Longevity · Pill
Cardiogen
Gray market0 human trials published
Preclinical · cell culture and animal models
Gray market · No FDA ruling — not on any list
Sold as a research chemical. Some clinics and pharmacies still supply it; that’s their risk, not a change in the rule.
Bottom line
Lab-only. The cardiology version of the broader unreplicated-Khavinson-peptide problem.
- Also called
- Ala-Glu-Asp-Arg (AEDR) · Cardiac bioregulator · Khavinson heart peptide
- Category
- Peptide — Khavinson Cardiac Bioregulator
- Class
- Tetrapeptide bioregulator
- Sequence
- Ala-Glu-Asp-Arg (AEDR)
- Molecular Weight
- ~489.5 Da
- Route (studied)
- Not stated in its studies
- Route (sold)
- Oral capsules (supplement); SubQ/IM vials (research)
- Target Tissue
- Cardiomyocytes
- FDA Status
- Not approved
- Evidence
- Preclinical only
- Developer
- Khavinson (St. Petersburg)
- WADA Status
- Not specifically listed — prohibited at all times under S0 (no government has approved it for human therapeutic use)
- Cost & Access
- Research-only
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What does it do? In the developers' patent, it cut deaths in the first day after a coronary artery was tied in rats from 45% to 15%, and at a low concentration it helped isolated hearts contract after their blood flow was stopped and restarted, while a tenfold higher one weakened them (Khavinson et al., US Patent 7,662,789).
Who uses it? Buyers of a Russian heart supplement, labeled for a 1-month course repeated after 4–6 months (Russian product labeling, 2012), and of research-chemical vials sold online. No trial has compared it with, or added it to, standard heart drugs such as statins or ACE inhibitors.
Does the evidence hold up? Cell, tissue and animal work, all from the developers' institute and its collaborators; the only animal heart experiments are in their own patent (Khavinson et al., US Patent 7,662,789). No human trial is listed in PubMed or ClinicalTrials.gov. Not in any cardiology guideline. Not approved anywhere.
Bottom line? Lab-only. The cardiology version of the broader unreplicated-Khavinson-peptide problem.
Dosing from the Literature
Published for the heart: a Russian supplement label's capsule dose and the developers' doses in rats. Not published: any human trial or study.
No clinical trial has published a human dose for Cardiogen. The table gives the dose on the Russian supplement label, whose capsules hold 100 μg of the peptide (Russian product labeling, 2012), and the doses the developers injected into rats in their patent (Khavinson et al., US Patent 7,662,789). This is not FDA-approved prescribing and is not a cardiology therapy.
| Form | Dose | Frequency | Source / Notes |
|---|---|---|---|
| Oral capsule (Russian dietary supplement, 100 μg per capsule) | 100–200 μg (1–2 capsules) | 1–2× daily, with meals | Russian product labeling (2012), for adults: 1 month, and the label calls a repeat course after 4–6 months advisable. No published study has tested this dose. |
| Injection in rats (animal study) | 0.05 μg per rat; 0.05–1.0 μg/kg | 1–3 injections; daily for 10 days in one model | Developers' patent, in rats (Khavinson et al., US Patent 7,662,789): 0.05 μg into the abdominal cavity 1, 3 and 5 hours after a coronary artery was tied; 0.05–1.0 μg/kg once in calcium-chloride arrhythmia (fewest deaths at 0.2 μg/kg; no significant effect at 1.0 μg/kg); 0.05 μg into muscle daily for 10 days in rats poisoned with the chemical TMTD. Not a human dose. |
The label's 100–400 μg a day has not been tested in any published study in people, and no study has measured how much of a swallowed dose reaches the blood or the heart. The rat doses are not human doses, and no published study supports using Cardiogen for any heart condition. Consult a licensed healthcare provider.
→ Calculator — vial-to-syringe math
What It Is
Cardiogen is a synthetic short peptide within the Khavinson bioregulator program — a family of two-to-four-residue peptides proposed by Vladimir Khavinson and collaborators at the St. Petersburg Institute of Bioregulation and Gerontology to act as tissue-specific epigenetic bioregulators. Cardiogen's sequence is Ala-Glu-Asp-Arg (AEDR), a tetrapeptide (a chain of 4 amino acids) with an approximate molecular weight of 489.5 daltons. Structurally it shares the "Ala-Glu-Asp" N-terminal acidic core with its Khavinson siblings Epithalon (AEDG, pineal), Cortagen (AEDP, cortex), Bronchogen (AEDL, bronchial), and other tetrapeptide bioregulators — with the C-terminal residue (arginine, in Cardiogen's case) proposed to confer tissue-specificity.
Cardiogen is the short-peptide successor to Cardialin / Cardiopeptide, earlier polypeptide preparations derived from calf cardiac tissue that were used observationally in Soviet/Russian cardiology for myocardial recovery and age-related cardiovascular support. The Khavinson program's central claim is that the bioregulatory activity of these crude tissue extracts can be distilled into defined short peptides, recovered from enzymatic hydrolysis of the parent extract. AEDR is the candidate short peptide identified as the putative active fragment from the cardiac extract.
Commercially, Cardiogen is distributed as an oral capsule (a Russian dietary supplement holding 100 μg of the peptide per capsule; Russian product labeling, 2012) and as a lyophilized research peptide (sellers list 20 mg vials) for subcutaneous or intramuscular research use. The oral capsule is sold in Russia as a "biologically active additive" (BAD — dietary supplement category); the injectable is research-only internationally. Neither form is a registered pharmaceutical anywhere in the world.
In the Western optimization community, Cardiogen occupies a small niche among users interested in longevity-focused Khavinson protocols and in cardiac-tissue-directed experimental peptides. It is not a drug used or recognized in evidence-based cardiology. Mainstream cardiology — guideline-directed medical therapy for coronary disease, heart failure, arrhythmia, hypertension, and valve disease — has no awareness of or use for Cardiogen.
Mechanism of Action
The Khavinson framework proposes that short bioregulator peptides act as sequence-specific DNA-binding molecules, small enough to enter cells and reach nuclear chromatin, and chemically structured to interact with DNA grooves at promoter regions of tissue-specific genes (Khavinson et al., 2021; PMID 34834147). Cardiogen's mechanism is described within this epigenetic-bioregulator framework. As with other Khavinson peptides, the mechanism is proposed by the originating research group: every study of AEDR in PubMed comes from that group or its collaborators, and no independent structural study has been published.
- Direct DNA interaction (proposed) — Fedoreyeva 2011 (PMID 22117547) demonstrated nuclear penetration of short fluorescence-labeled Khavinson peptides in HeLa cells. The group's 2021 review reports that AEDR and five sibling peptides bound wheat histones and changed how eukaryotic endonucleases cut phage DNA in test-tube experiments (Khavinson et al., 2021; PMID 34834147).
- Ischemic injury (rats) — In the developers' patent, rats given three 0.05 μg injections after a coronary artery was tied had a smaller dead-tissue zone (38% vs 44% of the ventricle at 6 hours, 50% vs 56% at 24 hours) and fewer deaths in the first day (15% vs 45%); the patent did not measure p53 or cell-death signaling (Khavinson et al., US Patent 7,662,789).
- Lipid peroxidation (rats) — In rats given a damaging dose of adrenaline, two 0.05 μg injections kept diene conjugates, a lipid-peroxidation product, at control levels in heart muscle (110 vs 176 nmol/g without the peptide); antioxidant enzymes were not measured (Khavinson et al., US Patent 7,662,789).
- Mitochondrial preservation — In the patent's infarcted rats, heart-muscle mitochondria kept their structure under the electron microscope at 24 hours, and in isolated rat heart cells kept short of oxygen, AEDR at 10 ng/ml normalized succinate oxidation (Khavinson et al., US Patent 7,662,789).
- Sequence and target tissue — The group reports that the direction of a short peptide's effect on cell differentiation depends on its structure: AEDL induced lung-cell differentiation, and AEDG and AEDP induced differentiation in epidermis, mesenchyme and nerve tissue (Khavinson et al., 2020; PMID 31808038). In test-tube binding, AEDG and AEDL, which differ only in their last residue, preferred different DNA sequences (Fedoreyeva et al., 2011; PMID 22117547). No study outside the group has tested whether arginine makes AEDR act on the heart.
- Systemic-epigenetic framing — Khavinson 2021 (Molecules, PMID 34834147) frames the Khavinson peptide family as epigenetic modulators acting on DNA methylation, histone status, and chromatin accessibility at tissue-specific gene sets.
Limitation: as with other Khavinson bioregulators, the mechanism is a hypothesis developed by one research program; the AEDR binding data above are fluorescence and enzyme experiments in test tubes (Khavinson et al., 2021; PMID 34834147). No structural (NMR or crystal) study of AEDR binding DNA and no independent ChIP-seq study has been published.
What the Research Shows
Cardiogen's published literature is concentrated in Russian-language and English-language Springer-indexed Khavinson-program publications. Evidence is preclinical — cell culture and animal models — with no randomized controlled human trials.
- Tissue-specific peptides in aged cell cultures (Khavinson/Linkova 2012, PMID 22808515) — Pancragen, bronchogen and vesugen raised differentiation markers in aged pancreatic, bronchial and prostate-fibroblast cultures. Cardiogen (AEDR) and heart cells were not part of the study.
- Post-ischemic injury models — The developers' patent reports a smaller dead-tissue zone and fewer deaths in rats after a coronary artery was tied, and better recovery of contraction in isolated rat and guinea-pig hearts at a low concentration but worse recovery at a tenfold higher one (Khavinson et al., US Patent 7,662,789). No study reports an effect on scarring.
- Systemic immune / cytokine — Other short Khavinson peptides (Vilon, Epithalon and Cortagen; not cardiogen) changed lymphocyte-activating-factor production by macrophages from young and old mice (Gumen 2006, PMID 17426849) — a broader immunomodulatory (adjusting the immune system up or down) axis beyond strictly cardiomyocyte effects.
- Program review (Khavinson 2021, PMID 34834147) — Systematic review of Khavinson-program peptide bioregulator literature, including AEDR, within the broader epigenetic-modulator framework.
- Cardialin / Cardiopeptide parent-extract era — Soviet-era observational reports on the polypeptide extract (not the synthetic tetrapeptide) describe symptomatic improvements in post-MI recovery and angina frequency. These reports do not directly validate AEDR.
- No human RCTs of AEDR — No double-blind, placebo-controlled trials of synthetic Cardiogen for any cardiovascular endpoint exist in English-indexed peer-reviewed journals.
- No head-to-head vs standard therapy — No trial has tested AEDR against or alongside guideline-directed medical therapy (statins, ACE-inhibitors, beta-blockers, SGLT2 inhibitors, sacubitril/valsartan, anticoagulation).
- No biomarker data — No human data on NT-proBNP, troponin, echo-derived EF, strain, or any validated cardiac biomarker response to AEDR.
Cardiogen's evidence base is preclinical, dominated by a single research program, and has not been independently replicated by Western cardiology research groups. No randomized controlled human trials exist. Mainstream cardiology does not recognize Cardiogen as a therapeutic. Using Cardiogen in place of guideline-directed medical therapy for heart failure, ischemic heart disease, arrhythmia, or hypertension is dangerous. Any community or vendor claim that Cardiogen "treats" cardiovascular disease is unsupported.
Human Data
The synthetic tetrapeptide Cardiogen (AEDR) has not been evaluated in published randomized controlled human trials. The accessible human-use information consists of:
- Cardialin / Cardiopeptide historical clinical experience (not AEDR) — The polypeptide parent extract was used observationally in Soviet-era cardiology for myocardial recovery, post-MI rehabilitation, and age-related cardiovascular support. These reports predate modern randomized-trial methodology and apply to the crude extract, not the defined AEDR tetrapeptide.
- Supplement-line post-market experience — The Khavinson bioregulator product line has been marketed in Russia as a dietary supplement since the early 2000s. Clinician and distributor observational reports exist but do not constitute controlled clinical evidence.
- No pharmacokinetics in humans — No published human PK/ADME data for AEDR. Oral-absorption assumptions within the Khavinson framework are derived from animal studies rather than validated human exposure-response data.
- No cardiology specialty-society recognition — ACC, AHA, ESC, HRS, and HFSA do not mention Cardiogen in guidance documents, scientific statements, or practice guidelines.
- No WADA or sports-performance data — No evidence of effect on exercise performance, cardiac output at exercise, VO₂ max, or any anti-doping-relevant endpoint.
In the context of Western evidence-based cardiology, Cardiogen would be described as a preclinical research compound with no established human efficacy for any cardiovascular indication.
Position Within Evidence-Based Cardiology
Placing Cardiogen in the broader cardiovascular therapeutic landscape is a useful discipline. Guideline-directed medical therapy for ischemic heart disease includes high-intensity statin therapy, ACE inhibitors or ARBs, beta-blockers, antiplatelet therapy (aspirin plus P2Y12 inhibitors where indicated), and SGLT2 inhibitors in diabetic and increasingly non-diabetic populations. Heart-failure therapy has been transformed by sacubitril/valsartan, SGLT2 inhibitors, mineralocorticoid receptor antagonists, and device therapy. Atrial fibrillation management rests on anticoagulation risk-stratified by CHA₂DS₂-VASc, rate or rhythm control, and increasingly ablation for appropriate candidates. Hypertension management is anchored in lifestyle modification plus first-line agents from four classes.
Each of these modalities has Phase 3 RCT support, meta-analytic confirmation, and decades of mortality/morbidity outcome data. Cardiogen has none. A compound with entirely preclinical mechanism data, no human RCTs, no mortality data, no morbidity data, and no specialty-society recognition cannot be compared meaningfully to any element of guideline-directed cardiovascular medicine. The honest framing is that Cardiogen is an experimental research tool peptide; guideline-directed medical therapy is the standard of care; substitution is dangerous.
Reconstitution & Storage
Sellers list research-chemical Cardiogen as lyophilized powder in 20 mg vials. The Russian supplement is a ready-made capsule holding 100 μg of the peptide (Russian product labeling, 2012).
| Vial | BAC Water | Concentration |
|---|---|---|
| 20 mg | 2 mL | 10 mg/mL (10,000 μg/mL) |
| 20 mg | 5 mL | 4 mg/mL (4,000 μg/mL) |
- Reconstitution — Reconstitution guides describe injecting bacteriostatic water slowly down vial wall at 45°, then swirling gently until fully dissolved rather than shaking.
- Oral-capsule product — The Russian label lists storage in a dry place, away from light, at 2–25°C, and a 5-year shelf life (Russian product labeling, 2012).
Side Effects & Risks
- Tolerability — The Russian label lists no side effects (Russian product labeling, 2012). No published study has reported on safety in people.
- Toxicology — The developers' patent reports no toxic reactions in mice given single injections of up to 5 mg/kg and no side effects in rats injected daily for 90 days or guinea pigs for 6 months at up to 1 mg/kg, though its blood table shows higher white-cell counts in guinea pigs given 1 μg/kg (Khavinson et al., US Patent 7,662,789). The full reports are not public, and no reproductive or genotoxicity study has been published.
- Not a substitute for cardiology therapy — No trial has compared Cardiogen with, or added it to, statins, ACE inhibitors, beta-blockers, SGLT2 inhibitors, anticoagulants or device therapy; ClinicalTrials.gov lists no Cardiogen trial. Taking it instead of guideline-directed treatment for ischemic heart disease, heart failure, atrial fibrillation or hypertension would give up treatments with proven benefit for one never tested in people.
- Allergy / intolerance — The Russian label lists intolerance of its components as a contraindication (Russian product labeling, 2012); no report of an allergic reaction to Cardiogen was found.
- Purity / source concerns — Sold as a research chemical, not an approved drug, so no FDA review covers its purity.
- Pregnancy / lactation / pediatric — The Russian label lists pregnancy and breastfeeding as contraindications and gives doses for adults only (Russian product labeling, 2012). No human safety data exist for these groups.
- Drug interactions — No pharmacokinetic or interaction study has been published, and the Russian label lists no interactions (Russian product labeling, 2012).
- WADA status — Not specifically named on the 2026 WADA Prohibited List; its S0 clause covers substances no other section names and no government has approved for human therapeutic use (WADA Prohibited List 2026).
- Theoretical epigenetic concerns — The group proposes that short peptides like this one bind DNA and histones and change gene activity (Khavinson et al., 2021); if so, effects on genes other than the intended ones are possible in theory. No study has looked for long-term effects on gene regulation in people.
Bloodwork & Monitoring
No trial, label or guideline sets monitoring for Cardiogen, and no published study has given it to people. In the developers' toxicity tests, rats injected daily for 90 days and guinea pigs for 6 months had their blood counts and blood chemistry checked; the only change reported was higher white-cell counts in guinea pigs given 1 μg/kg (Khavinson et al., US Patent 7,662,789).
Commonly Stacked With
No published study has tested Cardiogen together with another compound, and its Russian label names no combinations (Russian product labeling, 2012).
Legal Status
Cardiogen is not approved by the U.S. FDA for any indication and has not been the subject of an IND or NDA filing. It is not approved by the European Medicines Agency.
In Russia, Cardiogen is sold as a "biologically active additive" (BAD — dietary supplement) through Khavinson-affiliated distributors. It is not a registered pharmaceutical. The parent extract Cardialin / Cardiopeptide has a separate historical status.
Cardiogen is not on the FDA Category 2 Bulk Drug Substances list, and it was not among the 12 peptides FDA removed from that list in April 2026 (FDA 503A categories list, April 22, 2026). Absent a sponsor undertaking formal clinical development, it is unlikely to achieve a U.S. regulatory pathway.
Cardiogen is not specifically named on the WADA Prohibited List. WADA’s S0 clause (non-approved substances) prohibits at all times any pharmacological substance that no other section covers and that no government health authority has approved for human therapeutic use (WADA Prohibited List 2026).
No cardiology specialty-society guideline (ACC/AHA, ESC, HFSA, HRS) recognizes Cardiogen as a therapeutic. Standard guideline-directed medical therapy remains the standard of care for every cardiovascular indication.
Cardiogen is not approved for human use in the United States. The oral BAD form is distributed internationally through Khavinson-affiliated channels; the injectable lyophilized peptide is available through research-chemical suppliers for laboratory research use only. Personal-use import to the U.S. occupies a legal gray zone; bulk import is enforced against.
No U.S. compounding pharmacy can legally compound Cardiogen — it has no FDA-approved reference product and is not on the Category 1 bulk substance list.
Cardiogen was not among the 12 peptides FDA removed from Category 2 in April 2026 (FDA 503A categories list, April 22, 2026). Absent formal FDA development, it will remain unavailable through legitimate U.S. clinical channels.
Access and availability information as of April 2026. Kalios does not sell compounds.
Next Steps
References
- Khavinson VKh, Linkova NS, Polyakova VO, Kheifets OV, Tarnovskaya SI, Kvetnoy IM. Peptides tissue-specifically stimulate cell differentiation during their aging. Bulletin of Experimental Biology and Medicine. 2012;153(1):148-151. PMID: 22808515.
- Khavinson VKh, Popovich IG, Linkova NS, Mironova ES, Ilina AR. Peptide Regulation of Gene Expression: A Systematic Review. Molecules. 2021;26(22):7053. PMID: 34834147. DOI: 10.3390/molecules26227053.
- Fedoreyeva LI, Kireev II, Khavinson VKh, Vanyushin BF. Penetration of short fluorescence-labeled peptides into the nucleus in HeLa cells and the specific interaction of the peptides with deoxyribooligonucleotides and DNA in vitro. Biochemistry (Moscow). 2011;76(11):1210-1219. PMID: 22117547.
- Gumen AV, Kozinets IA, Shanin SN, Malinin VV, Rybakina EG. Production of lymphocyte-activating factors by mouse macrophages during aging and under the effect of short peptides. Bulletin of Experimental Biology and Medicine. 2006;142(3):360-362. PMID: 17426849.
- Khavinson VKh. Peptides and ageing. Neuroendocrinology Letters. 2002;23(Suppl 3):11-144. PMID: 12374906.
- Khavinson VKh, Malinin VV. Gerontological Aspects of Genome Peptide Regulation. Karger Publishers, Basel, 2005. ISBN 978-3-8055-7895-0. DOI: 10.1159/isbn.978-3-318-01193-7.
- Anisimov VN, Khavinson VKh. Peptide bioregulation of aging: results and prospects. Biogerontology. 2010;11(2):139-149. PMID: 19830585.
- Khavinson V, Linkova N, Diatlova A, Trofimova S. Peptide Regulation of Cell Differentiation. Stem Cell Reviews and Reports. 2020;16(1):118-125. PMID: 31808038. DOI: 10.1007/s12015-019-09938-8.
- Vanyushin BF, Khavinson VKh. Short Biologically Active Peptides as Epigenetic Modulators of Gene Activity. In: Doerfler W, Casadesús J (eds), Epigenetics — A Different Way of Looking at Genetics. Springer, 2016. DOI: 10.1007/978-3-319-27186-6_5.
- Linkova NS, Drobintseva AO, Orlova OA, Kuznetsova EP, Polyakova VO, Kvetnoy IM, Khavinson VKh. Peptide regulation of skin fibroblast functions during their aging in vitro. Bulletin of Experimental Biology and Medicine. 2016;161(1):175-178. PMID: 27259496. (Sibling tissue-specific peptide cell-culture paradigm.)
- Khavinson VKh, Bondarev IE, Butyugov AA. Epithalon peptide induces telomerase activity and telomere elongation in human somatic cells. Bulletin of Experimental Biology and Medicine. 2003;135(6):590-592. PMID: 12937682. (Sibling-peptide methodology reference.)
- Morozov VG, Khavinson VKh. Natural and synthetic thymic peptides as therapeutics for immune dysfunction. International Journal of Immunopharmacology. 1997;19(9-10):501-505. PMID: 9637345. (Program context.)
- Anisimov VN, Khavinson VKh, Mikhalski AI, Yashin AI. Effect of synthetic thymic and pineal peptides on biomarkers of ageing, survival and spontaneous tumour incidence in female CBA mice. Mech Ageing Dev. 2001;122(1):41-68. PMID: 11163623. (Program methodology reference.)
- Ivanov EI, Khavinson VKh. Peptide bioregulation and cardiovascular pathology. Advances in Gerontology. 2013;3(4):267-273. (Program-level cardiovascular framing.)
- FDA. Bulk Drug Substances Nominated for Use in Compounding Under Section 503A of the FD&C Act (503A categories list), versions updated April 15, April 22 and May 14, 2026. fda.gov/media/94155/download. Read October 3, 2026. (Notice that 12 peptides would leave Category 2 because their nominations were withdrawn; their removal; GHK-Cu, except injectable, back in Category 1.)
- Khavinson VKh, Ryzhak GA, Grigoriev EI, Ryadnova IYu. Peptide substance restoring myocardium function. US Patent 7,662,789 B2; February 16, 2010; from Russian patent RU 2255756 C1, filed June 22, 2004. patents.google.com/patent/US7662789B2. Read October 4, 2026. (The developers' patent on Ala-Glu-Asp-Arg: rat, guinea-pig and heart-cell experiments and animal toxicity tests; the Russian original gives the same figures.)
- Cardiogen® capsules 0.2 g (Russian dietary supplement): product instructions approved by the manufacturer, October 17, 2012, as reproduced in the RLS drug encyclopedia. rlsnet.ru/baa/kardiogen-32633, updated August 8, 2022. Read October 4, 2026. (In Russian. The "Russian product labeling" cited above: 100 μg of the peptide per capsule, dose and course, contraindications, storage at 2–25°C, 5-year shelf life.)
- World Anti-Doping Agency. Prohibited List 2026 (in effect January 1, 2026). S0, Non-approved substances. wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf. Read October 3, 2026.
Also for longevity
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Tested together in people
None published · Read the receipt →
Checked 18 Oct 2026