Crystagen peptide: the Glu-Asp-Pro immune bioregulator, what has been studied and what has not

Crystagen, or the EDP peptide, is a three-amino-acid peptide: glutamic acid, aspartic acid and proline. It is one of the synthetic short peptides, sometimes called cytogens, that the Khavinson group in St Petersburg designed as immune bioregulators after decades of work on the calf thymus extract thymalin. A 2022 review from the institute lists Crystagen (EDP) with the stated activity of immunoprotector ^[1], and a 2014 paper in the institute’s journal Advances in Gerontology names Crystagen alongside vilon, thymogen and a fourth peptide as short peptides with immunoprotective effects on the ageing spleen ^[2].

It is the least studied of the institute’s immune peptides. Thymogen, the Glu-Trp dipeptide, became a registered medicine in Russia with clinical studies going back to 1992; vilon, the Lys-Glu dipeptide, has animal cancer-prevention data; crystagen has neither. Its structural neighbours on this site are the other Khavinson tripeptides that share its Glu-Asp core: chonluten (Glu-Asp-Gly), ovagen (Glu-Asp-Leu), pinealon (Glu-Asp-Arg) and vesugen (Lys-Glu-Asp).

The word crystagen has no established meaning outside the institute’s product naming, and it should not be confused with the natural thymic hormone thymulin or with thymosin alpha-1, a licensed immune peptide, neither of which is related to it in structure.

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: crystagen for the immune system, vesugen for blood vessels, pinealon for the brain, cartalax for cartilage and so on. The synthetic peptides are called cytogens; the original extracts are called cytomaxes.

When reading claims about crystagen 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 crystagen has never been tested by anyone with no stake in the result.

The Khavinson group proposes that its short peptides enter cells, bind to specific DNA sequences in gene promoters and adjust the expression of tissue-specific genes, and that this is why a tripeptide might act on immune tissue in particular. For crystagen there is no published gene-expression study that we could find, so the mechanism is inferred from the family rather than shown for the molecule.

The clearest description of what EDP does in a dish comes from a 2011 paper in the Bulletin of Experimental Biology and Medicine on two tripeptides coded T-36 and T-38. At 0.1, 1 and 10 ng/mL, both inhibited the proliferation of embryonic mesenchymal stem cells, a transplantable rat fibroblast line and human K-562 erythroleukaemia cells, an effect the authors interpreted as possible antitumour activity; they had no effect on lymphocyte survival, adhesion, cytotoxicity or induced proliferation, and did not change the phagocytic or bactericidal activity of granulocytes. T-36 at 0.1 ng/mL increased the spontaneous proliferation of normal lymphocytes, from which the authors concluded that the tripeptides stimulate non-tumour immune cells in adults ^[4]. A 2012 paper from the same institute identifies T-36 as Glu-Asp-Pro ^[3].

In the ageing spleen, the 2014 study reported that crystagen activates B cells but, unlike vilon and thymogen, does not affect cell renewal in the spleen as it ages ^[2]. The institute’s transporter-modelling papers include EDP among 26 peptides docked to the LAT1, LAT2 and PEPT1 carriers, with a lower computed binding score than most of the others ^{[1] [5]}. These are computer models, and no experiment has measured EDP entering a cell.

Searches for crystagen benefits usually concern crystagen immune support, recovery from illness, autoimmune conditions and anti-ageing. We found no animal or human study of crystagen in any disease. The published evidence is as follows.

Immune cells in culture: the 2011 tripeptide study found that EDP did not alter most measures of lymphocyte or granulocyte function, inhibited the growth of embryonic and immortalised cells, and slightly increased spontaneous proliferation of normal lymphocytes at the lowest concentration tested ^[4]. That is a mixed result: a substance sold as an immune stimulant had no effect on the immune functions most often measured.

Spleen: in organotypic culture of ageing spleen tissue, crystagen activated the B-cell compartment but did not promote cell renewal, whereas vilon and a peptide coded R-1 activated T-helper cells and thymogen activated B cells while also increasing proliferation ^[2]. The paper is in Russian and its abstract does not give the species, ages or number of cultures.

Skin: in 2012 the institute added five tripeptides to skin explants from young and old rats. T-36, the Glu-Asp-Pro peptide, was among those that stimulated proliferation in young rat skin, an effect attributed to reduced expression of the pro-apoptotic protein p53; in old rat skin only Lys-Glu-Asp had a marked effect ^[3]. The authors proposed the tripeptides as candidates for skin regeneration research.

That is the whole of it. There is no crystagen study in mice or rats with infection, tumours, ageing or immune deficiency, and the institute’s own review of the clinical results of its peptide preparations does not mention crystagen ^[6]. The cell-culture study that examined Khavinson peptides in human THP-1 monocytes tested thymogen, vilon, thymalin, epitalon and chonluten, not crystagen ^[7].

We found no clinical trial, case series or case report of crystagen or Glu-Asp-Pro in people in PubMed, and no registered study on ClinicalTrials.gov. The developers’ 2013 summary of their clinical work lists thymalin, thymogen, vilon, epithalamin, prostatilen, cortexin and retinalamin, not crystagen ^[6]. Supplier claims that crystagen has been used to restore immunity in elderly patients or after chemotherapy do not correspond to any paper we could locate.

For comparison, the immune dipeptide from the same programme that did reach patients, thymogen, has a rat life-span and tumour study ^[8], Russian clinical reports and a failed US phase 3 trial under the name IM862; see the thymogen guide. A natural thymic peptide with two 1980s double-blind human trials is described in the thymulin guide.

There are no data. No study has given crystagen to an animal or a person and measured an immune outcome over time, so there is no published onset or duration of effect. The cell-culture findings were measured over days in a dish ^{[3] [4]} and say nothing about timing in a living organism.

No human dose exists because there are no human studies. In cell culture, EDP was used at 0.1, 1 and 10 ng/mL in the 2011 immune-cell study ^[4] and at similar nanogram-per-millilitre concentrations in the 2012 skin culture study ^[3]; the spleen study does not give a concentration in its abstract ^[2]. Suppliers sell crystagen 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 crystagen calculator or the general peptide calculator.

All published work on crystagen used cells or tissue explants in culture ^{[2] [3] [4]}. Research suppliers sell it as a freeze-dried powder for reconstitution with bacteriostatic water and as oral capsules. No data exist on the absorption, distribution or breakdown of Glu-Asp-Pro in animals or people by any route. The institute’s modelling papers argue that tripeptides could be absorbed through the PEPT1 transporter in the gut and enter cells through LAT carriers, and note that EDP scored lower than most of its peptides in those models ^{[1] [5]}.

There is no published safety information on crystagen in animals or people. The cell studies did not report toxicity ^{[3] [4]}, and one of them found that EDP inhibited the growth of embryonic stem cells and fibroblasts at nanogram concentrations ^[4], a finding the authors framed as antitumour but which is also an effect on normal dividing cells. Whether that matters in a living organism has not been examined.

A peptide marketed to modulate the immune system should be assumed to have the potential to do so in unwanted directions, in autoimmune disease, in people on immunosuppressants and during infection. None of these situations has been studied. Crystagen 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.

Crystagen is not an approved medicine in any country we are aware of. In Russia the institute’s synthetic tripeptides are sold as dietary supplements, not as registered drugs, in contrast to thymogen, which the same review describes as a medicinal product ^[1]. Outside Russia, products sold as crystagen 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.

Crystagen 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. We could not find a PubChem record for the all-L form of Glu-Asp-Pro, so we do not quote a molecular weight from that source; a certificate of analysis should state the measured mass and the purity by HPLC. Because the molecule is so small, a mass alone cannot distinguish it from another peptide of the same composition. Learn how to read a peptide COA and what third-party testing covers.

Compare crystagen prices across suppliers, including listings in the UK and US, and see our list of third-party tested suppliers. If a listing claims clinical results for crystagen, ask for the reference. Our guide to spotting a fake peptide supplier covers the other checks.