Epithalamin
An injectable peptide preparation extracted from bovine pineal gland, and the substance behind most of the longevity claims made online for its synthetic descendant Epitalon. It is an extract, not a molecule: NLM's own index defines it as an epiphysial polypeptide extract, and the primary literature calls Epitalon its synthetic analogue rather than its formula. This entry prints no sequence. Chemical databases print one anyway, because a lookup on the name returns Epitalon's record.
This is a extract. It contains many peptides and has no single sequence — printing one would be fabrication.
Bioregulator context
Target tissue: pineal gland (endocrine)
That a peptide fraction isolated from young pineal tissue restores the age-related decline in melatonin production and endocrine rhythm, and that repeated annual courses of it in people over 60, alone or with the thymic extract Thymalin, reduce age-related disease and mortality. The developers extend the claim to lifespan in three separate species.
Proposed to restore pineal melatonin synthesis and, through it, circadian and neuroendocrine regulation; the developers additionally propose direct transcriptional regulation by short peptide fragments within the extract, in the same nuclear-binding framework applied across the family. The animal lifespan paper attributes the effect specifically to antioxidant action rather than to gene regulation.
Mechanism
Claimed
Restores pineal function and melatonin rhythm, slows cardiovascular and general ageing, and extends life.
Actually established
Nothing about the mechanism is established, and for an extract part of the question is unanswerable: the entity whose mechanism would be described has no fixed composition. Melatonin rhythm normalisation has been reported in old monkeys and elderly people, and antioxidant effects in rat brain, but the papers that report them do not identify which constituent of the extract is responsible, and the substance most often used to argue the mechanism — epitalon — is a different, synthetic molecule.
How good is the evidence
PubMed indexed 102 records for the name on 2026-08-06, 70 of them mentioning it in title or abstract — one of the larger corpora in this family. The human evidence is real but concentrated and unblinded: a 266-person, 6-8 year course programme run jointly by the developers' institute in St Petersburg and the Institute of Gerontology in Kiev, and a Kiev cohort of 39 treated and 40 control coronary patients followed for 12 and then 15 years. Both report lower mortality. Neither describes blinding or a placebo. The animal evidence is a 1998 paper reporting mean-lifespan increases of 11-31% across Drosophila, two mouse strains and rats — an unusual breadth for one study, all of it from one laboratory.
Khavinson is an author on the 266-person programme, on both Kiev follow-up reports and on the animal lifespan paper. The Kiev group — Korkushko, Shatilo, Antonyuk-Shcheglova, Labunets — recurs across every human result here, so the two 'independent' institutes are in practice one long-running collaboration. The 2007 immune-rhythm paper is the only human study on this page without Khavinson as an author, and it shares two of its four authors with the others.
Claims, one at a time
Each claim carries its own evidence tier. A compound is never simply "well studied" — some of its claims may be, others not at all.
| Claim | Verdict | Evidence | Basis |
|---|---|---|---|
| Epithalamin is the tetrapeptide Ala-Glu-Asp-Gly (AEDG) | contradicted | Animal | It is not. NLM's MeSH supplementary concept defines epithalamin as an epiphysial polypeptide extract with its own CAS registry number, and the primary literature describes epitalon — which is AEDG — as 'a synthetic analogue of the pharmacopoeia drug epithalamin', i.e. as a separate substance modelled on it. The animal lifespan paper calls the material a 'pineal peptide preparation' throughout. The sequence circulates because a chemical-database lookup on the name 'Epithalamin' returns PubChem CID 219042, which is Epitalon's record; the codex resolver reproduced that collision on 2026-08-06. The composition gate cannot catch it, because the colliding record is a valid peptide whose formula matches its own sequence. The only tell is that two names resolve to one CID. |
| Repeated courses in elderly people reduce age-related disease and mortality | mixed | Human trial | Three reports point the same way. A 266-person programme over 6-8 years reports mortality 1.6-1.8-fold lower with Epithalamin, 2.5-fold lower combined with Thymalin, and 4.1-fold lower in a subgroup dosed annually for 6 years. A Kiev study of coronary patients reports 28% fewer deaths at 12 years and 2-fold lower cardiovascular mortality; its 15-year follow-up gives the group sizes as 39 treated and 40 control. Against that: no study describes blinding or a placebo, all three share authors including the compound's developer, the largest reports no per-group denominators or tests, and the 15-year paper's own title says the geroprotector comes from the pituitary gland while its abstract says pineal. No group outside this collaboration has attempted the result in the 24 years since the first report. |
| Extends lifespan in animals | mixed | Animal | One paper reports mean lifespan increased 11-31% (p<0.05) in female Drosophila, SHR mice, C3H/Sn mice and LIO rats, with maximum lifespan and 90% mortality also increased in flies, C3H/Sn mice and rats. Mortality rate fell 52% in flies and rats but was unchanged in SHR mice — the paper's own null result, and worth as much attention as the positives. Four species in one report from one laboratory, with the compound's developer as an author and no independent replication in the 28 years since, is a breadth that should raise the evidentiary bar rather than lower it. |
| Normalises melatonin and immune-endocrine rhythms | mixed | Observational | In elderly chronic coronary patients followed for 30 months, six courses of the preparation were associated with retention of the seasonal rhythms of thymic serum factor and hydrocortisone and a rise in autumn T-cell counts, where untreated elderly patients showed inverted or flattened rhythms. The design is a rhythm-observation study, not a controlled trial; allocation is not described; seasonal comparisons over 30 months are vulnerable to secular and cohort effects; and the authors link the rhythm changes to 'a benign clinical course' without quantifying either. |
The studies themselves
| Study | Design | Subjects | Quality |
|---|---|---|---|
Peptides of pineal gland and thymus prolong human life
Khavinson VKh, Morozov VG · Neuro endocrinology letters · 2003
PMID 14523363
|
observational / human | 266 — 266 elderly and older persons assessed jointly by the St Petersburg Institute of Bioregulation and Gerontology and the Institute of Gerontology, Kiev, over 6-8 years; bioregulators applied during the first 2-3 years | Human trial
risk of bias: high
authored by the developer |
Geroprotective effect of epithalamine (pineal gland peptide preparation) in elderly subjects with accelerated aging
Korkushko OV, Khavinson VKh, Shatilo VB, Antonyuk-Shcheglova IA · Bulletin of experimental biology and medicine · 2006
PMID 17426848
|
controlled_trial / human | — Elderly patients with coronary disease and accelerated cardiovascular ageing, Institute of Gerontology, Kiev; treated group and control group both on the same basic therapy, followed 12 years | Human trial
risk of bias: high
authored by the developer |
Peptide geroprotector from the pituitary gland inhibits rapid aging of elderly people: results of 15-year follow-up
Korkushko OV, Khavinson VKh, Shatilo VB, Antonyk-Sheglova IA · Bulletin of experimental biology and medicine · 2011
PMID 22451889
|
controlled_trial / human | 79 — 39 coronary patients receiving 6 courses of the preparation over 3 years in addition to basic therapy, and 40 coronary patients on basic therapy alone; Institute of Gerontology, Kiev; 15-year follow-up | Human trial
risk of bias: high
authored by the developer |
Pineal peptide preparation epithalamin increases the lifespan of fruit flies, mice and rats
Anisimov VN, Mylnikov SV, Khavinson VK · Mechanisms of ageing and development · 1998
PMID 9701766
|
animal_controlled / mixed | — Female Drosophila melanogaster, SHR mice, C3H/Sn mice and LIO rats | Animal
risk of bias: high
authored by the developer |
Effect of epithalamin on the rhythm of immune and endocrine systems functioning in patients with chronic coronary disease
Labunets IF, Butenko GM, Korkushko OV, Shatilo VB · Bulletin of experimental biology and medicine · 2007
PMID 18214303
|
observational / human | — Elderly and senile patients with chronic coronary disease, compared with young people; a subgroup received 6 courses of the preparation over 30 months. Institute of Gerontology, Kiev | Observational
risk of bias: high
|
- Epithalamin has no single amino-acid sequence, and no source publishes its composition in a form that would let a reader verify what is in a given batch. This entry prints none for that reason.
- Chemical databases print one anyway. A PubChem lookup on the name returns CID 219042, which is Epitalon's record; the codex resolver reproduced that collision on 2026-08-06 and the composition gate could not catch it, because Epitalon's formula legitimately matches Epitalon's sequence.
- It is not established how much of the evidence attributed to this extract was actually obtained with it rather than with the synthetic tetrapeptide, since the two are used interchangeably in secondary sources and sometimes within a single paper's discussion.
- No randomised, blinded, placebo-controlled trial of this preparation exists in the PubMed-indexed literature, in any language, for any indication.
- The mortality results have never been attempted by any group unconnected to the St Petersburg and Kiev collaboration, in the 24 years since the first report.
- No human pharmacokinetic data exists, and for an extract the term has no single meaning: there is no one molecule whose absorption or clearance could be measured.
- The Russian-language half of this 102-record corpus has not been read or assessed for this entry.
- No dose is recorded on any study on this page, because no full text has been read.