. The institute’s modelling papers argue that tripeptides could be absorbed through the PEPT1 transporter in the gut, which is a hypothesis from docking calculations ^[7].

There is no published safety information on ovagen in people. In old rats, the 2018 study reported no nephrotoxic effects on morphological examination and a rise in antioxidant enzyme activity ^[4], and the injury studies reported protection rather than harm ^{[2] [3]}. Those are short studies in small groups of rats from a single research network, and they did not look at other organs or at long-term exposure.

Two points deserve mention. First, EDL changed sodium and water handling by the kidney in rats ^{[3] [4]}; a substance that alters diuresis and sodium excretion is not inert, and its effect in people with kidney disease, on diuretics or with high blood pressure is unknown. Second, the cell-culture work reported that EDL suppresses p16, p21 and p53 in kidney cells ^[5]; these are tumour-suppressor and senescence pathways, and lowering them is not automatically desirable. Neither question has been studied. Ovagen is not named on the WADA Prohibited List or on the FDA’s compounding lists as far as we have seen, which reflects the absence of any regulatory review. For rules on possession and sale, see our legal status overview.

Ovagen is not an approved medicine in any country we are aware of. In Russia the institute’s synthetic tripeptides are sold as dietary supplements rather than as registered drugs, in contrast to thymogen, which the same review describes as a medicinal product ^[1]. Outside Russia, products sold as ovagen are unlicensed research chemicals labelled for laboratory use.

See the UK, US and Europe pages for the rules that apply where you are, and our explainer on what research peptides are.

Ovagen is a small, water-soluble peptide supplied as a freeze-dried powder. It is generally stored refrigerated, dry and away from light, and reconstituted solutions are kept cold and used within a limited period. See how to store peptides.

A tripeptide is cheap and easy to make, so purity should be high and the price low. A certificate of analysis for ovagen should show a mass close to 375 g/mol and purity by HPLC; because the molecule is so small, a mass alone cannot distinguish it from another peptide of the same composition, such as Glu-Leu-Asp. Learn how to read a peptide COA and what third-party testing covers.

Compare ovagen prices across suppliers, including listings in the UK and US, and see our list of third-party tested suppliers. If a listing describes ovagen as an ovarian peptide or cites clinical liver results, ask for the reference; the published work is on rat kidneys. Our guide to spotting a fake peptide supplier covers the other checks.