Cardiogen

What it is

Cardiogen belongs to the cytogens, the synthetic short peptides of the Khavinson school. The idea behind it: the active fragments are identified from organ extracts of young animals and rebuilt as short chains. For the heart, this is the sequence alanine, glutamic acid, aspartic acid, arginine. According to the developer group, exactly this tetrapeptide was found in the polypeptide complex of the heart using chromatography-mass spectrometry.

Important for putting it in context is the distinction from Chelohart. Chelohart is listed by vendors as the heart preparation of the Cytomax series, that is, as a natural complex of many peptides. Cardiogen, by contrast, is a single, precisely defined molecule. In some overviews the two names are mixed up, and occasionally the sequence Ala-Glu-Asp-Pro turns up in the process. That, however, is Cortagen, a peptide from the cerebral cortex extract Cortexin. Anyone looking for Cardiogen should look for AEDR.

A second risk of confusion: CardioGen-82 is the name of a rubidium generator for cardiac PET in nuclear medicine. It has nothing to do with the peptide, but it turns up in databases under almost the same name.

How it is supposed to work

The Khavinson school describes ultrashort peptides of two to seven amino acids as signaling molecules that enter the cell nucleus and nucleolus, bind to DNA and histones and thereby influence the reading of certain genes. For Cardiogen, this means specifically: it is said to trigger the synthesis of structural and metabolic proteins in heart muscle cells and thereby promote regeneration and resilience.

One building block of this explanation is measurable. In cultures of mouse fibroblasts, AEDR increased the cytoskeletal proteins actin, tubulin and vimentin 2- to 5-fold and the nuclear matrix proteins lamin A and C 2- to 3-fold. A more stable cell scaffold could explain why damaged heart tissue holds up better in the animal model.

How the peptide gets into the cell at all was investigated by the group using a computer model. Of 26 short peptides tested, AEDR was among those that bind best to the transporters LAT1, LAT2 and PEPT1. That makes uptake via these routes plausible; it has not been measured.

Place in the cardiovascular series

In the school’s classification, Cardiogen and Vesugen form a pair. A 2022 overview by the group describes the short peptides KED and AEDR as active components of the polypeptide complexes of blood vessels and the heart. KED, that is Vesugen, targets the inner vessel wall and regulated markers such as Ki67, connexin 43, VEGF and p53 in aging endothelial cells. AEDR, that is Cardiogen, targets the heart muscle itself. Both are said to intervene in what aging researchers call inflammaging: a smoldering, low-grade inflammation with which aged cells burden their surroundings and which promotes atherosclerosis, coronary heart disease and heart attack.

What was shown in the animal model

Besides the infarction experiment, the patent describes experiments on isolated guinea pig hearts after ischemia, on rats with adrenaline-induced heart muscle damage and with arrhythmias triggered by calcium chloride. The direction is the same throughout: less damage, fewer deaths, better function on the peptide.

Independently of the patent, tissue culture studies were published. In heart muscle explants from 3- and 24-month-old rats, Cardiogen showed the strongest growth-promoting effect of all substances tested and lowered the protein p53, a marker of programmed cell death. An earlier study found the stimulation in heart tissue of young and old animals as well.

What the studies show

Infarction model in rats (developers’ patent)

In 40 rats, a coronary artery was ligated. In the first 24 hours, 45 percent of the control animals and 15 percent of those treated with the tetrapeptide died. The glycogen content in the heart muscle was preserved on the peptide and fell threefold without it. The patent describes neither randomization nor blinding, and the data were not published in a peer-reviewed journal.

Heart muscle explants from young and old rats

Chalisova and colleagues compared Cardiogen with 20 amino acids in organotypic cultures from the hearts of 3- and 24-month-old rats (Adv Gerontol 2009). Cardiogen promoted cell proliferation most strongly in both age groups and lowered p53. The endpoint was the growth of the tissue pieces, not a measure of pumping function.

Cytoskeleton in fibroblasts

Khavinson and colleagues added AEDR to embryonic mouse fibroblasts (Bull Exp Biol Med 2012). Actin, tubulin and vimentin rose 2- to 5-fold, lamin A and C 2- to 3-fold. This supports the proposed mechanism, but does not come from heart muscle cells.

Sarcoma in aged rats

Levdik and Knyazkin studied aged rats with transplanted M-1 sarcoma (Bull Exp Biol Med 2009). Cardiogen inhibited tumor growth in a dose-dependent manner via hemorrhagic necrosis and increased apoptosis; the authors ruled out a direct cytotoxic effect.

Where the data stop

The gap is fundamental: there is no published study in humans, no data on absorption or residence time in the body and no entry in a public trial registry. The patent, too, contains only animal experiments. The most impressive figures, those on infarction mortality, appear in a patent by the developers; a 2022 review by the same group cites them, but refers to that very patent for them. Almost all studies come from one research environment; independent confirmation is missing.

The tissue specificity, the central promise of the bioregulators, is not strict either. In aged human prostate fibroblasts, Cardiogen also increased differentiation markers. This does not speak against the peptide, but it qualifies the idea that it acts only in the heart. Whether the animal findings carry over to humans after intake as a capsule is open: in the experiments, the peptide was injected.

Status, approval and legal

Cardiogen is not an approved medicine in Germany or the EU. As a food, it would require authorization under the Novel Food Regulation (EU) 2015/2283, which does not exist. It is traded as a research peptide not intended for humans; in the Russian-speaking world, the cytogen series has been sold for years. In sport, a non-approved substance falls under group S0 of the World Anti-Doping Agency and is prohibited at all times.

Safety

Systematic safety data in humans do not exist. The toxicity tests in the patent, including 6 months in 96 guinea pigs and a single administration at 5,000 times the intended dose without a toxic reaction, are statements by the developers and were collected only in animals. Interactions with heart medications such as beta blockers, anticoagulants or antiarrhythmics have never been studied. Anyone with heart disease discusses any supplement with their cardiologist and does not replace any prescribed therapy. There are no data for pregnancy and breastfeeding, and with research products, content and purity are unverified.

Sources

• Khavinson et al., US patent 7,662,789 (2010) – Peptide Substance Restoring Myocardium Function
• Khavinson et al., Cells 2022 – SASP of cardiovascular cells and peptide regulation
• Khavinson et al., Bull Exp Biol Med 2012 – AEDR increases cytoskeletal and nuclear matrix proteins
• Chalisova et al., Adv Gerontol 2009 – Cardiogen in heart muscle cultures of young and old rats
• Zakutskii et al., Adv Gerontol 2006 – tissue-specific effect of synthetic peptides in organ culture
• Levdik and Knyazkin, Bull Exp Biol Med 2009 – Cardiogen and M-1 sarcoma in aged rats
• Kheifets et al., Adv Gerontol 2010 – Cardiogen in aged prostate fibroblasts
• Khavinson et al., Biomolecules 2023 – transport of 26 ultrashort peptides via LAT and PEPT
• Anisimov et al., Neuro Endocrinol Lett 2004 – Cortagen is Ala-Glu-Asp-Pro
• WADA – Prohibited List (group S0)