Livagen
A synthetic Khavinson-class tetrapeptide proposed to act as a liver-specific bioregulator, restoring age- and stress-related changes in hepatocyte function through chromatin-level gene modulation.
Livagen is a short synthetic peptide developed by Vladimir Khavinson's group at the St. Petersburg Institute of Bioregulation and Gerontology, positioned as a hepatic bioregulator intended to normalize age-related changes in liver tissue. It is most often described as the tetrapeptide Lys-Glu-Asp-Ala (KEDA) and belongs to the same ultrashort peptide family as Epitalon, Pinealon, Vilon, and Thymogen. The evidence base derives almost entirely from Russian preclinical and small observational studies within a single research program, with no placebo-controlled RCTs indexed in Western literature. It has no regulatory approval and is sold as a research chemical or post-Soviet supplement capsule.
Class
Synthetic tetrapeptide bioregulator (Khavinson class)
Half-life
Not characterized in published literature
Routes
Oral / sublingual capsule, Subcutaneous, Intramuscular
Category
Longevity & Bioregulators
Researched benefits
What it's studied for
Liver cell regeneration
Russian rodent studies report increased hepatocyte proliferation markers and restoration of age-related liver morphology after KEDA treatment. Evidence is preclinical and confined largely to the Khavinson research program.
Hepatoprotection
Proposed to support hepatocyte function and normalize age- and stress-related hepatic changes. Small uncontrolled Russian observational series report modest improvements in ALT, AST, and total bilirubin over 20-30 day oral cycles in chronic hepatitis and fatty liver patients.
Chromatin activation of silenced genes
The central Khavinson claim is that the tetrapeptide enters hepatocyte nuclei and preferentially up-regulates transcription programs suppressed by aging and chronic stress, including modulation of rDNA expression and heterochromatin organization in aged hepatocytes. This mechanism awaits contemporary structural-biology validation.
Immune restoration via liver-mediated pathways
Class-level reviews of ultrashort di- and tripeptides document immunomodulatory activity in lymphoid and hematopoietic tissue, and Livagen is described as restoring lymphocyte activity through liver-mediated immune pathways. Evidence is at the peptide-class level rather than Livagen-specific.
Mechanism
How it works
Livagen's proposed mechanism is the standard Khavinson short-peptide bioregulator model applied to hepatic tissue, developed across roughly 35 years at the St. Petersburg Institute of Bioregulation and Gerontology. It posits three nested levels of action: passive membrane permeation, nuclear import, and sequence-selective chromatin modulation.
At roughly 447-460 daltons, the peptide is proposed to be small and polar enough to cross phospholipid bilayers without active transport. Tritiated-peptide distribution studies in rodents reported rapid tissue uptake after intraperitoneal or oral dosing, with radioactivity recovered from liver, thymus, brain, and testis within minutes. Because those experiments did not distinguish intact peptide from amino-acid catabolites, the claim that Livagen reaches the hepatocyte nucleus intact rests on inference rather than direct structural confirmation.
Once inside the hepatocyte, the model argues the tetrapeptide diffuses through nuclear pores (there is no karyopherin-based active import pathway) and binds specific chromatin regions via base-pair-level contacts with exposed histone tails and/or B-form DNA, producing sequence-selective chromatin decondensation and preferential activation of silenced age-associated genes. Russian publications describe modulation of rDNA expression and changes in heterochromatin organization in hepatocytes from aged rats after KEDA treatment. These claims require co-crystal structures, genome-wide ChIP-seq, and defined rescue experiments that have not been published in Western-indexed literature.
A more conservative interpretation treats Livagen as a rapidly absorbed source of constituent amino acids (lysine, glutamate, aspartate, alanine), whose effects could reflect acute substrate delivery for hepatic protein synthesis or non-specific amino-acid signaling. No G-protein-coupled receptor, nuclear receptor, or defined enzyme target has been identified; the peptide does not interact with FXR, PPAR-alpha, or mapped cytochrome P450 enzymes. The absence of a classical target is intrinsic to the bioregulator framework but is also why Western pharmaceutical developers have not pursued the molecule.
Dosing protocols
Dosing & administration
Dosing reflects protocols reported in research and community literature for educational purposes. It is not medical advice or a recommendation. Most peptides here are not approved for human use.
Reconstitution
Applies only to synthetic lyophilized KEDA peptide, not commercial capsules. Let the vial reach room temperature (10-15 min), swab both stoppers, and slowly inject bacteriostatic water (0.9% benzyl alcohol) down the vial wall rather than onto the pellet. For a 5 mg vial, 2 mL BAC water yields 2.5 mg/mL (0.25 mg per 10 units on a U100 insulin syringe): a 2 mg dose = 80 units (0.8 mL), a 2.5 mg dose = 100 units (1.0 mL). An alternative 3 mL reconstitution gives 1.67 mg/mL for finer dose adjustment. Allow passive dissolution (5-10 min, gentle swirling only), then store at 2-8 C. Do not freeze reconstituted solution; typical stability is 28-30 days refrigerated. Discard if cloudy or containing particulate.
Beginner (first cycle, cautious)
- Dose
- 1 x 20 mg oral capsule (nominal; ~2-4 mg actual peptide)
- Frequency
- Once daily
- Timing
- Sublingual for ~60 seconds then swallow, or oral on empty stomach 30-45 min before breakfast
- Duration
- 10 consecutive days, then stop
- Route
- Oral / sublingual
Use only capsules with third-party HPLC certificate of analysis. Minimum 60-day washout before repeating. Get a baseline metabolic panel (AST, ALT, bilirubin, GGT, ALP, albumin), repeat at cycle end and 6 weeks post-cycle. Stop for any rash, persistent headache, worsening enzymes, or new GI symptom.
Intermediate (experienced user)
- Dose
- 20 mg oral/sublingual OR 2-5 mg subcutaneous
- Frequency
- Once daily
- Timing
- Morning; SC into rotating abdomen/thigh sites
- Duration
- 10 consecutive days on, then off
- Route
- Oral / sublingual or subcutaneous
SC dosing uses reconstituted synthetic peptide and bypasses first-pass hydrolysis (theoretically higher exposure per mg, though PK is uncharacterized). Cycle within a rotating bioregulator program: Livagen days 1-10, then 60-70 day washout before the next peptide. Continue any evidence-graded hepatic support rather than substituting it.
Advanced (Khavinson multi-bioregulator rotation)
- Dose
- 20 mg sublingual daily OR 5 mg SC daily
- Frequency
- Once daily during each 10-day pulse
- Timing
- Month 1 days 1-10 Livagen; then rotating annual cycles interspersed with Epitalon, Pinealon, Thymogen
- Duration
- 10-day pulses separated by ~2-month washouts across an annual rotation
- Route
- Sublingual or subcutaneous
For users with 6+ months of bioregulator experience and stable baseline hepatic biochemistry. Baseline and annual comprehensive metabolic panel, CBC, and fasting lipid/glucose/insulin; liver ultrasound or elastography annually if any metabolic-syndrome history. Keep a cycle log (dose, source, lot, endpoints). This is a ritual layered on a sound hepatic and metabolic base, not an evidence-graded therapy.
- Dosing conventions come from Khavinson-group Russian publications and post-Soviet product labelling, not modern human pharmacokinetic studies.
- The dominant commercial format is a 20 mg oral capsule containing an undisclosed (historically 2-4 mg) amount of actual KEDA peptide, with the balance excipient.
- The 10-days-on / 60-90-days-off pattern is the uniform Khavinson convention; no dose-ranging or duration-comparison study establishes that 10 days is optimal.
- Do not exceed 20 mg oral or 5 mg SC per day without a clinical reason and supervision. Do not run continuous (year-round) dosing; the published protocol is always cyclical.
- Intranasal use has no Khavinson convention or pharmacokinetic support for Livagen. No formal renal or hepatic dose adjustment is published; avoid in significant renal impairment or decompensated liver disease.
- Younger adults with normal hepatic biochemistry should note the 'age-related restoration' rationale predicts smaller theoretical benefit. There is no paediatric use.
Evidence
Research & clinical studies (2)
Bioavailability and Biological Activities of Food-Derived Di- and Tripeptides: In Silico and In Vitro Studies
Examines biological activities and transport mechanisms of ultrashort di- and tripeptides including livagen, documenting immunomodulatory activity in lymphoid and hematopoietic tissues and transport via intestinal peptide transporters relevant to systemic bioavailability.
PMID 35457077Short Peptides in the Treatment of Age-Related Diseases
Summarizes geroprotective properties of short regulatory peptides including livagen, documenting effects on hematopoietic and lymphoid tissue function and longevity in animal models, with discussion of reduced age-related pathology in human cohorts from the Khavinson program.
PMID 31808038Combinations
Stacking & blends
Livagen + Glutathione
Hepatic antioxidant and detoxification support
Glutathione is described as synergistic with Livagen in an interaction matrix, pairing the peptide's proposed regenerative signaling with a primary hepatic antioxidant.
Livagen + NAD+
Liver anti-aging with mitochondrial support
NAD+ precursors are listed as compatible with Livagen and provide better-validated mitochondrial support, positioning Livagen as the experimental layer on a more evidence-graded base.
Khavinson bioregulator rotation
Multi-organ longevity cycling
Community convention rotates Livagen with other Khavinson tetrapeptides in 10-day pulses across an annual schedule, each targeting a different organ system (liver, pineal/general aging, brain, thymus/immune). No evidence of synergy exists beyond the theoretical framework.
Livagen on an evidence-graded hepatic base
Layer experimental bioregulator over proven liver support
Sources recommend Livagen sit on top of, not replace, evidence-graded interventions such as weight management, TUDCA for cholestatic biochemistry, and Berberine for NAFLD/metabolic support.
Safety
Side effects & considerations
Commonly reported effects
Contraindications & cautions
- Pregnancy
- Breastfeeding
- Paediatric use (under 18)
- Active hepatic malignancy (hepatocellular carcinoma or hepatic metastases)
- Known hypersensitivity to Livagen or any Khavinson bioregulator
- Decompensated cirrhosis (Child-Pugh B or C) except under specialist supervision
- Advanced NASH with significant fibrosis
- Active viral hepatitis B/C/D not on appropriate antiviral therapy
- Autoimmune hepatitis on immunosuppression
- Active or recent haematological or other malignancy
- Recent solid-organ transplant
- Severe renal impairment
No serious adverse events are reported in published Russian series, but total documented human exposure is likely only in the low hundreds, too small to detect rare events, and long-term safety of repeated bioregulator cycling has not been characterized by modern pharmacovigilance. Contraindications reflect clinical prudence rather than a formally studied adverse-event database. Use a vendor with third-party HPLC analysis and monitor baseline and post-cycle hepatic biochemistry. Do not stop antiviral therapy or replace hepatology care to run Livagen cycles.
FAQ
Livagen — common questions
What is Livagen and what is it supposed to do?
Livagen is a synthetic tetrapeptide (Lys-Glu-Asp-Ala, abbreviated KEDA) developed by Vladimir Khavinson's group as a hepatic bioregulator. The claim is that the peptide enters hepatocyte nuclei, modulates chromatin, and restores age-related declines in liver function. Russian rodent studies report chromatin-structural changes in aged hepatocytes and improvements in small human observational series. Outside Russia it is not a registered drug and the evidence base is thin.
Does Livagen actually work in humans?
The honest answer is that it is unknown. Russian observational series report modest improvements in ALT, AST, and total bilirubin across 20-30 day oral cycles in chronic hepatitis and fatty liver disease, but these are uncontrolled, unblinded, single-institute studies. No placebo-controlled, blinded RCT has been published in Western-indexed literature, and the reported changes cannot be distinguished from regression to the mean or concurrent lifestyle change.
What is the correct Livagen dose?
Khavinson-convention dosing is a 20 mg oral or sublingual capsule once daily for 10 consecutive days, followed by a 60-90 day washout. The 20 mg capsule contains an undisclosed amount of actual KEDA peptide (historically ~2-4 mg). For subcutaneous administration of synthetic lyophilized peptide, 2-5 mg daily for 10 days is the community convention. There is no published dose-ranging study; do not exceed 20 mg oral daily.
Is Livagen safe?
The safety signal from Russian literature is reassuring but thin. Reported short-term effects across 10-30 day cycles include mild nausea, dyspepsia, occasional headache, and rare mild rash, with no serious adverse events in published series. Total documented exposure is small, and long-term safety of intermittent cycling is uncharacterized. Pregnancy, breastfeeding, paediatric use, and active hepatic malignancy are absolute contraindications.
How does Livagen compare to TUDCA, SAMe, and silymarin?
All three are better-validated than Livagen for hepatic support. TUDCA has strong mechanistic support for cholestatic biochemistry, SAMe has RCT support in alcoholic and cholestatic liver disease, and silymarin has generally positive evidence. Each has pharmacokinetic characterization and known interaction profiles that Livagen lacks. For maximum hepatic benefit per dollar, prioritize TUDCA or silymarin; treat Livagen as an experimental add-on.
How does Livagen compare to the other Khavinson peptides?
Livagen belongs to a family of short peptides sharing the same 2-4 amino-acid structure and passive-diffusion-plus-chromatin-modulation claim, including Epitalon (pineal/general aging), Pinealon (brain), Thymogen and Vilon (thymus/immune), and organ-specific tetrapeptides. Among them Epitalon has the most published literature and Thymogen the most regulatory recognition; Livagen sits in the middle with specific liver targeting but modest literature.
Can I stack Livagen with other peptides or my existing liver protocol?
Community convention cycles Livagen with other bioregulators (Epitalon, Pinealon, Thymogen) in rotating 10-day cycles. Stacking with evidence-graded hepatic support such as Berberine, TUDCA, or weight management is sensible, with Livagen as the experimental layer on top rather than a replacement. Do not stop antiviral therapy for hepatitis or replace hepatology care for cirrhosis to run bioregulator cycles.
Is Livagen legal and detectable in sports testing?
Livagen is not on the WADA Prohibited List as of 2026 and is not a registered pharmaceutical in the US, EU, UK, Australia, or Canada; its status as a dietary supplement is ambiguous and importation for personal use sits in a grey zone. For competitive athletes, WADA's S0 non-approved-substance clause arguably covers any unregistered peptide, so no unregulated peptide is truly safe for tested athletes.
