Section 01
What it's used for
No real circadian-rhythm study
No published study has tested pinealon (Glu-Asp-Arg) on circadian rhythm. Related melatonin work used different peptides, epithalamin and epitalon, in old monkeys and elderly people; results don't transfer, and the paper omits group sizes.
▸Clinical wording
A search of PubMed and Europe PMC returned no published study in which pinealon (Glu-Asp-Arg) was administered and a circadian outcome was actually measured. The melatonin-rhythm research from the same Russian school used different preparations — epithalamin, a pineal extract, and epitalon, the tetrapeptide Ala-Glu-Asp-Gly — which were reported to restore night melatonin release in old rhesus monkeys and in elderly people. Those findings concern other molecules and cannot be transferred to pinealon; the abstract of that work does not state group sizes, and it was published in a Russian-language gerontology journal.
Melatonin claim lacks evidence
No study has measured melatonin in animals or people given pinealon. The nearest evidence is indirect: a 2020 review found the peptide raised serotonin in cultured rat brain cells, a melatonin precursor, but melatonin was never measured.
▸Clinical wording
No study was found that measured melatonin concentrations in animals or people after pinealon administration. The closest published link is indirect: a 2020 review by the Khavinson group reports that the EDR peptide increased serotonin synthesis in cultured rat cerebral cortex neurons and notes that serotonin is a precursor of melatonin — but melatonin itself was not measured in that work. Claims that pinealon reverses the age-related fall in melatonin are therefore not supported by published measurements.
Sleep claim, no published study
This use is described in vendor and community material, but searches turned up no published study that actually measured sleep in animals or people after giving pinealon, the EDR peptide, or Glu-Asp-Arg, in any species tested.
▸Clinical wording
This direction is described without published findings behind it. Searches of PubMed and Europe PMC combining pinealon, EDR peptide or Glu-Asp-Arg with sleep or insomnia returned no study in which sleep was measured in animals or in people.
Antioxidant effect in cell tests
In lab-grown rat brain and immune cells under stress, pinealon reduced harmful oxygen radicals and cell death. In aged rats under low-oxygen stress, it lowered inflammation markers. Nearly all this work is from one network, unreplicated.
▸Clinical wording
In cell culture, pinealon produced a dose-dependent reduction of reactive oxygen species accumulation in rat cerebellar granule cells, neutrophils and PC12 cells under oxidative stress, and reduced necrotic cell death measured by propidium iodide uptake. In aged rats subjected to acute hypoxic hypoxia, pinealon was reported to lower neuroinflammatory markers and caspase-3-related indices toward reference values. These effects are attributed by the authors to antioxidant and anti-apoptotic mechanisms and to direct peptide–DNA interaction; no study links them to a melatonin pathway. Almost all of this work comes from laboratories affiliated with the Khavinson group, and the studies are small, so the findings should be treated as unreplicated.
Learning effects in rat offspring
In pregnant rats fed a diet raising homocysteine, pinealon reportedly improved offspring learning and reduced cell damage in their brain cells. A separate rat study checked maze learning and a cell-death marker. Both small, same network.
▸Clinical wording
Rats were made hyperhomocysteinemic during pregnancy by dietary methionine loading; pinealon given to the dams was reported to improve spatial orientation and learning in the offspring and to reduce reactive oxygen species and necrotic cell counts in cerebellar neurons isolated from those offspring. A separate rat study reported effects of pinealon on navigation-maze learning and on caspase-3 in cortex and brainstem in young and old animals. Both are small Russian-language reports from the same research network, and the abstracts do not state group sizes.
Alzheimer's-model cells only
In brain-cell cultures from Alzheimer's-model mice, the peptide helped preserve nerve connections. A 2024 study found it cut DNA damage in neurons grown from elderly donors' skin cells, human cells in a dish. No trial in Alzheimer's.
▸Clinical wording
In hippocampal neuron cultures from 5xFAD transgenic mice, the EDR peptide was reported to interfere with the loss of dendritic spines and to help restore mushroom-shaped spine morphology; the same review reports increased SOD2 and GPX1 activity and reduced caspase-3 in related models. In a 2024 study, EDR reduced oxidative DNA damage and stimulated dendritogenesis in induced neurons derived from fibroblasts of elderly human donors — human cells in vitro, not treated patients. This is cell-culture and transgenic-animal evidence only; no trial has tested pinealon in Alzheimer's disease.
Small open-label human reports
In 72 brain-injury patients, adding oral pinealon to standard care improved memory and brain-wave measures. Other reports cover 32 patients, 110 people, and railway workers. All small, open-label, no placebo, from one research school.
▸Clinical wording
The 2020 Khavinson review reports that oral pinealon added to standard therapy in 72 patients with consequences of traumatic brain injury and cerebrasthenia improved memory, reduced errors on a correction test and increased the EEG alpha-index. Other human reports include 32 patients aged 41–83 with polymorbidity and organic brain syndrome in remission, a comparison of geroprotective regimens in 110 people, and an occupational-health series in railway locomotive crews. All of these are small, open-label, without placebo control, published in Russian-language gerontology journals by the same school; no randomised controlled trial of pinealon was found.
Section 02
Mechanism of Action
A claim of direct action on genes
- The originating group proposes the tripeptide acts inside the nucleus rather than through a receptor.
- Labelled peptide appeared in the cytoplasm, nucleus and nucleolus of cultured human cells.
- In cell-free tests it preferentially bound DNA fragments with certain repeat motifs and discriminated methylated cytosine.
- Computer modelling placed its lowest-energy docking sites in the control regions of several genes.
▸Clinical wording
Nuclear uptake and sequence-selective binding to DNA
The mechanism proposed by the originating group is direct nuclear action rather than receptor signalling. Fluorescein-labelled EDR (Glu-Asp-Arg) incubated with HeLa cells produced fluorescence in cytoplasm, nucleus and nucleolus, and in cell-free assays the tripeptide bound deoxyribooligonucleotides preferentially carrying CNG and CAG motifs while discriminating cytosine methylation status (Fedoreyeva 2011). Separate molecular modelling docked EDR into B-form double-stranded DNA and placed the lowest-energy sites in promoter regions of CASP3, NES, GAP43, APOE, SOD2, PPARA and PPARG (Khavinson 2021).
Antioxidant gene changes in rat brain
- In hypoxia-sensitive rats the peptide raised two antioxidant enzyme activities toward the levels of resistant animals.
- It also lowered a cell-death enzyme (caspase-3) in the brain alongside better maze scores.
- The same review reports more serotonin production in cultured rat cortical neurons.
- Proposed routes for crossing membranes come from computer docking only, not from experiments.
▸Clinical wording
Antioxidant and antiapoptotic gene expression in rodent brain
In hypoxia-sensitive rats, EDR administration raised superoxide dismutase 2 and glutathione peroxidase 1 activity toward the levels seen in naturally hypoxia-resistant animals, and lowered brain caspase-3 expression alongside better Morris maze scores; the same review reports increased serotonin synthesis in rat cortical neuron cultures and a predicted binding site in the TPH1 promoter (Khavinson 2020). Computational docking has also been used to argue that EDR could cross membranes via LAT1, LAT2 or PEPT1 transporters, but that work is modelling only (Khavinson 2023).
Fewer damaging oxygen radicals in cell tests
- The peptide restricted reactive oxygen buildup dose-dependently in three rodent cell types under oxidative stress.
- It also reduced necrotic cell death measured by a standard dye uptake test.
- Radical suppression saturated at low concentrations while cell cycle effects continued at higher ones.
- From that gap the authors inferred a second action at the genome level beyond radical scavenging.
▸Clinical wording
Limitation of ROS accumulation in cell culture
Pinealon restricted reactive oxygen species accumulation dose-dependently in rat cerebellar granule cells, neutrophils and PC12 cells challenged by receptor-dependent and receptor-independent oxidative stress, and reduced necrotic death measured by propidium iodide uptake. Protection came with a delayed time course of ERK1/2 activation and a shift in cell cycle distribution; because ROS suppression saturated at lower concentrations while cell-cycle effects continued at higher ones, the authors inferred a second, genome-level action beyond radical scavenging (Khavinson 2011).
Protecting synapse contact points in mice
- In mouse hippocampal cultures exposed to amyloid, the peptide raised mature spine counts by 71%.
- That returned spine numbers to control level and outperformed a related tripeptide at the same concentration.
- In an Alzheimer-model mouse strain, injected peptide likewise prevented dendritic spine loss.
- Benefit was also reported in rat offspring exposed to high homocysteine before birth.
▸Clinical wording
Dendritic spine preservation in amyloid synaptotoxicity models
In primary mouse hippocampal cultures exposed to amyloid, EDR at 200 ng/ml raised the number of mushroom spines by 71% and returned the count to control level, outperforming the related tripeptide KED at the same concentration (Kraskovskaya 2017). In 5xFAD-M mice, intraperitoneal EDR likewise prevented dendritic spine loss, and the DNA-docking analysis in the same report is offered as the proposed explanation (Khavinson 2021). Cognitive and antioxidant benefit was also reported in rat offspring exposed to prenatal hyperhomocysteinemia (Arutjunyan 2012).
Why this evidence stays weak
- Nearly all published work comes from one Russian research group and its affiliated laboratories.
- Independent replication, proof of DNA binding inside living neurons and registered clinical trials are absent.
- The nuclear transcription model remains a hypothesis built on docking and correlative expression data.
- No study shows the peptide raises melatonin, so the pineal link rests on the trade name.
▸Clinical wording
Weak evidence base and unsupported pineal claims
Nearly all published work on EDR comes from the Khavinson group and affiliated Russian laboratories; independent replication, structural or biochemical proof of DNA binding inside living neurons, and registered clinical trials are absent from the indexed literature, and several key reports sit in low-circulation gerontology journals. The nuclear-transcription model remains a hypothesis supported by docking and correlative expression data. No published study shows that EDR raises melatonin output or shifts clock-gene expression in pinealocytes; the pineal association rests on the trade name and on serotonin data, not on melatonin measurements.
Section 03
Biological Pathways
- Nuclear DNA binding hypothesisFluorescein-tagged EDR entered HeLa nuclei and nucleoli, and cell-free assays showed it bound DNA carrying CNG/CAG motifs, with modelling docking it into gene promoters (Fedoreyeva 2011; Khavinson 2021).
- Antioxidant gene expression in ratsIn hypoxia-sensitive rats, EDR raised superoxide dismutase 2 and glutathione peroxidase 1 activity toward hypoxia-resistant levels and lowered brain caspase-3 alongside better maze scores (Khavinson 2020).
- ROS limitation with a second actionPinealon dose-dependently limited ROS in cerebellar granule cells and PC12 cells, but cell-cycle effects continued past the dose where ROS suppression saturated, implying a genome-level action too (Khavinson 2011).
- Dendritic spine preservationIn hippocampal cultures exposed to amyloid, EDR restored mushroom spine counts to control level, outperforming tripeptide KED, and prevented spine loss in 5xFAD-M mice too (Kraskovskaya 2017; Khavinson 2021).
- Weak, single-group evidence baseNearly all EDR work comes from one Russian laboratory group; no published study shows it raises melatonin or shifts clock-gene expression, so the pineal-support claim rests on the trade name, not measurement.
Section 04
Dosage Information
Glu-Asp-Arg| Route / system | Context | Range studied | Limitation |
|---|---|---|---|
| Intramuscular — sole measured human dose | After head injury, 25 patients aged 31–60, in the patent | 1.0 µg, 10.0 µg or 5.0 mg once a day for 10 days, assigned by severity — about 0.011 µg/kg to 60 µg/kg for a 70–90 kg adult | Good results claimed in 59.4%, satisfactory in 31.9% — percentages 25 people cannot yield. No control group, no blinding, nothing published outside the patent. |
| Oral — workplace study | Train drivers, a Russian journal, 2012 | One capsule of 100 µg twice a day for two weeks — about 2.2–2.9 µg/kg a day for a 70–90 kg adult | The summary never says how many workers took part and describes no control group. What was measured was a "biological age" score, not a health outcome. |
| Oral — Russian supplement capsules | Manufacturer's leaflet for the capsule sold as a supplement | 1–2 capsules of 0.215 g, 1–2 times a day with food, 10–30 days, repeat in 4–6 months. The label names a peptide complex, not a dose. | A leaflet, not a finding: Russian supplements are registered with no check that they work. With no peptide amount, it cannot be set against the 100 µg capsule. |
| Subcutaneous — self-administration | Circulating practice around the 10–20 mg research vial | No agreed range: 100–300 µg a day up to 5–10 mg a day, in courses of 10–20 days — roughly 1 to 140 µg/kg for a 70–90 kg adult | A hundredfold spread with nothing to choose between its ends, by a route no study used. Only repetition on seller pages holds these numbers up. |
| Animal and cell models | Head injury and oxygen loss in rats; brain slices; crayfish | Rats: 10 µg/kg into muscle, 1 µg each in the belly for 10 days. In the dish: 1, 10 and 100 ng/ml on brain slices, 10 µg/ml on nerves. | Sudden injury and oxygen loss in rodents and one invertebrate, scored as cell survival. Nothing was scaled to a human; ageing and thinking were never measured. |
Results
Syringe Fill Level (100u syringe)
Set positive values for: Recommended dose per kg.
Research Use Only. This information is for educational and research purposes only. Not intended for medical advice or self-medication.
Section 05
Protocols
No protocols featuring this peptide yet. Browse All Protocols
Section 06
Stability & Storage
Storing the product
The registered form is capsules: they are kept in a dry place away from light at 2–25 °C, with a shelf life of 5 years. For the lyophilised vial sold as a research reagent there are no published storage conditions.
After opening
The liquid form sold as Pinealon Lingual is kept refrigerated for no more than 10 days once the bottle is opened. For the capsules the instruction sets no separate period after the pack is opened.
Section 07
Side Effects & Precautions
No dedicated toxicology, mutagenicity or reproductive-toxicity study of Pinealon was found, and no medicinal-product registration or registered clinical trial for it was found anywhere.
A negative signal in the only relevant study
In 32 patients aged 41 to 83, Pinealon was linked to prooxidant activity and a drop in CD34+ blood cells, interpreted as significant inhibition of haemopoiesis. Pinealon was given together with another peptide, Vesugen, so the effect cannot be attributed to Pinealon alone.
Human evidence is two studies, one group
Human data come from two open-label, uncontrolled studies by the same Ekaterinburg research group. No independent replication of either was found.
110-person comparison, with caveats
A 110-participant study compared oligopeptides, including Pinealon, against physiotherapy procedures for geroprotective safety.
- Oligopeptides tied with therapeutic massage for the safest ranking; the comparator was physiotherapy (carbon-dioxide baths, hyperbaric oxygenation), not placebo.
- Adverse-event rates and participant dropouts were not reported in the study.
No toxicology or reproductive testing found
No dedicated toxicology, mutagenicity or teratogenicity study of Pinealon was found. The only pregnancy-related data come from a rat efficacy experiment measuring benefit to offspring, not maternal toxicity or malformations. Vendor claims of such testing have no retrievable source.
No registration, no registered trial
Pinealon has no medicinal-product registration anywhere, and no registered clinical trial was found in any registry checked, including ClinicalTrials.gov and the Russian state registers.
Section 08
Regulatory Status
The only official status it holds is in Russia, where it is registered as a dietary supplement rather than a drug, and no completed human clinical trial of the peptide has ever been published.
Russia
Registered as a dietary supplement
Pinealon (also called EDR) is listed in the Russian pharmaceutical registry as a «биологически активная добавка» — a food supplement, not a licensed drug. That places it in a different regulatory track from the two Khavinson-group products that did become registered pharmaceuticals in Russia, Thymalin and Epithalamin; Pinealon belongs to the later «cytogen» family sold over the counter.
FDA / United States
Not an approved drug
Pinealon has no FDA-approved indication for any human use, is not on the 503A Bulks List and has never been submitted to the agency's bulk-substance nomination process; the same absence of review applies to the EMA in the European Union.
Clinical evidence
No completed human trials exist
A PubMed search for Pinealon or its EDR tripeptide code returns in-vitro and rodent studies only — ischemia models, hypoxia models and a mouse Alzheimer's model — all from the same St Petersburg institute that developed it. No Phase 1 safety study or later-phase efficacy trial has been published in an indexed journal.
The absence of an approved drug status does not make Pinealon a proven treatment, and supplement regulation varies sharply between countries — check the current rules of your own food and drug authority before relying on this summary.
Section 09
Research Studies
- [1]Penetration of short fluorescence-labeled peptides into the nucleus in HeLa cells and in vitro specific interaction of the peptides with deoxyribooligonucleotides and DNAFedoreyeva LI, Kireev II, Khavinson VKh, Vanyushin BF. · Biochemistry (Moscow) · 2011
- [2]Pinealon increases cell viability by suppression of free radical levels and activating proliferative processesKhavinson V, Ribakova Y, Kulebiakin K, Vladychenskaya E, Kozina L, Arutjunyan A, Boldyrev A. · Rejuvenation Research · 2011
- [3]Pinealon protects the rat offspring from prenatal hyperhomocysteinemiaArutjunyan A, Kozina L, Stvolinskiy S, Bulygina Y, Mashkina A, Khavinson V. · International Journal of Clinical and Experimental Medicine · 2012
- [4]Tripeptides Restore the Number of Neuronal Spines under Conditions of In Vitro Modeled Alzheimer's DiseaseKraskovskaya NA, Kukanova EO, Lin'kova NS, Popugaeva EA, Khavinson VK. · Bulletin of Experimental Biology and Medicine · 2017
- [5]EDR Peptide: Possible Mechanism of Gene Expression and Protein Synthesis Regulation Involved in the Pathogenesis of Alzheimer's DiseaseKhavinson V, Linkova N, Kozhevnikova E, Trofimova S. · Molecules · 2020
- [6]Neuroprotective Effects of Tripeptides-Epigenetic Regulators in Mouse Model of Alzheimer's DiseaseKhavinson V, Ilina A, Kraskovskaya N, Linkova N, Kolchina N, Mironova E, Erofeev A, Petukhov M. · Pharmaceuticals · 2021
- [7]Feasibility of Transport of 26 Biologically Active Ultrashort Peptides via LAT and PEPT Family TransportersKhavinson VK, Linkova NS, Rudskoy AI, Petukhov MG. · Biomolecules · 2023
Section 10
Frequently Asked Questions
No published study gave pinealon (the tripeptide Glu-Asp-Arg) and then measured a circadian or melatonin outcome, despite it being marketed as a pineal-gland bioregulator. What exists is preclinical work — reduced oxidative stress and cell death in cultured rat neurons, lower neuroinflammation markers in aged, oxygen-deprived rats — plus a handful of small, open-label, uncontrolled human reports from one Russian research network, with no randomised controlled trial found.
Both routes appear in small human reports but neither in a controlled trial. Intramuscular dosing was reported in 25 head-injury patients, and oral capsules were reported in a workplace study of train drivers measuring a 'biological age' score rather than a clinical outcome; both are uncontrolled and unblinded, so neither route's effectiveness is established.
This has never been measured. The intramuscular study ran 10 days and the oral workplace study ran two weeks, but neither reported when — or whether — an effect appeared during that window; both used broad outcome scores rather than tracking a symptom over time.
Published human use ranges from 1 microgram to 5 milligrams a day by injection in one small patent study, to 100 micrograms twice daily by mouth in another. Circulating self-administration practice — 100 micrograms to 10 milligrams a day — spans roughly a hundredfold and isn't derived from any comparative study.
Its regulatory status isn't clearly documented in the sourcing here. In Russia it's sold under a manufacturer's leaflet as a registered dietary supplement, a category with no requirement to demonstrate a product works. No FDA approval and no international scheduling status for pinealon specifically could be found.
Reported side effects are minimal, but that mainly reflects how little has been looked for: none of the human reports were placebo-controlled or systematically monitored for adverse events, and most come from the same small research network.
No — different peptides from the same Khavinson bioregulator research program. Pinealon is the tripeptide Glu-Asp-Arg; epitalon is a four-amino-acid peptide (Ala-Glu-Asp-Gly) studied for restoring night-time melatonin release in older animals and people. The melatonin-restoration findings associated with this research line come from epitalon and a related pineal extract, not from pinealon.