Epithalon | Reviews, Dosage, and Clinical Trials

Epithalon is a research peptide being studied for its wound healing and regenerative effects.

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    Compound Overview

    Class of Compound:

    Peptide

    Mechanism of Action:

    Epithalon upregulates telomerase activity and elongates telomeres, with the effect of delaying aging processes in reproductive and immune systems and increasing the longevity of test subjects

    Notable Studies:

    Also Known As:

    Epitalon, 307297-39-8, Epithalone, UNII-O65P17785G, O65P17785G, L-alanyl-L-alpha-glutamyl-L-alpha-aspartyl-glycine acetic acid

    Research Applications:

    • Anti-aging & longevity
    • Sleep enhancement
    • Disease prevention

    Risks:

    • Injection site pain
    • Lack of FDA approval
    • Research concentrated in one group

    Chemical Structure

    Epithalon structure

    What is Epithalon?

    Epithalon is a synthetic tetrapeptide isolate composed of the four amino acids alanine, glutamic acid, aspartic acid, and glycine. It is derived from epithalamin, a crude polypeptide extracted from the pineal gland [1].

    The synthetic peptide was developed in the 1980s by a research team led by Professor Vladimir Khavinson of the St. Petersburg Institute of Bioregulation and Gerontology and has since been the subject of extensive research in cell cultures, animals, and humans.

    Epithalon is generally available to licensed handlers, who may see it sold under names like “epitalon,” “epithalone,” and “AEDG peptide.” When sold for educational or scientific research, the peptide should be labeled as a “research chemical,” “reference material” or similar, and not intended for human use.

    Epithalon side effects

    What Does Epithalon Do?

    Epithalon upregulates telomerase activity and elongates telomeres, which has prompted research in areas including life extension, anti-aging, and the inhibition of tumorigenesis [2, 3].

    Known to regulate gene expression and protein synthesis, epithalon has been found to suppress both the CCl11 and HMGB1 genes, thereby increasing the lifespan of test subjects [4].
    It also has significant antioxidant effects and has been shown to inhibit carcinogenic receptor expression, which has led to research into its potential anti-tumor effects in breast and colorectal cancer [5, 6].

    Epithalon has been investigated as a potential treatment for rheumatoid arthritis and ulcerative colitis due to its ability to regulate biomolecules involved in the inflammation process, such as cytokines and C-reactive protein [7].

    The peptide has also been investigated as a regulator of the sleep cycle, as it increases levels of melatonin and endogenous gonadotropic hormones (FSG, LG, prolactin), which play a role in reproductive function but naturally decline with age [8].

    Epithalon Benefits | Clinical Trials

    Epithalon is classified as a research chemical outside of Russia, where it is used to treat menopause-related symptoms, anovulatory infertility, and hormone-dependent tumors [9].

    As noted by the Alzheimer’s Drug Discovery Foundation (ADDF), the bulk of research involving epithalamin and epithalon has been conducted in Russia (or formerly, the Soviet Union) and has not been subject to independent confirmation [1].

    The ADDF further notes that its review of epithalon has excluded roughly half of the approximately 110 epithalon/epithalamin articles published in the Russian language, though efforts have been made to refer to English translations where possible.

    Below, we present a summary of key epithalon benefits based on the research available.

    Epithalon and longevity

    It is known that epithalon regulates gene expression and protein synthesis, with the general effect of reducing mortality and delaying the progression of age-associated diseases in the elderly [4].

    In an in vitro study conducted by Professor Khavinson and colleagues in 2003, the team demonstrated that epithalon elongates telomeres and induces telomerase activity when introduced to telomerase-negative human fetal fibroblast cultures. The researchers concluded that epithalon may prolong the lifespan of cell populations through anti-senescence activity [2].

    In a human study published that same year, Khavinson and colleagues observed that elderly human subjects who received epithalamin treatment for two to three years experienced a 1.6-1.8 fold decreased mortality rate compared with a control group. Additionally, the researchers found that the epithalamin-treated patients exhibited reduced rates of:

    • Coronary artery disease
    • Hypertension
    • Osteoarthritis
    • Osteoporosis

    The researchers concluded that epithalon may be used for “health maintenance and age-related pathology prevention” in the elderly [10].

    Epithalon and sleep

    Animal studies have shown that the peptide increases melatonin may therefore enhance sleep and promote brain health.

    • A 1992 study by Anisimov et al. investigated the effect of epithalamin on the pineal and serum melatonin levels in elderly rats. The team noted that epithalamin increased melatonin production in rats, referencing past research showing that the administration of melatonin had the effect of increasing the rodents’ longevity [9].
    • A 2001 study by Khavinson et al. investigated the regulatory effect of epithalon on the production of melatonin and cortisol in senescent monkeys, finding that the peptide significantly stimulated melatonin synthesis, thus normalizing the circadian rhythm of cortisol secretion [11].
    • A 2004 study by Korkushko et al. found that epithalamin could be used to increase melatonin production by modulating the melatonin-producing function of the pineal gland [12].
    • In a 2013 study by Korenevsky et al., the researchers administered a combination of melatonin and epithalon to female rats exposed to suboptimal environmental factors, such as light pollution, finding that the combined therapy rectified various impairments of the hypothalamic-pituitary-gonadal axis [13].

    The link between melatonin and brain health has been clarified in more recent research by Chitimus et al., noting that melatonin has antioxidant properties and can help protect the brain from oxidative stress [14].

    Since oxidative stress may contribute to neurodegenerative disorders, there is strong research interest in epithalon’s role in optimizing sleep and maintaining overall brain health.

    Epithalon and DNA repair

    Research indicates that epithalon may be used to protect against and repair DNA damage, given its potent antioxidant activity. For example, it has been shown to:

    • Decrease levels of DNA damage when administered to senescence-accelerated mice [15];
    • Stimulate cortical neurons when administered intranasally to rodents [16];
    • Increase levels of the DNA-binding protein phosphor-CREB [17]; and,
    • Improve antioxidant defense systems in flies and rats [18, 19, 20]

    Epithalon and cancer research

    Preclinical studies in rats and cancer-prone mice suggest that epithalon may have utility in cancer prevention.

    • In a 2002 study by Anisimov et al., female transgenic FVB mice carrying the breast cancer gene HER-2/neu were given monthly injections of either vilon or epithalon. Researchers found that epithalon “markedly inhibited neoplasm development” and reduced the maximum size of breast adenocarcinomas by 33% compared with the control group [21].
    • A 2006 study by Kossoy et al. investigated the potential preventive effect of epithalon on spontaneous tumorigenesis in mice, finding that the peptide delayed development of metastases from spontaneous tumors, without any metastases found in the experimental mice [22].
    • A pair of studies conducted by Vinogradova et al. found that epithalon significantly inhibited the development of spontaneous tumors in rats exposed to constant natural light, thus prolonging their mean lifespan [23, 24].

    These studies highlight the potential anti-cancer properties of eptihalon in animal models and suggest that further research in this area remains warranted.

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    Epithalon Side Effects

    At least two epithalamin trials have shown that the peptide is well tolerated with a favorable safety profile, and causes no severe adverse effects in test subjects [1].

    According to the findings of a 15-year follow-up study on test subjects who had received up to six courses of epithalamin treatment, no adverse events were attributed to the peptide. In that study, the researchers concluded that epithalamin-treatment patients had “significantly lower mortality” than those of the control group [25].

    Despite its favorable safety record, researchers should note the possibility of injection-related side effects like inflammation, itching, swelling, or pain at the site of injection. These side effects are transient and typically subside within a day or two following injection.

    Researchers should follow all standard precautions to reduce the incidence of injection-related side effects, including procuring research-grade epithalon and injection supplies from a trusted source.

    Is Epithalon Safe?

    Epithalon injections are generally regarded as safe when administered by qualified researchers.

    When administered according to clinical guidelines, epithalon presents relatively few and minor potential side effects that cease after discontinuation of treatment.

    Researchers should take note of the two following risk factors:

    Impure epithalon

    Epithalon has not been approved outside of Russia, pending further study. Unfortunately, this has led to the illicit sale of unregulated products that are mislabeled as epithalon. Some of these products may contain harmful contaminants that can lead to systemic toxicity when injected. Avoid this by purchasing peptides from a reputable supplier.

    Signs of vendor legitimacy include certificates of third-party analysis to verify peptide purity as well as relevant disclaimers against misuse. A further safety concern highlighted by the ADDF is the possibility that synthetic or isolated preparation of epithalon may constrain impurities and pose a safety risk [1].

    Improper administration procedure

    Failure to comply with the guidelines for proper subcutaneous injections can lead to contamination and infection. Researchers must have access to sterile, high-quality supplies and adhere to standard methods of reconstitution, injection, and storage.

    In sum, epithalon has been deemed safe in clinical research contexts. Nonetheless, researchers are advised to avoid excessive use and contaminants. This requires getting acquainted with the pertinent literature and following best practices when incorporating epithalon into a research study. Lastly, researchers should stay abreast of emerging literature, particularly on the long-term effects of epithalon.

    Epithalon Dosage Calculator

    Insofar as epithalon is sold as a reference material, there are no universally agreed-upon guidelines for dosing the peptide in test subjects.

    Based on the work of Professor Khavinson and his research team, the International Peptide Society has published the following sample epithalon dosing protocol for anti-aging purposes (“the Russian Protocol”) [26]:

    • Total Dosage: 100mg epithalon
    • Frequency: Administer 10mg of epithalon daily, in one to two subcutaneous injections. For twice-daily injections, administer once in the morning and once at night.
    • Study Period: 10 days
    • Notes: Administer this protocol up to 2 times per year. Each course should be followed by a pause of at least four months.

    Alternatively, researchers may opt to administer an alternative protocol, involving half the total epithalon dosage, referred to in the literature as the “Ukrainian Protocol” [26]:

    • Total Dosage: 50mg epithalon
    • Frequency: Administer 1 subcutaneous injection of 10mg epithalon on days 1, 5, 9, 13, and 17 of the study period.
    • Study Period: 17 days
    • Notes: Administer this protocol up to 2 times per year. Each course should be followed by a pause of at least four months.

    Researchers should note that a single 100mg epithalon course under the Russian Protocol requires two 50mg epithalon vials, while a 50mg epithalon course under the Ukrainian Protocol requires one 50mg epithalon vial.

    Where to Buy Epithalon Online? | 2023 Guide

    Researchers may buy epithalon online as a research chemical from a variety of sources.

    However, not all research peptide vendors sell research-grade epithalon at reasonable prices, and many fail to make good on their promises of peptide quality and purity.

    At Peptides.org, we know the peptide industry inside and out, having tested numerous peptide vendors and rating each based on quality, cost, and shipping.

    In our experience, Peptide Sciences is the best place to buy injectable epithalon online.

    Here is what we love about this top vendor:

    • 99% pure peptides: Peptide Sciences contracts an independent laboratory to test all of its epithalon batches via HPLC-MS testing and publishes the corresponding lab reports online. Researchers do have to worry about receiving contaminated products when they shop here.
    • Low prices: As of this publication, a 20mg vial of epithalon costs just $95 while the larger 50mg epithalon vial costs $215. Researchers can save big when they order in bulk, with discounts starting from three vials.
    • Convenient payment options: Researchers can pay with select cryptocurrencies, credit cards (by Mesh payments), and a range of other secure payment methods including electronic check, FLEX payment, Apple Cash, Cash App, and Zelle.
    • Free U.S. shipping: U.S. orders over $200 ship free and typically arrive in 2-3 business days. The vendor ships to select international destinations as well, and fulfills international orders within 7-10 business days.
    • Excellent customer service: Peptide Sciences is renowned for its friendly customer service team that typically responds to customer email inquiries within one to two business days.

    While Peptide Sciences is our go-to vendor for buying injectable epithalon online, we recommend visiting PureRawz to obtain epithalon in nasal spray form.

    In our experience, the buying experience with PureRawz is comparable to buying from Peptide Sciences, and the former provides a range of quality peptide-based nasal sprays. Their research grade epithalon 100mg spray works well for researchers looking for a more convenient way to deliver peptides to research subjects.

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    FAQ

    Epithalon. Just. Works

    Epithalon has demonstrated anti-aging, sleep-promoting, and disease-fighting benefits and may be of interest to peptide researchers actively working in these areas.

    With its excellent safety profile and ease of administration, epithalon may be administered twice annually in two short courses for its anti-aging effects.

    Visit either of our top recommended suppliers to obtain high-purity epithalon for your research: Peptide Sciences for injectable epithalon and PureRawz for epithalon in nasal spray form.

    Epithalon

    References

    1. Epithalamin/Epithalon. (2022). Retrieved 2 May 2022, from https://www.alzdiscovery.org/uploads/cognitive_vitality_media/Epithalamin-and-Epithalon-Cognitive-Vitality-For-Researchers.pdf
    2. Khavinson VKh, Bondarev IE, Butyugov AA. Epithalon peptide induces telomerase activity and telomere elongation in human somatic cells. Bull Exp Biol Med. 2003 Jun;135(6):590-2. doi: 10.1023/a:1025493705728. PMID: 12937682.
    3. Khavinson V, Diomede F, Mironova E, Linkova N, Trofimova S, Trubiani O, Caputi S, Sinjari B. AEDG Peptide (Epitalon) Stimulates Gene Expression and Protein Synthesis during Neurogenesis: Possible Epigenetic Mechanism. Molecules. 2020 Jan 30;25(3):609. doi: 10.3390/molecules25030609. PMID: 32019204; PMCID: PMC7037223
    4. Khavinson VKh, Kuznik BI, Tarnovskaia SI, Lin'kova NS. [Peptides and CCL11 and HMGB1 as molecular markers of aging: literature review and own data]. Adv Gerontol. 2014;27(3):399-406. Russian. PMID: 25826983.
    5. Anisimov VN, Arutjunyan AV, Khavinson VK. Effects of pineal peptide preparation Epithalamin on free-radical processes in humans and animals. Neuro Endocrinol Lett. 2001;22(1):9-18. PMID: 11335874.
    6. Anisimov VN, Khavinson VK, Provinciali M, Alimova IN, Baturin DA, Popovich IG, Zabezhinski MA, Imyanitov EN, Mancini R, Franceschi C. Inhibitory effect of the peptide epitalon on the development of spontaneous mammary tumors in HER-2/neu transgenic mice. Int J Cancer. 2002 Sep 1;101(1):7-10. doi: 10.1002/ijc.10570. PMID: 12209581.
    7. Labunets IF, Butenko GM, Korkushko OV, Shatilo VB. Effect of epithalamin on the rhythm of immune and endocrine systems functioning in patients with chronic coronary disease. Bull Exp Biol Med. 2007 Apr;143(4):472-5. doi: 10.1007/s10517-007-0159-y. PMID: 18214303.
    8. Khavinson VKh, Morozov VG. Geroprotektornaia éffektivnost' timalina i épitalamina [Geroprotective effect of thymalin and epithalamin]. Adv Gerontol. 2002;10:74-84. Russian. PMID: 12577695.
    9. Anisimov VN, Bondarenko LA, Khavinson VKh. Effect of pineal peptide preparation (epithalamin) on life span and pineal and serum melatonin level in old rats. Ann N Y Acad Sci. 1992 Dec 26;673:53-7. doi: 10.1111/j.1749-6632.1992.tb27436.x. PMID: 1485734.
    10. Korkushko OV, Lapin BA, Goncharova ND, Khavinson VKh, Shatilo VB, Vengerin AA, Antoniuk-Shcheglova IA, Magdich LV. [Normalizing effect of the pineal gland peptides on the daily melatonin rhythm in old monkeys and elderly people]. Adv Gerontol. 2007;20(1):74-85. Russian. PMID: 17969590.
    11. Khavinson V, Goncharova N, Lapin B. Synthetic tetrapeptide epitalon restores disturbed neuroendocrine regulation in senescent monkeys. Neuro Endocrinol Lett. 2001 Aug;22(4):251-4. PMID: 11524632.
    12. Korkushko OV, Khavinson VKh, Shatilo VB, Magdich LV. Effect of peptide preparation epithalamin on circadian rhythm of epiphyseal melatonin-producing function in elderly people. Bull Exp Biol Med. 2004 Apr;137(4):389-91. doi: 10.1023/b:bebm.0000035139.31138.bf. PMID: 15452611.
    13. Korenevsky AV, Milyutina YP, Bukalyov AV, Baranova YP, Vinogradova IA, Arutjunyan AV. [Protective effect of melatonin and epithalon on hypothalamic regulation of reproduction in female rats in its premature aging model and on estrous cycles in senescent animals in various lighting regimes]. Adv Gerontol. 2013;26(2):263-274. Russian. PMID: 28976150.
    14. Chitimus DM, Popescu MR, Voiculescu SE, Panaitescu AM, Pavel B, Zagrean L, Zagrean AM. Melatonin's Impact on Antioxidative and Anti-Inflammatory Reprogramming in Homeostasis and Disease. Biomolecules. 2020 Aug 20;10(9):1211. doi: 10.3390/biom10091211. PMID: 32825327; PMCID: PMC7563541.
    15. Rosenfeld SV, Togo EF, Mikheev VS, Popovich IG, Khavinson VKh, Anisimov VN. Effect of epithalon on the incidence of chromosome aberrations in senescence-accelerated mice. Bull Exp Biol Med. 2002 Mar;133(3):274-6. doi: 10.1023/a:1015899003974. PMID: 12360351.
    16. Sibarov DA, Vol'nova AB, Frolov DS, Nozdrachev AD. Effects of intranasal administration of epitalon on neuron activity in the rat neocortex. Neurosci Behav Physiol. 2007 Nov;37(9):889-93. doi: 10.1007/s11055-007-0095-3. PMID: 17955380.
    17. Khavinson VKh, Linkova NS, Kvetnoy IM, Kvetnaia TV, Polyakova VO, Korf HW. Molecular cellular mechanisms of peptide regulation of melatonin synthesis in pinealocyte culture. Bull Exp Biol Med. 2012 Jun;153(2):255-8. English, Russian. doi: 10.1007/s10517-012-1689-5. PMID: 22816096.
    18. Anisimov VN, Mylnikov SV, Oparina TI, Khavinson VK. Effect of melatonin and pineal peptide preparation epithalamin on life span and free radical oxidation in Drosophila melanogaster. Mech Ageing Dev. 1997 Aug;97(2):81-91. doi: 10.1016/s0047-6374(97)01897-6. PMID: 9226628.
    19. Khavinson VK, Myl'nikov SV. Effect of pineal tetrapeptide on antioxidant defense in Drosophila melanogaster. Bull Exp Biol Med. 2000 Apr;129(4):355-6. doi: 10.1007/BF02439268. PMID: 10977918.
    20. Kozina LS, Arutjunyan AV, Khavinson VKh. Antioxidant properties of geroprotective peptides of the pineal gland. Arch Gerontol Geriatr. 2007;44 Suppl 1:213-6. doi: 10.1016/j.archger.2007.01.029. PMID: 17317455.
    21. Anisimov VN, Khavinsov VKh, Alimova IN, Provintsiali M, Manchini R, Francheski K. Epithalon inhibits tumor growth and expression of HER-2/neu oncogene in breast tumors in transgenic mice characterized by accelerated aging. Bull Exp Biol Med. 2002 Feb;133(2):167-70. doi: 10.1023/a:1015555023692. PMID: 12428286.
    22. Kossoy G, Anisimov VN, Ben-Hur H, Kossoy N, Zusman I. Effect of the synthetic pineal peptide epitalon on spontaneous carcinogenesis in female C3H/He mice. In Vivo. 2006 Mar-Apr;20(2):253-7. PMID: 16634527.
    23. Vinogradova IA, Bukalev AV, Zabezhinski MA, Semenchenko AV, Khavinson VKh, Anisimov VN. Effect of Ala-Glu-Asp-Gly peptide on life span and development of spontaneous tumors in female rats exposed to different illumination regimes. Bull Exp Biol Med. 2007 Dec;144(6):825-30. doi: 10.1007/s10517-007-0441-z. PMID: 18856211.
    24. Vinogradova IA, Bukalev AV, Zabezhinski MA, Semenchenko AV, Khavinson VKh, Anisimov VN. Geroprotective effect of ala-glu-asp-gly peptide in male rats exposed to different illumination regimens. Bull Exp Biol Med. 2008 Apr;145(4):472-7. doi: 10.1007/s10517-008-0121-7. PMID: 19110597.
    25. Korkushko OV, Khavinson VKh, Shatilo VB, Antonyk-Sheglova IA. Peptide geroprotector from the pituitary gland inhibits rapid aging of elderly people: results of 15-year follow-up. Bull Exp Biol Med. 2011 Jul;151(3):366-9. English, Russian. doi: 10.1007/s10517-011-1332-x. PMID: 22451889.
    26. Epithalon monograph final - peptidesociety.org. https://peptidesociety.org/wp-content/uploads/2018/07/Epithalon-Monograph-Final.pdf (Accessed November 9, 2022).